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Sample records for tumor lysis syndrome

  1. Tumor lysis syndrome in children

    International Nuclear Information System (INIS)

    Suarez, Amaranto

    2004-01-01

    Tumor lysis syndrome is a metabolic emergency characterized by electrolyte alteration with or without acute renal failure. It occurs mainly in patients with malignant tumors that have a high growth fraction, or after cytotoxic therapy, as a result of the massive degradation of malignant cells and the release of high amounts of intracellular elements that exceed the capacity of renal excretion. The objective of the treatment is the prevention of nephropathy due to uric acid deposits, and the correction of metabolic acidosis and electrolyte alterations. This paper reviews the incidence, the physiopathology, and the treatment of tumor lysis syndrome in children

  2. Rare incidence of tumor lysis syndrome in metastatic prostate cancer following treatment with docetaxel.

    Science.gov (United States)

    Bhardwaj, Sharonlin; Varma, Seema

    2018-03-01

    Tumor lysis syndrome is a serious and sometimes lethal complication of cancer treatment that is comprised of a set of metabolic disturbances along with clinical manifestations. Initiating chemotherapy in bulky, rapidly proliferating tumors causes rapid cell turnover that in turn releases metabolites into circulation that give rise to metabolic derangements that can be dangerous. This syndrome is usually seen in high-grade hematological malignancies. Less commonly, tumor lysis syndrome can present in solid tumors and even rarely in genitourinary tumors. In this report, the authors describe a specific case of tumor lysis syndrome in a patient with metastatic prostate cancer following treatment with docetaxel.

  3. Tumor lysis syndrome in a patient with metastatic colon cancer after treatment with oxaliplatin and 5-Fu

    Directory of Open Access Journals (Sweden)

    Ruo-Han Tseng

    2016-12-01

    Full Text Available Tumor lysis syndrome in solid tumors is a rare occurrence, with a poor prognosis. We present the case of a patient of recurrent colon cancer who received chemotherapy with FOLFOX regimen (lencovorin, fluorouracil, and oxaliplatin with subsequent tumor lysis. We present a recurrent rectal cancer patient suffered from tumor lysis syndrome after salvage FOLFOX regimen. After treat with CVVH with improved conscious status. In this case report, we had review the tumor lysis in solid tumor.

  4. Síndrome de lise tumoral: uma revisão abrangente da literatura Acute tumor lysis syndrome: a comprehensive review

    Directory of Open Access Journals (Sweden)

    Michael Darmon

    2008-09-01

    égias baseadas no risco dos pacientes são necessários para limitar a alta morbidade e mortalidade desta complicação.Tumor lysis syndrome is characterized by the massive destruction of malignant cells and the release in the extra-cellular space of their content. While Tumor lysis syndrome may occur spontaneously before treatment, it usually develops shortly after the initiation of cytotoxic chemotherapy. These metabolites can overwhelm the homeostatic mechanisms with development of hyperuricaemia, hyperkalaemia, hyperphosphataemia, and hypocalcaemia. These biological manifestations may lead to clinical manifestations including, acute kidney injury, seizure, or sudden death that require intensive care. Since clinical tumor lysis syndrome is associated with a poor prognosis both prevention of tumor lysis syndrome and prevention of clinical consequences of tumor lysis syndrome are mandatory. The objective of this review is to describe pathophysiological mechanisms, biological and clinical manifestations of tumor Lysis syndrome, and to provide upto-date guidelines to ensure prevention of tumor lysis syndrome. Review of selected studies on tumor lysis syndrome published at the PubMed database www.pubmed.gov during the last 20 years. Additional references were retrieved from the studies initially selected. Tumor lysis syndrome is a frequent and life-threatening complication of the newly diagnosed malignancies. Preventive measures, including hydration, uricolytic agents, eviction of factors predisposing to acute kidney injury and, in the more severe patients, on prophylactic renal replacement therapy, are required to prevent or limit clinical consequences of Tumor lysis syndrome. However optimal timing and modalities of prevention remains unknown and may be modified by the changing spectrum of patients at risk of tumor lysis syndrome. Development and validation of risk based strategies is required to limit the high morbidity and mortality of this complication.

  5. Tumor lysis syndrome following endoscopic radiofrequency interstitial thermal ablation of colorectal liver metastases.

    LENUS (Irish Health Repository)

    Barry, B D

    2012-02-03

    Radiofrequency interstitial thermal ablation (RITA) provides a palliative option for patients suffering from metastatic liver disease. This procedure can be performed using a laparoscopic approach with laparoscopic ultrasound used to position the RITA probe. We describe a case of laparoscopic RITA performed for colorectal liver metastasis that was complicated by tumor lysis syndrome (TLS) following treatment. We consider RITA to be a safe procedure, as supported by the literature, but where intracorporal tumor lysis is the treatment goal we believe that the systemic release of tumor products can overwhelm the excretory capacity; therefore, TLS is an inevitable consequence in some patients.

  6. Spontaneous Tumor Lysis Syndrome

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    Alicia C. Weeks MD

    2015-08-01

    Full Text Available Tumor lysis syndrome (TLS is a known complication of malignancy and its treatment. The incidence varies on malignancy type, but is most common with hematologic neoplasms during cytotoxic treatment. Spontaneous TLS is thought to be rare. This case study is of a 62-year-old female admitted with multisystem organ failure, with subsequent diagnosis of aggressive B cell lymphoma. On admission, laboratory abnormalities included renal failure, elevated uric acid (20.7 mg/dL, and 3+ amorphous urates on urinalysis. Oliguric renal failure persisted despite aggressive hydration and diuretic use, requiring initiation of hemodialysis prior to chemotherapy. Antihyperuricemic therapy and hemodialysis were used to resolve hyperuricemia. However, due to multisystem organ dysfunction syndrome with extremely poor prognosis, the patient ultimately expired in the setting of a terminal ventilator wean. Although our patient did not meet current TLS criteria, she required hemodialysis due to uric acid nephropathy, a complication of TLS. This poses the clinical question of whether adequate diagnostic criteria exist for spontaneous TLS and if the lack of currently accepted guidelines has resulted in the underestimation of its incidence. Allopurinol and rasburicase are commonly used for prevention and treatment of TLS. Although both drugs decrease uric acid levels, allopurinol mechanistically prevents formation of the substrate rasburicase acts to solubilize. These drugs were administered together in our patient, although no established guidelines recommend combined use. This raises the clinical question of whether combined therapy is truly beneficial or, conversely, detrimental to patient outcomes.

  7. Tumor Lysis Syndrome (TLS following intrathecal chemotherapy in a child with acute myelogenous leukemia (AML

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    Chana L. Glasser, MD

    2017-01-01

    Full Text Available Tumor Lysis Syndrome (TLS is a well-known complication of induction therapy for hematologic malignancies. It is characterized by rapid breakdown of malignant white blood cells (WBCs leading to metabolic derangements and serious morbidity if left untreated. Most commonly, TLS is triggered by systemic chemotherapy, however, there have been case reports of TLS following intrathecal (IT chemotherapy, all in patients with acute lymphoblastic leukemia (ALL/lymphoma. Here, we report the first case of a patient with acute myelogenous leukemia (AML who developed TLS following a single dose of IT cytosine arabinoside (Ara-C.

  8. Hyperphosphatemia during spontaneous tumor lysis syndrome culminate in severe hyphosphatemia at the time of blast crisis of Phneg CML to acute myelomoncytic leukemia

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    Salomon Ophira

    2012-08-01

    Full Text Available Abstract Extreme swing of phosphor from severe hyperphosphatemia to severe hypophosphatemia in a patient with blast crisis of myeloid origin was the result of imbalance between massive apoptosis of leukemic cells in the context of spontaneous tumor lysis syndrome and massive production of leukemic cells with only 1% of blast in peripheral blood. The mutated p53 protein suggested acting as oncogene in the presented case and possibly affecting phosphor status.

  9. Electrochemical lysis at the stage of endoresection for large posterior intraocular tumors

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    Yu. A. Belyy

    2012-01-01

    Full Text Available Purpose: to design the new combined technique of endoresection with intraoperative intraocular electrochemical lysis at the tumor destruction stage for large posterior intraocular tumors.Methods: 3 patients (3 eyes with large choroidal melanomas t3N0M0 (tumor thickness — 8-10 mm, base diameter — 13-15 mm, juxtapapillary localization. Mean age was 55.4 years old. Endoresection with intraoperational intraocular electrochemical lysis of the tumor was performed. Electrochemical lysis was performed with use of the technical unit ECU 300 (Soering, Germany and the original method of combined intratumoral positioning of two platinum electrodes: anode and cathode.Results: the tumor was removal completely in all 3 cases. the anatomical retinal reattachment was reached in all patients. Sclera was safe in all 3 cases. Visual acuity was not changed (NLP. At the place of the removal tumor a surgical choroidal coloboma without pigmentation all over scleral bed and periphery was shown in all cases in distant postoperative period (from 1.5 to 3 years. No local recurrences or metastasis were revealed in all patients.Conclusion: Further investigations in clinical group are necessarily to determinate the real possibilities of the combined method and the indications for endoresection with intraoperative intraocular electrochemical lysis for large intraocular tumors

  10. Transcatheter arterial embolization with trisacryl gelatin microspheres (Embosphere®) leads to life-threatening tumor lysis syndrome in a rectal carcinoid patient with hepatic metastases

    International Nuclear Information System (INIS)

    Lo, Yuan-Hao; Tsai, Ming-Tsun; Kuo, Chen-Yu; Liu, Wen-Sheng; Lee, Rheun-Chuan; Yeh, Yi-Chen; Li, Chung-Pin; Chen, Jinn-Yang; Chao, Yee

    2012-01-01

    The incidence of gastrointestinal carcinoids appears to be increasing, and the rectum is the third most common location. Transcatheter arterial embolization (TAE) with trisacryl gelatin microspheres (Embosphere ® ) has been reported as an effective method for hepatic metastases of rectal carcinoids. Complications are uncommon and usually of minor consequence. We report an unusual case of a 34-year-old man with tumor lysis syndrome following TAE with Embosphere ® in a patient with multiple hepatic metastases of a rectal carcinoid. Early detection and effective treatment are essential for this rare but potentially catastrophic complication

  11. Use of conivaptan to allow aggressive hydration to prevent tumor lysis syndrome in a pediatric patient with large-cell lymphoma and SIADH.

    Science.gov (United States)

    Rianthavorn, Pornpimol; Cain, Joan P; Turman, Martin A

    2008-08-01

    The available treatment options for hyponatremia secondary to SIADH are limited and not completely effective. Conivaptan is a vasopressin 1a and 2 receptor antagonist recently approved by the US Food and Drug Administration (FDA) for treating euvolemic and hypervolemic hyponatremia in adult patients. However, data on efficacy and safety of conivaptan in pediatrics are limited. We report a case of a 13-year-old boy with extensively metastasized anaplastic large-cell lymphoma. He also developed hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion (SIADH) prior to chemotherapy initiation. SIADH management in this case was complicated when fluid restriction was not safely attainable. Conivaptan played a significant role in this situation by allowing provision of a large amount of intravenous fluid prior to and during induction chemotherapy. It proved to be an important component in preventing uric acid nephropathy/tumor lysis syndrome. Conivaptan induced free-water clearance as indicated by increased urine output and decreased urine osmolality. The patient responded to conivaptan without any adverse effects.

  12. Lysis of fresh human solid tumors by autologous lymphocytes activated in vitro with lectins

    International Nuclear Information System (INIS)

    Mazumder, A.; Grimm, E.A.; Zhang, H.Z.; Rosenberg, S.A.

    1982-01-01

    Human peripheral blood lymphocytes (PBL), obtained from patients with a variety of cancers, were incubated in vitro with phytohemagglutinin, concanavalin A, and crude or lectin-free T-cell growth factors. The lectin-activated PBL of nine patients were capable of lysing fresh autologous tumor during a 4-hr 51Cr release assay. Multiple metastases from the same patient were equivalently lysed by these activated autologous PBL. No lysis of fresh PBL or lectin-induced lymphoblast cell targets was seen, although tumor, PBL, and lymphoblast cells were shown to be equally lysable using allosensitized cells. The activated cells could be expanded without loss of cytotoxicity in crude or lectin-free T-cell growth factors. The generation of cells lytic to fresh autologous tumor was dependent on the presence of adherent cells, although the lytic cell itself was not adherent. Proliferation was not involved in the induction of lytic cells since equal lysis was induced in irradiated and nonirradiated lymphocytes. Lectin was not required in the lytic assay, and the addition of alpha-methyl-D-mannoside to concanavalin A-activated lymphoid cells did not increase the lysis of fresh tumor cells. Activation by lectin for 3 days appears to be an efficient and convenient method for generating human cells lytic to fresh autologous tumor. These lytic cells may be of value for studies of the cell-mediated lysis of human tumor and possibly for tumor immunotherapy as well

  13. Hyperuricemia and tumor lysis syndrome in children with non-Hodgkin’s lymphoma and acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Betül Sevinir

    2011-03-01

    Full Text Available Objective: This study aimed to examine the incidence, clinical characteristics, and outcome of hyperuricemia and tumor lysis syndrome (TLS in children with non-Hodgkin’s lymphoma (NHL and acute lymphoblastic leukemia (ALL.Materials and Methods: This retrospective study included data from 327 patients (113 NHL and 214 ALL.Results: Hyperuricemia occurred in 26.5% and 12.6% of the patients with NHL and ALL, respectively. The corresponding figures for TLS were 15.9% and 0.47% (p=0.001. All hyperuricemic NHL patients had advanced disease and renal involvement was present in 53%. All hyperuricemic ALL patients had a leukocyte count >50,000 mm3 at the time of diagnosis. Among the hyperuricemic NHL and ALL patients, 96.6% and 66.6% had LDH ≥500 UI/L, respectively. Treatment consisted of hydration and allopurinol; none of the patients received urate oxidase. Among the patients that developed TLS, 26.3% had laboratory TLS, 42.1% had grade I or II TLS, and 31.6% had grade III or IV TLS. Uric acid levels returned to normal after a mean period of 3.5±2.5 and 3.05±0.8 d in NHL and ALL groups, respectively. In all, 7% of the patients with hyperuricemia required hemodialysis. None of the patients died.Conclusion: In this series the factors associated with a high-risk for TLS were renal involvement in NHL and high leucocyte count in ALL. Management with allopurinol and hydration was effective in this group of patients with high tumor burden.

  14. A case of cetuximab-related tumour lysis syndrome in metastatic rectal carcinoma

    Science.gov (United States)

    Haroon, Muhammad; Kwong, Whye Yan; Cantwell, Brian; Walker, Frank

    2010-01-01

    A 60-year-old man was diagnosed with a moderately differentiated adenocarcinoma in November 2006. The computed tomography (CT), magnetic resonance imaging (MRI) and whole-body positron emission tomography–CT (PET–CT) scan showed the presence of multiple liver metastases which were confined to its right lobe. He had the first session of a combined therapy with cetuximab and 5-fluorouracil (5-FU) in March 2009; however, soon afterwards, he presented with the symptoms, signs and biochemistry suggestive of tumour lysis syndrome. Our unusual case highlights that tumour lysis syndrome can also develop in ‘low risk’ category tumours, and that clinicians should be vigilant in identifying at-risk patients. PMID:28657052

  15. Capacity of tumor necrosis factor to augment lymphocyte-mediated tumor cell lysis of malignant mesothelioma

    International Nuclear Information System (INIS)

    Bowman, R.V.; Manning, L.S.; Davis, M.R.; Robinson, B.W.

    1991-01-01

    Recombinant human tumor necrosis factor (rHuTNF) was evaluated both for direct anti-tumor action against human malignant mesothelioma and for its capacity to augment the generation and lytic phases of lymphocyte-mediated cytotoxicity against this tumor. rHuTNF was directly toxic by MTT assay to one of two mesothelioma cell lines evaluated, but had no effect on susceptibility to subsequent lymphocyte-mediated lysis of either line. TNF alone was incapable of generating anti-mesothelioma lymphokine-activated killer cell (LAK) activity. Furthermore, it did not augment the degree or LAK activity produced by submaximal interleukin-2 (IL-2) concentrations nor did it augment lysis of mesothelioma cells by natural killer (NK) or LAK effector cells during the 4-hr 51chromium release cytolytic reaction. The studies also suggest that mesothelioma targets are less responsive to TNF plus submaximal IL-2 concentrations than the standard LAK sensitive target Daudi, raising the possibility that intermediate LAK sensitive tumors such as mesothelioma may require separate and specific evaluation in immunomodulation studies. This in vitro study indicates that use of low-dose rHuTNF and IL-2 is unlikely to be an effective substitute for high-dose IL-2 in generation and maintenance of LAK activity in adoptive immunotherapy for mesothelioma

  16. Síndrome de lisis tumoral en un paciente con cáncer de riñón tratado con sunitinib Tumor lysis syndrome in a patient with a renal carcinoma treated with sunitinib

    Directory of Open Access Journals (Sweden)

    Ezequiel Rodríguez-Reimúndes

    2011-04-01

    Full Text Available El síndrome de lisis tumoral (SLT es un trastorno metabólico que ocurre como consecuencia de una destrucción celular masiva. Se caracteriza por la presencia de hiperuricemia, hiperfosfatemia, hipocalcemia e hiperkalemia, y predispone al desarrollo de insuficiencia renal aguda. En la mayoría de los casos el SLT ocurre luego de instaurarse un tratamiento antitumoral y es más frecuente en tumores de alto grado de malignidad y alta sensibilidad a la quimioterapia. Presentamos el caso de un paciente con diagnóstico de cáncer de riñón recidivado que presenta un SLT e insuficiencia renal aguda luego de iniciar tratamiento con sunitinib.The tumor mor lysis syndrome (TLS is a metabolic disorder resulting from a massive tumor breakdown. It is characterized by hyperuricemia, hyperphosphatemia, hypocalcemia and hyperkalemia and predisposes to acute renal failure. TLS usually occurs after the initiation of cytotoxic therapy and is more frequent in the case of neoplasias with a high proliferative rate or that are highly chemo-sensitive. We report the case of a man with a recurrent kidney cancer who presented with a TLS and acute renal failure after initiation of sunitinib.

  17. 白血病合并肿瘤溶解综合征的诊治%Diagnosis and treatment of tumor lysis syndrome associated with leukemia

    Institute of Scientific and Technical Information of China (English)

    秘营昌

    2011-01-01

    肿瘤溶解综合征(TLS)是血液肿瘤科常见的急症,临床表现主要有高尿酸血症、高钾血症、高磷酸血症、低钙血症等,最终导致肾功能衰竭、心律失常、癫痫、神经系统并发症,甚至死亡.目前对TLS诊断、疾病危险度判断、治疗观点较一致,提高了TLS的诊断、治疗水平.%Tumor lysis syndrome (TLS) is a life-threatening oncological emergency characterized by metabolic abnormalities including hyperuricaernia,hyperphosphataemia,hyperkalaemia and hypocalcaemia. These metabolic complications will eventually lead to a series of complications. Now that the diagnosis of TI.S has been clarified, a panel of TLS experts have offered recommendations for evaluation of risks and prophylaxis of TLS to improve the prognosis of patients with TLS.

  18. The challenges of treating paraganglioma patients with 177Lu-DOTATATE PRRT: Catecholamine crises, tumor lysis syndrome and the need for modification of treatment protocols

    International Nuclear Information System (INIS)

    Makis, William; Mccann, Karey; Mcewan, Alexander J. B.

    2015-01-01

    A high percentage of paragangliomas express somatostatin receptors that can be utilized for targeted radioisotope therapy. The aim of this study was to describe and discuss the challenges of treating these tumors with 177 Lu-[DOTA0,Tyr3]octreotate (DOTATATE) radioisotope therapy using established protocols. Three paraganglioma patients were treated with 4–5 cycles of 177 Lu-DOTATATE and were evaluated for side effects and response to therapy. Two of the three patients developed severe adverse reactions following their first 177 Lu-DOTATATE treatment. One patient developed a catecholamine crisis and tumor lysis syndrome within hours of treatment, requiring intensive care unit (ICU) support, and another developed a catecholamine crisis 3 days after treatment, requiring hospitalization. The treatment protocols at our institution were subsequently modified by increasing the radioisotope infusion time from 15 to 30 min, as recommended in the literature, to 2–4 h and by reducing the administered dose of 177 Lu-DOTATATE. Subsequent 177 Lu-DOTATATE treatments utilizing the modified protocols were well tolerated, and response to therapy was achieved in all three patients, resulting in significantly improved quality of life. 177 Lu-DOTATATE is an exciting new therapeutic option in the management of paragangliomas; however, current treatment protocols described in the literature may need to be modified by lengthening the infusion time and/or lowering the initial treatment dose to prevent or reduce the severity of adverse reactions

  19. Spontaneous tumour lysis syndrome in a case of multiple myeloma – A rare occurrence

    Directory of Open Access Journals (Sweden)

    Kavitha Saravu

    2013-03-01

    Full Text Available We describe a case of a 40-year-old male patient who was found to have multiple myeloma with spontaneous tumour lysis syndrome (TLS, following a compression fracture of the L–2 vertebrae. Multiple myeloma was confirmed by bone marrow analysis and the M–band on serum protein electrophoresis. Hyperuricaemia (26.2 mg/dL, hyperkalaemia (> 7.0 mEq/L, hyperphosphatemia (16.2 mg of phosphorus/dL, normocalcemia and acute kidney injury, prior to anticancer treatment suggested spontaneous TLS. Inciting events for tumour lysis, such as chemotherapy, dehydration and exposure to steroids were absent. Patient received hydration, hypourecemic drugs and haemodialysis. This case report highlights the rare presentation of multiple myeloma with spontaneous TLS.

  20. The challenges of treating paraganglioma patients with {sup 177}Lu-DOTATATE PRRT: Catecholamine crises, tumor lysis syndrome and the need for modification of treatment protocols

    Energy Technology Data Exchange (ETDEWEB)

    Makis, William; Mccann, Karey; Mcewan, Alexander J. B. [Dept. of Diagnostic Imaging, Cross Cancer Institute, Alberta (China)

    2015-09-15

    A high percentage of paragangliomas express somatostatin receptors that can be utilized for targeted radioisotope therapy. The aim of this study was to describe and discuss the challenges of treating these tumors with {sup 177}Lu-[DOTA0,Tyr3]octreotate (DOTATATE) radioisotope therapy using established protocols. Three paraganglioma patients were treated with 4–5 cycles of {sup 177}Lu-DOTATATE and were evaluated for side effects and response to therapy. Two of the three patients developed severe adverse reactions following their first {sup 177}Lu-DOTATATE treatment. One patient developed a catecholamine crisis and tumor lysis syndrome within hours of treatment, requiring intensive care unit (ICU) support, and another developed a catecholamine crisis 3 days after treatment, requiring hospitalization. The treatment protocols at our institution were subsequently modified by increasing the radioisotope infusion time from 15 to 30 min, as recommended in the literature, to 2–4 h and by reducing the administered dose of {sup 177}Lu-DOTATATE. Subsequent {sup 177}Lu-DOTATATE treatments utilizing the modified protocols were well tolerated, and response to therapy was achieved in all three patients, resulting in significantly improved quality of life. {sup 177}Lu-DOTATATE is an exciting new therapeutic option in the management of paragangliomas; however, current treatment protocols described in the literature may need to be modified by lengthening the infusion time and/or lowering the initial treatment dose to prevent or reduce the severity of adverse reactions.

  1. Tumour lysis syndrome: A rare acute presentation of locally advanced testicular cancer – Case report and review of literature

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    Marcus Chow

    2016-01-01

    Full Text Available Tumour lysis syndrome (TLS is a potentially fatal complication of malignancy or its treatment. This uncommon syndrome comprises laboratory findings of hyperuricaemia, hypocalcaemia, hyperkalaemia and hyperphosphataemia. A literature search revealed a total of eight patients, with testicular cancer, who had TLS. All these patients had metastatic disease. We present a unique case of a 47-year-old gentleman we saw in clinic, who presented with a rapidly growing right groin mass and acute breathlessness, and discuss the diagnosis and management of TLS. TLS is extremely rare in testicular cancer but necessitates the awareness of urologists. TLS can occur spontaneously in testicular malignancy. Cell lysis in a rapidly proliferating germ cell tumour is a possible mechanism. The prompt identification and institution of management for TLS is crucial to improve clinical outcomes.

  2. Genetics Home Reference: hyperparathyroidism-jaw tumor syndrome

    Science.gov (United States)

    ... Twitter Home Health Conditions Hyperparathyroidism-jaw tumor syndrome Hyperparathyroidism-jaw tumor syndrome Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Hyperparathyroidism-jaw tumor syndrome is a condition characterized by ...

  3. Squamous cell carcinoma complicating an hereditary epidermo-lysis bullosa

    International Nuclear Information System (INIS)

    Mseddi, M.; Turki, H.; Marrekchi, S.; Abdelmaksoud, W.; Masmoudi, A.; Bouassida, S.; Zahaf, A.

    2004-01-01

    The dystrophic form of hereditary epidermo-lysis bullosa is associated with an increased frequency of squamous cell carcinoma. We report a new case. An 18-year-old patient, carrying a Hallopeau Siemens hereditary epidermo-lysis bullosa, presented a subcutaneous nodular lesion, for 1 year that ulcerated and budded with inguinal lymphadenopathy. The histological study ted to the conclusion of a well differentiated squamous cell carcinoma. The patient was treated surgically. Tumor and metastatic lymph nodes were excised. A radiotherapy was decided but the postoperative course was fatal due to an infection and to a deterioration of her general condition. Squamous cell carcinoma frequently occurs on the cicatricial lesion of hereditary epidermo-lysis bullosa and usually affects males with recessive hereditary epidermo-lysis bullosa. Metastases are frequent, precocious and multiple. The treatment may be surgical. The particularities of our observation are the young age of patient and the localization. (author)

  4. Paraneoplastic Cushing Syndrome Due To Wilm's Tumor.

    Science.gov (United States)

    Faizan, Mahwish; Manzoor, Jaida; Saleem, Muhammad; Anwar, Saadia; Mehmood, Qaiser; Hameed, Ambreen; Ali, Agha Shabbir

    2017-05-01

    Paraneoplastic syndromes are rare disorders that are triggered by an altered immune system response to neoplasm. Paraneoplastic syndromes may be the first or the most prominent manifestations of cancer. Wilm's tumor is the most frequent pediatric renal malignancy and usually presents with abdominal mass. Unusual presentations like acquired von Willebrand disease, sudden death due to pulmonary embolism and Cushing syndrome have been described in the literature. Cushing syndrome, as the presenting symptom of a malignant renal tumor in children, is a very rare entity. Few case reports are available in the literature exploring the option of preoperative chemotherapy as well as upfront nephrectomy. We report a rare case of paraneoplastic Cushing syndrome due to a Wilm's tumor. Based on gradual decrease of postoperative weight, blood pressure, serum adrenocorticotropic hormone, and plasma cortisol levels, along with histological confirmation of Wilm's tumor, paraneoplastic Cushing syndrome due to Wilm's tumor was confirmed.

  5. Paraneoplastic cushing syndrome due to wilm's tumor

    International Nuclear Information System (INIS)

    Faizan, M.; Anwar, S.; Hameed, A.; Manzoor, J.; Saleem, M.; Mehmood, Q.; Ali, A. S.

    2017-01-01

    Paraneoplastic syndromes are rare disorders that are triggered by an altered immune system response to neoplasm. Paraneoplastic syndromes may be the first or the most prominent manifestations of cancer. Wilm's tumor is the most frequent pediatric renal malignancy and usually presents with abdominal mass. Unusual presentations like acquired von Willebrand disease, sudden death due to pulmonary embolism and Cushing syndrome have been described in the literature. Cushing syndrome, as the presenting symptom of a malignant renal tumor in children, is a very rare entity. Few case reports are available in the literature exploring the option of preoperative chemotherapy as well as upfront nephrectomy. We report a rare case of paraneoplastic Cushing syndrome due to a Wilm's tumor. Based on gradual decrease of postoperative weight, blood pressure, serum adrenocorticotropic hormone, and plasma cortisol levels, alongwith histological confirmation of Wilm's tumor, paraneoplastic Cushing syndrome due to Wilm's tumor was confirmed. (author)

  6. Diphtheria toxin- and Pseudomonas A toxin-mediated apoptosis. ADP ribosylation of elongation factor-2 is required for DNA fragmentation and cell lysis and synergy with tumor necrosis factor-alpha.

    Science.gov (United States)

    Morimoto, H; Bonavida, B

    1992-09-15

    We have reported that diphtheria toxin (DTX) mediates target cell lysis and intranucleosomal DNA fragmentation (apoptosis) and also synergizes with TNF-alpha. In this paper, we examined which step in the pathway of DTX-mediated inhibition of protein synthesis was important for induction of cytolytic activity and for synergy. Using a DTX-sensitive tumor cell line, we first examined the activity of the mutant CRM 197, which does not catalyze the ADP ribosylation of elongation factor-2 (EF-2). CRM 197 was not cytolytic for target cells and did not mediate intranucleosomal DNA fragmentation of viable cells. The failure of CRM 197 to mediate target cell lysis suggested that the catalytic activity of DTX is prerequisite for target cell lysis. This was corroborated by demonstrating that MeSAdo, which blocks the biosynthesis of diphthamide, inhibited DTX-mediated protein synthesis inhibition and also blocked target cell lysis. Furthermore, the addition of nicotinamide, which competes with NAD+ on the DTX action site of EF-2, also blocked DTX-mediated lysis. These findings suggest that ADP-ribosylation of EF-2 may be a necessary step in the pathway leading to target cell lysis. In contrast to the sensitive line, the SKOV-3 tumor cell line is sensitive to protein synthesis inhibition by DTX but is not susceptible to cytolysis and apoptosis by DTX. Thus, protein synthesis inhibition by DTX is not sufficient to mediate target cell lysis. The synergy in cytotoxicity obtained with the combination of DTX and TNF-alpha was examined in order to determine the pathway mediated by DTX in synergy. Like the direct lysis by DTX, synergy was significantly reduced by MeSAdo and by nicotinamide. Furthermore, synergy was not observed with combination of CRM 197 and TNF-alpha. These results demonstrate that, in synergy, DTX may utilize the same pathway required for its cytolytic activity. Pseudomonas aeruginosa exotoxin shared most the properties shown for DTX. Altogether, these findings

  7. Primary cardiac tumors associated with genetic syndromes. A comprehensive review

    International Nuclear Information System (INIS)

    Lee, Elizabeth; Agarwal, Prachi P.; Mahani, Maryam Ghadimi; Lu, Jimmy C.; Dorfman, Adam L.; Srinivasan, Ashok

    2018-01-01

    Various cardiac tumors occur in the setting of a genetic syndrome such as myxomas in Carney complex and rhabdomyomas in tuberous sclerosis. Tumor biology can be different in syndromic forms, and on imaging children sometimes demonstrate additional manifestations of the underlying syndrome. We discuss the imaging appearance of cardiac tumors occurring in the framework of a genetic syndrome, the findings that suggest an underlying syndrome, and the impact on management. (orig.)

  8. Primary cardiac tumors associated with genetic syndromes. A comprehensive review

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Elizabeth; Agarwal, Prachi P. [University of Michigan Health System, University Hospital Division of Cardiothoracic Radiology, Department of Radiology, Ann Arbor, MI (United States); Mahani, Maryam Ghadimi [University of Michigan Health System, University Hospital Division of Cardiothoracic Radiology, Department of Radiology, Ann Arbor, MI (United States); University of Michigan Health System, Section of Pediatric Radiology, C.S. Mott Children' s Hospital, Department of Radiology, Ann Arbor, MI (United States); Lu, Jimmy C.; Dorfman, Adam L. [University of Michigan Health System, Section of Pediatric Radiology, C.S. Mott Children' s Hospital, Department of Radiology, Ann Arbor, MI (United States); C.S. Mott Children' s Hospital, University of Michigan Health System, Section of Pediatric Cardiology, Department of Pediatrics, Ann Arbor, MI (United States); Srinivasan, Ashok [University of Michigan Health System, Division of Neuroradiology, Department of Radiology, Ann Arbor, MI (United States)

    2018-02-15

    Various cardiac tumors occur in the setting of a genetic syndrome such as myxomas in Carney complex and rhabdomyomas in tuberous sclerosis. Tumor biology can be different in syndromic forms, and on imaging children sometimes demonstrate additional manifestations of the underlying syndrome. We discuss the imaging appearance of cardiac tumors occurring in the framework of a genetic syndrome, the findings that suggest an underlying syndrome, and the impact on management. (orig.)

  9. Comparison of lysis-centrifugation with lysis-filtration and a conventional unvented bottle for blood cultures.

    OpenAIRE

    Gill, V J; Zierdt, C H; Wu, T C; Stock, F; Pizzo, P A; MacLowry, J D

    1984-01-01

    Evaluation of a commercially available lysis-centrifugation blood culture system (Isolator, DuPont Co., Wilmington, Del.) and a lysis-filtration blood culture system for 3,111 cultures showed that both methods had comparable recoveries (73 and 68%, respectively) of significant aerobic and facultatively anaerobic isolates. The unvented conventional blood culture bottle had a recovery rate of 59%. Although the lysis-centrifugation and lysis-filtration systems had comparable recoveries of pathog...

  10. Cowden Syndrome and Concomitant Pulmonary Neuroendocrine Tumor

    DEFF Research Database (Denmark)

    Langer, Seppo W; Ringholm, Lene; Dali, Christine I

    2015-01-01

    Cowden Syndrome is a rare autosomal dominantly inherited disorder. Patients with Cowden Syndrome are at increased risk of various benign and malignant neoplasms in breast, endometrium, thyroid, gastrointestinal tract, and genitourinary system. Neuroendocrine tumors are ubiquitous neoplasms that may...

  11. Management of Pediatric Tumor Lysis Syndrome

    African Journals Online (AJOL)

    Urate oxidase in prevention and treatment of hyperuricemia associated with lymphoid malignancies. Leukemia. 1997. Nov;11(11):1813-6. 43. Elitek [package insert]. Bridgewater, NJ: Sanofi-. Aventis US LLC; 2009. 44. Pui CH, Mahmoud HH, Wiley JM, Woods GM,. Leverger G, Camitta B, Hastings C, Blaney SM, Relling.

  12. Stretching single fibrin fibers hampers their lysis.

    Science.gov (United States)

    Li, Wei; Lucioni, Tomas; Li, Rongzhong; Bonin, Keith; Cho, Samuel S; Guthold, Martin

    2017-09-15

    Blood clots, whose main structural component is a mesh of microscopic fibrin fibers, experience mechanical strain from blood flow, clot retraction and interactions with platelets and other cells. We developed a transparent, striated and highly stretchable substrate made from fugitive glue (a styrenic block copolymer) to investigate how mechanical strain affects lysis of single, suspended fibrin fibers. In this suspended fiber assay, lysis manifested itself by fiber elongation, thickening (disassembly), fraying and collapse. Stretching single fibrin fibers significantly hampered their lysis. This effect was seen in uncrosslinked and crosslinked fibers. Crosslinking (without stretching) also hampered single fiber lysis. Our data suggest that strain is a novel mechanosensitive factor that regulates blood clot dissolution (fibrinolysis) at the single fiber level. At the molecular level of single fibrin molecules, strain may distort, or hinder access to, plasmin cleavage sites and thereby hamper lysis. Fibrin fibers are the major structural component of a blood clot. We developed a highly stretchable substrate made from fugitive glue and a suspended fibrin fiber lysis assay to investigate the effect of stretching on single fibrin fibers lysis. The key findings from our experiments are: 1) Fibers thicken and elongate upon lysis; 2) stretching strongly reduces lysis; 3) this effect is more pronounced for uncrosslinked fibers; and 4) stretching fibers has a similar effect on reducing lysis as crosslinking fibers. At the molecular level, strain may distort plasmin cleavage sites, or restrict access to those sites. Our results suggest that strain may be a novel mechanobiological factor that regulates fibrinolysis. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  13. Factors influencing lysis time stochasticity in bacteriophage λ

    Directory of Open Access Journals (Sweden)

    Dennehy John J

    2011-08-01

    Full Text Available Abstract Background Despite identical genotypes and seemingly uniform environments, stochastic gene expression and other dynamic intracellular processes can produce considerable phenotypic diversity within clonal microbes. One trait that provides a good model to explore the molecular basis of stochastic variation is the timing of host lysis by bacteriophage (phage. Results Individual lysis events of thermally-inducible λ lysogens were observed using a temperature-controlled perfusion chamber mounted on an inverted microscope. Both mean lysis time (MLT and its associated standard deviation (SD were estimated. Using the SD as a measure of lysis time stochasticity, we showed that lysogenic cells in controlled environments varied widely in lysis times, and that the level of lysis time stochasticity depended on allelic variation in the holin sequence, late promoter (pR' activity, and host growth rate. In general, the MLT was positively correlated with the SD. Both lower pR' activities and lower host growth rates resulted in larger SDs. Results from premature lysis, induced by adding KCN at different time points after lysogen induction, showed a negative correlation between the timing of KCN addition and lysis time stochasticity. Conclusions Taken together with results published by others, we conclude that a large fraction of λ lysis time stochasticity is the result of random events following the expression and diffusion of the holin protein. Consequently, factors influencing the timing of reaching critical holin concentrations in the cell membrane, such as holin production rate, strongly influence the mean lysis time and the lysis time stochasticity.

  14. Benign and malignant tumors in Rubinstein-Taybi syndrome

    NARCIS (Netherlands)

    Boot, Max V.; van Belzen, Martine J.; Overbeek, Lucy I.; Hijmering, Nathalie; Mendeville, Matias; Waisfisz, Quinten; Wesseling, Pieter; Hennekam, Raoul C.; de Jong, Daphne

    2018-01-01

    Rubinstein-Taybi syndrome (RSTS) is a multiple congenital anomalies syndrome associated with mutations in CREBBP (70%) and EP300 (5-10%). Previous reports have suggested an increased incidence of specific benign and possibly also malignant tumors. We identified all known individuals diagnosed with

  15. Adrenocortical carcinoma, an unusual extracolonic tumor associated with Lynch II syndrome.

    Science.gov (United States)

    Medina-Arana, V; Delgado, L; González, L; Bravo, A; Díaz, H; Salido, E; Riverol, D; González-Aguilera, J J; Fernández-Peralta, A M

    2011-06-01

    Lynch syndrome (LS) is an autosomal dominant condition that predisposes to colorectal cancer and specific other tumors. Extracolonic tumors occur mainly in the endometrium, stomach, ovary, small intestine and urinary tract. The presence of rare tumors in patients belonging to families who have Lynch syndrome is always interesting, because the question arises whether these tumors should be considered as a coincidence or are related with the syndrome. In this last case, they are also the result of the defect in the mismatch repair system, opening the possibility of extending the tumor spectrum associated with the syndrome. Here we describe a patient from a Lynch syndrome family with a germline mutation c.2063T>G (p.M688R) in the MSH2 gene, who developed an adrenal cortical carcinoma, a tumor not usually associated with LS. We analyzed the adrenocortical tumour for microsatellite instability (MSI), LOH and the presence of the germline c.2063T>G (M688R) mutation. The adrenal cortical carcinoma showed the MSH2 mutation, loss of heterozygosity of the normal allele in the MSH2 gene and loss of immunohistochemical expression for MSH2 protein, but no microsatellite instability. Additionally, the adrenal cortical carcinoma did not harbour a TP53 mutation. The molecular study indicates that this adrenal cortical cancer is probably due to the mismatch repair defect.

  16. Multifocal tenosynovial giant cell tumors in a child with Noonan syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Meyers, Arthur B. [Children' s Hospital of Wisconsin, Department of Radiology, Milwaukee, WI (United States); Nemours Children' s Health System/Nemours Children' s Hospital, Department of Radiology, Orlando, FL (United States); Awomolo, Agboola O. [Children' s Hospital of Wisconsin, Department of Radiology, Milwaukee, WI (United States); Szabo, Sara [Medical College of Wisconsin and Children' s Hospital of Wisconsin, Department of Pathology, Milwaukee, WI (United States); Cincinnati Children' s Hospital Medical Center, Division of Pathology and Laboratory Medicine, Cincinnati, OH (United States)

    2017-03-15

    Noonan syndrome is a genetic disorder with variable expression of distinctive facial features, webbed neck, chest deformity, short stature, cryptorchidism and congenital heart disease. The association of Noonan syndrome and giant cell granulomas of the mandible is widely reported. However, Noonan syndrome may also be associated with single or multifocal tenosynovial giant cell tumors, also referred to as pigmented villonodular synovitis. We report a child with Noonan syndrome, giant cell granulomas of the mandible and synovial and tenosynovial giant cell tumors involving multiple joints and tendon sheaths who was initially misdiagnosed with juvenile idiopathic arthritis. It is important for radiologists to be aware of the association of Noonan syndrome and multifocal giant cell lesions, which can range from the more commonly described giant cell granulomas of the mandible to isolated or multifocal intra- or extra-articular tenosynovial giant cell tumors or a combination of all of these lesions. (orig.)

  17. Multifocal tenosynovial giant cell tumors in a child with Noonan syndrome.

    Science.gov (United States)

    Meyers, Arthur B; Awomolo, Agboola O; Szabo, Sara

    2017-03-01

    Noonan syndrome is a genetic disorder with variable expression of distinctive facial features, webbed neck, chest deformity, short stature, cryptorchidism and congenital heart disease. The association of Noonan syndrome and giant cell granulomas of the mandible is widely reported. However, Noonan syndrome may also be associated with single or multifocal tenosynovial giant cell tumors, also referred to as pigmented villonodular synovitis. We report a child with Noonan syndrome, giant cell granulomas of the mandible and synovial and tenosynovial giant cell tumors involving multiple joints and tendon sheaths who was initially misdiagnosed with juvenile idiopathic arthritis. It is important for radiologists to be aware of the association of Noonan syndrome and multifocal giant cell lesions, which can range from the more commonly described giant cell granulomas of the mandible to isolated or multifocal intra- or extra-articular tenosynovial giant cell tumors or a combination of all of these lesions.

  18. Multifocal tenosynovial giant cell tumors in a child with Noonan syndrome

    International Nuclear Information System (INIS)

    Meyers, Arthur B.; Awomolo, Agboola O.; Szabo, Sara

    2017-01-01

    Noonan syndrome is a genetic disorder with variable expression of distinctive facial features, webbed neck, chest deformity, short stature, cryptorchidism and congenital heart disease. The association of Noonan syndrome and giant cell granulomas of the mandible is widely reported. However, Noonan syndrome may also be associated with single or multifocal tenosynovial giant cell tumors, also referred to as pigmented villonodular synovitis. We report a child with Noonan syndrome, giant cell granulomas of the mandible and synovial and tenosynovial giant cell tumors involving multiple joints and tendon sheaths who was initially misdiagnosed with juvenile idiopathic arthritis. It is important for radiologists to be aware of the association of Noonan syndrome and multifocal giant cell lesions, which can range from the more commonly described giant cell granulomas of the mandible to isolated or multifocal intra- or extra-articular tenosynovial giant cell tumors or a combination of all of these lesions. (orig.)

  19. Synthesis and functioning of the colicin E1 lysis protein: Comparison with the colicin A lysis protein

    International Nuclear Information System (INIS)

    Cavard, D.

    1991-01-01

    The colicin E1 lysis protein, CelA, was identified as a 3-kDa protein in induced cells of Escherichia coli K-12 carrying pColE1 by pulse-chase labeling with either [ 35 S]cysteine or [ 3 H]lysine. This 3-kDa protein was acylated, as shown by [2- 3 H]glycerol labeling, and seemed to correspond to the mature CelA protein. The rate of modification and processing of CelA was different from that observed for Cal, the colicin A lysis protein. In contrast to Cal, no intermediate form was detected for CelA, no signal peptide accumulated, and no modified precursor form was observed after globomycin treatment. Thus, the rate of synthesis would not be specific to lysis proteins. Solubilization in sodium dodecyl sulfate of the mature forms of both CelA and Cal varied similarly at the time of colicin release, indicating a change in lysis protein structure. This particular property would play a role in the mechanism of colicin export. The accumulation of the signal peptide seems to be a factor determining the toxicity of the lysis proteins since CelA provoked less cell damage than Cal. Quasi-lysis and killing due to CelA were higher in degP mutants than in wild-type cells. They were minimal in pldA mutants

  20. Surveillance Recommendations for Children with Overgrowth Syndromes and Predisposition to Wilms Tumors and Hepatoblastoma

    NARCIS (Netherlands)

    Kalish, Jennifer M.; Doros, Leslie; Helman, Lee J.; Hennekam, Raoul C.; Kuiper, Roland P.; Maas, Saskia M.; Maher, Eamonn R.; Nichols, Kim E.; Plon, Sharon E.; Porter, Christopher C.; Rednam, Surya; Schultz, Kris Ann P.; States, Lisa J.; Tomlinson, Gail E.; Zelley, Kristin; Druley, Todd E.

    2017-01-01

    A number of genetic syndromes have been linked to increased risk for Wilms tumor (WT), hepatoblastoma (HB), and other embryonal tumors. Here, we outline these rare syndromes with at least a 1% risk to develop these tumors and recommend uniform tumor screening recommendations for North America.

  1. Genetics of Beckwith-Wiedemann syndrome-associated tumors: common genetic pathways

    NARCIS (Netherlands)

    Steenman, M.; Westerveld, A.; Mannens, M.

    2000-01-01

    A specific subset of solid childhood tumors-Wilms' tumor, adrenocortical carcinoma, rhabdomyosarcoma, and hepatoblastoma-is characterized by its association with Beckwith-Wiedemann syndrome. Genetic abnormalities found in these tumors affect the same chromosome region (11p15), which has been

  2. A Giant Heart Tumor in Neonate with Clinical Signs of Pierre - Robin Syndrome

    Science.gov (United States)

    Bejiqi, Ramush; Retkoceri, Ragip; Xhema-Bejiqi, Hana; Bejiqi, Rinor; Maloku, Arlinda

    2017-01-01

    Introduction: Pierre Robin syndrome is a congenital condition of facial abnormalities in humans. The three main features are: cleft palate, retrognathia and glossoptosis. Rarely heart tumors are associated with syndromes, mostly are isolated. Case report: In this presentation we describe a 3-weeks-old girl with Pierre-Robin syndrome and giant left ventricle tumor, diagnosed initially by transthoracic echocardiography. The purpose of this report is to review the literature on the fetuses and neonates with cardiac tumors in an attempt to determine the various ways which cardiac tumors differ clinically and morphologically in this age group. PMID:28790548

  3. Intraabdominal Compartment Syndrome Complicating Transurethral Resection of Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Sachin Narain

    2012-01-01

    Full Text Available Abdominal compartment syndrome can result from many different causes. We present a case where this dangerous syndrome occurred in the operating room during a transurethral resection of a bladder tumor. It was initially recognized by an elevation in the peak inspiratory pressure. We report the typical physiologic changes that occur with this syndrome and its treatment options.

  4. [Pseudomeigs syndrome in a patient with Krukenberg's tumor].

    Science.gov (United States)

    Bayod, M J Herráiz; Carlón, M Elorz; Idoate, M A

    2007-01-01

    We report the case of a fiftyone-year-old woman with a past medical history of Linfoma no Hodking and a gastric adenocarcinoma with signet ring cells. She came to our institution with a twenty month history of dysnea secondary to pleural effussion, bilateral lower extremity edema and probably had ascitis. On CT and US two bilateral pelvic masses were found and biopsied. The anatomopathological analysis showed bilateral ovarian implants from signet ring cell adenocarcinoma (Krukenberg tumor). This patient developed a PseudoMeigs syndrome consisting on malignant ovarian tumor asociated with ascitis and pleural effusion without malignant cells. Oncological patients who present with ascitis and benign pleural effusion, the diagnosis of PseudoMeigs syndrome should be considered.

  5. SHOCK SYNDROME IN A PATIENT WITH HYPOPITUITARISM DUE TO BRAIN TUMOR

    Directory of Open Access Journals (Sweden)

    Andreja Sinkovič

    2004-04-01

    Full Text Available Background. Shock syndrome is an acute tissue hypoperfusion. Early diagnosis and adequate symptomatic and causal treatment are mandatory. In spite of different etiologies (dehidration, bleeding, heart failure, sepsis, clinical signs and symptomes are similar (hypotension, tachicardia, tachipnoe, pallor, cold and wet skin, oliguria and metabolic acidosis. Rarely, the shock syndrome is the consequence of the adrenal insufficiency due to hypopituitarism caused by brain tumor where early treatment with hydrocortisone is urgent.Methods. This article presents a patient with a shock syndrome and multiorgan failure. Endocrinological testing and brain CT demonstrated an endocrinologically inactive tumor of hypophysis. The tumor was growing into adjacent hypophyseal tissue and causing hypopituitarism with secondary hypothyroidism and adrenal insufficiency and deficit of both gonadotropins and growth hormone.Conclusions. Primary or secondary adrenal insufficiency are among rare causes of shock syndrome. Whenever it is suspected, estimation of serum levels of cortisol and ACTH is necessary and immediate treatment with hydrocortisone should be instituted.

  6. Solubilization of proteins: the importance of lysis buffer choice.

    Science.gov (United States)

    Peach, Mandy; Marsh, Noelle; Miskiewicz, Ewa I; MacPhee, Daniel J

    2015-01-01

    The efficient extraction of proteins of interest from cells and tissues is not always straightforward. Here we demonstrate the differences in extraction of the focal adhesion protein Kindlin-2 from choriocarcinoma cells using NP-40 and RIPA lysis buffer. Furthermore, we demonstrate the use of a more denaturing urea/thiourea lysis buffer for solubilization, by comparing its effectiveness for solubilization of small heat-shock proteins from smooth muscle with the often utilized RIPA lysis buffer. Overall, the results demonstrate the importance of establishing the optimal lysis buffer for specific protein solubilization within the experimental workflow.

  7. Hyperparathyroidism-jaw Tumor Syndrome: An Overlooked Cause of Severe Hypercalcemia.

    Science.gov (United States)

    Mathews, Joseph Wolfgang; Winchester, Rhonda; Alsaygh, Nebras; Bartlett, Anne M; Luttrell, Louis

    2016-09-01

    Ossifying fibromas of the maxillofacial bones are an uncommon form of benign neoplasm usually treated by surgical excision. Up to 30% of patients with hyperparathyroidism-jaw tumor syndrome, a rare form of multiple endocrine neoplasia resulting from autosomal dominant inactivating mutation of the Hrpt2 tumor suppressor gene, initially present with ossifying fibromas. Coincident hypercalcemia because of the presence of parathyroid adenoma is common in these patients, of whom 15% may have or may develop parathyroid carcinoma. The authors present a case of severe postsurgical hypercalcemia after removal of a large maxillary ossifying fibroma in a patient with previously unrecognized hyperparathyroidism-jaw tumor AU3 syndrome. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  8. A Giant Heart Tumor in Neonate with Clinical Signs of Pierre - Robin Syndrome

    OpenAIRE

    Bejiqi, Ramush; Retkoceri, Ragip; Xhema-Bejiqi, Hana; Bejiqi, Rinor; Maloku, Arlinda

    2017-01-01

    Introduction: Pierre Robin syndrome is a congenital condition of facial abnormalities in humans. The three main features are: cleft palate, retrognathia and glossoptosis. Rarely heart tumors are associated with syndromes, mostly are isolated. Case report: In this presentation we describe a 3-weeks-old girl with Pierre-Robin syndrome and giant left ventricle tumor, diagnosed initially by transthoracic echocardiography. The purpose of this report is to review the literature on the fetuses and n...

  9. Pressure-mediated reduction of ultrasonically induced cell lysis

    International Nuclear Information System (INIS)

    Ciaravino, V.E.; Miller, M.W.; Carstensen, E.L.

    1981-01-01

    Chinese hamster V-79 cells, exposed in polystyrene tubes for 5 min to 1-MHz continuous-wave ultrasound, were lysed more by a 10 than a 5 W/cm 2 intensity. Higher atmospheric pressure was needed to eliminate lysis with the former relative to the latter intensity, but lysis by 10 W/cm 2 was completely climinated with 2 atm of hydrostatic pressure. The reduction in lysis per unit increase in atmospheric pressure was comparable for both ultrasound intensities

  10. Anti-PD-L1/TGFβR2 (M7824) fusion protein induces immunogenic modulation of human urothelial carcinoma cell lines, rendering them more susceptible to immune-mediated recognition and lysis.

    Science.gov (United States)

    Grenga, Italia; Donahue, Renee N; Gargulak, Morgan L; Lepone, Lauren M; Roselli, Mario; Bilusic, Marijo; Schlom, Jeffrey

    2018-03-01

    Avelumab has recently been approved by the Food and Drug Administration for the therapy of Merkel cell carcinoma and urothelial carcinoma. M7824 is a novel first-in-class bifunctional fusion protein comprising a monoclonal antibody against programmed death-ligand 1 (PD-L1, avelumab), fused to the extracellular domain of human transforming growth factor beta (TGFβ) receptor 2, which functions as a TGFβ "trap." Advanced urothelial tumors have been shown to express TGFβ, which possesses immunosuppressive properties that promote cancer progression and metastasis. The rationale for a combined molecule is to block the PD-1/PD-L1 interaction between tumor cells and immune cell infiltrate and simultaneously reduce or eliminate TGFβ from the tumor microenvironment. In this study, we explored the effect of M7824 on invasive urothelial carcinoma cell lines. Human urothelial (transitional cell) carcinoma cell lines HTB-4, HTB-1, and HTB-5 were treated with M7824, M7824mut (M7824 that is mutated in the anti-PD-L1 portion of the molecule and thus does not bind PD-L1), anti-PD-L1 (avelumab), or IgG1 isotype control monoclonal antibody, and were assessed for gene expression, cell-surface phenotype, and sensitivity to lysis by TRAIL, antigen-specific cytotoxic T lymphocytes and natural killer cells. M7824 retains the ability to mediate antibody-dependent cellular cytotoxicity of tumor cells, although in some cases to a lesser extent than anti-PD-L1. However, compared to anti-PD-L1, M7824 increases (A) gene expression of molecules involved in T-cell trafficking in the tumor (e.g., CXCL11), (B) TRAIL-mediated tumor cell lysis, and (C) antigen-specific CD8 + T-cell-mediated lysis of tumor cells. These studies demonstrate the immunomodulatory properties of M7824 on both tumor cell phenotype and immune-mediated lysis. Compared to anti-PD-L1 or M7824mut, M7824 induces immunogenic modulation of urothelial carcinoma cell lines, rendering them more susceptible to immune

  11. Lab-on-a-Disc Platform for Automated Chemical Cell Lysis

    Directory of Open Access Journals (Sweden)

    Moo-Jung Seo

    2018-02-01

    Full Text Available Chemical cell lysis is an interesting topic in the research to Lab-on-a-Disc (LOD platforms on account of its perfect compatibility with the centrifugal spin column format. However, standard procedures followed in chemical cell lysis require sophisticated non-contact temperature control as well as the use of pressure resistant valves. These requirements pose a significant challenge thereby making the automation of chemical cell lysis on an LOD extremely difficult to achieve. In this study, an LOD capable of performing fully automated chemical cell lysis is proposed, where a combination of chemical and thermal methods has been used. It comprises a sample inlet, phase change material sheet (PCMS-based temperature sensor, heating chamber, and pressure resistant valves. The PCMS melts and solidifies at a certain temperature and thus is capable of indicating whether the heating chamber has reached a specific temperature. Compared to conventional cell lysis systems, the proposed system offers advantages of reduced manual labor and a compact structure that can be readily integrated onto an LOD. Experiments using Salmonella typhimurium strains were conducted to confirm the performance of the proposed cell lysis system. The experimental results demonstrate that the proposed system has great potential in realizing chemical cell lysis on an LOD whilst achieving higher throughput in terms of purity and yield of DNA thereby providing a good alternative to conventional cell lysis systems.

  12. Lab-on-a-Disc Platform for Automated Chemical Cell Lysis.

    Science.gov (United States)

    Seo, Moo-Jung; Yoo, Jae-Chern

    2018-02-26

    Chemical cell lysis is an interesting topic in the research to Lab-on-a-Disc (LOD) platforms on account of its perfect compatibility with the centrifugal spin column format. However, standard procedures followed in chemical cell lysis require sophisticated non-contact temperature control as well as the use of pressure resistant valves. These requirements pose a significant challenge thereby making the automation of chemical cell lysis on an LOD extremely difficult to achieve. In this study, an LOD capable of performing fully automated chemical cell lysis is proposed, where a combination of chemical and thermal methods has been used. It comprises a sample inlet, phase change material sheet (PCMS)-based temperature sensor, heating chamber, and pressure resistant valves. The PCMS melts and solidifies at a certain temperature and thus is capable of indicating whether the heating chamber has reached a specific temperature. Compared to conventional cell lysis systems, the proposed system offers advantages of reduced manual labor and a compact structure that can be readily integrated onto an LOD. Experiments using Salmonella typhimurium strains were conducted to confirm the performance of the proposed cell lysis system. The experimental results demonstrate that the proposed system has great potential in realizing chemical cell lysis on an LOD whilst achieving higher throughput in terms of purity and yield of DNA thereby providing a good alternative to conventional cell lysis systems.

  13. Increased Resistance to osmotic lysis of sickled erythrocytes ...

    African Journals Online (AJOL)

    treated with CNw had significantly reduced osmotic lysis when compared with the untreated set (P<0.05, respectively) at various hypotonic NaCl concentrations. Various Hb genotypes exhibited a graded increase in osmotic pressure lysis in ...

  14. Radiofrequency thermal ablation of malignant hepatic tumors: post-ablation syndrome

    International Nuclear Information System (INIS)

    Choi, Jung Bin; Rhim, Hyunchul; Kim, Yongsoo; Koh, Byung Hee; Cho, On Koo; Seo, Heung Suk; Lee, Seung Ro

    2000-01-01

    To evaluate post-ablation syndrome after radiofrequency thermal ablation of malignant hepatic tumors. Forty-two patients with primary (n=3D29) or secondary (n=3D13) hepatic tumors underwent radiofrequency thermal ablation. A total of 65 nodules ranging in size from 1.1 to 5.0 (mean, 3.1) cm were treated percutaneously using a 50W RF generator with 15G expandable needle electrodes. We retrospectively evaluated the spectrum of post-ablation syndrome including pain, fever (≥3D 38 deg C), nausea, vomiting, right shoulder pain, and chest discomfort according to frequency, intensity and duration, and the findings were correlated with tumor location and number of ablations. We also evaluated changes in pre-/post-ablation serum aminotransferase (ALT/AST) and prothrombin time, and correlated these findings with the number of ablations. Post-ablation syndrome was noted in 29 of 42 patients (69.0%), and most symptoms improved with conservative treatment. The most important of these were abdominal plan (n=3D20, 47.6%), fever (n=3D8, 19.0%), and nausea (n=3D7, 16.7%), and four of 42 (9.5%) patients complained of severe pain. The abdominal pain lasted from 3 hours to 5.5 days (mean; 20.4 hours), the fever from 6 hours to 5 days (mean; 63.0 hours). And the nausea from 1 hours to 4 days (mean; 21.0 hours). Other symptoms were right shoulder pain (n=3D6, 14.3%), chest discomfort (n=3D3, 7.1%), and headache (n=3D3, 7.1%). Seventeen of 20 patients (85%) with abdominal pain had subcapsular tumor of the liver. There was significant correlation between pain, location of the tumor, and a number of ablations. After ablation, ALT/AST was elevated more than two-fold in 52.6%/73.7% of patients, respectively but there was no significant correlation with the number of ablation. Post-ablation syndrome is a frequent and tolerable post-procedural process after radiofrequency thermal ablation. The spectrum of this syndrome provides a useful guideline for the post-ablation management. (author)

  15. Chemical Cell Lysis System Applicable to Lab-on-a-Disc.

    Science.gov (United States)

    Lim, Dayeseul; Yoo, Jae Chern

    2017-09-01

    The design and fabrication of a heating system has been a significant challenge in implementing chemical lysis on a lab-on-a-disc (LOD). The proposed system contains a sample inlet, phase change material (PCM) array, heating chamber, and valve in a single disc, providing cost-effective, rapid, and fully automated chemical cell lysis. Compared to the conventional cell lysis system, our cell lysis system has many advantages, such as a compact structure that is easily integrated into the LOD and reduced processing time and labor. The experiments are conducted with Salmonella typhimurium strains to demonstrate the performance. The experimental results show that the proposed approach is greatly effective in realizing a chemical cell lysis system on an LOD with higher throughput in terms of purity and yield of DNA.

  16. Urea enhances cell lysis of Schizosaccharomyces pombe ura4 mutants.

    Science.gov (United States)

    Nishino, Kohei; Kushima, Misaki; Kaino, Tomohiro; Matsuo, Yasuhiro; Kawamukai, Makoto

    2017-07-01

    Cell lysis is induced in Schizosaccharomyces pombe ∆ura4 cells grown in YPD medium, which contains yeast extract, polypeptone, and glucose. To identify the medium components that induce cell lysis, we first tested various kinds of yeast extracts from different suppliers. Cell lysis of ∆ura4 cells on YE medium was observed when yeast extracts from OXOID, BD, Oriental, and Difco were used, but not when using yeast extract from Kyokuto. To determine which compounds induced cell lysis, we subjected yeast extract and polypeptone to GC-MS analysis. Ten kinds of compounds were detected in OXOID and BD yeast extracts, but not in Kyokuto yeast extract. Among them was urea, which was also present in polypeptone, and it clearly induced cell lysis. Deletion of the ure2 gene, which is responsible for utilizing urea, abolished the lytic effect of urea. The effect of urea was suppressed by deletion of pub1, and a similar phenotype was observed in the presence of polypeptone. Thus, urea is an inducer of cell lysis in S. pombe ∆ura4 cells.

  17. Emerging role of rasburicase in the management of increased plasma uric acid levels in patients with hematologic malignancies

    Directory of Open Access Journals (Sweden)

    LeAnne D Kennedy

    2011-02-01

    Full Text Available LeAnne D Kennedy1 Susannah Koontz2 Kamakshi Rao31Wake Forest University Baptist Medical Center, Winston Salem, NC, USA; 2Koontz Oncology Consulting LLC, Houston, TX, USA; 3UNC Hospitals, Chapel Hill, NC, USAAbstract: Tumor lysis syndrome (TLS is defined as a group of metabolic derangements that result from the massive and abrupt release of cellular components into the bloodstream after rapid lysis of tumor cells. Breakdown of released materials leads to a number of electrolyte abnormalities, including elevated uric acid concentrations in the blood (hyperuricemia, which carries potentially serious consequences. The diagnosis, prevention, and management of TLS is complicated by variability in definitions, differences in risk factors based on patient- and tumor-specific characteristics, and practitioner preferences in terms of pharmaceutical management strategies. The best prevention and management option for a particular patient depends on the patient’s baseline risk for TLS development, the severity of symptoms in the event of TLS development, practical management considerations, and financial implications of treatment.Keywords: tumor lysis syndrome, uric acid, rasburicase

  18. Giant Desmoid Tumor and Gardner Syndrome. Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Etcheverry MG

    2016-06-01

    Full Text Available Gardner´s syndrome represents a variant of the genetic disorder called familial adenomatous polyposis (FAP. The inherited pattern is autosomal dominant, however 20-25% of cases may represent new mutations. It is characterized by colonic polyposis with extracolonic manifestations as gastro-duodenal polyposis, osteomas, dental abnormalities and desmoid tumors.We report a case of a 25 years old man with family history of multiple surgeries caused by desmoid tumors without personal history. He visited our hospital complaining of a large tumor in the abdominal wall, and during the preoperative studies we identified colonic and gastroduodenal polyposis. Tumor resection was performed with safety margins that included the entire abdominal wall with total colectomy, ileal-rectal anastomosis and abdominal wall replacement with a protection visceral mesh. Gardner´s syndrome is a rare entity that is important to identify when we have a patient presenting with a desmoid tumor as in this case. Its association with colonic polyposis with high risk of malignant change demand an early aggressive treatment that will determine the survival of the patient.

  19. Reagentless mechanical cell lysis by nanoscale barbs in microchannels for sample preparation.

    Science.gov (United States)

    Di Carlo, Dino; Jeong, Ki-Hun; Lee, Luke P

    2003-11-01

    A highly effective, reagentless, mechanical cell lysis device integrated in microfluidic channels is reported. Sample preparation, specifically cell lysis, is a critical element in 'lab-on-chip' applications. However, traditional methods of cell lysis require purification steps or complicated fabrication steps that a simple mechanical method of lysis may avoid. A simple and effective mechanical cell lysis system is designed, microfabricated, and characterized to quantify the efficiency of cell lysis and biomolecule accessibility. The device functionality is based on a microfluidic filter region with nanostructured barbs created using a modified deep reactive ion etching process. Mechanical lysis is characterized by using a membrane impermeable dye. Three main mechanisms of micro-mechanical lysis are described. Quantitative measurements of accessible protein as compared to a chemically lysed sample are acquired with optical absorption measurements at 280 and 414 nm. At a flow rate of 300 microL min(-1) within the filter region total protein and hemoglobin accessibilities of 4.8% and 7.5% are observed respectively as compared to 1.9% and 3.2% for a filter without nanostructured barbs.

  20. 21 CFR 864.7275 - Euglobulin lysis time tests.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Euglobulin lysis time tests. 864.7275 Section 864.7275 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7275 Euglobulin lysis...

  1. MUC16 provides immune protection by inhibiting synapse formation between NK and ovarian tumor cells

    Directory of Open Access Journals (Sweden)

    Migneault Martine

    2010-01-01

    Full Text Available Abstract Background Cancer cells utilize a variety of mechanisms to evade immune detection and attack. Effective immune detection largely relies on the formation of an immune synapse which requires close contact between immune cells and their targets. Here, we show that MUC16, a heavily glycosylated 3-5 million Da mucin expressed on the surface of ovarian tumor cells, inhibits the formation of immune synapses between NK cells and ovarian tumor targets. Our results indicate that MUC16-mediated inhibition of immune synapse formation is an effective mechanism employed by ovarian tumors to evade immune recognition. Results Expression of low levels of MUC16 strongly correlated with an increased number of conjugates and activating immune synapses between ovarian tumor cells and primary naïve NK cells. MUC16-knockdown ovarian tumor cells were more susceptible to lysis by primary NK cells than MUC16 expressing controls. This increased lysis was not due to differences in the expression levels of the ligands for the activating receptors DNAM-1 and NKG2D. The NK cell leukemia cell line (NKL, which does not express KIRs but are positive for DNAM-1 and NKG2D, also conjugated and lysed MUC16-knockdown cells more efficiently than MUC16 expressing controls. Tumor cells that survived the NKL challenge expressed higher levels of MUC16 indicating selective lysis of MUC16low targets. The higher csMUC16 levels on the NKL resistant tumor cells correlated with more protection from lysis as compared to target cells that were never exposed to the effectors. Conclusion MUC16, a carrier of the tumor marker CA125, has previously been shown to facilitate ovarian tumor metastasis and inhibits NK cell mediated lysis of tumor targets. Our data now demonstrates that MUC16 expressing ovarian cancer cells are protected from recognition by NK cells. The immune protection provided by MUC16 may lead to selective survival of ovarian cancer cells that are more efficient in

  2. [Imaging manifestations and pathologic basis for hepatic capsular retraction syndrome caused by benign and malignant liver tumors].

    Science.gov (United States)

    Ou, Youkuan; Xiao, Enhua; Shang, Quanliang; Chen, Juan

    2015-10-01

    To investigate the imaging manifestations of CT, MRI and pathological basis for hepatic capsular retraction syndrome caused by benign and malignant liver tumors.
 CT or MRI images and pathological features for hepatic capsular retraction syndrome were retrospectively analyzed in 50 patients with benign and malignant liver tumors. Picture archive and communication system (PACS) was used to observe and compare the morphology, size, width, depth, edge of the capsular retraction and the status of liquid under the liver capsule. The structure, differentiation and proliferation of the tumor were analyzed under the microscope.
 There were malignant liver tumors in 44 patients and benign tumor in 6 patients. The smooth or rough for the edge of capsular retraction was significant difference between the benign tumors and the malignant tumors with three differentiated grades (all PBenign and malignant hepatic tumors may appear capsule retraction syndrome, but there are morphological differences between them. The differences are closely related with the lesion size, differentiated degree of tumor and fibrous tissue proliferation.

  3. Radiation-induced enhancement of enzymatic cell lysis of Micrococcus radiodurans

    International Nuclear Information System (INIS)

    Watanabe, H.; Takehisa, M.; Iizuka, H.

    1981-01-01

    The intact cells of M. radiodurans were rendered sensitive to the action of lytic enzyme (P2-2 enzyme) by irradiation. The radiation-induced enhancement of cell lysis with P2-2 enzyme was completely prevented by the addition of t-butanol and irradiation at liquid nitrogen temperature. These results indicate that the enhancement is due to indirect action resulting from OH radicals. Cell lysis by lysozyme was enhanced only when the cells were irradiated under N 2 O. The enhancement of cell lysis with lysozyme was also prevented by adding alcohols. On the other hand, when lipid components in cells were removed by extraction with n-butanol, the radiation-induced enhancement of cell lysis with P2-2 enzyme and lysozyme was not observed. From these results it is concluded that the enhancement of enzymatic cell lysis by irradiation is attributable to alteration in the lipid-rich layer of the cell wall caused by OH radicals

  4. Radiation-induced enhancement of enzymatic cell lysis of Micrococcus radiodurans

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, H.; Takehisa, M. [Japan Atomic Energy Research Inst., Takasaki, Gunma, Takasaki Radiation Chemistry Research Establishment (Japan); Iizuka, H.

    1981-10-15

    The intact cells of M. radiodurans were rendered sensitive to the action of lytic enzyme (P2-2 enzyme) by irradiation. The radiation-induced enhancement of cell lysis with P2-2 enzyme was completely prevented by the addition of t-butanol and irradiation at liquid nitrogen temperature. These results indicate that the enhancement is due to indirect action resulting from OH radicals. Cell lysis by lysozyme was enhanced only when the cells were irradiated under N{sub 2}O. The enhancement of cell lysis with lysozyme was also prevented by adding alcohols. On the other hand, when lipid components in cells were removed by extraction with n-butanol, the radiation-induced enhancement of cell lysis with P2-2 enzyme and lysozyme was not observed. From these results it is concluded that the enhancement of enzymatic cell lysis by irradiation is attributable to alteration in the lipid-rich layer of the cell wall caused by OH radicals.

  5. Lysis from without

    Science.gov (United States)

    2011-01-01

    In this commentary I consider use of the term “lysis from without” (LO) along with the phenomenon's biological relevance. LO originally described an early bacterial lysis induced by high-multiplicity virion adsorption and that occurs without phage production (here indicated as LOV). Notably, this is more than just high phage multiplicities of adsorption leading to bacterial killing. The action on bacteria of exogenously supplied phage lysin, too, has been described as a form of LO (here, LOL). LOV has been somewhat worked out mechanistically for T4 phages, has been used to elucidate various phage-associated phenomena including discovery of the phage eclipse, may be relevant to phage ecology, and, with resistance to LO (LOR), is blocked by certain phage gene products. Speculation as to the impact of LOV on phage therapy also is fairly common. Since LOV assays are relatively easily performed and not all phages are able to induce LOV, a phage's potential to lyse bacteria without first infecting should be subject to at least in vitro experimental confirmation before the LOV label is applied. The term “abortive infection” may be used more generally to describe non-productive phage infections that kill bacteria. PMID:21687534

  6. Keratocystic odontogenic tumors related to Gorlin-Goltz syndrome: A clinicopathological study.

    Science.gov (United States)

    Khaliq, Mohammed Israr Ul; Shah, Ajaz A; Ahmad, Irshad; Hasan, Shahid; Jangam, Sagar S; Farah; Anwar

    2016-01-01

    Assess clinicopathological features of patients with keratocystic odontogenic tumor (KCOT) associated with Gorlin-Goltz syndrome in our institution from 2004 to 2015. After histopathological analyses of KCOT related to Gorlin-Goltz syndrome, 7 patients were assessed. These patients presented a total of 15 primary and 2 recurrent KCOT. All patients presented a multiple KCOT, and 13 lesions were located in mandible (77%) and 4 (23%) in maxilla. Most of the tumors presented a unilocular pattern (71%) and had tooth association (88%). Four patients (57%) were in the age group of 10-19 years and three patients (43%) were in the age group of 20-29 years. There were four male and three female patients. KCOT is a frequent manifestation of Gorlin-Goltz syndrome and can be its first sign, mainly in young patients. The four patients presented with two lesions (57%) and three lesions in three patients (43%).

  7. Imaging study of lymphoreticular tumor development in ataxia-telangiectasia and Nijmegen breakage syndrome

    International Nuclear Information System (INIS)

    Martinez-Leon, M. I.; Ceres-Ruiz, L.; Cuesta, M. A.; Garcia-Martin, F. J.

