AIDS-related Kaposi sarcoma: findings on thallium-201 scintigraphy

International Nuclear Information System (INIS)

Lee, V.W.; Rosen, M.P.; Baum, A.; Cohen, S.E.; Cooley, T.P.; Liebman, H.A.

1988-01-01

No simple, noninvasive method is available for evaluating extracutaneous Kaposi sarcoma in AIDS patients or for following the tumor's response to treatment. We report our preliminary experience with thallium-201 scintigraphy in nine AIDS patients with proved Kaposi sarcoma. Eight of the nine had abnormal uptake of the radionuclide in skin, lymph nodes, oral cavity, vagina, and lungs. Only four of the nine had cutaneous Kaposi sarcoma at the time of scanning. All cutaneous and mucosal lesions were thallium avid. Two of the six patients with thallium-avid nodes underwent nodal biopsy. Both biopsies confirmed the diagnosis of Kaposi sarcoma. Cutaneous Kaposi sarcoma developed later in one of these patients, showing the efficacy of thallium scintigraphy for the early detection of extracutaneous lesions. These preliminary results show thallium avidity in Kaposi sarcoma involving the skin and various extracutaneous sites (lymph nodes, lung, mucosa, and vagina). Thallium scintigraphy is a potentially useful procedure for detecting extracutaneous Kaposi sarcoma in AIDS patients

Physiotherapy management of patients with HIV-associated Kaposi's sarcoma.

Science.gov (United States)

Harris-Love, Michael O; Shrader, Joseph A

2004-01-01

Kaposi's sarcoma is the most common form of cancer in patients with human immunodeficiency virus (HIV) infection. Although Kaposi sarcoma lesions may contribute to significant physical impairments, there is a lack of scientific literature detailing the role of physiotherapy in the treatment of HIV-associated Kaposi's sarcoma. The present Case Report includes two males, aged 36 and 39 years, seropositive for HIV with invasive Kaposi's sarcoma. Patient A was evaluated for bilateral foot pain caused by plantar surface Kaposi s sarcoma lesions that rendered him unable to walk. He progressed to walking 400feet after a treatment regimen of gait training with the use of custom plastazote sandals. Patient B was evaluated for right lower extremity lymphoedema secondary to invasive Kaposi's sarcoma. He experienced an 18% reduction in limb volume, a 38% reduction in pain and a 20 degrees increase in terminal knee flexion after therapeutic exercise and the use of compressive bandaging and garments. This Case Report suggests that physiotherapy interventions may be valuable in the conservative management of patients with HIV-associated Kaposi s sarcoma.

Kaposi's Sarcoma

Science.gov (United States)

... Name: Category: Share: Yes No, Keep Private Kaposi’s Sarcoma Share | Kaposi’s sarcoma (KS) is a vascular neoplasm of the skin ... symptoms of HIV infection. This type of Kaposi's sarcoma progresses slowly, with new lesions appearing every few ...

Radiological findings of pulmonary Kaposi's sarcoma. Manifestaciones radiologicas del sarcoma de Kaposi pulmonar

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Rosello, J.A.; Hernandez, S.; Arranz, M.; Jareo, J.; Ancoechea, J.

1994-01-01

Kaposi's sarcoma (KS) is the most common neoplasm in AIDS patients. The incidence of pulmonary involvement is approximately 20%. The radiological findings are reported in plain chest x-ray and computed tomography (CT) in 15 patients diagnosed as having pulmonary Kaposi's sarcoma, in whom concomitant pulmonary infection was ruled out. The most common radiological pattern was that of bilateral perihilar interstitial involvement (86%), while poorly defined multiple nodules seldom presented (13%). In 40% of cases, the pulmonary parenchymal lesion was accompanied by pleural effusion. This sign is useful in the differential diagnosis involving opportunistic P. carinii pneumonia, a very common process in these patients which rarely presents with pleural effusion. The chest CT finding that was most characteristic of pulmonary Kaposi's sarcoma was bilateral perihilar peribronchovascular enlargement. (Author)

Sarcoma de Kaposi em membros inferiores: relato de caso Kaposi sarcoma in the lower limbs: case report

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Jorge Agle Kalil

2010-12-01

Full Text Available O sarcoma de Kaposi é uma neoplasia angioproliferativa maligna que na maioria das vezes se restringe à pele e ao tecido subcutâneo; porém, pode aparecer de forma mais agressiva, atingindo a cavidade oral, o trato gastrointestinal e os pulmões (sarcoma de Kaposi visceral. É classificado com quatro variantes clínco-epidemiológicas: clássica, endêmica, iatrogênica e epidêmica, todas associadas ao herpes vírus humano tipo 8. O objetivo desta publicação foi relatar um caso raro de sarcoma de Kaposi em paciente idosa imunossuprimida, não relacionado à síndrome da imunodeficiência adquirida, que evoluiu de forma desfavorável em um período de cinco meses a partir do aparecimento de lesões bolhosas hemáticas e necróticas que, posteriormente, progrediram com intensa exsudação local, desidratação, insuficiência renal e piora do estado geral, evoluindo então a óbito, tendo como causa mortis a falência de múltiplos órgãos.The Kaposi sarcoma is an angio-proliferative malignant neoplasm that mostly affects the skin and subcutaneous tissue, although it can present in a more aggressive form, involving the oral cavity, lungs and gastrointestinal tract (visceral Kaposi sarcoma. It is classified into 4 clinical-epidemiological types: classic, endemic, iatrogenic and epidemic, all of them associated with the human herpesvirus 8. We report a rare case of Kaposi sarcoma in an elderly immunodepressed female patient, not related to the acquired immunodeficiency syndrome, that evolved fatally in five months, since the appearance of hematic necrotic bullous lesions which progressed with intense local exudation, dehydration, renal insufficiency and worsening of the clinical status, ending in death, caused by multiple organ failure.

Osseous Kaposi sarcoma in an HIV-positive patient

International Nuclear Information System (INIS)

Thanos, Loukas; Mylona, Sofia; Kalioras, Vasilios; Pomoni, Maria; Batakis, Nikolaos

2004-01-01

A case of osseous Kaposi sarcoma in a 35-year-old man is described. The patient (HIV-positive for 8 years) suffered from cutaneous Kaposi sarcoma and presented with right-sided chest pain. He underwent a chest CT scan that revealed three osteolytic lesions involving rib and vertebra with large soft tissue masses, without cutaneous lesions at these sites. CT-guided core needle biopsy led to a histological diagnosis of Kaposi sarcoma. (orig.)

Sarcoma de Kaposi em paciente transplantada renal em uso de Fk-506 Kaposi's Sarcoma in a renal transplant patient receiving Fk-506

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Jorge David Rocha Zanol

2002-12-01

Full Text Available O Sarcoma de Kaposi (SK é neoplasia maligna multicêntrica, cutânea e extracutânea, que tem sido descrita em pacientes transplantados renais que recebem terapia imunossupressora clássica. Este estudo descreve um caso de sarcoma de Kaposi em paciente transplantada renal recebendo FK-506, que surgiu 10 meses após o transplante.Kaposi's sarcoma is a cutaneous and extra cutaneous multicentric malignancy that has been widely described in renal-transplant patients under classic immunosuppressive therapy. This study describes a renal-transplant patient under immunosuppressive therapy with FK-506 who presented Kaposi's sarcoma 10 months after the transplantation.

Thoracic manifestations of Kaposi`s sarcoma in AIDS: radiological findings; Manifestacoes toracicas do sarcoma de Kaposi na sindrome da imunodeficiencia adquirida: aspectos radiologicos

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Marchiori, Edson [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Dept. de Radiologia; [Universidade Federal, Rio de Janeiro, RJ (Brazil); Baptista, Maria Ines Garcia; Cardenas, Gloria Pamela; Costa Praxedes, Marcia da [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Dept. de Radiologia; Boechat, Lucia de Fatima; Quaresma, Patricia Souto Maior [Universidade Federal, Rio de Janeiro, RJ (Brazil). Hospital Universitario Clementino Fraga Filho. Servico de Radiodiagnostico

1995-09-01

The radiological findings of 189 cases of Kaposi`s sarcoma occurring in patients with AIDS were studied. There was also made pathological correlations in these patients. Interstitial reticular infiltrations were frequently detected on thoracic examination showing paracardiac confluent areas. There was also lymphadenopathy, gross nodules and pleural fluid accumulation. Although there was no detection of any pathognomonic aspect, the interstitial reticular infiltration finding together with the paracardiac confluent areas and associated with gross nodules, is highly indicative to thoracic involvement by the disease. (author). 32 refs., 5 figs., 2 tabs.

Iatrogenic colorectal Kaposi sarcoma complicating a refractory ...

African Journals Online (AJOL)

Kaposi sarcoma is a mesenchymal tumor associated to a human herpes virus-8. It often occurs in human immunodeficiency virus-positive subjects. Colorectal localization is rare. We report the case of a colorectal Kaposi sarcoma complicating a refractory ulcerative colitis treated with surgery after the failure of ...

Advanced oral HIV-associated Kaposi sarcoma with facial ...

African Journals Online (AJOL)

Rapidly progressive facial lymphoedoema that develops concurrently with or immediately after rapid enlargement of oral Kaposi sarcoma in human immunodeficiency virus (HIV) -seropositive persons forebodes death. Previously, we reported on three patients with HIV-associated Kaposi sarcoma who had not been ...

Management of HIV associated Kaposi's Sarcoma in Malawi ...

African Journals Online (AJOL)

Kaposi's sarcoma is a common malignancy in Malawi and is often managed with single agent vincristine. This article outlines feasible combination chemotherapy for Kaposi's sarcoma in Malawi which should be made more widely available. Malawi Medical Journal Vol. 20 (4) 2008: pp. 129-132.

Structural basis for TatA oligomerization: an NMR study of Escherichia coli TatA dimeric structure.

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Yi Zhang

Full Text Available Many proteins are transported across lipid membranes by protein translocation systems in living cells. The twin-arginine transport (Tat system identified in bacteria and plant chloroplasts is a unique system that transports proteins across membranes in their fully-folded states. Up to date, the detailed molecular mechanism of this process remains largely unclear. The Escherichia coli Tat system consists of three essential transmembrane proteins: TatA, TatB and TatC. Among them, TatB and TatC form a tight complex and function in substrate recognition. The major component TatA contains a single transmembrane helix followed by an amphipathic helix, and is suggested to form the translocation pore via self-oligomerization. Since the TatA oligomer has to accommodate substrate proteins of various sizes and shapes, the process of its assembly stands essential for understanding the translocation mechanism. A structure model of TatA oligomer was recently proposed based on NMR and EPR observations, revealing contacts between the transmembrane helices from adjacent subunits. Herein we report the construction and stabilization of a dimeric TatA, as well as the structure determination by solution NMR spectroscopy. In addition to more extensive inter-subunit contacts between the transmembrane helices, we were also able to observe interactions between neighbouring amphipathic helices. The side-by-side packing of the amphipathic helices extends the solvent-exposed hydrophilic surface of the protein, which might be favourable for interactions with substrate proteins. The dimeric TatA structure offers more detailed information of TatA oligomeric interface and provides new insights on Tat translocation mechanism.

Kaposi's Sarcoma Of The Lung: A Case Report.

African Journals Online (AJOL)

user

2004-12-02

Dec 2, 2004 ... E-mail: eussiri@yahoo.com. Pulmonary Kaposi's sarcoma is a rare condition. Its diagnosis may be tricky due to its similarities in clinical and radiological features with pulmonary opportunistic infections as well as other lung lesions. Treatment for Kaposi's sarcoma include radiotherapy, chemotherapy and/or.

Relaxed evolution in the tyrosine aminotransferase gene tat in old world fruit bats (Chiroptera: Pteropodidae).

Science.gov (United States)

Shen, Bin; Fang, Tao; Yang, Tianxiao; Jones, Gareth; Irwin, David M; Zhang, Shuyi

2014-01-01

Frugivorous and nectarivorous bats fuel their metabolism mostly by using carbohydrates and allocate the restricted amounts of ingested proteins mainly for anabolic protein syntheses rather than for catabolic energy production. Thus, it is possible that genes involved in protein (amino acid) catabolism may have undergone relaxed evolution in these fruit- and nectar-eating bats. The tyrosine aminotransferase (TAT, encoded by the Tat gene) is the rate-limiting enzyme in the tyrosine catabolic pathway. To test whether the Tat gene has undergone relaxed evolution in the fruit- and nectar-eating bats, we obtained the Tat coding region from 20 bat species including four Old World fruit bats (Pteropodidae) and two New World fruit bats (Phyllostomidae). Phylogenetic reconstructions revealed a gene tree in which all echolocating bats (including the New World fruit bats) formed a monophyletic group. The phylogenetic conflict appears to stem from accelerated TAT protein sequence evolution in the Old World fruit bats. Our molecular evolutionary analyses confirmed a change in the selection pressure acting on Tat, which was likely caused by a relaxation of the evolutionary constraints on the Tat gene in the Old World fruit bats. Hepatic TAT activity assays showed that TAT activities in species of the Old World fruit bats are significantly lower than those of insectivorous bats and omnivorous mice, which was not caused by a change in TAT protein levels in the liver. Our study provides unambiguous evidence that the Tat gene has undergone relaxed evolution in the Old World fruit bats in response to changes in their metabolism due to the evolution of their special diet.

A Unique Case of Classic Kaposi's sarcoma restricted to the toes.

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Renteria, Anne S; Marshall, Vickie A; Sun, Yanyu; Chockalingam, Porselvi; Cooper, Jay S; Huang, Yiwu; Whitby, Denise

2013-01-01

Kaposi's sarcoma associated-herpesvirus causes all forms of Kaposi's sarcoma, and six major subtypes have been described based on the amino acid sequences of the open reading frame K1. A 71-year-old man from China, HIV negative, presented with nodules on the dorsal aspect of his toes. Biopsy confirmed the diagnosis of Kaposi's sarcoma and virology studies of his blood and saliva confirmed the presence of Kaposi's sarcoma associated-herpesvirus infection. Viral genotyping was consistent with subtype C3. Intervention has been deferred as our patient has remained clinically asymptomatic and without evident growth of his lesions over a 2-year follow up. We herein report the first known case of Kaposi's sarcoma restricted to the toes caused by the viral subtype C3 in an HIV-negative patient from Harbin, China.

[Association of Kaposi sarcoma--multiple myeloma. A new case].

Science.gov (United States)

Cohen, J D; Thomas, E; Garnier, N; Hellier, I; Durand, L; Guilhou, J J; Baldet, P; Blotman, F

2000-11-01

Kaposi's disease is an angiogenic multifocal cancer process that has several forms, namely Mediterranean, African, HIV-associated, and secondary to a preexisting immunodepressive state (hematological disorder, corticosteroid therapy, immunodepressive treatment). Whatever its form, Kaposi's sarcoma is probably associated with a chronic viral human herpes type 8 infection (HHV8). This virus has been implicated in the pathogenesis of multiple myeloma (17 cases recorded to date). In the present study, a further case of Kaposi's sarcoma associated with multiple myeloma has been reported. However, Epstein-Barr virus, cytomegalovirus, hepatitis B and C, HIV and HHV8 serologies were negative. Radiotherapy on the lower limbs was initiated. It is concluded that HHV8 does not appear to play a pathogenic role in cases of multiple myeloma, given the rarity of the association between Kaposi's sarcoma/multiple myeloma/HHV8.

Sarcoma de Kaposi: Etiología viral y transmisión sexual

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Luis Alejandro Gómez

1999-07-01

Full Text Available EI Sarcoma de Kaposi (SK es la neoplasia más común en los pacientes infectados con el Virus de la lnmunodeficiencia Humana (VIH, tiene relación directa con la progresión de la infección a SIDA y tiene valor como predictor de sobrevida de los pacientes. Históricamente se ha vinculado con factores directamente relacionados can el VlH como el gen tat y la proteína del mismo nombre, así como se ha sugerido una fuerte asociación con factores de crecimiento y drogas inmunosupresoras, en aquellos individuos que han presentado el sarcoma sin estar infectados par el VIH. Los más recientes estudios en torno a la tiopatogenia del SK, se han encaminado a la búsqueda de un agente causal de naturaleza viral llamado el Herpes, Virus Humano tipo 8 (HVH-8, que se transmite por contacto sexual y del cual se ha logrado establecer su presencia en fluido seminal y prostático, así como en las lesiones de SK y en otros tejidos del cuerpo como piel y mucosas. La cavidad oral es el sitio de más frecuente aparición del Sarcoma de Kaposi y por tanto ha sido de especial interés cuantificar la cantidad de HVH-8 que se encuentra en esta y en otras lesiones bucales asociadas con el SIDA, donde se ha encontrado el virus en relación can SK clínicamente visible y no se ha relacionado con otras lesiones orales asociadas al VIH. De igual manera se ha determinado la presencia del virus en la saliva de pacientes que presentan el SK lo que se ha relacionado can la alta posibilidad de transmisión del HVH-8 par prácticas de sex a oral.

Relaxed evolution in the tyrosine aminotransferase gene tat in old world fruit bats (Chiroptera: Pteropodidae.

Directory of Open Access Journals (Sweden)

Bin Shen

Full Text Available Frugivorous and nectarivorous bats fuel their metabolism mostly by using carbohydrates and allocate the restricted amounts of ingested proteins mainly for anabolic protein syntheses rather than for catabolic energy production. Thus, it is possible that genes involved in protein (amino acid catabolism may have undergone relaxed evolution in these fruit- and nectar-eating bats. The tyrosine aminotransferase (TAT, encoded by the Tat gene is the rate-limiting enzyme in the tyrosine catabolic pathway. To test whether the Tat gene has undergone relaxed evolution in the fruit- and nectar-eating bats, we obtained the Tat coding region from 20 bat species including four Old World fruit bats (Pteropodidae and two New World fruit bats (Phyllostomidae. Phylogenetic reconstructions revealed a gene tree in which all echolocating bats (including the New World fruit bats formed a monophyletic group. The phylogenetic conflict appears to stem from accelerated TAT protein sequence evolution in the Old World fruit bats. Our molecular evolutionary analyses confirmed a change in the selection pressure acting on Tat, which was likely caused by a relaxation of the evolutionary constraints on the Tat gene in the Old World fruit bats. Hepatic TAT activity assays showed that TAT activities in species of the Old World fruit bats are significantly lower than those of insectivorous bats and omnivorous mice, which was not caused by a change in TAT protein levels in the liver. Our study provides unambiguous evidence that the Tat gene has undergone relaxed evolution in the Old World fruit bats in response to changes in their metabolism due to the evolution of their special diet.

Modulation of microtubule assembly by the HIV-1 Tat protein is strongly dependent on zinc binding to Tat

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Muller Sylviane

2008-07-01

Full Text Available Abstract Background During HIV-1 infection, the Tat protein plays a key role by transactivating the transcription of the HIV-1 proviral DNA. In addition, Tat induces apoptosis of non-infected T lymphocytes, leading to a massive loss of immune competence. This apoptosis is notably mediated by the interaction of Tat with microtubules, which are dynamic components essential for cell structure and division. Tat binds two Zn2+ ions through its conserved cysteine-rich region in vitro, but the role of zinc in the structure and properties of Tat is still controversial. Results To investigate the role of zinc, we first characterized Tat apo- and holo-forms by fluorescence correlation spectroscopy and time-resolved fluorescence spectroscopy. Both of the Tat forms are monomeric and poorly folded but differ by local conformational changes in the vicinity of the cysteine-rich region. The interaction of the two Tat forms with tubulin dimers and microtubules was monitored by analytical ultracentrifugation, turbidity measurements and electron microscopy. At 20°C, both of the Tat forms bind tubulin dimers, but only the holo-Tat was found to form discrete complexes. At 37°C, both forms promoted the nucleation and increased the elongation rates of tubulin assembly. However, only the holo-Tat increased the amount of microtubules, decreased the tubulin critical concentration, and stabilized the microtubules. In contrast, apo-Tat induced a large amount of tubulin aggregates. Conclusion Our data suggest that holo-Tat corresponds to the active form, responsible for the Tat-mediated apoptosis.

Kaposi sarcoma appearing 20 year post renal transplant | Yassir ...

African Journals Online (AJOL)

A kidney- transplanted Saudi patient presented with a skin rash for which he was treated as fungal infection .The patient developed these lesions 20 years after transplantation. The clinical picture was that of Kaposi\\'s sarcoma which was confirmed by histopathology .The patient developed these lesions after he was shifted ...

Case Report Kaposi\\'s Sarcoma Of Rare Anatomical Site: A Report ...

African Journals Online (AJOL)

Kaposi's Sarcoma (KS) of unusual sites are commonly associated with immunodeficiency and it is therefore known as one of the AIDS defining tumors. KS of the conjunctiva and traumatized areas of the foot especially the sole are listed as some of the uncommon sites for this tumor. One of the patients developed oral thrush ...

Kaposi's sarcoma involving the thyroid in a patient with AIDS

International Nuclear Information System (INIS)

Krauth, P.H.; Katz, J.F.

1987-01-01

A 30-year-old man with acquired immune deficiency syndrome (AIDS) and Kaposi's sarcoma had a palpable thyroid mass and cervical lymphadenopathy. Nuclear medicine and ultrasound scans revealed multiple thyroid nodules. Results of biopsy showed Kaposi's sarcoma metastatic to the thyroid

Human herpesvirus 8 (HHV-8 and the etiopathogenesis of Kaposi's sarcoma Herpesvírus humano tipo 8 (HHV-8 e a etiopatogênese do sarcoma de Kaposi

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Jair Carneiro Leão

2002-08-01

Full Text Available OBJECTIVE: To review the current literature on human herpesvirus 8 with particular attention to the aspects related to the etiopathogenesis of Kaposi's sarcoma. MATERIALS AND METHODS: The authors searched original research and review articles on specific aspects of human herpesvirus 8 infection, including virology, epidemiology, transmission, diagnosis, natural history, therapy, and Kaposi's sarcoma etiopathogenesis. The relevant material was evaluated and reviewed. RESULTS: Human herpesvirus 8 is a recently discovered DNA virus that is present throughout the world but with major geographic variation. In the Western world, the virus, transmitted mainly by means of sexual contact, is strongly associated with Kaposi's sarcoma and body cavity-based lymphoma and more controversially with multiple myeloma and other non-proliferative disorders. There is no specific effective treatment, but HIV protease inhibitors may play an indirect role in the clearance of human herpesvirus 8 DNA from peripheral blood mononuclear cells of HIV-infected patients. Human herpesvirus 8 DNA is present in saliva, but there are as yet no documented cases of nosocomial transmission to health care workers. The prevalence of human herpesvirus 8 among health care workers is probably similar to that in the general population. CONCLUSION: Human herpesvirus 8 appears to be, at least in Western Europe and United States, restricted to a population at risk of developing Kaposi's sarcoma. Human herpesvirus 8 certainly has the means to overcome cellular control and immune responses and thus predispose carriers to malignancy, particularly Kaposi's sarcoma. The wide diffusion of Human herpesvirus 8 in classic Kaposi's sarcoma areas appears to represent an important factor in the high incidence of the disease. However, additional co-factors are likely to play a role in the development of Kaposi's sarcoma.OBJETIVO: O objetivo do presente artigo foi revisar a literatura recente em rela

Definitive Brachytherapy for Kaposi's Sarcoma

International Nuclear Information System (INIS)

Williams, A.; Ezzell, G.; Zalupski, M.; Fontanesi, J.