    2003-01-01

    Ataxia-telangiectasia (AT), or Louis-Bar syndrome, is an autosomal recessive illness characterized by progressive cerebellar ataxia, oculo-cutaneous telangiectasia, immunodeficiency combined with susceptibility to sinopulmonary infections and high incidence of neoplastic development. Nijmegen breakage syndrome (NBS) is a variant of AT, is also an autosomal recessive illness that presents cerebellar ataxia, as well as combined immunodeficiency and a tendency toward tumor development. Contrary to Louis-Bar syndrome, it doesn't present telangiectasia and exhibits a characteristics phenotype (short stature, bird-like face and microcephaly). Both entities are classified as syndrome of chromosomal instability or chromosomal fragility, a group which also includes Bloom syndrome and Fanconi anemia. All of these show an increase in the frequency of neoplastic pathologies, mainly lymphoid tumors. We present three patients,two with AT and one with NBS, who developed different lymphoma types in the course of the illness. We highlight the most outstanding aspects from a clinical-radiological point of view. (Author) 17 refs

  8. Metastatic neuroendocrine tumor with initial presentation of orbital apex syndrome

    Directory of Open Access Journals (Sweden)

    Yen-Yu Huang

    2017-03-01

    Full Text Available The possible etiologies of orbital apex syndrome range from inflammatory, infectious, neoplastic, iatrogenic/traumatic, to vascular processes. In patients without obvious infection or systemic cancer history, judicious use of corticosteroids is a reasonable strategy. We describe a 64-year-old man who presented with orbital apex syndrome and had progressed to total visual loss in three days after admission. Radiological imaging and pathological studies were consistent with a neuroendocrine tumor with multiple metastases. We recommend that a biopsy-proven specimen is warranted in patient with orbital apex syndrome even without a cancer history.

  9. A possible new syndrome with double endocrine tumors in association with an unprecedented type of familial heart-hand syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Yamagishi Masakazu

    2010-10-01

    Full Text Available Abstract Introduction The combination of a pituitary prolactinoma and an aldosterone-producing adrenal adenoma is extremely rare. To the best of our knowledge, double endocrine tumors in association with heart-hand syndrome have not previously been reported. Case presentation A 21-year-old Japanese woman presented with galactorrhea and decreased visual acuity. A large pituitary adenoma with an increased level of serum prolactin was apparent by computed tomography. She additionally showed mild hypertension (136/90 mmHg accompanied by hypokalemia. The plasma aldosterone concentration was increased. Computed tomography showed a mass in the right adrenal gland. No other tumors were found despite extensive imaging studies. Physical and radiographic examinations showed skeletal malformations of the hands and feet, including hypoplasia of the first digit in all four limbs. An atrial septal defect was demonstrated by echocardiography. Similar digital and cardiac abnormalities were detected in our patient's father, and a clinical diagnosis of hereditary heart-hand syndrome was made. Conclusion No established heart-hand syndrome was wholly compatible with the family's phenotype. Her father had no obvious endocrine tumors, implying that the parent of transmission determined variable phenotypic expression of the disease: heart-hand syndrome with multiple endocrine tumors from the paternal transmission or no endocrine tumor from the maternal transmission. This suggests that the gene or genes responsible for the disease may be under tissue-specific imprinting control.

  10. Giant cell tumor of distal phalanx in an adolescent with Goltz-Gorlin syndrome.

    Science.gov (United States)

    Borgers, A; Peters, S; Sciot, R; De Smet, L

    2014-01-01

    We report on a unique case of a young female patient with the Goltz-Gorlin syndrome who developed a giant cell tumor of bone in the distal phalanx of the thumb. This case is noteworthy because of the combination of some unusual features. Firstly, it is only the fifth case report on the association of giant cell tumor of bone and the Goltz-Gorlin syndrome. Also the localization of the lesion in the bones of the hand and the presentation at adolescent age is rarely seen.

  11. Microfluidic device for acoustic cell lysis

    Science.gov (United States)

    Branch, Darren W.; Cooley, Erika Jane; Smith, Gennifer Tanabe; James, Conrad D.; McClain, Jaime L.

    2015-08-04

    A microfluidic acoustic-based cell lysing device that can be integrated with on-chip nucleic acid extraction. Using a bulk acoustic wave (BAW) transducer array, acoustic waves can be coupled into microfluidic cartridges resulting in the lysis of cells contained therein by localized acoustic pressure. Cellular materials can then be extracted from the lysed cells. For example, nucleic acids can be extracted from the lysate using silica-based sol-gel filled microchannels, nucleic acid binding magnetic beads, or Nafion-coated electrodes. Integration of cell lysis and nucleic acid extraction on-chip enables a small, portable system that allows for rapid analysis in the field.

  12. Variable Potassium Concentrations: Which Is Right and Which Is Wrong?

    Science.gov (United States)

    Theparee, Talent; Benirschke, Robert C; Lee, Hong-Kee

    2017-05-01

    Reverse pseudohyperkalemia is a term used to describe in vitro, falsely elevated potassium concentrations in plasma specimens that occur in association with extreme leukocytosis and are commonly associated with hematologic malignant neoplasms. Tumor lysis syndrome is an in vivo lysis of tumor cells that leads to elevated levels of potassium, uric acid, phosphate, and lactate dehydrogenase, as well as decreased calcium concentrations. Herein, we report a case of a 66-year-old Caucasian man with stage IV mantle-cell lymphoma who has elevated levels of potassium, uric acid, and phosphorus, as well as a white blood cell (WBC) count greater than 100,000 cells per mm3. The patient initially was diagnosed as having tumor lysis syndrome. His subsequent potassium concentrations in whole blood remained elevated even after hemodialysis; however, his serum potassium concentrations were decreased. The patient then was diagnosed accurately as having reverse pseudohyperkalemia, and accurate potassium measurements were obtained via serum specimens. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Keratocystic odontogenic tumors related to Gorlin–Goltz syndrome: A clinicopathological study

    Science.gov (United States)

    Khaliq, Mohammed Israr Ul; Shah, Ajaz A.; Ahmad, Irshad; Hasan, Shahid; Jangam, Sagar S.; Farah; Anwar

    2015-01-01

    Background Assess clinicopathological features of patients with keratocystic odontogenic tumor (KCOT) associated with Gorlin–Goltz syndrome in our institution from 2004 to 2015. Method After histopathological analyses of KCOT related to Gorlin–Goltz syndrome, 7 patients were assessed. These patients presented a total of 15 primary and 2 recurrent KCOT. Results All patients presented a multiple KCOT, and 13 lesions were located in mandible (77%) and 4 (23%) in maxilla. Most of the tumors presented a unilocular pattern (71%) and had tooth association (88%). Four patients (57%) were in the age group of 10–19 years and three patients (43%) were in the age group of 20–29 years. There were four male and three female patients. Conclusion KCOT is a frequent manifestation of Gorlin–Goltz syndrome and can be its first sign, mainly in young patients. The four patients presented with two lesions (57%) and three lesions in three patients (43%). PMID:27195205

  14. Maintenance, endogeneous, respiration, lysis, decay and predation

    DEFF Research Database (Denmark)

    loosdrecht, Marc C. M. Van; Henze, Mogens

    1999-01-01

    mechanism is microbiologically correct. The lysis/decay model mechanism is a strongly simplified representation of reality. This paper tries to review the processes grouped under endogenous respiration in activated sludge models. Mechanisms and processes such as maintenance, lysis, internal and external...... decay, predation and death-regeneration are discussed. From recent microbial research it has become evident that cells do not die by themselves. Bacteria are however subject to predation by protozoa. Bacteria store reserve polymers that in absence of external substrate are used for growth...

  15. Micro Corona Ionizer as an Ozone Source for Bacterial Cell Lysis

    Science.gov (United States)

    Lee, Eun-Hee; Lim, Hyun Jeong; Chua, Beelee; Son, Ahjeong

    2015-04-01

    DNA extraction is a critical process of DNA assays including polymerase chain reaction (PCR), microarrays, molecular cloning, and DNA hybridization which has been well established and can be implemented by commercial kits. DNA extraction involves cell lysis, precipitation, and purification through the combination of physical and chemical processes. Cell lysis is essential to high DNA recovery yield which can be achieved via a variety of physical, chemical, and enzymatic methods. However, these methods were originally developed for bioassays that were labor intensive, time consuming, and vulnerable to contamination and inhibition. Here, we proposed to employ a micro corona ionizer as an ozone source to lyse bacterial cells. Ozone has been well known and used as a disinfectant which allows cell lysis and DNA extraction. Previously, we have shown that a micro corona ionizer is capable of generating a significant amount of ozone. In this study, we employed the micro corona ionizer for the bacterial cell lysis which consists of a 50 μm diameter cantilever wire as the discharge cathode and a 50 μm thick copper foil as anode. Applied voltages varied from 1900 to 2200 V with corresponding corona currents from 16 to 28 μA. The resultant ozone (concentration > 0.14 ppm) generated from the micro corona ionizer was bubbled into the sample via a miniature pump. We demonstrated the cell lysis of Pseudomonas putida as the target bacterium using the micro corona ionizer. At a flow rate of 38 ml/min and applied corona voltage of 2000 V, 98.5 ± 0.2% lysis (normalized to sonication result) was achieved after 10 min. In comparison, untreated and air-treated samples showed normalized % lysis of 11.9 ± 2.4 and 36.1 ± 1.7%, respectively. We also showed that the cell lysis efficiency could be significantly increased by increasing the flow rate and the applied corona voltage. By comparing the experimental results for continuous and pulsed treatment, we verified that the percentage of

  16. Patients with old age or proximal tumors benefit from metabolic syndrome in early stage gastric cancer.

    Directory of Open Access Journals (Sweden)

    Xiao-li Wei

    Full Text Available BACKGROUND: Metabolic syndrome and/or its components have been demonstrated to be risk factors for several cancers. They are also found to influence survival in breast, colon and prostate cancer, but the prognostic value of metabolic syndrome in gastric cancer has not been investigated. METHODS: Clinical data and pre-treatment information of metabolic syndrome of 587 patients diagnosed with early stage gastric cancer were retrospectively collected. The associations of metabolic syndrome and/or its components with clinical characteristics and overall survival in early stage gastric cancer were analyzed. RESULTS: Metabolic syndrome was identified to be associated with a higher tumor cell differentiation (P=0.036. Metabolic syndrome was also demonstrated to be a significant and independent predictor for better survival in patients aged >50 years old (P=0.009 in multivariate analysis or patients with proximal gastric cancer (P=0.047 in multivariate analysis. No association was found between single metabolic syndrome component and overall survival in early stage gastric cancer. In addition, patients with hypertension might have a trend of better survival through a good control of blood pressure (P=0.052 in univariate analysis. CONCLUSIONS: Metabolic syndrome was associated with a better tumor cell differentiation in patients with early stage gastric cancer. Moreover, metabolic syndrome was a significant and independent predictor for better survival in patients with old age or proximal tumors.

  17. Thrombin activatable fibrinolysis inhibitor and clot lysis time in pregnant patients with antiphospholipid syndrome: relationship with pregnancy outcome and thrombosis.

    Science.gov (United States)

    Martinez-Zamora, Maria Angeles; Tassies, Dolors; Carmona, Francisco; Espinosa, Gerard; Cervera, Ricard; Reverter, Juan Carlos; Balasch, Juan

    2009-12-01

    Antiphospholipid syndrome (APS) pregnancies are associated with thrombotic obstetric complications, despite treatment. This study evaluated Thrombin Activatable Fibrinolysis Inhibitor (TAFI) levels, TAFI gene polymorphisms and Clot Lysis Time (CLT) in pregnant patients with APS in relation to pregnancy outcome and thrombosis. Group 1 consisted of 67 pregnant patients with APS. Group 2 included 66 pregnant patients with uneventful term pregnancies and delivery. Patients were sampled during each trimester and at baseline. TAFI antigen and CLT and two polymorphisms of the TAFI gene, Ala147Thr and +1542C/G, were determined. Significantly prolonged CLT was found at baseline in Group 1. Allele distribution of the TAFI gene polymorphisms was similar in both groups. Basal TAFI and CLT in patients with APS having an adverse or a good obstetrical outcome were similar. Comparison of TAFI and CLT baseline levels in patients with APS with or without previous thrombosis showed no statistical differences. Patients with APS have impairment in fibrinolysis evidenced by prolonged CLT at baseline. TAFI and CLT do not seem to be useful as markers of obstetric outcome or risk of thrombosis in patients with APS.

  18. Renal tumor leading to acute respiratory distress syndrome – a rare ...

    African Journals Online (AJOL)

    Arun Kumar Agnihotri

    renal cell carcinoma (RCC). KEY WORDS: ARDS; Renal tumor; Adult respiratory distress syndrome. INTRODUCTIONᴪ. ARDS due to ... unable to maintain saturation in spite of high flow ... Blood investigations showed mild leukocytosis.

  19. Myofibroblastic tumor associated to superior vena cava syndrome

    International Nuclear Information System (INIS)

    Ortega Jaramillo, Hector; Durango Gutierrez, Luisa Fernanda; Perez Figueroa, Maria del Pilar

    2005-01-01

    Inflammatory myofibroblastic tumor (IMT) is an uncommon pathological entity of unknown cause, composed of differentiated myofibroblastic cells accompanied by plasma cells, lymphocytes and eosinophils, which involve extrapulmonary and pulmonary tissues. IMT has an unpredictable clinical course, rarely undergoes malignant transformation. Local invasion and involvement of the mediastinum and hiliar structures are unusual manifestations; however; we reports a case of superior vena cava syndrome and IMT

  20. Case report: long-term survival of an infant syndromic patient affected by atypical teratoid-rhabdoid tumor

    International Nuclear Information System (INIS)

    Modena, Piergiorgio; Maestro, Roberta; Giangaspero, Felice; Massimino, Maura; Sardi, Iacopo; Brenca, Monica; Giunti, Laura; Buccoliero, Anna Maria; Pollo, Bianca; Biassoni, Veronica; Genitori, Lorenzo; Antonelli, Manila

    2013-01-01

    Atypical teratoid rhabdoid tumor (ATRT) patients display a dismal median overall survival of less than 1 year. A consistent fraction of cases carries de-novo SMARCB1/INI1 constitutional mutations in the setting of the “rhabdoid tumor predisposition syndrome” and the outcome is worst in infant syndromic ATRT patients. We here describe a patient affected by mosaic Klinefelter syndrome and by rhabdoid tumor predisposition syndrome caused by constitutional SMARCB1/INI1 heterozygous mutation c.118C>T (Arg40X). Patient’s ATRT primary tumor occurred at 2 years of age concurrent with metastatic lesions. The patient was rendered without evidence of disease by combined surgery, high-dose poli-chemotherapy and craniospinal irradiation, followed by autologous hematopoietic stem cell transplantation. At the onset of a spinal lesion 5.5 years later, both tumors were pathologically and molecularly evaluated at the national central pathology review board and defined as ATRT in a syndromic patient, with strong evidence of a clonal origin of the two lesions. The patient was then treated according to SIOP guidelines and is now alive without evidence of disease 24 months after the detection of metastatic disease and 90 months after the original diagnosis. The report underscores the current utility of multiple comprehensive approaches for the correct diagnosis and clinical management of patients affected by rare and atypical brain neoplasms. Successful local control of disease and achievement of long-term survival is possible in ATRT patients even in the setting of rhabdoid tumor predisposition syndrome, infant age at diagnosis and metastatic spread of disease, thus justifying the efforts for the management of this severe condition

  1. Ovarian germ cell tumors with rhabdomyosarcomatous components and later development of growing teratoma syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Al-Jumaily Usama

    2012-01-01

    Full Text Available Abstract Introduction Development of a sarcomatous component in a germ cell tumor is an uncommon phenomenon. Most cases reported have a grim prognosis. Growing teratoma syndrome is also an uncommon phenomenon and occurs in approximately 2% to 7% of non seminomatous germ cell tumors and should be treated surgically. Case presentation We report the case of a 12-year-old Asian girl with an ovarian mixed germ cell tumor containing a rhabdomyosarcomatous component. She was treated with a germ cell tumor chemotherapy regimen and rhabdomyosarcoma-specific chemotherapy. Towards the end of her treatment, she developed a retroperitoneal mass that was increasing in size. It was completely resected, revealing a mature teratoma, consistent with growing teratoma syndrome. She is still in complete remission approximately three years after presentation. Conclusion The presence of rhabdomyosarcoma in a germ cell tumor should be treated by a combined chemotherapy regimen (for germ cell tumor and rhabdomyosarcoma. In addition, development of a mass during or after therapy with normal serum markers should raise the possibility of growing teratoma syndrome that should be treated surgically.

  2. Unusual association of non-anaplastic Wilms tumor and Cornelia de Lange syndrome: case report.

    Science.gov (United States)

    Santoro, Claudia; Apicella, Andrea; Casale, Fiorina; La Manna, Angela; Di Martino, Martina; Di Pinto, Daniela; Indolfi, Cristiana; Perrotta, Silverio

    2016-06-13

    Cornelia de Lange syndrome is the prototype for cohesinopathy disorders, which are characterized by defects in chromosome segregation. Kidney malformations, including nephrogenic rests, are common in Cornelia de Lange syndrome. Only one post-mortem case report has described an association between Wilms tumor and Cornelia de Lange syndrome. Here, we describe the first case of a living child with both diseases. Non-anaplastic triphasic nephroblastoma was diagnosed in a patient carrying a not yet reported mutation in NIPBL (c.4920 G > A). The patient had the typical facial appearance and intellectual disability associated with Cornelia de Lange syndrome in absence of limb involvement. The child's kidneys were examined by ultrasound at 2 years of age to exclude kidney abnormalities associated with the syndrome. She underwent pre-operative chemotherapy and nephrectomy. Seven months later she was healthy and without residual detectable disease. The previous report of such co-occurrence, together with our report and previous reports of nephrogenic rests, led us to wonder if there may be any causal relationship between these two rare entities. The wingless/integrated (Wnt) pathway, which is implicated in kidney development, is constitutively activated in approximately 15-20 % of all non-anaplastic Wilms tumors. Interestingly, the Wnt pathway was recently found to be perturbed in a zebrafish model of Cornelia de Lange syndrome. Mutations in cohesin complex genes and regulators have also been identified in several types of cancers. On the other hand, there is no clear evidence of an increased risk of cancer in Cornelia de Lange syndrome, and no other similar cases have been published since the fist one reported by Cohen, and this prompts to think Wilms tumor and Cornelia de Lange syndrome occurred together in our patient by chance.

  3. Unusual association of non-anaplastic Wilms tumor and Cornelia de Lange syndrome: case report

    International Nuclear Information System (INIS)

    Santoro, Claudia; Apicella, Andrea; Casale, Fiorina; La Manna, Angela; Di Martino, Martina; Di Pinto, Daniela; Indolfi, Cristiana; Perrotta, Silverio

    2016-01-01

    Cornelia de Lange syndrome is the prototype for cohesinopathy disorders, which are characterized by defects in chromosome segregation. Kidney malformations, including nephrogenic rests, are common in Cornelia de Lange syndrome. Only one post-mortem case report has described an association between Wilms tumor and Cornelia de Lange syndrome. Here, we describe the first case of a living child with both diseases. Non-anaplastic triphasic nephroblastoma was diagnosed in a patient carrying a not yet reported mutation in NIPBL (c.4920 G > A). The patient had the typical facial appearance and intellectual disability associated with Cornelia de Lange syndrome in absence of limb involvement. The child’s kidneys were examined by ultrasound at 2 years of age to exclude kidney abnormalities associated with the syndrome. She underwent pre-operative chemotherapy and nephrectomy. Seven months later she was healthy and without residual detectable disease. The previous report of such co-occurrence, together with our report and previous reports of nephrogenic rests, led us to wonder if there may be any causal relationship between these two rare entities. The wingless/integrated (Wnt) pathway, which is implicated in kidney development, is constitutively activated in approximately 15–20 % of all non-anaplastic Wilms tumors. Interestingly, the Wnt pathway was recently found to be perturbed in a zebrafish model of Cornelia de Lange syndrome. Mutations in cohesin complex genes and regulators have also been identified in several types of cancers. On the other hand, there is no clear evidence of an increased risk of cancer in Cornelia de Lange syndrome, and no other similar cases have been published since the fist one reported by Cohen, and this prompts to think Wilms tumor and Cornelia de Lange syndrome occurred together in our patient by chance

  4. Cushing Syndrome in a 6-Month-Old Infant due to Adrenocortical Tumor

    Directory of Open Access Journals (Sweden)

    Volmar KeithE

    2009-09-01

    Full Text Available Cushing syndrome is rare in infancy and usually due to an adrenocortical tumor (ACT. We report an infant with Cushing syndrome due to adrenocortical carcinoma. The patient presented at six months of age with a three-month history of growth failure, rapid weight gain, acne, and irritability. Physical examination showed obesity, hypertension, and Cushingoid features. Biochemical evaluation showed very high serum cortisol, mildly elevated testosterone, and suppressed ACTH. Abdominal MRI revealed a heterogeneous right adrenal mass extending into the inferior vena cava. Evaluation for metastases was negative. The tumor was removed surgically en bloc. Pathologic examination demonstrated low mitotic rate, but capsular and vascular invasion. She received no adjuvant therapy. Her linear growth has improved and Cushingoid features resolved. Hormonal markers and quarterly PET scans have been negative for recurrence 24 months postoperatively. In conclusion, adrenocortical neoplasms in children are rare, but should be considered in the differential diagnosis of Cushing syndrome.

  5. Doege-Potter syndrome presenting with hypoinsulinemic hypoglycemia in a patient with a malignant extrapleural solitary fibrous tumor: a case report

    Directory of Open Access Journals (Sweden)

    Schutt Robert C

    2013-01-01

    Full Text Available Abstract Introduction Doege-Potter syndrome is a paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia secondary to a solitary fibrous tumor. This tumor causes hypoglycemia by the secretion of a prohormone form of insulin-like growth factor II. We describe the diagnosis and management of Doege-Potter syndrome and the use of transarterial chemoembolization in a patient with a malignant extrapleural solitary fibrous tumor. Case presentation Our patient was a 64-year-old Caucasian woman who initially presented with urinary incontinence and was found to have a 14.5×9.0×9.0cm retroperitoneal solitary fibrous tumor compressing her bladder. Her tumor was surgically resected but recurred with multiple hepatic metastatic lesions. The hepatic metastases progressed despite systemic chemotherapy and treatment with doxorubicin transarterial chemoembolization. Her course was complicated by the development of recurrent fasting hypoglycemia, most likely secondary to Doege-Potter syndrome. Her hypoglycemia was managed with corticosteroid therapy and frequent scheduled nutrient intake overnight. Conclusions The rarity of hepatic solitary fibrous tumors and consequent lack of controlled trials make this report significant in that it describes the diagnostic approach to Doege-Potter syndrome, describes our experience with the use of doxorubicin transarterial chemoembolization, and presents management options for tumor-associated hypoglycemia in the case of extensive disease not amenable to surgical resection.

  6. effect of natural blue-green algal cells lysis on freshwater quality

    African Journals Online (AJOL)

    Compaq

    released into water due to algal cells lysis was performed by placing samples in two ... Keywords; Algae, cells lysis, Fatty acids, gas chromatography time-of-flight mass spectrometry, water quality ... Factors such as municipal and industrial.

  7. Tumor Therapeutics Work as Stress Inducers to Enhance Tumor Sensitivity to Natural Killer (NK) Cell Cytolysis by Up-regulating NKp30 Ligand B7-H6.

    Science.gov (United States)

    Cao, Guoshuai; Wang, Jian; Zheng, Xiaodong; Wei, Haiming; Tian, Zhigang; Sun, Rui

    2015-12-11

    Immune cells are believed to participate in initiating anti-tumor effects during regular tumor therapy such as chemotherapy, radiation, hyperthermia, and cytokine injection. One of the mechanisms underlying this process is the expression of so-called stress-inducible immunostimulating ligands. Although the activating receptor NKG2D has been proven to play roles in tumor therapy through targeting its ligands, the role of NKp30, another key activating receptor, is seldom addressed. In this study, we found that the NKp30 ligand B7-H6 was widely expressed in tumor cells and closely correlated to their susceptibility to NK cell lysis. Further studies showed that treatment of tumor cells with almost all standard tumor therapeutics, including chemotherapy (cisplatin, 5-fluorouracil), radiation therapy, non-lethal heat shock, and cytokine therapy (TNF-α), could up-regulate the expression of B7-H6 in tumor cells and enhance tumor sensitivity to NK cell cytolysis. B7-H6 shRNA treatment effectively dampened sensitization of tumor cells to NK-mediated lysis. Our study not only reveals the possibility that tumor therapeutics work as stress inducers to enhance tumor sensitivity to NK cell cytolysis but also suggests that B7-H6 could be a potential target for tumor therapy in the future. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Catheter placement for lysis of spontaneous intracerebral hematomas: does a catheter position in the core of the hematoma allow more effective and faster hematoma lysis?

    Science.gov (United States)

    Malinova, Vesna; Schlegel, Anna; Rohde, Veit; Mielke, Dorothee

    2017-07-01

    For the fibrinolytic therapy of intracerebral hematomas (ICH) using recombinant tissue plasminogen activator (rtPA), a catheter position in the core of the hematoma along the largest clot diameter was assumed to be optimal for an effective clot lysis. However, it never had been proven that core position indeed enhances clot lysis if compared with less optimal catheter positions. In this study, the impact of the catheter position on the effectiveness and on the time course of clot lysis was evaluated. We analyzed the catheter position using a relative error calculating the distance perpendicular to the catheter's center in relation to hematoma's diameter and evaluated the relative hematoma volume reduction (RVR). The correlation of the RVR with the catheter position was evaluated. Additionally, we tried to identify patterns of clot lysis with different catheter positions. The patient's outcome at discharge was evaluated using the Glasgow outcome score. A total of 105 patients were included in the study. The mean hematoma volume was 56 ml. The overall RVR was 62.7 %. In 69 patients, a catheter position in the core of the clot was achieved. We found no significant correlation between catheter position and hematoma RVR (linear regression, p = 0.14). Core catheter position leads to more symmetrical hematoma RVR. Faster clot lysis happens in the vicinity of the catheter openings. We found no significant difference in the patient's outcome dependent on the catheter position (linear regression, p = 0.90). The catheter position in the core of the hematoma along its largest diameter does not significantly influence the effectiveness of clot lysis after rtPA application.

  9. Analysis of GLUT-1, GLUT-3, and angiogenic index in syndromic and non-syndromic keratocystic odontogenic tumors

    Directory of Open Access Journals (Sweden)

    Rafaella Bastos LEITE

    2017-04-01

    Full Text Available Abstract The aim of this study was to evaluate the immunoexpression of glucose transporters 1 (GLUT-1 and 3 (GLUT-3 in keratocystic odontogenic tumors associated with Gorlin syndrome (SKOTs and non-syndromic keratocystic odontogenic tumors (NSKOTs, and to establish correlations with the angiogenic index. Seventeen primary NSKOTs, seven recurrent NSKOTs, and 17 SKOTs were selected for the study. The percentage of immunopositive cells for GLUT-1 and GLUT-3 in the epithelial component of the tumors was assessed. The angiogenic index was determined by microvessel count. The results were analyzed statistically using the nonparametric Kruskal-Wallis test and Spearman’s correlation test. High epithelial immunoexpression of GLUT-1 was observed in most tumors (p = 0.360. There was a higher frequency of negative cases for GLUT-3 in all groups. The few GLUT-3-positive tumors exhibited low expression of this protein in epithelial cells. No significant difference in the angiogenic index was observed between groups (p = 0.778. GLUT-1 expression did not correlate significantly with the angiogenic index (p > 0.05. The results suggest that the more aggressive biological behavior of SKOTs when compared to NSKOTs may not be related to GLUT-1 or GLUT-3 expression. GLUT-1 may play an important role in glucose uptake by epithelial cells of KOTs and this process is unlikely related to the angiogenic index. GLUT-1 could be a potential target for future development of therapeutic strategies for KOTs.

  10. Hyperparathyroidism-Jaw Tumor Syndrome: Results of surgical management

    Science.gov (United States)

    Mehta, Amit; Patel, Dhaval; Rosenberg, Avi; Boufraqech, Myriem; Ellis, Ryan J.; Nilubol, Naris; Quezado, Martha M.; Marx, Stephen J.; Simonds, William F.; Kebebew, Electron

    2014-01-01

    Background Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant disease secondary to germline inactivating mutations of the tumor suppressor gene HRPT2/CDC73. The aim of the present study is to determine the optimal surgical approach to parathyroid disease in patients with HPT-JT. Method A retrospective analysis of clinical and genetic features, parathyroid operative outcomes, and disease outcomes in seven unrelated HPT-JT families. Results Seven families had five distinct germline HRPT2/CDC73 mutations. Sixteen affected family members (median age of 30.7 years) were diagnosed with primary hyperparathyroidism. Fifteen of the 16 patients underwent preoperative tumor localization studies and uncomplicated bilateral neck exploration at initial operation - all were in biochemical remission at most recent follow up. 31% of patients had multiglandular involvement. 37.5% of patients developed parathyroid carcinoma (median overall survival 8.9 years; median follow-up 7.4 years). Long-term follow-up showed 20% of patients had recurrent primary hyperparathyroidism. Conclusions Given the high risk of malignancy and multiglandular involvement in our cohort, we recommend bilateral neck exploration and en-bloc resection of parathyroid tumors suspicious for cancer and life-long postoperative follow-up. PMID:25444225

  11. Hyperparathyroidism-jaw tumor syndrome: Results of operative management.

    Science.gov (United States)

    Mehta, Amit; Patel, Dhaval; Rosenberg, Avi; Boufraqech, Myriem; Ellis, Ryan J; Nilubol, Naris; Quezado, Martha M; Marx, Stephen J; Simonds, William F; Kebebew, Electron

    2014-12-01

    Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare, autosomal-dominant disease secondary to germline-inactivating mutations of the tumor suppressor gene HRPT2/CDC73. The aim of the present study was to determine the optimal operative approach to parathyroid disease in patients with HPT-JT. A retrospective analysis of clinical and genetic features, parathyroid operative outcomes, and disease outcomes in 7 unrelated HPT-JT families. Seven families had 5 distinct germline HRPT2/CDC73 mutations. Sixteen affected family members (median age, 30.7 years) were diagnosed with primary hyperparathyroidism (PHPT). Fifteen of the 16 patients underwent preoperative tumor localization studies and uncomplicated bilateral neck exploration at initial operation; all were in biochemical remission at most recent follow-up. Of these patients, 31% had multiglandular involvement; 37.5% of the patients developed parathyroid carcinoma (median overall survival, 8.9 years; median follow-up, 7.4 years). Long-term follow-up showed that 20% of patients had recurrent PHPT. Given the high risk of malignancy and multiglandular involvement in our cohort, we recommend bilateral neck exploration and en bloc resection of parathyroid tumors suspicious for cancer and life-long postoperative follow-up. Published by Elsevier Inc.

  12. Angiographic diagnosis of a pancreatic islet tumor in a patient with the WDHA syndrome

    International Nuclear Information System (INIS)

    Inamoto, K.; Yoshino, F.; Nakao, N.; Kawanaka, M.

    1980-01-01

    A patient with an islet cell tumor of the pancreas that produced the watery diarrhea, hypokalemia, achlorhydria syndrome is presented. On celiac angiography an extremely vascular mass was seen in the body of pancreas with hypertrophied arteries and persistent, dense tumor staining. (orig.) [de

  13. Pituitary tumors in patients with MEN1 syndrome

    Directory of Open Access Journals (Sweden)

    Luis V. Syro

    2012-01-01

    Full Text Available We briefly review the characteristics of pituitary tumors associated with multiple endocrine neoplasia type 1. Multiple endocrine neoplasia type 1 is an autosomal-dominant disorder most commonly characterized by tumors of the pituitary, parathyroid, endocrine-gastrointestinal tract, and pancreas. A MEDLINE search for all available publications regarding multiple endocrine neoplasia type 1 and pituitary adenomas was undertaken. The prevalence of pituitary tumors in multiple endocrine neoplasia type 1 may vary from 10% to 60% depending on the studied series, and such tumors may occur as the first clinical manifestation of multiple endocrine neoplasia type 1 in 25% of sporadic and 10% of familial cases. Patients were younger and the time between initial and subsequent multiple endocrine neoplasia type 1 endocrine lesions was significantly longer when pituitary disease was the initial manifestation of multiple endocrine neoplasia type 1. Tumors were larger and more invasive and clinical manifestations related to the size of the pituitary adenoma were significantly more frequent in patients with multiple endocrine neoplasia type 1 than in subjects with non-multiple endocrine neoplasia type 1. Normalization of pituitary hypersecretion was much less frequent in patients with multiple endocrine neoplasia type 1 than in subjects with non-multiple endocrine neoplasia type 1. Pituitary tumors in patients with multiple endocrine neoplasia type 1 syndrome tend to be larger, invasive and more symptomatic, and they tend to occur in younger patients when they are the initial presentation of multiple endocrine neoplasia type 1.

  14. Chemotherapy-induced hypocalcemia.

    Science.gov (United States)

    Ajero, Pia Marie E; Belsky, Joseph L; Prawius, Herbert D; Rella, Vincent

    2010-01-01

    To present a unique case of transient, asymptomatic chemotherapy-induced hypocalcemia not attributable to hypomagnesemia or tumor lysis syndrome and review causes of hypocalcemia related to cancer with and without use of chemotherapy. We present a case detailing the clinical and laboratory findings of a patient who had severe hypocalcemia during chemotherapy and discuss causes of hypocalcemia with an extensive literature review of chemotherapeutic agents associated with this biochemical abnormality. In a 90-year-old man, hypocalcemia developed during 2 courses of chemotherapy for Hodgkin lymphoma, with partial recovery between courses and normal serum calcium 10 months after completion of treatment. Magnesium, vitamin D, and parathyroid hormone levels were low normal. There was no evidence of tumor lysis syndrome. Of the various agents administered, vinca alkaloids seemed the most likely cause. Serial testing suggested that the underlying mechanism may have been acquired, reversible hypoparathyroidism. No other similar case was found in the published literature. The severe hypocalcemia in our patient could not be attributed to hypomagnesemia or tumor lysis syndrome, and it was clearly associated with the timing of his chemotherapeutic regimen. Possibilities include direct parathyroid hormone suppression or alteration of calcium sensing by the chemotherapeutic drugs. Serum calcium surveillance before and during chemotherapeutic management of cancer patients may reveal more instances and provide insight into the exact mechanism of this lesser known yet striking complication.

  15. Doege–Potter Syndrome, cause of nonislet cell tumor hypoglycemia: the first case report from Nepal

    Directory of Open Access Journals (Sweden)

    Pant V

    2017-08-01

    Full Text Available Vivek Pant,1 Suman Baral,2 Gita Sayami,3 Prakash Sayami4 1Department of Biochemistry, 2Endocrinology Unit, Department of Medicine, 3Department of Pathology, 4Manmohan Cardiothoracic vascular and transplant Center, Institute of Medicine (IOM, Tribhuvan University Teaching Hospital (TUTH, Kathmandu, Nepal Abstract: Doege–Potter syndrome (DPS, a paraneoplastic syndrome, presents as a hypoinsulinemic hypoglycemia from the ectopic secretion of insulin-like growth factor II from a solitary fibrous tumor which may be intrapleural or extrapleural in origin. We report a case of severe hypoglycemia in a 70-year old female initially admitted for resection of left sided solitary fibrous tumor of pleura. Investigation revealed true hypoglycemia, and DPS was diagnosed. The tumor was completely resected, after which no further hypoglycemic episodes were seen in 2 years follow-up. This is the first case of solitary fibrous tumor of pleura with DPS reported from Nepal. Keywords: insulin-like growth factor II, IGF-II, solitary fibrous tumor, hypoglycemia

  16. Universal tumor screening for Lynch syndrome: Assessment of the perspectives of patients with colorectal cancer regarding benefits and barriers.

    Science.gov (United States)

    Hunter, Jessica Ezzell; Zepp, Jamilyn M; Gilmore, Mari J; Davis, James V; Esterberg, Elizabeth J; Muessig, Kristin R; Peterson, Susan K; Syngal, Sapna; Acheson, Louise S; Wiesner, Georgia L; Reiss, Jacob A; Goddard, Katrina A B

    2015-09-15

    Universal tumor screening for Lynch syndrome, the most common form of hereditary colorectal cancer (CRC), has been recommended among all patients newly diagnosed with CRC. However, there is limited literature regarding patient perspectives of tumor screening for Lynch syndrome among patients with CRC who are not selected for screening based on family history criteria. A total of 145 patients aged 39 to 87 years were administered surveys assessing perceived risk, patient perspectives, and potential benefits of and barriers to tumor screening for Lynch syndrome. Associations between patient-specific and cancer-specific factors and survey responses were analyzed. The majority of participants perceived their risk of developing Lynch syndrome as being low, with 9 participants (6.2%) anticipating an abnormal screening result. However, most participants endorsed the potential benefits of screening for themselves and their families, with 84.8% endorsing ≥6 benefits and 50.3% endorsing all 8 benefits. Participants also endorsed few potential barriers to screening, with 89.4% endorsing ≤4 of 9 potential barriers. A common barrier was worry about the cost of additional testing and surveillance, which was endorsed by 54.5% of participants. The level of distress associated with tumor screening for Lynch syndrome, which was very low, was not associated with age or CRC stage. The results of the current study indicate that patients with CRC overall have a positive attitude toward tumor screening for Lynch syndrome, endorse the benefits of screening, and experience low levels of distress. These findings provide insight into patient attitudes toward tumor screening for Lynch syndrome among unselected patients with CRC to inform educational approaches that assist in patient decision-making and guide the successful implementation of screening programs. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

  17. Occurrence of DNET and other brain tumors in Noonan syndrome warrants caution with growth hormone therapy.

    Science.gov (United States)

    McWilliams, Geoffrey D; SantaCruz, Karen; Hart, Blaine; Clericuzio, Carol

    2016-01-01

    Noonan syndrome (NS) is an autosomal dominant developmental disorder caused by mutations in the RAS-MAPK signaling pathway that is well known for its relationship with oncogenesis. An 8.1-fold increased risk of cancer in Noonan syndrome has been reported, including childhood leukemia and solid tumors. The same study found a patient with a dysembryoplastic neuroepithelial tumor (DNET) and suggested that DNET tumors are associated with NS. Herein we report an 8-year-old boy with genetically confirmed NS and a DNET. Literature review identified eight other reports, supporting the association between NS and DNETs. The review also ascertained 13 non-DNET brain tumors in individuals with NS, bringing to 22 the total number of NS patients with brain tumors. Tumor growth while receiving growth hormone (GH) occurred in our patient and one other patient. It is unknown whether the development or progression of tumors is augmented by GH therapy, however there is concern based on epidemiological, animal and in vitro studies. This issue was addressed in a 2015 Pediatric Endocrine Society report noting there is not enough data available to assess the safety of GH therapy in children with neoplasia-predisposition syndromes. The authors recommend that GH use in children with such disorders, including NS, be undertaken with appropriate surveillance for malignancies. Our case report and literature review underscore the association of NS with CNS tumors, particularly DNET, and call attention to the recommendation that clinicians treating NS patients with GH do so with awareness of the possibility of increased neoplasia risk. © 2015 Wiley Periodicals, Inc.

  18. Posterior reversible leukoencephalopathy syndrome in children with hematologic disorders

    Directory of Open Access Journals (Sweden)

    Barış Malbora

    2010-09-01

    Full Text Available Objective: Posterior reversible leukoencephalopathy syndrome (PRES is characterized by headache, altered mental status, cortical blindness, and seizures associated with neuroradiological findings. It involves predominantly white matter of the parieto-occipital lobes. Several medications and disorders play a role in the etiology of PRES. In this study, we aimed to show how the prognosis of PRES in hematological diseases of childhood might be according to the etiological factors.Materials and Methods: Here, we report PRES in six patients, aged 4 to 14 years, with diagnoses of leukemia and aplastic anemia. Results: Suggested causes in our patients were chemotherapeutics, hypertension, infection and antimicrobial drug administration, tumor lysis syndrome, acute renal failure and hemodialysis, immunosuppressive drug administration, and hypomagnesemia. One of the patients died of sepsis, renal failure and pulmonary hemorrhage and another died of relapse after total recovery from PRES. The other four patients are under follow-up without problems. Conclusion: We suggest that PRES can recover fully with early diagnosis and treatment whereas it can show poor prognosis depending on the etiology.

  19. Isolation of Mycobacterium chelonei with the lysis-centrifugation blood culture technique.

    OpenAIRE

    Fojtasek, M F; Kelly, M T

    1982-01-01

    Mycobacterium chelonei was isolated from a patient by the lysis-centrifugation and the conventional two-bottle blood culture methods. The lysis-centrifugation method was significantly more sensitive and rapid than the conventional method in detecting and isolating this organism; quantitations done by this method were useful for monitoring response to therapy.

  20. Hypochlorite- and hypobromite-mediated radical formation and its role in cell lysis

    DEFF Research Database (Denmark)

    Hawkins, C L; Brown, B E; Davies, Michael Jonathan

    2001-01-01

    . In this study it is shown that HOBr induces red blood cell lysis at approximately 10-fold lower concentrations than HOCl, whereas with monocyte (THP1) and macrophage (J774) cells HOCl and HOBr induce lysis at similar concentrations. The role of radical formation during lysis has been investigated by EPR spin...... trapping, and it is shown that reaction of both oxidants with each cell type generates cell-derived radicals. Red blood cells exposed to nonlytic doses of HOCl generate novel nitrogen-centered radicals whose formation is GSH dependent. In contrast, HOBr gives rise to nitrogen-centered, membrane......-derived protein radicals. With lytic doses of either oxidant, protein (probably hemoglobin)-derived, nitrogen-centered radicals are observed. Unlike the red blood cells, treatment of monocytes and macrophages with HOCl gives significant radical formation only under conditions where cell lysis occurs concurrently...

  1. Benign Phyllodes Tumor Mimicking a Malignancy in a Turner Syndrome Woman with Hormone Replacement Therapy: A Case Report

    International Nuclear Information System (INIS)

    Lee, Woong Jae; Chong, Se Min; Pang, Jae Choon; Seo, Jae Seung; Byun, Jun Soo; Seok, Ju Won; Shin, Hee Jung; Gong, Gyung Yub

    2010-01-01

    Phyllodes tumor of the breast is a relatively rare fibroepithelial tumor. Turner syndrome is a condition that affects approximately 50 per 100,000 females and includes total or partial absence of one X chromosome in all or part of the cells, reduced final height, absence of female sex hormone, and infertility. In this case report, we describe the first case of a benign phyllodes tumor mimicking a malignancy at breast US in a 26-year-old woman with Turner syndrome who had been undergoing hormone replacement therapy

  2. Benign Phyllodes Tumor Mimicking a Malignancy in a Turner Syndrome Woman with Hormone Replacement Therapy: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Woong Jae; Chong, Se Min; Pang, Jae Choon; Seo, Jae Seung; Byun, Jun Soo; Seok, Ju Won [Chung-Ang University Medical Center, Chung-Ang University College of Medicine, Seoul (Korea, Republic of); Shin, Hee Jung; Gong, Gyung Yub [Asan Medical Center, University of Ulsan College of Mdeicine, Seoul (Korea, Republic of)

    2010-12-15

    Phyllodes tumor of the breast is a relatively rare fibroepithelial tumor. Turner syndrome is a condition that affects approximately 50 per 100,000 females and includes total or partial absence of one X chromosome in all or part of the cells, reduced final height, absence of female sex hormone, and infertility. In this case report, we describe the first case of a benign phyllodes tumor mimicking a malignancy at breast US in a 26-year-old woman with Turner syndrome who had been undergoing hormone replacement therapy

  3. Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome).

    Science.gov (United States)

    Buchanan, Daniel D; Rosty, Christophe; Clendenning, Mark; Spurdle, Amanda B; Win, Aung Ko

    2014-01-01

    Carriers of a germline mutation in one of the DNA mismatch repair (MMR) genes have a high risk of developing numerous different cancers, predominantly colorectal cancer and endometrial cancer (known as Lynch syndrome). MMR gene mutation carriers develop tumors with MMR deficiency identified by tumor microsatellite instability or immunohistochemical loss of MMR protein expression. Tumor MMR deficiency is used to identify individuals most likely to carry an MMR gene mutation. However, MMR deficiency can also result from somatic inactivation, most commonly methylation of the MLH1 gene promoter. As tumor MMR testing of all incident colorectal and endometrial cancers (universal screening) is becoming increasingly adopted, a growing clinical problem is emerging for individuals who have tumors that show MMR deficiency who are subsequently found not to carry an MMR gene mutation after genetic testing using the current diagnostic approaches (Sanger sequencing and multiplex ligation-dependent probe amplification) and who also show no evidence of MLH1 methylation. The inability to determine the underlying cause of tumor MMR deficiency in these "Lynch-like" or "suspected Lynch syndrome" cases has significant implications on the clinical management of these individuals and their relatives. When the data from published studies are combined, 59% (95% confidence interval [CI]: 55% to 64%) of colorectal cancers and 52% (95% CI: 41% to 62%) of endometrial cancers with MMR deficiency were identified as suspected Lynch syndrome. Recent studies estimated that colorectal cancer risk for relatives of suspected Lynch syndrome cases is lower than for relatives of those with MMR gene mutations, but higher than for relatives of those with tumor MMR deficiency resulting from methylation of the MLH1 gene promoter. The cause of tumor MMR deficiency in suspected Lynch syndrome cases is likely due to either unidentified germline MMR gene mutations, somatic cell mosaicism, or biallelic somatic

  4. The uncovering and characterization of a CCKoma syndrome in enteropancreatic neuroendocrine tumor patients

    DEFF Research Database (Denmark)

    Rehfeld, Jens F; Federspiel, Birgitte; Agersnap, Mikkel

    2016-01-01

    OBJECTIVE: Neuroendocrine tumors in the pancreas and the gastrointestinal tract may secrete hormones which cause specific syndromes. Well-known examples are gastrinomas, glucagonomas, and insulinomas. Cholecystokinin-producing tumors (CCKomas) have been induced experimentally in rats, but a CCKoma...... disease and diarrhea with permanently low gastrin in plasma suggest that CCKomas may mimic gastrinoma-like symptoms, because CCK peptides are full agonists of the gastrin/CCK-B receptor....

  5. Evaluation of Lysis Methods for the Extraction of Bacterial DNA for Analysis of the Vaginal Microbiota.

    Science.gov (United States)

    Gill, Christina; van de Wijgert, Janneke H H M; Blow, Frances; Darby, Alistair C

    2016-01-01

    Recent studies on the vaginal microbiota have employed molecular techniques such as 16S rRNA gene sequencing to describe the bacterial community as a whole. These techniques require the lysis of bacterial cells to release DNA before purification and PCR amplification of the 16S rRNA gene. Currently, methods for the lysis of bacterial cells are not standardised and there is potential for introducing bias into the results if some bacterial species are lysed less efficiently than others. This study aimed to compare the results of vaginal microbiota profiling using four different pretreatment methods for the lysis of bacterial samples (30 min of lysis with lysozyme, 16 hours of lysis with lysozyme, 60 min of lysis with a mixture of lysozyme, mutanolysin and lysostaphin and 30 min of lysis with lysozyme followed by bead beating) prior to chemical and enzyme-based DNA extraction with a commercial kit. After extraction, DNA yield did not significantly differ between methods with the exception of lysis with lysozyme combined with bead beating which produced significantly lower yields when compared to lysis with the enzyme cocktail or 30 min lysis with lysozyme only. However, this did not result in a statistically significant difference in the observed alpha diversity of samples. The beta diversity (Bray-Curtis dissimilarity) between different lysis methods was statistically significantly different, but this difference was small compared to differences between samples, and did not affect the grouping of samples with similar vaginal bacterial community structure by hierarchical clustering. An understanding of how laboratory methods affect the results of microbiota studies is vital in order to accurately interpret the results and make valid comparisons between studies. Our results indicate that the choice of lysis method does not prevent the detection of effects relating to the type of vaginal bacterial community one of the main outcome measures of epidemiological studies

  6. Evaluation of Lysis Methods for the Extraction of Bacterial DNA for Analysis of the Vaginal Microbiota.

    Directory of Open Access Journals (Sweden)

    Christina Gill

    Full Text Available Recent studies on the vaginal microbiota have employed molecular techniques such as 16S rRNA gene sequencing to describe the bacterial community as a whole. These techniques require the lysis of bacterial cells to release DNA before purification and PCR amplification of the 16S rRNA gene. Currently, methods for the lysis of bacterial cells are not standardised and there is potential for introducing bias into the results if some bacterial species are lysed less efficiently than others. This study aimed to compare the results of vaginal microbiota profiling using four different pretreatment methods for the lysis of bacterial samples (30 min of lysis with lysozyme, 16 hours of lysis with lysozyme, 60 min of lysis with a mixture of lysozyme, mutanolysin and lysostaphin and 30 min of lysis with lysozyme followed by bead beating prior to chemical and enzyme-based DNA extraction with a commercial kit.After extraction, DNA yield did not significantly differ between methods with the exception of lysis with lysozyme combined with bead beating which produced significantly lower yields when compared to lysis with the enzyme cocktail or 30 min lysis with lysozyme only. However, this did not result in a statistically significant difference in the observed alpha diversity of samples. The beta diversity (Bray-Curtis dissimilarity between different lysis methods was statistically significantly different, but this difference was small compared to differences between samples, and did not affect the grouping of samples with similar vaginal bacterial community structure by hierarchical clustering.An understanding of how laboratory methods affect the results of microbiota studies is vital in order to accurately interpret the results and make valid comparisons between studies. Our results indicate that the choice of lysis method does not prevent the detection of effects relating to the type of vaginal bacterial community one of the main outcome measures of

  7. Low-Cost Energy-Efficient 3-D Nano-Spikes-Based Electric Cell Lysis Chips

    KAUST Repository

    Riaz, Kashif

    2017-05-04

    Electric cell lysis (ECL) is a promising technique to be integrated with portable lab-on-a-chip without lysing agent due to its simplicity and fast processing. ECL is usually limited by the requirements of high power/voltage and costly fabrication. In this paper, we present low-cost 3-D nano-spikes-based ECL (NSP-ECL) chips for efficient cell lysis at low power consumption. Highly ordered High-Aspect-Ratio (HAR). NSP arrays with controllable dimensions were fabricated on commercial aluminum foils through scalable and electrochemical anodization and etching. The optimized multiple pulse protocols with minimized undesirable electrochemical reactions (gas and bubble generation), common on micro parallel-plate ECL chips. Due to the scalability of fabrication process, 3-D NSPs were fabricated on small chips as well as on 4-in wafers. Phase diagram was constructed by defining critical electric field to induce cell lysis and for cell lysis saturation Esat to define non-ECL and ECL regions for different pulse parameters. NSP-ECL chips have achieved excellent cell lysis efficiencies ηlysis (ca 100%) at low applied voltages (2 V), 2~3 orders of magnitude lower than that of conventional systems. The energy consumption of NSP-ECL chips was 0.5-2 mJ/mL, 3~9 orders of magnitude lower as compared with the other methods (5J/mL-540kJ/mL). [2016-0305

  8. Multiple keratocystic odontogenic tumors in a non-syndromic minor patient: Report of an unusual case

    Directory of Open Access Journals (Sweden)

    Shalu Rai

    2013-01-01

    Full Text Available Keratocystic odontogenic tumor (KCOT is developmental odontogenic cysts of epithelial origin known for their potentially aggressive behavior and significant rate of recurrences. Single odontogenic cysts are very well documented in the literature. Multiple (KCOT are principle features of nevoid basal cell carcinoma syndrome (naevoid basal cell carcinoma syndrome; Gorlin-Goltz syndrome. We report an intriguing case of multiple KCOT in a non-syndromic patient simultaneously occurring in maxilla as well as in mandible with brief highlight on molecular data and the treatment modality.

  9. Antibody-dependent cellular cytotoxicity (ADCC) activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells

    Science.gov (United States)

    Fantini, Massimo; Heery, Christopher R.; Gulley, James L.; Tsang, Kwong Yok; Schlom, Jeffrey

    2015-01-01

    Several anti-PD1/PD-L1 monoclonal antibodies (MAb) are currently providing evidence of clinical benefit in subsets of cancer patients. The mode of action of these MAbs is to inhibit PD1 on immune cells interacting with PD-L1 on tumor cells. These MAbs are either designed or engineered to eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been implicated as an important mechanism in several highly effective MAb-mediated cancer therapies. A fully human anti-PD-L1 MAb would potentially be able to block PD-L1/PD1 interactions and also mediate the ADCC lysis of tumor cells. MSB0010718C (designated avelumab) is a fully human IgG1 anti-PD-L1 MAb. The studies reported here demonstrate (a) the ability of avelumab to lyse a range of human tumor cells in the presence of PBMC or NK effectors; (b) IFNγ can enhance tumor cell PD-L1 expression and in some cases enhance ADCC tumor cell lysis; (c) purified NK cells are potent effectors for avelumab; (d) similar levels of avelumab-mediated ADCC lysis of tumor cells are seen using purified NK as effectors from either healthy donors or cancer patients; (e) very low levels of avelumab-mediated lysis are seen using whole PBMCs as targets; this finding complements results seen in analyses of PBMC subsets of patients receiving avelumab; and (f) the addition of IL12 to NK cells greatly enhances avelumab-mediated ADCC. These studies thus provide an additional mode of action for an anti-PD-L1 MAb and support the rationale for further studies to enhance avelumab-mediated ADCC activity. PMID:26014098

  10. Lysis-deficient phages as novel therapeutic agents for controlling bacterial infection

    Directory of Open Access Journals (Sweden)

    Kempashanaiah Nanjundappa

    2011-08-01

    Full Text Available Abstract Background Interest in phage therapy has grown over the past decade due to the rapid emergence of antibiotic resistance in bacterial pathogens. However, the use of bacteriophages for therapeutic purposes has raised concerns over the potential for immune response, rapid toxin release by the lytic action of phages, and difficulty in dose determination in clinical situations. A phage that kills the target cell but is incapable of host cell lysis would alleviate these concerns without compromising efficacy. Results We developed a recombinant lysis-deficient Staphylococcus aureus phage P954, in which the endolysin gene was rendered nonfunctional by insertional inactivation. P954, a temperate phage, was lysogenized in S. aureus strain RN4220. The native endolysin gene on the prophage was replaced with an endolysin gene disrupted by the chloramphenicol acetyl transferase (cat gene through homologous recombination using a plasmid construct. Lysogens carrying the recombinant phage were detected by growth in presence of chloramphenicol. Induction of the recombinant prophage did not result in host cell lysis, and the phage progeny were released by cell lysis with glass beads. The recombinant phage retained the endolysin-deficient genotype and formed plaques only when endolysin was supplemented. The host range of the recombinant phage was the same as that of the parent phage. To test the in vivo efficacy of the recombinant endolysin-deficient phage, immunocompromised mice were challenged with pathogenic S. aureus at a dose that results in 80% mortality (LD80. Treatment with the endolysin-deficient phage rescued mice from the fatal S. aureus infection. Conclusions A recombinant endolysin-deficient staphylococcal phage has been developed that is lethal to methicillin-resistant S. aureus without causing bacterial cell lysis. The phage was able to multiply in lytic mode utilizing a heterologous endolysin expressed from a plasmid in the propagation host

  11. Pancreatic non-functioning neuroendocrine tumor: a new entity genetically related to Lynch syndrome

    OpenAIRE

    Serracant Barrera, Anna; Serra Pla, Sheila; Blázquez Maña, Carmen María; Salas, Rubén Carrera; García Monforte, Neus; Bejarano González, Natalia; Romaguera Monzonis, Andreu; Andreu Navarro, Francisco Javier; Bella Cueto, Maria Rosa; Borobia, Francisco G.

    2017-01-01

    Some pancreatic neuroendocrine tumors (P-NETs) are associated with hereditary syndromes. An association between Lynch syndrome (LS) and P-NETs has been suggested, however it has not been confirmed to date. We describe the first case associating LS and P-NETs. Here we report a 65-year-old woman who in the past 20 years presented two colorectal carcinomas (CRC) endometrial carcinoma (EC), infiltrating ductal breast carcinoma, small intestine adenocarcinoma, two non-functioning P-NETs and seboma...

  12. Ovarian steroid cell tumor in women with polycystic ovarian syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Yarandi F

    2013-04-01

    Full Text Available Background: Steroid cell tumor is one of the rare ovarian tumors and forms 0.1% of all ovarian tumors, divided to three subgroups. Steroid cell tumor that are not otherwise specified (NOS are the most common type and represent 60% of steroid cell tumors. One of the most known signs of this tumor is hormonal function, especially androgenic effects of it. Primary treatment consists of eradication of tumor via surgery.Case presentation: The patient is a 29 years old female with history of poly cystic ovarian syndrome since 10 years ago, who attended to the clinic of General Women Hospital of Tehran in January 2011. In pelvic ultrasonography, there was a 6449mm mass in the right adnexa consisting of homogeneous component. She underwent laparotomy and unilateral salpingoophorectomy was done. Pathological report was steroid cell tumor of ovary.Conclusion: The aim of this study is reporting one of the rare tumors of ovary and assessment of the correct way of diagnosis and treatment of it.

  13. Antibody-Dependent Cellular Cytotoxicity Activity of a Novel Anti-PD-L1 Antibody Avelumab (MSB0010718C) on Human Tumor Cells.

    Science.gov (United States)

    Boyerinas, Benjamin; Jochems, Caroline; Fantini, Massimo; Heery, Christopher R; Gulley, James L; Tsang, Kwong Yok; Schlom, Jeffrey

    2015-10-01

    Several anti-PD-1/PD-L1 monoclonal antibodies (mAb) are currently providing evidence of clinical benefit in subsets of cancer patients. The mode of action of these mAbs is to inhibit PD-1 on immune cells interacting with PD-L1 on tumor cells. These mAbs are either designed or engineered to eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been implicated as an important mechanism in several highly effective mAb-mediated cancer therapies. A fully human anti-PD-L1 mAb would potentially be able to block PD-1/PD-L1 interactions and also mediate the ADCC lysis of tumor cells. MSB0010718C (designated avelumab) is a fully human IgG1 anti-PD-L1 mAb. The studies reported here demonstrate (i) the ability of avelumab to lyse a range of human tumor cells in the presence of PBMC or NK effectors; (ii) IFNγ can enhance tumor cell PD-L1 expression and, in some cases, enhance ADCC tumor cell lysis; (iii) purified NK cells are potent effectors for avelumab; (iv) similar levels of avelumab-mediated ADCC lysis of tumor cells are seen using purified NK as effectors from either healthy donors or cancer patients; (v) very low levels of avelumab-mediated lysis are seen using whole PBMCs as targets; this finding complements results seen in analyses of PBMC subsets of patients receiving avelumab; and (vi) the addition of IL12 to NK cells greatly enhances avelumab-mediated ADCC. These studies thus provide an additional mode of action for an anti-PD-L1 mAb and support the rationale for further studies to enhance avelumab-mediated ADCC activity. ©2015 American Association for Cancer Research.

  14. Non-syndromic multiple keratocyst odontogenic tumor: A rare case report

    Directory of Open Access Journals (Sweden)

    Abhijeet Alok

    2015-01-01

    Full Text Available Keratocystic odontogenic tumors (KCOTs are one of the most frequent features of nevoid basal cell carcinoma syndrome (NBCCS. The condition is linked with mutation in the PTCH gene. Partial expression of the gene may result in occurrence of multiple recurring odontogenic keratocysts (OKCs. Although KCOTs are common in clinical practice, simultaneous occurrence of multiple cysts in both the maxilla and mandible of a patient is rare. These patients have early propensity to develop multiple neoplasms like basal cell carcinoma and medulloblastoma. Hence, early diagnosis and treatment is of utmost importance in reducing the severity of the long-term sequelae of NBCCS. We report a rare case of multiple KCOTs in a non-syndromic male patient, with emphasis on its diagnosis, radiographic features, and treatment.

  15. Lysis of typhus-group rickettsia-infected targets by lymphokine activated killers

    International Nuclear Information System (INIS)

    Carl, M.; Dasch, G.A.

    1986-01-01

    The authors recently described a subset of OKT8, OKT3-positive lymphocytes from typhus-group rickettsia immune individuals which were capable of lysing autologous PHA-blasts or Epstein-Barr virus transformed B cells (LCL) infected with typhus-group rickettsiae. In order to determine if killing by these effectors was HLA-restricted, they stimulated peripheral blood mononuclear cells (PBMC) from typhus-group rickettsia immune individuals in vitro with typhus-group rickettsia-derived antigen for one week and then measured lysis of autologous LCL or HLA-mismatched LCL in a 4-6 hour Cr 51 -release assay. There was significant lysis of both the autologous and the HLA-mismatched infected targets as compared to the corresponding uninfected targets. Since this suggested that the effectors were lymphokine activated killers (LAK) rather than cytotoxic T lymphocytes, they then tested this hypothesis by stimulating PBMC from both immune and non-immune individuals in vitro for one week with purified interleukin 2 and measuring lysis of infected, autologous LCL. PBMC thus treated, from both immune and non-immune individuals, were capable of significantly lysing autologous, infected LCL as compared to the non-infected control. They therefore conclude that targets infected with typhus-group rickettsiae are susceptible to lysis to LAK

  16. The Perlman syndrome: familial renal dysplasia with Wilms tumor, fetal gigantism and multiple congenital anomalies.

    Science.gov (United States)

    Neri, G; Martini-Neri, M E; Katz, B E; Opitz, J M

    1984-09-01

    We describe a familial syndrome of renal dysplasia, Wilms tumor, hyperplasia of the endocrine pancreas, fetal gigantism, multiple congenital anomalies and mental retardation. This condition was previously described by Perlman et al [1973, 1975] and we propose to call it the "Perlman syndrome." It appears to be transmitted as an autosomal recessive trait. The possible relationships between dysplasia, neoplasia and malformation are discussed.

  17. Electrical lysis: dynamics revisited and advances in On-chip operation.

    Science.gov (United States)

    Morshed, Bashir; Shams, Maitham; Mussivand, Tofy

    2013-01-01

    Electrical lysis (EL) is the process of breaking the cell membrane to expose the internal contents under an applied high electric field. Lysis is an important phenomenon for cellular analysis, medical treatment, and biofouling control. This paper aims to review, summarize, and analyze recent advancements on EL. Major databases including PubMed, Ei Engineering Village, IEEE Xplore, and Scholars Portal were searched using relevant keywords. More than 50 articles published in English since 1997 are cited in this article. EL has several key advantages compared to other lysis techniques such as chemical, mechanical, sonication, or laser, including rapid speed of operation, ability to control, miniaturization, low cost, and low power requirement. A variety of cell types have been investigated for including protoplasts, E. coli, yeasts, blood cells, and cancer cells. EL has been developed and applied for decontamination, cytology, genetics, single-cell analysis, cancer treatment, and other applications. On-chip EL is a promising technology for multiplexed automated implementation of cell-sample preparation and processing with micro- or nanoliter reagents.

  18. The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity.

    Science.gov (United States)

    Mete, Ozgur; Duan, Kai

    2018-01-01

    Adrenal cortical tumors constitute a heterogeneous group of neoplasms with distinct clinical, morphological, and molecular features. Recent discoveries of specific genotype-phenotype correlations in adrenal cortical adenomas have transformed our understanding of their respective endocrine syndromes. Indeed, a proportion of patients with primary aldosteronism are now known to harbor adrenal cortical adenomas with heterogeneous molecular alterations ( KCNJ5, ATP1A1, ATP2B3 , and CACNA1D ) involving the calcium/calmodulin kinase signaling pathway. Several lines of evidence suggest that KCNJ5 -mutant aldosterone-producing adenomas have distinct clinicopathological phenotype compared to those harboring ATP1A1, ATP2B3 , and CACNA1D mutations. Benign adrenal cortical tumors presenting with Cushing syndrome often have diverse mutations ( PRKACA, PRKAR1A, GNAS, PDE11A , and PDE8B ) involving the cyclic AMP signaling pathway. In addition to cortisol-producing adenomas, bilateral micronodular adrenocortical disease and primary bilateral macronodular adrenal hyperplasia (PBMAH) have also expanded the spectrum of benign neoplasms causing adrenal Cushing disease. The recent discovery of inactivating ARMC5 germline mutations in PBMAH has challenged the old belief that this disorder is mainly a sporadic disease. Emerging evidence suggests that PBMAH harbors multiple distinct clonal proliferations, reflecting the heterogeneous genomic landscape of this disease. Although most solitary adrenal cortical tumors are sporadic, there is an increasing recognition that inherited susceptibility syndromes may also play a role in their pathogenesis. This review highlights the molecular and morphological heterogeneity of benign adrenal cortical neoplasms, reflected in the diverse presentations of primary aldosteronism and adrenal Cushing syndrome.

  19. TNF induction of EL4 hyposensitivity to lysis by recombinant (soluble) and membrane-associated TNFs: TNF binding, internalization, and degradation.

    Science.gov (United States)

    Fishman, M; Costlow, M

    1994-04-01

    EL4 mouse thymoma cells sensitive to TNF-mediated lysis only in the presence of cycloheximide (S-EL4) or in the presence or absence of cycloheximide (N-EL4) were used in these experiments. Murine tumor cell line (S-EL4) sensitivity to TNF cytotoxicity is augmented when cycloheximide is added together with TNF or when cycloheximide is added 1 hr before or after TNF. No enhanced sensitivity is observed when target cells are incubated with cycloheximide 2-4 hr before or after the addition of TNF. In the absence of cycloheximide, S-EL4 cells preexposed to murine TNF are less susceptible to lysis by TNF and TNF receptor-conjugated TNF but are lysed by integral membrane TNF. TNF-induced hyposensitivity is partially reversed by actinomycin D or by culturing the preexposed cells for 4 hr prior to TNF lytic assay. TNF preincubation of N- and S-EL4 cells results in an immediate decrease in 125I-TNF binding due to TNF receptor occupancy. Recovery of TNF-R occupancy and TNF internalization were subsequently noted.

  20. Anti-tumoral effect of the mitochondrial target domain of Noxa delivered by an engineered Salmonella typhimurium.

    Directory of Open Access Journals (Sweden)

    Jae-Ho Jeong

    Full Text Available Bacterial cancer therapy relies on the fact that several bacterial species are capable of targeting tumor tissue and that bacteria can be genetically engineered to selectively deliver therapeutic proteins of interest to the targeted tumors. However, the challenge of bacterial cancer therapy is the release of the therapeutic proteins from the bacteria and entry of the proteins into tumor cells. This study employed an attenuated Salmonella typhimurium to selectively deliver the mitochondrial targeting domain of Noxa (MTD as a potential therapeutic cargo protein, and examined its anti-cancer effect. To release MTD from the bacteria, a novel bacterial lysis system of phage origin was deployed. To facilitate the entry of MTD into the tumor cells, the MTD was fused to DS4.3, a novel cell-penetrating peptide (CPP derived from a voltage-gated potassium channel (Kv2.1. The gene encoding DS4.3-MTD and the phage lysis genes were placed under the control of PBAD , a promoter activated by L-arabinose. We demonstrated that DS4.3-MTD chimeric molecules expressed by the Salmonellae were anti-tumoral in cultured tumor cells and in mice with CT26 colon carcinoma.

  1. Tumor suppressor gene mutation in a patient with a history of hyperparathyroidism-jaw tumor syndrome and healed generalized osteitis fibrosa cystica: a case report and genetic pathophysiology review.

    Science.gov (United States)

    Parfitt, Joshua; Harris, Malcolm; Wright, John M; Kalamchi, Sabah

    2015-01-01

    Hyperparathyroidism-jaw tumor (HPT-JT) was first observed by Jackson in 1958 in a family who exhibited hyperparathyroidism and recurrent pancreatitis. The author noticed the presence of jaw tumors in the affected family and reported them as fibrous dysplasia. However, it was not until 1990 that a familial variety of hyperparathyroidism with fibro-osseous jaw tumors was recognized as HPT-JT syndrome and reported as a clinically and genetically distinct syndrome. Hyperparathyroidism generally arises from glandular hyperplasia or parathyroid adenomas, with only about 1% of cases resulting from parathyroid carcinoma. However, parathyroid carcinoma develops in about 15% of HPT-JT patients. The true incidence of HPT-JT is unknown, although the prevalence of about 100 published cases suggests its rarity. Twenty percent of HPT-JT cases have renal hamartomas or tumors, and female patients with HPT-JT have been reported to have carcinoma of the uterus. This syndrome appears to arise from a variety of mutations that deactivate the tumor suppressor gene CDC73 (also known as HRPT2) and its production of the tumor suppressor protein parafibromin. Functional parafibromin has 531 amino acids, and mutations result in a short nonfunctional protein. CDC73 disorders exhibit dominant germline gene behavior, with varying degrees of penetration. In most cases an affected person has 1 parent with the condition, which raises the need for family investigation and genetic counseling. We report a case of HPT-JT syndrome in a male patient who presented to the local community hospital 6 years previously with a history of back pain. Investigations showed elevated serum parathyroid hormone and calcium levels, and a technetium 99m sestamibi parathyroid scan showed increased activity at the site of the lower left gland that proved to be a substernal parathyroid carcinoma. The patient's parathyroid hormone level dropped from 126 to 97 pg/mL at 5 minutes and was 65 pg/mL at 10 minutes after excision

  2. Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Buchanan DD

    2014-10-01

    Full Text Available Daniel D Buchanan,1,2 Christophe Rosty,1,3,4 Mark Clendenning,1 Amanda B Spurdle,5 Aung Ko Win2 1Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia; 2Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia; 3Envoi Specialist Pathologists, Herston, QLD, Australia; 4School of Medicine, University of Queensland, Herston, QLD, Australia; 5Molecular Cancer Epidemiology Laboratory, Genetics and Computational Biology Division, QIMR Berghofer Medical Research Institute, Herston, QLD, AustraliaAbstract: Carriers of a germline mutation in one of the DNA mismatch repair (MMR genes have a high risk of developing numerous different cancers, predominantly colorectal cancer and endometrial cancer (known as Lynch syndrome. MMR gene mutation carriers develop tumors with MMR deficiency identified by tumor microsatellite instability or immunohistochemical loss of MMR protein expression. Tumor MMR deficiency is used to identify individuals most likely to carry an MMR gene mutation. However, MMR deficiency can also result from somatic inactivation, most commonly methylation of the MLH1 gene promoter. As tumor MMR testing of all incident colorectal and endometrial cancers (universal screening is becoming increasingly adopted, a growing clinical problem is emerging for individuals who have tumors that show MMR deficiency who are subsequently found not to carry an MMR gene mutation after genetic testing using the current diagnostic approaches (Sanger sequencing and multiplex ligation-dependent probe amplification and who also show no evidence of MLH1 methylation. The inability to determine the underlying cause of tumor MMR deficiency in these "Lynch-like" or "suspected Lynch syndrome" cases has significant implications on the clinical management of these individuals and their relatives. When the

  3. A simple method for quantification of allopurinol and oxipurinol in human serum by high-performance liquid chromatography with UV-detection

    NARCIS (Netherlands)

    Reinders, M.K.; Nijdam, L.C.; van Roon, E.N.; Movig, K.L.; Jansen, T.L.; Brouwers, J.R.

    2007-01-01

    Objectives: Allopurinol is a uric acid lowering drug used in the treatment of gout and the prevention of tumor lysis syndrome. Allopurinol and its active metabolite oxipurinol inhibit xanthine oxidase, which forms uric acid from xanthine and hypoxanthine. Therapeutic drug monitoring is an important

  4. Emerging role of rasburicase in the management of increased plasma uric acid levels in patients with hematologic malignancies

    Science.gov (United States)

    Kennedy, LeAnne D; Koontz, Susannah; Rao, Kamakshi

    2011-01-01

    Tumor lysis syndrome (TLS) is defined as a group of metabolic derangements that result from the massive and abrupt release of cellular components into the bloodstream after rapid lysis of tumor cells. Breakdown of released materials leads to a number of electrolyte abnormalities, including elevated uric acid concentrations in the blood (hyperuricemia), which carries potentially serious consequences. The diagnosis, prevention, and management of TLS is complicated by variability in definitions, differences in risk factors based on patient- and tumor-specific characteristics, and practitioner preferences in terms of pharmaceutical management strategies. The best prevention and management option for a particular patient depends on the patient’s baseline risk for TLS development, the severity of symptoms in the event of TLS development, practical management considerations, and financial implications of treatment. PMID:22287858

  5. Imaging study of lymphoreticular tumor development in ataxia-telangiectasia and Nijmegen breakage syndrome; Estudio por imagen del desarrollo de tumores linforreticulares en la ataxia telangiectasia y el sindrome de Nijmegen

    Energy Technology Data Exchange (ETDEWEB)

    Martinez-Leon, M. I.; Ceres-Ruiz, L.; Cuesta, M. A.; Garcia-Martin, F. J. [Hospital Materno-Infantil C.H.U. Carlos Haya. Malaga (Spain)

    2003-07-01

    Ataxia-telangiectasia (AT), or Louis-Bar syndrome, is an autosomal recessive illness characterized by progressive cerebellar ataxia, oculo-cutaneous telangiectasia, immunodeficiency combined with susceptibility to sinopulmonary infections and high incidence of neoplastic development. Nijmegen breakage syndrome (NBS) is a variant of AT, is also an autosomal recessive illness that presents cerebellar ataxia, as well as combined immunodeficiency and a tendency toward tumor development. Contrary to Louis-Bar syndrome, it doesn't present telangiectasia and exhibits a characteristics phenotype (short stature, bird-like face and microcephaly). Both entities are classified as syndrome of chromosomal instability or chromosomal fragility, a group which also includes Bloom syndrome and Fanconi anemia. All of these show an increase in the frequency of neoplastic pathologies, mainly lymphoid tumors. We present three patients,two with AT and one with NBS, who developed different lymphoma types in the course of the illness. We highlight the most outstanding aspects from a clinical-radiological point of view. (Author) 17 refs.