1996-01-01

Purpose: To assess the efficacy and possible complications in patients diagnosed with Kaposi's sarcoma and treated with definitive brachytherapy. Methods and Materials: Between January, 1995 and December, 1995, four patients with Kaposi's sarcoma (KS) were treated with brachytherapy. Three patients, all with positive HIV status were treated using Iridium 192 (Ir-192) sources via a high-dose rate remote afterloader. One patient with endemic KS was treated using the application of catheters loaded with Californium 252. Eight sites were treated and included scalp, feet, nose, penis, hand, neck, and back. Dose rate for Ir-192 was 330cGy/fx to a total dose of 990cGy. The Californium was delivered as 100nGy/b.i.d. to a total dose of 900nGy. Follow-up as ranged from 2-6 months. Results: All four patients remain alive. Seven of eight sites have had complete clinical response and each patient has reported durable pain relief that has not subsided through last follow-up of 1/96. Two of eight sites, both treated with surface mold technique with Californium 252 developed moist desquamation. The remaining six sites did not demonstrate significant toxicity. Conclusion: Brachytherapy can offer Kaposi's sarcoma patients results that are equivalent to external beam radiation therapy, with minimal complications, a shorter treatment time and potential cost effectiveness

Drugs Approved for Kaposi Sarcoma

Science.gov (United States)

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Kaposi sarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

Hepatic Kaposi sarcoma. Sonographic and computed tomographic aspects

International Nuclear Information System (INIS)

Defalque, D.; Menu, Y.; Nahum, H.; Matheron, S.; Girard, P.M.

1988-01-01

AIDS-related Kaposi sarcoma is most often multicentric and extensive. Hepatic involvement is unusual and asymptomatic. An anicteric cholestasis may exist. Ultrasonography shows a pedicular echogenic infiltration and a heterogeneous parenchyma with small hyperechoic nodules. On CT, these hypodense lesions are related to the involvement of the hepatic pedicle. This is linked to angiosarcomatous tumorous tissue infiltration of the liver evolving along portal branches. In a patient suffering from cutaneous or digestive Kaposi sarcoma lesions, these radiological aspects are suggestive of hepatic involvement [fr

Interaction of the phospholipid scramblase 1 with HIV-1 Tat results in the repression of Tat-dependent transcription

International Nuclear Information System (INIS)

Kusano, Shuichi; Eizuru, Yoshito

2013-01-01

Highlights: •PLSCR1 specifically interacted with HIV-1 Tat in vitro and in vivo. •PLSCR1 repressed Tat-dependent transactivation of the HIV-1 LTR. •Suppression of PLSCR1 expression enhanced the levels of HIV-1 transcripts. •PLSCR1 reduced the nuclear localization of Tat. -- Abstract: Human phospholipid scramblase 1 (PLSCR1) is an interferon (IFN)-stimulated gene and possesses an IFN-mediated antiviral function. We show here that PLSCR1 directly interacts with human immunodeficiency virus type-1 (HIV-1) Tat. This interaction occurs both in vitro and in vivo through amino acids 160–250 of PLSCR1. Overexpression of PLSCR1 efficiently represses the Tat-dependent transactivation of the HIV-1 long terminal repeat (LTR) and reduces the nuclear translocation of Tat. In addition, shRNA-mediated suppression of endogenous PLSCR1 expression enhances the levels of gag mRNA in an HIV-1-infected T-cell line. These findings indicate that PLSCR1 negatively regulates the Tat-dependent transactivation of the HIV-1 LTR during HIV-1 infection

Radiotherapy of epidemic Kaposi's sarcoma in patients with AIDS

International Nuclear Information System (INIS)

Westermann, V.A.; Mueller, R.P.; Adler, M.; Bendick, C.; Rasokat, H.

1990-01-01

From August 1986 to May 1989, 15 patients suffering from Kaposi's sarcoma and serologically proven HIV infections were treated in the Department of Radiotherapy, University of Cologne, Medical Hospital. All patients were male and homosexual. Therapeutic objectives were palliation of pain and functional impairment as well as elimination of the cosmetically disturbing Kaposi's sarcoma. 68 localizations (facial skin, torso, extremities, sole of the foot, penis, oral mucosa and oropharynx) were irradiated. Depending on the individual therapy regimen, photons or high-energy electrons up to a total dose of 26 to 40 Gy, with single doses of 1.8 to 2.5 Gy were applied four to five times a week. In 66% of the cases, complete remission was achieved within the area of irradiation at the dermal or mucosal level, with at most a discrete residual pigmentation of the cluster remaining. Partial remission with at least 50% regression or a distinctive residual pigmentation was achieved in 31%. In 3% of the cases, a less than 50% regression of the Kaposi's lesions were achieved after radiotherapy. There were five local recurrences. Treatment with radiation is an effective local therapy in epidemic Kaposi's sarcoma and yields good functional and cosmetic results and also provides relief from pain. (orig.) [de

Kaposi's sarcoma in the northern part of Nigeria: pre-aids era ...

African Journals Online (AJOL)

Background: In the last two decades, the incidence of Kaposi's sarcoma has increased due to acquired immune deficiency syndrome epidemic. This study was designed to highlight the characteristic features of Kaposi's sarcoma in our centre before this epidemic. Method: In a retrospective study, all histologically diagnosed ...

Kaposi sarcoma of the conjunctiva and eyelids associated with the acquired immunodeficiency syndrome

International Nuclear Information System (INIS)

Shuler, J.D.; Holland, G.N.; Miles, S.A.; Miller, B.J.; Grossman, I.

1989-01-01

Three studies were performed to assess more accurately the prevalence, natural history, and appropriate treatment of acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma involving ocular structures. The first study was a prospective examination of 100 male homosexuals with AIDS-related Kaposi sarcoma for signs of ophthalmic involvement. Of the 20 patients who had ophthalmic lesions, 16 had eyelid lesions and seven had conjunctival lesions. In four patients, the ophthalmic lesion was the first, and initially the only, clinically identified manifestation of Kaposi sarcoma. The second study was a retrospective review of all patients with ophthalmic Kaposi sarcoma examined at one institution over a six-year period to determine its natural history and response to therapy. Most lesions were slowly progressive and responded to systemic drug therapy. Six patients were successfully treated with radiation therapy to prevent complications. The third study was a retrospective review of all patients with AIDS-related ophthalmic Kaposi sarcoma treated with local irradiation by one radiation oncologist. Each of 12 patients showed a response to treatment, and ten had a complete resolution of lesions, but recurrences were common. Side effects included skin erythema in six patients and hair loss in one patient. For local treatment of ophthalmic Kaposi sarcoma, irradiation appears to be safe and effective for palliative therapy

Detection of Human Herpes Virus 8 in Kaposi's sarcoma tissues at ...

African Journals Online (AJOL)

Introduction: Human herpes virus-8, a γ2-herpes virus, is the aetiological agent of Kaposi sarcoma. Recently, Kaposi's sarcoma cases have increased in Zambia. However, the diagnosis of this disease is based on morphological appearance of affected tissues using histological techniques, and the association with its ...

MANIFESTATIONS OF AGGRESSIVE ATYPICAL KAPOSI'S ...

African Journals Online (AJOL)

... weight loss (86.8%), skin nodules (86.4%) and diarrhoea (55.3%). Virtually, all occupational groups were affected, with students, civil servants and businessmen topping the list. Key Words: Atypical Aggressive Kaposi's sarcoma, HIV infection. African Journal Of Clinical And Experimental Microbiology Jan 2004 Vol.5 No.1 ...

[Anorectal manifestations of sexually transmissible diseases. Kaposi's sarcoma].

Science.gov (United States)

Libeskind, M; Malbran, J; Agard, D; Pannetier, C; Lecouillard, C; Ivanovic, A

1984-01-01

The proctologist is above all concerned with the known recrudescence of venereal diseases. Examples reviewed are diseases of bacterial origin (syphilis, gonorrhea, soft chancre, donovanosis and chlamydiosis), appropriate antibiotic therapy and diseases of viral origin (herpes, condyloma acuminatum). Also noted are other bacterial, viral and parasitic diseases and, indeed, cancers of which Kaposi's sarcoma is the example, even though these are not manifested anorectally. New data on Kaposi's sarcoma, its' relationships with venereal disease and AIDS are presented. With these complex problems, the central role of male homosexuality and lowered cellular immunity widens considerably the professional scope of the proctologist.

How do I diagnose Microscopic challenge: Kaposi Sarcoma of the oral mucosa

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Gian Kayser

2015-09-01

Full Text Available Kaposi Sarcoma is a rare vascular neoplasm of the skin and mucosal membranes associated with human herpes virus 8 (HHV-8 infection. It is usually associated with severe suppression of the immune system, e. g. in the setting of human immune deficiency virus (HIV infection and aquired immune deficiency syndrome (AIDS. Here we present a case of a 33 year old female, who was diagnosed to be HIV-positive in march 2015. On physical examination petechial bleedings were recognized at the hard palate. The biopsy specimen showed an ulcerated squamous mucosa with granulation tissue. Single swollen endothelia within angulated vessels were suspicious for a vascular tumor. Immunohistochemical evaluation revealed proliferating endothelia positive for HHV-8. Thus, the diagnosis of a Kaposi Sarcoma within granulation tissue at the hard palate was made. The diagnosis of Kaposi Sarcoma can be very difficult, especially in the setting of concurrent inflammation. Immunohistochemical workup is therefore recommended and necessary to verify the diagnosis of Kaposi Sarcoma.

Combination Therapy for Advanced Kaposi Sarcoma

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In this clinical trial, adult patients with any form of advanced Kaposi sarcoma will be treated with liposomal doxorubicin and bevacizumab every 3 weeks for a maximum of six treatments.  Patients who respond to this therapy or have stable disease will rec

Extensive interactions between HIV TAT and TAF(II)250.

Science.gov (United States)

Weissman, J D; Hwang, J R; Singer, D S

2001-03-09

The HIV transactivator, Tat, has been shown to be capable of potent repression of transcription initiation. Repression is mediated by the C-terminal segment of Tat, which binds the TFIID component, TAF(II)250, although the site(s) of interaction were not defined previously. We now report that the interaction between Tat and TAF(II)250 is extensive and involves multiple contacts between the Tat protein and TAF(II)250. The C-terminal domain of Tat, which is necessary for repression of transcription initiation, binds to a segment of TAF(II)250 that encompasses its acetyl transferase (AT) domain (885-1034 amino acids (aa)). Surprisingly, the N-terminal segment of Tat, which contains its activation domains, also binds to TAF(II)250 and interacts with two discontinuous segments of TAF(II)250 located between 885 and 984 aa and 1120 and 1279 aa. Binding of Tat to the 885-984 aa segment of TAF(II)250 requires the cysteine-rich domain of Tat, but not the acidic or glutamine-rich domains. Binding by the N-terminal domain of Tat to the 1120-1279 aa TAF(II)250 segment does not involve the acidic, cysteine- or glutamine-rich domains. Repression of transcription initiation by Tat requires functional TAF(II)250. We now demonstrate that transcription of the HIV LTR does not depend on TAF(II)250 which may account for its resistance to Tat mediated repression.

Report of an autopsyzed case of Kaposi sarcoma developed in therapeutically irradiated region

International Nuclear Information System (INIS)

Tanahashi, Yoshio; Sato, Akihiko

1975-01-01

A case of Kaposi sarcoma developed in the right gluteal region of 57 year-old woman was reported in the present paper. The patient received surgical excision of uterine cervical cancer and also gastric cancer in the different time in her past history. Post-operative radiotherapy following uterine excision consisted of 3,350 to 3,650 R of respective 180 kV of X-ray and 60 Co. The mass developed in the region irradiated during the past deep therapy, and showed resistance to Linac irradiation and bleomycin. The masses which seemed to be the same with that in the skin developed in the both lung, and bleomycin administered was not effective. In addition, a mass developed in the right inguinal lymphnode which was considered to be the metastasis from cervical cancer, and was wholly excised. The patient died from pneumonia one year after the manifestation of Kaposi sarcoma. This case was very extraordinary because of the triplicated tumors, i.e., gastric cancer, uterine cervical cancer, and Kaposi sarcoma. The nature of Kaposi sarcoma was discussed from our experience and literature. Kaposi sarcoma in our case, was suggested to be a radiation-induced tumor, and the mechanism of occurrence was considered to be that of multi-centric tumor. (Tsukamoto, Y.)

Report of an autopsyed case of Kaposi sarcoma developed in therapeutically irradiated region

Energy Technology Data Exchange (ETDEWEB)

Tanahashi, Y; Sato, A [Tohoku Univ., Sendai (Japan). School of Medicine

1975-04-01

A case of Kaposi sarcoma developed in the right gluteal region of 57 year-old woman was reported in the present paper. The patient received surgical excision of uterine cervical cancer and also gastric cancer in the different time in her past history. Post-operative radiotherapy following uterine excision consisted of 3,350 to 3,650 R of respective 180 kV of X-ray and /sup 60/Co. The mass developed in the region irradiated during the past deep therapy, and showed resistance to Linac irradiation and bleomycin. The masses which seemed to be the same with that in the skin developed in the both lung, and bleomycin administered was not effective. In addition, a mass developed in the right inguinal lymphnode which was considered to be the metastasis from cervical cancer, and was wholly excised. The patient died from pneumonia one year after the manifestation of Kaposi sarcoma. This case was very extraordinary because of the triplicated tumors, i.e., gastric cancer, uterine cervical cancer, and Kaposi sarcoma. The nature of Kaposi sarcoma was discussed from our experience and literature. Kaposi sarcoma in our case, was suggested to be a radiation-induced tumor, and the mechanism of occurrence was considered to be that of multi-centric tumor.

The Tat protein of human immunodeficiency virus-1 enhances hepatitis C virus replication through interferon gamma-inducible protein-10

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Qu Jing

2012-04-01

Full Text Available Abstract Background Co-infection with human immunodeficiency virus-1 (HIV-1 and hepatitis C virus (HCV is associated with faster progression of liver disease and an increase in HCV persistence. However, the mechanism by which HIV-1 accelerates the progression of HCV liver disease remains unknown. Results HIV-1/HCV co-infection is associated with increased expression of interferon gamma-induced protein-10 (IP-10 mRNA in peripheral blood mononuclear cells (PBMCs. HCV RNA levels were higher in PBMCs of patients with HIV-1/HCV co-infection than in patients with HCV mono-infection. HIV-1 Tat and IP-10 activated HCV replication in a time-dependent manner, and HIV-1 Tat induced IP-10 production. In addition, the effect of HIV-1 Tat on HCV replication was blocked by anti-IP-10 monoclonal antibody, demonstrating that the effect of HIV-1 Tat on HCV replication depends on IP-10. Taken together, these results suggest that HIV-1 Tat protein activates HCV replication by upregulating IP-10 production. Conclusions HIV-1/HCV co-infection is associated with increased expression of IP-10 mRNA and replication of HCV RNA. Furthermore, both HIV-1 Tat and IP-10 activate HCV replication. HIV-1 Tat activates HCV replication by upregulating IP-10 production. These results expand our understanding of HIV-1 in HCV replication and the mechanism involved in the regulation of HCV replication mediated by HIV-1 during co-infection.

Imaging of Kaposi sarcoma in a transplanted liver: A rare case report

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Saumya Gupta

2015-06-01

Full Text Available In post-transplant patients, de novo malignancies such as post-transplant lymphoproliferative disease (PTLD, lung carcinoma, renal cell carcinoma, cutaneous malignancies, and Kaposi sarcoma are now seen. The immunotherapy used to prevent graft failure indirectly increases their risk. We present a rare case of visceral Kaposi sarcoma in a patient with orthotopic liver transplant.

Kaposi's sarcoma in organ transplant recipients. The Collaborative Transplantation Research Group of Ile de France.

Science.gov (United States)

Farge, D

1993-01-01

Kaposi's Sarcoma (KS) is a tumour of multicentric origin with increased frequency after organ transplantation. To date, only North American data from the Cincinnati Transplant Tumor Registry have given some information about this disease in organ transplant recipients, but its true prevalence still has to be determined. In order to analyze Kaposi's sarcoma after kidney, liver and heart transplantation, we performed a retrospective study using the oldest registry of organ transplant recipients in Europe. Among all 7923 organ transplant recipients recorded in the Groupe Collaboratif de Recherche en Transplantation de l'Ile de France (GCIF) registry from 1968 to 1990, we analyzed the prevalence and the clinical characteristics of Kaposi's sarcoma in 6229 kidney, 727 liver and 967 heart transplant recipients. In the subgroup of kidney transplant recipients, we assessed the role of cyclosporine on disease evolution. Overall prevalence of Kaposi's sarcoma after organ transplantation was 0.52%, but it was significantly higher among liver (1.24%) than among kidney (0.45%) and heart (0.41%) transplant recipients. Chronic hepatitis B surface antigen carriers were more frequent in liver than in kidney transplant recipients who developed Kaposi's sarcoma (66% vs 21%, p < 0.03). Following kidney transplantation, Kaposi's sarcoma was more severe in patients receiving cyclosporine (n = 16) when compared with those under conventional immunosuppression (n = 12). True prevalence of Kaposi's sarcoma among European transplant recipients is high (0.52%) and appeared significantly higher in liver compared with other organ transplant recipients. Cyclosporine seems to increase severity of the disease among kidney transplant recipient.

Relación entre el virus humano herpes 8 y el sarcoma de Kaposi en pacientes positivos y negativos para el VIH Relationship between human herpes virus 8 and Kaposi sarcomain HIV positive and negative patients

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BEATRIZ OROZCO

2007-09-01

Full Text Available Introducción. Parece existir una relación de causalidad entre la infección por el virus humano herpes 8 ( human Herpesvirus 8, HHV-8 y el desarrollo de sarcoma de Kaposi, especialmente en la población positiva para virus de inmunodeficiencia humana (VIH. Objetivo. Fue determinar la relación entre los resultados serológicos positivos para HHV-8 y el sarcoma de Kaposi en pacientes positivos y negativos para VIH de Medellín, buscando la relación con distintas variables. Materiales y métodos. Es un estudio descriptivo, de cohorte, prospectivo, del suero de 98 pacientes de diferentes instituciones de salud de Medellín, los cuales se dividieron en cuatro grupos para determinar por inmunofluorescencia su seropositividad frente a HHV-8 y poder asociar en forma univariada y bivariada con diferentes variables. Resultados. Se estudiaron 98 sueros. En el grupo de pacientes con sarcoma de Kaposi y VIH, 83,3% fueron positivos para HHV- 8, en el grupo sin sarcoma de Kaposi pero con sífilis, 20,8% fueron positivos para HHV-8, en el grupo sin sarcoma de Kaposi pero VIH positivos, 8% fueron positivos para HHV-8 y en el grupo de sueros de banco de sangre, 4% fueron positivos para HHV-8. La presencia de sarcoma de Kaposi no tuvo relación con la evolución de la enfermedad por VIH ni con el recuento de CD4/ml. Conclusiones. El HHV-8 circula en nuestro medio y existe una relación entre la infección por este virus y el desarrollo de sarcoma de Kaposi, especialmente en pacientes con enfermedades de transmisión sexual y VIH positivos.Background: Apparently, there is a relationship between human Herpesvirus 8 (HHV-8 infection and Kaposi´ sarcoma, especially in HIV-positive population. Objectives: To define the relationship between seropositivity against HHV- 8 and Kaposi´ sarcoma in an HIV positive and negative population from Medellín, looking for its relationship with different variables. Methods: It is a descriptive, cohort, prospective study which

Disseminated Kaposi sarcoma with epithelioid morphology in an HIV/AIDS patient: A previously unreported variant.

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Basra, Pukhraz; Paramo, Juan; Alexis, John

2018-04-16

Kaposi sarcoma is an oligoclonal HHV-8-driven vascular proliferation that was first described by a Viennese dermatologist Dr Moritz Kaposi. The disease has been seen in different clinical-epidemiological settings with a wide morphologic spectrum. We report a 52-year-old Caucasian man with HIV/AIDS and Kaposi sarcoma who presented with dyspnea and pleural effusion. He reported numerous tender subcutaneous nodules developing over the past few months on his chest, back and abdomen. An excisional biopsy of one of the nodules was performed. Touch preps revealed malignant cells in clusters. Microscopically, the neoplasm appeared undifferentiated with an epithelioid morphology, and involved the dermis and subcutaneous fat. Despite the medical history, Kaposi sarcoma was not considered foremost in the differential diagnosis. The malignant cells were positive for vimentin and negative for S100 protein, keratin AE1/3, CK7, CK20, napsin A, TTF-1 and synaptophysin. Additional stains revealed positivity for HHV-8, CD31 and D2-40, supporting the diagnosis of Kaposi sarcoma. Kaposi sarcoma has been well described with many variants that may cause diagnostic difficulty. An epithelioid variant has not been reported and consequently, may cause misinterpretation of an otherwise well-known entity that may become life threatening if appropriate treatment is not initiated in a timely manner. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Kaposi's sarcoma-associated herpesvirus infection and Kaposi's sarcoma in Brazil

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S. Ramos-da-Silva

2006-05-01

Full Text Available Kaposi's sarcoma (KS became a critical health issue with the emergence of acquired immunodeficiency syndrome (AIDS in the 1980s. Four clinical-epidemiological forms of KS have been described: classical KS, endemic KS, iatrogenic KS, and AIDS-associated KS. In 1994, Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus type 8 was identified by Chang and colleagues, and has been detected worldwide at frequencies ranging from 80 to 100%. The aim of the present study was to evaluate the frequency of KSHV infection in KS lesions from HIV-positive and HIV-negative patients in Brazil, as well as to review the current knowledge about KS transmission and detection. For these purposes, DNA from 51 cases of KS was assessed by PCR: 20 (39.2% cases of classical KS, 29 (56.9% of AIDS-associated KS and 2 (3.9% of iatrogenic KS. Most patients were males (7.5:1, M/F, and mean age was 47.9 years (SD = ± 18.7 years. As expected, HIV-positive KS patients were younger than patients with classical KS. On the other hand, patients with AIDS-associated KS have early lesions (patch and plaque compared to classical KS patients (predominantly nodular lesions. This is assumed to be the result of the early diagnose of KS in the HIV-positive setting. KSHV infection was detected by PCR in almost all cases (48/51; 94.1%, irrespectively of the clinical-epidemiological form of KS. These results show that KSHV is associated with all forms of KS in Brazilian patients, a fact that supports the role of this virus in KS pathogenesis.

Kaposi sarcoma herpesvirus pathogenesis

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Koch, Sandra; Schulz, Thomas F.

2017-01-01

Kaposi sarcoma herpesvirus (KSHV), taxonomical name human gammaherpesvirus 8, is a phylogenetically old human virus that co-evolved with human populations, but is now only common (seroprevalence greater than 10%) in sub-Saharan Africa, around the Mediterranean Sea, parts of South America and in a few ethnic communities. KSHV causes three human malignancies, Kaposi sarcoma, primary effusion lymphoma, and many cases of the plasmablastic form of multicentric Castleman's disease (MCD) as well as occasional cases of plasmablastic lymphoma arising from MCD; it has also been linked to rare cases of bone marrow failure and hepatitis. As it has colonized humans physiologically for many thousand years, cofactors are needed to allow it to unfold its pathogenic potential. In most cases, these include immune defects of genetic, iatrogenic or infectious origin, and inflammation appears to play an important role in disease development. Our much improved understanding of its life cycle and its role in pathogenesis should now allow us to develop new therapeutic strategies directed against key viral proteins or intracellular pathways that are crucial for virus replication or persistence. Likewise, its limited (for a herpesvirus) distribution and transmission should offer an opportunity for the development and use of a vaccine to prevent transmission. This article is part of the themed issue ‘Human oncogenic viruses’. PMID:28893942

A triad of lys12, lys41, arg78 spatial domain, a novel identified heparin binding site on tat protein, facilitates tat-driven cell adhesion.

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Jing Ai

Full Text Available Tat protein, released by HIV-infected cells, has a battery of important biological effects leading to distinct AIDS-associated pathologies. Cell surface heparan sulfate protoglycans (HSPGs have been accepted as endogenous Tat receptors, and the Tat basic domain has been identified as the heparin binding site. However, findings that deletion or substitution of the basic domain inhibits but does not completely eliminate Tat-heparin interactions suggest that the basic domain is not the sole Tat heparin binding site. In the current study, an approach integrating computational modeling, mutagenesis, biophysical and cell-based assays was used to elucidate a novel, high affinity heparin-binding site: a Lys12, Lys41, Arg78 (KKR spatial domain. This domain was also found to facilitate Tat-driven β1 integrin activation, producing subsequent SLK cell adhesion in an HSPG-dependent manner, but was not involved in Tat internalization. The identification of this new heparin binding site may foster further insight into the nature of Tat-heparin interactions and subsequent biological functions, facilitating the rational design of new therapeutics against Tat-mediated pathological events.

Seroconversion for human herpesvirus 8 during HIV infection is highly predictive of Kaposi's sarcoma

NARCIS (Netherlands)

Renwick, N.; Halaby, T.; Weverling, G. J.; Dukers, N. H.; Simpson, G. R.; Coutinho, R. A.; Lange, J. M.; Schulz, T. F.; Goudsmit, J.

1998-01-01

The finding of antibodies against human herpesvirus 8 (HHV-8) is associated with the occurrence of Kaposi's sarcoma in persons infected with HIV. However, the predictive value of HHV-8 antibodies for Kaposi's sarcoma in HIV infection is unknown. The Amsterdam Cohort Studies on HIV infection and AIDS

Poppers, Kaposi's sarcoma, and HIV infection: empirical example of a strong confounding effect?

Science.gov (United States)

Morabia, A

1995-01-01

Are there empirical examples of strong confounding effects? Textbooks usually show examples of weak confounding or use hypothetical examples of strong confounding to illustrate the paradoxical consequences of not separating out the effect of the studied exposure from that of second factor acting as a confounder. HIV infection is a candidate strong confounder of the spuriously high association reported between consumption of poppers, a sexual stimulant, and risk of Kaposi's sarcoma in the early phase of the AIDS epidemic. To examine this hypothesis, assumptions must be made on the prevalence of HIV infection among cases of Kaposi's sarcoma and on the prevalence of heavy popper consumption according to HIV infection in cases and controls. Results show that HIV infection may have confounded the poppers-Kaposi's sarcoma association. However, it cannot be ruled out that HIV did not qualify as a confounder because it was either an intermediate variable or an effect modifier of the association between popper inhalation and Kaposi's sarcoma. This example provides a basis to discuss the mechanism by which confounding occurs as well as the practical importance of confounding in epidemiologic research.

Tat-mediated protein delivery in living Caenorhabditis elegans

International Nuclear Information System (INIS)

Delom, Frederic; Fessart, Delphine; Caruso, Marie-Elaine; Chevet, Eric

2007-01-01

The Tat protein from HIV-1 fused with heterologous proteins traverses biological membranes in a transcellular process called: protein transduction. This has already been successfully exploited in various biological models, but never in the nematode worm Caenorhabditis elegans. TAT-eGFP or GST-eGFP proteins were fed to C. elegans worms, which resulted in the specific localization of Tat-eGFP to epithelial intestinal cells. This system represents an efficient tool for transcellular transduction in C. elegans intestinal cells. Indeed, this approach avoids the use of tedious purification steps to purify the TAT fusion proteins and allows for rapid analyses of the transduced proteins. In addition, it may represent an efficient tool to functionally analyze the mechanisms of protein transduction as well as to complement RNAi/KO in the epithelial intestinal system. To sum up, the advantage of this technology is to combine the potential of bacterial expression system and the Tat-mediated transduction technique in living worm

MD simulation of the Tat/Cyclin T1/CDK9 complex revealing the hidden catalytic cavity within the CDK9 molecule upon Tat binding.

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Kaori Asamitsu

Full Text Available In this study, we applied molecular dynamics (MD simulation to analyze the dynamic behavior of the Tat/CycT1/CDK9 tri-molecular complex and revealed the structural changes of P-TEFb upon Tat binding. We found that Tat could deliberately change the local flexibility of CycT1. Although the structural coordinates of the H1 and H2 helices did not substantially change, H1', H2', and H3' exhibited significant changes en masse. Consequently, the CycT1 residues involved in Tat binding, namely Tat-recognition residues (TRRs, lost their flexibility with the addition of Tat to P-TEFb. In addition, we clarified the structural variation of CDK9 in complex with CycT1 in the presence or absence of Tat. Interestingly, Tat addition significantly reduced the structural variability of the T-loop, thus consolidating the structural integrity of P-TEFb. Finally, we deciphered the formation of the hidden catalytic cavity of CDK9 upon Tat binding. MD simulation revealed that the PITALRE signature sequence of CDK9 flips the inactive kinase cavity of CDK9 into the active form by connecting with Thr186, which is crucial for its activity, thus presumably recruiting the substrate peptide such as the C-terminal domain of RNA pol II. These findings provide vital information for the development of effective novel anti-HIV drugs with CDK9 catalytic activity as the target.

Lymphoproliferative disorders in non-AIDS associated Kaposi's ...

African Journals Online (AJOL)

The association of the non-AIDS-related, classic fonn of Kaposi's sarcoma (KS) with secondary malignancies, especially Iymphoproliferative disorders, has frequently been noted. However, in endemic: African-type KS, such an association has been reported only rarely. A review of 62 non-AIDS-related cases of KS treated ...

HIV-associated cutaneous Kaposi's sarcoma - palliative local treatment by radiotherapy

International Nuclear Information System (INIS)

Saran, F.H.; Adamietz, I.A.; Thilmann, C.; Mose, S.; Boettcher, H.D.

1997-01-01

The increasing number of HIV-infected patients makes palliative treatment of HIV-associated Kaposi's sarcoma more common. We retrospectively evaluated a reduced fractionated radiotherapy with 20 Gy in respect to response rates and acute side-effects. From January 1992 to January 1995, 52 patients with HIV-associated Kaposi's sarcoma were treated with 133 single portals. Six weeks after the end of radiotherapy 42 patients with 124 portals were evaluable with respect to response rates and side-effects. Of the treated portals 32% were judged as complete responses (CR), 55% as partial responses (PR) and 12% as no change (NC). Skin reactions RTOG, grade 1 were seen in 74% of the patients. Compared with literature data the reduced overall dose of 20 Gy in 10 fractions led to a reduction of CRs by approximately 50% while the overall response rate remained equal. The success of radiotherapy for the nodular component of Kaposi's sarcoma can be improved, if a dose exceeding 20 Gy in 10 fractions is applied but at the cost of increasing side-effects in case that non-conventional fractionation schemes are used. (orig.)

Functional substitution by TAT-utrophin in dystrophin-deficient mice.

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Kevin J Sonnemann

2009-05-01

Full Text Available The loss of dystrophin compromises muscle cell membrane stability and causes Duchenne muscular dystrophy and/or various forms of cardiomyopathy. Increased expression of the dystrophin homolog utrophin by gene delivery or pharmacologic up-regulation has been demonstrated to restore membrane integrity and improve the phenotype in the dystrophin-deficient mdx mouse. However, the lack of a viable therapy in humans predicates the need to explore alternative methods to combat dystrophin deficiency. We investigated whether systemic administration of recombinant full-length utrophin (Utr or DeltaR4-21 "micro" utrophin (muUtr protein modified with the cell-penetrating TAT protein transduction domain could attenuate the phenotype of mdx mice.Recombinant TAT-Utr and TAT-muUtr proteins were expressed using the baculovirus system and purified using FLAG-affinity chromatography. Age-matched mdx mice received six twice-weekly intraperitoneal injections of either recombinant protein or PBS. Three days after the final injection, mice were analyzed for several phenotypic parameters of dystrophin deficiency. Injected TAT-muUtr transduced all tissues examined, integrated with members of the dystrophin complex, reduced serum levels of creatine kinase (11,290+/-920 U versus 5,950+/-1,120 U; PBS versus TAT, the prevalence of muscle degeneration/regeneration (54%+/-5% versus 37%+/-4% of centrally nucleated fibers; PBS versus TAT, the susceptibility to eccentric contraction-induced force drop (72%+/-5% versus 40%+/-8% drop; PBS versus TAT, and increased specific force production (9.7+/-1.1 N/cm(2 versus 12.8+/-0.9 N/cm(2; PBS versus TAT.These results are, to our knowledge, the first to establish the efficacy and feasibility of TAT-utrophin-based constructs as a novel direct protein-replacement therapy for the treatment of skeletal and cardiac muscle diseases caused by loss of dystrophin.

Simultaneous lymph node involvement by Castleman disease and Kaposi sarcoma

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Luciana Wernersbach Pinto

2011-02-01

Full Text Available Both multicentric Castleman disease and Kaposi sarcoma are more frequently observed in HIV infected patients. The coexistence of these Human herpesvirus 8 related lesions, in the same tissue, has been observed, but literature reports are scant. On the other hand, the expression of HHV-8-LANA-1 is easily demonstrable by immunohistochemistry. This has been shown to be a powerful tool for the diagnosis of these entities. The aim of this report is to communicate our experience with a case of multicentric Castleman disease occurring in the setting of HIV infection, which demonstrated microscopic Kaposi sarcoma in the same lymph node during the pathological work-up

Chylothorax associated with non-endemic Kaposi's sarcoma ...

African Journals Online (AJOL)

Chylothorax is a rare cause of pleural effusion, seen in approximately 2% of cases. In HIV-positive patients with Kaposi's sarcoma (KS), the development of chylothorax presents as a diagnostic challenge with an aggressive course and poor, often lethal outcome. In this clinical scenario, the aetiology of chylothorax may ...

Primary gastric Kaposi's sarcoma presenting first with upper ...

African Journals Online (AJOL)

Kaposi's sarcoma (KS) is the most common tumour among human immunodeficiency syndrome (HIV) infected individuals, but its involvement of the gastrointestinal tract was reported long before the acquired immunodeficiency syndrome (AIDS) epidemic. Although most cases of gastrointestinal KS are asymptomatic, ...

Viral oncogene-induced DNA damage response is activated in Kaposi sarcoma tumorigenesis.

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Sonja Koopal

2007-09-01

Full Text Available Kaposi sarcoma is a tumor consisting of Kaposi sarcoma herpesvirus (KSHV-infected tumor cells that express endothelial cell (EC markers and viral genes like v-cyclin, vFLIP, and LANA. Despite a strong link between KSHV infection and certain neoplasms, de novo virus infection of human primary cells does not readily lead to cellular transformation. We have studied the consequences of expression of v-cyclin in primary and immortalized human dermal microvascular ECs. We show that v-cyclin, which is a homolog of cellular D-type cyclins, induces replicative stress in ECs, which leads to senescence and activation of the DNA damage response. We find that antiproliferative checkpoints are activated upon KSHV infection of ECs, and in early-stage but not late-stage lesions of clinical Kaposi sarcoma specimens. These are some of the first results suggesting that DNA damage checkpoint response also functions as an anticancer barrier in virally induced cancers.

Lymphadenopathic kaposi sarcoma in an immunocompetent young ...

African Journals Online (AJOL)

Kaposi's sarcoma (KS) is a vascular lesion that usually originates from several sites in the mid-dermis extending into the dermis. Infection from human herpes virus type 8 (HHV-8) is the mostly associated cause. Several articles reported cases of KS, first in Africa, then worldwide because of its close association with HIV ...

Sarcoma de Kaposi en un adulto con trasplante renal Kaposi's sarcoma in an adult with renal transplantation

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Enrique Emilio Jiménez López

2010-07-01

Full Text Available Se presenta el caso clínico de un paciente con trasplante renal, atendido en el Hospital Provincial Docente "Saturnino Lora Torres" de Santiago de Cuba, que a los 12 meses de operado comenzó a presentar lesiones eritematosas en la piel. Los resultados de los exámenes complementarios, incluida la biopsia, confirmaron que se trataba de un sarcoma de Kaposi. El afectado egresó y continuó su seguimiento por consulta externa. A los 3 meses, la dermatopatía había desaparecido totalmente y disminuido a 50 % el índice de filtración glomerular.The case report of a patient with renal transplantion, attended in the «Saturnino Lora Torres» Teaching Provincial Hospital from Santiago de Cuba who, after 12 months of his surgery, began to present erythematous lesions in the skin is presented. The results of the additional tests, including the biopsy, confirmed that it was a Kaposi's sarcoma. He was discharged and continued his follow up through the out patient department. After 3 months, the dermatopathy had totally disappeared and the glomerular filtration index decreased to 50%.

Radiation therapy of Kaposi's sarcoma in AIDS: Memorial Sloan-Kettering experience

International Nuclear Information System (INIS)

Nisce, L.Z.; Safai, B.

1985-01-01

In 1980 the authors reported their experience in the management of Kaposi's sarcoma (KS) affecting elderly men of Jewish or Italian descent. Since the outbreak of KS in 1981 among young male homosexuals with acquired immune deficiency syndrome (AIDS) the KS in the elderly has been subsequently called classical Kaposi's sarcome (CKS) in order to differentiate it from the KS in AIDS. The radiosensitivity of CKS is well documented. This report describes the authors' early experience in the radiation therapy of KS in AIDS compared with CKS and also discusses the problems related to the irradiation of the immunocompromised patient

Construction of a novel chimera consisting of a chelator-containing Tat peptide conjugated to a morpholino antisense oligomer for technetium-99m labeling and accelerating cellular kinetics

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Zhang Yumin [Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655 (United States)]. E-mail: yumin.zhang@mpi.com; Tung, C.-H. [Center for Molecular Imaging Research, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA 02129 (United States); He Jiang [Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655 (United States); Liu Ning [Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655 (United States); Yanachkov, Ivan [GlSynthesis, Worcester, MA 01605 (United States); Liu Guozheng [Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655 (United States); Rusckowski, Mary [Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655 (United States); Vanderheyden, Jean-Luc [Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655 (United States)

2006-02-15

The attempt to target the limited copies of messenger RNA (mRNA) in vivo with radiolabeled nucleobase oligomers as antisense probes is challenging. Selecting an antisense molecule with superior properties, enhancing the cellular kinetics, and improving the radiolabeling chemistry would be the reasonable approach to accomplish this goal. The present study reports a method to construct a chimera of phosphorodiamidate morpholino nucleobase oligomer (MORF) covalently conjugated to a peptide containing a cell membrane transduction Tat peptide and an N{sub 2}S{sub 2} chelator for technetium-99m ({sup 99m}Tc) radiolabeling (N{sub 2}S{sub 2}-Tat-MORF). The radiolabeling properties and cellular kinetics of {sup 99m}Tc-N{sub 2}S{sub 2}-Tat-MORF were measured. As hypothesized, the preparation of {sup 99m}Tc-N{sub 2}S{sub 2}-Tat-MORF could be achieved by an instant one-step method with labeling efficiency greater than 95%, and the {sup 99m}Tc-N{sub 2}S{sub 2}-Tat-MORF showed distinct properties in cell culture from those of a control, the same MORF sequence without Tat but with mercaptoacetyltriglycine (MAG{sub 3}) as chelator for {sup 99m}Tc ({sup 99m}Tc-MAG{sub 3}-MORF). {sup 99m}Tc-N{sub 2}S{sub 2}-Tat-MORF achieved maximum accumulation of about 35% within 2 h, while {sup 99m}Tc-MAG{sub 3}-MORF showed lower and steadily increasing accumulations but of less than 1% in 24 h. These preliminary results demonstrated that the proposed chimera has properties for easy labeling, and {sup 99m}Tc-N{sub 2}S{sub 2}-Tat-MORF prepared by this method possesses enhanced cellular kinetics and merits further investigation for in vivo mRNA targeting.

The role of radiotherapy in the treatment of oral Kaposi's sarcoma. Place de la radiotherapie dans le traitement des sarcomes de Kaposi de la cavite buccale

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Frikha, H; Le Bourgeois, J P; Haddad, E; Piedbois, P; Le Pechoux, C; Ghilezan, M; Mazeron, J J [Hopital Henri-Mondor, 94 - Creteil (France)

1993-01-01

The role of radiotherapy in the treatment of oral Kaposi's sarcoma needs to be defined. Over the past six years, 400 patients with AIDS-related epidemic Kaposi's sarcoma were referred to the oncology department of Henri Mondor Hospital; about 50% had oral Kaposi's lesions. Only 29 of the latter group had received oral cavity irradiation; palliation of pain was the most common indication. The age range was from 26-46 yr with a mean of 36 yr. Twenty-five patients were treated by megavolt age irradiation (4 MV X-rays) 22 of whom received 15 Gy (2 Gy/fraction, 8 Gy/week) and three 30 Gy (15 Gy followed by 3 weeks rest, then a further series of 15 Gy). Five patients were treated by orthovoltage irradiation (45 kV) and received 10-20 Gy (one patient received the two methods of irradiation). Treatment was generally successful in achieving palliation: of the 22 patients who received 15 Gy, 13.6% achieved complete remission and 86.4% partial remission with disappearance of pain; however, toxicity related to severe mucositis, even at relatively low doses and in spite of anti-mycotic treatment, is an argument for restrictive use of this modality.

Kaposi's sarcoma in renal transplant recipients: Experience at ...

African Journals Online (AJOL)

Between August 1966 and December 1989, 989 renal transplant recipients were followed up at the Renal Transplant Unit of Johannesburg Hospital. Seventy-five (7%) patients developed a total of 95 malignancies of which 5 (6%) were Kaposi's sarcoma. All patients received immunosuppressive agents; steroids, ...

Prevalence of infection with human herpesvirus 8/Kaposi's sarcoma ...

African Journals Online (AJOL)

8)/Kaposi's sarcoma herpesvirus (KSHY) and to gain some insight into possible transmission dynamics of this novel virus in South Africa. Methods. Stored, anonymous serum from 50 patients with a ~ sexually transmitted disease (STD), ...

Effects of the TAT peptide orientation and relative location on the protein transduction efficiency.

Science.gov (United States)

Guo, Qingguo; Zhao, Guojie; Hao, Fengjin; Guan, Yifu

2012-05-01

To understand the protein transduction domain (PTD)-mediated protein transduction behavior and to explore its potential in delivering biopharmaceutic drugs, we prepared four TAT-EGFP conjugates: TAT(+)-EGFP, TAT(-)-EGFP, EGFP-TAT(+) and EGFP-TAT(-), where TAT(+) and TAT(-) represent the original and the reversed TAT sequence, respectively. These four TAT-EGFP conjugates were incubated with HeLa and PC12 cells for in vitro study as well as injected intraperitoneally to mice for in vivo study. Flow cytometric results showed that four TAT-EGFP conjugates were able to traverse HeLa and PC12 cells with almost equal transduction efficiency. The in vivo study showed that the TAT-EGFP conjugates could be delivered into different organs of mice with different transduction capabilities. Bioinformatic analyses and CD spectroscopic data revealed that the TAT peptide has no defined secondary structure, and conjugating the TAT peptide to the EGFP cargo protein would not alter the native structure and the function of the EGFP protein. These results conclude that the sequence orientation, the spatial structure, and the relative location of the TAT peptide have much less effect on the TAT-mediated protein transduction. Thus, the TAT-fused conjugates could be constructed in more convenient and flexible formats for a wide range of biopharmaceutical applications. © 2011 John Wiley & Sons A/S.

Die TAT-Z as voorspeller vir prestasiemotivering

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F. V. N. Cilliers

1979-11-01

Die gebruik van die TAT-Z, 'n projeksietoets vir Swartmans, word ondersoek om prestasiemotivering veral tydens die indiensnemingsituasie te voorspel. Positiewe resultate is op 3 van die 10 kaarte (nrs. 4, 6 en 9 van die TAT-Z verkry. Aanbevelings word gemaak aangaande die aanpassing van hierdie projeksietoets ten einde meer inligting oor prestasiemotivering, bloot te lê.

In vitro nuclear interactome of the HIV-1 Tat protein.