  6. A mechanism of acquired resistance to complement-mediated lysis by Entamoeba histolytica.

    Science.gov (United States)

    Gutiérrez-Kobeh, L; Cabrera, N; Pérez-Montfort, R

    1997-04-01

    Some Entamoeba histolytica strains resist complement-mediated lysis by serum. Susceptible and resistant strains activate the complement system equivalently, but resistant amebas evade killing by membrane attack complexes. Our objective was to determine the mechanism by which trophozoites of E. histolytica resist lysis by human serum. Amebas were made resistant to lysis by incubation with increasing concentrations of normal human serum. The possibility that resistant cells ingest membrane attack complexes was explored by subcellular fractionation of susceptible and resistant trophozoites treated with sublytic concentrations of human serum containing radiolabeled C9. In both cases, most of the label was in the fractions containing plasma membrane. The susceptible strain consistently showed more label associated with these fractions than the resistant strain. Thus, the possibility that the membrane attack complexes were released to the medium was explored. Both resistant and susceptible trophozoites release to the medium similar amounts of material excluded by Sepharose CL-2B in the presence or absence of normal human serum. Labeled C9 elutes together with the main bulk of proteins from the medium: this indicates that it is not in vesicles or high molecular weight aggregates. Coincubation of susceptible amebas with lysates of resistant trophozoites confers resistance to susceptible cells within 30 min. Resistance to lysis by serum can also be acquired by susceptible amebas after coincubation with lysates from human erythrocytes or after feeding them with whole human red blood cells. Resistant but not susceptible trophozoites show intense immunofluorescent staining on their surface with anti-human erythrocytic membrane antibody. These results suggest that amebas acquire resistance to lysis by serum by incorporating into their membranes complement regulatory proteins.

  7. Complement lysis activity in autologous plasma is associated with lower viral loads during the acute phase of HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Michael Huber

    2006-11-01

    Full Text Available BACKGROUND: To explore the possibility that antibody-mediated complement lysis contributes to viremia control in HIV-1 infection, we measured the activity of patient plasma in mediating complement lysis of autologous primary virus. METHODS AND FINDINGS: Sera from two groups of patients-25 with acute HIV-1 infection and 31 with chronic infection-were used in this study. We developed a novel real-time PCR-based assay strategy that allows reliable and sensitive quantification of virus lysis by complement. Plasma derived at the time of virus isolation induced complement lysis of the autologous virus isolate in the majority of patients. Overall lysis activity against the autologous virus and the heterologous primary virus strain JR-FL was higher at chronic disease stages than during the acute phase. Most strikingly, we found that plasma virus load levels during the acute but not the chronic infection phase correlated inversely with the autologous complement lysis activity. Antibody reactivity to the envelope (Env proteins gp120 and gp41 were positively correlated with the lysis activity against JR-FL, indicating that anti-Env responses mediated complement lysis. Neutralization and complement lysis activity against autologous viruses were not associated, suggesting that complement lysis is predominantly caused by non-neutralizing antibodies. CONCLUSIONS: Collectively our data provide evidence that antibody-mediated complement virion lysis develops rapidly and is effective early in the course of infection; thus it should be considered a parameter that, in concert with other immune functions, steers viremia control in vivo.

  8. Quantifying enzymatic lysis: estimating the combined effects of chemistry, physiology and physics

    International Nuclear Information System (INIS)

    Mitchell, Gabriel J; Weitz, Joshua S; Nelson, Daniel C

    2010-01-01

    The number of microbial pathogens resistant to antibiotics continues to increase even as the rate of discovery and approval of new antibiotic therapeutics steadily decreases. Many researchers have begun to investigate the therapeutic potential of naturally occurring lytic enzymes as an alternative to traditional antibiotics. However, direct characterization of lytic enzymes using techniques based on synthetic substrates is often difficult because lytic enzymes bind to the complex superstructure of intact cell walls. Here we present a new standard for the analysis of lytic enzymes based on turbidity assays which allow us to probe the dynamics of lysis without preparing a synthetic substrate. The challenge in the analysis of these assays is to infer the microscopic details of lysis from macroscopic turbidity data. We propose a model of enzymatic lysis that integrates the chemistry responsible for bond cleavage with the physical mechanisms leading to cell wall failure. We then present a solution to an inverse problem in which we estimate reaction rate constants and the heterogeneous susceptibility to lysis among target cells. We validate our model given simulated and experimental turbidity assays. The ability to estimate reaction rate constants for lytic enzymes will facilitate their biochemical characterization and development as antimicrobial therapeutics

  9. Quantifying enzymatic lysis: estimating the combined effects of chemistry, physiology and physics.

    Science.gov (United States)

    Mitchell, Gabriel J; Nelson, Daniel C; Weitz, Joshua S

    2010-10-04

    The number of microbial pathogens resistant to antibiotics continues to increase even as the rate of discovery and approval of new antibiotic therapeutics steadily decreases. Many researchers have begun to investigate the therapeutic potential of naturally occurring lytic enzymes as an alternative to traditional antibiotics. However, direct characterization of lytic enzymes using techniques based on synthetic substrates is often difficult because lytic enzymes bind to the complex superstructure of intact cell walls. Here we present a new standard for the analysis of lytic enzymes based on turbidity assays which allow us to probe the dynamics of lysis without preparing a synthetic substrate. The challenge in the analysis of these assays is to infer the microscopic details of lysis from macroscopic turbidity data. We propose a model of enzymatic lysis that integrates the chemistry responsible for bond cleavage with the physical mechanisms leading to cell wall failure. We then present a solution to an inverse problem in which we estimate reaction rate constants and the heterogeneous susceptibility to lysis among target cells. We validate our model given simulated and experimental turbidity assays. The ability to estimate reaction rate constants for lytic enzymes will facilitate their biochemical characterization and development as antimicrobial therapeutics.

  10. The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity

    Directory of Open Access Journals (Sweden)

    Ozgur Mete

    2018-03-01

    Full Text Available Adrenal cortical tumors constitute a heterogeneous group of neoplasms with distinct clinical, morphological, and molecular features. Recent discoveries of specific genotype–phenotype correlations in adrenal cortical adenomas have transformed our understanding of their respective endocrine syndromes. Indeed, a proportion of patients with primary aldosteronism are now known to harbor adrenal cortical adenomas with heterogeneous molecular alterations (KCNJ5, ATP1A1, ATP2B3, and CACNA1D involving the calcium/calmodulin kinase signaling pathway. Several lines of evidence suggest that KCNJ5-mutant aldosterone-producing adenomas have distinct clinicopathological phenotype compared to those harboring ATP1A1, ATP2B3, and CACNA1D mutations. Benign adrenal cortical tumors presenting with Cushing syndrome often have diverse mutations (PRKACA, PRKAR1A, GNAS, PDE11A, and PDE8B involving the cyclic AMP signaling pathway. In addition to cortisol-producing adenomas, bilateral micronodular adrenocortical disease and primary bilateral macronodular adrenal hyperplasia (PBMAH have also expanded the spectrum of benign neoplasms causing adrenal Cushing disease. The recent discovery of inactivating ARMC5 germline mutations in PBMAH has challenged the old belief that this disorder is mainly a sporadic disease. Emerging evidence suggests that PBMAH harbors multiple distinct clonal proliferations, reflecting the heterogeneous genomic landscape of this disease. Although most solitary adrenal cortical tumors are sporadic, there is an increasing recognition that inherited susceptibility syndromes may also play a role in their pathogenesis. This review highlights the molecular and morphological heterogeneity of benign adrenal cortical neoplasms, reflected in the diverse presentations of primary aldosteronism and adrenal Cushing syndrome.

  11. Failure-to-thrive syndrome associated with tumor formation by Madin-Darby canine kidney cells in newborn nude mice.

    Science.gov (United States)

    Brinster, Lauren R; Omeir, Romelda L; Foseh, Gideon S; Macauley, Juliete N; Snoy, Philip J; Beren, Joel J; Teferedegne, Belete; Peden, Keith; Lewis, Andrew M

    2013-08-01

    Tumors that formed in newborn nude mice that were inoculated with 10(7) Madin-Darby canine kidney (MDCK) cells were associated with a failure-to-thrive (FTT) syndrome consisting of growth retardation, lethargy, weakness, and dehydration. Scoliosis developed in 41% of affected pups. Pups were symptomatic by week 2; severely affected pups became moribund and required euthanasia within 3 to 4 wk. Mice with FTT were classified into categories of mild, moderate, and severe disease by comparing their weight with that of age-matched normal nude mice. The MDCK-induced tumors were adenocarcinomas that invaded adjacent muscle, connective tissue, and bone; 6 of the 26 pups examined had lung metastases. The induction of FTT did not correlate with cell-line aggressiveness as estimated by histopathology or the efficiency of tumor formation (tumor-forming dose 50% endpoint range = 10(2.8) to 10(7.5)); however, tumor invasion of the paravertebral muscles likely contributed to the scoliosis noted. In contrast to the effect of MDCK cells, tumor formation observed in newborn mice inoculated with highly tumorigenic, human-tumor-derived cell lines was not associated with FTT development. We suggest that tumor formation and FTT are characteristics of these MDCK cell inocula and that FTT represents a new syndrome that may be similar to the cachexia that develops in humans with cancer or other diseases.

  12. Inflammatory potential of the diet and colorectal tumor risk in persons with Lynch syndrome

    NARCIS (Netherlands)

    Brouwer, Jesca G.M.; Makama, Maureen; Woudenbergh, Van Geertruida J.; Vasen, Hans F.A.; Nagengast, Fokko M.; Kleibeuker, Jan H.; Kampman, Ellen; Duijnhoven, Van Fränzel J.B.

    2017-01-01

    Background: Persons with Lynch syndrome (LS) have high lifetime risk of developing colorectal tumors (CRTs) because of a germline mutation in one of their mismatch repair (MMR) genes. An important process in the development of CRTs is inflammation, which has been shown to be modulated by diet.

  13. Children with Idiopathic Hemihypertrophy and Beckwith-Wiedemann Syndrome Have Different Constitutional Epigenotypes Associated with Wilms Tumor

    OpenAIRE

    Niemitz, Emily L. ; Feinberg, Andrew P. ; Brandenburg, Sheri A. ; Grundy, Paul E. ; DeBaun, Michael R. 

    2005-01-01

    Idiopathic hemihypertrophy (IH) is a congenital overgrowth syndrome associated with an increased risk of embryonal cancers in childhood. A related developmental disorder is Beckwith-Wiedemann syndrome (BWS), which increases risk for embryonal cancers, including Wilms tumor. Constitutional epigenetic alterations associated with BWS have been well characterized and include epigenetic alterations of imprinted genes on 11p15. The frequency of hypermethylation of H19 in children with IH and Wilms ...

  14. Surgical strategies in endocrine tumors

    NARCIS (Netherlands)

    Schreinemakers, J.M.J.

    2010-01-01

    Endocrine surgery has become more custom-made throughout the years. Endocrine tumors can be sporadic or develop as part of familial syndromes. Several familial syndromes are known to cause endocrine tumors. The most common are multiple endocrine neoplasia (MEN) syndromes type 1, 2A and 2B. This

  15. [Treatment of surface burns with proteolytic enzymes: mathematic description of lysis kinetics].

    Science.gov (United States)

    Domogatskaia, A S; Domogatskiĭ, S P; Ruuge, E K

    2003-01-01

    The lysis of necrotic tissue by a proteolytic enzyme applied to the surface of a burn wound was studied. A mathematical model was proposed, which describes changes in the thickness of necrotic tissue as a function of the proteolytic activity of the enzyme. The model takes into account the inward-directed diffusion of the enzyme, the counterflow of interstitial fluid (exudates) containing specific inhibitors, and the extracellular matrix proteolysis. It was shown in terms of the quasi-stationary approach that the thickness of the necrotic tissue layer decreases exponentially with time; i.e., the lysis slows down as the thickness of the necrotic tissue layer decreases. The dependence of the characteristic time of this decrease on enzyme concentration was obtained. It was shown that, at high enzyme concentrations (more than 5 mg/ml), the entire time of lysis (after the establishment of quasi-stationary equilibrium) is inversely proportional to the concentration of the enzyme.

  16. Tumor-Associated Macrophages in Oncolytic Virotherapy: Friend or Foe?

    Directory of Open Access Journals (Sweden)

    Nicholas L. Denton

    2016-07-01

    Full Text Available Cancer therapy remains a challenge due to toxicity limitations of chemotherapy and radiation therapy. Oncolytic viruses that selectively replicate and destroy cancer cells are of increasing interest. In addition to direct cell lysis, these vectors stimulate an anti-tumor immune response. A key regulator of tumor immunity is the tumor-associated macrophage population. Macrophages can either support oncolytic virus therapy through pro-inflammatory stimulation of the anti-tumor response at the cost of hindering direct oncolysis or through immunosuppressive protection of virus replication at the cost of hindering the anti-tumor immune response. Despite similarities in macrophage interaction between adult and pediatric tumors and the abundance of research supporting macrophage modulation in adult tumors, there are few studies investigating macrophage modulation in pediatric cancers or modulation of immunotherapy. We review the current state of knowledge regarding macrophages in cancers and their influence on oncolytic virotherapy.

  17. Enhanced lysis of herpes simplex virus type 1-infected mouse cell lines by NC and NK effectors

    Energy Technology Data Exchange (ETDEWEB)

    Colmenares, C.; Lopez, C.

    1986-05-01

    Spontaneously cytotoxic murine lymphocytes lysed certain cell types infected by herpes simplex virus type 1 (HSV-1) better than uninfected cells. Although HSV-1 adsorbed to the surface of all the target cells, those in which the virus replicated more efficiently were lysed to a greater extent. As targets, the authors used cell lines that, when uninfected, were spontaneously lysed by NK cells (YAC-1) or by NC cells (WEHI-164). They also used a fibroblastoid cell line (M50) and a monocytic tumor line (PU51R), which were not spontaneously killed. NK cells lysed HSV-1-infected YAC cells better than uninfected cells, and an NC-like activity selectively lysed HSV-1-infected WEHI cells. These findings were consistent with the results of experiments performed to define the role of interferon in induction of virus-augmented cytolysis. Increased lysis of YAC-HSV and PU51R-HSV was entirely due to interferon activation and was completely abolished by performing the /sup 51/Cr-release assay in the presence of anti-interferon serum. The data show that HSV-1 infection of NK/NC targets induces increased cytotoxity, but the effector cell responsible for lysis is determined by the uninfected target, or by an interaction between the virus and target cell, rather than by a viral determinant alone.

  18. Evaluation of conventional castaneda and lysis centrifugation blood culture techniques for diagnosis of human brucellosis.

    Science.gov (United States)

    Mantur, Basappa G; Mangalgi, Smita S

    2004-09-01

    We investigated the role of the lysis centrifugation blood culture technique over the conventional Castaneda technique for the diagnosis of human brucellosis. The lysis centrifugation technique has been found to be more sensitive in both acute (20% higher sensitivity; P centrifugation was in the mean detection time, which was only 2.4 days in acute and 2.7 days in chronic cases, with 103 out of 110 (93.6%) and 17 out of 20 (85%) cultures from acute and chronic brucellosis, respectively, detected before the conventional culture was positive. Our results confirmed the potential usefulness of the lysis technique in diagnosis and institution of appropriate antibiotic therapy.

  19. Nucleation of holin domains and holes optimizes lysis timing of E. coli by phage λ

    Science.gov (United States)

    Ryan, Gillian; Rutenberg, Andrew

    2007-03-01

    Holin proteins regulate the precise scheduling of Escherichia coli lysis during infection by bacteriophage λ. Inserted into the host bacterium's inner membrane during infection, holins aggregate to form rafts and then holes within those rafts. We present a two-stage nucleation model of holin action, with the nucleation of condensed holin domains followed by the nucleation of holes within these domains. Late nucleation of holin rafts leads to a weak dependence of lysis timing on host cell size, though both nucleation events contribute equally to timing errors. Our simulations recover the accurate scheduling observed experimentally, and also suggest that phage-λ lysis of E.coli is optimized.

  20. Rapid kinetics of lysis in human natural cell-mediated cytotoxicity: some implications

    International Nuclear Information System (INIS)

    Bloom, E.T.; Babbitt, J.T.

    1983-01-01

    The entire lytic process of natural cell-mediated cytotoxicity against sensitive target cells can occur rapidly, within minutes. This was demonstrated by 51 chromium release and in single-cell assays. At the cellular level, most of the target cell lysis occurred within 15-30 min after binding to effector cells. The enriched natural killer cell subpopulation of lymphocytes obtained by Percoll density gradient centrifugation (containing greater than 70% large granular lymphocytes (LGL)) was the most rapidly lytic population by 51 chromium release. However, in the single-cell assay, the rate of lysis of bound target cells was quite similar for the LGL-enriched effector subpopulation and the higher density subpopulation of effector cells recognized previously. Both the light and dense effector cells contained similar numbers of target binding cells. Therefore, that the light subpopulation effected lysis more rapidly and to a greater extent than the dense subpopulation suggested that the low-density effector cells probably recycled more rapidly than those of higher density. This was corroborated by the finding that when conjugates were formed at 29 degrees C for the single-cell assay, a significant number of dead unconjugated targets could be observed only on the slides made with the LGL-enriched effector cells but not on those made with dense effector cell. Lysis continued to increase in the chromium-release assay probably because of recycling, recruitment, and/or heterogeneity of the effector cells, and/or because of heterogeneity or delayed death of the target cells

  1. Consequences of diagnosing a tumor predisposition syndrome in children with cancer: A literature review

    NARCIS (Netherlands)

    Postema, Floor A. M.; Hopman, Saskia M. J.; Hennekam, Raoul C.; Merks, Johannes H. M.

    2018-01-01

    Up to 8.5% of children with cancer have a genetic cause for their cancer: a tumor predisposition syndrome (TPS). Diagnosing a TPS is of great importance, as it may have major consequences for clinical care. Patients with TPSs require specific monitoring and management. We present an overview of the

  2. Relationship between laminin binding capacity and laminin expression on tumor cells sensitive or resistant to natural cell-mediated cytotoxicity

    International Nuclear Information System (INIS)

    Laybourn, K.A.; Varani, J.; Fligiel, S.E.G.; Hiserodt, J.C.

    1986-01-01

    Previous studies have identified the presence of laminin binding sites on murine NK and NC sensitive tumor cells by 125 I-laminin binding and laminin induced cell-cell aggregation. The finding that the addition of exogenous laminin inhibits NK/NC binding to sensitive tumor cells suggests laminin binding sites may serve as target antigens for NK cells. The present study extends earlier reports by analyzing a large panel of tumor cells for laminin binding capacity, laminin expression and sensitivity to NK/NC killing. The data indicate that all tumor cells which bind to NK/NC cells (8 lines tested) express laminin binding sites. All of these tumor cells were capable of competing for NK lysis of YAC-1 cells in cold target competition assays, and all bound enriched NK cells in direct single cell binding assays. In contrast, tumor cells expressing high levels of surface laminin (B16 melanomas, C57B1/6 fibrosarcomas, and RAS transfected 3T3 fibroblasts) but low levels of laminin binding capacity did not bind NK/NC cells and were resistant to lysis. These data support the hypothesis that expression of laminin/laminin binding sites may contribute to tumor cell sensitivity to NK/NC binding and/or killing

  3. Contribution of MLH1 constitutional methylation for Lynch syndrome diagnosis in patients with tumor MLH1 downregulation.

    Science.gov (United States)

    Pinto, Diana; Pinto, Carla; Guerra, Joana; Pinheiro, Manuela; Santos, Rui; Vedeld, Hege Marie; Yohannes, Zeremariam; Peixoto, Ana; Santos, Catarina; Pinto, Pedro; Lopes, Paula; Lothe, Ragnhild; Lind, Guro Elisabeth; Henrique, Rui; Teixeira, Manuel R

    2018-02-01

    Constitutional epimutation of the two major mismatch repair genes, MLH1 and MSH2, has been identified as an alternative mechanism that predisposes to the development of Lynch syndrome. In the present work, we aimed to investigate the prevalence of MLH1 constitutional methylation in colorectal cancer (CRC) patients with abnormal expression of the MLH1 protein in their tumors. In a series of 38 patients who met clinical criteria for Lynch syndrome genetic testing, with loss of MLH1 expression in the tumor and with no germline mutations in the MLH1 gene (35/38) or with tumors presenting the BRAF p.Val600Glu mutation (3/38), we screened for constitutional methylation of the MLH1 gene promoter using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in various biological samples. We found four (4/38; 10.5%) patients with constitutional methylation in the MLH1 gene promoter. RNA studies demonstrated decreased MLH1 expression in the cases with constitutional methylation when compared with controls. We could infer the mosaic nature of MLH1 constitutional hypermethylation in tissues originated from different embryonic germ layers, and in one family we could show that it occurred de novo. We conclude that constitutional MLH1 methylation occurs in a significant proportion of patients who have loss of MLH1 protein expression in their tumors and no MLH1 pathogenic germline mutation. Furthermore, we provide evidence that MLH1 constitutional hypermethylation is the molecular mechanism behind about 3% of Lynch syndrome families diagnosed in our institution, especially in patients with early onset or multiple primary tumors without significant family history. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  4. Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome.

    OpenAIRE

    Naves, Luciana A.; Daly, Adrian Francis; Dias, Luiz Augusto; Yuan, Bo; Zakir, Juliano Coelho Oliveira; Barra, Gustavo Barcellos; Palmeira, Leonor; Villa, Chiara; Trivellin, Giampaolo; Junior, Armindo Jreige; Neto, Florencio Figueiredo Cavalcante; Liu, Pengfei; Pellegata, Natalia S.; Stratakis, Constantine A.; Lupski, James R.

    2016-01-01

    X-linked acro-gigantism (X-LAG) syndrome is a newly described disease caused by microduplications on chromosome Xq26.3 leading to copy number gain of GPR101. We describe the clinical progress of a sporadic male X-LAG syndrome patient with an Xq26.3 microduplication, highlighting the aggressive natural history of pituitary tumor growth in the absence of treatment. The patient first presented elsewhere aged 5 years 8 months with a history of excessive growth for >2 years. His height was 163 cm,...

  5. Virus-specific HLA-restricted lysis of herpes simplex virus-infected human monocytes and macrophages mediated by cytotoxic T lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Torpey, D.J. III

    1987-01-01

    Freshly-isolated peripheral blood human monocytes and 5 day in vitro cultured macrophages were infected with herpes simplex virus type 1 (HSV-1), labeled with /sup 51/Cr, and used as target cells in a 12-14 hour cell-mediated cytotoxicity assay. Mononuclear leukocytes (MNL) from HSV-1 non-immune individuals, whether unstimulated or stimulated with HSV-1 antigen, did not mediate significant lysis of either target cell. HSV-immune MNL, both freshly-isolated and cultured for 5 days without antigen, demonstrated only low levels of natural killer (NK) cell-mediate lysis. MNL from HSV-immune individuals incubated for 5 days in vitro with HSV-1 antigen mediated significant virus-specific lysis of both target cells. Mean virus-specific lysis of autologous monocytes was 8.5(/+-/2.0)% compared to a three-fold greater virus-specific lysis of autologous macrophages. Greater than 70% of this lytic activity was mediated by Leu-11-negative, T3-positive cytotoxic T lymphocytes (CTL). Allogeneic target cells lacking a common HLA determinant were not significantly lysed while T8-positive CTL mediated infrequent lysis of target cells sharing a common HLA-A and/or HLA-B determinant. T4-positive lymphocytes were demonstrated to be the predominant cell mediating lysis of autologous target cells and allogeneic target cells sharing both HLA-A and/or HLA-B plus HLA-DR determinants with the CTL; the T4-positive cell was the sole CTL mediator of lysis of allogeneic target cells having a common HLA-DR determinant.

  6. Virus-specific HLA-restricted lysis of herpes simplex virus-infected human monocytes and macrophages mediated by cytotoxic T lymphocytes

    International Nuclear Information System (INIS)

    Torpey, D.J. III.

    1987-01-01

    Freshly-isolated peripheral blood human monocytes and 5 day in vitro cultured macrophages were infected with herpes simplex virus type 1 (HSV-1), labeled with 51 Cr, and used as target cells in a 12-14 hour cell-mediated cytotoxicity assay. Mononuclear leukocytes (MNL) from HSV-1 non-immune individuals, whether unstimulated or stimulated with HSV-1 antigen, did not mediate significant lysis of either target cell. HSV-immune MNL, both freshly-isolated and cultured for 5 days without antigen, demonstrated only low levels of natural killer (NK) cell-mediate lysis. MNL from HSV-immune individuals incubated for 5 days in vitro with HSV-1 antigen mediated significant virus-specific lysis of both target cells. Mean virus-specific lysis of autologous monocytes was 8.5(/+-/2.0)% compared to a three-fold greater virus-specific lysis of autologous macrophages. Greater than 70% of this lytic activity was mediated by Leu-11-negative, T3-positive cytotoxic T lymphocytes (CTL). Allogeneic target cells lacking a common HLA determinant were not significantly lysed while T8-positive CTL mediated infrequent lysis of target cells sharing a common HLA-A and/or HLA-B determinant. T4-positive lymphocytes were demonstrated to be the predominant cell mediating lysis of autologous target cells and allogeneic target cells sharing both HLA-A and/or HLA-B plus HLA-DR determinants with the CTL; the T4-positive cell was the sole CTL mediator of lysis of allogeneic target cells having a common HLA-DR determinant

  7. Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

    Science.gov (United States)

    Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R

    2016-06-01

    Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

  8. All-in-one nanowire-decorated multifunctional membrane for rapid cell lysis and direct DNA isolation.

    KAUST Repository

    So, Hongyun; Lee, Kunwoo; Murthy, Niren; Pisano, Albert P

    2014-01-01

    This paper describes a handheld device that uses an all-in-one membrane for continuous mechanical cell lysis and rapid DNA isolation without the assistance of power sources, lysis reagents, and routine centrifugation. This nanowire-decorated multifunctional membrane was fabricated to isolate DNA by selective adsorption to silica surface immediately after disruption of nucleus membranes by ultrasharp tips of nanowires for a rapid cell lysis, and it can be directly assembled with commercial syringe filter holders. The membrane was fabricated by photoelectrochemical etching to create microchannel arrays followed by hydrothermal synthesis of nanowires and deposition of silica. The proposed membrane successfully purifies high-quality DNA within 5 min, whereas a commercial purification kit needs more than an hour.

  9. All-in-one nanowire-decorated multifunctional membrane for rapid cell lysis and direct DNA isolation.

    KAUST Repository

    So, Hongyun

    2014-11-24

    This paper describes a handheld device that uses an all-in-one membrane for continuous mechanical cell lysis and rapid DNA isolation without the assistance of power sources, lysis reagents, and routine centrifugation. This nanowire-decorated multifunctional membrane was fabricated to isolate DNA by selective adsorption to silica surface immediately after disruption of nucleus membranes by ultrasharp tips of nanowires for a rapid cell lysis, and it can be directly assembled with commercial syringe filter holders. The membrane was fabricated by photoelectrochemical etching to create microchannel arrays followed by hydrothermal synthesis of nanowires and deposition of silica. The proposed membrane successfully purifies high-quality DNA within 5 min, whereas a commercial purification kit needs more than an hour.

  10. Effect of ultrasonic frequency on the mechanism of formic acid sono-lysis

    International Nuclear Information System (INIS)

    Chave, T.; Nikitenko, S.I.; Navarro, N.M.; Pochon, P.; Bisel, I.

    2011-01-01

    The kinetics and mechanism of formic acid sono-chemical degradation were studied at ultrasonic frequencies of 20, 200, and 607 kHz under argon atmosphere. Total yield of HCOOH sono-chemical degradation increases approximately 6-8-fold when the frequency increased from 20 to 200 or to 607 kHz. At low ultrasonic frequencies, HCOOH degradation has been attributed to oxidation with OH . radicals from water sono-lysis and to the HCOOH decarboxylation occurring at the cavitation bubble-liquid interface. With high-frequency ultrasound, the sono-chemical reaction is also influenced by HCOOH dehydration. Whatever the ultrasonic frequency, the sono-lysis of HCOOH yielded H 2 and CO 2 in the gas phase as well as trace, amounts of oxalic acid and formaldehyde in the liquid phase. However, CO and CH 4 formations were only detected under high frequency ultrasound. The most striking difference between low frequency and high frequency ultrasound is that the sono-lysis of HCOOH at high ultrasonic frequencies initiates Fischer-Tropsch hydrogenation of carbon monoxide. (authors)

  11. Rhabdoid tumor predisposition syndrome caused by SMARCB1 constitutional deletion: prenatal detection of new case of recurrence in siblings due to gonadal mosaicism.

    Science.gov (United States)

    Gigante, Laura; Paganini, Irene; Frontali, Marina; Ciabattoni, Serena; Sangiuolo, Federica Carla; Papi, Laura

    2016-01-01

    Rhabdoid tumors are aggressive malignancies that show loss-of-function mutations of SMARCB1 gene, a member of the SWI/SNF chromatin-remodeling complex controlling gene transcription. One-third of patients affected by rhabdoid tumor harbor a germ-line mutation of SMARCB1 defining a rhabdoid tumor predisposition syndrome. The occurrence of a second somatic mutation determines the development of neoplasia in a two-hit model. Most germ-line mutations occur de novo, and few cases of recurrence in a sibship have been described. Here we report on a new Italian family with recurrence of SMARCB1 germ-line deletion in two siblings due to gonadal mosaicism. The deletion was identified in the 9-month-old proband with malignant rhabdoid tumor of the right kidney and disseminated metastases. Testing of both parents confirmed the de novo origin of the mutation, but recurrence was then detected prenatally in a new pregnancy. This is the sixth family with malignant rhabdoid tumor predisposition syndrome with the recurrence of the same germ-line SMARCB1 mutation in the sibship but not in healthy parents, suggesting that gonadal mosaicism is a less rare event than supposed. The clinical outcome in our patient confirms previous data of poorer outcome in patients with rhabdoid tumor predisposition syndrome.

  12. Polyostotic fibrous dysplasia with gigantism and huge pelvic tumor: a rare case of McCune-Albright syndrome.

    Science.gov (United States)

    Sakayama, Kenshi; Sugawara, Yoshifumi; Kidani, Teruki; Fujibuchi, Taketsugu; Kito, Katsumi; Tanji, Nozomu; Nakamura, Atsushi

    2011-06-01

    We report a rare case of polyostotic fibrous dysplasia on endocrine hyperfunction with elevated human growth hormone and normal serum level of prolactin. There were some differential points of gender, gigantism, endocrine function, and GNAS gene from McCune-Albright syndrome. Malignant transformation was suspected in the pelvic tumor from imaging because rapid growth of the tumor by imaging was observed; however, no malignant change occurred in this case.

  13. The euglobulin clot lysis time to assess the impact of nanoparticles on fibrinolysis

    Energy Technology Data Exchange (ETDEWEB)

    Minet, Valentine, E-mail: valentine.minet@unamur.be; Alpan, Lutfiye; Mullier, François [University of Namur – UNamur, Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Nanosafety Center (NNC), NAmur Research Institute for Life Sciences NARILIS (Belgium); Toussaint, Olivier [Laboratory of Cellular Biochemistry and Biology (URBC) (Belgium); Lucas, Stéphane [University of Namur (UNamur), Research Centre for the Physics of Matter and Radiation (PMR-LARN), Namur Nanosafety Center NNC, NAmur Research Institute for Life Sciences NARILIS (Belgium); Dogné, Jean-Michel; Laloy, Julie, E-mail: julie.laloy@unamur.be [University of Namur – UNamur, Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Nanosafety Center (NNC), NAmur Research Institute for Life Sciences NARILIS (Belgium)

    2015-07-15

    Nanoparticles (NPs) are developed for many applications in various fields, including nanomedicine. The NPs used in nanomedicine may disturb homeostasis in blood. Secondary hemostasis (blood coagulation) and fibrinolysis are complex physiological processes regulated by activators and inhibitors. An imbalance of this system can either lead to the development of hemorrhages or thrombosis. No data are currently available on the impact of NPs on fibrinolysis. The objectives of this study are (1) to select a screening test to study ex vivo the impact of NPs on fibrinolysis and (2) to test NPs with different physicochemical properties. Euglobulin clot lysis time test was selected to screen the impact of some NPs on fibrinolysis using normal pooled plasma. A dose-dependent decrease in the lysis time was observed with silicon dioxide and silver NPs without disturbing the fibrin network. Carbon black, silicon carbide, and copper oxide did not affect the lysis time at the tested concentrations.

  14. Study of the phage production efficiency in the bacteria lysis processes

    International Nuclear Information System (INIS)

    Vidania Munoz, R. de; Garces, F.; Davila, C. A.

    1979-01-01

    In this work we present a search for the best production conditions of λvir andλ clear phages In E coli K12 and E coli C 6 00 infected cells respectively. By keeping fixed some parameters of the process as the bacterial and phage generation times and (he bacterial burst side, we have finder that the lysis yield is strongly dependent on the multiplicity and in a lesser degree on the infection time. It appears from the experimental results that other variables are important, as infection efficiency and approach time from phages to bacteria. We will try to describe the lysis phenomenon by a numerical model on the bases of the se experimental results. (Author) 11 refs

  15. Ectopic adrenocorticotropic hormone syndrome in a case of duodenal neuroendocrine tumor presenting with liver metastasis

    Directory of Open Access Journals (Sweden)

    J Khare

    2018-01-01

    Full Text Available Ectopic adrenocorticotropic hormone (ACTH syndrome is an uncommon disorder and comprises about 15% of all patients with Cushing's syndrome (CS. Duodenal carcinoids are rare, indolent tumors usually associated with a benign progression. We hereby report a rare case of CS resulting from ectopic ACTH secretion from a duodenal neuroendocrine tumor (NET presenting with liver metastasis. A 37-year-old female presented with abdominal discomfort and dyspepsia of 1-month duration. Ultrasound abdomen suggested a well-defined hypoechoic lesion in the left lobe of the liver, suggestive of neoplasia. On clinical examination, she had Cushingoid features and persistent hypokalemia. Midnight ACTH and cortisol levels were grossly elevated at 1027 pg/ml (n < 46 pg/ml and 87.56 μg/dl (n < 7.5 μg/ml, respectively. Both overnight and high-dose dexamethasone suppression test confirmed nonsuppressed cortisol levels - 86.04 and 84.42 μg/dl (n < 1.8 μg/ml, respectively. Magnetic resonance imaging brain showed a structurally normal pituitary gland. Computed tomography scan of the abdomen revealed hepatic lesion with bilateral adrenal enlargement. A diagnosis of ectopic ACTH-dependent CS was made. Intraoperatively, a duodenal lesion of 0.5 cm × 0.5 cm was identified alongside an 8 cm × 6 cm exophytic lesion in segment IV of the liver. Frozen section of the duodenal lesion was positive for NET. She underwent a Whipple's surgery, cholecystectomy, and left hepatic lobectomy. Postoperatively, she showed clinical and biochemical remission. Herewith, we report the third case of duodenal carcinoid tumor presenting as ectopic ACTH syndrome and the first with liver metastasis.

  16. Superiority of SDS lysis over saponin lysis for direct bacterial identification from positive blood culture bottle by MALDI-TOF MS.

    Science.gov (United States)

    Caspar, Yvan; Garnaud, Cécile; Raykova, Mariya; Bailly, Sébastien; Bidart, Marie; Maubon, Danièle

    2017-05-01

    Fast species diagnosis has an important health care impact, as rapid and specific antibacterial therapy is of clear benefit for patient's outcome. Here, a new protocol for species identification directly from positive blood cultures is proposed. Four in-house protocols for bacterial identification by MS directly from clinical positive blood cultures evaluating two lytic agents, SDS and saponin, and two protein extraction schemes, fast (FP) and long (LP) are compared. One hundred and sixty-eight identification tests are carried out on 42 strains. Overall, there are correct identifications to the species level in 90% samples for the SDS-LP, 60% for the SDS-FP, 48% for the saponin LP, and 43% for the saponin FP. Adapted scores allowed 92, 86, 72, and 53% identification for SDS-LP, SDS-FP, saponin LP, and saponin FP, respectively. Saponin lysis is associated with a significantly lower score compared to SDS (0.87 [0.83-0.92], p-value saponin lysis and the application of this rapid and cost-effective protocol in daily routine for microbiological agents implicated in septicemia. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Direct Cellular Lysis/Protein Extraction Protocol for Soil Metaproteomics

    Energy Technology Data Exchange (ETDEWEB)

    Chourey, Karuna [ORNL; Jansson, Janet [Lawrence Berkeley National Laboratory (LBNL); Verberkmoes, Nathan C [ORNL; Shah, Manesh B [ORNL; Chavarria, Krystle L. [Lawrence Berkeley National Laboratory (LBNL); Tom, Lauren M [Lawrence Berkeley National Laboratory (LBNL); Brodie, Eoin L. [Lawrence Berkeley National Laboratory (LBNL); Hettich, Robert {Bob} L [ORNL

    2010-01-01

    We present a novel direct protocol for deep proteome characterization of microorganisms in soil. The method employs thermally assisted detergent-based cellular lysis (SDS) of soil samples, followed by TCA precipitation for proteome extraction/cleanup prior to liquid chromatography-mass spectrometric characterization. This approach was developed and optimized using different soils inoculated with genome-sequenced bacteria (Gram-negative Pseudomonas putida or Gram-positive Arthrobacter chlorophenolicus). Direct soil protein extraction was compared to protein extraction from cells isolated from the soil matrix prior to lysis (indirect method). Each approach resulted in identification of greater than 500 unique proteins, with a wide range in molecular mass and functional categories. To our knowledge, this SDS-TCA approach enables the deepest proteome characterizations of microbes in soil to date, without significant biases in protein size, localization, or functional category compared to pure cultures. This protocol should provide a powerful tool for ecological studies of soil microbial communities.

  18. Tumor suppressor microRNAs are downregulated in myelodysplastic syndrome with spliceosome mutations

    DEFF Research Database (Denmark)

    Aslan, Derya; Garde, Christian; Nygaard, Mette Katrine

    2016-01-01

    Spliceosome mutations are frequently observed in patients with myelodysplastic syndromes (MDS). However, it is largely unknown how these mutations contribute to the disease. MicroRNAs (miRNAs) are small noncoding RNAs, which have been implicated in most human cancers due to their role in post...... the most downregulated miRNAs were several tumor-suppressor miRNAs, including several let-7 family members, miR-423, and miR-103a. Finally, we observed that the predicted targets of the most downregulated miRNAs were involved in apoptosis, hematopoiesis, and acute myeloid leukemia among other cancer......- and metabolic pathways. Our data indicate that spliceosome mutations may play an important role in MDS pathophysiology by affecting the expression of tumor suppressor miRNA genes involved in the development and progression of MDS....

  19. Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome.

    Science.gov (United States)

    Naves, Luciana A; Daly, Adrian F; Dias, Luiz Augusto; Yuan, Bo; Zakir, Juliano Coelho Oliveira; Barra, Gustavo Barcellos; Palmeira, Leonor; Villa, Chiara; Trivellin, Giampaolo; Júnior, Armindo Jreige; Neto, Florêncio Figueiredo Cavalcante; Liu, Pengfei; Pellegata, Natalia S; Stratakis, Constantine A; Lupski, James R; Beckers, Albert

    2016-02-01

    X-linked acro-gigantism (X-LAG) syndrome is a newly described disease caused by microduplications on chromosome Xq26.3 leading to copy number gain of GPR101. We describe the clinical progress of a sporadic male X-LAG syndrome patient with an Xq26.3 microduplication, highlighting the aggressive natural history of pituitary tumor growth in the absence of treatment. The patient first presented elsewhere aged 5 years 8 months with a history of excessive growth for >2 years. His height was 163 cm, his weight was 36 kg, and he had markedly elevated GH and IGF-1. MRI showed a non-invasive sellar mass measuring 32.5 × 23.9 × 29.1 mm. Treatment was declined and the family was lost to follow-up. At the age of 10 years and 7 months, he presented again with headaches, seizures, and visual disturbance. His height had increased to 197 cm. MRI showed an invasive mass measuring 56.2 × 58.1 × 45.0 mm, with compression of optic chiasma, bilateral cavernous sinus invasion, and hydrocephalus. His thyrotrope, corticotrope, and gonadotrope axes were deficient. Surgery, somatostatin analogs, and cabergoline did not control vertical growth and pegvisomant was added, although vertical growth continues (currently 207 cm at 11 years 7 months of age). X-LAG syndrome is a new genomic disorder in which early-onset pituitary tumorigenesis can lead to marked overgrowth and gigantism. This case illustrates the aggressive nature of tumor evolution and the challenging clinical management in X-LAG syndrome.

  20. Coincidence of Persistent Müllerian duct syndrome and testicular tumors in dogs.

    Science.gov (United States)

    Park, Eun Jung; Lee, Seok-Hee; Jo, Young-Kwang; Hahn, Sang-Eun; Go, Do-Min; Lee, Su-Hyung; Lee, Byeong-Chun; Jang, Goo

    2017-06-02

    Persistent Müllerian duct syndrome (PMDS), a rare form of male pseudohermaphroditism in dogs, is an abnormal sexual phenotype in males that is characterized by the existence of a hypoplastic oviduct, uterus, and cranial part of the vagina. Dogs suffering from PMDS are often accompanied by cryptorchidism. To date, it has been mainly found in the Miniature Schnauzer breed. In this report, two cases of PMDS with a malignant testicular tumor originating from cryptorchidism in breeds other than the Miniature Schnauzer breed are described. The patients were a seven-year-old male Maltese dog and a 17-year-old male mixed-breed dog weighing 3.8 kg. They also exhibited an enlarged prostate with or without abscess and an elevated serum estradiol level and were surgically treated to remove the testicular tumor and Müllerian duct derivatives. It is recommended that PMDS should be differentially diagnosed by ultrasonography and that orchiectomy be performed at an early age in patients suspected to have cryptorchidism to prevent the ectopic testes from becoming tumorous.

  1. Dark membrane lysis and photosensitization by 3-carbethoxypsoralen

    Energy Technology Data Exchange (ETDEWEB)

    Muller-Runkel, R.; Grossweiner, L.I. (Illinois Inst. of Tech., Chicago (USA). Dept. of Physics)

    1981-03-01

    Aqueous solutions of 3-carbethoxypsoralen (3-CPs) induced lysis of egg lecithin liposomes and whole human erythrocytes in the dark. Near-UV irradiation of 3-CPs sensitized the inactivation of lysozyme attributed to the production of reactive radical intermediates. The implications of these findings for the use of 3-CPs as a sensitizer in psoralen + UV-A (PUVA) therapy of psoriasis are discussed.

  2. Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE for Metastatic Neuroendocrine Tumor Occurring in Association with Multiple Endocrine Neoplasia Type 1 and Cushing's Syndrome.

    Science.gov (United States)

    Naik, Chinna; Basu, Sandip

    2017-01-01

    Neuroendocrine tumor (NET) occurring in association with other endocrine syndromes forms a distinct entity. The aim was to assess the therapy response profile of the routine peptide receptor radionuclide therapy (PRRT) in this relatively uncommon but clinically challenging subgroup of patients. A retrospective analysis was undertaken from the case records from those who were treated with 177 Lu-DOTATATE for metastatic NET. In addition to assessing the therapeutic efficacy, emphasis was also given to study lesional sites and scan pattern. A total of 5 cases were found: In this series of five cases, four belonged to multiple endocrine neoplasia type 1 (MEN1) syndrome; in these four MEN1 syndrome patients, the primary site of NET was thymic region ( n = 1), duodenum ( n = 1), and pancreas ( n = 2). The fifth case was of Cushing's syndrome with the primary site of NET in the thymus. A good symptomatic response was observed in all MEN1 syndrome cases (100%) and progression of symptoms in the patient with Cushing's syndrome. The biochemical response (assessed by measurement of tumor marker serum chromogranin A) demonstrated very good partial response (defined by more than 75% reduction of tumor marker) in 2 MEN1 cases and Cushing's syndrome, good partial response (25-75% reduction of tumor marker) in the remaining 2 MEN1 cases. Scan wise (assessed by technetium [ 99m Tc]-hydrazinonicotinamide [HYNIC]-tektrotyd [TOC]/ 68 Ga-DOTA-NOC/TATE positron emission tomography-computed tomography [PET-CT] and fluorodeoxyglucose [FDG] PET-CT) partial response was observed in 3 MEN1 cases, stable disease was noted in one MEN1 case and disease progression was noted in the patient with Cushing's syndrome. The change in FDG uptake was found to be an important sensitive scan parameter in the treatment evaluation of NETs compared to somatostatin receptor-based imaging in the cases with low MiB1 index. In our series, good palliative response to 177 Lu-DOTA-octreotate (DOTATATE) PRRT was

  3. Endocrine tumors other than thyroid tumors

    International Nuclear Information System (INIS)

    Takeichi, Norio; Dohi, Kiyohiko

    1992-01-01

    This paper discusses the tendency for the occurrence of tumors in the endocrine glands, other than the thyroid gland, in A-bomb survivors using both autopsy and clinical data. ABCC-RERF sample data using 4136 autopsy cases (1961-1977) revealed parathyroid tumors in 13 A-bomb survivors, including 3 with the associated hyperparathyroidism, with the suggestion of dose-dependent increase in the occurrence of tumors. Based on clinical data from Hiroshima University, 7 (46.7%) of 15 parathyroid tumors cases were A-bomb survivors. Data (1974-1987) from the Tumor Registry Committee (TRC) in Hiroshima Prefecture revealed that a relative risk of parathyroid tumors was 5.6 times higher in the entire group of A-bomb survivors and 16.2 times higher in the group of heavily exposed A-bomb survivors, suggesting the dose-dependent increase in their occurrence. Adrenal tumors were detected in 47 of 123 cases from the TRC data, and 15 (31.5%) of these 47 were A-bomb survivors. Particularly, 11 cases of adrenal tumors associated with Cushing syndrome included 6 A-bomb survivors (54.5%). The incidence of multiple endocrine gonadial tumors (MEGT) tended to be higher with increasing exposure doses; and the 1-9 rad group, the 10-99 rad group, and the 100 or more rad group had a risk of developing MEGT of 4.1, 5.7, and 7.1, respectively, relative to both the not-in the city group and the 0 rad group. These findings suggested that there is a correlation between A-bomb radiation and the occurrence of parathyroid tumors (including hyperparathyroidism), adrenal tumors associated with Cushing syndrome and MEGT (especially, the combined thyroid and ovarian tumors and the combined thyroid and parathyroid tumors). (N.K.)

  4. A self-lysis pathway that enhances the virulence of a pathogenic bacterium.

    Science.gov (United States)

    McFarland, Kirsty A; Dolben, Emily L; LeRoux, Michele; Kambara, Tracy K; Ramsey, Kathryn M; Kirkpatrick, Robin L; Mougous, Joseph D; Hogan, Deborah A; Dove, Simon L

    2015-07-07

    In mammalian cells, programmed cell death (PCD) plays important roles in development, in the removal of damaged cells, and in fighting bacterial infections. Although widespread among multicellular organisms, there are relatively few documented instances of PCD in bacteria. Here we describe a potential PCD pathway in Pseudomonas aeruginosa that enhances the ability of the bacterium to cause disease in a lung infection model. Activation of the system can occur in a subset of cells in response to DNA damage through cleavage of an essential transcription regulator we call AlpR. Cleavage of AlpR triggers a cell lysis program through de-repression of the alpA gene, which encodes a positive regulator that activates expression of the alpBCDE lysis cassette. Although this is lethal to the individual cell in which it occurs, we find it benefits the population as a whole during infection of a mammalian host. Thus, host and pathogen each may use PCD as a survival-promoting strategy. We suggest that activation of the Alp cell lysis pathway is a disease-enhancing response to bacterial DNA damage inflicted by the host immune system.

  5. Investigation of an optimal cell lysis method for the study of the zinc metalloproteome of Histoplasma capsulatum.

    Science.gov (United States)

    Donnell, Anna M; Lewis, Stephanie; Abraham, Sami; Subramanian, Kavitha; Figueroa, Julio Landero; Deepe, George S; Vonderheide, Anne P

    2017-10-01

    This work sought to assess optimal extraction conditions in the study of the metalloproteome of the dimorphic fungus Histoplasma capsulatum. One of the body's responses to H. capsulatum infection is sequestration of zinc within host macrophage (MØ), as reported by Vignesh et al. (Immunity 39:697-710, 2013) and Vignesh et al. (PLOS Pathog 9:E1003815, 2013). Thus, metalloproteins containing zinc were of greatest interest as it plays a critical role in survival of the fungus. One challenge in metalloproteomics is the preservation of the native structure of proteins to retain non-covalently bound metals. Many of the conventional cell lysis, separation, and identification techniques in proteomics are carried out under conditions that could lead to protein denaturation. Various cell lysis techniques were investigated in an effort to both maintain the metalloproteins during lysis and subsequent analysis while, at the same time, serving to be strong enough to break the cell wall, allowing access to cytosolic metalloproteins. The addition of 1% Triton x-100, a non-ionic detergent, to the lysis buffer was also studied. Seven lysis methods were considered and these included: Glass Homogenizer (H), Bead Beater (BB), Sonication Probe (SP), Vortex with 1% Triton x-100 (V, T), Vortex with no Triton x-100 (V, NT), Sonication Bath, Vortex, and 1% Triton x-100 (SB, V, T) and Sonication Bath, Vortex, and no Triton x-100 (SB, V, NT). A Qubit® Assay was used to compare total protein concentration and inductively coupled plasma-mass spectrometry (ICP-MS) was utilized for total metal analysis of cell lysates. Size exclusion chromatography coupled to ICP-MS (SEC-HPLC-ICP-MS) was used for separation of the metalloproteins in the cell lysate and the concentration of Zn over a wide molecular weight range was examined. Additional factors such as potential contamination sources were also considered. A cell lysis method involving vortexing H. capsulatum yeast cells with 500 μm glass beads

  6. Fatal antiphospholipid syndrome following endoscopic transnasal-transsphenoidal surgery for a pituitary tumor: A case report.

    Science.gov (United States)

    Li, Chiao-Zhu; Li, Chiao-Ching; Hsieh, Chih-Chuan; Lin, Meng-Chi; Hueng, Dueng-Yuan; Liu, Feng-Chen; Chen, Yuan-Hao

    2017-01-01

    The fatal type of antiphospholipid syndrome is a rare but life-threating condition. It may be triggered by surgery or infection. Endoscopic transnasal-transsphenoidal surgery is a common procedure for pituitary tumor. We report a catastrophic case of a young woman died of fatal antiphospholipid syndrome following endoscopic transnasal-transsphenoidal surgery. A 31-year-old woman of a history of stroke received endoscopic transnasal-transsphenoidal surgery for a pituitary tumor. The whole procedure was smooth. However, the patient suffered from acute delirium on postoperative day 4. Then, her consciousness became comatose state rapidly with dilatation of pupils. Urgent magnetic resonance imaging of brain demonstrated multiple acute lacunar infarcts. The positive antiphosphoipid antibody and severe thrombocytopenia were also noted. Fatal antiphospholipid syndrome was diagnosed. Plasma exchange, corticosteroids, anticoagulant agent were prescribed. The hemodynamic condition was gradually stable. However, the consciousness was still in deep coma. The patient died of organ donation 2 months later. If patients have a history of cerebral stroke in their early life, such as a young stroke, the APS and higher risk of developing fatal APS after major surgery should be considered. The optimal management of APS remains controversial. The best treatment strategies are only early diagnosis and aggressive therapies combing of anticoagulant, corticosteroid, and plasma exchange. The intravenous immunoglobulin is prescribed for patients with refractory APS.

  7. A bispecific nanobody approach to leverage the potent and widely applicable tumor cytolytic capacity of Vγ9Vδ2-T cells.

    Science.gov (United States)

    de Bruin, Renée C G; Veluchamy, John P; Lougheed, Sinéad M; Schneiders, Famke L; Lopez-Lastra, Silvia; Lameris, Roeland; Stam, Anita G; Sebestyen, Zsolt; Kuball, Jürgen; Molthoff, Carla F M; Hooijberg, Erik; Roovers, Rob C; Santo, James P Di; van Bergen En Henegouwen, Paul M P; Verheul, Henk M W; de Gruijl, Tanja D; van der Vliet, Hans J

    2017-01-01

    Though Vγ9Vδ2-T cells constitute only a small fraction of the total T cell population in human peripheral blood, they play a vital role in tumor defense and are therefore of major interest to explore for cancer immunotherapy. Vγ9Vδ2-T cell-based cancer immunotherapeutic approaches developed so far have been generally well tolerated and were able to induce significant clinical responses. However, overall results were inconsistent, possibly due to the fact that these strategies induced systemic activation of Vγ9Vδ2-T cells without preferential accumulation and targeted activation in the tumor. Here we show that a novel bispecific nanobody-based construct targeting both Vγ9Vδ2-T cells and EGFR induced potent Vγ9Vδ2-T cell activation and subsequent tumor cell lysis both in vitro and in an in vivo mouse xenograft model. Tumor cell lysis was independent of KRAS and BRAF tumor mutation status and common Vγ9Vδ2-T cell receptor sequence variations. In combination with the conserved monomorphic nature of the Vγ9Vδ2-TCR and the facile replacement of the tumor-specific nanobody, this immunotherapeutic approach can be applied to a large group of cancer patients.

  8. Dark membrane lysis and photosensitization by 3-carbethoxypsoralen

    International Nuclear Information System (INIS)

    Muller-Runkel, R.; Grossweiner, L.I.

    1981-01-01

    Aqueous solutions of 3-carbethoxypsoralen (3-CPs) induced lysis of egg lecithin liposomes and whole human erythrocytes in the dark. Near-UV irradiation of 3-CPs sensitized the inactivation of lysozyme attributed to the production of reactive radical intermediates. The implications of these findings for the use of 3-CPs as a sensitizer in psoralen + UV-A (PUVA) therapy of psoriasis are discussed. (author)

  9. Inhibition of pneumococcal autolysis in lysis-centrifugation blood culture.

    OpenAIRE

    Lehtonen, O P

    1986-01-01

    The recovery of Streptococcus pneumoniae from the Isolator lysis-centrifugation blood culture has been low in many studies. The poor survival of pneumococci was not due to toxicity of the Isolator medium but to autolysis before plating. This autolysis was completely inhibited by adding 10 mM phosphorylcholine to the Isolator medium.

  10. The Perlman syndrome: familial renal dysplasia with Wilms tumor, fetal gigantism and multiple congenital anomalies. 1984.

    Science.gov (United States)

    Neri, Giovanni; Martini-Neri, Maria Enrica; Katz, Ben E; Opitz, John M

    2013-11-01

    The ensuing paper by Professor Giovanni Neri and colleagues was originally published in 1984, American Journal of Medical Genetics 19:195–207. The original article described a new family with a condition that the authors designated as the Perlman syndrome. This disorder, while uncommon, is an important multiple congenital anomaly and dysplasia syndrome; the causative gene was recently identified. This paper is a seminal work and is graciously republished by Wiley-Blackwell in the Special Festschrift issue honoring Professor Neri. We describe a familial syndrome of renal dysplasia, Wilms tumor, hyperplasia of the endocrine pancreas, fetal gigantism, multiple congenital anomalies and mental retardation. This condition was previously described by Perlman et al. [1973, 1975] and we propose to call it the "Perlman syndrome." It appears to be transmitted as an autosomal recessive trait. The possible relationships between dysplasia, neoplasia and malformation are discussed. © 2013 Wiley Periodicals, Inc.

  11. The application of percutaneous lysis of epidural adhesions in patients with failed back surgery syndrome A aplicação da lise percutânea de aderências epidurais em pacientes com síndrome pós-laminectomia

    Directory of Open Access Journals (Sweden)

    He Chun-jing

    2012-04-01

    Full Text Available PURPOSE: To investigate the efficacy and the feasibility of application of percutaneous lysis of epidural adhesions in failed back surgery syndrome (FBSS using a stiff type guide wire and 4F vascular catheter. METHODS: Ninety two patients with FBSS were randomly divided into two groups, the control group (treated by injection dexamethasone only and percutaneous lysis of epidural adhesions group. Visual analog scale scores (VAS and therapeutic evaluation were observed in the preoperative, seven days postoperative, one month and six months postoperative. RESULTS: VAS scores for pain were significantly reduced in both groups at seven days. The VAS scores were in controlled group at one month, six months was significantly higher than that in epidural lysis group. However, there was no statistical difference in VAS scores of one month and six months when respectively compared to that of before operation in controlled group. Patients on epidural lysis reported clinical effectiveness rate was 50%. Patients on control was 5.26%, there was a statistical difference between two groups. CONCLUSION: Percutaneous lysis of epidural adhesions by using a stiff type guide wire and 4F vascular catheter is an effective method in the treatment of FBSS and it has a value in clinical application.OBJETIVO: Investigar a eficácia e a exequibilidade da aplicação da lise percutânea de aderências epidurais na síndrome pós-laminectomia usando um fio-guia tipo Stiff e um cateter vascular 4F. MÉTODOS: Noventa e dois pacientes com síndrome pós-laminectomia foram randomizados em dois grupos: grupo controle (tratado somente com injeção de dexametazona e grupo lise percutânea de aderências epidurais. Escores de escala visual analógica (VAS e avaliação terapêutica foram observadas no pré-operatório, no sétimo dia de pós-operatório, um mês e seis meses de pós-operatório. RESULTADOS: Escores VAS para dor foram significantemente reduzidos em ambos os grupos

  12. Evans Syndrome Presented with Marginal Zone Lymphoma and Duodenal Neuroendocrine Tumor in an Elderly Woman

    Directory of Open Access Journals (Sweden)

    Daniele D'Ambrosio

    2016-12-01

    Full Text Available Evans syndrome (ES is an autoimmune disorder characterized by simultaneous or sequential development of autoimmune hemolytic anemia, immune thrombocytopenia, and/or neutropenia. ES can be classified as a primary (idiopathic or secondary (associated with an underlying disease syndrome. We report a case of ES in an elderly patient in the presence of multiple trigger factors such as recent influenza vaccine, marginal zone lymphoma, and neuroendocrine tumor G1. Whether this association is casual or causal remains a matter of speculation. It is however necessary to have a thorough work-up in a newly diagnosed ES and a more accurate search of miscellaneous factors especially in elderly patients.

  13. Design and Modelling of a Microfluidic Electro-Lysis Device with Controlling Plates

    Science.gov (United States)

    Jenkins, A.; Chen, C. P.; Spearing, S.; Monaco, L. A.; Steele, A.; Flores, G.

    2006-04-01

    Many Lab-on-Chip applications require sample pre-treatment systems. Using electric fields to perform cell lysis in bio-MEMS systems has provided a powerful tool which can be integrated into Lab-on-a- Chip platforms. The major design considerations for electro-lysis devices include optimal geometry and placement of micro-electrodes, cell concentration, flow rates, optimal electric field (e.g. pulsed DC vs. AC), etc. To avoid electrolysis of the flowing solution at the exposed electrode surfaces, magnitudes and the applied voltages and duration of the DC pulse, or the AC frequency of the AC, have to be optimized for a given configuration. Using simulation tools for calculation of electric fields has proved very useful, for exploring alternative configurations and operating conditions for achieving electro cell-lysis. To alleviate the problem associated with low electric fields within the microfluidics channel and the high voltage demand on the contact electrode strips, two ''control plates'' are added to the microfluidics configuration. The principle of placing the two controlling plate-electrodes is based on the electric fields generated by a combined insulator/dielectric (glass/water) media. Surface charges are established at the insulator/dielectric interface. This paper discusses the effects of this interface charge on the modification of the electric field of the flowing liquid/cell solution.

  14. Presentation of a glomus carotid tumor as carotid sinus syndrome with syncopal episodes

    International Nuclear Information System (INIS)

    Dickschas, A.; Harmann, B.; Herzog, T.; Marienhagen, J.

    1987-01-01

    An 80 year old patient was referred to neurology for clarification of her episodes of syncope. A set of radiological examinations indicated a diagnosis of paraganglion of the left carotid bifurcation. Using this case, an attempt is made to provide recommendations concerning the order of step-wise visualization techniques of clarifying glomus carotid tumors. This unusual case also provides an impetus for considering the physiology and pathogenesis of different forms of carotid sinus syndrome. (orig.) [de

  15. Characteristics of recovery from the euthyroid sick syndrome induced by tumor necrosis factor alpha in cancer patients

    NARCIS (Netherlands)

    Feelders, R. A.; Swaak, A. J.; Romijn, J. A.; Eggermont, A. M.; Tielens, E. T.; Vreugdenhil, G.; Endert, E.; van Eijk, H. G.; Berghout, A.

    1999-01-01

    Cytokines have been implicated in the pathogenesis of the euthyroid sick syndrome. Isolated limb perfusion (ILP) with recombinant human tumor necrosis factor alpha (rTNF) and melphalan in patients with melanoma or sarcoma is accompanied by high systemic TNF levels. We examined the prolonged effects

  16. Normal human serum (HS) prevents oxidant-induced lysis of cultured endothelial cells (ECs)

    International Nuclear Information System (INIS)

    Callahan, K.S.; Harlan, J.M.

    1986-01-01

    Most studies demonstrating oxidant lysis of cultured ECs are performed in serum-free media or media containing low concentrations of bovine serum. The authors found that HS protects human and bovine ECs from lysis caused by reagent H 2 O 2 or glucose/glucose oxidase (GO)-generated H 2 O 2 . EC injury was assessed by 51 Cr release, cell detachment, or trypan blue dye exclusion. Protective HS activity was dose-dependent with concentrations greater than or equal to 25% preventing lethal injury. Cytotoxicity at 24 hrs, induced by 20 mU/ml GO, was 90.1 +/- 5.2% without HS vs 1.7 +/- 4.6% with 25% HS present (20 exp). Similar protection was observed with heparinized plasma. Of note, comparable concentrations of bovine serum were devoid of protective activity. Addition of fatty acid-free albumin to the media was also without protective effect. Preliminary characterization showed HS activity was stable to 60 0 C for 30 min, non-dialyzable at 25,000 MW cutoff, and retained in delipidated serum. The HS protection was not merely due to scavenging of exogenous H 2 O 2 as A23187-induced EC lysis was also prevented by HS. Protective activity was not reproduced by purified cerruloplasmin or transferrin. In conclusion, unidentified factor(s) present in HS protect cultured ECs from oxidant-induced lysis. Since endothelium is normally exposed to 100% plasma, the authors suggest that in vitro studies of oxidant-mediated injury be performed in the presence of HS. Factor(s) in HS may play an important role in modulating oxidant-induced vascular injury in vivo

  17. Laparoscopic Treatment of Sclerosing Stromal Tumor of the Ovary in a Woman With Gorlin-Goltz Syndrome: A Case Report and Review of the Literature.

    Science.gov (United States)

    Grechi, Gianluca; Clemente, Nicolò; Tozzi, Alessandra; Ciavattini, Andrea

    2015-01-01

    Gorlin-Goltz syndrome is a rare hereditary multisystemic disease. Multiple basal cell carcinomas, odontogenic keratocysts, and skeletal abnormalities are the main clinical manifestations of the syndrome, but several organs can be involved. Moreover, this condition is associated with the development of various benign and malignant tumors, even in the genital tract. This report describes a rare association between Gorlin-Goltz syndrome and the sclerosing stromal tumor of the ovary. Because the ultrasound and magnetic resonance imaging patterns of this tumor can be similar to those of a malignant neoplasm, prompt surgical intervention and histological confirmation of diagnosis is mandatory; however, this is a benign lesion and thus can be approached with a laparoscopic fertility-sparing surgery. Gynecologists should be aware of this possible association to provide appropriate counseling for these women, and to take a fertility-sparing laparoscopic approach whenever possible. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.

  18. Integration of nanoparticle cell lysis and microchip PCR for one-step rapid detection of bacteria.

    Science.gov (United States)

    Wan, Weijie; Yeow, John T W

    2012-04-01

    This paper describes an integrated microchip system as an efficient and cost-effective solution involving Nanotechnology and Lab-on-a-Chip technology for the rapid detection of bacteria. The system is based on using surface-modified gold nanoparticles for efficient cell lysis followed by microchip PCR without having to remove the nanoparticles from the PCR solution. Poly(quaternary ammonium) modified gold nanoparticles are used to provide a novel and efficient cell lysis method without the need to go through time-consuming, expensive and complicated microfabrication processes as most of current cell lysis methods for Lab-on-a-Chip applications do. It also facilitates the integration of cell lysis and PCR by sharing the same reaction chamber as PCR uses. It is integrated with a prototype microchip PCR system consisting of a physical microchip PCR device and an automated temperature control mechanism. The research work explores solutions for the problem of PCR inhibition caused by gold nanoparticles as well as for the problem of non-specific PCR amplification in the integrated microchip system. It also explores the possibility of greatly reducing PCR cycling time to achieve the same result compared to the protocol for a regular PCR machine. The simplicity of the setup makes it easy to be integrated with other Lab-on-a-Chip functional modules to create customized solutions for target applications.

  19. Comparison of the lysis centrifugation method with the conventional blood culture method in cases of sepsis in a tertiary care hospital.

    Science.gov (United States)

    Parikh, Harshal R; De, Anuradha S; Baveja, Sujata M

    2012-07-01

    Physicians and microbiologists have long recognized that the presence of living microorganisms in the blood of a patient carries with it considerable morbidity and mortality. Hence, blood cultures have become critically important and frequently performed test in clinical microbiology laboratories for diagnosis of sepsis. To compare the conventional blood culture method with the lysis centrifugation method in cases of sepsis. Two hundred nonduplicate blood cultures from cases of sepsis were analyzed using two blood culture methods concurrently for recovery of bacteria from patients diagnosed clinically with sepsis - the conventional blood culture method using trypticase soy broth and the lysis centrifugation method using saponin by centrifuging at 3000 g for 30 minutes. Overall bacteria recovered from 200 blood cultures were 17.5%. The conventional blood culture method had a higher yield of organisms, especially Gram positive cocci. The lysis centrifugation method was comparable with the former method with respect to Gram negative bacilli. The sensitivity of lysis centrifugation method in comparison to conventional blood culture method was 49.75% in this study, specificity was 98.21% and diagnostic accuracy was 89.5%. In almost every instance, the time required for detection of the growth was earlier by lysis centrifugation method, which was statistically significant. Contamination by lysis centrifugation was minimal, while that by conventional method was high. Time to growth by the lysis centrifugation method was highly significant (P value 0.000) as compared to time to growth by the conventional blood culture method. For the diagnosis of sepsis, combination of the lysis centrifugation method and the conventional blood culture method with trypticase soy broth or biphasic media is advocable, in order to achieve faster recovery and a better yield of microorganisms.

  20. Effects of copper, organic mercury and a mixture of the two on glycerol lysis of erythrocytes.

    OpenAIRE

    宮地,芳之

    1987-01-01

    The effects of copper, organic mercury and a mixture of the two on glycerol lysis of erythrocytes were examined. Copper ion and organic mercury (EMP; ethylmercury phosphate, and PCMB; sodium p-chloromercuricbenzoate) inhibited glycerol lysis of erythrocytes. The inhibitory effects was dependent on the incubation period. An equimolor solution of copper ion and EMP showed between copper ion and EMP. Similar results were obtained with copper and PCMB.

  1. Biological mechanisms of gallium-67 tumor deposition

    International Nuclear Information System (INIS)

    Okuyama, Shinichi; Takeda, Shumpei; Sato, Tachio; Takusagawa, Kimihiko; Awano, Takayuki.

    1979-01-01

    This investigation was undertaken in order to clarify the tumor deposition mechanisms of 67 Ga citrate, a ''universal tumor labeler''. An interspecies comparison of various tumors in the rat and mouse indicated that its highest deposition was in the undifferentiated cell type. Amongst the siblings of experimental tumors, cellular membrane negative charge is greater in the free-cell types than the island-formers: a short-term labeling study revealed a greater 67 Ga deposition in the free-cell types. A subcellar fractionation showed an initial association of 67 Ga with the nuclear and membrane fractions, and a later transition to the lysosomal. Hypotonic lysis revealed a paralleled release of 67 Ga and lysosomal key enzymes. Morphological abnormality of the cancer lysosomes was thought to agree with their Ga retention. This property was clinically confirmed by a scintiscoring technique. Treatment with cold gallium of tumors modified the biological parameters of tumor growth: in vitro it suppressed cell proliferation, reduced saturation density; and produced cellular pleomorphism. In vivo it increased tumor consistency by reducing central necrosis and increasing the viable cell layer thickness. Thus, 67 Ga deposition is closely related to various biological parameters of malignancy including the cellular membrane negative charge as cancer is a membrane disorder, and the lysosomal morphology and function. (author)

  2. Dramatic response to nivolumab in xeroderma pigmentosum skin tumor.

    Science.gov (United States)

    Chambon, Fanny; Osdoit, Sophie; Bagny, Kelly; Moro, Anne; Nguyen, Jacqueline; Réguerre, Yves

    2018-02-01

    We report the case of a 6-year-old female with xeroderma pigmentosum (XP) who developed a nonoperable scalp tumor, treated with anti-programmed cell death protein 1 (anti-PD-1) therapy (nivolumab). She presented with a sarcomatoid carcinoma of the scalp with bone lysis as well as vascular and meningeal contact. Nivolumab was initiated because it has emerged as a promising immunotherapy. We observed a dramatic tumor response with excellent tolerance. However, while on nivolumab therapy she developed two large skin melanomas and several squamous cell carcinomas, which have been resected. These results demonstrate that cancer immunotherapy in patients with XP can be impressive but complex and warrants further investigation. © 2017 Wiley Periodicals, Inc.

  3. Blood culture bottles are superior to lysis-centrifugation tubes for bacteriological diagnosis of spontaneous bacterial peritonitis.

    OpenAIRE

    Siersema, P D; de Marie, S; van Zeijl, J H; Bac, D J; Wilson, J H

    1992-01-01

    The conventional method of ascitic fluid culturing was compared with the bedside inoculation of ascites into blood culture bottles and into lysis-centrifugation tubes. The conventional culture method was compared with the blood culture bottle method in 31 episodes of spontaneous bacterial peritonitis (SBP). Cultures were positive with the conventional culture method in 11 (35%) episodes and with the blood culture bottle method in 26 (84%) episodes (P less than 0.001). The lysis-centrifugation...

  4. Esthesioneuroblastoma in Maffucci's syndrome

    International Nuclear Information System (INIS)

    Kurian, Sobha; Crowell, Edward B.; Ertan, Esmer; Rassekh, Christopher; Ducatman, Barbara

    2004-01-01

    Maffucci's syndrome consists of multiple cutaneous hemangiomas, dyschondroplasia, and enchondromas with potential for malignant change. We report a case of a 33-year-old man with Maffucci's syndrome who presented with a several month history of nasal congestion, facial pain, and diminished vision in his left eye. Radiological studies showed a large soft tissue mass centered in the sinonasal area, extending bilaterally into maxillary sinuses and orbits with compression of left optic nerve. Biopsy of the mass showed esthesioneuroblastoma (olfactory neuroblastoma). Chemotherapy resulted in initial improvement, but the tumor recurred and did not respond to further treatment, resulting in his death. Sarcomatous tumors are reported in Maffucci's syndrome, but this is a rare case of a neuroendocrine tumor in a patient with Maffucci's syndrome. (orig.)

  5. Local lysis with Alteplase for the treatment of acute embolic leg ischemia following the use of the Duett trademark closure device: preliminary results

    International Nuclear Information System (INIS)

    Schuermann, K.; Buecker, A.; Wingen, M.; Tacke, J.; Wein, B.; Guenther, R.W.; Janssens, U.

    2004-01-01

    Purpose: To analyze retrospectively the result of the alteplase lysis therapy of embolic complications following the use of the Duett closure device. Methods and Materials: For 3.5 years, the Duett closure device was used in 1,398 angiographies to close the femoral puncture site. The Duett device consists of a balloon and a liquid procoagulant containing collagen and thrombin, which is injected into the puncture tract under endovascular balloon protection of the arterial puncture site. In 9 patients (0.64%), the procoagulant was incidentally injected into the femoral artery causing acute leg ischemia. Eight patients received local lysis therapy with alteplase via a contralateral femoral access. One patient underwent surgery. On average, 21 mg alteplase (4-35 mg) were administered within 14 h (4-21 h). The course of the lysis was followed angiographyically and clinically. All patients were inteerviewed by telephone 23 months (4-35 months) later.Results: In 3 patients, lysis was complete. In 5 patients, only little thrombotic material remained. In all patients, symptoms of ischemia resolved completely within the first hours after initiation of lysis. In 5 cases, bleeding occurred at the puncture site closed with the Duett device during lysis, including development of a false aneurysm in 2 cases. Complications led to premature termination (n=2) or interruption of the lysis (n=3). All complications were treated conservatively. Clinically, long-term sequelae were paresthesia and hypoesthesia in the lower leg and foot in 2 patients treated with lysis, and in the patient who underwent surgery. (orig.) [de

  6. Experience with 99mTc-tektrotyd in the diagnosis of ectopic localization of acth-secreting tumors in patients with cushings syndrome

    International Nuclear Information System (INIS)

    Novikova, T.G.; Makeev, S.S.; Koval', S.S.; Guk, N.A.