LENUS (Irish Health Repository)

Gautier, Virginie W

2009-01-01

BACKGROUND: One facet of the complexity underlying the biology of HIV-1 resides not only in its limited number of viral proteins, but in the extensive repertoire of cellular proteins they interact with and their higher-order assembly. HIV-1 encodes the regulatory protein Tat (86-101aa), which is essential for HIV-1 replication and primarily orchestrates HIV-1 provirus transcriptional regulation. Previous studies have demonstrated that Tat function is highly dependent on specific interactions with a range of cellular proteins. However they can only partially account for the intricate molecular mechanisms underlying the dynamics of proviral gene expression. To obtain a comprehensive nuclear interaction map of Tat in T-cells, we have designed a proteomic strategy based on affinity chromatography coupled with mass spectrometry. RESULTS: Our approach resulted in the identification of a total of 183 candidates as Tat nuclear partners, 90% of which have not been previously characterised. Subsequently we applied in silico analysis, to validate and characterise our dataset which revealed that the Tat nuclear interactome exhibits unique signature(s). First, motif composition analysis highlighted that our dataset is enriched for domains mediating protein, RNA and DNA interactions, and helicase and ATPase activities. Secondly, functional classification and network reconstruction clearly depicted Tat as a polyvalent protein adaptor and positioned Tat at the nexus of a densely interconnected interaction network involved in a range of biological processes which included gene expression regulation, RNA biogenesis, chromatin structure, chromosome organisation, DNA replication and nuclear architecture. CONCLUSION: We have completed the in vitro Tat nuclear interactome and have highlighted its modular network properties and particularly those involved in the coordination of gene expression by Tat. Ultimately, the highly specialised set of molecular interactions identified will

Mechanisms of Kaposi's Sarcoma-Associated Herpesvirus Latency and Reactivation

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Fengchun Ye

2011-01-01

Full Text Available The life cycle of Kaposi's sarcoma-associated herpesvirus (KSHV consists of latent and lytic replication phases. During latent infection, only a limited number of KSHV genes are expressed. However, this phase of replication is essential for persistent infection, evasion of host immune response, and induction of KSHV-related malignancies. KSHV reactivation from latency produces a wide range of viral products and infectious virions. The resulting de novo infection and viral lytic products modulate diverse cellular pathways and stromal microenvironment, which promote the development of Kaposi's sarcoma (KS. The mechanisms controlling KSHV latency and reactivation are complex, involving both viral and host factors, and are modulated by diverse environmental factors. Here, we review the cellular and molecular basis of KSHV latency and reactivation with a focus on the most recent advancements in the field.

Maxillary Sinus Kaposi Sarcoma: Case Report in an HIV-Negative Patient with Thymoma

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Bernardo Carvalho Araújo

2017-01-01

Full Text Available Introduction. Kaposi sarcoma is an angioproliferative disorder that requires infection with human herpesvirus 8 (HHV-8 for its development. The majority of cases are associated with HIV infection or other immunocompromising conditions. Thymomas are occasionally associated to cytopenia, which may alter the patients’ immune responses. Methods. Case report using clinical records. Results. Case report of a 46-year-old male patient diagnosed with thymoma and myasthenia gravis. The patient was referred to an otolaryngology consultation with complaints of facial pain in the right malar region, interpreted as an acute sinusitis. Following examination, an expansive maxillary sinus mass was found, and endoscopic surgery was undertaken. After careful investigation, it was diagnosed as a Kaposi sarcoma. Conclusions. It is thought to be the first described case of a maxillary sinus Kaposi sarcoma in an HIV-negative patient. Thus, this entity has to be considered in the differential diagnosis of sinus masses, even in non-HIV patients.

Sarcoma de Kaposi primário do pênis Primary Kaposi's sarcoma of the penis

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Maira Mitsue Mukai

2009-10-01

Full Text Available Sarcoma de Kaposi é um tumor vascular que afeta a parede dos vasos linfáticos. Possui quatro formas: clássica, endêmica, iatrogênica e associada ao HIV. É uma doença sistêmica, maligna, multifatorial e de curso variável. A apresentação inicial no pênis é rara, e mais observada em pacientes HIV positivos. Em pacientes HIV negativos, os casos que ocorrem nesta região, apresentam-se com pápulas, nódulos, placas e lesões verruciformes, assintomáticas. Para o tratamento da forma clássica, dispõem-se de excisão cirúrgica, crioterapia, eletrocirurgia, laser e radioterapia. Neste trabalho, é relatado um caso raro de um paciente com a forma clássica, em região peniana tratado com sucesso com radioterapia.Kaposi's sarcoma is a vascular tumor involving the wall of lymphatic vessels. There are four types: classic, endemic, iatrogenic and HIV-associated. It is a systemic, malignant and multifactorial disease and has a variable course. The primary presentation on the penis is uncommon and is mainly observed in HIV-positive patients. In HIV-negative individuals, asymptomatic papules, nodules, plaques and verrucous lesions are found. The treatment for the classic form involves surgery, cryotherapy, electrosurgery, laser and radiation therapy. The authors present a rare case of a patient with the classic form on the penis, who was successfully treated by radiation therapy.

Creatine protects against mitochondrial dysfunction associated with HIV-1 Tat-induced neuronal injury

Science.gov (United States)

Stevens, Patrick R.; Gawryluk, Jeremy W.; Hui, Liang; Chen, Xuesong; Geiger, Jonathan D.

2015-01-01

HIV-1 infected individuals are living longer but experiencing a prevalence rate of over 50% for HIV-1 associated neurocognitive disorders (HAND) for which no effective treatment is available. Viral and cellular factors secreted by HIV-1 infected cells leads to neuronal injury and HIV-1 Tat continues to be implicated in the pathogenesis of HAND. Here we tested the hypothesis that creatine protected against HIV-1 Tat-induced neuronal injury by preventing mitochondrial bioenergetic crisis and/or redox catastrophe. Creatine blocked HIV-1 Tat1-72-induced increases in neuron cell death and synaptic area loss. Creatine protected against HIV-1 Tat-induced decreases in ATP. Creatine and creatine plus HIV-1 Tat increased cellular levels of creatine, and creatine plus HIV-1 Tat further decreased ratios of phosphocreatine to creatine observed with creatine or HIV-1 Tat treatments alone. Additionally, creatine protected against HIV-1 Tat-induced mitochondrial hypopolarization and HIV-1 Tat-induced mitochondrial permeability transition pore opening. Thus, creatine may be a useful adjunctive therapy against HAND. PMID:25613139

Complete histological regression of Kaposi's sarcoma following treatment with protease inhibitors despite persistence of HHV-8 in lesions

DEFF Research Database (Denmark)

Benfield, T L; Kirk, O; Elbrønd, B

1998-01-01

There is no current curative treatment for HIV-related Kaposi's sarcoma. The identification of human herpesvirus-8 as a possible aetiological agent suggests potential efficacy of anti-viral agents. We report here on the complete histological remission of Kaposi's sarcoma following treatment...

Human immunodeficiency virus negative Kaposi sarcoma and lymphoproliferative disorders

NARCIS (Netherlands)

Fossati, S; Boneschi, [No Value; Ferrucci, S; Brambilla, L

1999-01-01

BACKGROUND. The concomitant occurrence of more than one primary neoplasm in the same individual has led researchers to seek possible common etiopathogenetic factors. Kaposi sarcoma (KS) is a multicentric neoplasm of vascular origin and perhaps viral etiology. Four forms of KS are known: classic or

Case Presentation: Regression of Kaposi's Sarcoma in a Sudanese ...

African Journals Online (AJOL)

Introduction: Post-transplant malignancy is an increasing problem among patients receiving solid organ transplant worldwide. It has been related to recipient morbidity and mortality. Kaposi's sarcoma (KS) is a relatively common malignancy after kidney and solid organ transplantation, accounting for the majority of ...

Development of Tat-Conjugated Dendrimer for Transdermal DNA Vaccine Delivery.

Science.gov (United States)

Bahadoran, Azadeh; Moeini, Hassan; Bejo, Mohd Hair; Hussein, Mohd Zobir; Omar, Abdul Rahman

In order to enhance cellular uptake and to facilitate transdermal delivery of DNA vaccine, polyamidoamine (PAMAM) dendrimers conjugated with HIV transactivator of transcription (TAT) was developed. First, the plasmid DNA (pIRES-H5/GFP) nanoparticle was formulated using PAMAM dendrimer and TAT peptide and then characterized for surface charge, particle size, DNA encapsulation and protection of the pIRES-H5/GFP DNA plasmid to enzymatic digestion. Subsequently, the potency of the TAT-conjugated dendrimer for gene delivery was evaluated through in vitro transfection into Vero cells followed by gene expression analysis including western blotting, fluorescent microscopy and PCR. The effect of the TAT peptide on cellular uptake of DNA vaccine was studied by qRT-PCR and flow cytometry. Finally, the ability of TAT-conjugated PAMAM dendrimer for transdermal delivery of the DNA plasmid was assessed through artificial membranes followed by qRT-PCR and flow cytometry. TAT-conjugated PAMAM dendrimer showed the ability to form a compact and nanometre-sized polyplexes with the plasmid DNA, having the size range of 105 to 115 nm and a positive charge of +42 to +45 mV over the N/P ratio of 6:1(+/-).  In vitro transfection analysis into Vero cells confirms the high potency of TAT-conjugated PAMAM dendrimer to enhance the cellular uptake of DNA vaccine.  The permeability value assay through artificial membranes reveals that TAT-conjugated PAMAM has more capacity for transdermal delivery of the DNA compared to unmodified PAMAM dendrimer (Pdendrimer is a promising non-viral vector for transdermal use.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Diagnosis and treatment of HIV-related Kaposi's sarcoma

NARCIS (Netherlands)

Reyners, A.K.L.; Sprenger, H.G; Suurmeijer, A.J.H.; van der Graaf, W.T.A.

2006-01-01

A 42-year-old heterosexual man presented with bluish-purple spots on his skin and in his mouth cavity that had been present for a few months; a 48-year-old homosexual man had painful lymphadenopathy in the groins and left axilla. Both men appeared to have a Kaposi's sarcoma and to be HIV-positive.

Kaposi's Sarcoma-Associated Herpesvirus | Center for Cancer Research

Science.gov (United States)

The discovery of KSHV in 1994 was a historical landmark in tumor virology and human cancer research. KSHV's subsequent identification as a cause of Kaposi sarcoma and its association with primary effusion lymphoma and multicentric Castleman disease soon attracted the attention of hundreds of research laboratories and motivated thousands of virologists and oncologists to switch

RNA glycosidase and other agents target Tat to inhibit HIV-1 transcription.

Science.gov (United States)

Harrich, David; Jin, Hongping

2018-03-20

The HIV-1 tat gene encodes a small 86-104 amino acid protein depending on the HIV-1 strain. Tat is essential for HIV-1 replication through interactions with numerous cellular transcription factors. The interaction between Tat and P-TEFb, which is a cellular protein complex composed of cyclin T1 and CDK9, delivers P-TEFb to the newly transcribed viral mRNAs where phosphorylation of RNA polymerase II by CDK9 leads to highly efficient mRNA transcription. It has long been recognized that Tat is a potential anti-HIV-1 target and possibly a viral Achilles' heel. However, specifically targeting Tat without affecting normal host cell functions has been challenging. Means to inactivate Tat have been reported that includes small compounds, transdominant negative Tat proteins, and by plant-derived antivirals. Investigations of these agents have reported encouraging outcomes that inform and may hopefully affect strategies for a functional HIV-1 cure. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Gastrointestinal Kaposi Sarcoma Presenting In A Nigeria African ...

African Journals Online (AJOL)

Adult intussusception is a rare condition that is seen once in a while in surgical practice, 1. In this report we the case of a thirty –five year old Nigeria male on medical treatment of earlier diagnosed AIDS who had no evidence of cutaneous Kaposi sarcoma. He later presented with a palpable right lower quadrant mass and ...

Oesophageal cancer and Kaposi's Sarcoma in Malawi: a ...

African Journals Online (AJOL)

Given that oesophageal cancer (OC) is common in Malawi and its outcome is so dismal, would it be pragmatic to promptly mitigate the effects of smoking, alcohol and aflatoxins rather than seek a higher degree of local evidence for their role in OC? We retrospectively analysed a total of 13,217 OC and. Kaposi's sarcoma ...

Acroangiodermatite (pseudo-sarcoma de Kaposi

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Azulay Rubem David

2004-01-01

Full Text Available Acroangiodermatite é enfermidade rara, caracterizada por lesões eritêmato-violáceas bem delimitadas que acometem pernas e pés com aspecto semelhante ao do sarcoma de Kaposi. É relatado o caso de paciente do sexo feminino, de 57 anos, com início súbito de lesões eritêmato-violáceas nas pernas sem outras alterações. O caso acrescenta aprendizado por sua dificuldade diagnóstica e reafirma a importância da imuno-histoquímica. Trata-se da publicação do primeiro caso brasileiro.

The role of radiotherapy in the treatment of oral Kaposi's sarcoma. Place de la radiotherapie dans le traitement des sarcomes de Kaposi de la cavite buccale

Energy Technology Data Exchange (ETDEWEB)

Frikha, H.; Le Bourgeois, J.P.; Haddad, E.; Piedbois, P.; Le Pechoux, C.; Ghilezan, M.; Mazeron, J.J. (Hopital Henri-Mondor, 94 - Creteil (France))

1993-01-01

The role of radiotherapy in the treatment of oral Kaposi's sarcoma needs to be defined. Over the past six years, 400 patients with AIDS-related epidemic Kaposi's sarcoma were referred to the oncology department of Henri Mondor Hospital; about 50% had oral Kaposi's lesions. Only 29 of the latter group had received oral cavity irradiation; palliation of pain was the most common indication. The age range was from 26-46 yr with a mean of 36 yr. Twenty-five patients were treated by megavolt age irradiation (4 MV X-rays) 22 of whom received 15 Gy (2 Gy/fraction, 8 Gy/week) and three 30 Gy (15 Gy followed by 3 weeks rest, then a further series of 15 Gy). Five patients were treated by orthovoltage irradiation (45 kV) and received 10-20 Gy (one patient received the two methods of irradiation). Treatment was generally successful in achieving palliation: of the 22 patients who received 15 Gy, 13.6% achieved complete remission and 86.4% partial remission with disappearance of pain; however, toxicity related to severe mucositis, even at relatively low doses and in spite of anti-mycotic treatment, is an argument for restrictive use of this modality.

De novo anaplastic Kaposi sarcoma in a HIV-negative man: A case report and review of the literature

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Slim Charfi

2017-07-01

Full Text Available Anaplastic Kaposi sarcoma is a rare variant of Kaposi’s and is typically associated with an agressive clinical course. We report a case of a 67-year-old HIV negative man, presented with multiple, pink nodules on the left ankle and a keratotic lesion of the right heel. Initial histopathological exam concluded to an undifferentiated sarcoma. A second biopsy was performed and concluded to an anaplastic Kaposi sarcoma. Immunohistochemical study was positive for HHV8. Treatment consisted on a tumor excision of all lesions. Our case and the review of the literature highlight the benefit of the non conservative surgical treatment for this aggressive form of Kaposi sarcoma.

Interleukin-6 concentrations in the serum of patients with AIDS-associated Kaposi's sarcoma during treatment with interferon-alpha

NARCIS (Netherlands)

de Wit, R.; Raasveld, M. H.; ten Berge, R. J.; van der Wouw, P. A.; Bakker, P. J.; Veenhof, C. H.

1991-01-01

Interleukin-6 (IL-6) levels were determined in the serum of 14 HIV-1-infected patients with Kaposi's sarcoma, 10 HIV-1-infected patients without symptoms, and 10 healthy male subjects. IL-6 levels were also determined in the serum of the 14 patients with Kaposi's sarcoma during treatment with

Competition between Sec- and TAT-dependent protein translocation in Escherichia coli

DEFF Research Database (Denmark)

Cristóbal, S.; de Gier, J.-W.; Nielsen, Henrik

1999-01-01

-routed into the TAT pathway, suggesting that Sec-targeting signals in Lep can override TAT-targeting information in the TorA signal peptide. We also show that the TorA signal peptide can be converted into a Sec-targeting signal peptide by increasing the hydrophobicity of its h-region. Thus, beyond the twin...... the TorA TAT-targeting signal peptide to the Sec-dependent inner membrane protein leader peptidase (Lep). We find that the soluble, periplasmic P2 domain from Lep is re-routed by the TorA signal peptide into the TAT pathway. In contrast, the full-length TorA–Lep fusion protein is not re...

Direct effects of HIV-1 Tat on excitability and survival of primary dorsal root ganglion neurons: possible contribution to HIV-1-associated pain.

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Xianxun Chi

Full Text Available The vast majority of people living with human immunodeficiency virus type 1 (HIV-1 have pain syndrome, which has a significant impact on their quality of life. The underlying causes of HIV-1-associated pain are not likely attributable to direct viral infection of the nervous system due to the lack of evidence of neuronal infection by HIV-1. However, HIV-1 proteins are possibly involved as they have been implicated in neuronal damage and death. The current study assesses the direct effects of HIV-1 Tat, one of potent neurotoxic viral proteins released from HIV-1-infected cells, on the excitability and survival of rat primary dorsal root ganglion (DRG neurons. We demonstrated that HIV-1 Tat triggered rapid and sustained enhancement of the excitability of small-diameter rat primary DRG neurons, which was accompanied by marked reductions in the rheobase and resting membrane potential (RMP, and an increase in the resistance at threshold (R(Th. Such Tat-induced DRG hyperexcitability may be a consequence of the inhibition of cyclin-dependent kinase 5 (Cdk5 activity. Tat rapidly inhibited Cdk5 kinase activity and mRNA production, and roscovitine, a well-known Cdk5 inhibitor, induced a very similar pattern of DRG hyperexcitability. Indeed, pre-application of Tat prevented roscovitine from having additional effects on the RMP and action potentials (APs of DRGs. However, Tat-mediated actions on the rheobase and R(Th were accelerated by roscovitine. These results suggest that Tat-mediated changes in DRG excitability are partly facilitated by Cdk5 inhibition. In addition, Cdk5 is most abundant in DRG neurons and participates in the regulation of pain signaling. We also demonstrated that HIV-1 Tat markedly induced apoptosis of primary DRG neurons after exposure for longer than 48 h. Together, this work indicates that HIV-1 proteins are capable of producing pain signaling through direct actions on excitability and survival of sensory neurons.

Sarcoma de Kaposi: a propósito de un caso clínico, actualización del tema Kaposi 's sarcoma: a case report, update on the topic

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Anadely Gámez Pérez

2009-12-01

Full Text Available El sarcoma de Kaposi (KS por sus siglas en inglés es una enfermedad similar al cáncer. Se relaciona con la infección del VIH, y se presenta en estadios avanzados de la enfermedad, afectando el 20% de las personas con VIH que no toman medicamentos antirretrovirales. En Pinar del Río existe una baja incidencia de infección por VIH/SIDA. Dada la infrecuencia del Sarcoma de Kaposi se presenta un caso. Paciente de 50 años de edad, que después de un cuadro de dolor en epigastrio comienza con lesiones en la piel similares a hematoma en resolución, con centro más oscuro y nodular, que toman prácticamente todo el cuerpo. El paciente presenta ligera pérdida de peso, pero no prurito, no fiebre, no lesiones en mucosa oral. Se determinó Hb: 112g/l Hto: 0.34l/l Leucocitos: 4.4x10(9/l. Se encontró aumento de células mononucleares en el diferencial con linfopenia asociada; velocidad de sedimentación, colesterol, transaminasas, función renal y proteínas totales, normales, pero trombocitopenia moderada, acido úrico elevado. En el aspirado medular aparece predominio de linfocitos atípicos, con depresión relativa de las series hematopoyéticas. Gastroscopia, negativa. Biopsia de piel: Compatible con Sarcoma de Kaposi. VIH: tres exámenes durante el estudio con tiempo de intervalo entre ellos 3 meses desde el inicio resultaron negativos. Último examen viral a los 7 meses de iniciado el estudio (positivo con Western Blot.Kaposi´s Sarcoma (KS is a cancer-like disease. It is most frequent related to HIV infection, present in late stages of the disease and affecting 20 % of HIV infected people having no Highly Active Antiretroviral Therapy (HAART. Since in Pinar del Rio Province a low incidence rate of HIV/AIDS is observed , Kaposi´s Sarcoma is very infrequent. A 50 year-old male who after presenting an epigastralgia suffers from hematoma-like skin lesions, in resolution and when palpated the darker center was nodular. These lesions take

Systematic Analysis of the Functions of Lysine Acetylation in the Regulation of Tat Activity.

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Minghao He

Full Text Available The Tat protein of HIV-1 has several well-known properties, such as nucleocytoplasmic trafficking, transactivation of transcription, interaction with tubulin, regulation of mitotic progression, and induction of apoptosis. Previous studies have identified a couple of lysine residues in Tat that are essential for its functions. In order to analyze the functions of all the lysine residues in Tat, we mutated them individually to alanine, glutamine, and arginine. Through systematic analysis of the lysine mutants, we discovered several previously unidentified characteristics of Tat. We found that lysine acetylation could modulate the subcellular localization of Tat, in addition to the regulation of its transactivation activity. Our data also revealed that lysine mutations had distinct effects on microtubule assembly and Tat binding to bromodomain proteins. By correlation analysis, we further found that the effects of Tat on apoptosis and mitotic progression were not entirely attributed to its effect on microtubule assembly. Our findings suggest that Tat may regulate diverse cellular activities through binding to different proteins and that the acetylation of distinct lysine residues in Tat may modulate its interaction with various partners.

Etoposide for epidemic Kaposi's sarcoma: a phase II study

NARCIS (Netherlands)

Bakker, P. J.; Danner, S. A.; Lange, J. M.; Veenhof, K. H.

1988-01-01

Fourteen untreated patients with epidemic Kaposi's sarcoma stages III and IV were treated with etoposide 150 mg/m2 on 3 consecutive days every 4 weeks. No responses were observed. Myelosuppression was severe with white blood count WHO grade 3-4 in nine patients and with platelets WHO grade 3-4 in

management of epidemic kaposi's sarcoma: a recent concern in ...

African Journals Online (AJOL)

DENTISTRY. By: Dr. Jeff Luande, M.D.. Tanzania Tumor Centre. INTRODUCTION: Kaposi's Sarcoma in its classic endemic form has never been a concern in dental practice. Since early this decade the medical practice has witnessed an ever increasing new form of the same sarcoma in its more aggressive form called the ...

A Tat-conjugated Peptide Nucleic Acid Tat-PNA-DR Inhibits Hepatitis B Virus Replication In Vitro and In Vivo by Targeting LTR Direct Repeats of HBV RNA

Science.gov (United States)

Zeng, Zhengyang; Han, Shisong; Hong, Wei; Lang, Yange; Li, Fangfang; Liu, Yongxiang; Li, Zeyong; Wu, Yingliang; Li, Wenxin; Zhang, Xianzheng; Cao, Zhijian

2016-01-01

Hepatitis B virus (HBV) infection is a major cause of chronic active hepatitis, cirrhosis, and primary hepatocellular carcinoma, all of which are severe threats to human health. However, current clinical therapies for HBV are limited by potential side effects, toxicity, and drug-resistance. In this study, a cell-penetrating peptide-conjugated peptide nucleic acid (PNA), Tat-PNA-DR, was designed to target the direct repeat (DR) sequences of HBV. Tat-PNA-DR effectively inhibited HBV replication in HepG2.2.15 cells. Its anti-HBV effect relied on the binding of Tat-PNA-DR to the DR, whereby it suppressed the translation of hepatitis B e antigen (HBeAg), HBsAg, HBV core, hepatitis B virus x protein, and HBV reverse transcriptase (RT) and the reverse transcription of the HBV genome. Furthermore, Tat-PNA-DR administered by intravenous injection efficiently cleared HBeAg and HBsAg in an acute hepatitis B mouse model. Importantly, it induced an 80% decline in HBV DNA in mouse serum, which was similar to the effect of the widely used clinical drug Lamivudine (3TC). Additionally, a long-term hydrodynamics HBV mouse model also demonstrated Tat-PNA-DR's antiviral effect. Interestingly, Tat-PNA-DR displayed low cytotoxicity, low mouse acute toxicity, low immunogenicity, and high serum stability. These data indicate that Tat-PNA-DR is a unique PNA and a promising drug candidate against HBV. PMID:26978579

A Tat-conjugated Peptide Nucleic Acid Tat-PNA-DR Inhibits Hepatitis B Virus Replication In Vitro and In Vivo by Targeting LTR Direct Repeats of HBV RNA

Directory of Open Access Journals (Sweden)

Zhengyang Zeng

2016-01-01

Full Text Available Hepatitis B virus (HBV infection is a major cause of chronic active hepatitis, cirrhosis, and primary hepatocellular carcinoma, all of which are severe threats to human health. However, current clinical therapies for HBV are limited by potential side effects, toxicity, and drug-resistance. In this study, a cell-penetrating peptide-conjugated peptide nucleic acid (PNA, Tat-PNA-DR, was designed to target the direct repeat (DR sequences of HBV. Tat-PNA-DR effectively inhibited HBV replication in HepG2.2.15 cells. Its anti-HBV effect relied on the binding of Tat-PNA-DR to the DR, whereby it suppressed the translation of hepatitis B e antigen (HBeAg, HBsAg, HBV core, hepatitis B virus x protein, and HBV reverse transcriptase (RT and the reverse transcription of the HBV genome. Furthermore, Tat-PNA-DR administered by intravenous injection efficiently cleared HBeAg and HBsAg in an acute hepatitis B mouse model. Importantly, it induced an 80% decline in HBV DNA in mouse serum, which was similar to the effect of the widely used clinical drug Lamivudine (3TC. Additionally, a long-term hydrodynamics HBV mouse model also demonstrated Tat-PNA-DR's antiviral effect. Interestingly, Tat-PNA-DR displayed low cytotoxicity, low mouse acute toxicity, low immunogenicity, and high serum stability. These data indicate that Tat-PNA-DR is a unique PNA and a promising drug candidate against HBV.

Safety and immunogenicity of HIV-1 Tat toxoid in immunocompromised HIV-1-infected patients.

Science.gov (United States)

Gringeri, A; Santagostino, E; Muça-Perja, M; Mannucci, P M; Zagury, J F; Bizzini, B; Lachgar, A; Carcagno, M; Rappaport, J; Criscuolo, M; Blattner, W; Burny, A; Gallo, R C; Zagury, D

1998-01-01

To antagonize the deleterious effects of the HIV-1 toxin extracellular Tat on uninfected immune cells, we developed a new strategy of anti-HIV-1 vaccine using an inactivated but immunogenic Tat (Tat toxoid). Tat toxoid has been assayed for safety and immunogenicity in seropositive patients. The phase I vaccine clinical trial testing Tat toxoid preparation in Seppic Isa 51 oil adjuvant was performed on 14 HIV-1-infected asymptomatic although biologically immunocompromised individuals (500-200 CD4+ cells/mm3). Following as many as 8 injections, no clinical defects were observed. All patients exhibited an antibody (Ab) response to Tat, and some had cell-mediated immunity (CMI) as evaluated by skin test in vivo and T-cell proliferation in vitro. These results provide initial evidence of safety and potency of Tat toxoid vaccination in HIV-1-infected individuals.

Nucleolar protein trafficking in response to HIV-1 Tat: rewiring the nucleolus.

Science.gov (United States)

Jarboui, Mohamed Ali; Bidoia, Carlo; Woods, Elena; Roe, Barbara; Wynne, Kieran; Elia, Giuliano; Hall, William W; Gautier, Virginie W

2012-01-01

The trans-activator Tat protein is a viral regulatory protein essential for HIV-1 replication. Tat trafficks to the nucleoplasm and the nucleolus. The nucleolus, a highly dynamic and structured membrane-less sub-nuclear compartment, is the site of rRNA and ribosome biogenesis and is involved in numerous cellular functions including transcriptional regulation, cell cycle control and viral infection. Importantly, transient nucleolar trafficking of both Tat and HIV-1 viral transcripts are critical in HIV-1 replication, however, the role(s) of the nucleolus in HIV-1 replication remains unclear. To better understand how the interaction of Tat with the nucleolar machinery contributes to HIV-1 pathogenesis, we investigated the quantitative changes in the composition of the nucleolar proteome of Jurkat T-cells stably expressing HIV-1 Tat fused to a TAP tag. Using an organellar proteomic approach based on mass spectrometry, coupled with Stable Isotope Labelling in Cell culture (SILAC), we quantified 520 proteins, including 49 proteins showing significant changes in abundance in Jurkat T-cell nucleolus upon Tat expression. Numerous proteins exhibiting a fold change were well characterised Tat interactors and/or known to be critical for HIV-1 replication. This suggests that the spatial control and subcellular compartimentaliation of these cellular cofactors by Tat provide an additional layer of control for regulating cellular machinery involved in HIV-1 pathogenesis. Pathway analysis and network reconstruction revealed that Tat expression specifically resulted in the nucleolar enrichment of proteins collectively participating in ribosomal biogenesis, protein homeostasis, metabolic pathways including glycolytic, pentose phosphate, nucleotides and amino acids biosynthetic pathways, stress response, T-cell signaling pathways and genome integrity. We present here the first differential profiling of the nucleolar proteome of T-cells expressing HIV-1 Tat. We discuss how these

Kaposi sarcoma related to acquired immunodeficiency syndrome: hepatic findings on computed tomography and magnetic resonance imaging

Energy Technology Data Exchange (ETDEWEB)

Costa, Daniel Nobrega da; Viana, Publio Cesar Cavalcante; Maciel, Rosangela Pereira; Rocha, Manoel de Souza; Gebrim, Eloisa Maria Mello Santiago [Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas. Inst. de Radiologia]. E-mail: dnobrega@gmail.com

2008-03-15

Kaposi sarcoma is a neoplasm associated with immunosuppressive conditions, and involving blood and lymphatic vessels. It is the most frequent intrahepatic neoplasm in patients with acquired immunodeficiency syndrome. Computed tomography and magnetic resonance imaging demonstrate multiple small nodules, prominence and contrast-enhancement of periportal branches due to the presence of the neoplastic tissue. The authors report a case of a 47-year-old male patient with acquired immunodeficiency syndrome presenting disseminated Kaposi sarcoma. (author)

Kaposis sarcoma in a Nairobi Hospital | Onyango | East African ...

African Journals Online (AJOL)

Background: Kaposi's sarcoma (KS) is associated epidemiologically with HIV infection and a number of countries have reported a dramatic increase in the incidence of KS with the advent of AIDS. Although AIDS is prevalent in Kenya, no studies on the impact of AIDS on the pattern of KS has been carried out. Objective: To ...

Effects of altered TatC proteins on protein secretion efficiency via the twin-arginine translocation pathway of Bacillus subtilis

NARCIS (Netherlands)

Eijlander, Robyn T.; Kolbusz, Magdalena A.; Berendsen, Erwin M.; Kuipers, Oscar P.

Protein translocation via the Tat machinery in thylakoids and bacteria occurs through a cooperation between the TatA, TatB and TatC subunits, of which the TatC protein forms the initial Tat substrate-binding site. The Bacillus subtilis Tat machinery lacks TatB and comprises two separate TatAC

Kaposi's Sarcoma-Associated Herpesvirus-Related Solid Lymphoma Involving the Heart and Brain

Directory of Open Access Journals (Sweden)

Jason R. Andrews

2011-01-01

Full Text Available Since its discovery in 1994, Kaposi's sarcoma-associated herpesvirus (KSHV has been associated with lymphoproliferative disorders, particularly in patients infected with human immunodeficiency virus (HIV. The disorders most strongly linked to KSHV are multicentric Castleman's Disease (MCD, primary effusion lymphoma, and diffuse large B-cell lymphomas. We report an unusual case of KSHV-associated lymphoma in an HIV-infected patient manifesting with myocardial and central nervous system involvement. We discuss this case in the context of increasing array of KSHV-associated lymphomas. In the HIV-infected patient with a mass lesion, a history of cutaneous Kaposi's sarcoma and prolonged immunosuppression should alert clinicians as to the possibility of KSHV-associated lymphoproliferative disorders, in order to establish a timely diagnosis.

Radiation therapy for Kaposi's sarcoma associated with acquired immunodeficiency syndrome. Tokyo Metropolitan Komagome Hospital experience

International Nuclear Information System (INIS)

Ebara, Takeshi; Karasawa, Katsuyuki; Maebayashi, Katsuya; Kurosaki, Hiromasa; Ishikawa, Hitoshi; Kaizu, Toshihide; Tanaka, Yoshiaki; Akagi, Kumiko; Masuda, Gota

2000-01-01

Kaposi's sarcoma is frequently found in association with acquired immunodeficiency syndrome (AIDS). We report on radiotherapy for patients with AIDS-related Kaposi's sarcoma at Tokyo Metropolitan Komagome Hospital. Between April 1991 and May 1997, radiotherapy was given to 11 lesions in eight men with AIDS-related Kaposi's sarcoma to relieve their symptoms. The lesions involved the head and neck region, the legs, and the gastrointestinal tract. Radiotherapy was carried out with 4-MV photon through parallel opposed field or high energy electrons. Total doses ranged from 20 to 38 Gy, with a median of 30 Gy, delivered in 2- to 3-Gy fractions. Four patients were given other treatments prior to the radiotherapy. Acute reaction was evaluated according to the modified acute radiation morbidity scoring criteria of the Radiation Therapy Oncology Group (RTOG). Radiotherapy had relieved the symptoms in all patients at completion of this therapy. Lesions that involved the hard palate and vocal cords had completely disappeared. The lesions that received radiotherapy were controlled without symptoms until the patients died. Patients who had the head and neck region treated exhibited severe acute mucosal reaction (at a dose of 30 Gy, there was grade 2 morbidity by modified RTOG criteria, in two patients, and grade 3 in three patients) although the radiation therapy was completed for these patients. Radiotherapy promises a favorable outcome for symptom relief in AIDS-related Kaposi's sarcoma. (author)

Targeting mTOR in HIV-Negative Classic Kaposi's Sarcoma

Directory of Open Access Journals (Sweden)

Ofer Merimsky

2008-01-01

Full Text Available A 66-year old female with HIV-negative classic Kaposi's sarcoma responded to mTOR targeting by rapamycin. The response was well documented by PET-CT. This case provides supporting evidence that the mTOR pathway may be important in the tumorigenesis of KS and that rapamycin may have activity in this disease.

The HIV-1 transcriptional activator Tat has potent nucleic acid chaperoning activities in vitro.

Science.gov (United States)

Kuciak, Monika; Gabus, Caroline; Ivanyi-Nagy, Roland; Semrad, Katharina; Storchak, Roman; Chaloin, Olivier; Muller, Sylviane; Mély, Yves; Darlix, Jean-Luc

2008-06-01

The human immunodeficiency virus type 1 (HIV-1) is a primate lentivirus that causes the acquired immunodeficiency syndrome (AIDS). In addition to the virion structural proteins and enzyme precursors, that are Gag, Env and Pol, HIV-1 encodes several regulatory proteins, notably a small nuclear transcriptional activator named Tat. The Tat protein is absolutely required for virus replication since it controls proviral DNA transcription to generate the full-length viral mRNA. Tat can also regulate mRNA capping and splicing and was recently found to interfere with the cellular mi- and siRNA machinery. Because of its extensive interplay with nucleic acids, and its basic and disordered nature we speculated that Tat had nucleic acid-chaperoning properties. This prompted us to examine in vitro the nucleic acid-chaperoning activities of Tat and Tat peptides made by chemical synthesis. Here we report that Tat has potent nucleic acid-chaperoning activities according to the standard DNA annealing, DNA and RNA strand exchange, RNA ribozyme cleavage and trans-splicing assays. The active Tat(44-61) peptide identified here corresponds to the smallest known sequence with DNA/RNA chaperoning properties.

海马神经元中TAT-GluR6-9c-dansyl小肽的荧光观察%Delivery of GluR6-9c into hippocampal neurons by TAT transduction domain

Institute of Scientific and Technical Information of China (English)

纵艳艳; 裴冬生; 孙亚峰; 张光毅

2005-01-01

目的研究TAT-GluR6-9c-dansyl荧光小肽是否可以进入细胞内部.方法在培养的海马神经元中加入TAT-GluR6-9c-dansyl荧光小肽和对照肽TAT38-48-dansyl.结果用10 μmol/L TAT-GluR6-9c-dansyl处理的海马神经元在荧光显微镜下可以观到绿色荧光的出现,而对照肽TAT38-48-dansyl无荧光出现.结论 TAT-GluR6-9c-dansyl荧光小肽可以进入细胞.

Lack of activity of zidovudine in AIDS-associated Kaposi's sarcoma

NARCIS (Netherlands)

de Wit, R.; Reiss, P.; Bakker, P. J.; Lange, J. M.; Danner, S. A.; Veenhof, K. H.

1989-01-01

The efficacy of zidovudine (AZT) for treatment of patients with Kaposi's sarcoma as the initial manifestation of AIDS was determined in a non-randomized, phase-II clinical trial. Twenty-two patients were treated with zidovudine (300 mg 4 times daily for 8 weeks). In patients with stable disease or

Kaposi's sarcoma after alpha-interferon treatment for HIV-negative T ...

African Journals Online (AJOL)

Although interferon was successful in controlling the lymphoma the clinical course was complicated by the rapid development of aggressive, fatal Kaposi's sarcoma shortly after cessation of interferon treatment. It is suggested that the immunosuppressive effect of interferon therapy (or the T -cell lymphoma or both) may have ...

RECOVERY ACT - Thylakoid Assembly and Folded Protein Transport by the Tat Pathway

Energy Technology Data Exchange (ETDEWEB)

Dabney-Smith, Carole [Miami Univ., Oxford, OH (United States)

2016-07-18

Assembly of functional photosystems complete with necessary intrinsic (membrane-bound) and extrinsic proteins requires the function of at least 3 protein transport pathways in thylakoid membranes. Our research focuses on one of those pathways, a unique and essential protein transport pathway found in the chloroplasts of plants, bacteria, and some archaebacteria, the Twin arginine translocation (Tat) system. The chloroplast Tat (cpTat) system is thought to be responsible for the proper location of ~50% of thylakoid lumen proteins, several of which are necessary for proper photosystem assembly, maintenance, and function. Specifically, cpTat systems are unique because they transport fully folded and assembled proteins across ion tight membranes using only three membrane components, Tha4, Hcf106, and cpTatC, and the protonmotive force generated by photosynthesis. Despite the importance of the cpTat system in plants, the mechanism of transport of a folded precursor is not well known. Our long-term goal is to investigate the role protein transport systems have on organelle biogenesis, particularly the assembly of membrane protein complexes in thylakoids of chloroplasts. The objective of this proposal is to correlate structural changes in the membrane-bound cpTat component, Tha4, to the mechanism of translocation of folded-precursor substrates across the membrane bilayer by using a cysteine accessibility and crosslinking approach. Our central hypothesis is that the precursor passes through a proteinaceous pore of assembled Tha4 protomers that have undergone a conformational or topological change in response to transport. This research is predicated upon the observations that Tha4 exists in molar excess in the membrane relative to the other cpTat components; its regulated assembly to the precursor-bound receptor; and our data showing oligomerization of Tha4 into very large complexes in response to transport. Our rationale for these studies is that understanding cpTat

Controlling cellular P-TEFb activity by the HIV-1 transcriptional transactivator Tat.

Directory of Open Access Journals (Sweden)

Lisa Muniz

Full Text Available The human immunodeficiency virus 1 (HIV-1 transcriptional transactivator (Tat is essential for synthesis of full-length transcripts from the integrated viral genome by RNA polymerase II (Pol II. Tat recruits the host positive transcription elongation factor b (P-TEFb to the HIV-1 promoter through binding to the transactivator RNA (TAR at the 5'-end of the nascent HIV transcript. P-TEFb is a general Pol II transcription factor; its cellular activity is controlled by the 7SK small nuclear RNA (snRNA and the HEXIM1 protein, which sequester P-TEFb into transcriptionally inactive 7SK/HEXIM/P-TEFb snRNP. Besides targeting P-TEFb to HIV transcription, Tat also increases the nuclear level of active P-TEFb through promoting its dissociation from the 7SK/HEXIM/P-TEFb RNP by an unclear mechanism. In this study, by using in vitro and in vivo RNA-protein binding assays, we demonstrate that HIV-1 Tat binds with high specificity and efficiency to an evolutionarily highly conserved stem-bulge-stem motif of the 5'-hairpin of human 7SK snRNA. The newly discovered Tat-binding motif of 7SK is structurally and functionally indistinguishable from the extensively characterized Tat-binding site of HIV TAR and importantly, it is imbedded in the HEXIM-binding elements of 7SK snRNA. We show that Tat efficiently replaces HEXIM1 on the 7SK snRNA in vivo and therefore, it promotes the disassembly of the 7SK/HEXIM/P-TEFb negative transcriptional regulatory snRNP to augment the nuclear level of active P-TEFb. This is the first demonstration that HIV-1 specifically targets an important cellular regulatory RNA, most probably to promote viral transcription and replication. Demonstration that the human 7SK snRNA carries a TAR RNA-like Tat-binding element that is essential for the normal transcriptional regulatory function of 7SK questions the viability of HIV therapeutic approaches based on small drugs blocking the Tat-binding site of HIV TAR.

A Tat-grafted anti-nucleic acid antibody acquires nuclear-localization property and a preference for TAR RNA

International Nuclear Information System (INIS)

Jeong, Jong-Geun; Kim, Dong-Sik; Kim, Yong-Sung; Kwon, Myung-Hee

2011-01-01

Highlights: → We generate ' H3 Tat-3D8' by grafting Tat 48-60 peptide to VH CDR of 3D8 scFv antibody. → H3 Tat-3D8 antibody retains nucleic acid binding and hydrolyzing activities. → H3 Tat-3D8 acquires a preference for TAR RNA structure. → Properties of Tat 48-60 is transferred to an antibody via Tat-grafting into a CDR. -- Abstract: The 3D8 single chain variable fragment (3D8 scFv) is an anti-nucleic acid antibody that can hydrolyze nucleic acids and enter the cytosol of cells without reaching the nucleus. The Tat peptide, derived from the basic region of the HIV-1 Tat protein, translocates to cell nuclei and has TAR RNA binding activity. In this study, we generated a Tat-grafted antibody ( H3 Tat-3D8) by replacing complementarity-determining region 3 (CDR3) within the VH domain of the 3D8 scFv with a Tat 48-60 peptide (GRKKRRQRRRPPQ). H3 Tat-3D8 retained the DNA-binding and DNA-hydrolyzing activity of the scFv, and translocated to the nuclei of HeLa cells and preferentially recognized TAR RNA. Thus, the properties associated with the Tat peptide were transferred to the antibody via Tat-grafting without loss of the intrinsic DNA-binding and hydrolyzing activities of the 3D8 scFv antibody.

HIV-1 Tat regulates the expression of the dcw operon and stimulates the proliferation of bacteria.

Science.gov (United States)

Wei, Jinsong; Zhang, Yumin; Knapp, Pamela E; Zhao, Tianyong

2016-01-01

Infections of pathogenic bacteria are very common in acquired immunodeficiency syndrome (AIDS) patients. However, the biological effects of HIV-1 Tat on bacteria are incompletely understood. In this study, HIV-1 Tat was expressed in Escherichia coli and Pseudomonas aeruginosa (PA01) to investigate its biological effects on bacteria. Bacterial cells expressing either HIV-1 Tat1-86 (Tat1-86) or HIV-1 Tat1-72 (Tat1-72) grow significantly faster than those with either only an empty vector or an unrelated control (GFP or Rluc). Supplementation of purified HIV-1 Tat1-86 or Tat1-101 protein into bacterial culture medium stimulated the growth of both E. coli and PA01. The expression profile of certain cell division-associated genes, such as those in the division cell wall (dcw) operon (ftsA, ftsQ, ftsW and ftsZ), yafO and zipA, was altered in HIV-1 Tat1-86 expressing E. coli BL21(DE3). Furthermore, the expression of firefly luciferase (Fluc) reporter gene, when engineered for control by the dcw promoter and terminator, was enhanced by HIV-1 Tat in E. coli, confirming that HIV-1 Tat transcriptionally regulates the expression of the dcw operon. The finding that HIV-1 Tat stimulates bacterial growth whether it is produced intracellularly or applied extracellularly may have relevance for HIV patients who are highly susceptible to opportunistic bacterial infections. Contents category: Viruses -Retroviruses. The GenBank accession number for the sequence of HIV-1 Tat1-86 is AF324439.1. Copyright © 2015 Elsevier Ltd. All rights reserved.

Radiation therapy of epidemic kaposi sarcoma: the Henri-Mondor hospital experience (643 patients); Radiotherapie du sarcome de kaposi epidemique: l`experience de l`hopital Henri-Mondor (643 patients)

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Belembaogo, E; Kirova, Y; Frikha, H; Yu, S; Piedbois, P; Le Bourgeois, J P [Hopital Henri-Mondor, 94 - Creteil (France). Dept. de cancerologie

1998-01-01

From June 1986 to December 1996, 643 patients presenting with acquired immunodeficiency syndrome (AIDS)-related epidemic Kaposi`s sarcoma were treated with irradiation at the Oncology Department of Henri Mondor University Hospital. Three-hundred eighty-seven patients (60 %) had previously received a treatment with interferon (259 patients, 40.2 %), vinblastine (225 patients, 34.5 %), doxorubicin (22 patients, 3.4 %), bleomycin (19 patients, 2.9 %), and/or antiviral treatment (216, 33.5 %). The radiotherapy was delivered by 4 MeV OR 8 MeV electron beam for extended cutaneous fields and 45-100 kV x-ray for localized fields. The delivered dose was 20 Gy in 2 weeks (2.5 Gy/fraction, 4 fractions/week) followed by 2 weeks rest and second series of 10 Gy in 1 week. For oral cavity lesions, we used a series of 15.2 Gy was delivered (1.9 Gy/fraction, 4 fractions/week), followed for three patients by a 3 week rest and by a similar second series of 15.2 Gy.Six-hundred and twenty-one patients were evaluable and the objective response rate was 92 %, with e complete regression of clinical and functional symptoms for all patients. The skin tolerance was good, with 7.3 % grade I reactions, 69.3 % of grade II reactions, and 23.4 % grade III reactions. There was a correlation between recurrence rate and the occurrence of opportunistic infections. This analysis shows the efficacy of dose radiotherapy for treatment of epidemic Kaposi sarcoma. (author)

Interactive HIV-1 Tat and morphine-induced synaptodendritic injury is triggered through focal disruptions in Na⁺ influx, mitochondrial instability, and Ca²⁺ overload.