    2015-01-01

    The differential diagnosis of Cushings disease is often carried out with Cushings syndrome, caused by the presence of tumors producing bioactive ACTH or ACTH-like substance. The aim of the study was to determine the effectiveness of the use of scintigraphy with 99m Tc-Tektrotyd in the diagnosis of ectopic localization of ACTH-secreting tumors in patients with Cushings syndrome. The survey of 25 patients with elevated levels of ACTH in the peripheral blood, allowed in 10 (40 %) patients identify foci of increased uptake radiopharmaceutical analog of somatostatin. It was found that the scintigraphy 99m Tc-Tektrotyd is sensitive and specific method in determining the foci of ectopic ACTH production. The use of scintigraphy with 99m Tc-Tektrotyd may be a good alternative to studies with octreotide labeled with 1U In or 123 I in the diagnosis of ectopic ACTH syndrome due to lower radiation dose to the patient, the higher picture quality and greater availability of this radiopharmaceutical

  7. Recurrent ovarian Sertoli?Leydig cell tumor in a child with Peutz?Jeghers syndrome

    OpenAIRE

    Bellfield, Edward J.; Alemzadeh, Ramin

    2016-01-01

    We present a female child with Peutz?Jeghers syndrome (PJS) with a recurrent ovarian Sertoli?Leydig cell tumor (SLCT). SLCTs are relatively rare sex cord neoplasms that can occur in PJS. The patient was an African-American female who first presented at the age of 3 years with precocious puberty, and then at the age of 17 years with abdominal pain and irregular menses. In each case, she had resection of the mass, which included oophorectomy. To our knowledge, this is the first reported case in...

  8. Pituitary tumors containing cholecystokinin

    DEFF Research Database (Denmark)

    Rehfeld, J F; Lindholm, J; Andersen, B N

    1987-01-01

    We found small amounts of cholecystokinin in the normal human adenohypophysis and therefore examined pituitary tumors from 87 patients with acromegaly, Cushing's disease, Nelson's syndrome, prolactinoma, or inactive pituitary adenomas. Five adenomas associated with Nelson's syndrome contained......'s disease and 7 acromegaly with adenomas containing ACTH. The cholecystokinin peptides from the tumors were smaller and less sulfated than cholecystokinin from normal pituitary glands. We conclude that ACTH-producing pituitary cells may also produce an altered form of cholecystokinin....

  9. Revisiting bistability in the lysis/lysogeny circuit of bacteriophage lambda.

    Directory of Open Access Journals (Sweden)

    Michael Bednarz

    Full Text Available The lysis/lysogeny switch of bacteriophage lambda serves as a paradigm for binary cell fate decision, long-term maintenance of cellular state and stimulus-triggered switching between states. In the literature, the system is often referred to as "bistable." However, it remains unclear whether this term provides an accurate description or is instead a misnomer. Here we address this question directly. We first quantify transcriptional regulation governing lysogenic maintenance using a single-cell fluorescence reporter. We then use the single-cell data to derive a stochastic theoretical model for the underlying regulatory network. We use the model to predict the steady states of the system and then validate these predictions experimentally. Specifically, a regime of bistability, and the resulting hysteretic behavior, are observed. Beyond the steady states, the theoretical model successfully predicts the kinetics of switching from lysogeny to lysis. Our results show how the physics-inspired concept of bistability can be reliably used to describe cellular phenotype, and how an experimentally-calibrated theoretical model can have accurate predictive power for cell-state switching.

  10. A Case of Paraneoplastic Cushing Syndrome Presenting as Hyperglycemic Hyperosmolar Nonketotic Syndrome

    Directory of Open Access Journals (Sweden)

    Christina E. Brzezniak

    2017-04-01

    Full Text Available Carcinoid tumors are neuroendocrine tumors that mainly arise in the gastrointestinal tract, lungs, and bronchi. Bronchopulmonary carcinoids have been associated with Cushing syndrome, which results from ectopic adrenocorticotrophic hormone (ACTH secretion. We report the case of a 65-year-old man, a colonel in the US Air Force, with metastatic bronchopulmonary carcinoid tumors treated on a clinical trial who was hospitalized for complaints of increasing thirst, polydipsia, polyuria, weakness, and visual changes. Decompensated hyperglycemia suggested a diagnosis of hyperglycemic hyperosmolar nonketotic syndrome (HHNS. Additional findings, which included hypokalemia, hypernatremia, hypertension, metabolic alkalosis, moon facies, and striae, raised a red flag for an ectopic ACTH syndrome. Elevated ACTH levels confirmed Cushing syndrome. Treatment with a fluid replacement and insulin drip resulted in immediate symptomatic improvement. Cushing syndrome should be considered in carcinoid patients with physical stigmata such as moon facies and striae. HHNS may be the presenting clinical feature in patients with impaired glucose metabolism.

  11. Miniature acoustic wave lysis system and uses thereof

    Science.gov (United States)

    Branch, Darren W.; Vreeland, Erika Cooley; Smith, Gennifer Tanabe

    2016-12-06

    The present invention relates to an acoustic lysis system including a disposable cartridge that can be reversibly coupled to a platform having a small, high-frequency piezoelectric transducer array. In particular, the system releases viable DNA, RNA, and proteins from human or bacterial cells, without chemicals or additional processing, to enable high-speed sample preparation for clinical point-of-care medical diagnostics and use with nano/microfluidic cartridges. Also described herein are methods of making and using the system of the invention.

  12. A simple and novel modification of comet assay for determination of bacteriophage mediated bacterial cell lysis.

    Science.gov (United States)

    Khairnar, Krishna; Sanmukh, Swapnil; Chandekar, Rajshree; Paunikar, Waman

    2014-07-01

    The comet assay is the widely used method for in vitro toxicity testing which is also an alternative to the use of animal models for in vivo testing. Since, its inception in 1984 by Ostling and Johansson, it is being modified frequently for a wide range of application. In spite of its wide applicability, unfortunately there is no report of its application in bacteriophages research. In this study, a novel application of comet assay for the detection of bacteriophage mediated bacterial cell lysis was described. The conventional methods in bacteriophage research for studying bacterial lysis by bacteriophages are plaque assay method. It is time consuming, laborious and costly. The lytic activity of bacteriophage devours the bacterial cell which results in the release of bacterial genomic material that gets detected by ethidium bromide staining method by the comet assay protocol. The objective of this study was to compare efficacy of comet assay with different assay used to study phage mediated bacterial lysis. The assay was performed on culture isolates (N=80 studies), modified comet assay appear to have relatively higher sensitivity and specificity than other assay. The results of the study showed that the application of comet assay can be an economical, time saving and less laborious alternative to conventional plaque assay for the detection of bacteriophage mediated bacterial cell lysis. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. A Rare Cause of Prepubertal Gynecomastia: Sertoli Cell Tumor

    Directory of Open Access Journals (Sweden)

    Fatma Dursun

    2015-01-01

    Full Text Available Prepubertal gynecomastia due to testis tumors is a very rare condition. Nearly 5% of the patients with testicular mass present with gynecomastia. Sertoli cell tumors are sporadic in 60% of the reported cases, while the remaining is a component of multiple neoplasia syndromes such as Peutz-Jeghers syndrome and Carney complex. We present a 4-year-old boy with gynecomastia due to Sertoli cell tumor with no evidence of Peutz-Jeghers syndrome or Carney complex.

  14. Bilateral granulosa cell tumors: a novel malignant manifestation of multiple endocrine neoplasia 1 syndrome found in a patient with a rare menin in-frame deletion

    Directory of Open Access Journals (Sweden)

    Hall MJ

    2015-02-01

    Full Text Available Michael J Hall,1 Julie Innocent,2 Christina Rybak,1 Colleen Veloski,3 Walter J Scott,4 Hong Wu,5 John A Ridge,4 John P Hoffman,4 Hossein Borghaei,2 Aruna Turaka,6 Mary B Daly1 1Department of Clinical Genetics, 2Department of Medical Oncology, 3Department of Internal Medicine, 4Department of Surgical Oncology, 5Department of Pathology, 6Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA Introduction: Multiple endocrine neoplasia 1 (MEN1 is a cancer syndrome resulting from mutations of the MEN1 gene. The syndrome is characterized by neoplasia of the parathyroid and pituitary glands, and malignant tumors of the endocrine pancreas. Other manifestations include benign lipomas, angiofibromas, and carcinoid tumors commonly originating in the colon, thymus, and lung. This is the first report of MEN1 syndrome manifesting as bilateral granulosa cell ovarian tumors, and which is associated with a rare intronic mutation of the MEN1 gene. Case report: A 41-year-old woman presented with abdominal pain, increasing abdominal girth, and dysmenorrhea. Ultrasound demonstrated enlarged ovaries and uterine fibroids. After an exploratory laparotomy, she subsequently underwent bilateral salpingo–oophorectomy with hysterectomy where the pathology revealed bilateral cystic granulosa cell tumors of the ovaries. Additional workup including computed tomography imaging discovered a thymic mass, which the pathology showed was malignant, along with a pancreatic mass suspicious for a neuroendocrine tumor. Hyperparathyroidism was also discovered and was found to be secondary to a parathyroid adenoma. Genetic testing revealed an exceedingly rare mutation in the MEN1 gene (c.654 + 1 G>A. Discussion: Mutations of the menin gene leading to MEN1 syndrome are classically nonsense or missense mutations producing a dysfunctional protein product. Recently, researchers described a novel mutation of MEN1 (c.654 + 1 G>A in a male proband meeting the criteria

  15. Brain tumors and syndromes in children

    NARCIS (Netherlands)

    Bleeker, Fonnet E.; Hopman, Saskia M. J.; Merks, Johannes H. M.; Aalfs, Cora M.; Hennekam, Raoul C. M.

    2014-01-01

    (Brain) tumors are usually a disorder of aged individuals. If a brain tumor occurs in a child, there is a possible genetic susceptibility for this. Such genetic susceptibilities often show other signs and symptoms. Therefore, every child with a brain tumor should be carefully evaluated for the

  16. Mycobacterium tuberculosis bacteremia detected by the Isolator lysis-centrifugation blood culture system.

    OpenAIRE

    Kiehn, T E; Gold, J W; Brannon, P; Timberger, R J; Armstrong, D

    1985-01-01

    Mycobacterium tuberculosis was detected by the Isolator lysis-centrifugation blood culture system from the blood of a patient with tuberculosis of the breast. The organism also grew on conventional laboratory media inoculated with pleural fluid from the patient.

  17. Molecular Background of Colorectal Tumors From Patients with Lynch Syndrome Associated With Germline Variants in PMS2.

    Science.gov (United States)

    Ten Broeke, S W; van Bavel, T C; Jansen, A M L; Gómez-García, E; Hes, F J; van Hest, L P; Letteboer, T G W; Olderode-Berends, M J W; Ruano, D; Spruijt, L; Suerink, M; Tops, C M; van Eijk, R; Morreau, H; van Wezel, T; Nielsen, M

    2018-05-11

    Germline variants in the mismatch repair genes MLH1, MSH2 (EPCAM), MSH6, or PMS2 cause Lynch syndrome. Patients with these variants have an increased risk of developing colorectal cancers (CRCs) that differ from sporadic CRCs in genetic and histologic features. It has been a challenge to study CRCs associated with PMS2 variants (PMS2-associated CRCs) because these develop less frequently and in patients of older ages than colorectal tumors with variants in the other mismatch repair genes. We analyzed 20 CRCs associated with germline variants in PMS2, 22 sporadic CRCs, 18 CRCs with germline variants in MSH2, and 24 CRCs from patients with germline variants in MLH1. Tumor tissue blocks were collected from Dutch pathology departments in 2017. After extraction of tumor DNA, we used a platform designed to detect approximately 3000 somatic hotspot variants in 55 genes (including KRAS, APC, CTNNB1, and TP53). Somatic variant frequencies were compared using the Fisher's exact test. None of the PMS2-associated CRCs contained any somatic variants in the catenin beta 1 gene (CTNNB1), which encodes β-catenin, whereas 14/24 MLH1-associated CRCs (58%) contained variants in CTNNB1. Half of PMS2-associated CRCs contained KRAS variants, but only 20% of these were in hotspots that encoded G12D or G13D. These hotspot variants occurred more frequently in CRCs associated with variants in MLH1 (37.5%, P=.44) and MSH2 (and 71.4%, P=.035) than with variants in PMS2. In a genetic analysis of 84 colorectal tumors, we found tumors from patients with PMS2-associated Lynch syndrome to be distinct from colorectal tumors associated with defects in other mismatch repair genes. This might account for differences in development and less frequent occurrence. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. Noonan syndrome, PTPN11 mutations, and brain tumors. A clinical report and review of the literature.

    Science.gov (United States)

    Siegfried, Aurore; Cances, Claude; Denuelle, Marie; Loukh, Najat; Tauber, Maïté; Cavé, Hélène; Delisle, Marie-Bernadette

    2017-04-01

    Noonan syndrome (NS), an autosomal dominant disorder, is characterized by short stature, congenital heart defects, developmental delay, and facial dysmorphism. PTPN11 mutations are the most common cause of NS. PTPN11 encodes a non-receptor protein tyrosine phosphatase, SHP2. Hematopoietic malignancies and solid tumors are associated with NS. Among solid tumors, brain tumors have been described in children and young adults but remain rather rare. We report a 16-year-old boy with PTPN11-related NS who, at the age of 12, was incidentally found to have a left temporal lobe brain tumor and a cystic lesion in the right thalamus. He developed epilepsy 2 years later. The temporal tumor was surgically resected because of increasing crises and worsening radiological signs. Microscopy showed nodules with specific glioneuronal elements or glial nodules, leading to the diagnosis of dysembryoplastic neuroepithelial tumor (DNT). Immunohistochemistry revealed positive nuclear staining with Olig2 and pERK in small cells. SHP2 plays a key role in RAS/MAPK pathway signaling which controls several developmental cell processes and oncogenesis. An amino-acid substitution in the N-terminal SHP2 domain disrupts the self-locking conformation and leads to ERK activation. Glioneuronal tumors including DNTs and pilocytic astrocytomas have been described in NS. This report provides further support for the relation of DNTs with RASopathies and for the implication of RAS/MAPK pathways in sporadic low-grade glial tumors including DNTs. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  19. Adrenal scintigraphy with 131I-19-iodocholesterol in the diagnosis of Cushing's syndrome associated with adrenal tumor

    International Nuclear Information System (INIS)

    Barliev, G.B.

    1979-01-01

    Seven patients with Cushing's syndrome secondary to adrenocortial tumors were studied using 131 I-19-iodocholesterol. The diagnoses of all cases were verified histologically. In three cases with adenoma the uptake of the tracer was in the tumor only, while the two patients with adrenocortical carcinoma failed to show adrenal accumulation of the labelled compound. In two patients there was a hyperplasia-like scintigraphic pattern, while the stimulation and suppression biochemical tests suggested adrenal tumor. One of these cases was verified as a mixed form (adenoma plus hyperplasia), and the tumor bearing gland was significantly larger on the scan which helped the preoperative localization. In the other case, verified as bilateral multiple adrenocortical adenomas, the autonomus function of both adrenals was proved by dexamethasone suppression scanning. It seems reasonable to use the latter as an adjunctive diagnostic procedure in patients where there is a discrepancy between the standard scintiscan and the biochemical indexes of adrenal hyperfunction. (orig.) 891 MG/orig. 892 MBE [de

  20. PTCH1 Germline Mutations and the Basaloid Follicular Hamartoma Values in the Tumor Spectrum of Basal Cell Carcinoma Syndrome (NBCCS).

    Science.gov (United States)

    Ponti, Giovanni; Manfredini, Marco; Pastorino, Lorenza; Maccaferri, Monia; Tomasi, Aldo; Pellacani, Giovanni

    2018-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominantly inherited disorder characterized by multiple basal cell carcinomas (BCC), odontogenic tumors and various skeletal anomalies. Basaloid follicular hamartomas (BFHs) constitute rare neoplasms that can be detected in sporadic and familial settings as in the Basaloid Follicular Hamartoma Syndrome (BFHS). Although BFHS shares clinical, histopathological and genetic overlapping with the NBCCS, they are still considered two distinctive entities. The aim of our single-institution study was the analysis of a cohort of PTCH1-mutated patients in order to define clinical and biomolecular relationship between NBCCS and BFHs. In our study we evaluated PTCH1 gene-carrier probands affected by NBCCS to detect the incidence of BFHs and their correlation with this rare syndrome. Among probands we recognized 4 patients with BFHs. We found 15 germline PTCH1 mutations, uniformly distributed across the PTCH1 gene. Six of them had familial history of NBCCS, two of them were novel and have not been described previously. NBCCS and BFHS may be the same genetic entity and not two distinctive syndromes. The inclusion of BFH in the NBCCS cutaneous tumor spectrum might be useful for the recognition of misdiagnosed NBCCS cases that could benefit from tailored surveillance strategies. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Relative efficacy of the argon green, argon blue-green, and krypton red lasers for 10-0 nylon subconjunctival laser suture lysis.

    Science.gov (United States)

    Mudgil, A V; To, K W; Balachandran, R M; Janigian, R H; Tsiaras, W G

    1999-01-01

    To determine the optimal wavelength for subconjunctival laser suture lysis. 130 black monofilament 10-0 nylon sutures were sewn subconjunctivally into the bare sclera of enucleated rabbit globes. The lowest energy levels facilitating laser suture lysis were determined for the argon green (514.5 NM), argon blue-green (488.0 NM, 514.5 NM), and krypton red (647.1 NM) wavelengths. In addition, absorption spectroscopy was performed on the suture material and conjunctiva using the Perkin Elmer W/VIS Lambda 2 spectrometer. Krypton red produced the fewest buttonhole defects, and it was also the most efficient energy source for suture lysis (P = 0.0001) under nontenectomized conjunctiva. Absorbance spectra studies revealed peak absorbance at 628 NM for the 10-0 nylon suture material. Based on animal and absorption spectroscopy studies, krypton red may be a safer and more efficient wavelength for subconjunctival laser suture lysis.

  2. Ectopic corticotroph syndrome

    Directory of Open Access Journals (Sweden)

    Penezić Zorana

    2004-01-01

    Full Text Available INTRODUCTION Endogenous Cushing's syndrome is a clinical state resulting from prolonged, inappropriate exposure to excessive endogenous secretion of Cortisol and hence excess circulating free cortisol, characterized by loss of the normal feedback mechanisms of the hypothalamo-pituitary-adrenal axis and the normal circadian rhythm of cortisol secretion [2]. The etiology of Cushing's syndrome may be excessive ACTH secretion from the pituitary gland, ectopic ACTH secretion by nonpituitary tumor, or excessive autonomous secretion of cortisol from a hyperfunctioning adrenal adenoma or carcinoma. Other than this broad ACTH-dependent and ACTH-independent categories, the syndrome may be caused by ectopic CRH secretion, PPNAD, MAH, ectopic action of GIP or catecholamines, and other adrenel-dependent processes associated with adrenocortical hyperfunction. CASE REPORT A 31 year-old men with b-month history of hyperpigmentation, weight gain and proximal myopathy was refereed to Institute of Endocrinology for evaluation of hypercortisolism. At admission, patient had classic cushingoid habit with plethoric face, dermal and muscle atrophy, abdominal strie rubrae and centripetal obesity. The standard laboratory data showed hyperglycaemia and hypokaliemia with high potassium excretion level. The circadian rhythm of cortisol secretion was blunted, with moderately elevated ACTH level, and without cortisol suppression after low-dose and high-dose dexamethason suppression test. Urinary 5HIAA was elevated. Abdominal and sellar region magnetic resonance imaging was negative. CRH stimulation resulted in ACTH increase of 87% of basal, but without significant increase of cortisol level, only 7%. Thoracal CT scan revealed 14 mm mass in right apical pulmonary segment. A wedge resection of anterior segment of right upper lobe was performed. Microscopic evaluation showed tumor tissue consisting of solid areas of uniform, oval cells with eosinophilic cytoplasm and centrally

  3. Burkitts’s lymphoma – an atypical presentation

    Directory of Open Access Journals (Sweden)

    Ziade Farah

    2012-08-01

    Full Text Available Abstract Background In female adolescents and young adults, malignancies of the genital tract are the most frequent type of cancer, closely followed by Hodgkin’s and non-Hodgkin’s lymphomas. Case Presentation We report an unusual case of sporadic Burkitt’s lymphoma (BL presenting with massive bilateral ovarian infiltration, peritoneal carcinomatosis and diffuse nodular lesions of the stomach and the intestine mimicking Krukenberg tumor. Diagnostic biopsies were obtained by endoscopy of the upper gastrointestinal tract. With intensive chemotherapy, complete remission was rapidly achieved, without life-threatening tumor lysis syndrome. Conclusion Besides metastatic gastric adenocarcinoma, BL is an important differential diagnosis in adolescents presenting with Krukenberg tumor.

  4. Adrenocortical tumors in children

    Directory of Open Access Journals (Sweden)

    R.C. Ribeiro

    2000-10-01

    Full Text Available Childhood adrenocortical tumors (ACT are rare. In the USA, only about 25 new cases occur each year. In Southern Brazil, however, approximately 10 times that many cases are diagnosed each year. Most cases occur in the contiguous states of São Paulo and Paraná. The cause of this higher rate has not been identified. Familial genetic predisposition to cancer (p53 mutations and selected genetic syndromes (Beckwith-Wiedemann syndrome have been associated with childhood ACT in general but not with the Brazilian counterpart. Most of the affected children are young girls with classic endocrine syndromes (virilizing and/or Cushing. Levels of urinary 17-ketosteroids and plasma dehydroepiandrosterone sulfate (DHEA-S, which are abnormal in approximately 90% of the cases, provide the pivotal clue to a diagnosis of ACT. Typical imaging findings of pediatric ACT consist of a large, well-defined suprarenal tumor containing calcifications with a thin capsule and central necrosis or hemorrhage. The pathologic classification of pediatric ACT is troublesome. Even an experienced pathologist can find it difficult to differentiate carcinoma from adenoma. Surgery is the single most important procedure in the successful treatment of ACT. The role of chemotherapy in the management of childhood ACT has not been established although occasional tumors are responsive to mitotane or cisplatin-containing regimens. Because of the heterogeneity and rarity of the disease, prognostic factors have been difficult to establish in pediatric ACT. Patients with incomplete tumor resection or with metastatic disease at diagnosis have a dismal prognosis. In patients with localized and completely resected tumors, the size of the tumor has predictive value. Patients with large tumors have a much higher relapse rate than those with small tumors.

  5. [Maxillofacial and dental abnormalities in some multiple abnormality syndromes. "Cri du chat" syndrome, Wilms' tumor-aniridia syndrome; Sotos syndrome; Goldenhar syndrome].

    Science.gov (United States)

    Berio, A; Trucchi, R; Meliota, M

    1992-05-01

    The paper describes the maxillo-facial and dental anomalies observed in some chromosome and non-chromosome poly-malformative syndromes ("Cri du chat" syndrome; Wilms' tumour; Sotos' syndrome; Goldenhar's syndrome). The Authors emphasise the possibility of diagnosing these multiple deformity syndromes from maxillo-facial alterations in early infancy; anomalous tooth position and structure cal also be successfully treated immediately after the first appearance of teeth. This is a particularly promising field of pediatrics and preventive pediatric medicine.

  6. Role of the SRRz/Rz1 lambdoid lysis cassette in the pathoadaptive evolution of Shigella.

    Science.gov (United States)

    Leuzzi, Adriano; Grossi, Milena; Di Martino, Maria Letizia; Pasqua, Martina; Micheli, Gioacchino; Colonna, Bianca; Prosseda, Gianni

    2017-06-01

    Shigella, the etiological agent of bacillary dysentery (shigellosis), is a highly adapted human pathogen. It evolved from an innocuous ancestor resembling the Escherichia coli strain by gain and loss of genes and functions. While the gain process concerns the acquisition of the genetic determinants of virulence, the loss is related to the adaptation of the genome to the new pathogenic status and occurs by pathoadaptive mutation of antivirulence genes. In this study, we highlight that the SRRz/Rz 1 lambdoid lysis cassette, even though stably adopted in E. coli K12 by virtue of its beneficial effect on cell physiology, has undergone a significant decay in Shigella. Moreover, we show the antivirulence nature of the SRRz/Rz 1 lysis cassette in Shigella. In fact, by restoring the SRRz/Rz 1 expression in this pathogen, we observe an increased release of peptidoglycan fragments, causing an unbalance in the fine control exerted by Shigella on host innate immunity and a mitigation of its virulence. This strongly affects the virulence of Shigella and allows to consider the loss of SRRz/Rz 1 lysis cassette as another pathoadaptive event in the life of Shigella. Copyright © 2017 Elsevier GmbH. All rights reserved.

  7. What Causes Cushing's Syndrome?

    Science.gov (United States)

    ... Share Facebook Twitter Pinterest Email Print What causes Cushing syndrome? Cushing syndrome can develop for two reasons: Medication ... uhs ), thyroid, or thymus How Tumors Can Cause Cushing Syndrome Normally, the pituitary gland in the brain controls ...

  8. Aggregate Formation During the Viral Lysis of a Marine Diatom

    Directory of Open Access Journals (Sweden)

    Yosuke Yamada

    2018-05-01

    Full Text Available Recent studies have suggested that the viral lysis of microbes not only facilitates the conversion of particulate organic matter into dissolved organic matter, but also promotes the formation of organic aggregates, which enhance the export of organic carbon from the surface ocean to the deep sea. However, experimental data supporting this proposition are limited. Here, we tested the hypothesis that the viral infection of marine diatoms enhances aggregate formation. We used a model system consisting of Chaetoceros tenuissimus, a bloom-forming diatom with an approximate cell size of 3–10 μm, and a DNA virus, CtenDNAV type II, which replicates in the nucleus of C. tenuissimus. The volume of large particles (50–400 μm in equivalent spherical diameters, determined from photographic images was measured over time (up to 15 days in the diatom-alone control and a virus-added diatom culture. We also determined the concentrations of Coomassie-stainable particles (CSP, proteinaceous particles and transparent exopolymeric particles (TEP, acid-polysaccharide-rich particles with colorimetric methods. The total volume of large particles was significantly higher (5–59 fold in the virus-added diatoms than in the diatom-alone control during the period in which the viral lysis of the diatoms proceeded. One class of large particles produced in the virus-added diatoms was flake-shaped. The flakes were tightly packed and dense, and sank rapidly, possibly playing an important role in the vertical delivery of materials from the surface to the deep sea. The bulk CSP concentrations tended to be higher in the virus-added diatoms than in the diatom-alone control, whereas the reverse was true for the TEP. These results suggest that proteinaceous polymers are involved in aggregate formation. Our data support the emerging notion that the viral lysis of microbes facilitates aggregate formation and the export of organic carbon in the ocean.

  9. Syndrome in question: Gorlin-Goltz syndrome.

    Science.gov (United States)

    Ribeiro, Pauline Lyrio; Souza, João Basílio de; Abreu, Karina Demoner de; Brezinscki, Marisa Simon; Pignaton, Christine Chambo

    2016-01-01

    The Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is an uncommon disorder caused by a mutation in Patched, tumor suppressor gene. It is mainly characterized by numerous early onset basal cell carcinomas, odontogenic cysts of jaw and skeletal abnormalities. Due to the wide clinical spectrum, treatment and management of its modalities are not standardized and should be individualized and monitored by a multidisciplinary team. We report a typical case in a 30-year-old man with multiple basal cell carcinomas, keratotic pits of palmar creases and bifid ribs, with a history of several corrective surgeries for keratocystic odontogenic tumors, among other lesions characteristic of the syndrome.

  10. [Desmoid tumors in three patients].

    Science.gov (United States)

    Mohos, E; Kovács, T; Brittig, F; Nagy, A

    2001-12-01

    Desmoids are rare tumors of the connective tissue. It develops about 1:1000 times more in patients with familial adenomatous polyposis (FAP, Gardner syndrome) compared to normal population. It has been shown in molecular genetic examinations, that different mutations of the APC gene are responsible for desmoid tumors in FAP. It means, that this disease is one of the extraintestinal manifestations of Gardner syndrome. This tumor has high recurrence rate and is growing rapidly, and as a result it is the second most common cause of death in FAP patients. That is why genetic examination for FAP patients is advised to decide if the patient has higher risk for desmoid formation. If the result of the genetic test is positive, it is advisable to try to slow the progression of polyposis with medical treatment, and so to delay the date of the colectomy because the surgical intervention--and connective tissue damage--can induce desmoid formation in these patients. At the same time it is reasonable to examine and regularly control patients with sporadic desmoid tumors searching for other manifestations of Gardner syndrome (colon, stomach and duodenum polyposis, tumor of papilla Vateri, retinopathy, etc.). Palliative surgery is not indicated in patients with inoperable intraabdominal desmoid tumors, because partial resections (R1, R2, debulking) result in further tumor progression. In these patients medical treatment (sulindac, tamoxifen), chemotherapy (doxorubicin, dacarbazin) and radiotherapy or combination of them can result tumor remission. We describe our three patients (an abdominal wall desmoid four years following Cesarean section; a desmoid tumor in the retroperitoneum and in the pelvis diagnosed three years after total colectomy; and a retroperitoneal and abdominal wall desmoid one year after total colectomy) and etiology, diagnosis and therapy of desmoid tumors are discussed.

  11. Endocrine neoplasms in familial syndromes of hyperparathyroidism.

    Science.gov (United States)

    Li, Yulong; Simonds, William F

    2016-06-01

    Familial syndromes of hyperparathyroidism, including multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), and the hyperparathyroidism-jaw tumor (HPT-JT), comprise 2-5% of primary hyperparathyroidism cases. Familial syndromes of hyperparathyroidism are also associated with a range of endocrine and nonendocrine tumors, including potential malignancies. Complications of the associated neoplasms are the major causes of morbidities and mortalities in these familial syndromes, e.g., parathyroid carcinoma in HPT-JT syndrome; thymic, bronchial, and enteropancreatic neuroendocrine tumors in MEN1; and medullary thyroid cancer and pheochromocytoma in MEN2A. Because of the different underlying mechanisms of neoplasia, these familial tumors may have different characteristics compared with their sporadic counterparts. Large-scale clinical trials are frequently lacking due to the rarity of these diseases. With technological advances and the development of new medications, the natural history, diagnosis, and management of these syndromes are also evolving. In this article, we summarize the recent knowledge on endocrine neoplasms in three familial hyperparathyroidism syndromes, with an emphasis on disease characteristics, molecular pathogenesis, recent developments in biochemical and radiological evaluation, and expert opinions on surgical and medical therapies. Because these familial hyperparathyroidism syndromes are associated with a wide variety of tumors in different organs, this review is focused on those endocrine neoplasms with malignant potential. © 2016 Society for Endocrinology.

  12. Mazabraud's Syndrome Coexisting with a Uterine Tumor Resembling an Ovarian Sex Cord Tumor (UTROSCT): a Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Calisir, Cuneyt; Inan, Ulukan; Yavas, Ulas Savas; Isiksoy, Serap; Kaya, Tamer [Eskisehir Osmangazi University, Eskiseh (Korea, Republic of)

    2007-10-15

    Intramuscular myxoma is a relatively uncommon benign soft tissue tumor. Its association with fibrous dysplasia of bone represents a rare syndrome described by Mazabraud and Girard in 1957. The relationship between fibrous dysplasia and myxoma remains unclear. A common histogenesis has been proposed for both lesions. Wirth et al. has suggested a basic metabolic error of both tissues during the initial growth period, restricted to the region of bone involvement. Myxomas may appear at any age, but have a predilection for older individuals, occurring most commonly during the sixth and seventh decades of life. They are often located in the large muscles of the thigh, shoulder and buttocks. The majority of intramuscular myxomas are solitary. Cross-sectional techniques are essential in the preoperative planning of excision of soft tissue tumors. The ability to evaluate soft tissue myxomas is best accomplished with MR imaging. Myxomas typically demonstrate the following MR features: very sharply defined contour and homogeneous signal intensity. In particular, the lesions are significantly low in signal intensity on T1-weighted images and high in signal intensity on T2-weighted images. In the patient of this case, the MR appearance was in agreement with previously reported cases.

  13. Recent discoveries in the molecular genetics of Lynch syndrome.

    Science.gov (United States)

    Boland, C Richard

    2016-07-01

    Lynch syndrome is the inherited predisposition to cancer caused by a germline mutation in a DNA mismatch repair gene. The consequent tumors have a characteristic microsatellite instability (MSI) phenotype. Genomic sequencing of Lynch syndrome-associated colorectal cancers (CRCs) has demonstrated that these tumors have a substantially greater number of mutations than non-MSI CRCs, and that the target mutations driving tumor behavior are also different from what occurs in sporadic tumors. There are multiple non-Lynch syndrome entities that can create clinical confusion with that disease, including the acquired methylation of MLH1, Lynch-like syndrome, and Familial CRC-Type X. Patients with Lynch syndrome-associated CRCs have a substantially better prognosis, and there is growing evidence that this is due to the generation of immunogenic frameshift peptides as a consequence of defective DNA mismatch repair, and an effective immune response to the tumor.

  14. Low-Cost Energy-Efficient 3-D Nano-Spikes-Based Electric Cell Lysis Chips

    KAUST Repository

    Riaz, Kashif; Leung, Siu; Fan, Zhiyong; Lee, Yi-Kuen

    2017-01-01

    Electric cell lysis (ECL) is a promising technique to be integrated with portable lab-on-a-chip without lysing agent due to its simplicity and fast processing. ECL is usually limited by the requirements of high power/voltage and costly fabrication

  15. A case of persistent Müllerian duct syndrome with sertoli cell tumor and hydrometra in a dog.

    Science.gov (United States)

    Matsuu, Aya; Hashizume, Takuya; Kanda, Teppei; Nagano, Masashi; Sugiyama, Akihiko; Okamoto, Yoshiharu; Hikasa, Yoshiaki

    2009-03-01

    A 10-year-old Miniature Schnauzer with bilateral cryptorchidism and male external genitalia was referred with a history of abdominal enlargement. Upon exploratory laparotomy, two tumors and a connecting structure similar to fluid-filled uterus were recognized. After cytological and bacterial examinations of the fluid and histological examination, this dog was diagnosed with bilateral Sertoli cell tumor with hydrometra. The karyotype of this dog was 78, XY and the sry gene was detected positive by PCR. We diagnosed this dog as a case of persistent Müllerian duct syndrome (PMDS), which is male pseudohermaphroditism. This is the first report regarding the incidence of PMDS in Miniature Schnauzers in Japan, and it suggests the involvement of a gene carrier.

  16. Inactivation of the Tumor Suppressor Genes Causing the Hereditary Syndromes Predisposing to Head and Neck Cancer via Promoter Hypermethylation in Sporadic Head and Neck Cancers

    OpenAIRE

    Smith, Ian M.; Mithani, Suhail K.; Mydlarz, Wojciech K.; Chang, Steven S.; Califano, Joseph A.

    2010-01-01

    Fanconi anemia (FA) and dyskeratosis congenita (DC) are rare inherited syndromes that cause head and neck squamous cell cancer (HNSCC). Prior studies of inherited forms of cancer have been extremely important in elucidating tumor suppressor genes inactivated in sporadic tumors. Here, we studied whether sporadic tumors have epigenetic silencing of the genes causing the inherited forms of HNSCC. Using bisulfite sequencing, we investigated the incidence of promoter hypermethylation of the 17 Fan...

  17. Metabolic complications in oncology

    International Nuclear Information System (INIS)

    Sycova-Mila, Z.

    2012-01-01

    Currently, a lot of space and time is devoted to the therapy of oncologic diseases itself. To reach the good therapy results, complex care of the oncologic patient is needed. Management of complications linked with the disease itself and management of complications emerged after administration of chemotherapy, radiotherapy or targeted therapy, plays a significant role. In addition to infectious, hematological, neurological, cardiac or other complications, metabolic complications are relatively extensive and serious. One of the most frequent metabolic complications in oncology is tumor lysis syndrome, hyperuricemia, hypercalcaemia and syndrome of inappropriate secretion of antidiuretic hormone. (author)

  18. Clotrimazole enhances lysis of human erythrocytes induced by t-BHP.

    Science.gov (United States)

    Lisovskaya, Irene L; Shcherbachenko, Irina M; Volkova, Rimma I; Ataullakhanov, Fazoil I

    2009-08-14

    Clotrimazole (CLT) is an antifungal and antimalarial agent also effective as a Gardos channel inhibitor. In addition, CLT possesses antitumor properties. Recent data provide evidence that CLT forms a complex with heme (hemin), which produces a more potent lytic effect than heme alone. This study addressed the effect of CLT on the lysis of normal human erythrocytes induced by tert-butyl hydroperoxide (t-BHP). For the first time, it was shown that 10 microM CLT significantly enhanced the lytic effect of t-BHP on erythrocytes in both Ca(2+)-containing and Ca(2+)-free media, suggesting that the effect is not related to Gardos channels. CLT did not affect the rate of free radical generation, the kinetics of GSH degradation, methemoglobin formation and TBARS generation; therefore, we concluded that CLT does not cause additional oxidative damage to erythrocytes treated with t-BHP. It is tempted to speculate that CLT enhances t-BHP-induced changes in erythrocyte volume and lysis largely by forming a complex with hemin released during hemoglobin oxidation in erythrocytes: the CLT-hemin complex destabilizes the cell membrane more potently than hemin alone. If so, the effect of CLT on cell membrane damage during free-radical oxidation may be used to increase the efficacy of antitumor therapy.

  19. Comparison of the lysis-centrifugation and agitated biphasic blood culture systems for detection of fungemia.

    Science.gov (United States)

    Murray, P R

    1991-01-01

    Although the detection of fungemia has been improved by the use of vented or biphasic blood culture bottles, the best recovery and earliest detection have been reported in the Isolator lysis-centrifugation system. It was recently demonstrated that improved detection of both bacteria and fungi was accomplished by mechanically agitating blood culture bottles for the first 24 h of incubation. In this study the detection of fungemia by use of the Isolator system was compared with that of an agitated biphasic system. A total of 182 fungi were isolated from blood specimens inoculated into both culture systems. No difference in the overall recovery of fungi or individual species of yeasts was observed between the two systems. However, all seven isolates of Histoplasma capsulatum were recovered in the Isolator system only. The time required to detect fungemia with each of the two systems was also compared. No statistically significant difference was observed. From the data collected during this 18-month study, it can be concluded that the overall recovery and time of detection of yeasts are equivalent in the lysis-centrifugation system and the agitated biphasic blood culture system. The lysis-centrifugation system is still superior for the detection of filamentous fungi such as H. capsulatum. PMID:1993772

  20. A super-family of transcriptional activators regulates bacteriophage packaging and lysis in Gram-positive bacteria

    Science.gov (United States)

    Quiles-Puchalt, Nuria; Tormo-Más, María Ángeles; Campoy, Susana; Toledo-Arana, Alejandro; Monedero, Vicente; Lasa, Íñigo; Novick, Richard P.; Christie, Gail E.; Penadés, José R.

    2013-01-01

    The propagation of bacteriophages and other mobile genetic elements requires exploitation of the phage mechanisms involved in virion assembly and DNA packaging. Here, we identified and characterized four different families of phage-encoded proteins that function as activators required for transcription of the late operons (morphogenetic and lysis genes) in a large group of phages infecting Gram-positive bacteria. These regulators constitute a super-family of proteins, here named late transcriptional regulators (Ltr), which share common structural, biochemical and functional characteristics and are unique to this group of phages. They are all small basic proteins, encoded by genes present at the end of the early gene cluster in their respective phage genomes and expressed under cI repressor control. To control expression of the late operon, the Ltr proteins bind to a DNA repeat region situated upstream of the terS gene, activating its transcription. This involves the C-terminal part of the Ltr proteins, which control specificity for the DNA repeat region. Finally, we show that the Ltr proteins are the only phage-encoded proteins required for the activation of the packaging and lysis modules. In summary, we provide evidence that phage packaging and lysis is a conserved mechanism in Siphoviridae infecting a wide variety of Gram-positive bacteria. PMID:23771138

  1. Leukocyte Lysis and Cytokine Induction by the Human Sexually Transmitted Parasite Trichomonas vaginalis.

    Directory of Open Access Journals (Sweden)

    Frances Mercer

    2016-08-01

    Full Text Available Trichomonas vaginalis (Tv is an extracellular protozoan parasite that causes the most common non-viral sexually transmitted infection: trichomoniasis. While acute symptoms in women may include vaginitis, infections are often asymptomatic, but can persist and are associated with medical complications including increased HIV susceptibility, infertility, pre-term labor, and higher incidence of cervical cancer. Heightened inflammation resulting from Tv infection could account for these complications. Effective cellular immune responses to Tv have not been characterized, and re-infection is common, suggesting a dysfunctional adaptive immune response. Using primary human leukocyte components, we have established an in vitro co-culture system to assess the interaction between Tv and the cells of the human immune system. We determined that in vitro, Tv is able to lyse T-cells and B-cells, showing a preference for B-cells. We also found that Tv lysis of lymphocytes was mediated by contact-dependent and soluble factors. Tv lysis of monocytes is far less efficient, and almost entirely contact-dependent. Interestingly, a common symbiont of Tv, Mycoplasma hominis, did not affect cytolytic activity of the parasite, but had a major impact on cytokine responses. M. hominis enabled more diverse inflammatory cytokine secretion in response to Tv and, of the cytokines tested, Tv strains cleared of M. hominis induced only IL-8 secretion from monocytes. The quality of the adaptive immune response to Tv is therefore likely influenced by Tv symbionts, commensals, and concomitant infections, and may be further complicated by direct parasite lysis of effector immune cells.

  2. Leukocyte Lysis and Cytokine Induction by the Human Sexually Transmitted Parasite Trichomonas vaginalis

    Science.gov (United States)

    Mercer, Frances; Diala, Fitz Gerald I.; Chen, Yi-Pei; Molgora, Brenda M.; Ng, Shek Hang; Johnson, Patricia J.

    2016-01-01

    Trichomonas vaginalis (Tv) is an extracellular protozoan parasite that causes the most common non-viral sexually transmitted infection: trichomoniasis. While acute symptoms in women may include vaginitis, infections are often asymptomatic, but can persist and are associated with medical complications including increased HIV susceptibility, infertility, pre-term labor, and higher incidence of cervical cancer. Heightened inflammation resulting from Tv infection could account for these complications. Effective cellular immune responses to Tv have not been characterized, and re-infection is common, suggesting a dysfunctional adaptive immune response. Using primary human leukocyte components, we have established an in vitro co-culture system to assess the interaction between Tv and the cells of the human immune system. We determined that in vitro, Tv is able to lyse T-cells and B-cells, showing a preference for B-cells. We also found that Tv lysis of lymphocytes was mediated by contact-dependent and soluble factors. Tv lysis of monocytes is far less efficient, and almost entirely contact-dependent. Interestingly, a common symbiont of Tv, Mycoplasma hominis, did not affect cytolytic activity of the parasite, but had a major impact on cytokine responses. M. hominis enabled more diverse inflammatory cytokine secretion in response to Tv and, of the cytokines tested, Tv strains cleared of M. hominis induced only IL-8 secretion from monocytes. The quality of the adaptive immune response to Tv is therefore likely influenced by Tv symbionts, commensals, and concomitant infections, and may be further complicated by direct parasite lysis of effector immune cells. PMID:27529696

  3. Sulfolobus Turreted Icosahedral Virus c92 Protein Responsible for the Formation of Pyramid-Like Cellular Lysis Structures

    DEFF Research Database (Denmark)

    Snyder, Jamie C; Brumfield, Susan K; Peng, Nan

    2011-01-01

    Host cells infected by Sulfolobus turreted icosahedral virus (STIV) have been shown to produce unusual pyramid-like structures on the cell surface. These structures represent a virus-induced lysis mechanism that is present in Archaea and appears to be distinct from the holin/endolysin system desc...... disruption of c92 within STIV demonstrates that c92 is an essential protein for virus replication. Immunolocalization of c92 shows that the protein is localized to the cellular membranes forming the pyramid-like structures.......Host cells infected by Sulfolobus turreted icosahedral virus (STIV) have been shown to produce unusual pyramid-like structures on the cell surface. These structures represent a virus-induced lysis mechanism that is present in Archaea and appears to be distinct from the holin/endolysin system...... described for DNA bacteriophages. This study investigated the STIV gene products required for pyramid formation in its host Sulfolobus solfataricus. Overexpression of STIV open reading frame (ORF) c92 in S. solfataricus alone is sufficient to produce the pyramid-like lysis structures in cells. Gene...

  4. Gorham syndrome of the thorax and cervical spine: CT and MRI findings

    International Nuclear Information System (INIS)

    Chung, C.; Yu, J.S.; Resnick, D.; Vaughan, L.M.; Haghighi, P.

    1997-01-01

    Gorham syndrome is a rare disorder that is characterized by local osseous invasion and surrounding soft tissues by an angiomatous mass, eventually causing lysis of the affected bone. To date, only four cases have reported the MR imaging appearance of this disease and the findings have been variable. We present a case involving the cervical and thoracic spine and part of the osseous hemithorax with attention to the MR findings. (orig.). With 4 figs

  5. Esthesioneuroblastoma in Maffucci's syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kurian, Sobha; Crowell, Edward B. [West Virginia University, Section of Hematology/Oncology, Department of Medicine, Health Science Center, Morgantown (United States); Ertan, Esmer; Rassekh, Christopher [West Virginia University, Department of Otolaryngology, Morgantown (United States); Ducatman, Barbara [West Virginia University, Department of Pathology, Morgantown (United States)

    2004-10-01

    Maffucci's syndrome consists of multiple cutaneous hemangiomas, dyschondroplasia, and enchondromas with potential for malignant change. We report a case of a 33-year-old man with Maffucci's syndrome who presented with a several month history of nasal congestion, facial pain, and diminished vision in his left eye. Radiological studies showed a large soft tissue mass centered in the sinonasal area, extending bilaterally into maxillary sinuses and orbits with compression of left optic nerve. Biopsy of the mass showed esthesioneuroblastoma (olfactory neuroblastoma). Chemotherapy resulted in initial improvement, but the tumor recurred and did not respond to further treatment, resulting in his death. Sarcomatous tumors are reported in Maffucci's syndrome, but this is a rare case of a neuroendocrine tumor in a patient with Maffucci's syndrome. (orig.)

  6. TumorNext-Lynch-MMR: a comprehensive next generation sequencing assay for the detection of germline and somatic mutations in genes associated with mismatch repair deficiency and Lynch syndrome.

    Science.gov (United States)

    Gray, Phillip N; Tsai, Pei; Chen, Daniel; Wu, Sitao; Hoo, Jayne; Mu, Wenbo; Li, Bing; Vuong, Huy; Lu, Hsiao-Mei; Batth, Navanjot; Willett, Sara; Uyeda, Lisa; Shah, Swati; Gau, Chia-Ling; Umali, Monalyn; Espenschied, Carin; Janicek, Mike; Brown, Sandra; Margileth, David; Dobrea, Lavinia; Wagman, Lawrence; Rana, Huma; Hall, Michael J; Ross, Theodora; Terdiman, Jonathan; Cullinane, Carey; Ries, Savita; Totten, Ellen; Elliott, Aaron M

    2018-04-17

    The current algorithm for Lynch syndrome diagnosis is highly complex with multiple steps which can result in an extended time to diagnosis while depleting precious tumor specimens. Here we describe the analytical validation of a custom probe-based NGS tumor panel, TumorNext-Lynch-MMR, which generates a comprehensive genetic profile of both germline and somatic mutations that can accelerate and streamline the time to diagnosis and preserve specimen. TumorNext-Lynch-MMR can detect single nucleotide variants, small insertions and deletions in 39 genes that are frequently mutated in Lynch syndrome and colorectal cancer. Moreover, the panel provides microsatellite instability status and detects loss of heterozygosity in the five Lynch genes; MSH2 , MSH6 , MLH1 , PMS2 and EPCAM . Clinical cases are described that highlight the assays ability to differentiate between somatic and germline mutations, precisely classify variants and resolve discordant cases.

  7. Neuroendocrine Tumor, diagnostic difficulties

    Directory of Open Access Journals (Sweden)

    Pedro Oliveira

    2017-06-01

    Full Text Available Ectopic adrenocorticotropic hormone (ACTH secretion is a rare disease. A 51 years old woman, with a Cushing syndrome secondary to ectopic ACTH secretion, diagnosed in 2009, with mediastinal lymphadenopathy, whose biopsy was compatible with lung small cell carcinoma, staged as IIIB using TNM classification. No other lesions were found in patient study. The patient was submitted to chemotherapy, associated to ketoconazole 200 mg twice daily, with partial remission of both conditions. Three years later was admitted with an aggravation of Cushing syndrome. There was no evidence of progression of pulmonary disease. A cystic lesion in the pancreatic uncinated process was found by abdominal CT scan and with avid uptake by DOTANOC PET discreet in anterior mediastinal lymphadenopathy. Biopsy of pancreatic mass revealed a neuroendocrine tumor. Pulmonary masses were biopsied again and was in favor of neuroendocrine tumor. It was assumed the diagnosis of pancreatic neuroendocrine tumor with mediastinal metastasis. The patient initiated lanreotid (120 mg, monthly, subcutaneous in association with ketoconazole. After 5 months of therapy, patient died with sepsis secondary to pneumonia. Neuroendocrine tumours are rare, difficult to diagnose and with poor prognosis when associated with ectopic ACTH secreting Cushing syndrome.

  8. Paraneoplastic syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1994-03-01

    Paraneoplastic syndromes (PNS) comprise a diverse group of disorders that are associated with cancer but unrelated to the size, location, metastases, or physiologic activities of the mature tissue of origin. They are remote effects of tumors that may appear as signs, symptoms, or syndromes which can mimic other disease conditions encountered in veterinary medicine. Recognition of PNS is valuable for several reasons: the observed abnormalities may represent tumor cell markers and facilitate early diagnosis of the tumor; they may allow assessment of premalignant states; they may aid in the search metastases; they may help quantify and monitor response to therapy; and, they may provide insight into the study of malignant transformation and oncogene expression. This review will concentrate on the pathophysiology, diagnosis, and treatment of some of the common PNS encountered in veterinary medicine.

  9. Radiological features of familial Gorlin-Goltz syndrome.

    Science.gov (United States)

    Hegde, Shruthi; Shetty, Shishir Ram

    2012-03-01

    Gorlin-Goltz syndrome is an autosomal dominant disorder principally characterized by cutaneous basal cell carcinomas, multiple keratocystic odontogenic tumors, and skeletal anomalies. This syndrome may be diagnosed early by dentist because keratocystic odontogenic tumors are usually one of the first manifestations of the syndrome. Early diagnosis and treatment are of utmost importance in reducing the severity of long term sequelae of this syndrome. This report presents a rare event of Gorlin-Goltz syndrome occurring in a 39-year-old male and his 8-year-old daughter. The clinical and investigative features of this familial disorder has been described in detail.

  10. Radiological features of familial Gorlin-Goltz syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Hegde, Shruthi; Shetty, Shishir Ram [AB Shetty Memorial Institute of Dental Sciences, Nitte University, Mangalore (India)

    2012-03-15

    Gorlin-Goltz syndrome is an autosomal dominant disorder principally characterized by cutaneous basal cell carcinomas, multiple keratocystic odontogenic tumors, and skeletal anomalies. This syndrome may be diagnosed early by dentist because keratocystic odontogenic tumors are usually one of the first manifestations of the syndrome. Early diagnosis and treatment are of utmost importance in reducing the severity of long term sequelae of this syndrome. This report presents a rare event of Gorlin-Goltz syndrome occurring in a 39-year-old male and his 8-year-old daughter. The clinical and investigative features of this familial disorder has been described in detail.

  11. Radiological features of familial Gorlin-Goltz syndrome

    International Nuclear Information System (INIS)

    Hegde, Shruthi; Shetty, Shishir Ram

    2012-01-01

    Gorlin-Goltz syndrome is an autosomal dominant disorder principally characterized by cutaneous basal cell carcinomas, multiple keratocystic odontogenic tumors, and skeletal anomalies. This syndrome may be diagnosed early by dentist because keratocystic odontogenic tumors are usually one of the first manifestations of the syndrome. Early diagnosis and treatment are of utmost importance in reducing the severity of long term sequelae of this syndrome. This report presents a rare event of Gorlin-Goltz syndrome occurring in a 39-year-old male and his 8-year-old daughter. The clinical and investigative features of this familial disorder has been described in detail.

  12. Beckwith-Wiedemann syndrome

    Science.gov (United States)

    ... most common tumors in children with this syndrome. Causes Beckwith-Wiedemann syndrome is caused by a defect ... Fanaroff AA, Walsh MC, eds. Fanaroff and Martin's Neonatal-Perinatal Medicine . 10th ed. ... MA. Hypoglycemia. In: Kliegman RM, Stanton BF, St. Geme JW, ...

  13. Urate oxidase for the prevention and treatment of tumour lysis syndrome in children with cancer.

    Science.gov (United States)

    Cheuk, Daniel Kl; Chiang, Alan Ks; Chan, Godfrey Cf; Ha, Shau Yin

    2017-03-08

    Tumour lysis syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Previous reviews did not find clear evidence of benefit of urate oxidase in children with cancer. This review is the second update of a previously published Cochrane review. To assess the effects and safety of urate oxidase for the prevention and treatment of TLS in children with malignancies. In March 2016 we searched CENTRAL, MEDLINE, Embase, and CINAHL. In addition, we searched the reference lists of all identified relevant papers, trials registers and other databases. We also screened conference proceedings and we contacted experts in the field and the manufacturer of rasburicase, Sanofi-aventis. Randomised controlled trials (RCT) and controlled clinical trials (CCT) of urate oxidase for the prevention or treatment of TLS in children under 18 years with any malignancy. Two review authors independently extracted trial data and assessed individual trial quality. We used risk ratios (RR) for dichotomous data and mean difference (MD) for continuous data. We included seven trials, involving 471 participants in the treatment groups and 603 participants in the control groups. No new studies were identified in the update. One RCT and five CCTs compared urate oxidase and allopurinol. Three trials tested Uricozyme, and three trials tested rasburicase for the prevention of TLS.The RCT did not evaluate the primary outcome (incidence of clinical TLS). It showed no clear evidence of a difference in mortality (both all-cause mortality (Fisher's exact test P = 0.23) and mortality due to TLS (no deaths in either group)), renal failure (Fisher's exact test P = 0.46), and adverse effects between the treatment and the control groups (Fisher's exact test P = 1.0). The frequency of normalisation of uric acid at four hours (10 out of 10 participants in the treatment group versus zero out of nine participants in the control group, Fisher's exact test P oxidase (RR 9.10, 95

  14. A comparison of the intoxication pathways of tumor necrosis factor and diphtheria toxin

    International Nuclear Information System (INIS)

    Chang, M.P.

    1988-01-01

    The mechanism by which tumor necrosis factor-alpha (TNF) initiates tumor cell destruction is unknown. We have approached this problem by comparing the biological properties of TNF with diphtheria toxin (DTx), a well-characterized cytotoxin. Initial studies with human U937 cells revealed that a transient exposure to low pH enhances the cytotoxic activity of TNF. Detailed studies on the interaction of TNF with pure lipid vesicles revealed that the acid-enhanced cytolytic activity of this cytokine is correlated with the acquisition of membrane binding and insertion properties. Significantly, an increase in target membrane stabilization was observed in the presence of TNF; hence, TNF is not directly lytic for membranes. In susceptible target cells, DTx induces the release of 51 Cr- and 75 Se-labeled proteins within 7 h. Although DTx-triggered cell death has generally been accepted as a straightforward effect of translation inhibition, little or no cell lysis was observed over a 20-30 h period when target cells were exposed to cycloheximide, amino acid deficient medium or metabolic poisons even though protein synthesis was inhibited to levels observed with DTx. The protein synthesis inhibition and cytolytic activities of DTx showed similar dose-dependencies, target cell specificities, and sensitivities to NH 4 Cl inhibition. DTx-induced DNA fragmentation preceded cells lysis and did not occur in cells that were treated with the other protein synthesis inhibitors

  15. Noonan syndrome - a new survey.

    Science.gov (United States)

    Tafazoli, Alireza; Eshraghi, Peyman; Koleti, Zahra Kamel; Abbaszadegan, Mohammadreza

    2017-02-01

    Noonan syndrome (NS) is an autosomal dominant disorder with vast heterogeneity in clinical and genetic features. Various symptoms have been reported for this abnormality such as short stature, unusual facial characteristics, congenital heart abnormalities, developmental complications, and an elevated tumor incidence rate. Noonan syndrome shares clinical features with other rare conditions, including LEOPARD syndrome, cardio-facio-cutaneous syndrome, Noonan-like syndrome with loose anagen hair, and Costello syndrome. Germline mutations in the RAS-MAPK (mitogen-activated protein kinase) signal transduction pathway are responsible for NS and other related disorders. Noonan syndrome diagnosis is primarily based on clinical features, but molecular testing should be performed to confirm it in patients. Due to the high number of genes associated with NS and other RASopathy disorders, next-generation sequencing is the best choice for diagnostic testing. Patients with NS also have higher risk for leukemia and specific solid tumors. Age-specific guidelines for the management of NS are available.

  16. Study of a novel cell lysis method with titanium dioxide for Lab-on-a-Chip devices.

    Science.gov (United States)

    Wan, Weijie; Yeow, John T W

    2011-06-01

    In this paper, a novel method is proposed and demonstrated to be able to lyse gram-negative (E. coli) bacteria cells for Lab-on-a-Chip applications. The proposed method incorporates using titanium dioxide particles as photocatalysts and a miniaturized UV LED array as an excitation light source to perform cell lysis on microchips. The experimental result demonstrates the feasibility of the proposed prototype device. The working device suggests an inexpensive, easy to be fabricated and effective way for microchip cell lysis. The miniaturized UV LED array and the microchip with a reaction chamber can be easily integrated with other functional components to form a customized whole Lab-on-a-Chip system.

  17. The microbiome in PTEN hamartoma tumor syndrome.

    Science.gov (United States)

    Byrd, Victoria; Getz, Ted; Padmanabhan, Roshan; Arora, Hans; Eng, Charis

    2018-03-01

    Germline PTEN mutations defining PTEN hamartoma tumor syndrome (PHTS) confer heritable predisposition to breast, endometrial, thyroid and other cancers with known age-related risks, but it remains impossible to predict if any individual will develop cancer. In the general population, gut microbial dysbiosis has been linked to cancer, yet is unclear whether these are associated in PHTS patients. In this pilot study, we aimed to characterize microbial composition of stool, urine, and oral wash from 32 PTEN mutation-positive individuals using 16S rRNA gene sequencing. PCoA revealed clustering of the fecal microbiome by cancer history ( P  = 0.03, R 2  = 0.04). Fecal samples from PHTS cancer patients had relatively more abundant operational taxonomic units (OTUs) from family Rikenellaceae and unclassified members of Clostridia compared to those from non-cancer patients, whereas families Peptostreptococcaceae, Enterobacteriaceae, and Bifidobacteriaceae represented relatively more abundant OTUs among fecal samples from PHTS non-cancer patients. Functional metagenomic prediction revealed enrichment of the folate biosynthesis, genetic information processing and cell growth and death pathways among fecal samples from PHTS cancer patients compared to non-cancer patients. We found no major shifts in overall diversity and no clustering by cancer history among oral wash or urine samples. Our observations suggest the utility of an expanded study to interrogate gut dysbiosis as a potential cancer risk modifier in PHTS patients. © 2018 The authors.

  18. Lynch syndrome-associated neoplasms

    DEFF Research Database (Denmark)

    Shia, Jinru; Holck, Susanne; Depetris, Giovanni

    2013-01-01

    It was a century ago that Warthin, a pathologist, first described the clinical condition now known as Lynch syndrome. One hundred years later, our understanding of this syndrome has advanced significantly. Much of the progress took place over the last 25 years and was marked by a series...... of interacting developments from the disciplines of clinical oncology, pathology, and molecular genetics, with each development serving to guide or enhance the next. The advancement of our understanding about the pathology of Lynch syndrome associated tumors exemplifies such intimate interplay among disciplines....... Today, accumulative knowledge has enabled surgical pathologists to detect tumors that are likely to be associated with Lynch syndrome, and the pathologist is playing an increasingly more important role in the care of these patients. The pathologist's ability is afforded primarily by information gained...

  19. Spectroscopic techniques (Moessbauer spectrometry, NMR, ESR...) as tools to resolve doubtful NMR images: Study of the craniopharyngioma tumor

    International Nuclear Information System (INIS)

    Rimbert, J.N.; Dumas, F.; Lafargue, C.; Kellershohn, C.; Brunelle, F.; Lallemand, D.

    1990-01-01

    Craniopharyngioma, an intracranial tumor, exhibits hyperintensity in the Spin-Echo-T 2 -NMR image and a hyposignal in the SE-T 1 -image. However, in some cases (15-20% cases), hypersignals are seen in both SE-T 1 and T 2 -MRI. Using spectroscopic techniques, Moessbauer spectrometry in particular, we have demonstrated that the T 1 hypersignal is due to ferritin, dissolved in the cystic liquid, after tumor cell lysis, in the course of time. Other possible reasons inducing a shortening of the T 1 relaxation time (presence of lipids, intratumoral hemorrhage) have been rejected. (orig.)

  20. Determining Human Clot Lysis Time (in vitro with Plasminogen/Plasmin from Four Species (Human, Bovine, Goat, and Swine

    Directory of Open Access Journals (Sweden)

    Omaira Cañas Bermúdez

    2015-05-01

    Full Text Available Cardiovascular disease is the leading cause of death worldwide, including failures in the plasminogen/plasmin system which is an important factor in poor lysis of blood clots. This article studies the fibrinolytic system in four species of mammals, and it identifies human plasminogen with highest thrombolysis efficiency. It examines plasminogen from four species (human, bovine, goat, and swine and identifies the most efficient one in human clot lysis in vitro. All plasminogens were identically purified by affinity chromatography. Human fibrinogen was purified by fractionation with ethanol. The purification of both plasminogen and fibrinogen was characterized by one-dimensional SDS-PAGE (10%. Human clot formation in vitro and its dissolution by plasminogen/plasmin consisted of determining lysis time from clot formation to its dilution. Purification of proteins showed greater than 95% purity, human plasminogen showed greater ability to lyse clot than animal plasminogen. The article concludes that human plasminogen/plasmin has the greatest catalysis and efficiency, as it dissolves human clot up to three times faster than that of irrational species.

  1. Familial tumoral calcinosis and hyperostosis-hyperphosphataemia syndrome are different manifestations of the same disease: novel missense mutations in GALNT3

    International Nuclear Information System (INIS)

    Joseph, Leo; Joseph, Selvanayagam; Hing, Sandra N.; Idowu, Bernadine D.; Delaney, David; Presneau, Nadege; O'Donnell, Paul; Diss, Tim; Flanagan, Adrienne Margaret

    2010-01-01

    To report on the biochemistry and clinical and genetic findings of two siblings, the younger sister presenting with recurrent bone pain of the radius and ulna, and medullary sclerosis, and the older brother with soft tissue calcific deposits (tumoral calcinosis) but who later developed bone pain. Both were found to be hyperphosphaturic. The index family comprised four individuals (father, mother, brother, sister). The affected siblings were the offspring of a non-consanguineous Indian family of Tamil origin. Bidirectional sequencing was performed on the DNA from the index family and on 160 alleles from a population of 80 unrelated unaffected control individuals of Tamil extraction and 72 alleles from individuals of non-Tamil origin. Two symptomatic siblings were found to harbour previously unreported compound heterozygous missense UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase 3 (GalNAc-transferase; GALNT3) mutations in exon 4 c.842A>G and exon 5 c.1097T>G. This sequence variation was not detected in the control DNA. This is the first report of siblings exhibiting stigmata of familial tumoral calcinosis and hyperostosis-hyperphosphataemia syndrome with documented evidence of autosomal recessive missense GALNT3 mutations. The findings from this family add further evidence to the literature that familial tumoral calcinosis and hyperostosis-hyperphosphataemia syndrome are manifestations of the same disease and highlight the importance of appropriate metabolic and genetic investigations. (orig.)

  2. Familial tumoral calcinosis and hyperostosis-hyperphosphataemia syndrome are different manifestations of the same disease: novel missense mutations in GALNT3

    Energy Technology Data Exchange (ETDEWEB)

    Joseph, Leo; Joseph, Selvanayagam [Vinodhagan Memorial Hospital and Dr. Joseph' s Ortho Clinic, Department of Orthopaedic Surgery, Thanjavur (India); Hing, Sandra N.; Idowu, Bernadine D.; Delaney, David [Royal National Orthopaedic Hospital NHS Trust, Department of Histopathology, Stanmore, Middlesex (United Kingdom); Presneau, Nadege [University College London (UCL), Cancer Institute, London (United Kingdom); O' Donnell, Paul [Royal National Orthopaedic Hospital NHS Trust, Department of Radiology, Stanmore, Middlesex (United Kingdom); University College London (UCL), Institute of Orthopaedics and Musculoskeletal Science, Stanmore (United Kingdom); University College London (UCL), The Institute of Orthopaedics and Musculoskeletal Science, London (United Kingdom); Diss, Tim [University College London Hospital (UCLH) NHS Trust, Rockefeller Building, Department of Histopathology, London (United Kingdom); Flanagan, Adrienne Margaret [Royal National Orthopaedic Hospital NHS Trust, Department of Histopathology, Stanmore, Middlesex (United Kingdom); University College London (UCL), Cancer Institute, London (United Kingdom); University College London Hospital (UCLH) NHS Trust, Rockefeller Building, Department of Histopathology, London (United Kingdom); University College London (UCL), Institute of Orthopaedics and Musculoskeletal Science, Stanmore (United Kingdom); Institute of Orthopaedics and Musculoskeletal Science, Stanmore, Middlesex (United Kingdom)

    2010-01-15

    To report on the biochemistry and clinical and genetic findings of two siblings, the younger sister presenting with recurrent bone pain of the radius and ulna, and medullary sclerosis, and the older brother with soft tissue calcific deposits (tumoral calcinosis) but who later developed bone pain. Both were found to be hyperphosphaturic. The index family comprised four individuals (father, mother, brother, sister). The affected siblings were the offspring of a non-consanguineous Indian family of Tamil origin. Bidirectional sequencing was performed on the DNA from the index family and on 160 alleles from a population of 80 unrelated unaffected control individuals of Tamil extraction and 72 alleles from individuals of non-Tamil origin. Two symptomatic siblings were found to harbour previously unreported compound heterozygous missense UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase 3 (GalNAc-transferase; GALNT3) mutations in exon 4 c.842A>G and exon 5 c.1097T>G. This sequence variation was not detected in the control DNA. This is the first report of siblings exhibiting stigmata of familial tumoral calcinosis and hyperostosis-hyperphosphataemia syndrome with documented evidence of autosomal recessive missense GALNT3 mutations. The findings from this family add further evidence to the literature that familial tumoral calcinosis and hyperostosis-hyperphosphataemia syndrome are manifestations of the same disease and highlight the importance of appropriate metabolic and genetic investigations. (orig.)

  3. Paraneoplastic Sjogren’s syndrome in gastric cancer

    Directory of Open Access Journals (Sweden)

    R F Khamitov

    2018-04-01

    Full Text Available In clinical practice, various masks of oncological diseases are often found. Some of them can manifest as a variety of syndromes or symptom complexes that resemble many non-oncologic diseases, including diffuse connective tissue diseases. In some cases, paraneoplastic syndrome facilitates diagnosing a malignant neoplasm in the early stages, but, unfortunately, can also mimic the tumor process by its more prominent manifestations, which lead to late establishment of the true cause of the disease, and therefore postpone specific treatment, creating significant clinical problems. Aim of the study was to reveal pathogenetic relationship between cancer and paraneoplastic syndrome on the example of our clinical observation. A clinical case of diagnosed paraneoplastic syndrome in the form of secondary Sjogren's syndrome, which developed long before the diagnosis of stomach cancer was made, as well as the results of clinical, instrumental, and laboratory examination of the patient, are presented. Questions of epidemiology, etiopathogenesis, and clinical picture of paraneoplastic syndrome are covered. The presented clinical case made it possible to outline the features of the course of paraneoplastic Sjogren's syndrome in gastric cancer and to identify a number of criteria for the diagnostic algorithm of this nosology. In particular, such criteria include general pathogenetic mechanisms, development only in malignant tumors, nonspecific clinical and laboratory manifestations, lack of parallelism with local symptoms of the tumor, the possibility of occurrence of paraneoplastic Sjogren's syndrome before development of local tumor symptoms and reappearance after its relapse. Oncologic diseases are characterized not only by specific symptoms characteristic for a certain organ damage (pain, bleeding, dysfunction, etc., but also by a variety of nonspecific manifestations (fatigue, subfebrile temperature, weight loss, etc. regardless of the nature, location and

  4. [Etiologic spectrum of solitary constitutional syndrome].

    Science.gov (United States)

    Hernández Hernández, J L; Matorras Galán, P; Riancho Moral, J A; González-Macías, J

    2002-07-01

    To know the spectrum of diseases responsible for the solitary constitutional syndrome in our setting. This syndrome was defined as a clinical picture characterized by the presence of asthenia, anorexia, and weight loss of at least 5% of body weight in the last six months, not associated with any other symptom or sign suggesting the diagnosis of an organ or system disease. All patients diagnosed of the solitary constitutional syndrome (328) in a tertiary-care level teaching hospital between January 1991 and December 1996. Fifty-two (170) percent of patients with solitary constitutional syndrome were males and 48% (158) females. The mean age was 65.4%, ranging from 15 to 97 years. The average of the monthly estimated weight loss was 3 to 4 kilograms. A total of 115 (35%) malignant neoplasms and 5 (1.5%) benign tumors were diagnosed. The most common malignant tumors corresponded to the digestive tract (51.3% of the total malignant tumors). The second cause in frequency of the solitary constitutional syndrome corresponded to psychiatric diseases, with a total of 80 patients (24.3%). A total of 116 non-neoplastic organic diseases were detected, with digestive tract diseases --mainly peptic disease-- being the most common cause in this group. After follow-up, only in twenty cases were we unable to detect the underlying disease responsible for the syndrome. In nine of these, the solitary constitutional syndrome was self-limited. Forty-four percent of patients had at least another concomitant disease and in 24% of patients more than one associated condition was found. The most common diseases responsible for the solitary constitutional syndrome were, by decreasing frequency, malignant tumors, psychiatric disorders, and non-malignant organic diseases located in the digestive tract. A better knowledge of the etiological spectrum of this syndrome might be useful for a more efficient management of these patients.

  5. Malignancy in Noonan syndrome and related disorders.

    Science.gov (United States)

    Smpokou, P; Zand, D J; Rosenbaum, K N; Summar, M L

    2015-12-01

    Noonan syndrome (NS) and related disorders, such as NS with multiple lentigines (formerly called LEOPARD syndrome), cardiofaciocutaneous syndrome, and Costello syndrome, constitute an important group of developmental malformation syndromes with variable clinical and molecular features. Their underlying pathophysiologic mechanism involves dysregulation of the Ras/mitogen-activated protein kinase signaling pathway, an essential mediator of developmental and growth processes in the prenatal and postnatal setting. Malignant tumor development is an important complication encountered in other RASopathies, such as neurofibromatosis type 1, but the neoplastic risks and incidence of malignant tumors are less clearly defined in NS and related disorders of the Noonan spectrum. Malignant tumor development remains an important complication variably seen in the RASopathies and, thus, a clear understanding of the underlying risks is essential for appropriate clinical care in this patient population. This review discusses previously published reports of malignancies in individuals with RASopathies of the Noonan spectrum. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Plasma Clot Lysis Time and Its Association with Cardiovascular Risk Factors in Black Africans

    NARCIS (Netherlands)

    Z. de Lange (Zelda); M. Pieters (Marlien); J.C. Jerling (Johann); A. Kruger (Annamarie); D.C. Rijken (Dingeman)

    2012-01-01

    textabstractStudies in populations of European descent show longer plasma clot lysis times (CLT) in patients with cardiovascular disease (CVD) than in controls. No data are available on the association between CVD risk factors and fibrinolytic potential in black Africans, a group undergoing rapid

  7. Genetics Home Reference: Guillain-Barré syndrome

    Science.gov (United States)

    ... Nyati KK, Verma A, Rizwan A, Paliwal VK. Tumor necrosis factor-alpha polymorphisms and expression in Guillain-Barré syndrome. Hum Immunol. 2010 Sep;71(9):905-10. doi: 10.1016/j.humimm.2010.06.013. Epub 2010 Jun 19. ... L. Association of tumor necrosis factor polymorphisms with Guillain-Barré syndrome. Eur ...