Science.gov (United States)

Fitting, Sylvia; Knapp, Pamela E; Zou, Shiping; Marks, William D; Bowers, M Scott; Akbarali, Hamid I; Hauser, Kurt F

2014-09-17

Synaptodendritic injury is thought to underlie HIV-associated neurocognitive disorders and contributes to exaggerated inflammation and cognitive impairment seen in opioid abusers with HIV-1. To examine events triggering combined transactivator of transcription (Tat)- and morphine-induced synaptodendritic injury systematically, striatal neuron imaging studies were conducted in vitro. These studies demonstrated nearly identical pathologic increases in dendritic varicosities as seen in Tat transgenic mice in vivo. Tat caused significant focal increases in intracellular sodium ([Na(+)]i) and calcium ([Ca(2+)]i) in dendrites that were accompanied by the emergence of dendritic varicosities. These effects were largely, but not entirely, attenuated by the NMDA and AMPA receptor antagonists MK-801 and CNQX, respectively. Concurrent morphine treatment accelerated Tat-induced focal varicosities, which were accompanied by localized increases in [Ca(2+)]i and exaggerated instability in mitochondrial inner membrane potential. Importantly, morphine's effects were prevented by the μ-opioid receptor antagonist CTAP and were not observed in neurons cultured from μ-opioid receptor knock-out mice. Combined Tat- and morphine-induced initial losses in ion homeostasis and increases in [Ca(2+)]i were attenuated by the ryanodine receptor inhibitor ryanodine, as well as pyruvate. In summary, Tat induced increases in [Na(+)]i, mitochondrial instability, excessive Ca(2+) influx through glutamatergic receptors, and swelling along dendrites. Morphine, acting via μ-opioid receptors, exacerbates these excitotoxic Tat effects at the same subcellular locations by mobilizing additional [Ca(2+)]i and by further disrupting [Ca(2+)]i homeostasis. We hypothesize that the spatiotemporal relationship of μ-opioid and aberrant AMPA/NMDA glutamate receptor signaling is critical in defining the location and degree to which opiates exacerbate the synaptodendritic injury commonly observed in neuro

HAART in hand: The change in Kaposi's sarcoma presentation in ...

African Journals Online (AJOL)

Background. HIV/AIDS-related Kaposi's sarcoma (HIV-KS) is a public health problem in South Africa (SA). It is AIDS defining. There have been no studies evaluating its prevalence since the national roll-out of highly active antiretroviral therapy (HAART). Objective. To evaluate the effect of HAART on the disease profile of ...

Morphine Tolerance and Physical Dependence Are Altered in Conditional HIV-1 Tat Transgenic Mice.

Science.gov (United States)

Fitting, Sylvia; Stevens, David L; Khan, Fayez A; Scoggins, Krista L; Enga, Rachel M; Beardsley, Patrick M; Knapp, Pamela E; Dewey, William L; Hauser, Kurt F

2016-01-01

Despite considerable evidence that chronic opiate use selectively affects the pathophysiologic consequences of human immunodeficiency virus type 1 (HIV-1) infection in the nervous system, few studies have examined whether neuro-acquired immune deficiency syndrome (neuroAIDS) might intrinsically alter the pharmacologic responses to chronic opiate exposure. This is an important matter because HIV-1 and opiate abuse are interrelated epidemics, and HIV-1 patients are often prescribed opiates as a treatment of HIV-1-related neuropathic pain. Tolerance and physical dependence are inevitable consequences of frequent and repeated administration of morphine. In the present study, mice expressing HIV-1 Tat in a doxycycline (DOX)-inducible manner [Tat(+)], their Tat(-) controls, and control C57BL/6 mice were chronically exposed to placebo or 75-mg morphine pellets to explore the effects of Tat induction on morphine tolerance and dependence. Antinociceptive tolerance and locomotor activity tolerance were assessed using tail-flick and locomotor activity assays, respectively, and physical dependence was measured with the platform-jumping assay and recording of other withdrawal signs. We found that Tat(+) mice treated with DOX [Tat(+)/DOX] developed an increased tolerance in the tail-flick assay compared with control Tat(-)/DOX and/or C57/DOX mice. Equivalent tolerance was developed in all mice when assessed by locomotor activity. Further, Tat(+)/DOX mice expressed reduced levels of physical dependence to chronic morphine exposure after a 1-mg/kg naloxone challenge compared with control Tat(-)/DOX and/or C57/DOX mice. Assuming the results seen in Tat transgenic mice can be generalized to neuroAIDS, our findings suggest that HIV-1-infected individuals may display heightened analgesic tolerance to similar doses of opiates compared with uninfected individuals and show fewer symptoms of physical dependence. Copyright © 2015 by The American Society for Pharmacology and Experimental

Pre-micro RNA signatures delineate stages of endothelial cell transformation in Kaposi sarcoma.

Directory of Open Access Journals (Sweden)

Andrea J O'Hara

2009-04-01

Full Text Available MicroRNAs (miRNA have emerged as key regulators of cell lineage differentiation and cancer. We used precursor miRNA profiling by a novel real-time QPCR method (i to define progressive stages of endothelial cell transformation cumulating in Kaposi sarcoma (KS and (ii to identify specific miRNAs that serve as biomarkers for tumor progression. We were able to compare primary patient biopsies to well-established culture and mouse tumor models. Loss of mir-221 and gain of mir-15 expression demarked the transition from merely immortalized to fully tumorigenic endothelial cells. Mir-140 and Kaposi sarcoma-associated herpesvirus viral miRNAs increased linearly with the degree of transformation. Mir-24 emerged as a biomarker specific for KS.

Potent inhibition of HIV-1 replication by a Tat mutant.

Directory of Open Access Journals (Sweden)

Luke W Meredith

Full Text Available Herein we describe a mutant of the two-exon HIV-1 Tat protein, termed Nullbasic, that potently inhibits multiple steps of the HIV-1 replication cycle. Nullbasic was created by replacing the entire arginine-rich basic domain of wild type Tat with glycine/alanine residues. Like similarly mutated one-exon Tat mutants, Nullbasic exhibited transdominant negative effects on Tat-dependent transactivation. However, unlike previously reported mutants, we discovered that Nullbasic also strongly suppressed the expression of unspliced and singly-spliced viral mRNA, an activity likely caused by redistribution and thus functional inhibition of HIV-1 Rev. Furthermore, HIV-1 virion particles produced by cells expressing Nullbasic had severely reduced infectivity, a defect attributable to a reduced ability of the virions to undergo reverse transcription. Combination of these inhibitory effects on transactivation, Rev-dependent mRNA transport and reverse transcription meant that permissive cells constitutively expressing Nullbasic were highly resistant to a spreading infection by HIV-1. Nullbasic and its activities thus provide potential insights into the development of potent antiviral therapeutics that target multiple stages of HIV-1 infection.

Neoplasms HIV associated Kaposi sarcoma not

International Nuclear Information System (INIS)

Lombardo, K.; Sosa, A.; Krygier, G.; Muse, I.

2004-01-01

Abstract - The incidence of malignancies in virus carriers acquired immunodeficiency (HIV) has increased in conjunction with the disease during the past decade. 40% of all AIDS patients develop cancer during the course of HIV infection. Kaposi's sarcoma (KS), Non-Hodgkin lymphoma (NHL) and cervical cancer have an impact extremely high in HIV infected patients, and they are considered as disease AIDS-defining stage. Many reports suggest that other neoplasms they can have a high impact on the population of HIV carrier, including head and neck carcinoma, rectal cancer - anal, plasma cytomas, and melanoma lung cancer. Methods - We examined the spectrum of cancer in HIV-infected patients, specifically neoplasms except Kaposi sarcoma diagnosed between 1/1998 - 6/2004. Information on age, sex, factors was gathered risk for AIDS, neoplasms and mortality rate. Results: The total number of patients in our study was 21 patients, what 15 were male (71%) and 6 females (29%); the median age was 36 (29-70). Tumors were reported: 11 Non-Hodgkin lymphomas (52%), 2 Hodgkin's lymphoma (6.6%), 1 medullary thyroid cancer (6.6%), 1 melanoma (6.6%), 1 rectal cancer (5%) and three head and neck cancers (14%), 1 cancer 1 lung and breast cancer. Five of the patients were intravenous drug abusers (24%); 4 patients were homosexual, bisexual March 8 straight, on 6 patients know the data. Conclusions - The spectrum of malignancies associated with infection HIV in our study was similar to that described in other populations. ratio between the immune system and the epidemiology of the virus-induced tumors is to importance to identify new therapeutic approaches in the treatment and / or prevention of these neoplasms

Acroangiodermatitis mimicking Kaposi's sarcoma in an HIV-positive man.

Science.gov (United States)

Goorney, B P; Newsham, J; Fitzgerald, D; Motta, L

2018-06-01

Kaposi's sarcoma (KS) is the commonest human immunodeficiency virus (HIV)-related malignancy with its characteristic cutaneous morphological appearance and histopathological features. However, it can be simulated by other co-morbid opportunistic infections and unrelated dermatological conditions. We describe such a case of acroangiodermatitis in an HIV co-infected man, based on exclusion of KS histologically and the absence of human herpesvirus 8, the causative agent of KS.

Deciphering structure-activity relationships in a series of Tat/TAR inhibitors.

Science.gov (United States)

Pascale, Lise; González, Alejandro López; Di Giorgio, Audrey; Gaysinski, Marc; Teixido Closa, Jordi; Tejedor, Roger Estrada; Azoulay, Stéphane; Patino, Nadia

2016-11-01

A series of pentameric "Polyamide Amino Acids" (PAAs) compounds derived from the same trimeric precursor have been synthesized and investigated as HIV TAR RNA ligands, in the absence and in the presence of a Tat fragment. All PAAs bind TAR with similar sub-micromolar affinities but their ability to compete efficiently with the Tat fragment strongly differs, IC50 ranging from 35 nM to >2 μM. While NMR and CD studies reveal that all PAA interact with TAR at the same site and induce globally the same RNA conformational change upon binding, a comparative thermodynamic study of PAA/TAR equilibria highlights distinct TAR binding modes for Tat competitor and non-competitor PAAs. This led us to suggest two distinct interaction modes that have been further validated by molecular modeling studies. While the binding of Tat competitor PAAs induces a contraction at the TAR bulge region, the binding of non-competitor ones widens it. This could account for the distinct PAA ability to compete with Tat fragment. Our work illustrates how comparative thermodynamic studies of a series of RNA ligands of same chemical family are of value for understanding their binding modes and for rationalizing structure-activity relationships.

Inhibition of Non Canonical HIV-1 Tat Secretion Through the Cellular Na+,K+-ATPase Blocks HIV-1 Infection

Directory of Open Access Journals (Sweden)

Silvia Agostini

2017-07-01

Full Text Available Besides its essential role in the activation of HIV-1 gene expression, the viral Tat protein has the unusual property of trafficking in and out of cells. In contrast to Tat internalization, the mechanism involved in extracellular Tat release has so far remained elusive. Here we show that Tat secretion occurs through a Golgi-independent pathway requiring binding of Tat with three short, non-consecutive intracytoplasmic loops at the C-terminus of the cellular Na+,K+-ATPase pump alpha subunit. Ouabain, a pump inhibitor, blocked this interaction and prevented Tat secretion; virions produced in the presence of this drug were less infectious, consistent the capacity of virion-associated Tat to increase HIV-1 infectivity. Treatment of CD4+ T-cells with short peptides corresponding to the Tat-binding regions of the pump alpha subunit impaired extracellular Tat release and blocked HIV-1 replication. Thus, non canonical, extracellular Tat secretion is essential for viral infectivity.

Changing patterns of Kaposi's sarcoma in Danish acquired immunodeficiency syndrome patients with complete follow-up. The Danish Study Group for HIV Infection (DASHI)

DEFF Research Database (Denmark)

Lundgren, Jens Dilling; Melbye, M; Pedersen, C

1995-01-01

The objective was to study changes in the occurrence of human immunodeficiency virus type 1-related Kaposi's sarcoma and the association with degree of immunodeficiency over time. Danish patients with acquired immunodeficiency syndrome (AIDS) diagnosed between 1979 and 1990 (n = 687) were followed...... the proportion of patients who died with Kaposi's sarcoma remained constant over time. Furthermore, the CD4 cell count at time of AIDS for patients diagnosed with Kaposi's sarcoma has declined in recent years. A CD4 cell count liter at the time of AIDS diagnosis predicted an increased risk...

Trade-Space Analysis Tool for Constellations (TAT-C)

Science.gov (United States)

Le Moigne, Jacqueline; Dabney, Philip; de Weck, Olivier; Foreman, Veronica; Grogan, Paul; Holland, Matthew; Hughes, Steven; Nag, Sreeja

2016-01-01

Traditionally, space missions have relied on relatively large and monolithic satellites, but in the past few years, under a changing technological and economic environment, including instrument and spacecraft miniaturization, scalable launchers, secondary launches as well as hosted payloads, there is growing interest in implementing future NASA missions as Distributed Spacecraft Missions (DSM). The objective of our project is to provide a framework that facilitates DSM Pre-Phase A investigations and optimizes DSM designs with respect to a-priori Science goals. In this first version of our Trade-space Analysis Tool for Constellations (TAT-C), we are investigating questions such as: How many spacecraft should be included in the constellation? Which design has the best costrisk value? The main goals of TAT-C are to: Handle multiple spacecraft sharing a mission objective, from SmallSats up through flagships, Explore the variables trade space for pre-defined science, cost and risk goals, and pre-defined metrics Optimize cost and performance across multiple instruments and platforms vs. one at a time.This paper describes the overall architecture of TAT-C including: a User Interface (UI) interacting with multiple users - scientists, missions designers or program managers; an Executive Driver gathering requirements from UI, then formulating Trade-space Search Requests for the Trade-space Search Iterator first with inputs from the Knowledge Base, then, in collaboration with the Orbit Coverage, Reduction Metrics, and Cost Risk modules, generating multiple potential architectures and their associated characteristics. TAT-C leverages the use of the Goddard Mission Analysis Tool (GMAT) to compute coverage and ancillary data, streamlining the computations by modeling orbits in a way that balances accuracy and performance.TAT-C current version includes uniform Walker constellations as well as Ad-Hoc constellations, and its cost model represents an aggregate model consisting of

Methamphetamine and HIV-Tat alter murine cardiac DNA methylation and gene expression

Energy Technology Data Exchange (ETDEWEB)

Koczor, Christopher A., E-mail: ckoczor@emory.edu; Fields, Earl; Jedrzejczak, Mark J.; Jiao, Zhe; Ludaway, Tomika; Russ, Rodney; Shang, Joan; Torres, Rebecca A.; Lewis, William

2015-11-01

This study addresses the individual and combined effects of HIV-1 and methamphetamine (N-methyl-1-phenylpropan-2-amine, METH) on cardiac dysfunction in a transgenic mouse model of HIV/AIDS. METH is abused epidemically and is frequently associated with acquisition of HIV-1 infection or AIDS. We employed microarrays to identify mRNA differences in cardiac left ventricle (LV) gene expression following METH administration (10 d, 3 mg/kg/d, subcutaneously) in C57Bl/6 wild-type littermates (WT) and Tat-expressing transgenic (TG) mice. Arrays identified 880 differentially expressed genes (expression fold change > 1.5, p < 0.05) following METH exposure, Tat expression, or both. Using pathway enrichment analysis, mRNAs encoding polypeptides for calcium signaling and contractility were altered in the LV samples. Correlative DNA methylation analysis revealed significant LV DNA methylation changes following METH exposure and Tat expression. By combining these data sets, 38 gene promoters (27 related to METH, 11 related to Tat) exhibited differences by both methods of analysis. Among those, only the promoter for CACNA1C that encodes L-type calcium channel Cav1.2 displayed DNA methylation changes concordant with its gene expression change. Quantitative PCR verified that Cav1.2 LV mRNA abundance doubled following METH. Correlative immunoblots specific for Cav1.2 revealed a 3.5-fold increase in protein abundance in METH LVs. Data implicate Cav1.2 in calcium dysregulation and hypercontractility in the murine LV exposed to METH. They suggest a pathogenetic role for METH exposure to promote LV dysfunction that outweighs Tat-induced effects. - Highlights: • HIV-1 Tat and methamphetamine (METH) alter cardiac gene expression and epigenetics. • METH impacts gene expression or epigenetics more significantly than Tat expression. • METH alters cardiac mitochondrial function and calcium signaling independent of Tat. • METH alters DNA methylation, expression, and protein abundance of

Methamphetamine and HIV-Tat alter murine cardiac DNA methylation and gene expression

International Nuclear Information System (INIS)

Koczor, Christopher A.; Fields, Earl; Jedrzejczak, Mark J.; Jiao, Zhe; Ludaway, Tomika; Russ, Rodney; Shang, Joan; Torres, Rebecca A.; Lewis, William

2015-01-01

This study addresses the individual and combined effects of HIV-1 and methamphetamine (N-methyl-1-phenylpropan-2-amine, METH) on cardiac dysfunction in a transgenic mouse model of HIV/AIDS. METH is abused epidemically and is frequently associated with acquisition of HIV-1 infection or AIDS. We employed microarrays to identify mRNA differences in cardiac left ventricle (LV) gene expression following METH administration (10 d, 3 mg/kg/d, subcutaneously) in C57Bl/6 wild-type littermates (WT) and Tat-expressing transgenic (TG) mice. Arrays identified 880 differentially expressed genes (expression fold change > 1.5, p < 0.05) following METH exposure, Tat expression, or both. Using pathway enrichment analysis, mRNAs encoding polypeptides for calcium signaling and contractility were altered in the LV samples. Correlative DNA methylation analysis revealed significant LV DNA methylation changes following METH exposure and Tat expression. By combining these data sets, 38 gene promoters (27 related to METH, 11 related to Tat) exhibited differences by both methods of analysis. Among those, only the promoter for CACNA1C that encodes L-type calcium channel Cav1.2 displayed DNA methylation changes concordant with its gene expression change. Quantitative PCR verified that Cav1.2 LV mRNA abundance doubled following METH. Correlative immunoblots specific for Cav1.2 revealed a 3.5-fold increase in protein abundance in METH LVs. Data implicate Cav1.2 in calcium dysregulation and hypercontractility in the murine LV exposed to METH. They suggest a pathogenetic role for METH exposure to promote LV dysfunction that outweighs Tat-induced effects. - Highlights: • HIV-1 Tat and methamphetamine (METH) alter cardiac gene expression and epigenetics. • METH impacts gene expression or epigenetics more significantly than Tat expression. • METH alters cardiac mitochondrial function and calcium signaling independent of Tat. • METH alters DNA methylation, expression, and protein abundance of

Sarcoma de Kaposi relacionado à síndrome da imunodeficiência adquirida: características do comprometimento hepático na tomografia computadorizada e na ressonância magnética Kaposi sarcoma related to acquired immunodeficiency syndrome: hepatic findings on computed tomography and magnetic resonance imaging

Directory of Open Access Journals (Sweden)

Daniel Nobrega da Costa

2008-04-01

Full Text Available Sarcoma de Kaposi é uma neoplasia associada a condições de imunossupressão que acomete os vasos linfáticos e sanguíneos. É a neoplasia intra-hepática mais comum na síndrome da imunodeficiência adquirida. A tomografia computadorizada e a ressonância magnética revelam múltiplos pequenos nódulos, proeminência e realce dos planos periportais, devido à presença de tecido neoplásico. Os autores descrevem um caso de paciente masculino, de 47 anos de idade, com síndrome da imunodeficiência adquirida e sarcoma de Kaposi disseminado.Kaposi sarcoma is a neoplasm associated with immunosuppressive conditions, and involving blood and lymphatic vessels. It is the most frequent intrahepatic neoplasm in patients with acquired immunodeficiency syndrome. Computed tomography and magnetic resonance imaging demonstrate multiple small nodules, prominence and contrast-enhancement of periportal branches due to the presence of the neoplastic tissue. The authors report a case of a 47-year-old male patient with acquired immunodeficiency syndrome presenting disseminated Kaposi sarcoma.

Antibodies to the HIV-1 Tat protein correlated with nonprogression to AIDS: a rationale for the use of Tat toxoid as an HIV-1 vaccine.

Science.gov (United States)

Zagury, J F; Sill, A; Blattner, W; Lachgar, A; Le Buanec, H; Richardson, M; Rappaport, J; Hendel, H; Bizzini, B; Gringeri, A; Carcagno, M; Criscuolo, M; Burny, A; Gallo, R C; Zagury, D

1998-01-01

To investigate which immune parameters, such as antibodies against HIV-1 specificities, or viral parameters, such as p24 antigenemia, are predictive of disease progression. We performed studies on serum collected from individuals exhibiting two extremes of disease evolution--67 fast progressors (FP) and 182 nonprogressors (NP)--at their enrollment. After a 1- to 2-year clinical follow-up of 104 nonprogressors after their enrollment, we could determine the best serologic predictors for disease progression. We investigated levels of antibodies to tetanus toxoid and to HIV antigens including Env, Gag, Nef, and Tat proteins, as well as p24 antigenemia, viremia, CD4 cell count, and interferon-alpha (IFN-alpha) titers in FPs and NPs, and we correlated these data with clinical and biologic signs of progression. p24 Antigenemia, a marker of viral replication, and anti-Tat antibodies were highly and inversely correlated in both groups (P < .001). Furthermore, anti-p24 antibodies and low serum IFN-alpha levels were correlated to the NP versus the FP cohort. Finally, among NPs, only antibodies to Tat and not to the other HIV specificities (Env, Nef, Gag) were significantly predictive of clinical stability during their follow-up. Antibodies toward HIV-1 Tat, which are inversely correlated to p24 antigenemia, appear as a critical marker for a lack of disease progression. This study strongly suggests that rising anti-Tat antibodies through active immunization may be beneficial in AIDS vaccine development to control viral replication.

Intelligent tit-for-tat in the iterated prisoner's dilemma game

Science.gov (United States)

Baek, Seung Ki; Kim, Beom Jun

2008-07-01

We seek a route to the equilibrium where all the agents cooperate in the iterated prisoner’s dilemma game on a two-dimensional plane, focusing on the role of tit-for-tat strategy. When a time horizon, within which a strategy can recall the past, is one time step, an equilibrium can be achieved as cooperating strategies dominate the whole population via proliferation of tit-for-tat. Extending the time horizon, we filter out poor strategies by simplified replicator dynamics and observe a similar evolutionary pattern to reach the cooperating equilibrium. In particular, the rise of a modified tit-for-tat strategy plays a central role, which implies how a robust strategy is adopted when provided with an enhanced memory capacity.

HIV-1 TAT protein enhances sensitization to methamphetamine by affecting dopaminergic function.

Science.gov (United States)

Kesby, James P; Najera, Julia A; Romoli, Benedetto; Fang, Yiding; Basova, Liana; Birmingham, Amanda; Marcondes, Maria Cecilia G; Dulcis, Davide; Semenova, Svetlana

2017-10-01

Methamphetamine abuse is common among humans with immunodeficiency virus (HIV). The HIV-1 regulatory protein TAT induces dysfunction of mesolimbic dopaminergic systems which may result in impaired reward processes and contribute to methamphetamine abuse. These studies investigated the impact of TAT expression on methamphetamine-induced locomotor sensitization, underlying changes in dopamine function and adenosine receptors in mesolimbic brain areas and neuroinflammation (microgliosis). Transgenic mice with doxycycline-induced TAT protein expression in the brain were tested for locomotor activity in response to repeated methamphetamine injections and methamphetamine challenge after a 7-day abstinence period. Dopamine function in the nucleus accumbens (Acb) was determined using high performance liquid chromatography. Expression of dopamine and/or adenosine A receptors (ADORA) in the Acb and caudate putamen (CPu) was assessed using RT-PCR and immunohistochemistry analyses. Microarrays with pathway analyses assessed dopamine and adenosine signaling in the CPu. Activity-dependent neurotransmitter switching of a reserve pool of non-dopaminergic neurons to a dopaminergic phenotype in the ventral tegmental area (VTA) was determined by immunohistochemistry and quantified with stereology. TAT expression enhanced methamphetamine-induced sensitization. TAT expression alone decreased striatal dopamine (D1, D2, D4, D5) and ADORA1A receptor expression, while increasing ADORA2A receptors expression. Moreover, TAT expression combined with methamphetamine exposure was associated with increased adenosine A receptors (ADORA1A) expression and increased recruitment of dopamine neurons in the VTA. TAT expression and methamphetamine exposure induced microglia activation with the largest effect after combined exposure. Our findings suggest that dopamine-adenosine receptor interactions and reserve pool neuronal recruitment may represent potential targets to develop new treatments for

Radiation therapy for Kaposi's sarcoma associated with acquired immunodeficiency syndrome. Tokyo Metropolitan Komagome Hospital experience

Energy Technology Data Exchange (ETDEWEB)

Ebara, Takeshi [Municipal Kanbara General Hospital, Fujikawa, Shizuoka (Japan); Karasawa, Katsuyuki; Maebayashi, Katsuya; Kurosaki, Hiromasa; Ishikawa, Hitoshi; Kaizu, Toshihide; Tanaka, Yoshiaki; Akagi, Kumiko; Masuda, Gota

2000-12-01

Kaposi's sarcoma is frequently found in association with acquired immunodeficiency syndrome (AIDS). We report on radiotherapy for patients with AIDS-related Kaposi's sarcoma at Tokyo Metropolitan Komagome Hospital. Between April 1991 and May 1997, radiotherapy was given to 11 lesions in eight men with AIDS-related Kaposi's sarcoma to relieve their symptoms. The lesions involved the head and neck region, the legs, and the gastrointestinal tract. Radiotherapy was carried out with 4-MV photon through parallel opposed field or high energy electrons. Total doses ranged from 20 to 38 Gy, with a median of 30 Gy, delivered in 2- to 3-Gy fractions. Four patients were given other treatments prior to the radiotherapy. Acute reaction was evaluated according to the modified acute radiation morbidity scoring criteria of the Radiation Therapy Oncology Group (RTOG). Radiotherapy had relieved the symptoms in all patients at completion of this therapy. Lesions that involved the hard palate and vocal cords had completely disappeared. The lesions that received radiotherapy were controlled without symptoms until the patients died. Patients who had the head and neck region treated exhibited severe acute mucosal reaction (at a dose of 30 Gy, there was grade 2 morbidity by modified RTOG criteria, in two patients, and grade 3 in three patients) although the radiation therapy was completed for these patients. Radiotherapy promises a favorable outcome for symptom relief in AIDS-related Kaposi's sarcoma. (author)

HIV-1 Tat depresses DNA-PKCS expression and DNA repair, and sensitizes cells to ionizing radiation

International Nuclear Information System (INIS)

Sun Yi; Huang Yuechen; Xu Qinzhi; Wang Huiping; Bai Bei; Sui Jianli; Zhou Pingkun

2006-01-01

Purpose There is accumulating evidence that cancer patients with human immmunodeficiency virus-1/acquired immunodeficency syndrome (HIV-1/AIDS) have more severe tissue reactions and often develop cutaneous toxic effects when subjected to radiotherapy. Here we explored the effects of the HIV-1 Tat protein on cellular responses to ionizing radiation. Methods and Materials Two Tat-expressing cell lines, TT2 and TE671-Tat, were derived from human rhabdomyosarcoma cells by transfecting with the HIV-1 tat gene. Radiosensitivity was determined using colony-forming ability. Gene expression was assessed by cDNA microarray and immunohybridization. The Comet assay and γ-H2AX foci were use to detect DNA double-strand breaks (DSBs) and repair. Radiation-induced cell cycle changes were detected by flow cytometry. Results The radiosensitivity of TT2 and TE671-Tat cells was significantly increased as compared with parental TE671 cells or the control TE671-pCI cells. Tat also increased proliferation activity. The comet assay and γH2AX foci detection revealed a decreased capacity to repair radiation-induced DNA DSBs in Tat-expressing cells. Microarray assay demonstrated that the DNA repair gene DNA-PKcs, and cell cycle-related genes Cdc20, Cdc25C, KIF2C and CTS1 were downregulated in Tat-expressing cells. Depression of DNA-PKcs in Tat-expressing cells was further confirmed by RT-PCR and immuno-hybridization analysis. Tat-expressing cells exhibited a prolonged S phase arrest after 4 Gy γ-irradiation, and a noticeable delay in the initiation and elimination of radiation-induced G 2 /M arrest as compared with parental cells. In addition, the G 2 /M arrest was incomplete in TT2 cells. Moreover, HIV-1 Tat resulted in a constitutive overexpression of cyclin B1 protein. Conclusion HIV-1 Tat protein sensitizes cells to ionizing radiation via depressing DNA repair and dysregulating cell cycle checkpoints. These observations provide new insight into the increased tissue reactions of AIDS

Effect of the peptide Tat(49-57) on the bio-distribution and similar radiopharmaceuticals dosimetry of the bombesin; Efecto del peptido TAT(49-57) sobre la biodistribucion y dosimetria de radiofarmacos analogos de la bombesina

Energy Technology Data Exchange (ETDEWEB)

Santos C, C. L.

2011-07-01

The gastrin-releasing peptide receptor (GRP-r) is over-expressed in prostate and breast cancer. {sup 99m}Tc-Bombesin ({sup 99m}Tc-Bn) has been reported as a radiopharmaceutical with specific cell GRP-r binding. The HIV Tat(49-57)-derived peptide has been used to deliver a large variety of molecules to cell nuclei. New hybrid radiopharmaceuticals of type {sup 99m}Tc-N{sub 2}S{sub 2}-Tat(49-57)-Lys{sup 3}-Bn ({sup 99m}Tc-Tat-Bn) and {sup 188}Re-N{sub 2}S{sub 2}-Tat(49-57)-Lys{sup 3}-Bn ({sup 188}Re-Tat-Bn), would increase cell uptake and internalized in cancer cell nuclei could act as an effective system of targeted radiotherapy using Auger and internal conversion (I C) electron emissions near DNA. The aim of this research was to prepare and assess in vitro and in vivo uptake kinetics in cancer cells of {sup 99m}Tc/{sup 188}Re-Tat-Bn and the in vitro nucleus and cytoplasm internalization kinetics in GRP receptor-positive cancer cells as well as to evaluate the subcellular-level radiation absorbed dose associated with the observed effect on cancer cell DNA proliferation. Structures of N{sub 2}S{sub 2}-Tat-Bn and Tc/Re(O)N{sub 2}S{sub 2}-Tat-Bn were calculated by an Mm procedure. {sup 99m}Tc-Tat-Bn and {sup 188}Re-Tat-Bn were synthesized and stability studies carried out by HPLC and I TLC-Sg analyses in serum and cysteine solutions. In vitro internalization was tested using human prostate cancer Pc 3 cells and breast carcinoma cell lines MDA-Mb 231 and MCF 7. Nuclei from cells were isolated using a nuclear extraction kit. Total disintegrations in each subcellular compartment were calculated by integration of experimental time activity kinetic curves. Nucleus internalization was corroborated by con focal microscopy images using immunofluorescent labelled Tat-Bn. Biodistribution was determined in Pc 3 tumor-bearing nude mice. The Penelope code was used to simulate and calculate the absorbed dose by contribution of {beta}, Auger and I C electrons in the cytoplasm and

HIV-1 Tat and AIDS-associated cancer: targeting the cellular anti-cancer barrier?

Directory of Open Access Journals (Sweden)

Daniel René

2008-05-01

Full Text Available Abstract The acquired immunodeficiency syndrome (AIDS is accompanied by a significant increase in the incidence of neoplasms. Several causative agents have been proposed for this phenomenon. These include immunodeficiency and oncogenic DNA viruses and the HIV-1 protein Tat. Cancer in general is closely linked to genomic instability and DNA repair mechanisms. The latter maintains genomic stability and serves as a cellular anti-cancer barrier. Defects in DNA repair pathway are associated with carcinogenesis. This review focuses on newly discovered connections of the HIV-1 protein Tat, as well as cellular co-factors of Tat, to double-strand break DNA repair. We propose that the Tat-induced DNA repair deficiencies may play a significant role in the development of AIDS-associated cancer.

Favourable effect of chemotherapy on clinical symptoms and human herpesvirus-8 DNA load in a patient with Kaposi's sarcoma presenting with fever and anemia

NARCIS (Netherlands)

Prins, J. M.; Sol, C. J.; Renwick, N.; Goudsmit, J.; Veenstra, J.; Reiss, P.

1999-01-01

The case of a patient infected with human immunodeficiency virus type 1 (HIV-1) with Kaposi's sarcoma who presented with fever of unknown origin, severe anemia, thrombocytopenia and hypoalbuminemia but only limited involvement of the skin is presented. Chemotherapy directed at Kaposi's sarcoma

Intracellular trafficking of superparamagnetic iron oxide nanoparticles conjugated with TAT peptide: 3-dimensional electron tomography analysis

International Nuclear Information System (INIS)

Nair, Baiju G.; Fukuda, Takahiro; Mizuki, Toru; Hanajiri, Tatsuro; Maekawa, Toru

2012-01-01

Highlights: ► We study the intracellular localisation of TAT-SPIONs using 3-D electron tomography. ► 3-D images of TAT-SPIONs in a cell are clearly shown. ► Release of TAT-SPIONs from endocytic vesicles into the cytoplasm is clearly shown. -- Abstract: Internalisation of nanoparticles conjugated with cell penetrating peptides is a promising approach to various drug delivery applications. Cell penetrating peptides such as transactivating transcriptional activator (TAT) peptides derived from HIV-1 proteins are effective intracellular delivery vectors for a wide range of nanoparticles and pharmaceutical agents thanks to their amicable ability to enter cells and minimum cytotoxicity. Although different mechanisms of intracellular uptake and localisation have been proposed for TAT conjugated nanoparticles, it is necessary to visualise the particles on a 3-D plane in order to investigate the actual intracellular uptake and localisation. Here, we study the intracellular localisation and trafficking of TAT peptide conjugated superparamagnetic ion oxide nanoparticles (TAT-SPIONs) using 3-D electron tomography. 3-D tomograms clearly show the location of TAT-SPIONs in a cell and their slow release from the endocytic vesicles into the cytoplasm. The present methodology may well be utilised for further investigations of the behaviours of nanoparticles in cells and eventually for the development of nano drug delivery systems.

A real-time view of the TAR:Tat:P-TEFb complex at HIV-1 transcription sites

Directory of Open Access Journals (Sweden)

Knezevich Anna

2007-05-01

Full Text Available Abstract HIV-1 transcription is tightly regulated: silent in long-term latency and highly active in acutely-infected cells. Transcription is activated by the viral protein Tat, which recruits the elongation factor P-TEFb by binding the TAR sequence present in nascent HIV-1 RNAs. In this study, we analyzed the dynamic of the TAR:Tat:P-TEFb complex in living cells, by performing FRAP experiments at HIV-1 transcription sites. Our results indicate that a large fraction of Tat present at these sites is recruited by Cyclin T1. We found that in the presence of Tat, Cdk9 remained bound to nascent HIV-1 RNAs for 71s. In contrast, when transcription was activated by PMA/ionomycin, in the absence of Tat, Cdk9 turned-over rapidly and resided on the HIV-1 promoter for only 11s. Thus, the mechanism of trans-activation determines the residency time of P-TEFb at the HIV-1 gene, possibly explaining why Tat is such a potent transcriptional activator. In addition, we observed that Tat occupied HIV-1 transcription sites for 55s, suggesting that the TAR:Tat:P-TEFb complex dissociates from the polymerase following transcription initiation, and undergoes subsequent cycles of association/dissociation.

The role of radiotherapy in the treatment of a conventional Kaposi sarcoma; Place de la radiotherapie dans le traitement du sarcome de Kaposi classique

Energy Technology Data Exchange (ETDEWEB)

El Omrani, A.; Khouchani, M.; El Morjani, T.; Mharech, A.; Tahri, A. [CHU Mohammed-VI, Marrakech (Morocco)

2011-10-15

The authors report a study which aimed at establishing the epidemio-clinical and evolution profile of patients irradiated for a localized Kaposi sarcoma. This retrospective study is based on 10 patients treated between 2005 and 2009. All patients have been irradiated. Even though this pathology is a matter of discussion for its viral or genetic origin, its radio-sensitivity results in local control and a longer survival. Short communication

Diagnosis of pulmonary Kaposi's sarcoma in AIDS patients.

Science.gov (United States)

Jeyapalan, M; Steffenson, S

1997-02-01

Pulmonary Kaposi's sarcoma (KS) is one of the many manifestations of AIDS. There are no specific tests for its early diagnosis. Because its symptoms may be similar to tuberculosis, it may be diagnosed incorrectly and treated as such. Consequently, by the time of the correct diagnosis, valuable time will have been lost for effective medical care that could positively impact prognosis. The discussion in this case study is focused on pulmonary KS with an interest in improving premorbid diagnosis that may lead to an earlier recognition and better treatment of the disease.

Enquête internationale sur l'état de l'art et l'état de la pratique en géotechnique

Science.gov (United States)

Acosta-Martinez, Hugo; Delage, Pierre; Nicks, Jennifer; Day, Peter

2018-05-01

Cet article présente une synthèse des résultats de l'enquête internationale sur l'état de l'art et l'état de la pratique en ingénierie géotechnique lancée par le Groupe présidentiel des entreprises associées et le Comité de supervision technique de la Société internationale de mécanique des sols et de géotechnique en mars 2017. Il résume également les discussions qui ont eu lieu sur le sujet durant le 19e CIMSG à Séoul, le 20 septembre 2017.

Interaction between HIV-1 Tat and DNA-PKcs modulates HIV transcription and class switch recombination.

Science.gov (United States)

Zhang, Shi-Meng; Zhang, He; Yang, Tian-Yi; Ying, Tian-Yi; Yang, Pei-Xiang; Liu, Xiao-Dan; Tang, Sheng-Jian; Zhou, Ping-Kun

2014-01-01

HIV-1 tat targets a variety of host cell proteins to facilitate viral transcription and disrupts host cellular immunity by inducing lymphocyte apoptosis, but whether it influences humoral immunity remains unclear. Previously, our group demonstrated that tat depresses expression of DNA-PKcs, a critical component of the non-homologous end joining pathway (NHEJ) of DNA double-strand breaks repair, immunoglobulin class switch recombination (CSR) and V(D)J recombination, and sensitizes cells to ionizing radiation. In this study, we demonstrated that HIV-1 Tat down-regulates DNA-PKcs expression by directly binding to the core promoter sequence. In addition, Tat interacts with and activates the kinase activity of DNA-PKcs in a dose-dependent and DNA independent manner. Furthermore, Tat inhibits class switch recombination (CSR) at low concentrations (≤ 4 µg/ml) and stimulates CSR at high concentrations (≥ 8 µg/ml). On the other hand, low protein level and high kinase activity of DNA-PKcs promotes HIV-1 transcription, while high protein level and low kinase activity inhibit HIV-1 transcription. Co-immunoprecipitation results revealed that DNA-PKcs forms a large complex comprised of Cyclin T1, CDK9 and Tat via direct interacting with CDK9 and Tat but not Cyclin T1. Taken together, our results provide new clues that Tat regulates host humoral immunity via both transcriptional depression and kinase activation of DNA-PKcs. We also raise the possibility that inhibitors and interventions directed towards DNA-PKcs may inhibit HIV-1 transcription in AIDS patients.

Human immunodeficiency virus-1 protein Tat induces excitotoxic loss of presynaptic terminals in hippocampal cultures.

Science.gov (United States)

Shin, Angela H; Thayer, Stanley A

2013-05-01

Human immunodeficiency virus (HIV) infection of the CNS produces dendritic damage that correlates with cognitive decline in patients with HIV-associated neurocognitive disorders (HAND). HIV-induced neurotoxicity results in part from viral proteins shed from infected cells, including the HIV transactivator of transcription (Tat). We previously showed that Tat binds to the low density lipoprotein receptor-related protein (LRP), resulting in overactivation of NMDA receptors, activation of the ubiquitin-proteasome pathway, and subsequent loss of postsynaptic densities. Here, we show that Tat also induces a loss of presynaptic terminals. The number of presynaptic terminals was quantified using confocal imaging of synaptophysin fused to green fluorescent protein (Syn-GFP). Tat-induced loss of presynaptic terminals was secondary to excitatory postsynaptic mechanisms because treatment with an LRP antagonist or an NMDA receptor antagonist inhibited this loss. Treatment with nutlin-3, an E3 ligase inhibitor, prevented Tat-induced loss of presynaptic terminals. These data suggest that Tat-induced loss of presynaptic terminals is a consequence of excitotoxic postsynaptic activity. We previously found that ifenprodil, an NR2B subunit-selective NMDA receptor antagonist, induced recovery of postsynaptic densities. Here we show that Tat-induced loss of presynaptic terminals was reversed by ifenprodil treatment. Thus, Tat-induced loss of presynaptic terminals is reversible, and this recovery can be initiated by inhibiting a subset of postsynaptic NMDA receptors. Understanding the dynamics of synaptic changes in response to HIV infection of the CNS may lead to the design of improved pharmacotherapies for HAND patients. Copyright © 2012 Elsevier Inc. All rights reserved.

Intracellular trafficking of superparamagnetic iron oxide nanoparticles conjugated with TAT peptide: 3-dimensional electron tomography analysis

Energy Technology Data Exchange (ETDEWEB)

Nair, Baiju G.; Fukuda, Takahiro; Mizuki, Toru; Hanajiri, Tatsuro [Bio-Nano Electronics Research Centre, Toyo University, Saitama 350-8585 (Japan); Maekawa, Toru, E-mail: maekawa@toyo.jp [Bio-Nano Electronics Research Centre, Toyo University, Saitama 350-8585 (Japan)

2012-05-18

Highlights: Black-Right-Pointing-Pointer We study the intracellular localisation of TAT-SPIONs using 3-D electron tomography. Black-Right-Pointing-Pointer 3-D images of TAT-SPIONs in a cell are clearly shown. Black-Right-Pointing-Pointer Release of TAT-SPIONs from endocytic vesicles into the cytoplasm is clearly shown. -- Abstract: Internalisation of nanoparticles conjugated with cell penetrating peptides is a promising approach to various drug delivery applications. Cell penetrating peptides such as transactivating transcriptional activator (TAT) peptides derived from HIV-1 proteins are effective intracellular delivery vectors for a wide range of nanoparticles and pharmaceutical agents thanks to their amicable ability to enter cells and minimum cytotoxicity. Although different mechanisms of intracellular uptake and localisation have been proposed for TAT conjugated nanoparticles, it is necessary to visualise the particles on a 3-D plane in order to investigate the actual intracellular uptake and localisation. Here, we study the intracellular localisation and trafficking of TAT peptide conjugated superparamagnetic ion oxide nanoparticles (TAT-SPIONs) using 3-D electron tomography. 3-D tomograms clearly show the location of TAT-SPIONs in a cell and their slow release from the endocytic vesicles into the cytoplasm. The present methodology may well be utilised for further investigations of the behaviours of nanoparticles in cells and eventually for the development of nano drug delivery systems.

The effects of HIV-1 regulatory TAT protein expression on brain reward function, response to psychostimulants and delay-dependent memory in mice.

Science.gov (United States)

Kesby, James P; Markou, Athina; Semenova, Svetlana

2016-10-01

Depression and psychostimulant abuse are common comorbidities among humans with immunodeficiency virus (HIV) disease. The HIV regulatory protein TAT is one of multiple HIV-related proteins associated with HIV-induced neurotoxicity. TAT-induced dysfunction of dopamine and serotonin systems in corticolimbic brain areas may result in impaired reward function, thus, contributing to depressive symptoms and psychostimulant abuse. Transgenic mice with doxycycline-induced TAT protein expression in the brain (TAT+, TAT- control) show neuropathology resembling brain abnormalities in HIV+ humans. We evaluated brain reward function in response to TAT expression, nicotine and methamphetamine administration in TAT+ and TAT- mice using the intracranial self-stimulation procedure. We evaluated the brain dopamine and serotonin systems with high-performance liquid chromatography. The effects of TAT expression on delay-dependent working memory in TAT+ and TAT- mice using the operant delayed nonmatch-to-position task were also assessed. During doxycycline administration, reward thresholds were elevated by 20% in TAT+ mice compared with TAT- mice. After the termination of doxycycline treatment, thresholds of TAT+ mice remained significantly higher than those of TAT- mice and this was associated with changes in mesolimbic serotonin and dopamine levels. TAT+ mice showed a greater methamphetamine-induced threshold lowering compared with TAT- mice. TAT expression did not alter delay-dependent working memory. These results indicate that TAT expression in mice leads to reward deficits, a core symptom of depression, and a greater sensitivity to methamphetamine-induced reward enhancement. Our findings suggest that the TAT protein may contribute to increased depressive-like symptoms and continued methamphetamine use in HIV-positive individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aids-related kaposi's sarcoma in a four year old child: the challenge ...

African Journals Online (AJOL)

Background: AIDSrelated Kaposi's sarcoma (KS) is an AIDS-defining illness and is now increasingly recognized in children infected with HIV. Many of these cases are missed due to low index of suspicion. Vertical transmission of HIV is the commonest route of transmission in children and this is preventable by early ...