  8. Development of synchronous VHL syndrome tumors reveals contingencies and constraints to tumor evolution

    DEFF Research Database (Denmark)

    Fisher, Rosalie; Horswell, Stuart; Rowan, Andrew

    2014-01-01

    are contingent upon the nature of 3p loss of heterozygosity occurring early in tumorigenesis. However, despite distinct 3p events, genomic, proteomic and immunohistochemical analyses reveal evidence for convergence upon the PI3K-AKT-mTOR signaling pathway. Four germline tumors in this young patient...... a germline VHL mutation, the evolutionary principles of contingency and convergence in tumor development are complementary. In this small set of patients with early stage VHL-associated tumors, there is reduced mutation burden and limited evidence of intra-tumor heterogeneity....

  9. The Germline MLH1 K618A Variant and Susceptibility to Lynch Syndrome-Associated Tumors

    Science.gov (United States)

    Medeiros, Fabiola; Lindor, Noralane M.; Couch, Fergus J.; Highsmith, W. Edward

    2013-01-01

    Missense variants discovered during sequencing of cancer susceptibility genes can be problematic for clinical interpretation. MLH1 K618A, which results from a 2-bp alteration (AAG→GCG) leading to a substitution of lysine to alanine in codon 618, has variously been interpreted as a pathogenic mutation, a variant of unknown significance, and a benign polymorphism. We evaluated the role of MLH1 K618A in predisposition to cancer by genotyping 1512 control subjects to assess its frequency in the general population. We also reviewed the literature concerning MLH1 K618A in families with colorectal cancer. The measured allele frequency of the K618A variant was 0.40%, which is remarkably close to the 0.44% summarized from 2491 control subjects in the literature. K618A was over-represented in families with suspected Lynch syndrome. In 1366 families, the allele frequency was 0.88% (OR = 2.1, 95% CI = 1.3 to 3.5; P = 0.006). In studies of sporadic cancers of the type associated with Lynch syndrome, K618A was over-represented in 1742 cases (allele frequency of 0.83) (OR = 2.0, 95% CI = 1.2 to 3.2; P = 0.008). We conclude that MLH1 K618A is not a fully penetrant Lynch syndrome mutation, although it is not without effect, appearing to increase the risk of Lynch syndrome-associated tumors approximately twofold. Our systematic assessment approach may be useful for variants in other genes. PMID:22426235

  10. Plasma clot lysis time and its association with cardiovascular risk factors in black Africans.

    Directory of Open Access Journals (Sweden)

    Zelda de Lange

    Full Text Available Studies in populations of European descent show longer plasma clot lysis times (CLT in patients with cardiovascular disease (CVD than in controls. No data are available on the association between CVD risk factors and fibrinolytic potential in black Africans, a group undergoing rapid urbanisation with increased CVD prevalence. We investigated associations between known CVD risk factors and CLT in black Africans and whether CLTs differ between rural and urban participants in light of differences in CVD risk.Data from 1000 rural and 1000 urban apparently healthy black South Africans (35-60 years were cross-sectionally analysed.Increased PAI-1(act, BMI, HbA1c, triglycerides, the metabolic syndrome, fibrinogen concentration, CRP, female sex and positive HIV status were associated with increased CLTs, while habitual alcohol consumption associated with decreased CLT. No differences in CLT were found between age and smoking categories, contraceptive use or hyper- and normotensive participants. Urban women had longer CLT than rural women while no differences were observed for men.CLT was associated with many known CVD risk factors in black Africans. Differences were however observed, compared to data from populations of European descent available in the literature, suggesting possible ethnic differences. The effect of urbanisation on CLT is influenced by traditional CVD risk factors and their prevalence in urban and rural communities.

  11. Plasma clot lysis time and its association with cardiovascular risk factors in black Africans.

    Science.gov (United States)

    de Lange, Zelda; Pieters, Marlien; Jerling, Johann C; Kruger, Annamarie; Rijken, Dingeman C

    2012-01-01

    Studies in populations of European descent show longer plasma clot lysis times (CLT) in patients with cardiovascular disease (CVD) than in controls. No data are available on the association between CVD risk factors and fibrinolytic potential in black Africans, a group undergoing rapid urbanisation with increased CVD prevalence. We investigated associations between known CVD risk factors and CLT in black Africans and whether CLTs differ between rural and urban participants in light of differences in CVD risk.Data from 1000 rural and 1000 urban apparently healthy black South Africans (35-60 years) were cross-sectionally analysed.Increased PAI-1(act), BMI, HbA1c, triglycerides, the metabolic syndrome, fibrinogen concentration, CRP, female sex and positive HIV status were associated with increased CLTs, while habitual alcohol consumption associated with decreased CLT. No differences in CLT were found between age and smoking categories, contraceptive use or hyper- and normotensive participants. Urban women had longer CLT than rural women while no differences were observed for men.CLT was associated with many known CVD risk factors in black Africans. Differences were however observed, compared to data from populations of European descent available in the literature, suggesting possible ethnic differences. The effect of urbanisation on CLT is influenced by traditional CVD risk factors and their prevalence in urban and rural communities.

  12. Cordycepin enhances Epstein-Barr virus lytic infection and Epstein-Barr virus-positive tumor treatment efficacy by doxorubicin.

    Science.gov (United States)

    Du, Yinping; Yu, Jieshi; Du, Li; Tang, Jun; Feng, Wen-Hai

    2016-07-01

    The consistent latent presence of Epstein-Barr virus (EBV) in tumor cells offers potential for virus-targeted therapies. The switch from the latent form of EBV to the lytic form in tumor cells can lead to tumor cell lysis. In this study, we report that a natural small molecule compound, cordycepin, can induce lytic EBV infection in tumor cells. Subsequently, we demonstrate that cordycepin can enhance EBV reactivating capacity and EBV-positive tumor cell killing ability of low dose doxorubicin. The combination of cordycepin and doxorubicin phosphorylates CCAAT/enhancer binding protein β (C/EBPβ) through protein kinase C (PKC)-p38 mitogen activated protein kinases (p38 MAPK) signaling pathway, and C/EBPβ is required for the activation of lytic EBV infection. Most importantly, an in vivo experiment demonstrates that the combination of cordycepin and doxorubicin is more effective in inhibiting tumor growth in SCID mice than is doxorubicin alone. Our findings establish that cordycepin can enhance the efficacy of conventional chemotherapy for treatment of EBV-positive tumors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Concerning the role of cell lysis-cryptic growth in anaerobic side-stream reactors: the single-cell analysis of viable, dead and lysed bacteria.

    Science.gov (United States)

    Foladori, P; Velho, V F; Costa, R H R; Bruni, L; Quaranta, A; Andreottola, G

    2015-05-01

    In the Anaerobic Side-Stream Reactor (ASSR), part of the return sludge undergoes alternating aerobic and anaerobic conditions with the aim of reducing sludge production. In this paper, viability, enzymatic activity, death and lysis of bacterial cells exposed to aerobic and anaerobic conditions for 16 d were investigated at single-cell level by flow cytometry, with the objective of contributing to the understanding of the mechanisms of sludge reduction in the ASSR systems. Results indicated that total and viable bacteria did not decrease during the anaerobic phase, indicating that anaerobiosis at ambient temperature does not produce a significant cell lysis. Bacteria decay and lysis occurred principally under aerobic conditions. The aerobic decay rate of total bacteria (bTB) was considered as the rate of generation of lysed bacteria. Values of bTB of 0.07-0.11 d(-1) were measured in anaerobic + aerobic sequence. The enzymatic activity was not particularly affected by the transition from anaerobiosis to aerobiosis. Large solubilisation of COD and NH4(+) was observed only under anaerobic conditions, as a consequence of hydrolysis of organic matter, but not due to cell lysis. The observations supported the proposal of two independent mechanisms contributing equally to sludge reduction: (1) under anaerobic conditions: sludge hydrolysis of non-bacterial material, (2) under aerobic conditions: bacterial cell lysis and oxidation of released biodegradable compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Noonan syndrome – a new survey

    Science.gov (United States)

    Tafazoli, Alireza; Eshraghi, Peyman; Koleti, Zahra Kamel

    2016-01-01

    Noonan syndrome (NS) is an autosomal dominant disorder with vast heterogeneity in clinical and genetic features. Various symptoms have been reported for this abnormality such as short stature, unusual facial characteristics, congenital heart abnormalities, developmental complications, and an elevated tumor incidence rate. Noonan syndrome shares clinical features with other rare conditions, including LEOPARD syndrome, cardio-facio-cutaneous syndrome, Noonan-like syndrome with loose anagen hair, and Costello syndrome. Germline mutations in the RAS-MAPK (mitogen-activated protein kinase) signal transduction pathway are responsible for NS and other related disorders. Noonan syndrome diagnosis is primarily based on clinical features, but molecular testing should be performed to confirm it in patients. Due to the high number of genes associated with NS and other RASopathy disorders, next-generation sequencing is the best choice for diagnostic testing. Patients with NS also have higher risk for leukemia and specific solid tumors. Age-specific guidelines for the management of NS are available. PMID:28144274

  15. Bloom syndrome in sibs: first reports of hepatocellular carcinoma and Wilms tumor with documented anaplasia and nephrogenic rests.

    Science.gov (United States)

    Jain, D; Hui, P; McNamara, J; Schwartz, D; German, J; Reyes-Múgica, M

    2001-01-01

    The triad of small body size, immunodeficiency, and sun-sensitive facial erythema characterizes the phenotype Bloom syndrome (BS), a rare autosomal recessive disorder with a striking predisposition to multiple types of cancers that arise earlier than expected in the general population. Here we report two sibs with BS. The older, a 15-year-old-girl, developed a hepatocellular carcinoma, a neoplasm not yet reported in association with BS. Her younger brother developed an anaplastic Wilms tumor (WT) associated with nephrogenic rests at the age of 31/2 years, and this was followed by a myelodysplastic syndrome. Complex cytogenetic abnormalities were identified in all three neoplasms. These examples expand the spectrum of malignancies occurring in BS to include liver cell neoplasms, and confirm the association of nephrogenic rests with WT, even in the setting of BS.

  16. [Ultrasound dynamics lysis apex thrombus as an objective criterion of effectiveness of anticoagulation therapy in venous thrombosis].

    Science.gov (United States)

    Kalinin, R E; Suchkov, I A; Pshennikov, A S; Agapov, A B

    2016-01-01

    To assess the effectiveness of anticoagulant therapy (ACT) for the treatment of patients with deep venous thrombosis (DVT) of the lower extremities. The study considered ultrasonic characteristics of lysis of the proximal part of thrombus: localization and nature of venous thrombosis, the length and diameter of the proximal floating part of the thrombus, and duration of the venous thrombosis. Depending on the ACT options patients were divided into 3 groups: Group 1 (18 patients) received rivaroxaban, group 2 (19 patients) received enoxaparin sodium with subsequent transition to warfarin, and 3 group (19 patietns) received enoxaparin sodium, followed by administration of rivaroxaban. Treatment with rivaroxaban was preferable over standard ACT with enoxaparin/warfarin with regards to the lysis of thrombus when duration of thrombosis did not exceed 10 days. In 10.5% of patients who received warfarin flotation of thrombi remained for 14 days; the length of the floating part of the thrombi did not exceed 3 cm. Such circumstances and inability to reach a therapeutic INR value required cava filter placement. Treatment with enoxaparin sodium followed by the administration of rivaroxaban was found to be the most efficient ACT regimen as there was no negative dynamics of ultrasound characteristics of lysis of thrombi at any duration of the disease.

  17. Polymer Coatings in 3D-Printed Fluidic Device Channels for Improved Cellular Adherence Prior to Electrical Lysis.

    Science.gov (United States)

    Gross, Bethany C; Anderson, Kari B; Meisel, Jayda E; McNitt, Megan I; Spence, Dana M

    2015-06-16

    This paper describes the design and fabrication of a polyjet-based three-dimensional (3D)-printed fluidic device where poly(dimethylsiloxane) (PDMS) or polystyrene (PS) were used to coat the sides of a fluidic channel within the device to promote adhesion of an immobilized cell layer. The device was designed using computer-aided design software and converted into an .STL file prior to printing. The rigid, transparent material used in the printing process provides an optically transparent path to visualize endothelial cell adherence and supports integration of removable electrodes for electrical cell lysis in a specified portion of the channel (1 mm width × 0.8 mm height × 2 mm length). Through manipulation of channel geometry, a low-voltage power source (500 V max) was used to selectively lyse adhered endothelial cells in a tapered region of the channel. Cell viability was maintained on the device over a 5 day period (98% viable), though cell coverage decreased after day 4 with static media delivery. Optimal lysis potentials were obtained for the two fabricated device geometries, and selective cell clearance was achieved with cell lysis efficiencies of 94 and 96%. The bottleneck of unknown surface properties from proprietary resin use in fabricating 3D-printed materials is overcome through techniques to incorporate PDMS and PS.

  18. Demonstration of NK cell-mediated lysis of varicella-zoster virus (VZV)-infected cells: characterization of the effector cells

    Energy Technology Data Exchange (ETDEWEB)

    Tilden, A.B.; Cauda, R.; Grossi, C.E.; Balch, C.M.; Lakeman, A.D.; Whitley, R.J.

    1986-06-01

    Infection with varicella-zoster virus (VZV) rendered RAJI cells more susceptible to lysis by non-adherent blood lymphocytes. At an effector to target ratio of 80:1 the mean percentage of /sup 51/Cr release of VZV-infected RAJI cells was 41 +/- 12%, whereas that of uninfected RAJI cells was 15 +/- 6%. The increased susceptibility to lysis was associated with increased effector to target conjugate formation in immunofluorescence binding assays. The effector cells cytotoxic for VZV-infected RAJI cells were predominantly Leu-11a/sup +/ Leu-4/sup -/ granular lymphocytes as demonstrated by fluorescence-activated cell sorting. The effector cell active against VZV-infected RAJI cells appeared similar to those active against herpes simplex virus (HSV)-infected cells, because in cold target competition experiments the lysis of /sup 51/Cr-labeled VZV-infected RAJI cells was efficiently inhibited by either unlabeled VZV-infected RAJI cells (mean 71% inhibition, 2:1 ratio unlabeled to labeled target) or HSV-infected RAJI cells (mean 69% inhibition) but not by uninfected RAJI cells (mean 10% inhibition). In contrast, competition experiments revealed donor heterogeneity in the overlap between effector cells for VZV- or HSV-infected RAJI vs K-562 cells.

  19. Spectroscopic techniques (Mössbauer spectrometry, NMR, ESR,…) as tools to resolve doubtful NMR images: Study of the craniopharyngioma tumor

    Science.gov (United States)

    Rimbert, J. N.; Dumas, F.; Lafargue, C.; Kellershohn, C.; Brunelle, F.; Lallemand, D.

    1990-07-01

    Craniopharyngioma, an intracranial tumor, exhibits hyperintensity in the Spin-Echo-T2-NMR image and a hyposignal in the SE-T1-image. However, in some cases (15-20% cases), hypersignals are seen in both SE-T1 and T2-MRI. Using spectroscopic techniques, Mössbauer spectrometry in particular, we have demonstrated that the T1 hypersignal is due to ferritin, dissolved in the cystic liquid, after tumor cell lysis, in the course of time. Other possible reasons inducing a shortening of the T1 relaxation time (presence of lipids, intratumoral hemorrhage) have been rejected.

  20. A novel clot lysis assay for recombinant plasminogen activator.

    Science.gov (United States)

    Jamialahmadi, Oveis; Fazeli, Ahmad; Hashemi-Najafabadi, Sameereh; Fazeli, Mohammad Reza

    2015-03-01

    Recombinant plasminogen activator (r-PA, reteplase) is an engineered variant of alteplase. When expressed in E. coli, it appears as inclusion bodies that require refolding to recover its biological activity. An important step following refolding is to determine the activity of refolded protein. Current methods for enzymatic activity of thrombolytic drugs are costly and complex. Here a straightforward and low-cost clot lysis assay was developed. It quantitatively measures the activity of the commercial reteplase and is also capable of screening refolding conditions. As evidence for adequate accuracy and sensitivity of the current assay, r-PA activity measurements are shown to be comparable to those obtained from chromogenic substrate assay.

  1. Genetic counseling and cascade genetic testing in Lynch syndrome.

    Science.gov (United States)

    Hampel, Heather

    2016-07-01

    Lynch syndrome is the most common cause of inherited colorectal and endometrial cancers. Individuals with Lynch syndrome have a 10-80 % lifetime risk for colorectal cancer and a 15-60 % lifetime risk for endometrial cancer. Both cancers are preventable through chemoprevention, intensive cancer surveillance, and risk-reducing surgery options. Efforts to identify as many individuals with Lynch syndrome as possible will prevent cancers and save lives. This includes the traditional cancer genetic counseling model whereby individuals with and without cancer are evaluated for a possible Lynch syndrome diagnosis based on their personal and family history of colon polyps and cancers. It also includes universal tumor screening for Lynch syndrome whereby all individuals with colorectal or endometrial cancer are screened for tumor features of Lynch syndrome at the time of diagnosis. Those with tumors suspicious for Lynch syndrome are referred for cancer genetic counseling regardless of their family history of cancer. This two approaches must be maximized to attain high patient reach. Finally, and perhaps most importantly, cascade testing among the at-risk relatives of those diagnosed with Lynch syndrome is critically important to maximize the diagnosis of individuals with Lynch syndrome. In fact, the cost-effectiveness of universal tumor screening for Lynch syndrome relies entirely on counseling and testing as many at-risk individuals as possible since young unaffected individuals stand to benefit the most from an early diagnosis of Lynch syndrome. This approach must be optimized to achieve high family reach. It will take a concerted effort from patients, clinicians and public health officials to improve current approaches to the diagnosis of Lynch syndrome and the prevention and treatment of Lynch syndrome-associated cancer but these lessons can be applied to other conditions as the ultimate example of personalized medicine.

  2. Dietary B vitamin and methionine intake and MTHFR C677T genotype on risk of colorectal tumors in Lynch syndrome: the GEOLynch cohort study

    NARCIS (Netherlands)

    Jung, A.Y.; van Duijnhoven, F.J.B.; Nagengast, F.M.; Botma, A.; Heine-Broring, R.C.; Kleibeuker, J.H.; Vasen, H.F.A.; Harryvan, J.L.; Winkels, R.M.; Kampman, E.

    2014-01-01

    Purpose: Dietary intake of B vitamins and methionine, essential components of DNA synthesis and methylation pathways, may influence colorectal tumor (CRT) development. The impact of B vitamins on colorectal carcinogenesis in individuals with Lynch syndrome (LS) is unknown but is important given

  3. Sulfolobus turreted icosahedral virus c92 protein responsible for the formation of pyramid-like cellular lysis structures.

    Science.gov (United States)

    Snyder, Jamie C; Brumfield, Susan K; Peng, Nan; She, Qunxin; Young, Mark J

    2011-07-01

    Host cells infected by Sulfolobus turreted icosahedral virus (STIV) have been shown to produce unusual pyramid-like structures on the cell surface. These structures represent a virus-induced lysis mechanism that is present in Archaea and appears to be distinct from the holin/endolysin system described for DNA bacteriophages. This study investigated the STIV gene products required for pyramid formation in its host Sulfolobus solfataricus. Overexpression of STIV open reading frame (ORF) c92 in S. solfataricus alone is sufficient to produce the pyramid-like lysis structures in cells. Gene disruption of c92 within STIV demonstrates that c92 is an essential protein for virus replication. Immunolocalization of c92 shows that the protein is localized to the cellular membranes forming the pyramid-like structures.

  4. The novel RAF1 mutation p.(Gly361Ala) located outside the kinase domain of the CR3 region in two patients with Noonan syndrome, including one with a rare brain tumor.

    Science.gov (United States)

    Harms, Frederike L; Alawi, Malik; Amor, David J; Tan, Tiong Y; Cuturilo, Goran; Lissewski, Christina; Brinkmann, Julia; Schanze, Denny; Kutsche, Kerstin; Zenker, Martin

    2018-02-01

    Noonan syndrome is characterized by typical craniofacial dysmorphism, postnatal growth retardation, congenital heart defect, and learning difficulties and belongs to the RASopathies, a group of neurodevelopmental disorders caused by germline mutations in genes encoding components of the RAS-MAPK pathway. Mutations in the RAF1 gene are associated with Noonan syndrome, with a high prevalence of hypertrophic cardiomyopathy (HCM). RAF1 mutations cluster in exons encoding the conserved region 2 (CR2), the kinase activation segment of the CR3 domain, and the C-terminus. We present two boys with Noonan syndrome and the identical de novo RAF1 missense variant c.1082G>C/p.(Gly361Ala) affecting the CR3, but located outside the kinase activation segment. The p.(Gly361Ala) mutation has been identified as a RAF1 allele conferring resistance to RAF inhibitors. This amino acid change favors a RAF1 conformation that allows for enhanced RAF dimerization and increased intrinsic kinase activity. Both patients with Noonan syndrome showed typical craniofacial dysmorphism, macrocephaly, and short stature. One individual developed HCM and was diagnosed with a disseminated oligodendroglial-like leptomeningeal tumor (DOLT) of childhood at the age of 9 years. While there is a well-established association of NS with malignant tumors, especially childhood hemato-oncological diseases, brain tumors have rarely been reported in Noonan syndrome. Our data demonstrate that mutation scanning of the entire coding region of genes associated with Noonan syndrome is mandatory not to miss rare variants located outside the known mutational hotspots. © 2017 Wiley Periodicals, Inc.

  5. Turner syndrome and meningioma: support for a possible increased risk of neoplasia in Turner syndrome.

    Science.gov (United States)

    Pier, Danielle B; Nunes, Fabio P; Plotkin, Scott R; Stemmer-Rachamimov, Anat O; Kim, James C; Shih, Helen A; Brastianos, Priscilla; Lin, Angela E

    2014-01-01

    Neoplasia is uncommon in Turner syndrome, although there is some evidence that brain tumors are more common in Turner syndrome patients than in the general population. We describe a woman with Turner syndrome (45,X) with a meningioma, in whom a second neoplasia, basal cell carcinomas of the scalp and nose, developed five years later in the absence of therapeutic radiation. Together with 7 cases of Turner syndrome with meningioma from a population-based survey in the United Kingdom, and 3 other isolated cases in the literature, we review this small number of patients for evidence of risk factors related to Turner syndrome, such as associated structural anomalies or prior treatment. We performed histological and fluorescent in situ hybridization (FISH) of 22q (NF2 locus) analyses of the meningeal tumor to search for possible molecular determinants. We are not able to prove causation between these two entities, but suggest that neoplasia may be a rare associated medical problem in Turner syndrome. Additional case reports and extension of population-based studies are needed. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  6. STUDIES ON THE BACTERIOPHAGE OF D'HERELLE : IX. EVIDENCE OF HYDROLYSIS OF BACTERIAL PROTEIN DURING LYSIS.

    Science.gov (United States)

    Hetler, D M; Bronfenbrenner, J

    1928-07-31

    1. During the process of lysis by bacteriophage, there is an appreciable increase in the amount of free amino acid present in the culture. 2. The increase of free amino acid is due to hydrolysis of bacterial protein.

  7. Cell-density-dependent lysis and sporulation of Myxococcus xanthus in agarose microbeads.

    OpenAIRE

    Rosenbluh, A; Nir, R; Sahar, E; Rosenberg, E

    1989-01-01

    Vegetative cells of Myxococcus xanthus were immobilized in 25-microns-diameter agarose microbeads and incubated in either growth medium or sporulation buffer. In growth medium, the cells multiplied, glided to the periphery, and then filled the beads. In sporulation buffer, up to 90% of the cells lysed and ca. 50% of the surviving cells formed resistant spores. A strong correlation between sporulation and cell lysis was observed; both phenomena were cell density dependent. Sporulation proficie...

  8. Resistance of some leukemic blasts to lysis by lymphokine activated killer (LAK) cells

    Energy Technology Data Exchange (ETDEWEB)

    Panayotides, P; Sjoegren, A -M; Reizenstein, P; Porwit, A. Immunopathology Lab., Dept. of Pathology, Karolinska Hospital, Stockholm; Wasserman, J

    1988-01-01

    Peripheral blood mononuclear cells (PBMC) from healthy donors and AML patients in remission were stimulated with phytohemagglutinin (PHA) and recombinant interleukin-2 (IL-2). These stimulated cells (lymphokine activated killer (LAK) cells) showed increased DNA synthesis as measured by /sup 3/H-Thymidine uptake. A synergistic effect of PHA and IL-2 was found. LAK cells' ability to kill acute myeloid leukemia (AML) blasts was investigated by the /sup 51/Cr release assay. LAK cells showed a cytotoxicity (over 10% specific /sup 51/Cr release) against 9/12 leukemic blasts, even at effector/target (E/T) ratios as low as 5:1. However, on average only 22.2% (SD 11.8) and 36.5% (SD 12.5) /sup 51/Cr release were obtained in 4- and 18-hour cytotoxicity assays, respectively, at an E/T ratio of 20:1. Leukemic blasts in 3/12 AML cases and normal PBMC were entirely resistant to lysis, even at an E/T ratio of 80:1. Susceptibility to lysis was not correlated to peanut-agglutinin receptor expression. LAK cells were more cytotoxic towards the K-562 cell line (natural killer activity) than unstimulated PBMC.

  9. SUNCT syndrome associated with pituitary tumor: case report Síndrome SUNCT associada a tumor de hipófise: relato de caso

    Directory of Open Access Journals (Sweden)

    Pedro A.S. Rocha Filho

    2006-06-01

    Full Text Available For twelve years, the subject of this report, a 38-year-old man, presented a clinical condition compatible with the SUNCT (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing syndrome. He presented a stabbing and intense daily pain located in the left pre-auricular and temporal regions. Each of these intense pain attacks lasted around one minute and presented a frequency of two to eight times per day. The pain was associated with ipsilateral lacrimation, conjunctival injection and rhinorrhea. MRI revealed a pituitary tumor with little suprasellar extent. The subject’s serial assays of prolactin, GH, TSH and ACTH were within normal levels. Following transsphenoidal hypophysectomy, with complete removal of the tumor, the subject no more presented pain. The pathological diagnosis was non-secreting adenoma. Fourteen months after the surgery, he remains symptom-free.O paciente relatado neste artigo apresentou uma condição clínica compatível com síndrome SUNCT (cefaléia de curta duração, unilateral, neuralgiforme com hiperemia conjuntival e lacrimejamento. Ele referia dor diária, intensa, em facada, localizada na região pré-auricular e temporal esquerdas. Cada ataque de dor permanecia por cerca de um minuto, com freqüência de duas a oito vezes por dia. A dor se acompanhava de lacrimejamento ipsolateral, congestão conjuntival e rinorréia. A RM mostrou um tumor de hipófise com pouca extensão suprasselar. Dosagens de prolactina, GH, TSH e ACTH estavam em níveis normais. Foi então submetido a hipofisectomia transesfenoidal com remoção completa do tumor após o que a dor cessou completamente. O diagnóstico anátomo-patológico foi adenoma não secretor. Quatorze meses após a cirurgia, o paciente permanecia livre de dor.

  10. Lynch Syndrome: An Updated Review

    Directory of Open Access Journals (Sweden)

    Rishabh Sehgal

    2014-06-01

    Full Text Available Lynch syndrome is one of the most common cancer susceptibility syndromes. Individuals with Lynch syndrome have a 50%–70% lifetime risk of colorectal cancer, 40%–60% risk of endometrial cancer, and increased risks of several other malignancies. It is caused by germline mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2. In a subset of patients, Lynch syndrome is caused by 3' end deletions of the EPCAM gene, which can lead to epigenetic silencing of the closely linked MSH2. Relying solely on age and family history based criteria inaccurately identifies eligibility for Lynch syndrome screening or testing in 25%–70% of cases. There has been a steady increase in Lynch syndrome tumor screening programs since 2000 and institutions are rapidly adopting a universal screening approach to identify the patients that would benefit from genetic counseling and germline testing. These include microsatellite instability testing and/or immunohistochemical testing to identify tumor mismatch repair deficiencies. However, universal screening is not standard across institutions. Furthermore, variation exists regarding the optimum method for tracking and disclosing results. In this review, we summarize traditional screening criteria for Lynch syndrome, and discuss universal screening methods. International guidelines are necessary to standardize Lynch syndrome high-risk clinics.

  11. Neonatal Cushing Syndrome: A Rare but Potentially Devastating Disease.

    Science.gov (United States)

    Tatsi, Christina; Stratakis, Constantine A

    2018-03-01

    Neonatal Cushing syndrome (CS) is most commonly caused by exogenous administration of glucocorticoids and rarely by endogenous hypercortisolemia. CS owing to adrenal lesions is the most common cause of endogenous CS in neonates and infants, and adrenocortical tumors (ACTs) represent most cases. Many ACTs develop in the context of a TP53 gene mutation, which causes Li-Fraumeni syndrome. More rarely, neonatal CS presents as part of other syndromes such as McCune-Albright syndrome or Beckwith-Wiedemann syndrome. Management usually includes resection of the primary tumor with or without additional medical treatment, but manifestations may persist after resolution of hypercortisolemia. Published by Elsevier Inc.

  12. Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    International Nuclear Information System (INIS)

    Tonelli, Francesco; Giudici, Francesco; Giusti, Francesca; Brandi, Maria Luisa

    2012-01-01

    We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present

  13. A rare ovarian tumor, leydig stromal cell tumor, presenting with virilization: a case report

    Directory of Open Access Journals (Sweden)

    Soheila Aminimoghaddam

    2012-11-01

    Full Text Available  Abstract Leydig stromal cell tumor is a rare ovarian tumor that belongs to the group of sex-cord stromal tumors. They produce testosterone leading to hyperandrogenism. We present a 41yr old woman with symptoms of virilization and a mass of right adenex via ultra Sonography, and a rise of total and free serum testosterone. An ovarian source of androgen was suspected and a surgery performed. A diagnosis of leydig-stromal cell tumor was confirmed. Our report is a reminder that although idiopathic hirsutism and other benign androgen excess disorder like Polycystic Ovarian Syndrome (PCOs are common, ovarian mass should be considered in differential diagnosis. 

  14. Arthroscopic lysis and lavage in patients with temporomandibular anterior disc displacement without reduction

    Czech Academy of Sciences Publication Activity Database

    Machoň, V.; Šedý, Jiří; Klíma, K.; Hirjak, D.; Foltán, R.

    2012-01-01

    Roč. 41, č. 1 (2012), s. 109-113 ISSN 0901-5027 R&D Projects: GA MŠk(CZ) LC554; GA ČR GAP304/10/0320 Grant - others:GA MŠk(CZ) 1M0538 Program:1M Institutional research plan: CEZ:AV0Z50390703 Keywords : temporomandibular joint * arthroscopic lysis * arthroscopic lavage Subject RIV: FJ - Surgery incl. Transplants Impact factor: 1.521, year: 2012

  15. Mouse Models Recapitulating Human Adrenocortical Tumors: What is lacking?

    Directory of Open Access Journals (Sweden)

    Felicia Leccia

    2016-07-01

    Full Text Available Adrenal cortex tumors are divided into benign forms such as primary hyperplasias and adrenocortical adenomas (ACAs, and malignant forms or adrenocortical carcinomas (ACCs. Primary hyperplasias are rare causes of ACTH-independent hypercortisolism. ACAs are the most common type of adrenal gland tumors and they are rarely functional, i.e producing steroids. When functional, adenomas result in endocrine disorders such as Cushing’s syndrome (hypercortisolism or Conn’s syndrome (hyperaldosteronism. In contrast, ACCs are extremely rare but highly aggressive tumors that may also lead to hypersecreting syndromes. Genetic analyses of patients with sporadic or familial forms of adrenocortical tumors led to the identification of potentially causative genes, most of them being involved in PKA, Wnt/β-catenin and P53 signaling pathways. Development of mouse models is a crucial step to firmly establish the functional significance of candidate genes, to dissect mechanisms leading to tumors and endocrine disorders and in fine to provide in vivo tools for therapeutic screens. In this article we will provide an overview on the existing mouse models (xenografted and genetically engineered of adrenocortical tumors by focusing on the role of PKA and Wnt/β-catenin pathways in this context. We will discuss the advantages and limitations of models that have been developed heretofore and we will point out necessary improvements in the development of next generation mouse models of adrenal diseases.

  16. Vulnerability of cultured canine lung tumor cells to NK cell-mediated cytolysis

    International Nuclear Information System (INIS)

    Haley, P.J.; Kohr, J.M.; Kelly, G.; Muggenburg, B.A.; Guilmette, B.A.

    1988-01-01

    Five cell lines, designated as canine lung epithelial cell (CLEP), derived from radiation induced canine lung tumors and canine thyroid adeno-carcinoma (CTAC) cells were compared for their susceptibility to NK cell-mediated cytolysis using peripheral blood lymphocytes from normal, healthy Beagle dogs as effector cells. Effector cells and chromium 51 radiolabeled target cells were incubated for 16 h at ratios of 12.5:1, 25:1, 50:1, and 100:1. Increasing cytolysis was observed for all cell lines as the effector-to-target-cell ratios increased from 12.5:1 to 100:1. The percent cytotoxicity was significantly less for all lung tumor cell lines as compared to CTAC at the 100:1 ratio. One lung tumor cell line, CLEP-9, had 85% of the lytic vulnerability of the CTAC cell line and significantly greater susceptibility to NK cell-mediated lysis than all of the other lung tumor cell lines. Susceptibility to NK cell cytolysis did not correlate with in vivo malignant behavior of the original tumor. These data suggest that cultured canine lung tumor cells are susceptible to NK cell cytolytic activity in vitro and that at least one of these cell lines (CLEP-9) is a candidate for substitution of the standard canine NK cell target, CTAC, in NK cell assays. The use of lung tumor cells in NK cell assays may provide greater insight into the control of lung tumors by immune mechanisms. (author)

  17. "Mixed germ cell testicular tumor" in an adult female

    Directory of Open Access Journals (Sweden)

    Udasimath Shivakumarswamy

    2012-01-01

    Full Text Available The androgen insensitivity (testicular feminization syndrome was described by Morris in phenotypic females with 46XY karyotype, presenting with primary amenorrhea, adequate breast development, and absent or scanty pubic or axillary hair. Gonads consist usually of seminiferous tubules without spermatogenesis. These patients have a 5-10% risk of developing germ cell tumors, usually after the complete development of secondary female sexual characteristics. We hereby report a case considered as a female with married life of 15 years, who was operated for severe abdominal pain. Phenotype characters were that of female. Microscopic examination of the tumor from the abdomen revealed germinoma and yolk sac tumor with adjacent seminiferous tubules. Karyotyping showed 46XY. Final diagnosis of malignant mixed germ cell tumor in androgen insensitivity syndrome was made. Surveillance may be the most appropriate option when these conditions are initially diagnosed in adulthood to prevent development of germ cell tumors.

  18. Changes in bacterial and eukaryotic community structure after mass lysis of filamentous cyanobacteria associated with viruses

    NARCIS (Netherlands)

    Hannen, E.J. van; Zwart, G.; Agterveld, M.P. van; Gons, H.J.; Ebert, J.; Laanbroek, H.J.

    1999-01-01

    During an experiment in two laboratory-scale enclosures filled with lake water (130 liters each) we noticed the almost-complete lysis of the cyanobacterial population. Based on electron microscopic observations of viral particles inside cyanobacterial filaments and counts of virus-like particles,

  19. Changes in bacterial and eukaryotic community structure after mass lysis of filamentous cyanobacteria associated with viruses

    NARCIS (Netherlands)

    Van Hannen, E.J.; Zwart, G.; Van Agterveld, M.P.; Gons, H.J.; Ebert, J.; Laanbroek, H.J.

    1999-01-01

    During an experiment in two laboratory-scale enclosures filled with lake water (130 liters each) we noticed the almost-complete lysis of the cyanobacterial population. Based on electron microscopic observations of viral particles inside cyanobacterial filaments and counts of virus-like particles, we

  20. Mass entrapment and lysis of Mesodinium rubrum cells in mucus threads observed in cultures with Dinophysis

    DEFF Research Database (Denmark)

    Ojamäe, Karin; Hansen, Per Juel; Lips, Inga

    2016-01-01

    The entrapment and death of the ciliate Mesodinium rubrum in the mucus threads in cultures with Dinophysis is described and quantified. Feeding experiments with different concentrations and predator–prey ratios of Dinophysis acuta, Dinophysis acuminata and M. rubrum to study the motility loss...... and aggregate formation of the ciliates and the feeding behaviour of Dinophysis were carried out. In cultures of either Dinophysis species, the ciliates became entrapped in the mucus, which led to the formation of immobile aggregates of M. rubrum and subsequent cell lysis. The proportion of entrapped ciliates...... was influenced by the concentration of Dinophysis and the ratio of predator and prey in the cultures. At high cell concentrations of prey (136 cells mL−1) and predator (100 cells mL−1), a maximum of 17% of M. rubrum cells became immobile and went through cell lysis. Ciliates were observed trapped in the mucus...

  1. Acute Respiratory Distress Syndrome Caused by Leukemic Infiltration of the Lung

    Directory of Open Access Journals (Sweden)

    Yao-Kuang Wu

    2008-05-01

    Full Text Available Respiratory distress syndrome resulting from leukemic pulmonary infiltrates is seldom diagnosed antemortem. Two 60- and 80-year-old women presented with general malaise, progressive shortness of breath, and hyperleukocytosis, which progressed to acute respiratory distress syndrome (ARDS after admission. Acute leukemia with pulmonary infection was initially diagnosed, but subsequent examinations including open lung biopsy revealed leukemic pulmonary infiltrates without infection. In one case, the clinical condition and chest radiography improved initially after combination therapy with chemotherapy for leukemia and aggressive pulmonary support. However, new pulmonary infiltration on chest radiography and hypoxemia recurred, which was consistent with acute lysis pneumopathy. Despite aggressive treatment, both patients died due to rapidly deteriorating condition. Leukemic pulmonary involvement should be considered in acute leukemia patients with non-infectious diffusive lung infiltration, especially in acute leukemia with a high blast count.

  2. Biological variation in tPA-induced plasma clot lysis time.

    Science.gov (United States)

    Talens, Simone; Malfliet, Joyce J M C; Rudež, Goran; Spronk, Henri M H; Janssen, Nicole A H; Meijer, Piet; Kluft, Cornelis; de Maat, Moniek P M; Rijken, Dingeman C

    2012-10-01

    Hypofibrinolysis is a risk factor for venous and arterial thrombosis, and can be assessed by using a turbidimetric tPA-induced clot lysis time (CLT) assay. Biological variation in clot lysis time may affect the interpretation and usefulness of CLT as a risk factor for thrombosis. Sufficient information about assay variation and biological variation in CLT is not yet available. Thus, this study aimed to determine the analytical, within-subject and between-subject variation in CLT. We collected blood samples from 40 healthy individuals throughout a period of one year (average 11.8 visits) and determined the CLT of each plasma sample in duplicate. The mean (± SD) CLT was 83.8 (± 11.1) minutes. The coefficients of variation for total variation, analytical variation, within-subject variation and between-subject variation were 13.4%, 2.6%, 8.2% and 10.2%, respectively. One measurement can estimate the CLT that does not deviate more than 20% from its true value. The contribution of analytical variation to the within-subject variation was 5.0%, the index of individuality was 0.84 and the reference change value was 23.8%. The CLT was longer in the morning compared to the afternoon and was slightly longer in older individuals (> 40 years) compared to younger (≤40 years) individuals. There was no seasonal variation in CLT and no association with air pollution. CLT correlated weakly with fibrinogen, C-reactive protein, prothrombin time and thrombin generation. This study provides insight into the biological variation of CLT, which can be used in future studies testing CLT as a potential risk factor for thrombosis.

  3. Tumor macroenvironment and metabolism.

    Science.gov (United States)

    Al-Zoughbi, Wael; Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-04-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organs. Amino acids, and distinct lipid and lipoprotein species can be essential for further tumor growth. The role of glucose in tumor metabolism has been studied extensively. Cancer-associated cachexia is the most important tumor-associated systemic syndrome and not only affects the quality of life of patients with various malignancies but is estimated to be the cause of death in 15%-20% of all cancer patients. On the other hand, systemic metabolic diseases such as obesity and diabetes are known to influence tumor development. Furthermore, the clinical implications of the tumor macroenvironment are explored in the context of the patient's outcome with special consideration for pediatric tumors. Finally, ways to target the tumor macroenvironment that will provide new approaches for therapeutic concepts are described. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. A case of Werner's syndrome associated with osteosarcoma.

    Science.gov (United States)

    Murata, K; Hatamochi, A; Shinkai, H; Ishikawa, Y; Kawaguchi, N; Goto, M

    1999-10-01

    We described a case of Werner's syndrome associated with osteosarcoma. A 37-year-old Japanese man was diagnosed as having Werner's syndrome by the presence of juvenile cataracts, skin sclerosis and hyperpigmentation of the feet, high-pitched voice, characteristic bird-like appearance of the face with beak-shaped nose, thinning of the entire skin and hyperkeratoses on soles, hyperlipemia, hyperuricemia, diabetes melitus, and the mutated responsible gene (WRN). He had a 3-month history of a tumor on his left forearm. Histologically, the tumor included four histological patterns; a malignant fibrous histiocytoma-like, a desmoid-like, a dermatofibrosarcoma protuberans-like, and a chondrosarcoma-like pattern. Tumoral osteoid formation was also found in the tumor. Therefore, the tumor was diagnosed as osteosarcoma.

  5. Brooke-Spiegler syndrome

    Directory of Open Access Journals (Sweden)

    Layegh Pouran

    2008-01-01

    Full Text Available The Brooke-Spiegler syndrome (BSS is an uncommon autosomal dominant disorder characterized by a high affinity to form multiple adnexal neoplasia (skin appendage tumors, especially trichoepitheliomas and cylindromas, and occasionally spiradenomas, which usually appear in the second or third decade of life. To date, only a few cases with this syndrome have been reported. This case report describes a 26-year-old woman who presented to the dermatology department of Qaem Hospital with tumoral lesions on her scalp, face, and forearm. Her father and younger brother were also affected. On examination, several round-to-oval skin-colored papules with a smooth pearly surface measuring 2 to 6 mm in diameter were seen on the mid-face, particularly in the nasolabial folds, the upper lip. Tumors and nodules seen on the scalp were pinkish red, dome-shaped, and to some extent, pedunculated with surface telangiectasia and induration. Histopathology of the facial papules showed trichoepithelioma while that of a scalp nodule showed cylindroma.

  6. Cystic degeneration of neuro endocrine tumor of pancreas and ...

    African Journals Online (AJOL)

    Pancreatic endocrine tumors (PETs) or islet cell tumors are rare lesions, the incidence of which is estimated to be less than 1 per 100,000 person-years in the general population . PETs can be divided into functional (exhibit a distinct clinical syndrome due to hormone hypersecretion) and non-functional tumors. The majority ...

  7. Gorlin-goltz syndrome

    Directory of Open Access Journals (Sweden)

    B V Shobha

    2011-01-01

    Full Text Available Gorlin-Goltz syndrome also known as nevoid basal cell carcinoma syndrome (NBCCS is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by keratocystic odontogenic tumors (KCOT in the jaw, multiple basal cell carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic examination in the first decade of life, as KCOTs are usually one of the first manifestations of the NBCCS syndrome. This article reports the case of a 12-year-old girl with Gorlin-Goltz syndrome, emphasizing its clinical and radiographic manifestation. This study highlights the importance of health professionals in the early diagnosis of this syndrome and a multidisciplinary approach to provide a better diagnosis and prognosis.

  8. Lynch Syndrome: Genomics Update and Imaging Review.

    Science.gov (United States)

    Cox, Veronica L; Saeed Bamashmos, Anas A; Foo, Wai Chin; Gupta, Shiva; Yedururi, Sireesha; Garg, Naveen; Kang, Hyunseon Christine

    2018-01-01

    Lynch syndrome is the most common hereditary cancer syndrome, the most common cause of heritable colorectal cancer, and the only known heritable cause of endometrial cancer. Other cancers associated with Lynch syndrome include cancers of the ovary, stomach, urothelial tract, and small bowel, and less frequently, cancers of the brain, biliary tract, pancreas, and prostate. The oncogenic tendency of Lynch syndrome stems from a set of genomic alterations of mismatch repair proteins. Defunct mismatch repair proteins cause unusually high instability of regions of the genome called microsatellites. Over time, the accumulation of mutations in microsatellites and elsewhere in the genome can affect the production of important cellular proteins, spurring tumorigenesis. Universal testing of colorectal tumors for microsatellite instability (MSI) is now recommended to (a) prevent cases of Lynch syndrome being missed owing to the use of clinical criteria alone, (b) reduce morbidity and mortality among the relatives of affected individuals, and (c) guide management decisions. Organ-specific cancer risks and associated screening paradigms vary according to the sex of the affected individual and the type of germline DNA alteration causing the MSI. Furthermore, Lynch syndrome-associated cancers have different pathologic, radiologic, and clinical features compared with their sporadic counterparts. Most notably, Lynch syndrome-associated tumors tend to be more indolent than non-Lynch syndrome-associated neoplasms and thus may respond differently to traditional chemotherapy regimens. The high MSI in cases of colorectal cancer reflects a difference in the biologic features of the tumor, possibly with a unique susceptibility to immunotherapy. © RSNA, 2018.

  9. An Isolated Pulmonary Hematoma Mimicking a Lung Tumor as the Initial Finding of Vascular Ehlers-Danlos Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Eun Ju; Lee, Ki Nam; Choi, Pil Jo [Dept. of Radiology, Dong-A University Medicine Center, Dong-A University College of Medicine, Busan (Korea, Republic of); Ki, Chang Seok [Dept. of Radiology, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-09-15

    The vascular type of Ehlers-Danlos syndrome (vEDS) is an uncommon inherited disorder characterized by abnormalities in type III collagen, presenting itself as arterial dissection or rupture. We report a case of an isolated pulmonary hematoma mimicking a lung tumor in an 18-year-old man which turned out to be the initial finding of vEDS. Pneumothorax and hemothorax occurred repeatedly for 15 months following the surgical removal of the mass, and were treated by repeated left upper and lower lobectomy and thoracotomy. The diagnosis of vEDS was confirmed by pathologic and genetic studies.

  10. An Isolated Pulmonary Hematoma Mimicking a Lung Tumor as the Initial Finding of Vascular Ehlers-Danlos Syndrome

    International Nuclear Information System (INIS)

    Kang, Eun Ju; Lee, Ki Nam; Choi, Pil Jo; Ki, Chang Seok

    2012-01-01

    The vascular type of Ehlers-Danlos syndrome (vEDS) is an uncommon inherited disorder characterized by abnormalities in type III collagen, presenting itself as arterial dissection or rupture. We report a case of an isolated pulmonary hematoma mimicking a lung tumor in an 18-year-old man which turned out to be the initial finding of vEDS. Pneumothorax and hemothorax occurred repeatedly for 15 months following the surgical removal of the mass, and were treated by repeated left upper and lower lobectomy and thoracotomy. The diagnosis of vEDS was confirmed by pathologic and genetic studies.

  11. Isolation and Expression of the Lysis Genes of Actinomyces naeslundii Phage Av-1

    Science.gov (United States)

    Delisle, Allan L.; Barcak, Gerard J.; Guo, Ming

    2006-01-01

    Like most gram-positive oral bacteria, Actinomyces naeslundii is resistant to salivary lysozyme and to most other lytic enzymes. We are interested in studying the lysins of phages of this important oral bacterium as potential diagnostic and therapeutic agents. To identify the Actinomyces phage genes encoding these species-specific enzymes in Escherichia coli, we constructed a new cloning vector, pAD330, that can be used to enrich for and isolate phage holin genes, which are located adjacent to the lysin genes in most phage genomes. Cloned holin insert sequences were used to design sequencing primers to identify nearby lysin genes by using whole phage DNA as the template. From partial digestions of A. naeslundii phage Av-1 genomic DNA we were able to clone, in independent experiments, inserts that complemented the defective λ holin in pAD330, as evidenced by extensive lysis after thermal induction. The DNA sequence of the inserts in these plasmids revealed that both contained the complete lysis region of Av-1, which is comprised of two holin-like genes, designated holA and holB, and an endolysin gene, designated lysA. We were able to subclone and express these genes and determine some of the functional properties of their gene products. PMID:16461656

  12. Analysis of five streptokinase formulations using the euglobulin lysis test and the plasminogen activation assay

    Directory of Open Access Journals (Sweden)

    Couto L.T.

    2004-01-01

    Full Text Available Streptokinase, a 47-kDa protein isolated and secreted by most group A, C and G ß-hemolytic streptococci, interacts with and activates human protein plasminogen to form an active complex capable of converting other plasminogen molecules to plasmin. Our objective was to compare five streptokinase formulations commercially available in Brazil in terms of their activity in the in vitro tests of euglobulin clot formation and of the hydrolysis of the plasmin-specific substrate S-2251(TM. Euglobulin lysis time was determined using a 96-well microtiter plate. Initially, human thrombin (10 IU/ml and streptokinase were placed in individual wells, clot formation was initiated by the addition of plasma euglobulin, and turbidity was measured at 340 nm every 30 s. In the second assay, plasminogen activation was measured using the plasmin-specific substrate S-2251(TM. Streptase(TM was used as the reference formulation because it presented the strongest fibrinolytic activity in the euglobulin lysis test. The Unitinase(TM and Solustrep(TM formulations were the weakest, showing about 50% activity compared to the reference formulation. All streptokinases tested activated plasminogen but significant differences were observed. In terms of total S-2251(TM activity per vial, Streptase(TM (75.7 ± 5.0 units and Streptonase(TM (94.7 ± 4.6 units had the highest activity, while Unitinase(TM (31.0 ± 2.4 units and Strek(TM (32.9 ± 3.3 units had the weakest activity. Solustrep(TM (53.3 ± 2.7 units presented intermediate activity. The variations among the different formulations for both euglobulin lysis test and chromogenic substrate hydrolysis correlated with the SDS-PAGE densitometric results for the amount of 47-kDa protein. These data show that the commercially available clinical streptokinase formulations vary significantly in their in vitro activity. Whether these differences have clinical implications needs to be investigated.

  13. HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells.

    Science.gov (United States)

    Gornalusse, Germán G; Hirata, Roli K; Funk, Sarah E; Riolobos, Laura; Lopes, Vanda S; Manske, Gabriel; Prunkard, Donna; Colunga, Aric G; Hanafi, Laïla-Aïcha; Clegg, Dennis O; Turtle, Cameron; Russell, David W

    2017-08-01

    Polymorphisms in the human leukocyte antigen (HLA) class I genes can cause the rejection of pluripotent stem cell (PSC)-derived products in allogeneic recipients. Disruption of the Beta-2 Microglobulin (B2M) gene eliminates surface expression of all class I molecules, but leaves the cells vulnerable to lysis by natural killer (NK) cells. Here we show that this 'missing-self' response can be prevented by forced expression of minimally polymorphic HLA-E molecules. We use adeno-associated virus (AAV)-mediated gene editing to knock in HLA-E genes at the B2M locus in human PSCs in a manner that confers inducible, regulated, surface expression of HLA-E single-chain dimers (fused to B2M) or trimers (fused to B2M and a peptide antigen), without surface expression of HLA-A, B or C. These HLA-engineered PSCs and their differentiated derivatives are not recognized as allogeneic by CD8 + T cells, do not bind anti-HLA antibodies and are resistant to NK-mediated lysis. Our approach provides a potential source of universal donor cells for applications where the differentiated derivatives lack HLA class II expression.

  14. HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells

    Science.gov (United States)

    Gornalusse, Germán G.; Hirata, Roli K.; Funk, Sarah; Riolobos, Laura; Lopes, Vanda S.; Manske, Gabriel; Prunkard, Donna; Colunga, Aric G.; Hanafi, Laïla-Aïcha; Clegg, Dennis O.; Turtle, Cameron; Russell, David W.

    2017-01-01

    Polymorphisms in the human leukocyte antigen (HLA) class I genes can cause the rejection of pluripotent stem cell (PSC)-derived products in allogeneic recipients. Disruption of the Beta-2 Microglobulin (B2M) gene eliminates surface expression of all class I molecules, but leaves the cells vulnerable to lysis by natural killer (NK) cells. Here we show that this ‘missing self’ response can be prevented by forced expression of minimally polymorphic HLA-E molecules. We use adeno-associated virus (AAV)-mediated gene editing to knock in HLA-E genes at the B2M locus in human PSCs in a manner that confers inducible, regulated, surface expression of HLA-E single-chain dimers (fused to B2M) or trimers (fused to B2M and a peptide antigen), without surface expression of HLA-A, B or C. These HLA-engineered PSCs and their differentiated derivatives are not recognized as allogeneic by CD8+ T cells, do not bind anti-HLA antibodies, and are resistant to NK-mediated lysis. Our approach provides a potential source of universal donor cells for applications where the differentiated derivatives lack HLA class II expression. PMID:28504668

  15. Sinusoidal Obstruction Syndrome during Treatment for Wilms' Tumor: A Life-threatening Complication.

    Science.gov (United States)

    Totadri, Sidharth; Trehan, Amita; Bansal, Deepak; Jain, Richa

    2017-01-01

    Survival rates exceed 90% in Wilms' tumor (WT). Actinomycin-D (ACT-D) which is indispensable in the management of WT is associated with the development of sinusoidal obstruction syndrome (SOS), a potentially fatal complication. The aim is to study the presentation, management, and outcome of SOS complicating ACT-D administration in WT. Retrospective file review conducted in a Pediatric Hematology-Oncology unit. Patients diagnosed and treated for WT from January 2012 to December 2015 were analyzed. SOS was diagnosed clinically, based on McDonalds criteria, requiring two of the following: jaundice, hepatomegaly and/or right upper quadrant pain, weight gain with or without ascites. Of 104 patients treated, SOS occurred in 5 (4.8%). Age: 6 months to 5 years, 3 were girls. Tumor involved left kidney in 3, right in 1 and a horseshoe kidney in 1. Histopathology was consistent with WT in 4 and clear cell sarcoma kidney in 1. One had pulmonary metastases. Three developed SOS preoperatively and two during adjuvant chemotherapy. None received radiotherapy. Clinical manifestations comprised of jaundice, hepatomegaly, ascites/weight gain, respiratory distress, hypotension, and encephalopathy. Laboratory findings included thrombocytopenia, elevated serum transaminases, and coagulopathy. Treatment included fluid restriction, broad spectrum antibiotics, and transfusional support. Two children received N-acetyl cysteine infusion. Defibrotide was administered to two patients. Four recovered and one succumbed to multi-organ failure. Two patients were safely re-challenged with 50% doses of ACT-D. SOS is a clinical diagnosis. Systematic supportive care can enable complete recovery. Under close monitoring, re-challenge of ACT-D can be performed in gradually escalating doses.

  16. Highly efficient elimination of colorectal tumor-initiating cells by an EpCAM/CD3-bispecific antibody engaging human T cells.

    Directory of Open Access Journals (Sweden)

    Ines Herrmann

    2010-10-01

    Full Text Available With their resistance to genotoxic and anti-proliferative drugs and potential to grow tumors and metastases from very few cells, cancer stem or tumor-initiating cells (TICs are a severe limitation for the treatment of cancer by conventional therapies. Here, we explored whether human T cells that are redirected via an EpCAM/CD3-bispecific antibody called MT110 can lyse colorectal TICs and prevent tumor growth from TICs. MT110 recognizes EpCAM, a cell adhesion molecule expressed on TICs from diverse human carcinoma, which was recently shown to promote tumor growth through engagement of elements of the wnt pathway. MT110 was highly potent in mediating complete redirected lysis of KRAS-, PI3 kinase- and BRAF-mutated colorectal TICs, as demonstrated in a soft agar assay. In immunodeficient mice, MT110 prevented growth of tumors from a 5,000-fold excess of a minimally tumorigenic TIC dose. T cells engaged by MT110 may provide a potent therapeutic means to eradicate TICs and bulk tumor cells derived thereof.

  17. [Intraoperative lysis and neurostimulation as added therapy in surgery of popliteal artery aneurysm].

    Science.gov (United States)

    Peiper, C; Heye, K; Ktenidis, K; Horsch, S

    1997-01-01

    Additional therapy of symptomatic popliteal artery aneurysm includes intraoperative lysis for the treatment of the descending thrombosis and spinal cord stimulation for cases of chronic deterioration of the peripheral perfusion state. Between 1989 and 1996, we treated 50 patients with 55 symptomatic aneurysms using this concept, 18 of them as emergency cases. We reached a postoperative amputation rate of 12.7% and good long-term functional results in 34 of 37 patients.

  18. Disseminated intravascular coagulation in solid tumors

    International Nuclear Information System (INIS)

    Terzieff, V.; Alonso, I.; Vázquez, A.

    2004-01-01

    It is estimated that 20-25% of cases of disseminated intravascular coagulation (DIC) relate to an underlying neoplasia primarily hematologic. It is estimated that about 5% of patients with solid tumors have CID clinic, although the incidence of subclinical alterations is much higher. The CID is not limited to the activation of the coagulation cascade, which leads to bleeding micro thrombosis and consumption of coagulation factors. Solid tumors are frequently associated adenocarcinomas producers mucin (especially gastric), usually in the context of a disseminated disease. The mucin may act as a promoter of the cascade, but probably it is a multi-event. High levels of TNF to produced by the tumor mass and chemotherapy-induced cell lysis have Also linked. Although the bleeding is usually oriented diagnosis, the most frequent cause of death is thrombosis. There are no specific tests for diagnosis. Elevated levels of D-dimer and products oriented fibrinogen degradation diagnosis. No reduction fibrinogen and almost always, one thrombocytopenia consumption. Treatment is complex and there is no consensus on many points. To recover the lost factors for consumption, it is recommended to use fresh frozen plasma and / or washed red blood cells. the heparin anticoagulation low dose is indicated since the disease causal can not be controlled quickly, but should not be initiated if there thrombocytopenia 50.000.El under profuse bleeding can require the use of tranexamic acid or EACA. Acute DIC, the case of our patient, is rare and very serious

  19. Impaired respiration elicits SrrAB-dependent programmed cell lysis and biofilm formation in Staphylococcus aureus

    Science.gov (United States)

    Mashruwala, Ameya A; van de Guchte, Adriana; Boyd, Jeffrey M

    2017-01-01

    Biofilms are communities of microorganisms attached to a surface or each other. Biofilm-associated cells are the etiologic agents of recurrent Staphylococcus aureus infections. Infected human tissues are hypoxic or anoxic. S. aureus increases biofilm formation in response to hypoxia, but how this occurs is unknown. In the current study we report that oxygen influences biofilm formation in its capacity as a terminal electron acceptor for cellular respiration. Genetic, physiological, or chemical inhibition of respiratory processes elicited increased biofilm formation. Impaired respiration led to increased cell lysis via divergent regulation of two processes: increased expression of the AtlA murein hydrolase and decreased expression of wall-teichoic acids. The AltA-dependent release of cytosolic DNA contributed to increased biofilm formation. Further, cell lysis and biofilm formation were governed by the SrrAB two-component regulatory system. Data presented support a model wherein SrrAB-dependent biofilm formation occurs in response to the accumulation of reduced menaquinone. DOI: http://dx.doi.org/10.7554/eLife.23845.001 PMID:28221135

  20. Retrospective study of paraneoplastic neurological syndromes in a Chinese Han population from Shandong, East China.

    Science.gov (United States)

    Miao, Shuai; Liao, Shaohua; Li, Heng; Niu, Bing; Hu, Huaiqiang; Qian, Ying; Guo, Hongwei; Cao, Bingzhen

    2018-02-05

    To analyze the clinical features, diagnostic strategies and therapeutic methods associated with paraneoplastic neurological syndromes. A retrospective study of paraneoplastic neurological syndromes was performed at a single center in Shandong, East China. The medical records and follow-up data of 28 patients were intensively reviewed between February 2011 and December 2014. Twenty-four (85.7%) patients experienced subacute or chronic onset of disease, and the most common symptoms reported were mild myasthenia and paresthesias. Twenty-five (89.3%) patients presented nervous system lesions prior to occult tumors, and the median time frame between paraneoplastic neurological syndromes onset and the diagnosis of a tumor was 15 weeks. Sensorimotor neuropathy, Lambert-Eaton myasthenic syndrome and limbic encephalitis were the three most common neurological syndromes reported. Elevated serum tumor markers were observed in 44.0% of patients, while 40.7% of patients were positive for onconeural antibodies. Tumors were detected in 21 (75.0%) patients after repeated whole-body screening, and lung carcinomas were the most common primary tumor detected. Seventeen patients received anti-tumor or immunological therapy, and clinical symptoms were relieved in 13 (76.5%) of these patients. In the majority of paraneoplastic neurological syndromes patients, the onset of disease is subacute or chronic with mild clinical symptoms. Nervous system lesions usually occur prior to occult tumors with complicated and various clinical manifestations. Neither tumor markers nor onconeural antibodies exhibit a high rate of occurrence, while repeated whole-body screening is helpful in identifying occult tumors. Early diagnosis and treatment are crucial to these patients.

  1. Role for Genetic Anticipation in Lynch Syndrome

    DEFF Research Database (Denmark)

    Nilbert, Mef; Timshel, Susanne; Bernstein, Inge

    2009-01-01

    PURPOSE: Anticipation (ie, an earlier age at onset in successive generations) is linked to repeat expansion in neurodegenerative syndromes, whereas its role in hereditary cancer is unclear. We assessed anticipation in Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]), in which DNA...... mismatch repair (MMR) defects cause early and accelerated tumor development with a broad tumor spectrum. PATIENTS AND METHODS: In the population-based Danish HNPCC registry, 407 MMR gene mutation carriers who had developed cancer associated with Lynch syndrome, were identified. These individuals formed 290....... The effect remained when cancers diagnosed at surveillance were excluded, applied to maternal as well as paternal inheritance, and was independent of the MMR gene mutated. CONCLUSION: The effect from anticipation demonstrated in this large, population-based Lynch syndrome cohort underscores the need...

  2. Lysis of Gymnodinium breve by cultures of the green alga Nannochloris eucaryotum.

    Science.gov (United States)

    Pérez, E; Sawyers, W G; Martin, D F

    2001-01-01

    Laboratory cultures of Florida's red tide organism, Gymnodinium breve, were killed by the green alga Nannochloris eucaryotum. Studies involved organism-organism interaction as well as organism-cell-free culture (N. eucaryotum) interaction. Both studies demonstrated that N. eucaryotum adversely affected Florida's red tide organism. The lysis has been attributed to compounds called APONINs (apparent oceanic naturally occurring cytolins). N. eucaryotum crude APONIN was extracted from cell-free cultures, partially purified and fractionated. The fractions were bioassayed against G. breve, and 'fingerprints' of the deleterious fractions were obtained.

  3. Microfluidic systems and methods for transport and lysis of cells and analysis of cell lysate

    Science.gov (United States)

    Culbertson, Christopher T [Oak Ridge, TN; Jacobson, Stephen C [Knoxville, TN; McClain, Maxine A [Knoxville, TN; Ramsey, J Michael [Knoxville, TN

    2008-09-02

    Microfluidic systems and methods are disclosed which are adapted to transport and lyse cellular components of a test sample for analysis. The disclosed microfluidic systems and methods, which employ an electric field to rupture the cell membrane, cause unusually rapid lysis, thereby minimizing continued cellular activity and resulting in greater accuracy of analysis of cell processes.

  4. Clinicopathological comparison of colorectal and endometrial carcinomas in patients with Lynch-like syndrome versus patients with Lynch syndrome.

    Science.gov (United States)

    Mas-Moya, Jenny; Dudley, Beth; Brand, Randall E; Thull, Darcy; Bahary, Nathan; Nikiforova, Marina N; Pai, Reetesh K

    2015-11-01

    Screening for DNA mismatch repair (MMR) deficiency in colorectal and endometrial carcinomas identifies patients at risk for Lynch syndrome. Some patients with MMR-deficient tumors have no evidence of a germline mutation and have been described as having Lynch-like syndrome. We compared the clinicopathological features of colorectal and endometrial carcinomas in patients with Lynch-like syndrome and Lynch syndrome. Universal screening identified 356 (10.6%) of 3352 patients with colorectal carcinoma and 72 (33%) of 215 patients with endometrial carcinoma with deficient DNA MMR. Sixty-six patients underwent germline mutation analysis with 45 patients (68%) having evidence of a germline MMR gene mutation confirming Lynch syndrome and 21 patients (32%) having Lynch-like syndrome with no evidence of a germline mutation. Most patients with Lynch-like syndrome had carcinoma involving the right colon compared to patients with Lynch syndrome (93% versus 45%; P Lynch syndrome confirmed by germline mutation analysis. Synchronous or metachronous Lynch syndrome-associated carcinoma was more frequently identified in patients with Lynch syndrome compared to Lynch-like syndrome (38% versus 7%; P = .04). There were no significant differences in clinicopathological variables between patients with Lynch-like syndrome and Lynch syndrome with endometrial carcinoma. In summary, 32% of patients with MMR deficiency concerning Lynch syndrome will have Lynch-like syndrome. Our results demonstrate that patients with Lynch-like syndrome are more likely to have right-sided colorectal carcinoma, less likely to have synchronous or metachronous Lynch syndrome-associated carcinoma, and less likely to demonstrate isolated loss of MSH6 expression within their tumor. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Optimization of dendritic cell loading with tumor cell lysates for cancer immunotherapy.

    Science.gov (United States)

    Hatfield, Paul; Merrick, Alison E; West, Emma; O'Donnell, Dearbhaile; Selby, Peter; Vile, Richard; Melcher, Alan A

    2008-09-01

    The immune response to cancer is critically determined by the way in which tumor cells die. As necrotic, stress-associated death can be associated with activation of antitumor immunity, whole tumor cell antigen loading strategies for dendritic cell (DC)-based vaccination have commonly used freeze-thaw "necrotic" lysates as an immunogenic source of tumor-associated antigens. In this study, the effect of such lysates on the ability of DCs to mature in response to well-established maturation stimuli was examined, and methods to enhance lysate-induced DC activation explored. Freeze-thaw lysates were prepared from murine tumor cell lines and their effects on bone marrow-derived DC maturation and function examined. Unmodified freeze-thaw tumor cell lysates inhibited the toll-like receptor-induced maturation and function of bone marrow-derived DCs, preventing up-regulation of CD40, CD86, and major histocompatibility complex class II, and reducing secretion of inflammatory cytokines [interleukin (IL)-12 p70, tumor necrosis factor-alpha, and IL-6]. Although IL-10 secretion was increased by lysate-pulsed DCs, this was not responsible for the observed suppression of IL-12. Although activation of the nuclear factor-kappaB pathway remained intact, the kinase activity of phosphorylated p38 mitogen-activated protein kinase was inhibited in lysate-pulsed DCs. Lysate-induced DC suppression was partially reversed in vitro by induction of tumor cell stress before lysis, and only DCs loaded with stressed lysates afforded protection against tumor challenge in vivo. These data suggest that ex vivo freeze-thaw of tumor cells does not effectively mimic in vivo immunogenic necrosis, and advocates careful characterization and optimization of tumor cell-derived vaccine sources for cancer immunotherapy.

  6. Primary Testicular Carcinoid Tumor presenting as Carcinoid Heart Disease

    Directory of Open Access Journals (Sweden)

    Manjunath L Chikkaraddi

    2015-01-01

    Full Text Available Primary carcinoid tumors of the testis are very rare, and they seldom present with carcinoid syndrome. We report a hereto unreported instance, where a patient with a long-standing testicular mass presented with carcinoid heart disease, an uncommon form of carcinoid syndrome. He presented with symptoms of right heart failure, episodic facial flushing and was found to have severe right-sided valvular heart disease. His urinary 5-hydroxy indole acetic acid level was elevated. He underwent orchidectomy and the histopathology confirmed a testicular carcinoid tumor.

  7. Three molecular pathways model colorectal carcinogenesis in Lynch syndrome.

    Science.gov (United States)

    Ahadova, Aysel; Gallon, Richard; Gebert, Johannes; Ballhausen, Alexej; Endris, Volker; Kirchner, Martina; Stenzinger, Albrecht; Burn, John; von Knebel Doeberitz, Magnus; Bläker, Hendrik; Kloor, Matthias

    2018-07-01

    Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR) genes. MMR deficiency has long been regarded as a secondary event in the pathogenesis of Lynch syndrome colorectal cancers. Recently, this concept has been challenged by the discovery of MMR-deficient crypt foci in the normal mucosa. We aimed to reconstruct colorectal carcinogenesis in Lynch syndrome by collecting molecular and histology evidence from Lynch syndrome adenomas and carcinomas. We determined the frequency of MMR deficiency in adenomas from Lynch syndrome mutation carriers by immunohistochemistry and by systematic literature analysis. To trace back the pathways of pathogenesis, histological growth patterns and mutational signatures were analyzed in Lynch syndrome colorectal cancers. Literature and immunohistochemistry analysis demonstrated MMR deficiency in 491 (76.7%) out of 640 adenomas (95% CI: 73.3% to 79.8%) from Lynch syndrome mutation carriers. Histologically normal MMR-deficient crypts were found directly adjacent to dysplastic adenoma tissue, proving their role as tumor precursors in Lynch syndrome. Accordingly, mutation signature analysis in Lynch colorectal cancers revealed that KRAS and APC mutations commonly occur after the onset of MMR deficiency. Tumors lacking evidence of polypous growth frequently presented with CTNNB1 and TP53 mutations. Our findings demonstrate that Lynch syndrome colorectal cancers can develop through three pathways, with MMR deficiency commonly representing an early and possibly initiating event. This underlines that targeting MMR-deficient cells by chemoprevention or vaccines against MMR deficiency-induced frameshift peptide neoantigens holds promise for tumor prevention in Lynch syndrome. © 2018 UICC.

  8. Diagnostic Modalities for FGF23-Producing Tumors in Patients with Tumor-Induced Osteomalacia

    Directory of Open Access Journals (Sweden)

    Seiji Fukumoto

    2014-06-01

    Full Text Available Fibroblast growth factor 23 (FGF23 is a hormone that is produced by osteocytes and regulates phosphate and vitamin D metabolism through binding to the Klotho-FGF receptor complex. Excessive actions of FGF23 cause several kinds of hypophosphatemic rickets/osteomalacia. Tumor-induced rickets/osteomalacia (TIO is a paraneoplastic syndrome caused by overproduction of FGF23 from the responsible tumors. Because TIO is cured by complete resection of the causative tumors, it is of great clinical importance to locate these tumors. Several imaging methods including skeletal survey by magnetic resonance imaging and octreotide scintigraphy have been used to identify the tumors that cause TIO. However, none of these imaging studies indicate that the detected tumors are actually producing FGF23. Recently, systemic venous sampling was conducted for locating FGF23-producing tumor in suspected patients with TIO and demonstrated that this test might be beneficial to a subset of patient. Further studies with more patients are necessary to establish the clinical utility of venous sampling in patients with TIO.

  9. Evaluation of tumor-induced osteomalacia with 111In-pentetreotide scintigraphy.

    Science.gov (United States)

    Palot Manzil, Fathima Fijula; Bhambhvani, Pradeep G; O'Malley, Janis P

    2013-12-01

    In cases of nonhereditary osteomalacia associated with hypophosphatemia and inadequate response to vitamin D supplementation, one should consider the possibility of tumor-induced osteomalacia, a paraneoplastic syndrome caused by small mesenchymal tumors often found in obscure locations. We present a case of tumor-induced osteomalacia in which (111)In-pentetreotide scintigraphy aided in accurate localization of the culprit brachial plexus tumor and cure after resection.

  10. Leukocyte function-associated antigen-1-dependent lysis of Fas+ (CD95+/Apo-1+) innocent bystanders by antigen-specific CD8+ CTL.

    Science.gov (United States)

    Kojima, H; Eshima, K; Takayama, H; Sitkovsky, M V

    1997-09-15

    Exquisite specificity toward Ag-bearing cells (cognate targets) is one of the most important properties of CD8+ CTL-mediated cytotoxicity. Using highly Ag-specific CD8+ CTL lines and clones, which spare noncognate, Ag-free targets, we found that in the presence of Ag-bearing targets the CTL acquire the ability to lyse noncognate target cells (bystanders). It is shown that the unexpectedly rapid and efficient lysis of bystanders by Ag-activated CTL is mediated by a Fas ligand (FasL)/Fas-based mechanism and does not depend on perforin. The CTL lysed Fas-expressing bystanders, but spared the Fas-negative or anti-Fas mAb-resistant bystander cells. Accordingly, the FasL-deficient gld/gld CTL did not kill bystanders, while perforin-deficient CTL did. Unlike anti-Fas mAb-induced cell death, the lysis of bystanders was not only FasL/Fas dependent but also required adhesion molecule LFA-1 on the surface of the activated CTL. Lysis of bystanders is viewed as acceptable "collateral" damage, but the persistent presence of activated CTL could result in immunopathologies involving functional Fas-expressing tissues.

  11. Molecular subtype classification of urothelial carcinoma in Lynch syndrome

    DEFF Research Database (Denmark)

    Therkildsen, Christina; Eriksson, Pontus; Höglund, Mattias

    2018-01-01

    Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome......-associated UC. Thus, Lynch syndrome-associated UC of the upper urinary tract and the urinary bladder were identified in the Danish hereditary non-polyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial...... carcinomas. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed...

  12. Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in pleuropulmonary blastoma / DICER1 syndrome: a unique variant of the two-hit tumor suppression model [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Mark Brenneman

    2018-01-01

    Full Text Available Pleuropulmonary blastoma (PPB is the most frequent pediatric lung tumor and often the first indication of a pleiotropic cancer predisposition, DICER1 syndrome, comprising a range of other individually rare, benign and malignant tumors of childhood and early adulthood. The genetics of DICER1-associated tumorigenesis are unusual in that tumors typically bear neomorphic missense mutations at one of five specific “hotspot” codons within the RNase IIIb domain of DICER 1, combined with complete loss of function (LOF in the other allele. We analyzed a cohort of 124 PPB children for predisposing DICER1 mutations and sought correlations with clinical phenotypes. Over 70% have inherited or de novo germline LOF mutations, most of which truncate the DICER1 open reading frame. We identified a minority of patients who have no germline mutation, but are instead mosaic for predisposing DICER1 mutations. Mosaicism for RNase IIIb domain hotspot mutations defines a special category of DICER1 syndrome patients, clinically distinguished from those with germline or mosaic LOF mutations by earlier onsets and numerous discrete foci of neoplastic disease involving multiple syndromic organ sites. A final category of PBB patients lack predisposing germline or mosaic mutations and have sporadic (rather than syndromic disease limited to a single PPB tumor bearing tumor-specific RNase IIIb and LOF mutations. We propose that acquisition of a neomorphic RNase IIIb domain mutation is the rate limiting event in DICER1-associated tumorigenesis, and that distinct clinical phenotypes associated with mutational categories reflect the temporal order in which LOF and RNase IIIb domain mutations are acquired during development.

  13. END STAGE RENAL DISEASE IN PATIENTS WITH WILMS TUMOR: RESULTS FROM THE NATIONAL WILMS TUMOR STUDY GROUP AND THE U.S. RENAL DATA SYSTEM

    OpenAIRE

    Breslow, Norman E.; Grigoriev, Yevgeny A.; Peterson, Susan M.; Collins, Allan J.; Ritchey, Michael L.; Green, Daniel M.

    2005-01-01

    Purpose: To accurately assess the full spectrum of end stage renal disease (ESRD) in Wilms tumor survivors by combining the unique resources of the National Wilms Tumor Study Group (NWTSG) and the U.S. Renal Data System (USRDS), and to confirm preliminary reports of an increased incidence of ESRD in those with the Wilms tumor-aniridia (WAGR) syndrome.

  14. A case report of Muir-Torre syndrome in a woman with breast cancer and MSI-Low skin squamous cell carcinoma

    OpenAIRE

    Kientz, Caroline; Joly, Marie-Odile; Faivre, Laurence; Clemenson, Alix; Dalac, Sophie; Lepage, C?me; Chapusot, Caroline; Jacquot, Caroline; Schiappa, Renaud; Lebrun, Marine

    2017-01-01

    Background The tumor spectrum in the Lynch syndrome is well defined, comprising an increased risk of developing colonic and extracolonic malignancies. Muir-Torre syndrome is a variant with a higher risk of skin disease. Patients have been described carrying mutations in the mismatch repair genes and presenting tumors with unusual histology or affected organ not part of the Lynch syndrome spectrum. Hence, the real link between Lynch syndrome, or Muir-Torre syndrome, and these tumors remains di...

  15. RNA integrity as a quality indicator during the first steps of RNP purifications : A comparison of yeast lysis methods

    Directory of Open Access Journals (Sweden)

    Jansen Ralf-Peter

    2004-10-01

    Full Text Available Abstract Background The completion of several genome-sequencing projects has increased our need to assign functions to newly identified genes. The presence of a specific protein domain has been used as the determinant for suggesting a function for these new genes. In the case of proteins that are predicted to interact with mRNA, most RNAs bound by these proteins are still unknown. In yeast, several protocols for the identification of protein-protein interactions in high-throughput analyses have been developed during the last years leading to an increased understanding of cellular proteomics. If any of these protocols or similar approaches shall be used for the identification of mRNA-protein complexes, the integrity of mRNA is a critical factor. Results We compared the effect of different lysis protocols on RNA integrity. We report dramatic differences in RNA stability depending on the method used for yeast cell lysis. Glass bead milling and French Press lead to degraded mRNAs even in the presence of RNase inhibitors. Thus, they are not suitable to purify intact mRNP complexes or to identify specific mRNAs bound to proteins. Conclusion We suggest a novel protocol, grinding deep-frozen cells, for the preparation of protein extracts that contain intact RNAs, as lysis method for the purification of mRNA-protein complexes from yeast cells.

  16. Very High Throughput Electrical Cell Lysis and Extraction of Intracellular Compounds Using 3D Carbon Electrodes in Lab-on-a-Chip Devices

    Directory of Open Access Journals (Sweden)

    Philippe Renaud

    2012-08-01

    Full Text Available Here we present an electrical lysis throughput of 600 microliters per minute at high cell density (108 yeast cells per ml with 90% efficiency, thus improving the current common throughput of one microliter per minute. We also demonstrate the extraction of intracellular luciferase from mammalian cells with efficiency comparable to off-chip bulk chemical lysis. The goal of this work is to develop a sample preparation module that can act as a stand-alone device or be integrated to other functions already demonstrated in miniaturized devices, including sorting and analysis, towards a true lab-on-a-chip.

  17. Sinusoidal Obstruction Syndrome during Treatment for Wilms' Tumor: A Life-threatening Complication

    Science.gov (United States)

    Totadri, Sidharth; Trehan, Amita; Bansal, Deepak; Jain, Richa

    2017-01-01

    Context: Survival rates exceed 90% in Wilms' tumor (WT). Actinomycin-D (ACT-D) which is indispensable in the management of WT is associated with the development of sinusoidal obstruction syndrome (SOS), a potentially fatal complication. Aims: The aim is to study the presentation, management, and outcome of SOS complicating ACT-D administration in WT. Settings and Design: Retrospective file review conducted in a Pediatric Hematology-Oncology unit. Materials and Methods: Patients diagnosed and treated for WT from January 2012 to December 2015 were analyzed. SOS was diagnosed clinically, based on McDonalds criteria, requiring two of the following: jaundice, hepatomegaly and/or right upper quadrant pain, weight gain with or without ascites. Results: Of 104 patients treated, SOS occurred in 5 (4.8%). Age: 6 months to 5 years, 3 were girls. Tumor involved left kidney in 3, right in 1 and a horseshoe kidney in 1. Histopathology was consistent with WT in 4 and clear cell sarcoma kidney in 1. One had pulmonary metastases. Three developed SOS preoperatively and two during adjuvant chemotherapy. None received radiotherapy. Clinical manifestations comprised of jaundice, hepatomegaly, ascites/weight gain, respiratory distress, hypotension, and encephalopathy. Laboratory findings included thrombocytopenia, elevated serum transaminases, and coagulopathy. Treatment included fluid restriction, broad spectrum antibiotics, and transfusional support. Two children received N-acetyl cysteine infusion. Defibrotide was administered to two patients. Four recovered and one succumbed to multi-organ failure. Two patients were safely re-challenged with 50% doses of ACT-D. Conclusions: SOS is a clinical diagnosis. Systematic supportive care can enable complete recovery. Under close monitoring, re-challenge of ACT-D can be performed in gradually escalating doses. PMID:29333010

  18. Carcinoids tumors of the digestive tract

    International Nuclear Information System (INIS)

    Carvalho, S.M.R. de; Prais, M.; Matushita, J.P.K.; Matushita, J.S.

    1989-01-01

    Eighteen cases of carcinoid tumors in the digestive tract have been analyzed. They have been selected at Hospital dos Servidores do Estado do Rio de Janeiro, taking into account patients, age and sex, lesions' location and size, clinical manifestations, presence of metastases as well as a classical carcinoid syndrome establisment. Carcinoid tumors come from the digestive tract 'argenta fim'' cells, the ones which produce endocrines. Such endocrines are responsible for a great number of clinical manifestations. The classical syndrome is directly related to the presence of hepatic metastases. The authors propose to correlate what has been found with descriptions in medical literature emphasizing the radiographic aspects which have been observed. A frequent ''apendicular'' location and the difficulty of giving a precise diagnosis before surgery is also emphasized. (author) [pt

  19. Biological activity analysis of native and recombinant streptokinase using clot lysis and chromogenic substrate assay.

    Science.gov (United States)

    Mahboubi, Arash; Sadjady, Seyyed Kazem; Mirzaei Saleh Abadi, Mohammad; Azadi, Saeed; Solaimanian, Roya

    2012-01-01

    DETERMINATION OF STREPTOKINASE ACTIVITY IS USUALLY ACCOMPLISHED THROUGH TWO ASSAY METHODS: a) Clot lysis, b) Chromogenic substrate assay. In this study the biological activity of two streptokinase products, namely Streptase®, which is a native product and Heberkinasa®, which is a recombinant product, was determined against the third international reference standard using the two forementioned assay methods. The results indicated that whilst the activity of Streptase® was found to be 101 ± 4% and 97 ± 5% of the label claim with Clot lysis and Chromogenic substrate assay respectively, for Heberkinasa® the potency values obtained were 42 ± 5% and 92.5 ± 2% of the label claim respectively. To shed some light on the reason for this finding, the n-terminal sequence of the streptokinase molecules present in the two products was determined. The results showed slight differences in the amino acid sequence of the recombinant product in comparison to the native one at the amino terminus. This finding supports those of other workers who found that n-terminal sequence of the streptokinase molecule can have significant effect on the activity of this protein.

  20. Symptomatic Cushing's syndrome and hyperandrogenemia in a steroid cell ovarian neoplasm: a case report.

    Science.gov (United States)

    Sedhom, Ramy; Hu, Sophia; Ohri, Anupam; Infantino, Dorian; Lubitz, Sara

    2016-10-12

    Malignant steroid cell tumors of the ovary are rare and frequently associated with hormonal abnormalities. There are no guidelines on how to treat rapidly progressive Cushing's syndrome, a medical emergency. A 67-year-old white woman presented to our hospital with rapidly developing signs and symptoms of Cushing's syndrome secondary to a steroid-secreting tumor. Her physical and biochemical manifestations of Cushing's syndrome progressed, and she was not amenable to undergoing conventional chemotherapy secondary to the debilitating effects of high cortisol. Her rapidly progressive Cushing's syndrome ultimately led to her death, despite aggressive medical management with spironolactone, ketoconazole, mitotane, and mifepristone. We report an unusual and rare case of Cushing's syndrome secondary to a malignant steroid cell tumor of the ovary. The case is highlighted to discuss the complications of rapidly progressive Cushing's syndrome, an underreported and often unrecognized endocrine emergency, and the best available evidence for treatment.

  1. Lynch syndrome: still not a familiar picture

    Directory of Open Access Journals (Sweden)

    Hes Frederik J

    2008-02-01

    Full Text Available Abstract Background Germ line mutations in mismatch repair genes underlie Lynch syndrome and predispose carriers for colorectal carcinoma and malignancies in many other organ systems. Case presentation A large Lynch syndrome family with 15 affected family members and involvement in 7 organs is reported. It illustrates a lack of awareness and knowledge about this hereditary tumor syndrome among doctors as well as patients. None of the described family members underwent presymptomatic screening on the basis of the family history. Conclusion Hereditary features, like young age at diagnosis, multiple tumors in multiple organs and a positive family history, should lead to timely referral of suspected cases for genetic counseling and diagnostics. For Lynch syndrome, these features can be found in the Amsterdam and Bethesda criteria. Subsequently, early identification of mutation carriers might have diminished, at least in part, the high and early morbidity and mortality observed in this family.

  2. A Cushing's syndrome patient's severe insomnia and morning blood pressure surge both improved after her left adrenal tumor resection.

    Science.gov (United States)

    Imaizumi, Yuki; Ibaraki, Ai; Asada, Satoshi; Tominaga, Mitsuhiro; Hayashi, Hiroyuki; Tsuchihashi, Takuya; Eguchi, Kazuo; Kario, Kazuomi; Taketomi, Akira

    2016-12-01

    Underlying mechanisms of the elevated risks of hypertension and cardiovascular disease (CVD) in Cushing's syndrome (CS) are unclear. We treated an adult woman with CS because of a cortisol-secreting adrenal tumor. After tumor resection, the 24-h blood pressure (BP) level improved from 156/91 to 131/84 mmHg; the morning BP surprisingly improved from 174/98 to 127/93 mmHg, although we reduced her antihypertensive medication. Her sleep quality (by the Pittsburgh Sleep Quality Index) improved from 7 to 2 points. Disturbed circadian BP rhythm is often observed in CS, but was reported only as altered nocturnal BP fall. This is the first report showing the disappearance of the morning BP surge evaluated by ambulatory BP monitoring with postsurgery sleep quality improvement. Poor-quality sleep, followed by exaggerated morning BP surge may thus be a cause of CS-related cardiovascular events. Sleep quality and BP circadian rhythm evaluations may clarify hypertension and high CVD risk in CS.

  3. Conservative management of pineal tumors - Mayo clinic experience

    International Nuclear Information System (INIS)

    Laws, E.R.; Abay, E.O.; Forbes, G.S.; Grado, G.L.; Bruckman, J.E.; Scott, M.

    1984-01-01

    The typical pineal tumor occurs in an adolescent boy with subacute increased intracranial pressure and Parinaud's syndrome. Diagnosis is confirmed by CT scanning, and long-term survival usually following shunting and radiation therapy. Direct surgical methods for successful treatment of suitable pineal tumors have evolved and may be utilized with relatively low risk in appropriate cases

  4. Reduction of excess sludge in a sequencing batch reactor by lysis-cryptic growth using quick lime for disintegration under low temperature.

    Science.gov (United States)

    Lv, Xiao-Mei; Song, Ju-Sheng; Li, Ji; Zhai, Kun

    2017-08-01

    In the present study, quick-lime-based thermal-alkaline sludge disintegration (SD) under low temperature was combined with cryptic growth to investigate the excess sludge reduction efficiency in the sequencing batch reactor (SBR). The optimized condition of SD was as follows: T = 80℃, pH = 11, t = 180 min, and the SD rate was about 42.1%. With 65.6% of excess sludge disintegrated and returned to the SBR, the system achieved sludge reduction rate of about 40.1%. The lysis-cryptic growth still obtained satisfactory sludge reduction efficiency despite the comparative low SD rate, which suggested that disintegration rate might not be the decisive factor for cryptic-growth-based sludge reduction. Lysis-cryptic growth did not impact the effluent quality, yet the phosphorus removal performance was enhanced, with effluent total phosphorus concentration decreased by 0.3 mg/L (33%). Crystal compounds of calcium phosphate precipitate were detected in the system by Fourier transform infrared spectroscopy and X-ray diffraction, which indicated the phosphorus removal potential of SD using lime. Moreover, endogenous dehydrogenase activity of activated sludge in the lysis-cryptic system was enhanced, which was beneficial for sludge reduction. SD and cryptic growth in the present study demonstrates an economical and effective approach for sludge reduction.

  5. Association of Down's syndrome and testicular cancer.

    Science.gov (United States)

    Dieckmann, K P; Rübe, C; Henke, R P

    1997-05-01

    We present additional clinical evidence for the suspected association of Down's syndrome and testicular germ cell tumors. Four cases of Down's syndrome and testicular cancer are reported. The literature was reviewed for previous cases and analysis regarding common features. The 4 patients were 29 to 35 years old and had clinical stage I seminoma of the testis. Two patients received prophylactic abdominal radiotherapy, 1 is being followed and 1 received adjuvant carboplatin treatment. There was no relapse at followup of 1 to 8 years. One patient also had contralateral cryptorchidism. A total of 16 cases with the association of Down's syndrome and testicular germ cell cancer was documented previously. Evidence for the suspected association of Down's syndrome and testicular cancer is now accumulating. Etiologically it is suspected that, along with genetically determined malformations in many other organs in trisomy 21, the gonads also undergo maldevelopment, thus creating the conditions for step 1 of germ cell tumor oncogenesis in utero. Physicians caring for patients with Down's syndrome should be aware of the possible association with testicular neoplasms.

  6. Comparison of clot lysis activity and biochemical properties of originator tenecteplase (Metalyse® with those of an alleged biosimilar

    Directory of Open Access Journals (Sweden)

    Werner eKliche

    2014-02-01

    Full Text Available The bioengineered tissue plasminogen activator tenecteplase is an important treatment modality of acute myocardial infarction recommended by international guidelines. Following introduction of originator tenecteplase (brand names Metalyse® and TNKase®, a ‘biosimilar’ tenecteplase became available for commercial use in India under the brand name Elaxim® in the absence of Indian biosimilar guidelines which came into force from September 15th, 2012. Based on a report of biochemical and fibrinolytical differences between Metalyse and Elaxim, we have systematically compared them in a range of routine quality testing assays. As compared to Metalyse, Elaxim exhibited less clot lysis activity and contained less of the two-chain form of tenecteplase. Even upon full in vitro conversion to the two-chain form Elaxim exhibited less clot lysis activity. This was linked to differences in sialic acid content and glycosylation pattern with Elaxim exhibiting less bi- and more tetra-antennary glycosylation, leading to different charge heterogeneity profile. Regarding purity, Elaxim contained more tenecteplase aggregates and, in contrast to Metalyse, considerable amounts of Chinese hamster ovary cell protein. Taken together these data demonstrate that Metalyse and Elaxim differ considerably in clot lysis activity and biochemical properties. These data question whether Elaxim indeed can be considered a ‘biosimilar’ of Metalyse, i.e. whether and to which extent the clinical efficacy and safety properties of Metalyse can be extrapolated to Elaxim in the absence of comparative clinical data.

  7. Molecular subtype classification of urothelial carcinoma in Lynch syndrome.

    Science.gov (United States)

    Therkildsen, Christina; Eriksson, Pontus; Höglund, Mattias; Jönsson, Mats; Sjödahl, Gottfrid; Nilbert, Mef; Liedberg, Fredrik

    2018-05-23

    Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome-associated UC. Thus, Lynch syndrome-associated UC of the upper urinary tract and the urinary bladder were identified in the Danish hereditary non-polyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial carcinomas. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed and compared with sporadic bladder cancer. The 41 Lynch syndrome-associated UC developed at a mean age of 61 years with 59% women. mRNA expression profiling and immunostaining classified the majority of the Lynch syndrome-associated UC as Urothelial-like tumors with only 20% being Genomically Unstable, Basal/SCC-like or other subtypes. The subtypes were associated with stage, grade, and microsatellite instability. Comparison to larger data sets revealed that Lynch syndrome-associated UC share molecular similarities with sporadic UC. In conclusion, transcriptomic and immunohistochemical profiling identifies a predominance of the Urothelial-like molecular subtype in Lynch syndrome and reveals that the molecular subtypes of sporadic bladder cancer are relevant also within this hereditary, mismatch-repair defective subset. This article is protected by copyright. All rights reserved. Molecular Oncology (2018) © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  8. PMS2 involvement in patients suspected of Lynch syndrome.

    Science.gov (United States)

    Niessen, Renée C; Kleibeuker, Jan H; Westers, Helga; Jager, Paul O J; Rozeveld, Dennie; Bos, Krista K; Boersma-van Ek, Wytske; Hollema, Harry; Sijmons, Rolf H; Hofstra, Robert M W

    2009-04-01

    It is well-established that germline mutations in the mismatch repair genes MLH1, MSH2, and MSH6 cause Lynch syndrome. However, mutations in these three genes do not account for all Lynch syndrome (suspected) families. Recently, it was shown that germline mutations in another mismatch repair gene, PMS2, play a far more important role in Lynch syndrome than initially thought. To explore this further, we determined the prevalence of pathogenic germline PMS2 mutations in a series of Lynch syndrome-suspected patients. Ninety-seven patients who had early-onset microsatellite instable colorectal or endometrial cancer, or multiple Lynch syndrome-associated tumors and/or were from an Amsterdam Criteria II-positive family were selected for this study. These patients carried no pathogenic germline mutation in MLH1, MSH2, or MSH6. When available, tumors were investigated for immunohistochemical staining (IHC) for PMS2. PMS2 was screened in all patients by exon-by-exon sequencing. We identified four patients with a pathogenic PMS2 mutation (4%) among the 97 patients we selected. IHC of PMS2 was informative in one of the mutation carriers, and in this case, the tumor showed loss of PMS2 expression. In conclusion, our study confirms the finding of previous studies that PMS2 is more frequently involved in Lynch syndrome than originally expected.

  9. Mandibular phosphaturic mesenchymal tumor-mixed connective tissue variant in a young girl.

    Science.gov (United States)

    Luo, Lisa; Low, Nelson; Vandervord, John

    2013-11-01

    Phosphaturic mesenchymal tumor-mixed connective tissue variant (PMTMCT) is an extremely rare tumor associated with tumor-induced osteomalacia. The majority occur in middle age and arise from the extremities. This report describes a young girl with PMTMCT arising in the mandible and with no evidence of paraneoplastic syndrome.

  10. Clot lysis time in platelet-rich plasma: method assessment, comparison with assays in platelet-free and platelet-poor plasmas, and response to tranexamic acid.

    Science.gov (United States)

    Panes, Olga; Padilla, Oslando; Matus, Valeria; Sáez, Claudia G; Berkovits, Alejandro; Pereira, Jaime; Mezzano, Diego

    2012-01-01

    Fibrinolysis dysfunctions cause bleeding or predisposition to thrombosis. Platelets contain several factors of the fibrinolytic system, which could up or down regulate this process. However, the temporal relationship and relative contributions of plasma and platelet components in clot lysis are mostly unknown. We developed a clot lysis time (CLT) assay in platelet-rich plasma (PRP-CLT, with and without stimulation) and compared it to a similar one in platelet-free plasma (PFP) and to another previously reported test in platelet-poor plasma (PPP). We also studied the differential effects of a single dose of tranexamic acid (TXA) on these tests in healthy subjects. PFP- and PPP-CLT were significantly shorter than PRP-CLT, and the three assays were highly correlated (p plasma PAI-1, von Willebrand factor, fibrinogen, LDL-cholesterol, and triglycerides (p platelet aggregation/secretion, platelet counts, and pro-coagulant tests to explore factor X activation by platelets, PRP clotting time, and thrombin generation in PRP. Among all the studied variables, PFP-CLT was independently associated with plasma PAI-1, LDL-cholesterol, and triglycerides and, additionally, stimulated PRP-CLT was also independently associated with plasma fibrinogen. A single 1 g dose of TXA strikingly prolonged all three CLTs, but in contrast to the results without the drug, the lysis times were substantially shorter in non-stimulated or stimulated PRP than in PFP and PPP. This standardized PRP-CLT may become a useful tool to study the role of platelets in clot resistance and lysis. Our results suggest that initially, the platelets enmeshed in the clot slow down the fibrinolysis process. However, the increased clot resistance to lysis induced by TXA is overcome earlier in platelet-rich clots than in PFP or PPP clots. This is likely explained by the display of platelet pro-fibrinolytic effects. Focused research is needed to disclose the mechanisms for the relationship between CLT and plasma

  11. Afferent loop syndrome - a case report

    International Nuclear Information System (INIS)

    Borges, Ana Karina Nascimento; Pinheiro, Marco Antonio Lopes; Galvao, Cristine Norwig

    2000-01-01

    The afferent loop syndrome occurs in patients with previous gastric surgery for tumor, when there is anastomotic edema, use of inappropriate reconstruction technique for gastro jejunostomy or recurrent gastric cancer. Complaints such jaundice, intermittent abdominal distension associated with pain, and vomiting should be investigated in order to rule out this syndrome. (author)

  12. Gorlin Goltz Syndrome : A Review

    Directory of Open Access Journals (Sweden)

    M S Deepa

    2003-01-01

    Full Text Available Gorlin syndrome is a rare autosomal dominant disorder characterized by multiple basal cell carcinomas, odontogenic keratocysts, tumors, and systemic anomalies. Early diac-iosis and treatment :s of utmost importance in reducing the severity of the long-term sequelae of this syndrome. and review of literature documenting both major and lesser-known manifestations of this disorder is given here.

  13. Aggressive fibromatosis of the neck in a patient with Gardner's syndrome

    International Nuclear Information System (INIS)

    Rai, A.T.; Nguyen, T.P.; Hogg, J.P.; Gabriele, F.J.

    2001-01-01

    We report a patient with Gardner's syndrome who, in addition to a total colectomy, had multiple excisions of desmoid tumors in both thighs. He presented with left-sided neck swelling and pain. MRI was highly suggestive of desmoid tumors in multiple neck muscles. To our knowledge this is the first description of diffuse fibromatosis of the neck in association with Gardner's syndrome. (orig.)

  14. Defective nucleolar localization and dominant interfering properties of a parafibromin L95P missense mutant causing the hyperparathyroidism-jaw tumor syndrome

    Science.gov (United States)

    Panicker, Leelamma M.; Zhang, Jian-Hua; Dagur, Pradeep K.; Gastinger, Matthew J.; Simonds, William F.

    2011-01-01

    The hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a familial cancer syndrome that can result from germline inactivation of HRPT2/CDC73, a putative tumor suppressor gene that encodes parafibromin, a component of the transcriptional regulatory PAF1 complex with homology to the yeast protein Cdc73p. The vast majority of HRPT2/CDC73 germline mutations identified have been truncation or frameshift mutations, and loss-of-function due to missense mutation is rare. We report here a kindred with HPT-JT due to a germline L95P missense mutation in parafibromin. The mutant parafibromin was studied in vitro to understand the basis of its presumed loss-of-function. When transfected in cultured cells the L95P mutant was expressed to a lower level than wild-type parafibromin, a difference that was not overcome by inhibition of the proteasome degradation pathway. The L95P mutant parafibromin retained the ability to assemble with endogenous PAF1 complex components as evidenced by co-immunoprecipitation. Analysis of subcellular localization showed that the L95P mutant was markedly deficient in nucleolar localization compared to the wild-type, an impairment likely resulting from disruption of a putative nucleolar localization signal immediately upstream of the L95P mutation. Transfection of the L95P parafibromin mutant, but not the wild type, enhanced cell-cycle progression and increased cell survival in NIH-3T3 and HEK 293 cells, resulting apparently from dominant interference with endogenous parafibromin action. The simultaneous loss of nucleolar localization and acquisition of a growth stimulatory phenotype with the L95P mutation raise the possibility that parafibromin must interact with targets in the nucleolus to fully execute its tumor suppressor functions. PMID:20304979

  15. Marfan syndrome with multiseptate pneumothorax and mandibular fibrous dysplasia

    Directory of Open Access Journals (Sweden)

    Kate A

    2009-01-01

    Full Text Available We describe a rare case of pneumothorax due to Marfan syndrome associated with fibrous dysplasia of the mandible. Marfan syndrome and fibrous dysplasia were possibly due to a common etiological factor. The association between the two and other tumors described in literature related to Marfan syndrome is discussed.

  16. Molecular Pathogenesis of Pancreatic Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Robert Grützmann

    2010-11-01

    Full Text Available Pancreatic neuroendocrine tumors (PNETs are rare primary neoplasms of the pancreas and arise sporadically or in the context of genetically determined syndromes. Depending on hormone production and sensing, PNETs clinically manifest due to a hormone-related syndrome (functional PNET or by symptoms related to tumor bulk effects (non-functional PNET. So far, radical surgical excision is the only therapy to cure the disease. Development of tailored non-surgical approaches has been impeded by the lack of experimental laboratory models and there is, therefore, a limited understanding of the complex cellular and molecular biology of this heterogeneous group of neoplasm. This review aims to summarize current knowledge of tumorigenesis of familial and sporadic PNETs on a cellular and molecular level. Open questions in the field of PNET research are discussed with specific emphasis on the relevance of disease management.

  17. Molecular Pathogenesis of Pancreatic Neuroendocrine Tumors

    International Nuclear Information System (INIS)

    Ehehalt, Florian; Franke, Ellen; Pilarsky, Christian; Grützmann, Robert

    2010-01-01

    Pancreatic neuroendocrine tumors (PNETs) are rare primary neoplasms of the pancreas and arise sporadically or in the context of genetically determined syndromes. Depending on hormone production and sensing, PNETs clinically manifest due to a hormone-related syndrome (functional PNET) or by symptoms related to tumor bulk effects (non-functional PNET). So far, radical surgical excision is the only therapy to cure the disease. Development of tailored non-surgical approaches has been impeded by the lack of experimental laboratory models and there is, therefore, a limited understanding of the complex cellular and molecular biology of this heterogeneous group of neoplasm. This review aims to summarize current knowledge of tumorigenesis of familial and sporadic PNETs on a cellular and molecular level. Open questions in the field of PNET research are discussed with specific emphasis on the relevance of disease management

  18. Inducible and transmissible genetic events and pediatric tumors of the nervous system

    International Nuclear Information System (INIS)

    Rice, Jerry M.

    2006-01-01

    Tumors of the nervous system most often occur in both children and adults as sporadic events with no family history of the disease, but they are also among the clinical manifestations of a significant number of familial cancer syndromes, including familial retinoblastoma, neurofibromatosis 1 and 2, tuberous sclerosis, and Cowden, Turcot, Li-Fraumeni and nevoid basal cell carcinoma (Gorlin) syndromes. All of these syndromes involve transmissible genetic risk resulting from loss of a functional allele, or inheritance of a structurally defective allele, of a specific gene. These genes include RB1, NF1, NF2, TSC1, TSC2, TP53, PTEN, APC, hMLH1, hPSM2, and PTCH, most of which function as tumor suppressor genes. The same genes are also observed in mutated and inactive forms, or are deleted, in tumor cells in sporadic cases of the same tumors. The nature of the mutational events that give rise to these inactivated alleles suggests a possible role of environmental mutagens in their causation. However, only external ionizing radiation at high doses is clearly established as an environmental cause of brain, nerve and meningeal tumors in humans. Transplacental carcinogenesis studies in rodents and other species emphasize the extraordinary susceptibility of the developing mammalian nervous system to carcinogenesis, but the inverse relationship of latency to dose suggests that low transplacental exposures to genotoxicants are more likely to result in brain tumors late in life, rather than in childhood. While not all neurogenic tumor-related genes in humans have similar effects in experimental rodents, genetically engineered mice (GEM) increasingly provide useful insights into the combined effects of multiple tumor suppressor genes and of gene-environment interactions in the genesis of brain tumors, especially pediatric brain tumors such as medulloblastoma. (author)

  19. Surgical treatment of bilateral nondisplaced isthmic lysis by interlaminar fixation device

    Directory of Open Access Journals (Sweden)

    Keyvan Mostofi

    2017-01-01

    Full Text Available Study Design: Spondylolysis is a defect in the portion of pars interarticularis. The latter affects approximately 6% of the population. It is caused by repetitive trauma in hyperextension. Low back pain is the most common symptom. Methods: We implanted interspinous process devices in 12 patients with isthmic lysis without spondylolisthesis for low back pain. The purpose of the surgery was to conduct a minimally invasive procedure. Results: In eight cases, patients became asymptomatic. In two cases, there has been a considerable improvement. In two cases, no change had been noted. Conclusion: This good result motivates us to consider this approach a part of therapeutic arsenal for some cases of spondylolysis.

  20. Rasburicase-induced Hemolytic Anemia in an Adolescent With Unknown Glucose-6-Phosphate Dehydrogenase Deficiency.

    Science.gov (United States)

    Akande, Manzilat; Audino, Anthony N; Tobias, Joseph D

    2017-01-01

    Rasburicase, used in the prevention and treatment of tumor lysis syndrome (TLS), may cause hemolytic anemia and methemoglobinemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Although routine screening for G6PD deficiency has been recommended, given the turnaround time for test results and the urgency to treat TLS, such screening may not be feasible. We report a case of rasburicase-induced hemolytic anemia without methemoglobinemia in an adolescent with T-cell lymphoblastic lymphoma, TLS, and previously unrecognized G6PD deficiency. Previous reports of hemolytic anemia with rasburicase are reviewed, mechanisms discussed, and preventative strategies presented.

  1. Sensitivity of fibroblast growth factor 23 measurements in tumor-induced osteomalacia

    DEFF Research Database (Denmark)

    Imel, Erik A; Peacock, Munro; Pitukcheewanont, Pisit

    2006-01-01

    Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome of hypophosphatemia, decreased renal phosphate reabsorption, normal or low serum 1,25-dihydryxyvitamin-D concentration, myopathy, and osteomalacia. Fibroblast growth factor 23 (FGF23) is a phosphaturic protein overexpressed in tumors t...

  2. Endovascular treatment of stenoses in the superior vena cava syndrome caused by non-tumoral lesions

    Energy Technology Data Exchange (ETDEWEB)

    Bornak, A.; Ris, H.-B.; Probst, H.; Corpataux, J.-M. [Department of Thoracic and Vascular Surgery, Centre Hospitalier Universitaire Vaudois, Bugnon 46, 1011 Lausanne (Switzerland); Wicky, S. [Department of Radiodiagnostic and Interventional Radiology, Centre Hospitalier Universitaire Vaudois, Bugnon 46, 1011 Lausanne (Switzerland); Milesi, I. [Department of Angiology, Centre Hospitalier Universitaire Vaudois, Bugnon 46, 1011 Lausanne (Switzerland)

    2003-05-01

    We report our experience in percutaneous treatment of non-tumoral superior vena cava syndrome (SVCS) between December 1998 and July 2001. During a period of 2.5 years, 9 patients (age range 27-84 years, mean age 50 years) were treated percutaneously for significant non-tumoral SVCS. Symptomatic SVCS were due to dialysis catheters (7), central line (1) and radiation therapy (1). In thrombotic occlusions and severe stenosis, a preliminary in situ thrombolysis was achieved before angioplasty. Patients were followed by echo-Doppler, computed tomography angiography (CTA), magnetic resonance angiography (MRA), or phlebography. Complete recanalization of the veins and immediate resolution of symptomatic SVCS were obtained in all patients, with no procedure-related complication. Thirteen stents were placed in 9 patients with a mean clinical follow-up of 9.1 months (range 2-23 months). One hundred percent patency at 6 months was obtained. Two patients recurred twice and were treated with new stent placement. At 12 months the patency was 67% and assisted patency was 100%. Stent placement in benign symptomatic SVCS is a safe and minimally invasive procedure, with no technical and clinical complications in our experience. It allowed immediate relief of symptoms, and in dialysed patients could provide continued use of hemodialysis access. Close clinical surveillance is mandatory to assess stent patency. (orig.)

  3. Endovascular treatment of stenoses in the superior vena cava syndrome caused by non-tumoral lesions

    International Nuclear Information System (INIS)

    Bornak, A.; Ris, H.-B.; Probst, H.; Corpataux, J.-M.; Wicky, S.; Milesi, I.

    2003-01-01

    We report our experience in percutaneous treatment of non-tumoral superior vena cava syndrome (SVCS) between December 1998 and July 2001. During a period of 2.5 years, 9 patients (age range 27-84 years, mean age 50 years) were treated percutaneously for significant non-tumoral SVCS. Symptomatic SVCS were due to dialysis catheters (7), central line (1) and radiation therapy (1). In thrombotic occlusions and severe stenosis, a preliminary in situ thrombolysis was achieved before angioplasty. Patients were followed by echo-Doppler, computed tomography angiography (CTA), magnetic resonance angiography (MRA), or phlebography. Complete recanalization of the veins and immediate resolution of symptomatic SVCS were obtained in all patients, with no procedure-related complication. Thirteen stents were placed in 9 patients with a mean clinical follow-up of 9.1 months (range 2-23 months). One hundred percent patency at 6 months was obtained. Two patients recurred twice and were treated with new stent placement. At 12 months the patency was 67% and assisted patency was 100%. Stent placement in benign symptomatic SVCS is a safe and minimally invasive procedure, with no technical and clinical complications in our experience. It allowed immediate relief of symptoms, and in dialysed patients could provide continued use of hemodialysis access. Close clinical surveillance is mandatory to assess stent patency. (orig.)

  4. Medical Therapy for Cushing's Syndrome in the Twenty-first Century.

    Science.gov (United States)

    Tritos, Nicholas A; Biller, Beverly M K

    2018-06-01

    Medical therapy has a useful adjunctive role in many patients with Cushing's syndrome. Patients with pituitary corticotroph adenomas who have received radiation therapy to the sella require medical therapy until the effects of radiation therapy occur. In addition, patients with Cushing's syndrome who cannot undergo surgery promptly, including those who are acutely ill and cannot safely undergo tumor resection, may benefit from medical therapy as a bridge to surgery. Other possible candidates for medical therapy are those with unresectable tumors or those whose tumor location remains unknown despite adequate diagnostic evaluation. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Constitutional MLH1 methylation presenting with colonic polyposis syndrome and not Lynch syndrome.

    Science.gov (United States)

    Kidambi, Trilokesh D; Blanco, Amie; Van Ziffle, Jessica; Terdiman, Jonathan P

    2016-04-01

    At least one-third of patients meeting clinical criteria for Lynch syndrome will have no germline mutation and constitutional epimutations leading to promoter methylation of MLH1 have been identified in a subset of these patients. We report the first case of constitutional MLH1 promoter methylation associated with a colonic polyposis syndrome in a 39 year-old man with a family history of colorectal cancer (CRC) and a personal history of 21 polyps identified over 8 years as well as the development of two synchronous CRCs over 16 months who was evaluated for a hereditary cancer syndrome. Immunohistochemistry (IHC) of multiple tumors showed absent MLH1 and PMS2 expression, though germline testing with Sanger sequencing and multiplex ligation-dependent probe amplification of these mismatch repair genes (MMR) genes was negative. A next generation sequencing panel of 29 genes also failed to identify a pathogenic mutation. Hypermethylation was identified in MLH1 intron 1 in tumor specimens along with buccal cells and peripheral white blood cells, confirming the diagnosis of constitutional MLH1 promoter methylation. This case highlights that constitutional MLH1 methylation should be considered in the differential diagnosis for a polyposis syndrome if IHC staining shows absent MMR gene expression.

  6. Neuroendocrine tumors: fascination and infrequency Tumores neuroendocrinos: fascinación e infrecuencia

    Directory of Open Access Journals (Sweden)

    M. J. Varas Lorenzo

    2009-03-01

    Full Text Available In this article, I review and update of gastro-entero-pancreatic neuroendocrine tumors, which so much fascination have risen among healthcare providers on grounds of their infrequency, hormonal syndromes, and high survival rate, is performed based on references from the past fifteen years.Se efectúa una revisión y puesta al día, basándose en citas bibliográficas de los últimos quince años, de los tumores neuroendocrinos gastroenteropancreáticos, que tanta fascinación han provocado en el estamento médico por su infrecuencia, síndromes hormonales y supervivencia elevada.

  7. Application of Doehlert experimental design in the optimization of experimental variables for the Pseudozyma sp. (CCMB 306 and Pseudozyma sp. (CCMB 300 cell lysis

    Directory of Open Access Journals (Sweden)

    Amanda Reges de Sena

    2012-12-01

    Full Text Available This study aimed to verify the influence of pH and temperature on the lysis of yeast using experimental design. In this study, the enzymatic extract containing β-1,3-glucanase and chitinase, obtained from the micro-organism Moniliophthora perniciosa, was used. The experiment showed that the best conditions for lysis of Pseudozyma sp. (CCMB 306 and Pseudozyma sp. (CCMB 300 by lytic enzyme were pH 4.9 at 37 ºC and pH 3.9 at 26.7 ºC, respectively. The lytic enzyme may be used for obtaining various biotechnology products from yeast.

  8. Mesothelioma of the testis and nephrotic syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Bacchetta Justine

    2009-06-01

    Full Text Available Abstract Introduction Paraneoplastic glomerulopathies are rare manifestations of neoplastic disease to be distinguished from iatrogenic renal damage. Solid tumors are preferentially associated with membranous nephropathy, whereas Hodgkin's lymphomas are associated with minimal change disease. Case presentation We report a 63-year-old Caucasian male diagnosed with a mesothelioma of the tunica vaginalis testis who, secondary to this, also presented with a nephrotic syndrome due to minimal change disease. In the present case, the paraneoplastic etiology of the nephrotic syndrome can be discussed on four unusual elements: minimal change lesions were found; the glomerulopathy was very sensitive to corticosteroids; the nephrotic syndrome occurred 11 months after the diagnosis of the primary malignancy, but concomitantly with the recurrence; and the nephrotic syndrome did not decrease with tumor control and did not recur when the mesothelioma escaped treatment. No other etiologies could nevertheless explain this phenomenon. Conclusion Paraneoplastic nephrotic syndrome is often associated with membranous nephropathy in patients with solid tumors, especially in patients with lung and gastrointestinal tract neoplasia. The management of these patients is associated with a symptomatic treatment such as sodium and water restriction, diuretics and ACE inhibitors and a prophylaxis of specific complications of nephrotic syndrome including thromboembolism, infections and lipid abnormalities. Treatment of neoplasia must be undertaken rapidly, treatments must be regularly analyzed and drugs binding to albumin may be used with precaution.

  9. Optic nerve pilomyxoid astrocytoma in a patient with Noonan syndrome.

    Science.gov (United States)

    Nair, Sushmita; Fort, John A; Yachnis, Anthony T; Williams, Charles A

    2015-06-01

    Noonan syndrome (NS; MIM 163950) is an autosomal dominant syndrome which is clinically diagnosed by the distinct facial features, short stature, cardiac anomalies and developmental delay. About 50% of cases are associated with gain of function mutations in PTPN11 gene which leads to activation of the RAS/mitogen-activated protein kinase signaling pathway. This is known to have a role in tumorigenesis. Despite this, only limited reports of solid tumors (Fryssira H, Leventopoulos G, Psoni S, et al. Tumor development in three patients with Noonan syndrome. Eur J Pediatr 2008;167:1025-1031; Schuettpelz LG, McDonald S, Whitesell K et al. Pilocytic astrocytoma in a child with Noonan syndrome. Pediatr Blood Cancer 2009;53:1147-1149; Sherman CB, Ali-Nazir A, Gonzales-Gomez I, et al. Primary mixed glioneuronal tumor of the central nervous system in a patient with Noonan syndrome. J Pediatr Hematol Oncol 2009;31:61-64; Sanford RA, Bowman R, Tomita T, et al. A 16 year old male with Noonan's syndrome develops progressive scoliosis and deteriorating gait. Pediatr Neurosurg 1999;30:47-52) and no prior reports of optic gliomas have been described in patients with NS. We present here a patient with NS with a PTPN11 mutation and an optic pathway pilomyxoid astrocytoma. © 2015 Wiley Periodicals, Inc.

  10. Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

    Directory of Open Access Journals (Sweden)

    Yeliz Bilir

    2014-01-01

    Full Text Available Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts, the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

  11. Intra-Abdominal Testicular Seminoma in a Woman with Testicular Feminization Syndrome

    Directory of Open Access Journals (Sweden)

    Darshana D. Rasalkar

    2011-01-01

    Full Text Available We report a case of intra-abdominal testicular tumor in a 36-year-old married lady presenting with chief complaints of primary amenorrhea. The patient was later diagnosed with testicular feminization syndrome, a form of male pseudohermaphroditism. This testicular tumor was histologically proven as seminoma. Due to rarity, imaging findings in patients with testicular feminization syndrome and intraabdominal testicular tumor have been poorly documented. So far, only one case report had described the combined role of CT and MR imaging in intraabdominal testicular sex-cord stromal tumor. To our knowledge, this case is first to document USG and MR imaging in addition to MR spectroscopy features in intraabdominal testicular seminoma.

  12. Low-dose radiation enhances therapeutic HPV DNA vaccination in tumor-bearing hosts.

    Science.gov (United States)

    Tseng, Chih-Wen; Trimble, Cornelia; Zeng, Qi; Monie, Archana; Alvarez, Ronald D; Huh, Warner K; Hoory, Talia; Wang, Mei-Cheng; Hung, Chien-Fu; Wu, T-C

    2009-05-01

    Current therapeutic approaches to treatment of patients with bulky cervical cancer are based on conventional in situ ablative modalities including cisplatin-based chemotherapy and radiation therapy. The 5-year survival of patients with nonresectable disease is dismal. Because over 99% of squamous cervical cancer is caused by persistent infection with an oncogenic strain of human papillomavirus (HPV), particularly type 16 and viral oncoproteins E6 and E7 are functionally required for disease initiation and persistence, HPV-targeted immune strategies present a compelling opportunity in which to demonstrate proof of principle. Sublethal doses of radiation and chemotherapeutic agents have been shown to have synergistic effect in combination with either vaccination against cancer-specific antigens, or with passive transfer of tumor-specific cytotoxic T lymphocytes (CTLs). Here, we explored the combination of low-dose radiation therapy with DNA vaccination with calreticulin (CRT) linked to the mutated form of HPV-16 E7 antigen (E7(detox)), CRT/E7(detox) in the treatment of E7-expressing TC-1 tumors. We observed that TC-1 tumor-bearing mice treated with radiotherapy combined with CRT/E7(detox) DNA vaccination generated significant therapeutic antitumor effects and the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of treated mice. Furthermore, treatment with radiotherapy was shown to render the TC-1 tumor cells more susceptible to lysis by E7-specific CTLs. In addition, we observed that treatment with radiotherapy during the second DNA vaccination generated the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of TC-1 tumor-bearing mice. Finally, TC-1 tumor-bearing mice treated with the chemotherapy in combination with radiation and CRT/E7(detox) DNA vaccination generate significantly enhanced therapeutic antitumor effects. The clinical implications of the study are discussed.

  13. Hepatopathy-thrombocytopenia syndrome after actinomycin-D therapy: treatment with defibrotide.

    Science.gov (United States)

    Martín-Lázaro, Juan F; Palanca, Daniel; Garcia-Iñiguez, Juan P; Madurga, Paula; Carboné, Ana

    2013-02-01

    We report a case of administration compassionate use defibrotide in a 13-year-old girl with Sinusoidal Obstructive Syndrome and thrombocytopenia, also known as Hepatopathy--Thrombocytopenia Syndrome (HTS) during chemotherapy for Wilms' tumor.

  14. Rectal Cancer in a Patient with Bartter Syndrome: A Case Report.

    Science.gov (United States)

    Fujino, Shiki; Miyoshi, Norikatsu; Ohue, Masayuki; Mukai, Mikio; Kukita, Yoji; Hata, Taishi; Matsuda, Chu; Mizushima, Tsunekazu; Doki, Yuichiro; Mori, Masaki

    2017-05-12

    A woman with rectal cancer was scheduled for surgery. However, she also had hypokalemia, hyperreninemia, and hyperaldosteronism in the absence of any known predisposing factors or endocrine tumors. She was given intravenous potassium, and her blood abnormalities stabilized after tumor resection. Genetic analysis revealed mutations in several genes associated with Bartter syndrome (BS) and Gitelman syndrome, including SLC12A1 , CLCNKB , CASR , SLC26A3 , and SLC12A3 . Prostaglandin E2 (PGE2) plays an important role in BS and worsens electrolyte abnormalities. The PGE2 level is reportedly increased in colorectal cancer, and in the present case, immunohistochemical examination revealed an increased PGE2 level in the tumor. We concluded that the tumor-related PGE2 elevation had worsened the patient's BS, which became more manageable after tumor resection.

  15. Myxoid variant of adrenocortical tumors. Report of two cases with unique entity

    International Nuclear Information System (INIS)

    Suzuki, Rumi; Ito, Yukio; Okamoto, Takahiro; Iihara, Masatoshi; Obara, Takao; Tsuiki, Mika; Takano, Kazue; Nishikawa, Toshio; Aiba, Motohiko

    2007-01-01

    Cases in the title are reported. Case 1, a 57-year old female, had fracture and reduced limbic muscular force due to Cushing syndrome. CT image gave a big tumor in the left adrenal and 131 I-adosterol scintigraphy revealed the increased and decreased 131 I accumulation in the left and right adrenal, respectively: the carcinoma suspected. Only tumor portion was dissected out and was found to be an adenoma in histology. Case 2, a 50-year old male, had Cushing syndrome and extreme obesity. Previous CT presented a big tumor in the left adrenal; biopsy was performed under CT; and before surgery, the tumor was partly calcified in CT, which was found to be a carcinoma. In both cases, histology gave findings of the interstitial and extracellular disposition of myxoid material and of pseudoglandular pattern. (R.T.)

  16. Dual paraneoplastic syndromes: small cell lung carcinoma-related oncogenic osteomalacia, and syndrome of inappropriate antidiuretic hormone secretion: report of a case and review of the literature.

    Science.gov (United States)

    Tantisattamo, Ekamol; Ng, Roland C K

    2011-07-01

    Acquired isolated renal phosphate wasting associated with a tumor, known as oncogenic osteomalacia or tumor-induced osteomalacia, is a rare paraneoplastic syndrome caused by overproduction of fibroblast growth factor 23. Oncogenic osteomalacia is usually associated with benign mesenchymal tumors. Syndrome of inappropriate antidiuretic hormone secretion (SIADH), on the other hand, is a common paraneoplastic syndrome caused by small cell carcinoma (SCC). Concomitant oncogenic osteomalacia and SIADH associated with SCC is very rare with only 4 other cases reported in the literature. The authors report a case of small cell lung cancer (SCLC)-related renal wasting hypophosphatemia and concurrent SIADH, and review the literature reporting 9 other cases of SCC associated with oncogenic osteomalacia. Almost half of reported cases of renal phosphate wasting associated with SCC concomitantly presented with SIADH. These cases had initial serum phosphorus level lower and survival periods shorter than those without SIADH. This rare combination of a dual paraneoplastic syndrome and low serum phosphorus may be a poor prognostic sign. In addition, both renal phosphate wasting and SIADH usually occur in a short period of time before identification of SCC. Therefore, renal wasting hypophosphatemia with concomitant SIADH/hyponatremia should prompt a search for SCC rather than a benign mesenchymal tumor.

  17. Tumor producing fibroblast growth factor 23 localized by two-staged venous sampling.

    NARCIS (Netherlands)

    Boekel, G.A.J van; Ruinemans-Koerts, J.; Joosten, F.; Dijkhuizen, P.; Sorge, A.A. van; Boer, H. de

    2008-01-01

    BACKGROUND: Tumor-induced osteomalacia is a rare paraneoplastic syndrome characterized by hypophosphatemia, renal phosphate wasting, suppressed 1,25-dihydroxyvitamin D production, and osteomalacia. It is caused by a usually benign mesenchymal tumor producing fibroblast growth factor 23 (FGF-23).

  18. Telotristat ethyl: proof of principle and the first oral agent in the management of well-differentiated metastatic neuroendocrine tumor and carcinoid syndrome diarrhea.

    Science.gov (United States)

    Masab, Muhammad; Saif, Muhammad Wasif

    2017-12-01

    Metastatic neuroendocrine tumors (NETs) are associated with carcinoid syndrome that is typically characterized by diarrhea, cutaneous flushing and bronchospasm. Treatment with somatostatin analogues (SSA) improves the symptom burden but a significant proportion of patients stop responding to SSA therapy eventually. Novel agents with the potential to effectively control the symptoms are urgently needed. This article reviews an in-depth analysis of the phase I-III clinical trials determining the clinical rationale for the use of tryptophan hydroxylase inhibitor, telotristat ethyl in patients with well-differentiated metastatic NETs and uncontrolled carcinoid syndrome. Telotristat ethyl has already been approved for the treatment of inadequately controlled carcinoid syndrome symptoms in metastatic NET patients on SSA therapy. Results from multiple phase I-III clinical studies of telotristat ethyl therapy have reported a significant decrease in the daily bowel movement frequency, increase in quality of life and the subsequent decrease in annual health costs related to carcinoid syndrome symptoms in NET patients. The associated decrease in urinary 5-hydroxyindoleacetic acid (u5-HIAA) provides evidence that telotristat ethyl effectively decreases serotonin production, and therefore, offers a rationale to investigate this agent to mitigate serotonin-mediated complications in this patient population, especially cardiac valvular disease or mesenteric fibrosis.

  19. ROHHAD Syndrome: The Girl who Forgets to Breathe.

    Science.gov (United States)

    Sanklecha, Mukesh; Sundaresan, Suba; Udani, Vrajesh

    2016-04-01

    ROHHAD syndrome is an exceedingly rare cause of central hypoventilation. A 7-year-old girl with ROHHAD syndrome who had central hypoventilation, rapid weight gain, multiple cardiac arrests and hyperprolactinemia. She required prolonged and repeated ventilation, and finally died due to complications of ventilation. ROHHAD Syndrome should be suspected in any child who presents with obesity, behavioral changes or autonomic instability following a neural crest tumor.

  20. Tailored imaging of islet cell tumors of the pancreas amidst increasing options

    NARCIS (Netherlands)

    Fiebrich, Helle-Brit; van Asselt, Sophie J.; Brouwers, Adrienne H.; van Dullemen, Hendrik M.; Pijl, Milan E. J.; Elsinga, Philip H.; Links, Thera P.; de Vries, Elisabeth G. E.

    Pancreatic islet cell tumors are neuroendocrine tumors, which can produce hormones and can arise as part of multiple endocrine neoplasia type 1 or von-Hippel-Lindau-disease, two genetically well-defined hereditary cancer syndromes. Currently, technical innovation improves conventional and specific

  1. [Tumors of the central nervous system].

    Science.gov (United States)

    Alegría-Loyola, Marco Antonio; Galnares-Olalde, Javier Andrés; Mercado, Moisés

    2017-01-01

    Central nervous system (CNS) tumors constitute a heterogeneous group of neoplasms that share a considerable morbidity and mortality rate. Recent advances in the underlying oncogenic mechanisms of these tumors have led to new classification systems, which, in turn, allow for a better diagnostic approach and therapeutic planning. Most of these neoplasms occur sporadically and several risk factors have been found to be associated with their development, such as exposure to ionizing radiation or electromagnetic fields and the concomitant presence of conditions like diabetes, hypertension and Parkinson's disease. A relatively minor proportion of primary CNS tumors occur in the context of hereditary syndromes. The purpose of this review is to analyze the etiopathogenesis, clinical presentation, diagnosis and therapy of CNS tumors with particular emphasis in the putative risk factors mentioned above.

  2. Pituitary Tumors in Childhood: an update in their diagnosis, treatment and molecular genetics

    Science.gov (United States)

    Keil, Margaret F.; Stratakis, Constantine A.

    2009-01-01

    Pituitary tumors are rare in childhood and adolescence, with a reported prevalence of up to 1 per million children. Only 2 - 6% of surgically treated pituitary tumors occur in children. Although pituitary tumors in children are almost never malignant and hormonal secretion is rare, these tumors may result in significant morbidity. Tumors within the pituitary fossa are of two types mainly, craniopharyngiomas and adenomas; craniopharyngiomas cause symptoms by compressing normal pituitary, causing hormonal deficiencies and producing mass effects on surrounding tissues and the brain; adenomas produce a variety of hormonal conditions such as hyperprolactinemia, Cushing disease and acromegaly or gigantism. Little is known about the genetic causes of sporadic lesions, which comprise the majority of pituitary tumors, but in children, more frequently than in adults, pituitary tumors may be a manifestation of genetic conditions such as multiple endocrine neoplasia type 1 (MEN 1), Carney complex, familial isolated pituitary adenoma (FIPA), and McCune-Albright syndrome. The study of pituitary tumorigenesis in the context of these genetic syndromes has advanced our knowledge of the molecular basis of pituitary tumors and may lead to new therapeutic developments. PMID:18416659

  3. Garcin syndrome with hypopituitarism

    International Nuclear Information System (INIS)

    Abe, K.; Mezaki, T.; Hirono, N.; Udaka, F.; Kameyama, M.

    1988-01-01

    We report a Garcin syndrome due to nasopharyngeal carcinoma invading the skull base. MR imaging of this patient shows the position of the tumour and reveals how to the tumor invaded the skull and the effect of treatment. (orig.)

  4. BASED TO CLINICAL CASE. VON HIPLEA-LINDAU SYNDROME

    Directory of Open Access Journals (Sweden)

    Brzeziński Piotr

    2011-01-01

    Full Text Available von Hippel-Lindau syndrome (VHL is a rare, genetic multi-system disorder characterized by the abnormal growth of tumors in certain parts of the body (angiomatosis. The tumors of the central nervous system (CNS are benign and are comprised of a nest of blood vessels and are called hemangioblastomas. Hemangioblastomas may develop in the brain, the retina of the eyes, and other areas of the nervous system. Other types of tumors develop in the adrenal glands, the kidneys, or the pancreas. Symptoms of VHL vary among patients and depend on the size and location of the tumors. Symptoms may include headaches, problems with balance and walking, dizziness, weakness of the limbs, vision problems, and high blood pressure. Cysts (fluid-filled sacs and/or tumors (benign or cancerous may develop around the hemangioblastomas and cause the symptoms listed above. Individuals with VHL are also at a higher risk than normal for certain types of cancer, especially kidney cancer. Based on the case of 30-year old patient with characteristics of von Hippel-Lindau syndrome as phakomatosis.

  5. Gorlin-Goltz syndrome: A series of three cases.

    Science.gov (United States)

    Patankar, Amod P; Kshirsagar, Rajesh A; Dugal, Arun; Mishra, Akshay; Ram, Hari

    2014-01-01

    The Gorlin-Goltz syndrome (GGS) is also known as nevoid basal cell carcinoma syndrome. It is characterized by multiple keratocystic odontogenic tumors (KCOTs) in the jaw, multiple basal cell nevi carcinomas and skeletal abnormities. The syndrome may be diagnosed early by a dentist during the routine radiographic exams in the first decade of life, since the KCOTs are usually one of the first manifestations of the syndrome. This article reports the series of 3 cases, emphasizing its clinical and radiographic manifestations of GGS.

  6. Study of the phage production efficiency in the bacteria lysis processes; Estudio del rendimiento en fagos para los procesos de lisis bacteriana

    Energy Technology Data Exchange (ETDEWEB)

    Vidania Munoz, R de; Garces, F; Davila, C A

    1979-07-01

    In this work we present a search for the best production conditions of {lambda}vir and{lambda} clear phages In E coli K12 and E coli C{sub 6}00 infected cells respectively. By keeping fixed some parameters of the process as the bacterial and phage generation times and the bacterial burst side, we have found that the lysis yield is strongly dependent on the multiplicity and in a lesser degree on the infection time. It appears from the experimental results that other variables are important, as infection efficiency and approach time from phages to bacteria. We will try to describe the lysis phenomenon by a numerical model on the bases of the se experimental results. (Author) 11 refs.

  7. Studies on cytotoxic and clot lysis activity of probiotically fermented cocktail juice prepared using Camellia sinensis and Punica grantum

    Science.gov (United States)

    Biswas, Ananya; Deori, Meenakshi; Nivetha, A.; Mohansrinivasan, V.

    2017-11-01

    In the current research the effect of probiotic microorganisms viz; Lactococcus lactis and Lactobacillus plantarum on fermentation of Camellia sinensis and Punica grantum was studied. In vitro test were done to analyze the anticancer, antioxidant and atherosclerosis (clot lysis) properties of fermented juice. The juice was fermented for 48 and 96h, during which concentration of phenolic content, total acid content and free radical scavenging activity of the sample was analyzed by DPPH assay (α, α-diphenyl-β-picrylhydrazyl). Dropping of pH was observed after 48 h of fermentation. The clot lysis activity was found to be 80 % in 100μl concentration of fermented cocktail juice. The 96 h fermented sample has shown around 70% inhibition against colon cancer cell lines. Analytical study of HPLC proves the organic acid production such as ascorbic acid in superior amount for 96h of fermented sample, Based on the retention time, the corresponding peaks were detected at 4.919 and 4.831 min.

  8. The role of computed tomography in the localization of adrenal cortex tumors

    International Nuclear Information System (INIS)

    Baranowska, B.; Misiorowski, W.; Pacho, R.; Wysocki, M.; Kobuszewska, M.; Zgliczynski, S.; Medical Center of Postgraduate Education, Warsaw

    1982-01-01

    The aim of this study was to evaluate the usefulness of computed tomography in the localisation of adrenal tumors producing aldosterone and cortisol. One case each of Conn's and Cushing's syndrome are described. The diagnosis of Conn's syndrome was established by demonstrating an elevated plasma aldosterone level 'at rest' and its decrease after stimulation, the absence of plasma renin activity and a lowered plasma potassium level. The diagnosis of Cushing's syndrome due to adrenal adenoma was established by demonstrating the typical clinical features, an abnormal diurnal rhythm of cortisol and ACTH secretion and an increased urine excretion of 17-OHCS without suppression by large doses of dexamethasone. The localisation and the size of the tumors as determined by computed tomography were confirmed during surgery. (orig.) [de

  9. Temporary reversal by topotecan of marked insulin resistance in a patient with myelodysplastic syndrome: case report and possible mechanism for tumor necrosis factor alpha (TNF-alpha)-induced insulin resistance.

    Science.gov (United States)

    Huntington, M O; Krell, K E; Armour , W E; Liljenquist, J E

    2001-06-01

    Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of insulin resistance in obesity and diabetes through its ability to decrease the tyrosine kinase activity of the insulin receptor. We report here a remarkable degree of insulin resistance in a patient with adult respiratory distress syndrome and myelodysplasia.

  10. Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity.

    Science.gov (United States)

    Hamilton, Gerhard; Rath, Barbara

    2017-04-01

    Immune checkpoint inhibition holds great promise for selected tumors. The human monoclonal antibody (mAB) avelumab is directed to programmed death ligand-1 (PD-L1) and is supposed to inhibit the immunosuppressive PD-L1/PD-1 interaction and, furthermore, effect antibody-dependent cytotoxicity (ADCC) lysis of tumor cells. Areas covered: This article presents an overview of the current means to activate the antitumor immune defense by targeting PD-1 or PD-L1 with mABs and their possible role in ADCC-mediated tumor cell elimination. Expert opinion: Avelumab contains a Fc region which can bind cognate receptors on immune effector cells and induce ADCC-mediated tumor cell lysis, in contrast to other mABs directed to PD-1/PD-L1 which lack the ability to trigger ADCC due to belonging to the IgG4 subclass or possessing a mutated Fc region. Preclinical and clinical data indicate that avelumab can be safely administered to cancer patients with a toxicity profile comparable to other mABs and without lysis of PD-L1-positive activated immune cells. This antibody yielded durable responses in a phase II trial in advanced Merkel cell carcinoma patients. Tumor cell lysis by avelumab prevents cells from resorting to alternative checkpoints as shown by targeting PD-1 and the upregulation of TIM-3.

  11. Continuous nucleus extraction by optically-induced cell lysis on a batch-type microfluidic platform.

    Science.gov (United States)

    Huang, Shih-Hsuan; Hung, Lien-Yu; Lee, Gwo-Bin

    2016-04-21

    The extraction of a cell's nucleus is an essential technique required for a number of procedures, such as disease diagnosis, genetic replication, and animal cloning. However, existing nucleus extraction techniques are relatively inefficient and labor-intensive. Therefore, this study presents an innovative, microfluidics-based approach featuring optically-induced cell lysis (OICL) for nucleus extraction and collection in an automatic format. In comparison to previous micro-devices designed for nucleus extraction, the new OICL device designed herein is superior in terms of flexibility, selectivity, and efficiency. To facilitate this OICL module for continuous nucleus extraction, we further integrated an optically-induced dielectrophoresis (ODEP) module with the OICL device within the microfluidic chip. This on-chip integration circumvents the need for highly trained personnel and expensive, cumbersome equipment. Specifically, this microfluidic system automates four steps by 1) automatically focusing and transporting cells, 2) releasing the nuclei on the OICL module, 3) isolating the nuclei on the ODEP module, and 4) collecting the nuclei in the outlet chamber. The efficiency of cell membrane lysis and the ODEP nucleus separation was measured to be 78.04 ± 5.70% and 80.90 ± 5.98%, respectively, leading to an overall nucleus extraction efficiency of 58.21 ± 2.21%. These results demonstrate that this microfluidics-based system can successfully perform nucleus extraction, and the integrated platform is therefore promising in cell fusion technology with the goal of achieving genetic replication, or even animal cloning, in the near future.

  12. Tumor-specific loss of 11p15.5 alleles in del11p13 Wilms tumor and in familial adrenocortical carcinoma

    International Nuclear Information System (INIS)

    Henry, I.; Grandjouan, S.; Couillin, P.

    1989-01-01

    The authors have compared constitutional and tumor genotypes in nine cases of hereditary Wilms tumor (WT) and in three unrelated cases of familial adrenocortical carcinoma (ADCC). Since susceptibility to these tumors can be observed in malformation syndromes associated with a constitutional deletion of band 11p13 (WT) and with a constitutional duplication of band 11p15.5 (WT, ADCC), they investigated these two candidate regions by using 11p polymorphic markers. As expected, somatic chromosomal events, resulting in a loss of heterozygosity limited to region 11p15.5, were observed in the tumor of two familial cases of adrenocortical carcinoma. Surprisingly, however, analysis of the WT of two patients with a constitutional deletion of band 11p13, associated with aniridia, genitourinary abnormalities, and mental retardation (WAGR syndrome), revealed a loss of heterozygosity limited to region 11p15.5. These data therefore suggest that observation of a specific loss of heterozygosity may not necessarily point to the site of the initial germinal mutation. Together with previous similar observations of a loss of heterozygosity limited to 11p15.5 in breast cancer and in rhabdomyosarcoma, the data suggest that region 11p15.5 may carry a non-tissue-specific gene that could be involved in genetic predisposition, in tumor progression, or in both

  13. Beckwith-Wiedemann syndrome and bilateral adrenal pheochromocytoma: sonography and MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Baldisserotto, Matteo; Peletti, Adriana Barcellos; Araujo, Manoel Angelo de; Pertence, Ana Paula Cardoso; Dora, Marcelo Dourado; Maciel, Elines Oliva; Gaiger, Ana Maria [Hospital da Crianca Conceicao, Departamento de Radiologia, Porto Alegre, RS (Brazil)

    2005-11-01

    Beckwith-Wiedemann syndrome is characterized by a group of clinical abnormalities, the most frequent of which are omphalocele, macroglossia, gigantism, neonatal hypoglycemia and umbilical hernia. The association of this syndrome with malignant tumors is well documented. We report a child with this syndrome associated with bilateral adrenal pheochromocytoma. (orig.)

  14. Beckwith-Wiedemann syndrome and bilateral adrenal pheochromocytoma: sonography and MRI findings

    International Nuclear Information System (INIS)

    Baldisserotto, Matteo; Peletti, Adriana Barcellos; Araujo, Manoel Angelo de; Pertence, Ana Paula Cardoso; Dora, Marcelo Dourado; Maciel, Elines Oliva; Gaiger, Ana Maria

    2005-01-01

    Beckwith-Wiedemann syndrome is characterized by a group of clinical abnormalities, the most frequent of which are omphalocele, macroglossia, gigantism, neonatal hypoglycemia and umbilical hernia. The association of this syndrome with malignant tumors is well documented. We report a child with this syndrome associated with bilateral adrenal pheochromocytoma. (orig.)

  15. Integrated tumor and germline whole-exome sequencing identifies mutations in MAPK and PI3K pathway genes in an adolescent with rosette-forming glioneuronal tumor of the fourth ventricle

    Science.gov (United States)

    Lin, Frank Y.; Bergstrom, Katie; Person, Richard; Bavle, Abhishek; Ballester, Leomar Y.; Scollon, Sarah; Raesz-Martinez, Robin; Jea, Andrew; Birchansky, Sherri; Wheeler, David A.; Berg, Stacey L.; Chintagumpala, Murali M.; Adesina, Adekunle M.; Eng, Christine; Roy, Angshumoy; Plon, Sharon E.; Parsons, D. Williams

    2016-01-01

    The integration of genome-scale studies such as whole-exome sequencing (WES) into the clinical care of children with cancer has the potential to provide insight into the genetic basis of an individual's cancer with implications for clinical management. This report describes the results of clinical tumor and germline WES for a patient with a rare tumor diagnosis, rosette-forming glioneuronal tumor of the fourth ventricle (RGNT). Three pathogenic gene alterations with implications for clinical care were identified: somatic activating hotspot mutations in FGFR1 (p.N546K) and PIK3CA (p.H1047R) and a germline pathogenic variant in PTPN11 (p.N308S) diagnostic for Noonan syndrome. The molecular landscape of RGNT is not well-described, but these data are consistent with prior observations regarding the importance of the interconnected MAPK and PI3K/AKT/mTOR signaling pathways in this rare tumor. The co-occurrence of FGFR1, PIK3CA, and PTPN11 alterations provides further evidence for consideration of RGNT as a distinct molecular entity from pediatric low-grade gliomas and suggests potential therapeutic strategies for this patient in the event of tumor recurrence as novel agents targeting these pathways enter pediatric clinical trials. Although RGNT has not been definitively linked with cancer predisposition syndromes, two prior cases have been reported in patients with RASopathies (Noonan syndrome and neurofibromatosis type 1 [NF1]), providing an additional link between these tumors and the mitogen-activated protein kinase (MAPK) signaling pathway. In summary, this case provides an example of the potential for genome-scale sequencing technologies to provide insight into the biology of rare tumors and yield both tumor and germline results of potential relevance to patient care. PMID:27626068

  16. Initiation of universal tumor screening for Lynch syndrome in colorectal cancer patients as a model for the implementation of genetic information into clinical oncology practice.

    Science.gov (United States)

    Cohen, Stacey A; Laurino, Mercy; Bowen, Deborah J; Upton, Melissa P; Pritchard, Colin; Hisama, Fuki; Jarvik, Gail; Fichera, Alessandro; Sjoding, Britta; Bennett, Robin L; Naylor, Lorraine; Jacobson, Angela; Burke, Wylie; Grady, William M

    2016-02-01

    Lynch syndrome confers a hereditary predisposition to colorectal and other cancers. Universal tumor screening (UTS) for Lynch syndrome is recommended by several professional societies, but the implementation can be complex. This article describes the evaluation, process development, and initiation of Lynch syndrome UTS at a tertiary referral cancer center. A multidisciplinary team developed the new process design. Issues in 5 themes were noted: timing, funding, second-opinion patients, result processing, and the role of genetics providers. A committee approach was used to examine each issue for process-improvement development. The issues related to testing were addressed individually for the successful implementation of UTS at the institutional level. In the conventional-care period, 9 of 30 cases (30%) received Lynch syndrome screening, and 4 cases were referred to medical genetics. During the 6 months following the implementation of UTS, 32 of 44 patients (73%) received Lynch syndrome screening. The 13 unscreened patients all had identified reasons for nonscreening (eg, financial limitations). Ten patients were referred to medical genetics, which identified no new cases of Lynch syndrome, but a low-risk adenomatous polyposis coli (APC) variant was detected in 1 individual. The implementation of effective Lynch syndrome UTS can feasibly alter practice at the institutional level. This experience with the assessment and management of issues relevant to the successful implementation of a new clinical care paradigm based on emerging technology has implications for the uptake of advances across molecular oncology into clinical practice, and this is highly relevant in the current era of rapidly evolving genomic technology. © 2015 American Cancer Society.

  17. Persistent Mullerian Duct Syndrome with Transverse Testicular ...

    African Journals Online (AJOL)

    Eastham JA, McEvoy K, Sullivan R, Chandrasoma P. A case of simultaneous bilateral nonseminomatous testicular tumors in persistent müllerian duct syndrome. J Urol 1992;148:407-8. 8. Shinmura Y, Yokoi T, Tsutsui Y. A case of clear cell adenocarcinoma of the müllerian duct in persistent müllerian duct syndrome: The first ...

  18. Nevoid basal cell carcinoma syndrome. Profile of genetic and environmental factors in oncogenesis

    International Nuclear Information System (INIS)

    Howell, J.B.

    1984-01-01

    Nevoid basal cell carcinomas (NBCCs) are a prototype of a genetic form of basal cell carcinoma. These basal cell cancers, rather than being caused by genetic factors alone, are most likely the product of genetic and environmental factors. The NBCC syndrome provides a model for studying tumors induced by ionizing radiation and for viewing carcinogenesis as a multistage process explainable by a minimum of two steps. The interaction of genetic and environmental factors in producing tumors to which an individual is predisposed can be studied in patients with the NBCC syndrome and childhood medulloblastoma that was treated by radiation therapy. Individuals with the NBCC syndrome represent a special subgroup with a hereditary predisposition to basal cell carcinoma in whom ionizing radiation may supply the subsequent mutation necessary for tumor development. The genetically altered epidermis underlying the palm and sole pits found in patients with the syndrome represents basal cell carcinoma in situ from which basal cell carcinomas develop, albeit infrequently. The restrained biologic behavior of most of these tumors contrasts with the usual destructive behavior of the NBCCs of the head and neck in the same patient

  19. Broad spectrum of neuropsychiatric phenotypes associated with white matter disease in PTEN hamartoma tumor syndrome.

    Science.gov (United States)

    Balci, Tugce B; Davila, Jorge; Lewis, Denice; Boafo, Addo; Sell, Erick; Richer, Julie; Nikkel, Sarah M; Armour, Christine M; Tomiak, Eva; Lines, Matthew A; Sawyer, Sarah L

    2018-01-01

    White matter lesions have been described in patients with PTEN hamartoma tumor syndrome (PHTS). How these lesions correlate with the neurocognitive features associated with PTEN mutations, such as autism spectrum disorder (ASD) or developmental delay, has not been well established. We report nine patients with PTEN mutations and white matter changes on brain magnetic resonance imaging (MRI), eight of whom were referred for reasons other than developmental delay or ASD. Their clinical presentations ranged from asymptomatic macrocephaly with normal development/intellect, to obsessive compulsive disorder, and debilitating neurological disease. To our knowledge, this report constitutes the first detailed description of PTEN-related white matter changes in adult patients and in children with normal development and intelligence. We present a detailed assessment of the neuropsychological phenotype of our patients and discuss the relationship between the wide array of neuropsychiatric features and observed white matter findings in the context of these individuals. © 2017 Wiley Periodicals, Inc.

  20. Real world outcomes and management strategies for venetoclax-treated chronic lymphocytic leukemia patients in the United States.

    Science.gov (United States)

    Mato, Anthony R; Thompson, Meghan; Allan, John N; Brander, Danielle M; Pagel, John M; Ujjani, Chaitra S; Hill, Brian T; Lamanna, Nicole; Lansigan, Frederick; Jacobs, Ryan; Shadman, Mazyar; Skarbnik, Alan P; Pu, Jeffrey J; Barr, Paul M; Sehgal, Alison R; Cheson, Bruce D; Zent, Clive S; Tuncer, Hande H; Schuster, Stephen J; Pickens, Peter V; Shah, Nirav N; Goy, Andre; Winter, Allison M; Garcia, Christine; Kennard, Kaitlin; Isaac, Krista; Dorsey, Colleen; Gashonia, Lisa M; Singavi, Arun K; Roeker, Lindsey E; Zelenetz, Andrew; Williams, Annalynn; Howlett, Christina; Weissbrot, Hanna; Ali, Naveed; Khajavian, Sirin; Sitlinger, Andrea; Tranchito, Eve; Rhodes, Joanna; Felsenfeld, Joshua; Bailey, Neil; Patel, Bhavisha; Burns, Timothy F; Yacur, Melissa; Malhotra, Mansi; Svoboda, Jakub; Furman, Richard R; Nabhan, Chadi

    2018-06-07

    Venetoclax is a BCL2 inhibitor approved for 17p-deleted relapsed/refractory chronic lymphocytic leukemia with activity following kinase inhibitors. We conducted a multicenter retrospective cohort analysis of patients with CLL treated with venetoclax to describe outcomes, toxicities, and treatment selection following venetoclax discontinuation. A total of 141 chronic lymphocytic leukemia patients were included (98% relapsed/refractory). Median age at venetoclax initiation was 67 years (range 37-91), median prior therapies was 3 (0-11), 81% unmutated IGHV, 45% del(17p), and 26.8% complex karyotype (≥ 3 abnormalities). Prior to venetoclax initiation, 89% received a B-cell receptor antagonist. For tumor lysis syndrome prophylaxis, 93% received allopurinol, 92% normal saline, and 45% rasburicase. Dose escalation to the maximum recommended dose of 400 mg daily was achieved in 85% of patients. Adverse events of interest included neutropenia in 47.4%, thrombocytopenia in 36%, tumor lysis syndrome in 13.4%, neutropenic fever in 11.6%, and diarrhea in 7.3%. The overall response rate to venetoclax was 72% (19.4% complete remission). With a median follow up of 7 months, median progression free survival and overall survival for the entire cohort have not been reached. To date, 41 venetoclax treated patients have discontinued therapy and 24 have received a subsequent therapy, most commonly ibrutinib. In the largest clinical experience of venetoclax-treated chronic lymphocytic leukemia patients , the majority successfully completed and maintained a maximum recommended dose. Response rates and duration of response appear comparable to clinical trial data. Venetoclax was active in patients with mutations known to confer ibrutinib resistance. Optimal sequencing of newer chronic lymphocytic leukemia therapies requires further study. Copyright © 2018, Ferrata Storti Foundation.

  1. Pediatric imaging in DICER1 syndrome

    International Nuclear Information System (INIS)

    Bueno, Marta Tijerin; Martinez-Rios, Claudia; Ahyad, Rayan A.; Greer, Mary-Louise C.; Puente Gregorio, Alejandro de la; Villani, Anita; Malkin, David; Druker, Harriet; Van Engelen, Kalene; Gallinger, Bailey; Aronoff, Laura; Grant, Ronald

    2017-01-01

    DICER1 syndrome, arising from a mutation in the DICER1 gene mapped to chromosome 14q32, is associated with an increased risk of a range of benign and malignant neoplasms. To determine the spectrum of abnormalities and imaging characteristics in patients with DICER1 syndrome at a tertiary pediatric hospital. This retrospective analysis evaluated imaging in patients ≤18 years with DICER1 germline variants between January 2004 and July 2016. An imaging database search including keywords pleuropulmonary blastoma, cystic nephroma, pineoblastoma, embryonal rhabdomyosarcoma, ovarian sex cord-stromal tumor, ovarian Sertoli-Leydig cell tumor and DICER1 syndrome, was cross-referenced against the institutional Cancer Genetics Program database, excluding patients with negative/unknown DICER1 gene testing. Sixteen patients were included (12 females; mean age at presentation: 4.2 years, range: 14 days to 17 years), with surveillance imaging encompassing the following modalities: chest X-ray and CT; abdominal, pelvic and neck US; and brain and whole-body MRI. Malignant lesions (68.8% of patients) included pleuropulmonary blastoma (5), pineoblastoma (3), ovarian Sertoli-Leydig cell tumor (1), embryonal rhabdomyosarcoma (1) and renal sarcoma (1); benign lesions (37.5% of patients) included thyroid cysts (2), thyroid nodules (2), cystic nephroma (2), renal cysts (1) and pineal cyst (1). A common lesional appearance observed across modalities and organs was defined as the ''cracked windshield'' sign. The spectrum of DICER1-related tumors and the young age at presentation suggest early surveillance of at-risk patients is critical, while minimizing exposure to ionizing radiation. (orig.)

  2. Pediatric imaging in DICER1 syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Bueno, Marta Tijerin; Martinez-Rios, Claudia; Ahyad, Rayan A.; Greer, Mary-Louise C. [The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, Ontario (Canada); University of Toronto, Department of Medical Imaging, Toronto, Ontario (Canada); Puente Gregorio, Alejandro de la [Hospital Son Espases, Radiotherapy Department, Palma de Mallorca (Spain); Villani, Anita; Malkin, David [University of Toronto, Department of Pediatrics, Toronto, Ontario (Canada); The Hospital for Sick Children, Division of Hematology/Oncology, Toronto, Ontario (Canada); The Hospital for Sick Children, Genetics and Genomic Biology Program, Toronto, Ontario (Canada); Druker, Harriet [The Hospital for Sick Children, Division of Hematology/Oncology, Toronto, Ontario (Canada); The Hospital for Sick Children, Department of Genetic Counselling, Toronto, Ontario (Canada); The Hospital for Sick Children, Department of Molecular Genetics, Toronto, Ontario (Canada); Van Engelen, Kalene [The Hospital for Sick Children, Genetics and Genomic Biology Program, Toronto, Ontario (Canada); Gallinger, Bailey [The Hospital for Sick Children, Genetics and Genomic Biology Program, Toronto, Ontario (Canada); The Hospital for Sick Children, Department of Genetic Counselling, Toronto, Ontario (Canada); The Hospital for Sick Children, Department of Molecular Genetics, Toronto, Ontario (Canada); Aronoff, Laura [The Hospital for Sick Children, Division of Hematology/Oncology, Toronto, Ontario (Canada); Grant, Ronald [University of Toronto, Department of Pediatrics, Toronto, Ontario (Canada); The Hospital for Sick Children, Division of Hematology/Oncology, Toronto, Ontario (Canada)

    2017-09-15

    DICER1 syndrome, arising from a mutation in the DICER1 gene mapped to chromosome 14q32, is associated with an increased risk of a range of benign and malignant neoplasms. To determine the spectrum of abnormalities and imaging characteristics in patients with DICER1 syndrome at a tertiary pediatric hospital. This retrospective analysis evaluated imaging in patients ≤18 years with DICER1 germline variants between January 2004 and July 2016. An imaging database search including keywords pleuropulmonary blastoma, cystic nephroma, pineoblastoma, embryonal rhabdomyosarcoma, ovarian sex cord-stromal tumor, ovarian Sertoli-Leydig cell tumor and DICER1 syndrome, was cross-referenced against the institutional Cancer Genetics Program database, excluding patients with negative/unknown DICER1 gene testing. Sixteen patients were included (12 females; mean age at presentation: 4.2 years, range: 14 days to 17 years), with surveillance imaging encompassing the following modalities: chest X-ray and CT; abdominal, pelvic and neck US; and brain and whole-body MRI. Malignant lesions (68.8% of patients) included pleuropulmonary blastoma (5), pineoblastoma (3), ovarian Sertoli-Leydig cell tumor (1), embryonal rhabdomyosarcoma (1) and renal sarcoma (1); benign lesions (37.5% of patients) included thyroid cysts (2), thyroid nodules (2), cystic nephroma (2), renal cysts (1) and pineal cyst (1). A common lesional appearance observed across modalities and organs was defined as the ''cracked windshield'' sign. The spectrum of DICER1-related tumors and the young age at presentation suggest early surveillance of at-risk patients is critical, while minimizing exposure to ionizing radiation. (orig.)

  3. A Case Report of Gorlin-goltz Syndrome

    Directory of Open Access Journals (Sweden)

    Shima Nafarzadeh

    2016-04-01

    Full Text Available Nevoid basal cell carcinoma syndrome (Gorlin syndrome is an autosomal dominant inherited condition that exhibits high penetrance and variable expressivity. The syndrome is caused by mutations in patched (PTCH, a tumor suppressor gene that has been mapped to chromosome 9q22.3-q31. Gorlin-goltz syndrome (GGS is characterised by the presence of multiple odontogenic keratocysts in the jaws, basal cell carcinomas, palmar and plantar pits and intracranial calcifications. Here, we present a case of familial GGS, characterised by multiple odontogenic keratocysts, broad nasal ridge, hypertelorism, enlarged head circumference and dermoid cysts.

  4. Surgical treatment of tumor-induced osteomalacia: a retrospective review of 40 cases with extremity tumors.

    Science.gov (United States)

    Sun, Zhi-jian; Jin, Jin; Qiu, Gui-xing; Gao, Peng; Liu, Yong

    2015-02-26

    Tumor-induced osteomalacia (TIO) is a rare syndrome typically caused by mesenchymal tumors. It has been shown that complete tumor resection may be curative. However, to our knowledge, there has been no report of a large cohort to exam different surgical approaches. This study was aimed to assess outcomes of different surgical options of patients with tumor-induced osteomalacia at a single institution. Patients with extremity tumors treated in our hospital from January, 2004 to July, 2012 were identified. The minimum follow-up period was 12 months. Patient's demography, tumor location, preoperative preparation, type of surgeries were summarized, and clinical outcomes were recorded. Successful treatment was defined as significant symptom improvement, normal serum phosphorus and significant improvement or normalization of bone mineral density at the last follow-up. Differences between patients with soft tissue tumors and bone tumors were compared. There were 40 (24 male and 16 female) patients identified, with an average age of 44 years. The tumors were isolated in either soft tissue (25 patients) or bone (12 patients) and combined soft tissue and bone invasion was observed in 3 patients. For the primary surgery, tumor resection and tumor curettage were performed. After initial surgical treatment, six patients then received a second surgery. Four patients were found to have malignant tumors base on histopathology. With a minimum follow-up period of 12 months, 80% of patients (32/40) were treated successfully, including 50% of patients (2/4) with malignant tumors. Compared to patients with bone tumor, surgical results were better in patient with soft tissue tumor. Surgical treatment was an effective way for TIO. Other than tumor curettage surgery, tumor resection is the preferred options for these tumors.

  5. Soil pretreatment and fast cell lysis for direct polymerase chain reaction from forest soils for terminal restriction fragment length polymorphism analysis of fungal communities

    Directory of Open Access Journals (Sweden)

    Fei Cheng

    Full Text Available Abstract Humic substances in soil DNA samples can influence the assessment of microbial diversity and community composition. Using multiple steps during or after cell lysis adds expenses, is time-consuming, and causes DNA loss. A pretreatment of soil samples and a single step DNA extraction may improve experimental results. In order to optimize a protocol for obtaining high purity DNA from soil microbiota, five prewashing agents were compared in terms of their efficiency and effectiveness in removing soil contaminants. Residual contaminants were precipitated by adding 0.6 mL of 0.5 M CaCl2. Four cell lysis methods were applied to test their compatibility with the pretreatment (prewashing + Ca2+ flocculation and to ultimately identify the optimal cell lysis method for analyzing fungal communities in forest soils. The results showed that pretreatment with TNP + Triton X-100 + skim milk (100 mM Tris, 100 mM Na4P2O7, 1% polyvinylpyrrolidone, 100 mM NaCl, 0.05% Triton X-100, 4% skim milk, pH 10.0 removed most soil humic contaminants. When the pretreatment was combined with Ca2+ flocculation, the purity of all soil DNA samples was further improved. DNA samples obtained by the fast glass bead-beating method (MethodFGB had the highest purity. The resulting DNA was successfully used, without further purification steps, as a template for polymerase chain reaction targeting fungal internal transcribed spacer regions. The results obtained by terminal restriction fragment length polymorphism analysis indicated that the MethodFGB revealed greater fungal diversity and more distinctive community structure compared with the other methods tested. Our study provides a protocol for fungal cell lysis in soil, which is fast, convenient, and effective for analyzing fungal communities in forest soils.

  6. The Waardenburg Syndrome Type 4 Gene, SOX10, Is a Novel Tumor-associated Antigen Identified in a Patient with a Dramatic Response to Immunotherapy

    Science.gov (United States)

    Khong, Hung T.; Rosenberg, Steven A.

    2008-01-01

    In this study, we have identified, for the first time, the presence of de novo cellular immune reactivity against the transcription factor SOX10, using tumor-infiltrating lymphocytes obtained from a patient who experienced a dramatic clinical response to immunotherapy. SOX10 acts as a critical transactivator of tyrosinase-related protein-2 during melanoblast development and a potent transactivator of micropthalmia-associated transcription factor, which is considered to be a master gene that controls the development and postnatal survival of melanocytes. Mutations in SOX10 result in Waardenburg syndrome type 4. The overlapping epitopes AWISKPPGV and SAWISKPPGV, designated SOX10: 332–340 and SOX10: 331–340, respectively, were recognized by tumor-infiltrating lymphocyte clone M37 in an HLA-A2-restricted fashion. PMID:12036907

  7. A case of Meigs' syndrome with preceding pericardial effusion in advance of pleural effusion.

    Science.gov (United States)

    Okuda, Kenichi; Noguchi, Satoshi; Narumoto, Osamu; Ikemura, Masako; Yamauchi, Yasuhiro; Tanaka, Goh; Takai, Daiya; Fukayama, Masashi; Nagase, Takahide

    2016-05-10

    Meigs' syndrome is defined as the presence of a benign ovarian tumor with pleural effusion and ascites that resolve after removal of the tumor. The pathogenesis of the production of ascites and pleural effusion in this syndrome remains unknown. Aside from pleural effusion and ascites, pericardial effusion is rarely observed in Meigs' syndrome. Here, we report the first case of Meigs' syndrome with preceding pericardial effusion in advance of pleural effusion. An 84-year-old Japanese non-smoking woman with a history of lung cancer, treated by surgery, was admitted due to gradual worsening of dyspnea that had occurred over the previous month. She had asymptomatic and unchanging pericardial effusion and a pelvic mass, which had been detected 3 and 11 years previously, respectively. The patient was radiologically followed-up without the need for treatment. Two months before admission, the patient underwent a right upper lobectomy for localized lung adenocarcinoma and intraoperative pericardial fenestration confirmed that the pericardial effusion was not malignant. However, she began to experience dyspnea on exertion leading to admission. A chest, abdomen, and pelvis computed tomography scan confirmed the presence of right-sided pleural and pericardial effusion and ascites with a left ovarian mass. Repeated thoracentesis produced cultures that were negative for any microorganism and no malignant cells were detected in the pleural effusions. Pleural fluid accumulation persisted despite a tube thoracostomy for pleural effusion drainage. With a suspicion of Meigs' syndrome, the patient underwent surgical resection of the ovarian mass and histopathological examination of the resected mass showed ovarian fibroma. Pleural and pericardial effusion as well as ascites resolved after tumor resection, confirming a diagnosis of Meigs' syndrome. This clinical course suggests a strong association between pericardial effusion and ovarian fibroma, as well as pleural and peritoneal

  8. Phosphaturic mesenchymal tumor of the tibia with oncogenic osteomalacia in a teenager.

    Science.gov (United States)

    Farmakis, Shannon G; Siegel, Marilyn J

    2015-08-01

    Phosphaturic mesenchymal tumor is an uncommon cause of a paraneoplastic syndrome that can be associated with osteogenic osteomalacia. This tumor most commonly occurs in middle-aged men and women. We report a rare case of a phosphaturic mesenchymal tumor in a 16-year-old girl with multiple fractures as a result of severe osteoporosis. CT and MRI showed a mass arising from the tibia.

  9. E2F1-mediated human POMC expression in ectopic Cushing's syndrome.

    Science.gov (United States)

    Araki, Takako; Liu, Ning-Ai; Tone, Yukiko; Cuevas-Ramos, Daniel; Heltsley, Roy; Tone, Masahide; Melmed, Shlomo

    2016-11-01

    Cushing's syndrome is caused by excessive adrenocorticotropic hormone (ACTH) secretion derived from pituitary corticotroph tumors (Cushing disease) or from non-pituitary tumors (ectopic Cushing's syndrome). Hypercortisolemic features of ectopic Cushing's syndrome are severe, and no definitive treatment for paraneoplastic ACTH excess is available. We aimed to identify subcellular therapeutic targets by elucidating transcriptional regulation of the human ACTH precursor POMC (proopiomelanocortin) and ACTH production in non-pituitary tumor cells and in cell lines derived from patients with ectopic Cushing's syndrome. We show that ectopic hPOMC transcription proceeds independently of pituitary-specific Tpit/Pitx1 and demonstrate a novel E2F1-mediated transcriptional mechanism regulating hPOMC We identify an E2F1 cluster binding to the proximal hPOMC promoter region (-42 to +68), with DNA-binding activity determined by the phosphorylation at Ser-337. hPOMC mRNA expression in cancer cells was upregulated (up to 40-fold) by the co-expression of E2F1 and its heterodimer partner DP1. Direct and indirect inhibitors of E2F1 activity suppressed hPOMC gene expression and ACTH by modifying E2F1 DNA-binding activity in ectopic Cushing's cell lines and primary tumor cells, and also suppressed paraneoplastic ACTH and cortisol levels in xenografted mice. E2F1-mediated hPOMC transcription is a potential target for suppressing ACTH production in ectopic Cushing's syndrome. © 2016 Society for Endocrinology.

  10. Coenzyme Q10 and pro-inflammatory markers in children with Down syndrome: clinical and biochemical aspects.

    Science.gov (United States)

    Zaki, Moushira E; El-Bassyouni, Hala T; Tosson, Angie M S; Youness, Eman; Hussein, Jihan

    Evidence of oxidative stress was reported in individuals with Down syndrome. There is a growing interest in the contribution of the immune system in Down syndrome. The aim of this study is to evaluate the coenzyme Q10 and selected pro-inflammatory markers such as interleukin 6 and tumor necrosis factor α in children with Down syndrome. Eighty-six children (5-8 years of age) were enrolled in this case-control study from two public institutions. At the time of sampling, the patients and controls suffered from no acute or chronic illnesses and received no therapies or supplements. The levels of interleukin 6, tumor necrosis factor α, coenzyme Q10, fasting blood glucose, and intelligence quotient were measured. Forty-three young Down syndrome children and forty-three controls were included over a period of eight months (January-August 2014). Compared with the control group, the Down syndrome patients showed significant increase in interleukin 6 and tumor necrosis factor α (p=0.002), while coenzyme Q10 was significantly decreased (p=0.002). Also, body mass index and fasting blood glucose were significantly increased in patients. There was a significantly positive correlation between coenzyme Q10 and intelligence quotient levels, as well as between interleukin 6 and tumor necrosis factor α. Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  11. Coenzyme Q10 and pro-inflammatory markers in children with Down syndrome: clinical and biochemical aspects

    Directory of Open Access Journals (Sweden)

    Moushira E. Zaki

    Full Text Available Abstract: Objective: Evidence of oxidative stress was reported in individuals with Down syndrome. There is a growing interest in the contribution of the immune system in Down syndrome. The aim of this study is to evaluate the coenzyme Q10 and selected pro-inflammatory markers such as interleukin 6 and tumor necrosis factor α in children with Down syndrome. Methods: Eighty-six children (5-8 years of age were enrolled in this case-control study from two public institutions. At the time of sampling, the patients and controls suffered from no acute or chronic illnesses and received no therapies or supplements. The levels of interleukin 6, tumor necrosis factor α, coenzyme Q10, fasting blood glucose, and intelligence quotient were measured. Results: Forty-three young Down syndrome children and forty-three controls were included over a period of eight months (January-August 2014. Compared with the control group, the Down syndrome patients showed significant increase in interleukin 6 and tumor necrosis factor α (p = 0.002, while coenzyme Q10 was significantly decreased (p = 0.002. Also, body mass index and fasting blood glucose were significantly increased in patients. There was a significantly positive correlation between coenzyme Q10 and intelligence quotient levels, as well as between interleukin 6 and tumor necrosis factor α. Conclusion: Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms.

  12. Ileocecal Adenocarcinoma and Ureteral Transitional Cell Carcinoma with Multiple Sebaceous Tumors and Keratoacanthomas in a Case of Muir-Torre Syndrome

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    Michael C. Lynch

    2010-01-01

    Full Text Available Cutaneous neoplasms including sebaceous tumors, keratoacanthomas, and basal cell carcinomas with sebaceous differentiation can be markers of internal malignancy associated with the Muir-Torre Syndrome (MTS. We report a 56-year-old man with a diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC and ureteral transitional cell carcinoma who subsequently developed two sebaceous gland neoplasms and several keratoacanthomas, leading to the diagnosis of MTS. Our case highlights the clinical advantages of immunohistochemistry (IHC in identifying mutations in the mismatch repair (MMR genes responsible for both HNPCC and MTS. The importance of continued clinical suspicion in the dermatological assessment of patients with sebaceous neoplasms is emphasized.

  13. Paragangliomas and paraganglioma syndromes

    Science.gov (United States)

    Boedeker, Carsten Christof

    2012-01-01

    Paragangliomas are rare tumors of neural crest origin. They are benign in the majority of cases and are characterized by a strong vascularisation. In the head and neck region they most commonly occur as carotid body tumors. Jugulotympanic and especially vagal paragangliomas are seen less frequently. Complete surgical resection represents the only curative treatment option even though resection of locally advanced tumors regularly results in lesions of the lower cranial nerves and major vessels. Appoximately 30% of all head and neck paragangliomas (HNPs) are hereditary and associated with different tumor syndromes. The paraganglioma syndromes 1, 3 and 4 (PGL 1, 3 and 4) make up the majority of those familial cases. PGL 1 is associated with mutations of the succinate dehydrogenase subunit D (SDHD) gene, PGL 3 is caused by SDHC and PGL 4 by SDHB gene mutations. Multiple HNPs and the occurance of HNPs together with pheochromocytomas are seen in SDHD as well as SDHB mutation carriers. In patients with SDHB mutations the risk for the development of malignant paraganglial tumors is significantly higher compared to SDHC and SDHD patients as well as patients with sporadic tumors. SDHC mutation carriers almost exclusively present with benign HNP that are unifocal in the majority of cases. The role of transmission is autosomal dominant for all three symptoms. Interestingly, there is a “parent-of-origin-dependent-inheritance” in subjects with SDHD gene mutations. This means that the disease phenotype may only become present if the mutation is inherited through the paternal line. We recommend screening for mutations of the genes SDHB, SDHC and SDHD in patients with HNPs. Certain clinical parameters can help to set up the order in which the three genes should be tested. PMID:22558053

  14. Association between Interleukin-10-1082 G/A and Tumor Necrosis Factor-α 308 G/A Gene Polymorphisms and Respiratory Distress Syndrome in Iranian Preterm Infants

    OpenAIRE

    Khoshdel, Abolfazl; Kheiri, Soleiman; Omidvari, Peyman; Moradi, Fahimeh; Hamidi, Majid; Teimori, Hossein

    2017-01-01

    Cytokine polymorphisms may contribute to the prevalence of respiratory distress syndrome. The present study was done to investigate the frequency of interleukin- (IL-) 10 and tumor necrosis factor- (TNF-) ? gene polymorphisms and their association with the risk of RDS in preterm infants. One-hundred and nineteen patients with RDS and 119 healthy preterm infants were enrolled. PCR restriction fragment length polymorphism was used to determine the frequency of IL-10 and TNF-? genotypes at -1082...

  15. Urological cancer related to familial syndromes

    Directory of Open Access Journals (Sweden)

    Walter Henriques da Costa

    Full Text Available ABSTRACT Cancer related to hereditary syndromes corresponds to approximately 5-10% of all tumors. Among those from the genitourinary system, many tumors had been identified to be related to genetic syndromes in the last years with the advent of new molecular genetic tests. New entities were described or better characterized, especially in kidney cancer such as hereditary leiomyomatosis renal cell carcinoma (HLRCC, succinate dehydrogenase kidney cancer (SDH-RCC, and more recently BAP1 germline mutation related RCC. Among tumors from the bladder or renal pelvis, some studies had reinforced the role of germline mutations in mismatch repair (MMR genes, especially in young patients. In prostate adenocarcinoma, besides mutations in BRCA1 and BRCA2 genes that are known to increase the incidence of high-risk cancer in young patients, new studies have shown mutation in other gene such as HOXB13 and also polymorphisms in MYC, MSMB, KLK2 and KLK3 that can be related to hereditary prostate cancer. Finally, tumors from testis that showed an increased in 8 - 10-fold in siblings and 4 - 6-fold in sons of germ cell tumors (TGCT patients, have been related to alteration in X chromosome. Also genome wide association studies GWAS pointed new genes that can also be related to increase of this susceptibility.

  16. Efficacy of Surgical Therapy for Carotid Body Tumors

    Institute of Scientific and Technical Information of China (English)

    Li-shan Lian; Chang-wei Liu; Heng Guan; Yue-hong Zheng; Xing-ming Chen; Yong-jun Li

    2011-01-01

    Objective To evaluate the efficacy of surgical therapy for carotid body tumors.Methods A retrospective analysis was conducted,covering the diagnosis,surgical procedure,post-operative complications,and prognosis of 120 cases of carotid body tumors in Peking Union Medical College Hospital from 1949 to May,2011.Results Surgical excision was successfully performed in 111 cases with 117 tumors.In all those cases,50 underwent simple tumor resection,42 underwent resection of tumors and ligation of the external carotid arteries,7 underwent co-resection of tumors and common carotid arteries,internal carotid arteries,as well as external arteries without vascular reconstruction,and the other 12 cases experienced tumor resection and vascular reconstruction as internal carotid arteries were involved.After operation,3 cases developed cerebral infarction,30 cases showed cranial nerve palsy,including 15 cases of hypoglossal nerve damage,10 cases of vagus paralysis,and 5 cases of Horner's syndrome.Conclusion It is essential to make a proper surgical strategy,which can reduce postoperative complications.

  17. Fibrogenesis and carcinoid tumor - a case report

    Directory of Open Access Journals (Sweden)

    Eduardo Fonseca Alves Filho

    2012-06-01

    Full Text Available Carcinoid tumors are rare. They may appear in the entire gastrointestinal and respiratory tracts, with single or multiple occurrences. Prognosis is dependent on the size and location. Symptoms may appear in carcinoid syndrome, related to active substances, especially serotonin. One important aspect associated with these tumors and usually ignored is fibrogenesis. This is a case report of a patient with carcinoid tumor of the terminal ileum, treated by laparoscopy, associated with fat and fibrosis infiltration.Tumores carcinoides são pouco frequentes, podem surgir em todo o trato gastrointestinal e respiratório, podem ser únicos ou múltiplos. O prognóstico depende do tamanho e da localização do tumor. Podem ocorrer sintomas relacionados à síndrome carcinoide, decorrente da produção de substâncias ativas, em especial serotonina. Um aspecto comumente ignorado associado a estes tumores é a estimulação da fibrogênese. Relatamos um caso de tumor carcinoide de íleo, tratado por videolaparoscopia, associado à infiltração fibroadiposa.

  18. Using 18F FDG PET/CT to Detect an occult Mesenchymal Tumor Causing Oncogenic Osteomalacia

    International Nuclear Information System (INIS)

    Seo, Hyo Jung; Choi, Yun Jung; Kim, Hyun Jeong; Jeong, Yong Hyu; Cho, Arthur; Lee, Jae Hoon; Yun, Mijin; Lee, Jong Doo; Kang, Won Jun

    2011-01-01

    Oncogenic osteomalacia is a rare paraneoplastic syndrome characterized by renal phosphate excretion, hypophosphatemia, and osteomalacia. This syndrome is often caused by tumors of mesenchymal origin. Patients with oncogenic osteomalacia have abnormal bone mineralization, resulting in a high frequency of fractures. Tumor resection is the treatment of choice, as it will often correct the metabolic imbalance. Although oncogenic osteomalacia is a potentially curable disease, diagnosis is difficult and often delayed because of the small size and sporadic location of the tumor. Bone scintigraphy and radiography best characterize osteoma lacia; magnetic resonance imaging findings are nonspecific. Here, we report a case of oncogenic osteomalacia secondary to a phosphaturic mesenchymal tumor that was successfully detected by 18F fluorodeoxyglucose positron emission tomography/computed tomography ( 18F FDG PET/CT). This case illustrates the advantages of 18F FDG PET/CT in detecting the occult mesenchymal tumor that causes oncogenic osteomalacia.

  19. Colorectal cancer: genetic abnormalities, tumor progression, tumor heterogeneity, clonal evolution and tumor-initiating cells.

    Science.gov (United States)

    Testa, Ugo; Pelosi, Elvira; Castelli, Germana

    2018-04-13

    Colon cancer is the third most common cancer worldwide. Most colorectal cancer occurrences are sporadic, not related to genetic predisposition or family history; however, 20-30% of patients with colorectal cancer have a family history of colorectal cancer and 5% of these tumors arise in the setting of a Mendelian inheritance syndrome. In many patients, the development of a colorectal cancer is preceded by a benign neoplastic lesion: either an adenomatous polyp or a serrated polyp. Studies carried out in the last years have characterized the main molecular alterations occurring in colorectal cancers, showing that the tumor of each patient displays from two to eight driver mutations. The ensemble of molecular studies, including gene expression studies, has led to two proposed classifications of colorectal cancers, with the identification of four/five non-overlapping groups. The homeostasis of the rapidly renewing intestinal epithelium is ensured by few stem cells present at the level of the base of intestinal crypts. Various experimental evidence suggests that colorectal cancers may derive from the malignant transformation of intestinal stem cells or of intestinal cells that acquire stem cell properties following malignant transformation. Colon cancer stem cells seem to be involved in tumor chemoresistance, radioresistance and relapse.

  20. Ovarian Fibroma with Meigs Syndrome associated with Elevated CA125 - A Rare Case

    Directory of Open Access Journals (Sweden)

    Prasad. K. Shetty

    2010-07-01

    Full Text Available Postmenopausal women with solid adnexal masses, ascites and pleural effusion with elevated CA 125 are highly suggestive for malignant ovarian tumor. However in literature 28 cases Meigs syndrome (Benign ovarian tumor, ascites and right pleural effusion with raised CA 125 have been reported. We report a case of Meigs syndrome caused by right ovarian fibroma with elevated serum CA125 level in a postmenopausal woman

  1. Axillary basal cell carcinoma in patients with Goltz-Gorlin syndrome: report of basal cell carcinoma in both axilla of a woman with basal cell nevus syndrome and literature review.

    Science.gov (United States)

    Cohen, Philip R

    2014-08-17

    Basal cell carcinoma of the axilla, an area that is not usually exposed to the sun, is rare. Individuals with basal cell nevus syndrome, a disorder associated with a mutation in the patch 1 (PTCH1) gene, develop numerous basal cell carcinomas. To describe a woman with basal cell nevus syndrome who developed a pigmented basal cell carcinoma in each of her axilla and to review the features of axillary basal cell carcinoma patients with Goltz-Gorlin syndrome. Pubmed was used to search the following terms: axillary basal cell carcinoma and basal cell nevus syndrome. The papers and their citations were evaluated. Basal cell nevus syndrome patients with basal cell carcinoma of the axilla were observed in two women; this represents 2.5% (2 of 79) of the patients with axillary basal cell carcinoma. Both women had pigmented tumors that were histologically nonaggressive. The cancers did not recur after curettage or excision. Basal cell carcinoma of the axilla has only been described in 79 individuals; two of the patients were women with pigmented tumors who had basal cell nevus syndrome. Similar to other patients with axillary basal cell carcinoma, the tumors were histologically nonaggressive and did not recur following treatment. Whether PTCH1 gene mutation predisposes basal cell nevus patients to develop axillary basal cell carcinomas remains to be determined.

  2. Locally advanced transverse colon cancer with Trousseau’s syndrome

    Directory of Open Access Journals (Sweden)

    V. A. Aliyev

    2012-01-01

    Full Text Available Migratory venous thrombosis is a manifestation of the rare paraneoplastic syndrome in patients with malignant neoplasms. The paper describes successful surgical treatment in a young patient with a colon tumor associated with Trousseau’s syndrome. The latter manifesting itself as ischemia forced urgent surgeons to amputate the lower third of the left leg. Locally advanced transverse colon cancer spreading to the great vessels was subsequently diagnosed. All paraneoplastic manifestations disappeared after tumor removal. The patient was professionally given surgical, anesthesiological, and resuscitative aids that not only improved his quality of life, but also gave the chance to prolong it.

  3. Development and implementation of tPA clot lysis activity assay using ACL TOP™ hemeostasis testing system in QC laboratories

    Directory of Open Access Journals (Sweden)

    Lichun Huang

    2017-12-01

    Full Text Available This report describes the design, development, validation and long-term performance of tPA clot lysis activity assay using Advanced Chemistry Line Total Operational Performance (ACL TOP™ Homeostasis Testing System. The results of the study demonstrated robust and stable performance of the analytical method. The accuracy of the assay, expressed by percent recovery is 98–99%. The intermediate precision and repeatability precision, expressed as Relative Standard Deviation (RSD, was 3% and less than 2% respectively. The validated range is from 70% to 130% of the target potency of 5.8 × 105 IU/mg. The linearity of this range, expressed in correlation coefficient, is 0.997. After the assay is transferred to a QC laboratory, the assay retained high accuracy and precision with a success rate of >99%. Keywords: Potency assay, Clot lysis, Comparability, Automation

  4. Sciatic nerve tumor and tumor-like lesions - uncommon pathologies

    Energy Technology Data Exchange (ETDEWEB)

    Wadhwa, Vibhor; Thakkar, Rashmi S.; Carrino, John A.; Chhabra, Avneesh [Johns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Maragakis, Nicholas; Hoeke, Ahmet; Sumner, Charlotte J.; Lloyd, Thomas E. [Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD (United States); Belzberg, Allan J. [Johns Hopkins University School of Medicine, Department of Neurosurgery, Baltimore, MD (United States)

    2012-07-15

    Sciatic nerve mass-like enlargement caused by peripheral nerve sheath tumors or neurocutaneous syndromes such as neurofibromatosis or schwannomatosis has been widely reported. Other causes of enlargement, such as from perineuroma, fibromatosis, neurolymphoma, amyloidosis, endometriosis, intraneural ganglion cyst, Charcot-Marie-Tooth disease, and chronic inflammatory demyelinating polyneuropathy are relatively rare. High-resolution magnetic resonance imaging (MRI) is an excellent non-invasive tool for the evaluation of such lesions. In this article, the authors discuss normal anatomy of the sciatic nerve and MRI findings of the above-mentioned lesions. (orig.)

  5. Rubinstein-Taybi syndrome predisposing to non-WNT, non-SHH, group 3 medulloblastoma.

    Science.gov (United States)

    Bourdeaut, Franck; Miquel, Catherine; Richer, Wilfrid; Grill, Jacques; Zerah, Michel; Grison, Camille; Pierron, Gaelle; Amiel, Jeanne; Krucker, Clementine; Radvanyi, Francois; Brugieres, Laurence; Delattre, Olivier

    2014-02-01

    Medulloblastomas (MB) are classified in four subgroups: the well defined WNT and Sonic Hedgehog (SHH) subgroups, and the less defined groups 3 and 4. They occasionally occur in the context of a cancer predisposition syndrome. While germline APC mutations predispose to WNT MB, germline mutations in SUFU, PTCH1, and TP53 predispose to SHH tumors. We report on a child with a Rubinstein-Taybi syndrome (RTS) due to a germline deletion in CREBBP, who developed a MB. Biological profilings demonstrate that this tumor belongs to the group 3. RTS may therefore be the first predisposition syndrome identified for non-WNT/non-SHH MB. © 2013 Wiley Periodicals, Inc.

  6. Paraneoplastic neurological syndromes with anti-hu antibodies : Pathogenesis and treatment

    NARCIS (Netherlands)

    A.H.C. de Jongste (Arjen)

    2015-01-01

    markdownabstract__Abstract__ Paraneoplastic neurological syndromes (PNS) are remote effects of cancer that are neither caused by invasion of the tumor or its metastasis, nor by infection, ischemia, metabolic and nutritional deficits, surgery or other forms of tumor treatment.1 PNS cause severe

  7. Tumor-induced osteomalacia

    Science.gov (United States)

    Chong, William H; Molinolo, Alfredo A; Chen, Clara C; Collins, Michael T

    2012-01-01

    Tumor-induced osteomalacia (TIO) is a rare and fascinating paraneoplastic syndrome in which patients present with bone pain, fractures, and muscle weakness. The cause is high blood levels of the recently identified phosphate and vitamin D-regulating hormone, fibroblast growth factor 23 (FGF23). In TIO, FGF23 is secreted by mesenchymal tumors that are usually benign, but are typically very small and difficult to locate. FGF23 acts primarily at the renal tubule and impairs phosphate reabsorption and 1α-hydroxylation of 25-hydroxyvitamin D, leading to hypophosphatemia and low levels of 1,25-dihydroxy vitamin D. A step-wise approach utilizing functional imaging (F-18 fluorodeoxyglucose positron emission tomography and octreotide scintigraphy) followed by anatomical imaging (computed tomography and/or magnetic resonance imaging), and, if needed, selective venous sampling with measurement of FGF23 is usually successful in locating the tumors. For tumors that cannot be located, medical treatment with phosphate supplements and active vitamin D (calcitriol or alphacalcidiol) is usually successful; however, the medical regimen can be cumbersome and associated with complications. This review summarizes the current understanding of the pathophysiology of the disease and provides guidance in evaluating and treating these patients. Novel imaging modalities and medical treatments, which hold promise for the future, are also reviewed. PMID:21490240

  8. Malignant transformation of a chiasmatic pilocytic astrocytoma in a patient with diencephalic syndrome

    International Nuclear Information System (INIS)

    Wal, Ester P.J. van der; Edwards-Brown, Mary; Azzarelli, Biagio

    2003-01-01

    Chiasmatic gliomas with metastatic spread are rare in children and are usually associated with diencephalic syndrome. They are mostly pilocytic astrocytomas and their transformation to high-grade astrocytomas has never previously been reported in the pediatric population. We report leptomeningeal spread of a chiasmatic pilocytic astrocytoma in a child presenting with diencephalic syndrome. He was treated with chemotherapy and radiation. The tumor recurred with transformation into a high-grade astrocytoma. Radiation therapy may have played a role in transformation of the tumor, but more research is needed to further clarify the biological behavior of this tumor. (orig.)

  9. Cushing's Syndrome From Pituitary Microadenoma and Pulmonary Nodules.

    Science.gov (United States)

    Tating, Dan Louie Renz P; Montevirgen, Natasha Denise S; Cajucom, Loyda

    2016-03-01

    Cushing's syndrome is a state of cortisol excess, possibly from a tumor in the pituitary gland, the adrenal gland, or an ectopic nonpituitary ACTH-secreting source. The first form, pituitary in origin, was originally described by Harvey Cushing, MD, and was labeled as Cushing's disease. Long-term therapy with glucocorticoids also can lead to iatrogenic Cushing's syndrome.

  10. Upper urinary tract carcinoma in Lynch syndrome cases.

    Science.gov (United States)

    Crockett, David G; Wagner, David G; Holmäng, Sten; Johansson, Sonny L; Lynch, Henry T

    2011-05-01

    Patients with Lynch syndrome are much more likely to have generally rare upper urinary tract urothelial carcinoma but not bladder urothelial carcinoma. While the risk has been quantified, to our knowledge there is no description of how this population of patients with Lynch syndrome and upper urinary tract cancer differs from the general population with upper urinary tract cancer. We obtained retrospective data on a cohort of patients with Lynch syndrome from the Hereditary Cancer Center in Omaha, Nebraska and compared the data to those on a control general population from western Sweden. These data were supplemented by a new survey about exposure to known risk factors. Of the patients with Lynch syndrome 91% had mutations in MSH2 rather than in MSH1 and 79% showed upper tract urothelial carcinoma a mean of 15.85 years after prior Lynch syndrome-type cancer. Median age at diagnosis was 62 years vs 70 in the general population (p Lynch syndrome 51% had urothelial carcinoma in the ureter while it occurred in the renal pelvis in 65% of the general population (p = 0.0013). Similar numbers of high grade tumors were found in the Lynch syndrome and general populations (88% and 74%, respectively, p = 0.1108). Upper urinary tract tumors develop at a younger age and are more likely to be in the ureter with an almost equal gender ratio in patients with Lynch syndrome. It has high grade potential similar to that in the general population. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  11. A Review of Von Hippel-Lindau Syndrome

    Directory of Open Access Journals (Sweden)

    Neha Varshney

    2017-08-01

    Full Text Available Von Hippel-Lindau syndrome (VHL is a familial neoplastic condition seen in approximately 1 in 36,000 live births. It is caused by germline mutations of the tumor suppressor gene VHL, located on the short arm of chromosome 3. While the majority of the affected individuals have a positive family history, up to 20% of cases arise from de novo mutations. VHL syndrome is characterized by the presence of benign and malignant tumors affecting the central nervous system, kidneys, adrenals, pancreas, and reproductive organs. Common manifestations include hemangioblastomas of the brain, spinal cord, and retina; pheochromocytoma and paraganglioma; renal cell carcinoma; pancreatic cysts and neuroendocrine tumors; and endolymphatic sac tumors. Diagnosis of VHL is prompted by clinical suspicion and confirmed by molecular testing. Management of VHL patients is complex and multidisciplinary. Routine genetic testing and surveillance using various diagnostic techniques are used to help monitor disease progression and implement treatment options. Despite recent advances in clinical diagnosis and management, life expectancy for VHL patients remains low at 40–52 years. This article provides an overview of the major clinical, histological, and radiological findings, as well as treatment modalities.

  12. Identification of MSH2 inversion of exons 1-7 in clinical evaluation of families with suspected Lynch syndrome.

    Science.gov (United States)

    Mork, Maureen E; Rodriguez, Andrea; Taggart, Melissa W; Rodriguez-Bigas, Miguel A; Lynch, Patrick M; Bannon, Sarah A; You, Y Nancy; Vilar, Eduardo

    2017-07-01

    Traditional germline sequencing and deletion/duplication analysis does not detect Lynch syndrome-causing mutations in all individuals whose colorectal or endometrial tumors demonstrate mismatch repair (MMR) deficiency. Unique inversions and other rearrangements of the MMR genes have been reported in families with Lynch syndrome. In 2014, a recurrent inversion of MSH2 exons 1-7 was identified in five families suspected to have Lynch syndrome. We aimed to describe our clinical experience in identifying families with this specific inversion. Four probands whose Lynch syndrome-associated tumors demonstrated absence of MSH2/MSH6 staining and who had negative MMR germline testing were evaluated for the MSH2 inversion of exons 1-7, offered during initial genetic workup or upon routine clinical follow-up. All four probands tested positive for the MSH2 inversion. Proband cancer diagnoses included colon and endometrial adenocarcinoma and sebaceous adenoma. A variety of Lynch syndrome-associated cancers were reported in the family histories, although only one family met Amsterdam II criteria. Thirteen at-risk relatives underwent predictive testing. MSH2 inversion of exons 1-7 was found in four probands previously suspected to have Lynch syndrome based on family history and tumor testing. This testing should be offered routinely to patients with tumors demonstrating loss of MSH2/MSH6 staining.

  13. Stabilizing additives added during cell lysis aid in the solubilization of recombinant proteins.

    Directory of Open Access Journals (Sweden)

    David J Leibly

    Full Text Available Insoluble recombinant proteins are a major issue for both structural genomics and enzymology research. Greater than 30% of recombinant proteins expressed in Escherichia coli (E. coli appear to be insoluble. The prevailing view is that insolubly expressed proteins cannot be easily solubilized, and are usually sequestered into inclusion bodies. However, we hypothesize that small molecules added during the cell lysis stage can yield soluble protein from insoluble protein previously screened without additives or ligands. We present a novel screening method that utilized 144 additive conditions to increase the solubility of recombinant proteins expressed in E. coli. These selected additives are natural ligands, detergents, salts, buffers, and chemicals that have been shown to increase the stability of proteins in vivo. We present the methods used for this additive solubility screen and detailed results for 41 potential drug target recombinant proteins from infectious organisms. Increased solubility was observed for 80% of the recombinant proteins during the primary and secondary screening of lysis with the additives; that is 33 of 41 target proteins had increased solubility compared with no additive controls. Eleven additives (trehalose, glycine betaine, mannitol, L-Arginine, potassium citrate, CuCl(2, proline, xylitol, NDSB 201, CTAB and K(2PO(4 solubilized more than one of the 41 proteins; these additives can be easily screened to increase protein solubility. Large-scale purifications were attempted for 15 of the proteins using the additives identified and eight (40% were prepared for crystallization trials during the first purification attempt. Thus, this protocol allowed us to recover about a third of seemingly insoluble proteins for crystallography and structure determination. If recombinant proteins are required in smaller quantities or less purity, the final success rate may be even higher.

  14. Prediction of recurrent venous thromboembolism by clot lysis time: a prospective cohort study.

    Science.gov (United States)

    Traby, Ludwig; Kollars, Marietta; Eischer, Lisbeth; Eichinger, Sabine; Kyrle, Paul A

    2012-01-01

    Venous thromboembolism (VTE) is a chronic disease, which tends to recur. Whether an abnormal fibrinolytic system is associated with an increased risk of VTE is unclear. We assessed the relationship between fibrinolytic capacity (reflected by clot lysis time [CLT]) and risk of recurrent VTE. We followed 704 patients (378 women; mean age 48 yrs) with a first unprovoked VTE for an average of 46 months after anticoagulation withdrawal. Patients with natural coagulation inhibitor deficiency, lupus anticoagulant, cancer, homozygosity for factor V Leiden or prothrombin mutation, or requirement for indefinite anticoagulation were excluded. Study endpoint was symptomatic recurrent VTE. For measurement of CLT, a tissue factor-induced clot was lysed by adding tissue-type plasminogen activator. Time between clot formation and lysis was determined by measuring the turbidity. 135 (19%) patients had recurrent VTE. For each increase in CLT of 10 minutes, the crude relative risk (RR) of recurrence was 1.13 (95% CI 1.02-1.25; p = 0.02) and was 1.08 (95% CI 0.98-1.20; p = 0.13) after adjustment for age and sex. For women only, the adjusted RR was 1.14 (95% CI, 0.91-1.42, p = 0.22) for each increase in CLT of 10 minutes. CLT values in the 4(th) quartile of the female patient population, as compared to values in the 1(st) quartile, conferred a risk of recurrence of 3.28 (95% CI, 1.07-10.05; p = 0.04). No association between CLT and recurrence risk was found in men. Hypofibrinolysis as assessed by CLT confers a moderate increase in the risk of recurrent VTE. A weak association between CLT and risk of recurrence was found in women only.

  15. Prediction of recurrent venous thromboembolism by clot lysis time: a prospective cohort study.

    Directory of Open Access Journals (Sweden)

    Ludwig Traby

    Full Text Available Venous thromboembolism (VTE is a chronic disease, which tends to recur. Whether an abnormal fibrinolytic system is associated with an increased risk of VTE is unclear. We assessed the relationship between fibrinolytic capacity (reflected by clot lysis time [CLT] and risk of recurrent VTE. We followed 704 patients (378 women; mean age 48 yrs with a first unprovoked VTE for an average of 46 months after anticoagulation withdrawal. Patients with natural coagulation inhibitor deficiency, lupus anticoagulant, cancer, homozygosity for factor V Leiden or prothrombin mutation, or requirement for indefinite anticoagulation were excluded. Study endpoint was symptomatic recurrent VTE. For measurement of CLT, a tissue factor-induced clot was lysed by adding tissue-type plasminogen activator. Time between clot formation and lysis was determined by measuring the turbidity. 135 (19% patients had recurrent VTE. For each increase in CLT of 10 minutes, the crude relative risk (RR of recurrence was 1.13 (95% CI 1.02-1.25; p = 0.02 and was 1.08 (95% CI 0.98-1.20; p = 0.13 after adjustment for age and sex. For women only, the adjusted RR was 1.14 (95% CI, 0.91-1.42, p = 0.22 for each increase in CLT of 10 minutes. CLT values in the 4(th quartile of the female patient population, as compared to values in the 1(st quartile, conferred a risk of recurrence of 3.28 (95% CI, 1.07-10.05; p = 0.04. No association between CLT and recurrence risk was found in men. Hypofibrinolysis as assessed by CLT confers a moderate increase in the risk of recurrent VTE. A weak association between CLT and risk of recurrence was found in women only.

  16. [Dropped head syndrome as first manifestation of primary hyperparathyroid myopathy].

    Science.gov (United States)

    Ota, Kiyobumi; Koseki, Sayo; Ikegami, Kenji; Onishi, Iichiroh; Tomimitsu, Hiyoryuki; Shintani, Shuzo

    2018-03-28

    75 years old woman presented with 6-month history of progressive dropped head syndrome. Neurological examination revealed moderate weakness of flexor and extensor of neck and mild weakness of proximal appendicular muscles with normal deep tendon reflexes. The needle electromyography showed short duration and low amplitude motor unit potential. No fibrillation potentials or positive sharp waves were seen. Biopsy of deltoid muscle was normal. Laboratory studies showed elevated levels of serum calcium (11.8 mg/dl, upper limit of normal 10.1) and intact parathyroid hormone (104 pg/ml, upper limit of normal 65), and decreased level of serum phosphorus (2.3 mg/dl, lower limit of normal 2.7). Ultrasonography and enhanced computed tomography revealed a parathyroid tumor. The tumor was removed surgically. Pathological examination proved tumor to be parathyroid adenoma. Dropped head and weakness of muscles were dramatically improved within a week after the operation. Although hyperparathyroidism is a rare cause of dropped head syndrome, neurologists must recognize hyperparathyroidism as a treatable cause of dropped head syndrome.

  17. Multiple keratocysts of the mandible in association with Gorlin-Goltz syndrome: A rare case report.

    Science.gov (United States)

    Kulkarni, Gayithri Harish; Khaji, Shahanavaj I; Metkari, Suryakant; Kulkarni, Harish S; Kulkarni, Reshma

    2014-07-01

    Nevoid basal cell carcinoma syndrome is a syndrome with wide variety of manifestations ranging from oral lesions to skeletal deformities. It calls for due responsibility of maxillofacial surgeon to diagnose the syndrome because very often they are the first health professionals to see the patient for the treatment of keratocystic odontogenic tumor. Keratocystic odontogenic tumor has been the topic of numerous investigators, is known for its potentially aggressive behavior, significant rate of recurrences. KCOT often occurs as a solitary lesion, in some instances multiple keratocysts may occur in association with a syndrome called Gorlin-Goltz syndrome (nevoid BCC, jaw cyst bifid rib basal cell nevus syndrome). Here, we present a case of multiple keratocysts in the mandible in association with skeletal, ocular, cutaneous anomalies in the given clinical scenario, which has profound relevance in the clinical dental practice.

  18. Multiple keratocysts of the mandible in association with Gorlin-Goltz syndrome: A rare case report

    Directory of Open Access Journals (Sweden)

    Gayithri Harish Kulkarni

    2014-01-01

    Full Text Available Nevoid basal cell carcinoma syndrome is a syndrome with wide variety of manifestations ranging from oral lesions to skeletal deformities. It calls for due responsibility of maxillofacial surgeon to diagnose the syndrome because very often they are the first health professionals to see the patient for the treatment of keratocystic odontogenic tumor. Keratocystic odontogenic tumor has been the topic of numerous investigators, is known for its potentially aggressive behavior, significant rate of recurrences. KCOT often occurs as a solitary lesion, in some instances multiple keratocysts may occur in association with a syndrome called Gorlin-Goltz syndrome (nevoid BCC, jaw cyst bifid rib basal cell nevus syndrome. Here, we present a case of multiple keratocysts in the mandible in association with skeletal, ocular, cutaneous anomalies in the given clinical scenario, which has profound relevance in the clinical dental practice.

  19. Carcinoid tumors: Challenges and considerations during anesthetic management

    Directory of Open Access Journals (Sweden)

    Sukhminder Jit Singh Bajwa

    2015-01-01

    Full Text Available Carcinoid tumors are rare, slow-growing neoplasms of neuroendocrine tissues from enterochromaffin or kulchitsky cells, which have the potential to metastasize. The mediators released from these tumors when bypass the hepatic metabolism, can lead to the possible development of carcinoid syndrome. This is a life-threatening complication, which can lead to profound hemodynamic instability, especially in a peri-operative period, when the patient is exposed to various types of noxious stimuli. Off late, use of octreotide, a synthetic analog of somatostatin, has significantly reduced the peri-operative morbidity and mortality. The current review discusses the various anesthetic challenges and considerations during peri-operative management of carcinoid tumors.

  20. Prolactin-secreting adenoma as part of the multiple endocrine neoplasia--type I (MEN-I) syndrome.

    Science.gov (United States)

    Levine, J H; Sagel, J; Rosebrock, G; Gonzalez, J J; Nair, R; Rawe, S; Powers, J M

    1979-06-01

    Two patients presented with the galactorrhea-amenorrhea syndrome. One patient had previously had parathyroid hyperplasia and the other an insulinoma. Preoperative evaluation of each patient revealed hyperprolactinemia and radiological evidence of an abnormal sella turcica. Pituitary adenomas were identified and removed at surgery. Immunostaining techniques confirmed the presence of prolactin-containing cells in both tumors. We propose that prolactin-secreting tumors be considered as part of the MEN-I syndrome, and that patients presenting with the galactorrhea-amenorrhea syndrome be screened and followed sequentially for evidence of other endocrine neoplasia.

  1. Regulated programmed lysis of recombinant Salmonella in host tissues to release protective antigens and confer biological containment

    OpenAIRE

    Kong, Wei; Wanda, Soo-Young; Zhang, Xin; Bollen, Wendy; Tinge, Steven A.; Roland, Kenneth L.; Curtiss, Roy

    2008-01-01

    We have devised and constructed a biological containment system designed to cause programmed bacterial cell lysis with no survivors. We have validated this system, using Salmonella enterica serovar Typhimurium vaccines for antigen delivery after colonization of host lymphoid tissues. The system is composed of two parts. The first component is Salmonella typhimurium strain χ8937, with deletions of asdA and arabinose-regulated expression of murA, two genes required for peptidoglycan synthesis a...

  2. Using {sup 18F} FDG PET/CT to Detect an occult Mesenchymal Tumor Causing Oncogenic Osteomalacia

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Hyo Jung; Choi, Yun Jung; Kim, Hyun Jeong; Jeong, Yong Hyu; Cho, Arthur; Lee, Jae Hoon; Yun, Mijin; Lee, Jong Doo; Kang, Won Jun [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    2011-09-15

    Oncogenic osteomalacia is a rare paraneoplastic syndrome characterized by renal phosphate excretion, hypophosphatemia, and osteomalacia. This syndrome is often caused by tumors of mesenchymal origin. Patients with oncogenic osteomalacia have abnormal bone mineralization, resulting in a high frequency of fractures. Tumor resection is the treatment of choice, as it will often correct the metabolic imbalance. Although oncogenic osteomalacia is a potentially curable disease, diagnosis is difficult and often delayed because of the small size and sporadic location of the tumor. Bone scintigraphy and radiography best characterize osteoma lacia; magnetic resonance imaging findings are nonspecific. Here, we report a case of oncogenic osteomalacia secondary to a phosphaturic mesenchymal tumor that was successfully detected by {sup 18F} fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18F} FDG PET/CT). This case illustrates the advantages of {sup 18F} FDG PET/CT in detecting the occult mesenchymal tumor that causes oncogenic osteomalacia.

  3. A Late Onset of Adrenocortical Cancer Assosiated with Beckwith-Wiedemann Syndrome

    Directory of Open Access Journals (Sweden)

    N S Kuznetsov

    2014-06-01

    Full Text Available Beckwith-Wiedemann syndrome (BWS is a genetic overgrowth disorder involving a predisposition to tumor development. The common features of Beckwith-Wiedemann syndrome include omphalocele, macroglos- sia and macrosomia. The increased risk for neoplasia is concentrated in the first eight years of life. However, this case presents a late onset of adrenocortical cancer assosiated with Beckwith-Wiedemann syndrome.

  4. In vitro induction of tumor-specific immunity

    International Nuclear Information System (INIS)

    Chism, S.E.; Burton, R.C.; Grail, D.L.; Bell, P.M.; Warner, N.L.

    1977-01-01

    The cellular competitive inhibition 51 Cr-release assay makes two distinct contributions to the in vitro study of cell-mediated immunity. It allows target cells which are not amenable to isotopic labelling to be investigated for their antigenic specificity and it provides a means, complementary to the direct cytotoxicity assay, of estimating qualitative and quantitative differences in antigen expression on intact normal and neoplastic cells. Various parameters of a micro- 51 Cr-release inhibition assay have been studied, and it was found that the assay conditions markedly influenced both the sensitivity and specificity. It is concluded that optimal assay conditions for specificity include: 1) moderate levels of lysis on the linear part of the CL/T titration curve, 2) avoidance of prolonged assay times, and 3) low ratios of blocker to target cells. When tumor cells with large cell volumes are used as competitive inhibitor (blocker) cells, non-specific blocking will occur; limits have been defined for this particular micro-inhibition assay which, in general, exclude these effects

  5. Fibrosis and carcinoid syndrome: from causation to future therapy.

    Science.gov (United States)

    Druce, Maralyn; Rockall, Andrea; Grossman, Ashley B

    2009-05-01

    Carcinoid tumors are part of a heterogeneous group of gastrointestinal and pancreatic endocrine tumors that are characterized by their capacity to produce and secrete hormones, 5-hydroxytryptamine, tachykinins and other mediators. These substances are thought to be responsible for the collection of symptoms, which include diarrhea, flushing and wheezing, that is known as carcinoid syndrome. Fibrosis that occurs either local to or distant from the primary tumor is one of the hallmarks of carcinoid tumors that originate from the midgut. The fibrotic process can occur in the mesentery as a desmoplastic response and may lead to obstruction of the small bowel, but it can also occur in the lungs, skin or retroperitoneum. Importantly, up to one-third of patients develop cardiac valvulopathy. One or more products that are secreted by the tumor and enter into the circulation are likely to have a role in this process. This Review discusses the incidence and prevalence of fibrosis in carcinoid syndrome and explores evidence to date for causative agents, in particular the roles of 5-hydroxytryptamine and elements of the downstream signaling pathway. Improved understanding of the etiology of carcinoid-tumor-related fibrosis may lead to better treatments for this condition than those we currently have.

  6. Tumors in the region of the sella turcica; Tumoren der Sellaregion

    Energy Technology Data Exchange (ETDEWEB)

    Reith, W. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostischeund Interventionelle Neuroradiologie, Homburg/Saar (Germany)

    2009-07-15

    Tumors of the pituitary gland can lead to limitation of hypophysis function (hypophysis insufficiency) or hypersecretion of different hormones (acromegaly, Cushing's syndrome, prolactinoma, TSH-secreting adenoma). The optic chiasma lies in close proximity to the pituitary gland and can be compressed by tumors leading to visual disturbances (bilateral hemianopsia). Tumors can be separated into hormone secreting and hormone inactive tumors, as well as into microadenoma with a diameter <10 mm and macroadenomas >10 mm. A rare group of tumors of the hypophysis region are craniopharyngiomas, meningiomas, germinomas, gliomas, metastases and granulomotous inflammations, such as sarcoidosis and tuberculosis. (orig.) [German] Bei Tumoren der Hypophysenregion kann es zu einer Einschraenkung der Hypophysenfunktion (Hypophyseninsuffizienz) kommen, aber auch zu einem Hypersekretionssyndrom (Akromegalie, Cushing-Syndrom, Prolaktinom, TSH-sezernierendes Adenom). Unmittelbar ueber der Hypophysenregion liegt das Chiasma opticum, wodurch es bei Tumoren der Hypophysenregion zur Beeintraechtigung des Sehens kommen kann, meist als Verschlechterung des Sehfeldes beider Augen nach lateral (bitemporale Hemianopsie). Man unterscheidet hormonaktive und -inaktive Tumoren. Es werden Mikroadenome mit einem Durchmesser bis 10 mm und Makroadenome, die groesser als 10 mm sind, unterschieden. Eine seltenere Gruppe von Tumoren der Hypophysenregion sind die Kraniopharyngeome, Meningeome, Germinome, Gliome, Metastasen und granulomatoese Entzuendungen (Sarkoidose, Tuberkulose). (orig.)

  7. Evaluation of cell lysis procedures and use of a micro fluidic system for an automated DNA-based cell identification in interplanetary missions

    Science.gov (United States)

    Hall, J. A.; Felnagle, E.; Fries, M.; Spearing, S.; Monaco, L.; Steele, A.

    2006-12-01

    A Modular Assay System for Solar System Exploration (MASSE) is being developed to include sample handling, pre-treatment, separation and analysis of biological target compounds by both DNA and protein microarrays. To better design sensitive and accurate initial upstream sample handling of the MASSE instrument, experiments investigating the sensitivity and potential extraction bias of commercially available DNA extraction kits between classes of environmentally relevant prokaryotes such as gram-negative bacteria ( Escherichia coli), gram-positive bacteria ( Bacillus megatarium), and Archaea ( Haloarcula marismortui) were performed. For extractions of both planktonic cultures and spiked Mars simulated regolith, FTA ® paper demonstrated the highest sensitivity, with detection as low as ˜1×10 1 cells and ˜3.3×10 2 cells, respectively. In addition to the highest sensitivity, custom modified application of FTA ® paper extraction protocol is the simplest in terms of incorporation into MASSE and displayed little bias in sensitivity with respect to prokaryotic cell type. The implementation of FTA paper for environmental microbiology investigations appears to be a viable and effective option potentially negating the need for other pre-concentration steps such as filtration and negating concerns regarding extraction efficiency of cells. In addition to investigations on useful technology for upstream sample handling in MASSE, we have also evaluated the potential for μTAS to be employed in the MASSE instrument by employing proprietary lab-on-a-chip development technology to investigate the potential for microfluidic cell lysis of different prokaryotic cells employing both chemical and biological lysis agents. Real-time bright-field microscopy and quantitative PMT detection indicated that that gram positive, gram negative and archaeal cells were effectively lyzed in a few seconds using the microfluidic chip protocol developed. This included employing a lysis buffer with

  8. Happle-tinschert syndrome: Report of a case with hemimegalencephaly

    Energy Technology Data Exchange (ETDEWEB)

    Oezgur, Anil; Cabuk, Gonca; Arpaci, Rabia; Baz, Kiymet; Katar, Demet [Mersin University Faculty of Medicine, Mersin (Turkmenistan)

    2014-08-15

    Happle-Tinschert syndrome is a disorder causing unilateral segmentally arranged basaloid follicular hamartomas of the skin associated with ipsilateral osseous, dental and cerebral abnormalities including tumors. Although a case with hemimegalencephaly was previously described, this is the first report of Happle-Tinschert syndrome with discrepant short left leg, ipsilateral skin lesions, hemimegalencephaly and frontal polymicrogyria.

  9. Happle-tinschert syndrome: Report of a case with hemimegalencephaly

    International Nuclear Information System (INIS)

    Oezgur, Anil; Cabuk, Gonca; Arpaci, Rabia; Baz, Kiymet; Katar, Demet

    2014-01-01

    Happle-Tinschert syndrome is a disorder causing unilateral segmentally arranged basaloid follicular hamartomas of the skin associated with ipsilateral osseous, dental and cerebral abnormalities including tumors. Although a case with hemimegalencephaly was previously described, this is the first report of Happle-Tinschert syndrome with discrepant short left leg, ipsilateral skin lesions, hemimegalencephaly and frontal polymicrogyria.

  10. Pancoast syndrome: A rare presentation of non-Hodgkin′s lymphoma

    Directory of Open Access Journals (Sweden)

    Anirban Sarkar

    2013-01-01

    Full Text Available Pancoast syndrome is a common presentation of bronchogenic carcinoma, but other malignancies are rarely cited as its cause. Pancoast syndrome due to non-Hodgkin′s lymphoma is rarely described in the literature. Here, we report a case of Pancoast syndrome due to non-Hodgkin′s lymphoma to increase the awareness of the clinicians regarding essentiality of tissue diagnosis of Pancoast tumor before starting the treatment.

  11. An intraventricular clear cell meningioma revealed by an inflammatory syndrome in a male adult: a case report.

    Science.gov (United States)

    Cassereau, J; Lavigne, C; Michalak-Provost, S; Ghali, A; Dubas, F; Fournier, H D

    2008-07-01

    Intraventricular meningiomas are infrequent intracranial tumors. Clinical symptoms are mainly due to an increased intracranial pressure or a direct pressure on the surrounding brain structures. Inflammatory syndrome was described in some patients with chordoid meningiomas. Here we report a case of right intraventricular clear cell meningioma in a 50-year-old man who presented with fever, headache, and inflammatory syndrome. Clinical and biological normalization was rapidly obtained after tumor removal. Immunohistochemical examination showed tumor cells and lymphocytes positivity for the pyrogenic cytokine interleukin-6, with a same intensity. To our knowledge, this is the first case described in the literature concerning an adult man with an intraventricular clear cell meningioma associated with a systemic inflammatory syndrome.

  12. A case of neuroblastoma in DICER1 syndrome: Chance finding or noncanonical causation?

    Science.gov (United States)

    Saskin, Avi; de Kock, Leanne; Sabbaghian, Nelly; Apellaniz-Ruiz, Maria; Bozkurt, Ceyhun; Bouron-Dal Soglio, Dorothée; Foulkes, William D

    2018-01-01

    DICER1 syndrome is an inherited disorder associated with at least a dozen rare, mainly pediatric-onset tumors. Its characterization remains incomplete. Some studies suggested that neuroblastoma (NB) may be involved in this syndrome. Here, we describe the case of a 14-year-old female presenting with a multinodular goiter (MNG) and a collision tumor composed of NB and cystic nephroma (CN). She is a carrier of a deleterious germline mutation in exon 23 of DICER1 and harbored different somatic mutations in the CN and MNG. However, no second hit was found in the NB, questioning its status as a DICER1-related tumor. © 2017 Wiley Periodicals, Inc.

  13. Gorlin-Goltz syndrome.

    Science.gov (United States)

    Şereflican, Betül; Tuman, Bengü; Şereflican, Murat; Halıcıoğlu, Sıddıka; Özyalvaçlı, Gülzade; Bayrak, Seval

    2017-09-01

    Gorlin-Goltz syndrome is a rare multisystemic disease inherited in an autosomal dominant pattern. It is characterized by numerous basal cell carcinoma of the skin, jaw cysts, and skeletal anomalies such as frontal bossing, vertebral anomalies, palmoplantar pits, and falx cerebri calcification. There is a tendency to tumors including medullablastoma, fibroma, rabdomyoma, leiomyosarcoma etc.. The diagnosis is based on major and minor clinical and radiologic criteria. Early diagnosis and treatment are of utmost importance in reducing the severity of long-term sequelae of this syndrome. In this article, we present a 15-year-old boy who was admitted to our clinic with brown-black papules and plaques on his scalp and was thought to have Gorlin-Goltz syndrome. He had a history of medulloblastoma that was treated with surgical resection followed by cranial radiotherapy and unilateral retinoblastoma. We present this case, because association of Gorlin-Goltz syndrome and retinoblastoma has not been described previously in the literature and we aimed to draw attention to radiation-induced basal cell carcinomas.

  14. Lynch syndrome-associated extracolonic tumors are rare in two extended families with the same EPCAM deletion.

    Science.gov (United States)

    Lynch, Henry T; Riegert-Johnson, Douglas L; Snyder, Carrie; Lynch, Jane F; Hagenkord, Jill; Boland, C Richard; Rhees, Jennifer; Thibodeau, Stephen N; Boardman, Lisa A; Davies, Janine; Kuiper, Roland P; Hoogerbrugge, Nicoline; Ligtenberg, Marjolijn J L

    2011-10-01

    The Lynch syndrome (LS) is an inherited cancer syndrome showing a preponderance of colorectal cancer (CRC) in context with endometrial cancer and several other extracolonic cancers, which is due to pathogenic mutations in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, and PMS2. Some families were found to show a LS phenotype without an identified MMR mutation, although there was microsatellite instability and absence of MSH2 expression by immunohistochemistry. Studies of a subset of these families found a deletion at the 3' end of the epithelial cell adhesion molecule (EPCAM) gene, causing transcription read-through resulting in silencing of MSH2 through hypermethylation of its promoter. The tumor spectrum of such families appears to differ from classical LS. Our study of two large families (USA Family R and Dutch Family A) with an EPCAM deletion was carried out using each institution's standard family study protocol. DNA was extracted from peripheral blood and EPCAM deletion analysis was performed. Both families were found to harbor the same deletion at the 3' end of EPCAM. Analysis showed that the deletion originated from a common ancestor. Family R and Family A members showed segregation of CRC with the presence of this EPCAM mutation. Compared with classic LS, there were almost no extracolonic cancers. Members of Family R and Family A, all with the same EPCAM deletion, predominantly presented with CRC but no LS-associated endometrial cancer, confirming findings seen in other, smaller, LS families with EPCAM mutations. In these EPCAM mutation carriers, cancer surveillance should be focused on CRC.

  15. Transarterial chemoembolization for primary and metastatic liver tumors

    Directory of Open Access Journals (Sweden)

    Popov M.V.

    2016-12-01

    Full Text Available The literature review presents the methodology of transarterial chemoembolization (TACE — widely used method of treatment of primary and secondary liver tumors. The TACE role as a neoadjuvant therapy and the role in the management of unresectable primary and secondary liver tumors are shown. The morphofunctional basis of TACE, benefits of superselective intra-arterial administration of cytostatic agents especially in combination with ischemic impact on a tumor are described. The subject of the choice of the chemotherapeutic agent is also touched; modern drug-loaded microspheres which allow the use of higher doses of the chemotherapeutic drug without increasing systemic effect and prolong its effect on tumor are described. Lack of correlation of presence and severity of a post-embolization syndrome with success of the procedure is noted.

  16. Mayer–Rokitansky–Kuster–Hauser syndrome: Syndrome of Mullerian agenesis – A report of two cases

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    Sushma Yalavarthi

    2017-01-01

    Full Text Available The Mayer–Rokitansky–Kuster–Hauser syndrome (MRKH syndrome, simply called Rokitansky syndrome or vaginal aplasia of the uterus, is a congenital condition that is characterized by the absence of the uterus and vagina, but ovaries are present and the external genitalia are normal. It affects at least 1 out of 4500 women. MRKH may be isolated (Type I, but it is more frequently associated with renal, vertebral, and to a lesser extent, auditory and cardiac defects (MRKH Type II or Mullerian duct aplasia, Renal dysplasia, and Cervical Somite anomalies association - mullerian duct aplasia, renal dysplasia, and cervical somite anomalies. There were very few cases of MRKH syndrome reported in the literature. Here, we report two cases of MRKH syndrome, one in a 20-year-old woman who presented with primary amenorrhea (MRKH Type I and the other in a 65-year-old woman with primary amenorrhea and associated renal malformations and a rare ovarian sertoliform variant of endometrioid tumor (MRKH Type II.

  17. The surgery of peripheral nerves (including tumors)

    DEFF Research Database (Denmark)

    Fugleholm, Kåre

    2013-01-01

    Surgical pathology of the peripheral nervous system includes traumatic injury, entrapment syndromes, and tumors. The recent significant advances in the understanding of the pathophysiology and cellular biology of peripheral nerve degeneration and regeneration has yet to be translated into improved...... surgical techniques and better outcome after peripheral nerve injury. Decision making in peripheral nerve surgery continues to be a complex challenge, where the mechanism of injury, repeated clinical evaluation, neuroradiological and neurophysiological examination, and detailed knowledge of the peripheral...... nervous system response to injury are prerequisite to obtain the best possible outcome. Surgery continues to be the primary treatment modality for peripheral nerve tumors and advances in adjuvant oncological treatment has improved outcome after malignant peripheral nerve tumors. The present chapter...

  18. The Lynch syndrome: a management dilemma.

    Science.gov (United States)

    Palumbo, Piergaspare; Amatucci, Chiara; Perotti, Bruno; Dezzi, Claudia; Girolami, Marco; Illuminati, Giulio; Angelici, Alberto M

    2013-05-01

    The case of a familial Lynch syndrome is reported. The criteria for early diagnosis, management and surveillance are briefly reviewed. A germline mutation of genes responsible for mismatch repair is at the basis of the Lynch syndrome. Carriers are predisposed to colorectal cancer and other tumors. Two members of the presently reported family developed colorectal cancer, whereas two others developed other neoplasms. The syndrome was confirmed in members of the same family with appropriate genetic workup. Clinical examination and endoscopy were consequently scheduled once-a-year. Given the high risk of neoplastic disease, such yearly controls can be proposed as the standard follow-up of this condition.

  19. Chronic recurrent Gorham-Stout syndrome with cutaneous involvement

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    Nahum Duker

    2010-09-01

    Full Text Available Type IV osteolysis or Gorham-Stout syndrome is a rare condition characterized by recurrent vascular tumors that disrupt normal anatomical architecture. Gorham-Stout syndrome is most commonly associated with the skeletal system with resulting replacement of bone with scar tissue following tumor regression. The loss of entire bones has given Gorham-Stout syndrome the moniker vanishing bone disease. Natural progression of Gorham-Stout syndrome is characterized by spontaneous disease resolution. However, rare variants of recurrent, progressive, and/or systemic disease have been reported. We present a patient with a history of recurrent Gorham-Stout disease refractory to all treatment options considered. In addition to skeletal disease, our patient had soft tissue and cutaneous involvement, thus reflecting the more aggressive disease variant. Previous surgical attempts to control disease had been ineffective and the patient was referred to us for radiation therapy. Treatment with external beam radiation therapy resulted in good local control and symptom palliation, but full disease resolution was never accomplished. In addition to presentation of this patient, a review of the literature on etiological hypotheses and past/future treatment options was conducted and is included.

  20. Meigs’ Syndrome with elevated serum CA125: Case Report and Review of the Literature

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    Emrullah Tanrikut

    2012-03-01

    Full Text Available Backround: Elevated serum CA125 levels in postmenopausal women with solid adnexal masses, ascites, and pleural effusion are highly suggestive for malignant ovarian tumor. We aimed,malignant ovarian tumors clinically mimicking a case of syndrome meigs.\tCase: Forty-four years old patient with diagnosis of Meigs syndrome\tConclusion: Adnexal mass in patients with high CA 125 levels should be consider malignancy. Presence of pleural efussion increases suspicion of malignancy.

  1. Understanding tumor anabolism and patient catabolism in cancer-associated cachexia

    Science.gov (United States)

    Schcolnik-Cabrera, Alejandro; Chávez-Blanco, Alma; Domínguez-Gómez, Guadalupe; Dueñas-González, Alfonso

    2017-01-01

    Cachexia is a multifactorial paraneoplastic syndrome commonly associated with advanced stages of cancer. Cachexia is responsible for poor responses to antitumoral treatment and death in close to one-third of affected patients. There is still an incomplete understanding of the metabolic dysregulation induced by a tumor that leads to the appearance and persistence of cachexia. Furthermore, cachexia is irreversible, and there are currently no guidelines for its diagnosis or treatments for it. In this review, we aim to discuss the current knowledge about cancer-associated cachexia, starting with generalities about cancer as the generator of this syndrome, then analyzing the characteristics of cachexia at the biochemical and metabolic levels in both the tumor and the patient, and finally discussing current therapeutic approaches to treating cancer-associated cachexia. PMID:28560061

  2. [A comparative study of blood culture conventional method vs. a modified lysis/centrifugation technique for the diagnosis of fungemias].

    Science.gov (United States)

    Santiago, Axel Rodolfo; Hernández, Betsy; Rodríguez, Marina; Romero, Hilda

    2004-12-01

    The purpose of this work was to compare the efficacy of blood culture conventional method vs. a modified lysis/centrifugation technique. Out of 450 blood specimens received in one year, 100 where chosen for this comparative study: 60 from patients with AIDS, 15 from leukemic patients, ten from febrile neutropenic patients, five from patients with respiratory infections, five from diabetics and five from septicemic patients. The specimens were processed, simultaneously, according to the above mentioned methodologies with daily inspections searching for fungal growth in order to obtain the final identification of the causative agent. The number (40) of isolates recovered was the same using both methods, which included; 18 Candida albicans (45%), ten Candida spp. (25%), ten Histoplasma capsulatum (25%), and two Cryptococcus neoformans (5%). When the fungal growth time was compared by both methods, growth was more rapid when using the modified lysis/centrifugation technique than when using the conventional method. Statistical analysis revealed a significant difference (pcentrifugation technique showed to be more efficacious than the conventional one, and therefore the implementation of this methodology is highly recommended for the isolation of fungi from blood.

  3. Rare post-operative complications of large mediastinal tumor resection

    Directory of Open Access Journals (Sweden)

    Mohsen Mirmohammadsadeghi

    2015-03-01

    Full Text Available Background: There are some reports in the literature, which suggest that cardiac tamponade drainage may transiently affect systolic function and also cause acute respiratory distress syndrome (ARDS. We did not find any reports of acute ventricular failure and ARDS secondary to mediastinal tumor resection without tamponade. Case Report: Here we report a 48-year-old woman presenting with massive pericardial effusion without tamponade in whom tumor was resected through median sternotomy using cardiopulmonary bypass. ARDS and acute heart failure were two rare complications that happened at the end of the operation secondary to a sudden decompression of the heart from tumor pressure. Conclusion: ARDS and acute heart failure are two rare complications, which can happen after large mediastinal tumor resection.

  4. Upregulation of HLA Class I Expression on Tumor Cells by the Anti-EGFR Antibody Nimotuzumab

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    Greta Garrido

    2017-10-01

    Full Text Available Defining how epidermal growth factor receptor (EGFR-targeting therapies influence the immune response is essential to increase their clinical efficacy. A growing emphasis is being placed on immune regulator genes that govern tumor – T cell interactions. Previous studies showed an increase in HLA class I cell surface expression in tumor cell lines treated with anti-EGFR agents. In particular, earlier studies of the anti-EGFR blocking antibody cetuximab, have suggested that increased tumor expression of HLA class I is associated with positive clinical response. We investigated the effect of another commercially available anti-EGFR antibody nimotuzumab on HLA class I expression in tumor cell lines. We observed, for the first time, that nimotuzumab increases HLA class I expression and its effect is associated with a coordinated increase in mRNA levels of the principal antigen processing and presentation components. Moreover, using 7A7 (a specific surrogate antibody against murine EGFR, we obtained results suggesting the importance of the increased MHC-I expression induced by EGFR-targeted therapies display higher in antitumor immune response. 7A7 therapy induced upregulation of tumor MHC-I expression in vivo and tumors treated with this antibody display higher susceptibility to CD8+ T cells-mediated lysis. Our results represent the first evidence suggesting the importance of the adaptive immunity in nimotuzumab-mediated antitumor activity. More experiments should be conducted in order to elucidate the relevance of this mechanism in cancer patients. This novel immune-related antitumor mechanism mediated by nimotuzumab opens new perspectives for its combination with various immunotherapeutic agents and cancer vaccines.

  5. A Classic Case of Basal Cell Nevus Syndrome

    Directory of Open Access Journals (Sweden)

    Dattaprasad Dadhe

    2015-01-01

    Full Text Available The basal cell nevus syndrome is an autosomal dominant inherited condition characterized mainly by basal cell carcinomas, multiple keratinizing odontogenic tumors, and other systemic anomalies. As these manifestations do not alter the patient′s lifestyle, most of the cases are diagnosed through oral abnormalities. A classic case of basal cell nevus syndrome fulfilling almost all the major and minor criteria has been reported here.

  6. [Diagnosis and surgical management in gastrointestinal neuroendocrine tumors].

    Science.gov (United States)

    Tomulescu, V; Stănciulea, O; Dima, S; Herlea, V; Stoica Mustafa, E; Dumitraşcu, T; Pechianu, C; Popescu, I

    2011-01-01

    Neuroendocrine tumors, known as carcinoid tumors constitute a heterogeneous group of neoplasms that present many clinical challenges. They secrete peptides and neuroamines that cause specific clinical syndromes. Assessment of specific or general tumors markers offers high sensitivity in establishing the diagnosis and they also have prognostic significance. Management strategies include curative surgery, whenever possible-that can be rarely achieved, palliative surgery, chemotherapy, radiologic therapy, such as radiofrequency ablation and chemoembolisations and somatostatin analogues therapy in order to control the symptoms. The aim of this paper is to review recent publications in this field and to give recommendations that take into account current advances in order to facilitate improvement in management and outcome.

  7. Clinicopathological Features and Management of Cancers in Lynch Syndrome

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    Markku Aarnio

    2012-01-01

    Full Text Available Lynch syndrome (LS is characterized by an autosomal dominant inheritance of the early onset of colorectal cancer (CRC and endometrial cancer, as well as increased risk for several other cancers including gastric, urinary tract, ovarian, small bowel, biliary tract, and brain tumors. The syndrome is due to a mutation in one of the four DNA mismatch repair (MMR genes MLH1, MSH2, MSH6, or PMS2. The majority of LS patients and families can now be identified, and the underlying mutation detected using genetic diagnostics. Regular surveillance for CRC and endometrial cancer has proved beneficial for mutation carriers. However, screening for other tumors is also recommended even though experiences in the screening of these tumors is limited. Prophylactic colectomy, prophylactic hysterectomy, and bilateral salpingo-oophorectomy may be reasonable options for selected patients with LS. This paper describes the features and management of LS.

  8. Nelson Syndrome: Update on Therapeutic Approaches.

    Science.gov (United States)

    Azad, Tej D; Veeravagu, Anand; Kumar, Sunny; Katznelson, Laurence

    2015-06-01

    To review the pathophysiology and therapeutic modalities availble for Nelson syndrome. We reviewed the current literature including managment for Nelson syndrome. For patients with NS, surgical intervention is often the first-line therapy. With refractory NS or tumors with extrasellar involvement, radiosurgery offers an important alternative or adjuvant option. Pharmacologic interventions have demonstrated limited usefulness, although recent evidence supports the feasibility of a novel somatostatin analog for patients with NS. Modern neuroimaging, improved surgical techniques, and the advent of stereotactic radiotherapy have transformed the management of NS. An up-to-date understanding of the pathophysiology underlying Nelson Syndrome and evidence-based management is imperative. Early detection may allow for more successful therapy in patients with Nelson Syndrome. Improved radiotherapeutic interventions and rapidly evolving pharmacologic therapies offer an opportunity to create targeted, multifocal treatment regiments for patients with Nelson Syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. A case of retroperitoneal carcinoid tumor which was radioeffective

    International Nuclear Information System (INIS)

    Nishimura, Kazuo; Ogawa, Osamu; Yoshimura, Naoki; Nakagawa, Takashi; Takahashi, Rei; Sasaki, Miharu.

    1984-01-01

    A 51-year-old man was referred to our hospital on May, 24, 1978, with complaints of lower abdominal pain, lower abdominal mass, constipation and pollakisuria. Physical examination revealed a lower abdominal tumor which was smooth, elastic soft and of childs' head size. IVP and urethrography revealed left nonvisualizing kidney, right hydronephrosis and deformity of bladder. CT scan revealed a large intrapelvic mass. Under the diagnosis of retroperitoneal tumor, operation was done on June, 29, 1978. Adhesive changes between the tumor, sacrococcyx and left internal iliac artery was so severe that the tumor could not be resected, and only biopsy-specimen was taken. Pathohistological diagnosis of the tumor was carcinoid tumor. He received postoperative radiation therapy with total dosis of 5000 rad in 5 weeks, and complete remission was obtained. Now, more than 5 years have passed after operation, no recurrence was detected. Carcinoid tumors are rare and generally are not radioeffective, but some cases without carcinoid syndrome, including our case, are radioeffective. So radiation therapy should be the second choice of treatment for carcinoid tumor. (author)

  10. Tumor-induced osteomalacia

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    Pablo Florenzano

    2017-12-01

    Full Text Available Tumor-induced osteomalacia (TIO is a rare paraneoplastic syndrome clinically characterized by bone pain, fractures and muscle weakness. It is caused by tumoral overproduction of fibroblast growth factor 23 (FGF23 that acts primarily at the proximal renal tubule, decreasing phosphate reabsorption and 1α-hydroxylation of 25 hydroxyvitamin D, thus producing hypophosphatemia and osteomalacia. Lesions are typically small, benign mesenchymal tumors that may be found in bone or soft tissue, anywhere in the body. In up to 60% of these tumors, a fibronectin-1(FN1 and fibroblast growth factor receptor-1 (FGFR1 fusion gene has been identified that may serve as a tumoral driver. The diagnosis is established by the finding of acquired chronic hypophosphatemia due to isolated renal phosphate wasting with concomitant elevated or inappropriately normal blood levels of FGF23 and decreased or inappropriately normal 1,25-OH2-Vitamin D (1,25(OH2D. Locating the tumor is critical, as complete removal is curative. For this purpose, a step-wise approach is recommended, starting with a thorough medical history and physical examination, followed by functional imaging. Suspicious lesions should be confirmed by anatomical imaging, and if needed, selective venous sampling with measurement of FGF23. If the tumor is not localized, or surgical resection is not possible, medical therapy with phosphate and active vitamin D is usually successful in healing the osteomalacia and reducing symptoms. However, compliance is often poor due to the frequent dosing regimen and side effects. Furthermore, careful monitoring is needed to avoid complications such us secondary/tertiary hyperparathyroidism, hypercalciuria, and nephrocalcinosis. Novel therapeutical approaches are being developed for TIO patients, such as image-guided tumor ablation and medical treatment with the anti-FGF23 monoclonal antibody KRN23 or anti FGFR medications. The case of a patient with TIO is presented to

  11. Radiological diagnostics in CUP syndrome; Radiologische Diagnostik des CUP-Syndroms

    Energy Technology Data Exchange (ETDEWEB)

    Kazmierczak, P.M.; Nikolaou, K.; Graser, A.; Reiser, M.F.; Cyran, C.C. [Klinikum der Ludwig-Maximilians-Universitaet, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany); Rominger, A. [Klinikum der Ludwig-Maximilians-Universitaet, Campus Grosshadern, Klinik und Poliklinik fuer Nuklearmedizin, Muenchen (Germany)

    2014-02-15

    , diffusion), e.g. investigation of breast carcinoma or prostate carcinoma. Whole body staging stands at the beginning of the diagnostic algorithm in CUP syndrome to localize a potential primary tumor. Clinically, contrast-enhanced CT of the neck, thorax and abdomen is frequently applied; however, many studies have demonstrated augmented sensitivity of {sup 18}F-FDG PET-CT for the detection of primary tumors and metastatic tumor manifestations. (orig.) [German] Im therapeutischen Management des Cancer-of-unknown-primary(CUP)-Syndroms spielt die bildgebende Diagnostik eine zentrale Rolle zur Lokalisation des Primaertumors, zur Identifikation von Tumoren, fuer die ein dediziertes Behandlungsschema zur Verfuegung steht, sowie zur Charakterisierung klinisch-pathologischer Subentitaeten, die das weitere diagnostische und therapeutische Procedere bestimmen und eine Einschaetzung der Prognose erlauben. Zur Verfuegung stehende radiologische Modalitaeten umfassen die Projektionsradiographie, die Computertomographie (CT), die Magnetresonanztomographie (MRT) und die Sonographie sowie die Hybridverfahren Positronenemissionstomographie(PET)-CT und MR-PET. In der Ganzkoerperbildgebung hat die CT eine hohe Sensitivitaet fuer Tumoren, die haeufig als metastasierte Tumorerkrankung auftreten. Nach aktueller Literatur ist die CT bei Patienten mit Pankreaskarzinom in 86% der Faelle diagnostisch, bei Patienten mit Kolonkarzinom in 36% und bei Patienten mit Bronchialkarzinom in 74%. Des Weiteren zeigte eine Metaanalyse, dass bei Patienten mit Plattenepithelkarzinom und zervikalen Lymphknotenmetastasen die CT in 22% der Faelle den Primaertumor lokalisieren konnte, im Vergleich zu 36% Detektionsrate der MRT und 28-57% der PET-CT mit {sup 18}F-FDG (Fluordesoxyglukose). Der MRT kommt auf Grund des hohen Weichteilkontrasts und der Moeglichkeit zur funktionellen Bildgebung besondere Bedeutung bei der Lokalisation primaer okkulter Tumoren bei Organuntersuchungen zu, z. B. beim Mamma- oder dem

  12. Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer

    Science.gov (United States)

    Carethers, John M; Stoffel, Elena M

    2015-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management. PMID:26309352

  13. Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer.

    Science.gov (United States)

    Carethers, John M; Stoffel, Elena M

    2015-08-21

    Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management.

  14. Changes in clot lysis levels of reteplase and streptokinase following continuous wave ultrasound exposure, at ultrasound intensities following attenuation from the skull bone

    Directory of Open Access Journals (Sweden)

    Roijer Anders

    2008-08-01

    Full Text Available Abstract Background Ultrasound (US has been used to enhance thrombolytic therapy in the treatment of stroke. Considerable attenuation of US intensity is however noted if US is applied over the temporal bone. The aim of this study was therefore to explore possible changes in the effect of thrombolytic drugs during low-intensity, high-frequency continuous-wave ultrasound (CW-US exposure. Methods Clots were made from fresh venous blood drawn from healthy volunteers. Each clot was made from 1.4 ml blood and left to coagulate for 1 hour in a plastic test-tube. The thrombolytic drugs used were, 3600 IU streptokinase (SK or 0.25 U reteplase (r-PA, which were mixed in 160 ml 0.9% NaCl solution. Continuous-wave US exposure was applied at a frequency of 1 MHz and intensities ranging from 0.0125 to 1.2 W/cm2. For each thrombolytic drug (n = 2, SK and r-PA and each intensity (n = 9 interventional clots (US-exposed, n = 6 were submerged in thrombolytic solution and exposed to CW-US while control clots (also submerged in thrombolytic solution, n = 6 were left unexposed to US. To evaluate the effect on clot lysis, the haemoglobin (Hb released from each clot was measured every 20 min for 1 hour (20, 40 and 60 min. The Hb content (mg released was estimated by spectrophotometry at 540 nm. The difference in effect on clot lysis was expressed as the difference in the amount of Hb released between pairs of US-exposed clots and control clots. Statistical analysis was performed using Wilcoxon's signed rank test. Results Continuous-wave ultrasound significantly decreased the effects of SK at intensities of 0.9 and 1.2 W/cm2 at all times (P 2 and at 1.2 W/cm2, following 40 min exposure at 0.3, 0.6, 0.9 and at 1.2 W/cm2, and following 60 min of exposure at 0.05 0.3, 0.6, 0.9 and at 1.2 W/cm2 (all P Conclusion Increasing intensities of CW-US exposure resulted in increased clot lysis of r-PA-treated blood clots, but decreased clot lysis of SK-treated clots.

  15. Empty sella syndrome

    International Nuclear Information System (INIS)

    Park, Chang Yoon

    1973-01-01

    The enlarged sella was encountered ordinarily as intrasellar lesion such as pituitary tumor or secondary increased intracranial pressure without certain mechanism. 1951 Busch discovered from his extensive autopsy cases that defects or incomplete attachment of diaphragm sella brings sella enlargement either slightly or moderately enlarged sella with subarachnoid extension. Toennis et al in 1955 discussed enlarged sella due to via infundibular defects or loosely attached stalk area of diaphragm sella from secondary increased intracranial pressure. Du Boulay and others differentiate the entity of none tumor origin of sella enlargement either from raised intracranial pressure or parasella changes, Hence, 'empty sella' was loosely used terminology. We observed following three representative cases in various empty sella syndrome. Case 1: air extended into the sella by pneumoencephalogram. Case 2: chiasma recess herniated into the sella secondary to dilated third ventricle from right thalamic tumor extension. Case 3: enlarged sella firstly mimic intrasella tumor but found intrasella fluid of cerebro-spinal content of extended subarchnoid space into sella. Above changes readily observed by pneumoencephalogram and other means

  16. Polyostotic fibrous dysplasia associated with intramuscular myxomas: Mazabraud's syndrome

    International Nuclear Information System (INIS)

    Lassance Cabral, C.E.; Guedes, P.; Celso Cruz, L. Jr.; Smith, J.; Rezende, J.F.

    1998-01-01

    Mazabraud's syndrome, though uncommon, is reported increasingly frequently. It represents an entity readily recognisable radiologically on MR imaging. Awareness of the syndrome, particularly when the myxoma is solitary, can prevent misdiagnosis of intramuscular myxomas (especially when large) as malignant mesenchymal tumors containing myxoid tissue. We review the 34 cases previously reported in the literature and include a recent case from our center. (orig.)

  17. RAEDER PARATRIGEMINAL SYNDROME IN A PATIENT WITH A MASS LESION IN THE MAXILLARY SINUS

    Directory of Open Access Journals (Sweden)

    Vyara Kirkova

    2010-12-01

    Full Text Available Raeder paratrigeminal syndrome is a rare syndrome, characterized by severe unilateral facial pain and headache in the distribution of the ophthalmic division of the trigeminal nerve in combination with ipsilateral oculosympathetic palsy or Horner syndrome. We describe a case of a 65-year-old male patient with a large tumor in the right maxillary sinus who presented with the rare Raeder syndrome.

  18. Multiple desmoid tumors in a patient with familial adenomatous polyposis caused by the novel W421X mutation Tumor desmoide múltiple en un paciente con poliposis adenomatosa familiar originada por la nueva mutación W421X

    Directory of Open Access Journals (Sweden)

    Orestis Ioannidis

    2012-03-01

    Full Text Available Familial adenomatous polyposis (FAP is a rare syndrome characterized by the presence of hundreds to thousands of colorectal adenomas and is responsible for less than 1% of all colorectal cancers. The syndrome is also characterized by extra-colorectal features including amongst others upper gastrointestinal tract polyps and desmoid tumors. The syndrome is inherited by an autosomal dominant gene, the adenomatous polyposis coli (APC gene. We present the physical history, clinical presentation, diagnosis and treatment of a patient with a novel germline APC mutation, the W421X mutation, which resulted in FAP presenting with about a hundred colorectal polyps, gastric hyperplastic polyps and multiple aggressive intra-abdominal and extra-abdominal desmoid tumors.

  19. A Case Report of Maffucci Syndrome

    Directory of Open Access Journals (Sweden)

    Gh. Eshghi

    2013-01-01

    Full Text Available Introduction: Maffucci syndrome is a rare clinical entity (approximately 200 cases have been reported in the medical literature with a combination occurrence of multiple enchodroma and vascular tumors. Case Report: Our patient was an 18 year old girl born in a non-consanguineous marriage with finger and toe bones disorders (enchondroma causing deformity of fingers and toes with multiple vascular tumors (cavernous hemangioma in the distal upper and lower limbs. Entire laboratory investigations including thyroid function tests were normal. Cardiovascular ex-amination including EKG and echocardiography were also normal. The abnormal findings on brain CT SCAN with contrast were not observed. Angiographic and histologic stud-ies confirmed the cavernous hemangioma and radiography of fingers and toes approved bone lesions (enchondroma. Conclusion: A diagnosis of Maffucci syndrome was made by the above mentioned measures.(Sci J Hamadan Univ Med Sci 2013; 19 (4:82-85

  20. Nelson syndrome: historical perspectives and current concepts.

    Science.gov (United States)

    Hornyak, Mark; Weiss, Martin H; Nelson, Don H; Couldwell, William T

    2007-01-01

    The appearance of an adrenocorticotropic hormone (ACTH)-producing tumor after bilateral adrenalectomy for Cushing disease was first described by Nelson in 1958. The syndrome that now bears his name was characterized by hyperpigmentation, a sellar mass, and increased plasma ACTH levels. The treatment of Cushing disease has changed drastically since the 1950s, when the choice was adrenalectomy. Thus, the occurrence, diagnosis, and treatment of Nelson syndrome have changed as well. In the modern era of high-resolution neuroimaging, transsphenoidal microneurosurgery, and stereotactic radiosurgery, Nelson syndrome has become a rare entity. The authors describe the history of the diagnosis and treatment of Nelson syndrome. In light of the changes described, the authors believe this disease must be reevaluated in the contemporary era and a modern paradigm adopted.

  1. Watery diarrhea syndrome in an adult with ganglioneuroma-pheochromocytoma: identification of vasoactive intestinal peptide, calcitonin, and catecholamines and assessment of their biologic activity.

    Science.gov (United States)

    Trump, D L; Livingston, J N; Baylin, S B

    1977-10-01

    A case of adult ganglioneuroma-pheochromocytoma with an associated watery diarrhea syndrome is reported. High levels of vasoactive intestinal peptide (VIP) were found in preoperative serum and in tumor tissue. The serum VIP levels fell to normal, and the watery diarrhae syndrome completely ceased following removal of the tumor. In addition to containing VIP, the tumor was rich in catecholamines, and calcitonin. Peptide hormone-containing extracts and catecholamine extracts from the tumor both activated the adenyl cyclase system and increased lipolytic activity in a preparation of isolated rat fat cells. The findings in this patient further link VIP with neural crest tissues, and suggest the importance of determining catecholamine levels in patients with the watery diarrhea syndrome.

  2. Hyphal growth of phagocytosed Fusarium oxysporum causes cell lysis and death of murine macrophages.

    Science.gov (United States)

    Schäfer, Katja; Bain, Judith M; Di Pietro, Antonio; Gow, Neil A R; Erwig, Lars P

    2014-01-01

    Fusarium oxysporum is an important plant pathogen and an opportunistic pathogen of humans. Here we investigated phagocytosis of F. oxysporum by J774.1 murine cell line macrophages using live cell video microscopy. Macrophages avidly migrated towards F. oxysporum germlings and were rapidly engulfed after cell-cell contact was established. F. oxysporum germlings continued hyphal growth after engulfment by macrophages, leading to associated macrophage lysis and escape. Macrophage killing depended on the multiplicity of infection. After engulfment, F. oxysporum inhibited macrophages from completing mitosis, resulting in large daughter cells fused together by means of a F. oxysporum hypha. These results shed new light on the initial stages of Fusarium infection and the innate immune response of the mammalian host.

  3. Clinical Investigation of Adrenal Incidentalomas in Japanese Patients of the Fukuoka Region with Updated Diagnostic Criteria for Sub-clinical Cushing's Syndrome.

    Science.gov (United States)

    Abe, Ichiro; Sugimoto, Kaoru; Miyajima, Tetsumasa; Ide, Tomoko; Minezaki, Midori; Takeshita, Kaori; Takahara, Saori; Nakagawa, Midori; Fujimura, Yuki; Kudo, Tadachika; Miyajima, Shigero; Taira, Hiroshi; Ohe, Kenji; Ishii, Tatsu; Yanase, Toshihiko; Kobayashi, Kunihisa

    2018-04-27

    Objectives We retrospectively investigated the clinical and endocrinological characteristics of adrenal incidentalomas. Methods We studied 61 patients who had been diagnosed with adrenal incidentalomas and had undergone detailed clinical and endocrinological evaluations while hospitalized. We used common criteria to diagnose the functional tumors, but for sub-clinical Cushing's syndrome, we used an updated set of diagnosis criteria: serum cortisol ≥1.8 μg/dL after a positive response to a 1-mg dexamethasone suppression test if the patient has a low morning ACTH level (Cushing's syndrome and sub-clinical Cushing's syndrome), and 25 (41.0%) had non-functional tumors. Compared with the non-functional tumor group, the primary aldosteronism group and the cortisol-secreting adenoma group were significantly younger and had significantly lower rates of hypokalemia, whereas the pheochromocytoma group had significantly larger tumors and a significantly lower body mass index. Conclusion Our study found a larger percentage of functional tumors among adrenal incidentalomas than past reports, partly because we used a lower serum cortisol level after a dexamethasone suppression test to diagnose sub-clinical Cushing's syndrome and because all of the patients were hospitalized and could therefore receive more detailed examinations. Young patients with hypokalemia or lean patients with large adrenal tumors warrant particularly careful investigation.

  4. Embryonal rhabdomyosarcoma in a patient with a heterozygous frameshift variant in the DICER1 gene and additional manifestations of the DICER1 syndrome.

    Science.gov (United States)

    Fremerey, Julia; Balzer, Stefan; Brozou, Triantafyllia; Schaper, Joerg; Borkhardt, Arndt; Kuhlen, Michaela

    2017-07-01

    Germline mutations in the DICER1 gene are associated with an inherited cancer predisposition syndrome also known as the DICER1-syndrome, which is implicated in a broad range of tumors including pleuropulmonary blastoma, ovarian Sertoli-Leydig cell tumors, ciliary body medulloepithelioma (CBME), pituitary blastoma, embryonal rhabdomyosarcoma (eRMS), anaplastic renal sarcoma as well as ocular, sinonasal tumors ovarian sex-cord tumors, thyroid neoplasia and cystic nephroma. This study describes a novel, heterozygous frameshift DICER1 mutation in a patient, who is affected by different tumors of the DICER1-syndrome, including eRMS, CBME and suspected pleuropulmonary blastoma type I. By whole-exome sequencing of germline material using peripheral blood-derived DNA, we identified a single base pair duplication within the DICER1 gene (c.3405 dupA) that leads to a frameshift and results in a premature stop in exon 21 (p.Gly1136Arg). The metachronous occurrence of two unrelated tumor entities (eRMS and CBME) in a very young child within a short timeframe should have raised the suspicion of an underlying cancer susceptibility syndrome and should be prompt tested for DICER1.

  5. Case Report of a Left Atrial Myxoma Associated with Carney%u2019s Syndrome

    Directory of Open Access Journals (Sweden)

    Anil Ozen

    2016-05-01

    Full Text Available Primary cardiac neoplasms are very rare as compared to metastatic tumors. 70% to 80% of them are benign myxomas. Complications of myxomas include cyst and microabscess formation, embolization, syncope and sudden death. Rarely, cardiac myxomas are associated with primary nodular adrenal cortical disease, mammary fibroadenomas, testicular tumors or pitiutary adenomas with gigantism or acromegaly known as Carney%u2019s syndrome. We present a patient with a left atrial myxoma who underwent reoperation associated with Carney%u2019s syndrome.

  6. Molecular changes preceding endometrial and ovarian cancer: a study of consecutive endometrial specimens from Lynch syndrome surveillance.

    Science.gov (United States)

    Niskakoski, Anni; Pasanen, Annukka; Lassus, Heini; Renkonen-Sinisalo, Laura; Kaur, Sippy; Mecklin, Jukka-Pekka; Bützow, Ralf; Peltomäki, Päivi

    2018-03-27

    Molecular alterations preceding endometrial and ovarian cancer and the sequence of events are unknown. Consecutive specimens from lifelong surveillance for Lynch syndrome provides a natural setting to address such questions. To molecularly define the multistep gynecological tumorigenesis, DNA mismatch repair gene mutation carriers with endometrial or ovarian carcinoma or endometrial hyperplasia were identified from a nation-wide registry and endometrial biopsy specimens taken from these individuals during 20 years of screening were collected. A total of 213 endometrial and ovarian specimens from Lynch syndrome individuals and 197 histology-matched (non-serous) samples from sporadic cases were available for this investigation. The specimens were profiled for markers linked to endometrial and ovarian tumorigenesis, including ARID1A protein expression, mismatch repair status, and tumor suppressor gene promoter methylation. In Lynch syndrome-associated endometrial and ovarian carcinomas, ARID1A protein was lost in 61-100% and mismatch repair was deficient in 97-100%, compared to 0-17% and 14-44% in sporadic cases (P = 0.000). ARID1A loss appeared in complex hyperplasia and deficient mismatch repair and tumor suppressor gene promoter methylation in histologically normal endometrium. Despite quantitative differences between Lynch syndrome and sporadic cases, ARID1A expression, mismatch repair, and tumor suppressor gene promoter methylation divided endometrial samples from both patient groups into three categories of increasing abnormality, comprising normal endometrium and simple hyperplasia (I), complex hyperplasia with or without atypia (II), and endometrial cancer (III). Complex hyperplasias without vs. with atypia were molecularly indistinguishable. In conclusion, surveillance specimens from Lynch syndrome identify mismatch repair deficiency, tumor suppressor gene promoter methylation, and ARID1A loss as early changes in tumor development. Our findings are

  7. Non-syndromic Keratocystic Odontogenic Tumor Involving the Maxillary Sinus: Case Report

    Directory of Open Access Journals (Sweden)

    Rabelo, Gustavo Davi

    2010-09-01

    Full Text Available Introduction: The odontogenic keratocyst tumor is rarely found in maxilla. Case Report: This article describes a report of a case of a 60-year-old Caucasian female with an asymptomatic growth in the region of the posterior maxilla tumor diagnosed as odontogenic keratocyst. We discuss the diagnosis and workup for this type of injury.

  8. Temporal lobe pleomorphic xanthoastrocytoma and acquired BRAF mutation in an adolescent with the constitutional 22q11.2 deletion syndrome.

    Science.gov (United States)

    Murray, Jeffrey C; Donahue, David J; Malik, Saleem I; Dzurik, Yvette B; Braly, Emily Z; Dougherty, Margaret J; Eaton, Katherine W; Biegel, Jaclyn A

    2011-05-01

    DiGeorge syndrome, or velocardiofacial syndrome (DGS/VCFS), is a rare and usually sporadic congenital genetic disorder resulting from a constitutional microdeletion at chromosome 22q11.2. While rare cases of malignancy have been described, likely due to underlying immunodeficiency, central nervous system tumors have not yet been reported. We describe an adolescent boy with DGS/VCFS who developed a temporal lobe pleomorphic xanthoastrocytoma. High-resolution single nucleotide polymorphism array studies of the tumor confirmed a constitutional 22q11.21 deletion, and revealed acquired gains, losses and copy number neutral loss of heterozygosity of several chromosomal regions, including a homozygous deletion of the CDKN2A/B locus. The tumor also demonstrated a common V600E mutation in the BRAF oncogene. This is the first reported case of a patient with DiGeorge syndrome developing a CNS tumor of any histology and expands our knowledge about low-grade CNS tumor molecular genetics.

  9. Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA.

    Science.gov (United States)

    Schrader, Kasmintan A; Cheng, Donavan T; Joseph, Vijai; Prasad, Meera; Walsh, Michael; Zehir, Ahmet; Ni, Ai; Thomas, Tinu; Benayed, Ryma; Ashraf, Asad; Lincoln, Annie; Arcila, Maria; Stadler, Zsofia; Solit, David; Hyman, David M; Hyman, David; Zhang, Liying; Klimstra, David; Ladanyi, Marc; Offit, Kenneth; Berger, Michael; Robson, Mark

    2016-01-01

    Tumor genetic sequencing identifies potentially targetable genetic alterations with therapeutic implications. Analysis has concentrated on detecting tumor-specific variants, but recognition of germline variants may prove valuable as well. To estimate the burden of germline variants identified through routine clinical tumor sequencing. Patients with advanced cancer diagnoses eligible for studies of targeted agents at Memorial Sloan Kettering Cancer Center are offered tumor-normal sequencing with MSK-IMPACT, a 341-gene panel. We surveyed the germline variants seen in 187 overlapping genes with Mendelian disease associations in 1566 patients who had undergone tumor profiling between March and October 2014. The number of presumed pathogenic germline variants (PPGVs) and variants of uncertain significance per person in 187 genes associated with single-gene disorders and the proportions of individuals with PPGVs in clinically relevant gene subsets, in genes consistent with known tumor phenotypes, and in genes with evidence of second somatic hits in their tumors. The mean age of the 1566 patients was 58 years, and 54% were women. Presumed pathogenic germline variants in known Mendelian disease-associated genes were identified in 246 of 1566 patients (15.7%; 95% CI, 14.0%-17.6%), including 198 individuals with mutations in genes associated with cancer susceptibility. Germline findings in cancer susceptibility genes were concordant with the individual's cancer type in only 81 of 198 cases (40.9%; 95% CI, 34.3%-47.9%). In individuals with PPGVs retained in the tumor, somatic alteration of the other allele was seen in 39 of 182 cases (21.4%; 95% CI, 16.1%-28.0%), of which 13 cases did not show a known correlation of the germline mutation and a known syndrome. Mutations in non-cancer-related Mendelian disease genes were seen in 55 of 1566 cases (3.5%; 95% CI, 27.1%-45.4%). Almost every individual had more than 1 variant of uncertain significance (1565 of 1566 patients; 99

  10. A new mutation causing autosomal dominant periodic fever syndrome in a Danish family

    DEFF Research Database (Denmark)

    Weyhreter, Heike; Schwartz, Marianne; Kristensen, Tim D

    2003-01-01

    We describe four members in a family of 8 individuals over 3 generations with the autosomal dominant inherited periodic fever syndrome tumor necrosis factor receptor-associated periodic syndrome (TRAPS). The patients had recurrent episodes of fever, abdominal pain, arthritis, and rash. We examined...

  11. A Simple Method for DNA Extraction from Mature Date Palm Leaves: Impact of Sand Grinding and Composition of Lysis Buffer

    Science.gov (United States)

    Arif, Ibrahim A.; Bakir, Mohammad A.; Khan, Haseeb A.; Ahamed, Anis; Al Farhan, Ahmad H.; Al Homaidan, Ali A.; Al Sadoon, Mohammad; Bahkali, Ali H.; Shobrak, Mohammad

    2010-01-01

    Molecular marker techniques have been widely used for cultivar identification of inbred date palms (Phoenix dactylifera L.; Arecaceae) and biodiversity conservation. Isolation of highly pure DNA is the prerequisite for PCR amplification and subsequent use such as DNA fingerprinting and sequencing of genes that have recently been developed for barcoding. To avoid problems related to the preservation and use of liquid nitrogen, we examined sterile sand for grinding the date palm leaves. Individual and combined effects of sodium chloride (NaCl), polyvinylpyrrolidone (PVP) and lithium chloride (LiCl) with the cetyltrimethylammonium bromide (CTAB) method for a DNA yield of sufficient purity and PCR amplification were evaluated in this study. Presence of LiCl and PVP alone or together in the lysis buffer did not significantly improve the DNA yield and purity compared with the addition of NaCl. Our study suggested that grinding of date palm leaf with sterile sand and inclusion of NaCl (1.4 M) in the lysis buffer without the costly use of liquid nitrogen, PVP and LiCl, provides a DNA yield of sufficient purity, suitable for PCR amplification. PMID:20957085

  12. Tumor stroma with senescence-associated secretory phenotype in steatohepatitic hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Jee San Lee

    Full Text Available Senescence secretome was recently reported to promote liver cancer in an obese mouse model. Steatohepatitic hepatocellular carcinoma (SH-HCC, a new variant of HCC, has been found in metabolic syndrome patients, and pericellular fibrosis, a characteristic feature of SH-HCC, suggests that alteration of the tumor stroma might play an important role in SH-HCC development. Clinicopathological characteristics and tumor stroma showing senescence and senescence-associated secretory phenotype (SASP were investigated in 21 SH-HCCs and 34 conventional HCCs (C-HCCs. The expression of α-smooth muscle actin (α-SMA, p21Waf1/Cif1, γ-H2AX, and IL-6 was investigated by immunohistochemistry or immunofluorescence. SH-HCCs were associated with older age, higher body mass index, and a higher incidence of metabolic syndrome, compared to C-HCC (P <0.05, all. The numbers of α-SMA-positive cancer-associated fibroblasts (CAFs (P = 0.049 and α-SMA-positive CAFs co-expressing p21Waf1/Cif1 (P = 0.038, γ-H2AX (P = 0.065, and IL-6 (P = 0.048 were greater for SH-HCCs than C-HCCs. Additionally, non-tumoral liver from SH-HCCs showed a higher incidence of non-alcoholic fatty liver disease and a higher number of α-SMA-positive stellate cells expressing γ-H2AX and p21Waf1/Cif1 than that from C-HCCs (P <0.05, all. In conclusion, SH-HCCs are considered to occur more frequently in metabolic syndrome patients. Therein, senescent and damaged CAFs, as well as non-tumoral stellate cells, expressing SASP including IL-6 may contribute to the development of SH-HCC.

  13. A Restricted Spectrum of Mutations in the SMAD4 Tumor-Suppressor Gene Underlies Myhre Syndrome

    Science.gov (United States)

    Caputo, Viviana; Cianetti, Luciano; Niceta, Marcello; Carta, Claudio; Ciolfi, Andrea; Bocchinfuso, Gianfranco; Carrani, Eugenio; Dentici, Maria Lisa; Biamino, Elisa; Belligni, Elga; Garavelli, Livia; Boccone, Loredana; Melis, Daniela; Andria, Generoso; Gelb, Bruce D.; Stella, Lorenzo; Silengo, Margherita; Dallapiccola, Bruno; Tartaglia, Marco

    2012-01-01

    Myhre syndrome is a developmental disorder characterized by reduced growth, generalized muscular hypertrophy, facial dysmorphism, deafness, cognitive deficits, joint stiffness, and skeletal anomalies. Here, by performing exome sequencing of a single affected individual and coupling the results to a hypothesis-driven filtering strategy, we establish that heterozygous mutations in SMAD4, which encodes for a transducer mediating transforming growth factor β and bone morphogenetic protein signaling branches, underlie this rare Mendelian trait. Two recurrent de novo SMAD4 mutations were identified in eight unrelated subjects. Both mutations were missense changes altering Ile500 within the evolutionary conserved MAD homology 2 domain, a well known mutational hot spot in malignancies. Structural analyses suggest that the substituted residues are likely to perturb the binding properties of the mutant protein to signaling partners. Although SMAD4 has been established as a tumor suppressor gene somatically mutated in pancreatic, gastrointestinal, and skin cancers, and germline loss-of-function lesions and deletions of this gene have been documented to cause disorders that predispose individuals to gastrointestinal cancer and vascular dysplasias, the present report identifies a previously unrecognized class of mutations in the gene with profound impact on development and growth. PMID:22243968

  14. Proteus Syndrome With a Cranial Intraosseous Lipoma.

    Science.gov (United States)

    Wolfswinkel, Erik M; Imahiyerobo, Thomas A; McComb, J Gordon; Sanchez-Lara, Pedro A; Urata, Mark M

    2017-11-01

    Intraosseous lipomas are almost exclusively seen in the long bones. Presence in the craniofacial skeleton is extremely rare. A 7-year-old male is presented with a marked craniofacial deformation from a bony tumor containing an intraosseous lipoma. This finding established a clinical diagnosis of Proteus syndrome. Given the size of the tumor, producing an extensive deformity, three-dimensional modeling was used to generate a three-dimensional printed implant. The process to achieve a successful outcome is herein described.

  15. Neuroendocrine carcinoma of the ampulla of Vater causing ectopic adrenocorticotropic hormone-dependent Cushing's syndrome.

    Science.gov (United States)

    Kato, Akihisa; Hayashi, Kazuki; Naitoh, Itaru; Seno, Kyoji; Okada, Yukiko; Ban, Tesshin; Kondo, Hiromu; Nishi, Yuji; Umemura, Shuichiro; Hori, Yasuki; Natsume, Makoto; Joh, Takashi

    2016-07-01

    Ectopic adrenocorticotropic hormone (ACTH) is rarely secreted by neuroendocrine tumors. Although neuroendocrine tumors may occur at any site in the gastrointestinal system, they very rarely occur in the ampulla of Vater and have a poor prognosis. The present study described the first Cushing's syndrome as a result of ectopic ACTH arising from the ampulla of Vater neuroendocrine carcinoma. A 69-year-old female was admitted with clinical features of Cushing's syndrome, confirmed biochemically by hypokalemia, and elevated levels of ACTH and cortisol. In further investigations, a tumor of the ampulla of Vater and liver metastases were detected. Pathological analysis of the biopsy confirmed a neuroendocrine carcinoma, which was immunohistochemically positive for chromogranin A, synaptophysin, cluster of differentiation 56 and ACTH. Therefore, the present study diagnosed a functional and metastatic neuroendocrine carcinoma of the ampulla of Vater with ectopic ACTH production causing Cushing's syndrome. The patient succumbed to mortality 4 months later, despite administration of combined chemotherapy with irinotecan and cisplatin.

  16. Cauda equina syndrome as the initial presenting clinical feature of medulloblastoma: a case report

    Directory of Open Access Journals (Sweden)

    Al-Otaibi Faisal

    2012-05-01

    Full Text Available Abstract Introduction Medulloblastoma is one of the most common pediatric brain malignancies. The usual presenting clinical features are related to posterior fossa syndrome or/and hydrocephalus. Cauda equina syndrome is a very rare presentation for this disease. Case presentation We describe the case of a three-year-old boy with cauda equina syndrome as the initial presenting clinical feature for medulloblastoma. He was initially diagnosed as having a spinal tumor by magnetic resonance imaging scan. Subsequently, a cranial magnetic resonance imaging scan revealed a posterior fossa tumor with features of dissemination. He had substantial improvement after treatment. This case report is complemented by a literature review related to this unusual presentation. Conclusions Medulloblastoma primarily presenting with cauda equina syndrome is very rare. However, spinal drop metastasis should be considered in the pediatric age group to avoid suboptimal management.

  17. A case of Noonan's syndrome with terminal renal failure and neoplasmic disease

    International Nuclear Information System (INIS)

    Wierzbowska-Lange, B.; Sieniawska, M.; Polanski, J.; Kisiel, M.

    1993-01-01

    A 16 year old boy with Noonan syndrome diagnosed in the 3rd month of life was treated for renal insufficiency and hepatic tumor. Hemodialisis was started in preparation for surgery. Exacerbation of renal insufficiency occurred after surgical removal of the hepatic tumor together with the right hepatic lobe. Histopathologic examination showed adenoma hepatocellulare. Cysts in the extraperitoneal space appeared in the following months and were identified as cystes dysontogenetici benigni ''hamartia''. Renal function deteriorated during this time to end stage renal disease. The authors emphasize the possibility of good mental development in a patients with Noonan syndrome as well as the presence of urinary tract abnormalities and renal insufficiency of unknown origin - a phenomenon that has not yet been reported in other cases of Noonan syndrome. (author)

  18. Combined Ovarian and Adrenal Venous Sampling in the Localization of Adrenocorticotropic Hormone-Independent Ectopic Cushing Syndrome.

    Science.gov (United States)

    Chen, Shi; Li, Ran; Zhang, Xiaobo; Lu, Lin; Li, Ji; Pan, Hui; Zhu, Huijuan

    2018-03-01

    Cushing syndrome is rarely caused by the secretion of cortisol from ovarian tumors. In clinical decision-making, it is important to determine whether the ovarian tumor is capable of secreting cortisol. Selective ovarian and adrenal venous sampling is scarcely reported in the localization of ACTH-independent ectopic Cushing syndrome. We present a case of 40-year-old Chinese woman who had weight gain, hirsutism, hypertension, and menstrual disorder over 6 months. Her physical examination and biochemical assessment revealed adrenocorticotropic hormone-independent Cushing syndrome. Adrenal computed tomography scan indicated no abnormality. A mass of 5.7 cm × 4.2 cm × 3.4 cm was discovered by pelvic ultrasonography. Somatostatin receptor scintigraphy revealed no abnormal radioactivity intake. Combined ovarian and adrenal venous sampling together with a cortisol assay were conducted. Results revealed cortisol concentration of the right-side ovarian vein, left-side ovarian vein, and peripheral vein of 268.60, 29.00, and 35.18 μg/dL, respectively, suggesting a right-side ovarian origin. A right-side salpingo-oophorectomy was performed and the pathological diagnosis revealed ovarian steroid cell tumor, not otherwise specified. The cortisol level was substantially lower after the patient underwent surgery and symptoms of Cushing syndrome disappeared. At 3-year follow-up, the patient remained disease free, and no tumor was observed on pelvic ultrasonogram. Combined ovarian and adrenal venous sampling is valuable in the localization of adrenocorticotropic hormone-independent ectopic Cushing syndrome.

  19. Hereditary syndromes with enhanced radiosensitivity

    International Nuclear Information System (INIS)

    Lohmann, D.

    2000-01-01

    Sensitivity to ionizing radiation is modified by heritable genetic factors. This is exemplified by heritable disorders that are characterized by predisposition to the development of neoplasms. Cells derived from patients with ataxia telangiectasia, Nijmegen breakage syndrome and ataxia telangiektasia-like disorder show a markedly changed reaction to exposure to ionizing radiation. Correspondingly, at least in patients with ataxia telangiectasia, an enhanced radiosensitivity that is of clinical importance has been observed. In addition to these recessive disorders, some autosomal dominant cancer predisposition syndromes are associated with increased radiosensitivity. As cells from these patients still have a normal allele (that is dominant over the mutant allele), the cellular phenotype is most often normal. Specifically, there is no overtly altered reaction in response to ionizing radiation. Nevertheless, two dominant cancer predisposition syndromes, namely hereditary retinoblastoma and naevoid basal cell carcinoma syndrome, are associated with a enhanced radiosensitivity as indicated by increased development of tumors following radiation therapy. (orig.) [de

  20. Clot formation and lysis in platelet rich plasma of healthy donors and patients with resistant hypertension

    Directory of Open Access Journals (Sweden)

    I. I. Patalakh

    2018-04-01

    Full Text Available Hemostatic balance in blood is affected by numerous factors, including coagulation and fibrinolytic proteins, the wide spectrum of their inhibitors, and blood cells. Since platelets can participate in contradictory processes, they significantly complicate the whole picture. Therefore, nowadays the development of global assays of hemostasis, which can reflect the physiological process of hemostasis and can be used for point-of-care diagnosis of thrombosis, is crucial. This paper outlines a new approach we used to analyze the capabilities of clot waveform analysis tools to distinguish the response of platelet-rich plasma from healthy donors and patients with arterial hypertension caused by stimulation of coagulation and lysis (with exogenous thrombin and recombinant tissue-type plasminogen activator, respectively. In donor plasma, when the clot degradation was accompanied by 40 IU/ml of recombinant tissue-type plasminogen activator, platelets potentiated fibrinolysis more than coagulation, which ultimately shifts the overall balance to a profibrinolytic state. At the same time, for patients with hypertension, platelets, embedded in clot obtained from platelet-rich plasma, showed a weaker ability to stimulate fibrinolysis. The obtained data gives the evidence that platelets can act not only as procoagulants but also as profibrinolytics. By simultaneously amplifying coagulation and fibrinolysis, making their rates comparable, platelets would control plasma procoagulant activity, thereby regulating local hemostatic balance, the size and lifetime of the clot. Moreover, clot waveform analysis may be used to distinguish the effects of platelet-rich plasma on clotting or lysis of fibrin clots in healthy donors and patients with essential hypertension.

  1. Locally aggressive and multifocal phosphaturic mesenchymal tumors: two unusual cases of tumor-induced osteomalacia.

    Science.gov (United States)

    Higley, Meghan; Beckett, Brooke; Schmahmann, Sandra; Dacey, Elizabeth; Foss, Erik

    2015-12-01

    Tumor-induced osteomalacia (TIO) has long been recognized as a clinical paraneoplastic syndrome. The identification of a unique histopathologic entity, the phosphaturic mesenchymal tumor (PMT), as a distinct etiology for TIO has been a more recent discovery. The majority of published cases describe a solitary, non-aggressive appearing soft tissue or osseous lesions in patients with osteomalacia; aggressive appearing or multifocal lesions appear to be exceedingly rare. These tumors characteristically secrete fibroblast growth factor 23 (FGF23). Elevated serum levels of FGF23 result in phosphate wasting and osteomalacia. In the majority of cases, laboratory abnormalities and clinical signs and symptoms of osteomalacia precede identification of the causative lesion by years. Following diagnosis, complete resection with wide margins to prevent local recurrence is most often curative. Imaging characteristics of PMT are diverse and remain incompletely defined, as the majority of previous publications are outside of the radiologic literature. We present multiple imaging modalities in two cases of patients with debilitating osteomalacia and unusual appearing PMTs: one with a locally aggressive lesion leading to pathologic fracture, the second presenting with exceedingly rare multifocal PMT.

  2. Perlman syndrome : Four additional cases and review

    NARCIS (Netherlands)

    Henneveld, HT; van Lingen, RA; Hamel, BCJ; Stolte-Dijkstra, [No Value; van Essen, AJ

    1999-01-01

    Perlman syndrome was first described in 1973 and comprises nephromegaly with renal dysplasia and Wilms tumor, macrosomia, cryptorchidism, and multiple facial anomalies. Polyhydramnios and hypoglycaemia are often found. Twelve children have been described from six different families. Five came from

  3. Venous Thoracic Outlet Compression and the Paget-Schroetter Syndrome: A Review and Recommendations for Management

    International Nuclear Information System (INIS)

    Thompson, J. F.; Winterborn, R. J.; Bays, S.; White, H.; Kinsella, D. C.; Watkinson, A. F.

    2011-01-01

    Paget Schroetter syndrome, or effort thrombosis of the axillosubclavian venous system, is distinct from other forms of upper limb deep vein thrombosis. It occurs in younger patients and often is secondary to competitive sport, music, or strenuous occupation. If untreated, there is a higher incidence of disabling venous hypertension than was previously appreciated. Anticoagulation alone or in combination with thrombolysis leads to a high rate of rethrombosis. We have established a multidisciplinary protocol over 15 years, based on careful patient selection and a combination of lysis, decompressive surgery, and postoperative percutaneous venoplasty. During the past 10 years, a total of 232 decompression procedures have been performed. This article reviews the literature and presents the Exeter Protocol along with practical recommendations for management.

  4. Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis.

    Science.gov (United States)

    Cheng, Yu-Shen; Labavitch, John; VanderGheynst, Jean S

    2015-05-01

    Microalgae have been proposed as a potential feedstock for biofuel production; however, cell disruption is usually required for collection and utilization of cytoplasmic polysaccharides and lipids. Virus infection might be one approach to disrupt the cell wall. The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. Cytoplasmic starch accumulation increased from 5% to approximately 35% of the total dry weight when yeast extract decreased from 1 to 0.25 g L(-1). When cells were cultured with the lowest nitrogen levels, the total polysaccharide accounted for more than 50% of the cell wall, which was 1.7 times higher than the content in cells cultured with the highest nitrogen levels. The C/N ratio of the algal biomass decreased by a factor of approximately 2 when yeast extract increased from 0.25 to 1 g L(-1). After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. The results have implications on management of nitrogen for both the synthesis of products from algae and product recovery via viral lysis.

  5. Genetic anticipation in Swedish Lynch syndrome families

    OpenAIRE

    von Salomé, Jenny; Boonstra, Philip S.; Karimi, Masoud; Silander, Gustav; Stenmark-Askmalm, Marie; Gebre-Medhin, Samuel; Aravidis, Christos; Nilbert, Mef; Lindblom, Annika; Lagerstedt-Robinson, Kristina

    2017-01-01

    Among hereditary colorectal cancer predisposing syndromes, Lynch syndrome (LS) caused by mutations in DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2 is the most common. Patients with LS have an increased risk of early onset colon and endometrial cancer, but also other tumors that generally have an earlier onset compared to the general population. However, age at first primary cancer varies within families and genetic anticipation, i.e. decreasing age at onset in successive generations, ha...

  6. Lipopolysaccharide aggravated DOI-induced Tourette syndrome: elaboration for recurrence of Tourette syndrome.

    Science.gov (United States)

    Hongyan, Long; Zhenyang, Si; Chunyan, Wang; Qingqing, Pan

    2017-12-01

    Tourette syndrome (TS) is a neurological disorder characterized by highest familial recurrence rate among neuropsychiatric diseases with complicated inheritance. Recurrence of Tourette syndrome was frequently observed in clinical. Unexpectedly, the mechanism of recurrence of Tourette syndrome was failure to elucidate. Here, we first shown that lipopolysaccharide(LPS) may played an important role in the recurrence of Tourette syndrome. The TS model in rats was induced by DOI (the selective 5-HT2A/2C agonist 1-(2, 5-dimethoxy-4-iodophenyl) -2- aminopropane). The rats were randomly divided into 4 groups:(1)Control;(2) Control + LPS; (2)TS; (3)TS + LPS. The results demonstrated that the LPS treatment significantly increased stereotypic score and autonomic activity. LPS treatment also significantly increased inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum and striatum. Also, highly expressed TLR4, MyD88, P-NF-κBp65, P-IκBα in TS rats were increased respectively by LPS treatment as indicted in western blot analysis and immunohistochemistry analysis. Thus, it was supposed that lipopolysaccharide(LPS) may played an important role in the recurrence of Tourette syndrome and its mechanism was related to TLR/NF-κB pathway.

  7. Clinical Presentation and Diagnosis of Neuroendocrine Tumors.

    Science.gov (United States)

    Vinik, Aaron I; Chaya, Celine

    2016-02-01

    Neuroendocrine tumors (NETs) are slow-growing neoplasms capable of storing and secreting different peptides and neuroamines. Some of these substances cause specific symptom complexes, whereas others are silent. They usually have episodic expression, and the diagnosis is often made at a late stage. Although considered rare, the incidence of NETs is increasing. For these reasons, a high index of suspicion is needed. In this article, the different clinical syndromes and the pathophysiology of each tumor as well as the new and emerging biochemical markers and imaging techniques that should be used to facilitate an early diagnosis, follow-up, and prognosis are reviewed. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Nonislet Cell Tumor Hypoglycemia in a Patient with Adrenal Cortical Carcinoma

    Directory of Open Access Journals (Sweden)

    Se Won Kim

    2016-01-01

    Full Text Available Nonislet cell tumor hypoglycemia (NICTH is a rare but serious paraneoplastic syndrome in which a tumor secretes incompletely processed precursors of insulin-like growth factor-II (IGF-II, causing hypoglycemia. Here, we report an exceptional case of NICTH caused by nonfunctioning adrenocortical carcinoma in a 39-year-old male with recurrent hypoglycemia. The patient’s serum IGF-II/IGF-I ratio had increased to 27.8. The serum level of the IGF-II/IGF-I ratio was normalized after removal of the tumor, and the hypoglycemic attacks no longer occurred after the operation.

  9. Comprehensive Mutation Analysis of PMS2 in a Large Cohort of Probands Suspected of Lynch Syndrome or Constitutional Mismatch Repair Deficiency Syndrome.

    Science.gov (United States)

    van der Klift, Heleen M; Mensenkamp, Arjen R; Drost, Mark; Bik, Elsa C; Vos, Yvonne J; Gille, Hans J J P; Redeker, Bert E J W; Tiersma, Yvonne; Zonneveld, José B M; García, Encarna Gómez; Letteboer, Tom G W; Olderode-Berends, Maran J W; van Hest, Liselotte P; van Os, Theo A; Verhoef, Senno; Wagner, Anja; van Asperen, Christi J; Ten Broeke, Sanne W; Hes, Frederik J; de Wind, Niels; Nielsen, Maartje; Devilee, Peter; Ligtenberg, Marjolijn J L; Wijnen, Juul T; Tops, Carli M J

    2016-11-01

    Monoallelic PMS2 germline mutations cause 5%-15% of Lynch syndrome, a midlife cancer predisposition, whereas biallelic PMS2 mutations cause approximately 60% of constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer syndrome. Recently improved DNA- and RNA-based strategies are applied to overcome problematic PMS2 mutation analysis due to the presence of pseudogenes and frequent gene conversion events. Here, we determined PMS2 mutation detection yield and mutation spectrum in a nationwide cohort of 396 probands. Furthermore, we studied concordance between tumor IHC/MSI (immunohistochemistry/microsatellite instability) profile and mutation carrier state. Overall, we found 52 different pathogenic PMS2 variants explaining 121 Lynch syndrome and nine CMMRD patients. In vitro mismatch repair assays suggested pathogenicity for three missense variants. Ninety-one PMS2 mutation carriers (70%) showed isolated loss of PMS2 in their tumors, for 31 (24%) no or inconclusive IHC was available, and eight carriers (6%) showed discordant IHC (presence of PMS2 or loss of both MLH1 and PMS2). Ten cases with isolated PMS2 loss (10%; 10/97) harbored MLH1 mutations. We confirmed that recently improved mutation analysis provides a high yield of PMS2 mutations in patients with isolated loss of PMS2 expression. Application of universal tumor prescreening methods will however miss some PMS2 germline mutation carriers. © 2016 WILEY PERIODICALS, INC.

  10. Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

    Science.gov (United States)

    2017-09-26

    Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

  11. Viral lysis of Phaeocystis pouchetii: implications for algal population dynamics and heterotrophic C, N and P cycling

    DEFF Research Database (Denmark)

    Haaber, Jakob Brandt Borup; Middelboe, Mathias

    2009-01-01

    in the microbial food web was associated with significant N and P mineralization, supporting the current view that viral lysates can be an important source of inorganic nutrients in marine systems. In the presence of R. salina, the generated NH(4)(+) supported 11% of the observed R. salina growth. Regrowth...... of virus-resistant P. pouchetii following cell lysis was observed in long-term incubations (150 days), and possibly influenced by nutrient availability and competition from R. salina. The observed impact of viral activity on autotrophic and heterotrophic processes provides direct experimental evidence...

  12. Donor-Cell Origin High-Risk Myelodysplastic Syndrome Synchronous with an Intracranial Meningioma-Like Tumor, 8 Years after Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    G. Brás

    2017-01-01

    Full Text Available Secondary neoplasias are well known consequences of radiotherapy or chemotherapy for a primary cancer. In this report, we describe two rare secondary neoplasias occurring in the same patient: a meningioma-like intracranial tumor and high-risk myelodysplastic syndrome (MDS of donor-cells origin, both diagnosed simultaneously, 8 years after an allogeneic hematopoietic stem cell transplantation (allo-HSCT for chronic lymphocytic leukemia (CLL. Due to an engraftment failure during the first allo-HSCT of a matched related donor for CLL treatment, the salvage treatment was a second allo-HSCT. At the moment of meningioma-like tumor diagnosis, the patient was pancytopenic due to high-risk MDS, so it was decided to postpone a surgical intervention until hematological improvement. For the high-risk MDS of donor-cells origin the chosen treatment was induction with intensive chemotherapy. Due to refractory disease, the patient was treated with 5-azacitidine and donor-lymphocytes infusion with no response and, finally, a third allo-HSCT of a matched unrelated donor was performed. The patient died 6 months after the third allo-HSCT, in cytogenetic remission but without hematological recovery, due to an intracranial hemorrhage with origin in the meningioma-like tumor.

  13. Effects of X-irradiation on artificial blood vessel wall degradation by invasive tumor cells

    International Nuclear Information System (INIS)

    Heisel, M.A.; Laug, W.E.; Stowe, S.M.; Jones, P.A.

    1984-01-01

    Artificial vessel wall cultures, constructed by growing arterial endothelial cells on preformed layers of rat smooth muscle cells, were used to evaluate the effects of X-irradiation on tumor cell-induced tissue degradation. Bovine endothelial cells had radiation sensitivities similar to those of rat smooth muscle cells. Preirradiation of smooth muscle cells, before the addition of human fibrosarcoma (HT 1080) cells, did not increase the rate of degradation and destruction by the invasive cells. However, the degradation rate was decreased if the cultures were irradiated after the addition of HT 1080 cells. The presence of bovine endothelial cells markedly inhibited the destructive abilities of fibrosarcoma cells, but preirradiation of artificial vessel walls substantially decreased their capabilities to resist HT 1080-induced lysis. These findings suggest that the abilities of blood vessels to limit extravasation may be compromised by ionizing radiation

  14. Cytogenetics and molecular genetics of Wilms' tumor of childhood

    NARCIS (Netherlands)

    Slater, R. M.; Mannens, M. M.

    1992-01-01

    We describe the way in which application of cytogenetic and molecular genetic techniques to the study of Wilms' tumor (WT) of the kidney and the associated congenital disorders, such as sporadic aniridia and the Beckwith-Wiedemann syndrome, has led to identification of two regions on the short arm

  15. DSGOST inhibits tumor growth by blocking VEGF/VEGFR2-activated angiogenesis.

    Science.gov (United States)

    Choi, Hyeong Sim; Lee, Kangwook; Kim, Min Kyoung; Lee, Kang Min; Shin, Yong Cheol; Cho, Sung-Gook; Ko, Seong-Gyu

    2016-04-19

    Tumor growth requires a process called angiogenesis, a new blood vessel formation from pre-existing vessels, as newly formed vessels provide tumor cells with oxygen and nutrition. Danggui-Sayuk-Ga-Osuyu-Saenggang-Tang (DSGOST), one of traditional Chinese medicines, has been widely used in treatment of vessel diseases including Raynaud's syndrome in Northeast Asian countries including China, Japan and Korea. Therefore, we hypothesized that DSGOST might inhibit tumor growth by targeting newly formed vessels on the basis of its historical prescription. Here, we demonstrate that DSGOST inhibits tumor growth by inhibiting VEGF-induced angiogenesis. DSGOST inhibited VEGF-induced angiogenic abilities of endothelial cells in vitro and in vivo, which resulted from its inhibition of VEGF/VEGFR2 interaction. Furthermore, DSGOST attenuated pancreatic tumor growth in vivo by reducing angiogenic vessel numbers, while not affecting pancreatic tumor cell viability. Thus, our data conclude that DSGOST inhibits VEGF-induced tumor angiogenesis, suggesting a new indication for DSGOST in treatment of cancer.

  16. Hyphal growth of phagocytosed Fusarium oxysporum causes cell lysis and death of murine macrophages.

    Directory of Open Access Journals (Sweden)

    Katja Schäfer

    Full Text Available Fusarium oxysporum is an important plant pathogen and an opportunistic pathogen of humans. Here we investigated phagocytosis of F. oxysporum by J774.1 murine cell line macrophages using live cell video microscopy. Macrophages avidly migrated towards F. oxysporum germlings and were rapidly engulfed after cell-cell contact was established. F. oxysporum germlings continued hyphal growth after engulfment by macrophages, leading to associated macrophage lysis and escape. Macrophage killing depended on the multiplicity of infection. After engulfment, F. oxysporum inhibited macrophages from completing mitosis, resulting in large daughter cells fused together by means of a F. oxysporum hypha. These results shed new light on the initial stages of Fusarium infection and the innate immune response of the mammalian host.

  17. Universal screening for Lynch syndrome in endometrial cancers: frequency of germline mutations and identification of patients with Lynch-like syndrome.

    Science.gov (United States)

    Dillon, Jessica L; Gonzalez, Jorge L; DeMars, Leslie; Bloch, Katarzyna J; Tafe, Laura J

    2017-12-01

    Lynch syndrome (LS) is an inherited clinical syndrome characterized by a high risk of colorectal, endometrial (lifetime risk of up to 60%), ovarian, and urinary tract cancers. The diagnosis is confirmed by identification of germline mutations in the DNA mismatch repair genes MLH1, PMS2, MSH2, MSH6, or EPCAM. In 2015, our institution implemented universal screening of endometrial cancer (EC) hysterectomy specimens by mismatch repair immunohistochemistry (IHC) with reflex MLH1 promoter hypermethylation analysis for tumors with loss of MLH1/PMS2 expression. Patients with tumors negative for MLH1 methylation and those with a loss of the heterodimer pair MSH2 and MSH6, or isolated loss of either PMS2 or MSH6 were referred to the Familial Cancer Program for genetic counseling and consideration of germline testing. Between May 2015 to Dec 2016, 233 EC patients were screened by IHC for LS with a median age of 63 years. Sixty tumors (27%) had abnormal IHC staining results. Fifty-one (22%) harbored heterodimeric loss of MLH1 and PMS2, 49 of which showed MLH1 promoter methylation (1 failure, 1 negative). One showed loss of MLH1/PMS2 and MSH6, 2 showed loss of MSH2/MSH6, and 6 had isolated loss of MSH6 only. Ten patients underwent genetic counseling, and germline testing was performed in 8; LS was confirmed in 5 patients (2.1%). In addition, 3 patients with negative germline testing and presumed Lynch-like syndrome were identified and offered additional somatic testing. Universal screening for LS in EC patients has yielded positive results for identification of patients at risk for this inherited syndrome. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Concurrent insulinoma with mosaic Turner syndrome: A case report.

    Science.gov (United States)

    Wang, Shaoyun; Yang, Lijuan; Li, Jie; Mu, Yiming

    2015-03-01

    Turner syndrome is a chromosomal abnormality in which the majority of patients have a 45XO karyotype, while a small number have a 45XO/47XXX karyotype. Congenital adrenal hyperplasia has been previously reported in patients with Turner syndrome. Although insulinomas are the most common type of functioning pancreatic neuroendocrine tumor and have been reported in patients with multiple endocrine neoplasias, the tumors have not been reported in patients with mosaic Turner syndrome. The present study reports the first case of an insulinoma in a patient with 45XO/47XXX mosaic Turner syndrome. The patient suffered from recurrent hypoglycemia, which was relieved following ingestion of glucose or food. A 5-h glucose tolerance test was performed and the levels of glucose, C-Peptide and insulin were detected. In addition, computed tomography (CT) and ultrasound scanning were performed to evaluate the possibility of an insulinoma. Pathological examination and karyotyping were performed on a surgical specimen and a whole blood sample, respectively. The patient was found to suffer from premature ovarian failure, and a physical examination was consistent with a diagnosis of Turner syndrome. An ultrasound scan demonstrated streak ovaries and the patient was found to have a 45XO/47XXX karyotype. Furthermore, a lesion was detected in the pancreas following CT scanning, which was identified as an insulinoma following surgical removal and histological examination. In conclusion, the present study reports the first case of an insulinoma in a patient with mosaic Turner syndrome. Since mosaic Turner syndrome and insulinoma are rare diseases, an association may exist that has not been previously identified.

  19. Mediastinal mixed germ cell tumor in an infertile male with Klinefelter syndrome:A case report and literature review

    Directory of Open Access Journals (Sweden)

    Dinesh Pradhan

    2015-01-01

    Full Text Available Klinefelter syndrome (KS is a well-documented abnormality of the sex chromosome, with an incidence of 1 in 600 newborn males. It is characterized by a 47, XXY or a mosaic karyotype, hypergonadotrophic hypogonadism, infertility, reduced body hair, gynecomastia, and tall stature. Different neoplasms such as breast, testicular, and lymphoreticular malignancies may occur in 1% to2% of the cases with KS. Herein we describe a case of mediastinal mixed germ cell tumor (GCT in a 40-year-old male with KS. Interestingly, this case also had mitral valve prolapse, and an incidental papillary microcarcinoma of the thyroid gland. In view of the presence of pulmonary nodules, antemortem differential diagnoses considered were mycobacterial infection, lymphoma, thymic carcinoma, and a primary/metastatic neoplasm of the lung. As GCT was not considered, the serum markers of a GCT were not performed. The diagnosis of this rare mediastinal mixed GCT with KS was made at autopsy.

  20. Lysis of Chlamydomonas reinhardtii by high-intensity focused ultrasound as a function of exposure time.

    Science.gov (United States)

    Bigelow, Timothy A; Xu, Jin; Stessman, Dan J; Yao, Linxing; Spalding, Martin H; Wang, Tong

    2014-05-01

    Efficient lysis of microalgae for lipid extraction is an important concern when processing biofuels. Historically, ultrasound frequencies in the range of 10-40 kHz have been utilized for this task. However, greater efficiencies might be achievable if higher frequencies could be used. In our study, we evaluated the potential of using 1.1 MHz ultrasound to lyse microalgae for biofuel production while using Chlamydomonas reinhardtii as a model organism. The ultrasound was generated using a spherically focused transducer with a focal length of 6.34 cm and an active diameter of 6.36 cm driven by 20 cycle sine-wave tone bursts at a pulse repetition frequency of 2 kHz (3.6% duty cycle). The time-average acoustic power output was 26.2 W while the spatial-peak-pulse-average intensity (ISPPA) for each tone burst was 41 kW/cm(2). The peak compressional and rarefactional pressures at the focus were 102 and 17 MPa, respectively. The exposure time was varied for the different cases in the experiments from 5s to 9 min and cell lysis was assessed by quantifying the percentage of protein and chlorophyll release into the supernate as well as the lipid extractability. Free radical generation and lipid oxidation for the different ultrasound exposures were also determined. We found that there was a statistically significant increase in lipid extractability for all of the exposures compared to the control. The longer exposures also completely fragmented the cells releasing almost all of the protein and chlorophyll into the supernate. The cavitation activity did not significantly increase lipid oxidation while there was a minor trend of increased free radical production with increased ultrasound exposure. Copyright © 2013 Elsevier B.V. All rights reserved.