Preliminary study on the inhibition of nuclear internalization of Tat peptides by conjugation with a receptor-specific peptide and fluorescent dyes

Science.gov (United States)

Shen, Duanwen; Liang, Kexiang; Ye, Yunpeng; Tetteh, Elizabeth; Achilefu, Samuel

2006-02-01

Numerous studies have shown that basic Tat peptide (48-57) internalized non-specifically in cells and localized in the nucleus. However, localization of imaging agents in cellular nucleus is not desirable because of the potential mutagenesis. When conjugated to the peptides that undergo receptor-mediated endocytosis, Tat peptide could target specific cells or pathologic tissue. We tested this hypothesis by incorporating a somatostatin receptor-avid peptide (octreotate, Oct) and two different fluorescent dyes, Cypate 2 (Cy2) and fluorescein 5'-carboxlic acid (5-FAM), into the Tat-peptide sequence. In addition to the Cy2 or 5-FAM-labeled Oct conjugated to Tat peptide (Tat) to produce Tat-Oct-Cypate2 or Tat-Oct-5-FAM, we also labeled the Tat the Tat peptide with these dyes (Tat-Cy2 and Tat-5-FAM) to serve as positive control. A somatostatin receptor-positive pancreatic tumor cell line, AR42J, was used to assess cell internalization. The results show that Tat-5-FAM and Tat-Cypate2 localized in both nucleus and cytoplasm of the cells. In contrast to Tat-Oct-Cypate2, which localized in both the cytoplasm and nucleus, Tat-Oct-5-FAM internalized in the cytoplasm but not in the nucleus of AR42J cells. The internalizations were inhibited by adding non-labeled corresponding peptides, suggesting that the endocytoses of each group of labeled and the corresponding unlabeled compounds occurred through a common pathway. Thus, fluorescent probes and endocytosis complex between octreotate and somatostatin receptors in cytoplasm could control nuclear internalization of Tat peptides.

Immunohistochemical detection of the latent nuclear antigen-1 of the human herpesvirus type 8 to differentiate cutaneous epidemic Kaposi sarcoma and its histological simulators Detecção imuno-histoquímica do antígeno nuclear latente-1 do herpesvirus tipo 8 para diferenciar o sarcoma de Kaposi epidêmico cutâneo de seus simuladores histológicos

Directory of Open Access Journals (Sweden)

Patricia Fonseca Pereira

2013-04-01

Full Text Available Kaposi's sarcoma is the most common neoplasia diagnosed in AIDS patients and the expression of the human herpesvirus-8 (HHV-8 latent nuclear antigen-1 has been useful for its histological diagnosis. The aim of this study is to confirm that immunohistochemistry is a valuable tool for differentiating KS from its simulators in skin biopsies of HIV patients. Immunohistochemical and histological analyses were performed in 49 Kaposi's sarcoma skin biopsies and 60 of its histological simulators. Positivity was present in the 49 Kaposi's sarcoma skin biopsies and no staining was observed in the 60 simulators analyzed, resulting in sensibility and specificity of 100%. HHV-8 immunohistochemical detection is an effective tool for diagnosing Kaposi's sarcoma, especially in early lesions in which neoplastic features are not evident. It also contributes to its histological differential diagnosis.O sarcoma de Kaposi é a neoplasia mais diagnosticada em pacientes com SIDA e a expressão do antígeno nuclear latente-1 do herpesvírus humano tipo-8 (HHV-8 tem se mostrado útil no seu diagnóstico histológico. O objetivo deste estudo é confirmar que o método imuno-histoquímico é uma ferramenta útil para diferenciar o sarcoma de Kaposi cutâneo de seus simuladores histológicos em pacientes HIV positivos. Análise histológica e imuno-histoquímica foram realizadas em 49 casos de sarcoma de Kaposi cutâneo e 60 casos de seus simuladores histológicos. Positividade à imuno-histoquímica para o antígeno nuclear latente 1 do HHV-8 foi observada nos 49 casos de sarcoma de Kaposi e nenhuma reação foi detectada nos 60 simuladores analisados, resultando em 100% de sensibilidade e especificidade. A detecção do HHV-8 por imuno-histoquímica é uma ferramenta útil para o diagnóstico de sarcoma de Kaposi, especialmente na lesão inicial cujo caráter neoplásico não é evidente, e contribui para seu diagnóstico diferencial histológico.

États financiers 2015–2016

International Development Research Centre (IDRC) Digital Library (Canada)

une assurance raisonnable qu'il pourra réaliser ses objectifs. .... les employés et leur procure des services de santé avant ...... indépendance, à un audit des états financiers annuels, conformément aux normes d'audit généralement reconnues.

L'état de plasma le feu de l'Univers

CERN Document Server

Lehner, Thierry

2004-01-01

Dans l'Antiquité, les Grecs considéraient que les constituants du monde dérivaient de quatre éléments essentiels : la terre, l'eau, l'air et le feu. Il n'est pas difficile de voir dans les trois premiers l'équivalent de nos états solide, liquide et gazeux. Mais l'état physique le plus répandu dans l'Univers - correspondant au feu des Anciens - n'est apparu que récemment et n'a été reconnu par la communauté des physiciens qu'en 1928 : c'est le plasma. Cet état très étrange - gazeux, électrique, lumineux, impalpable - reste le plus exotique et le plus inattendu. Il a donné naissance aux trois autres états puisque, à l'exception des éléments ultra-légers que sont l'hydrogène et l'hélium, tous ceux qui constituent notre monde (carbone, oxygène, fer, etc.) sont apparus dans ces fourneaux gigantesques, ces monstres de plasma, qu'étaient les premières étoiles. La vie elle-même en découle par ricochet, ce qui a permis de dire que nous ne sommes que des " poussières d'étoiles ". Décou...

Biocompatible anionic polymeric microspheres as priming delivery system for effetive HIV/AIDS Tat-based vaccines.

Directory of Open Access Journals (Sweden)

Fausto Titti

Full Text Available Here we describe a prime-boost regimen of vaccination in Macaca fascicularis that combines priming with novel anionic microspheres designed to deliver the biologically active HIV-1 Tat protein and boosting with Tat in Alum. This regimen of immunization modulated the IgG subclass profile and elicited a balanced Th1-Th2 type of humoral and cellular responses. Remarkably, following intravenous challenge with SHIV89.6Pcy243, vaccinees significantly blunted acute viremia, as compared to control monkeys, and this control was associated with significantly lower CD4+ T cell depletion rate during the acute phase of infection and higher ability to resume the CD4+ T cell counts in the post-acute and chronic phases of infection. The long lasting control of viremia was associated with the persistence of high titers anti-Tat antibodies whose profile clearly distinguished vaccinees in controllers and viremics. Controllers, as opposed to vaccinated and viremic cynos, exhibited significantly higher pre-challenge antibody responses to peptides spanning the glutamine-rich and the RGD-integrin-binding regions of Tat. Finally, among vaccinees, titers of anti-Tat IgG1, IgG3 and IgG4 subclasses had a significant association with control of viremia in the acute and post-acute phases of infection. Altogether these findings indicate that the Tat/H1D/Alum regimen of immunization holds promise for next generation vaccines with Tat protein or other proteins for which maintenance of the native conformation and activity are critical for optimal immunogenicity. Our results also provide novel information on the role of anti-Tat responses in the prevention of HIV pathogenesis and for the design of new vaccine candidates.

Application of Bacillus sp. TAT105 to reduce ammonia emissions during pilot-scale composting of swine manure.

Science.gov (United States)

Kuroda, Kazutaka; Tanaka, Akihiro; Furuhashi, Kenich; Nakasaki, Kiyohiko

2017-12-01

Thermophilic ammonium-tolerant bacterium Bacillus sp. TAT105 grows and reduces ammonia (NH 3 ) emissions by assimilating ammonium nitrogen during composting of swine feces. To evaluate the efficacy of a biological additive containing TAT105 at reducing NH 3 emissions, composting tests of swine manure on a pilot scale (1.8 m 3 ) were conducted. In the TAT105-added treatment, NH 3 emissions and nitrogen loss were lower than those in the control treatment without TAT105. No significant difference was detected in losses in the weight and volatile solids between the treatments. Concentration of thermophilic ammonium-tolerant bacteria in the compost increased in both treatments at the initial stage of composting. In the TAT105-added treatment, bacterial concentration reached ~10 9 colony-forming units per gram of dry matter, several-fold higher than that in the control and stayed at the same level until the end. These results suggest that TAT105 grows during composting and reduces NH 3 emissions in TAT105-added treatment.

Inhibition of GABAergic Neurotransmission by HIV-1 Tat and Opioid Treatment in the Striatum Involves μ-opioid Receptors

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Changqing Xu

2016-11-01

Full Text Available Due to combined antiretroviral therapy (cART, human immunodeficiency virus type 1 (HIV-1 is considered a chronic disease with high prevalence of mild forms of neurocognitive impairments, also referred to as HIV-associated neurocognitive disorders (HAND. Although opiate drug use can exacerbate HIV-1 Tat-induced neuronal damage, it remains unknown how and to what extent opioids interact with Tat on the GABAergic system. We conducted whole-cell recordings in mouse striatal slices and examined the effects of HIV-1 Tat in the presence and absence of morphine (1 μM and damgo (1 μM on GABAergic neurotransmission. Results indicated a decrease in the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs and miniature IPSCs (mIPSCs by Tat (5 – 50 nM in a concentration-dependent manner. The significant Tat-induced decrease in IPSCs was abolished when removing extracellular and/or intracellular calcium. Treatment with morphine or damgo alone significantly decreased the frequency, but not amplitude of IPSCs. Interestingly, morphine but not damgo indicated an additional downregulation of the mean frequency of mIPSCs in combination with Tat. Pretreatment with naloxone (1 μM and CTAP (1 μM prevented the Tat-induced decrease in sIPSCs frequency but only naloxone prevented the combined Tat and morphine effect on mIPSCs frequency. Results indicate a Tat- or opioid-induced decrease in GABAergic neurotransmission via µ-opioid receptors with combined Tat and morphine effects involving additional opioid receptor-related mechanisms. Exploring the interactions between Tat and opioids on the GABAergic system may help to guide future research on HAND in the context of opiate drug use.

In vitro assessment of TAT — Ciliary Neurotrophic Factor therapeutic potential for peripheral nerve regeneration

International Nuclear Information System (INIS)

Barbon, Silvia; Stocco, Elena; Negro, Alessandro; Dalzoppo, Daniele; Borgio, Luca; Rajendran, Senthilkumar; Grandi, Francesca; Porzionato, Andrea; Macchi, Veronica; De Caro, Raffaele

2016-01-01

In regenerative neurobiology, Ciliary Neurotrophic Factor (CNTF) is raising high interest as a multifunctional neurocytokine, playing a key role in the regeneration of injured peripheral nerves. Despite its promising trophic and regulatory activity, its clinical application is limited by the onset of severe side effects, due to the lack of efficient intracellular trafficking after administration. In this study, recombinant CNTF linked to the transactivator transduction domain (TAT) was investigated in vitro and found to be an optimized fusion protein which preserves neurotrophic activity, besides enhancing cellular uptake for therapeutic advantage. Moreover, a compelling protein delivery method was defined, in the future perspective of improving nerve regeneration strategies. Following determination of TAT-CNTF molecular weight and concentration, its specific effect on neural SH-SY5Y and PC12 cultures was assessed. Cell proliferation assay demonstrated that the fusion protein triggers PC12 cell growth within 6 h of stimulation. At the same time, the activation of signal transduction pathway and enhancement of cellular trafficking were found to be accomplished in both neural cell lines after specific treatment with TAT-CNTF. Finally, the recombinant growth factor was successfully loaded on oxidized polyvinyl alcohol (PVA) scaffolds, and more efficiently released when polymer oxidation rate increased. Taken together, our results highlight that the TAT domain addiction to the protein sequence preserves CNTF specific neurotrophic activity in vitro, besides improving cellular uptake. Moreover, oxidized PVA could represent an ideal biomaterial for the development of nerve conduits loaded with the fusion protein to be delivered to the site of nerve injury. - Highlights: • TAT-CNTF is an optimized fusion protein that preserves neurotrophic activity. • In neural cell lines, TAT-CNTF triggers the activation of signal transduction. • Fast cellular uptake of TAT-CNTF was

In vitro assessment of TAT — Ciliary Neurotrophic Factor therapeutic potential for peripheral nerve regeneration

Energy Technology Data Exchange (ETDEWEB)

Barbon, Silvia, E-mail: silvia.barbon@yahoo.it [Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via Marzolo 5, 35131 Padua (Italy); Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling (TES) ONLUS, Via De Sanctis 10, Caselle di Selvazzano Dentro, 35030 Padua (Italy); Stocco, Elena, E-mail: elena.stocco@gmail.com [Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via Marzolo 5, 35131 Padua (Italy); Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling (TES) ONLUS, Via De Sanctis 10, Caselle di Selvazzano Dentro, 35030 Padua (Italy); Negro, Alessandro, E-mail: alessandro.negro@unipd.it [Department of Biomedical Sciences, University of Padova, Via Colombo 3, 35121 Padua (Italy); Dalzoppo, Daniele, E-mail: daniele.dalzoppo@unipd.it [Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via Marzolo 5, 35131 Padua (Italy); Borgio, Luca, E-mail: borgio.luca@gmail.com [Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via Marzolo 5, 35131 Padua (Italy); Rajendran, Senthilkumar, E-mail: senthilstem@gmail.com [Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via Marzolo 5, 35131 Padua (Italy); Grandi, Francesca, E-mail: francesca.grandi7825@gmail.com [Department of Women' s and Children' s Health, Pediatric Surgery, University of Padua, Via Giustiniani 3, 35121 Padua (Italy); Porzionato, Andrea, E-mail: andrea.porzionato@unipd.it [Section of Human Anatomy, Department of Molecular Medicine, University of Padua, Via Gabelli 65, 35121 Padua (Italy); Macchi, Veronica, E-mail: veronica.macchi@unipd.it [Section of Human Anatomy, Department of Molecular Medicine, University of Padua, Via Gabelli 65, 35121 Padua (Italy); De Caro, Raffaele, E-mail: raffaele.decaro@unipd.it [Section of Human Anatomy, Department of Molecular Medicine, University of Padua, Via Gabelli 65, 35121 Padua (Italy); and others

2016-10-15

In regenerative neurobiology, Ciliary Neurotrophic Factor (CNTF) is raising high interest as a multifunctional neurocytokine, playing a key role in the regeneration of injured peripheral nerves. Despite its promising trophic and regulatory activity, its clinical application is limited by the onset of severe side effects, due to the lack of efficient intracellular trafficking after administration. In this study, recombinant CNTF linked to the transactivator transduction domain (TAT) was investigated in vitro and found to be an optimized fusion protein which preserves neurotrophic activity, besides enhancing cellular uptake for therapeutic advantage. Moreover, a compelling protein delivery method was defined, in the future perspective of improving nerve regeneration strategies. Following determination of TAT-CNTF molecular weight and concentration, its specific effect on neural SH-SY5Y and PC12 cultures was assessed. Cell proliferation assay demonstrated that the fusion protein triggers PC12 cell growth within 6 h of stimulation. At the same time, the activation of signal transduction pathway and enhancement of cellular trafficking were found to be accomplished in both neural cell lines after specific treatment with TAT-CNTF. Finally, the recombinant growth factor was successfully loaded on oxidized polyvinyl alcohol (PVA) scaffolds, and more efficiently released when polymer oxidation rate increased. Taken together, our results highlight that the TAT domain addiction to the protein sequence preserves CNTF specific neurotrophic activity in vitro, besides improving cellular uptake. Moreover, oxidized PVA could represent an ideal biomaterial for the development of nerve conduits loaded with the fusion protein to be delivered to the site of nerve injury. - Highlights: • TAT-CNTF is an optimized fusion protein that preserves neurotrophic activity. • In neural cell lines, TAT-CNTF triggers the activation of signal transduction. • Fast cellular uptake of TAT-CNTF was

TIT FOR TAT in sticklebacks and the evolution of cooperation

Science.gov (United States)

Milinski, Manfred

1987-01-01

The problems of achieving mutual cooperation can be formalized in a game called the Prisoner's Dilemma in which selfish defection is always more rewarding than cooperation1. If the two protagonists have a certain minimum probability of meeting again a strategy called TIT FOR TAT is very successful2. In TIT FOR TAT the player cooperates on the first move and thereafter does whatever the opponent did on the previous move. I have studied the behaviour of fish when confronting a potential predator, because conflicts can arise within pairs of fish in these circumstances which I argue resemble a series of games of Prisoner's Dilemma. Using a system of mirrors, single three-spined sticklebacks (Gasterosteus aculeatus) approaching a live predator were provided with either a simulated cooperating companion or a simulated defecting one. In both cases the test fish behaved according to TIT FOR TAT supporting the hypothesis that cooperation can evolve among egoists.

Kaposi's sarcoma herpesvirus and HIV-1 seroprevalences in prostitutes in Djibouti.

Science.gov (United States)

Marcelin, Anne-Geneviève; Grandadam, Marc; Flandre, Philippe; Nicand, Elisabeth; Milliancourt, Catherine; Koeck, Jean-Louis; Philippon, Michel; Teyssou, Remy; Agut, Henri; Dupin, Nicolas; Calvez, Vincent

2002-10-01

Kaposi's sarcoma herpesvirus (KSHV) is linked causally to Kaposi's sarcoma. Epidemiological studies have shown that KSHV transmission can occur during sex among homosexual men, but heterosexual transmission seems to be very rare in KSHV low prevalence countries. A seroepidemiological study was conducted to determine whether KSHV is transmitted sexually between heterosexuals in an endemic country. Sera from 282 subjects of African origin living in Djibouti were tested for antibodies to KSHV and HIV-1. Among the 282 individuals, 43 were female prostitutes working in the streets (group 1), 123 were female prostitutes working in luxury bars (group 2), 41 were non-prostitute females (group 3), and 75 were non-prostitute males (group 4). KSHV seroprevalence was 26, 20, 17, and 36% in groups 1, 2, 3, and 4, respectively. The seroprevalence of KSHV is not different between street or bar prostitutes and non-prostitute females (OR = 1.67; P = 0.34 and OR = 1.18; P = 0.73). These results suggest that in this endemic country commercial sex work does not seem to be a risk factor for KSHV infection and provides evidence against heterosexual transmission of KSHV in the female population studied. Copyright 2002 Wiley-Liss, Inc.

Protein complexes associated with the Kaposi's sarcoma-associated herpesvirus-encoded LANA

International Nuclear Information System (INIS)

Kaul, Rajeev; Verma, Subhash C.; Robertson, Erle S.

2007-01-01

Kaposi's sarcoma-associated herpesvirus (KSHV) is the major biological cofactor contributing to development of Kaposi's sarcoma. KSHV establishes a latent infection in human B cells expressing the latency-associated nuclear antigen (LANA), a critical factor in the regulation of viral latency. LANA is known to modulate viral and cellular gene expression. We report here on some initial proteomic studies to identify cellular proteins associated with the amino and carboxy-terminal domains of LANA. The results of these studies show an association of known cellular proteins which support LANA functions and have identified additional LANA-associated proteins. These results provide new evidence for complexes involving LANA with a number of previously unreported functional classes of proteins including DNA polymerase, RNA helicase and cell cycle control proteins. The results also indicate that the amino terminus of LANA can interact with its carboxy-terminal domain. This interaction is potentially important for facilitating associations with other cell cycle regulatory proteins which include CENP-F identified in association with both the amino and carboxy-termini. These novel associations add to the diversity of LANA functions in relation to the maintenance of latency and subsequent transformation of KSHV infected cells

HIV-1 Tat protein induces glial cell autophagy through enhancement of BAG3 protein levels.

Science.gov (United States)

Bruno, Anna Paola; De Simone, Francesca Isabella; Iorio, Vittoria; De Marco, Margot; Khalili, Kamel; Sariyer, Ilker Kudret; Capunzo, Mario; Nori, Stefania Lucia; Rosati, Alessandra

2014-01-01

BAG3 protein has been described as an anti-apoptotic and pro-autophagic factor in several neoplastic and normal cells. We previously demonstrated that BAG3 expression is elevated upon HIV-1 infection of glial and T lymphocyte cells. Among HIV-1 proteins, Tat is highly involved in regulating host cell response to viral infection. Therefore, we investigated the possible role of Tat protein in modulating BAG3 protein levels and the autophagic process itself. In this report, we show that transfection with Tat raises BAG3 levels in glioblastoma cells. Moreover, BAG3 silencing results in highly reducing Tat- induced levels of LC3-II and increasing the appearance of sub G0/G1 apoptotic cells, in keeping with the reported role of BAG3 in modulating the autophagy/apoptosis balance. These results demonstrate for the first time that Tat protein is able to stimulate autophagy through increasing BAG3 levels in human glial cells.

Combined zidovudine and interferon-alpha treatment in patients with AIDS-associated Kaposi's sarcoma

NARCIS (Netherlands)

de Wit, R.; Danner, S. A.; Bakker, P. J.; Lange, J. M.; Eeftinck Schattenkerk, J. K.; Veenhof, C. H.

1991-01-01

The effectiveness of addition of interferon-alpha (IFN-alpha) to zidovudine in patients with AIDS-associated Kaposi's sarcoma was assessed in a non-randomized, phase II clinical trial. Twenty-one patients were treated with oral zidovudine (600 mg daily) and IFN-alpha was increased to 18 MU daily for

Effect of the peptide Tat(49-57) on the bio-distribution and similar radiopharmaceuticals dosimetry of the bombesin

International Nuclear Information System (INIS)

Santos C, C. L.

2011-01-01

The gastrin-releasing peptide receptor (GRP-r) is over-expressed in prostate and breast cancer. 99m Tc-Bombesin ( 99m Tc-Bn) has been reported as a radiopharmaceutical with specific cell GRP-r binding. The HIV Tat(49-57)-derived peptide has been used to deliver a large variety of molecules to cell nuclei. New hybrid radiopharmaceuticals of type 99m Tc-N 2 S 2 -Tat(49-57)-Lys 3 -Bn ( 99m Tc-Tat-Bn) and 188 Re-N 2 S 2 -Tat(49-57)-Lys 3 -Bn ( 188 Re-Tat-Bn), would increase cell uptake and internalized in cancer cell nuclei could act as an effective system of targeted radiotherapy using Auger and internal conversion (I C) electron emissions near DNA. The aim of this research was to prepare and assess in vitro and in vivo uptake kinetics in cancer cells of 99m Tc/ 188 Re-Tat-Bn and the in vitro nucleus and cytoplasm internalization kinetics in GRP receptor-positive cancer cells as well as to evaluate the subcellular-level radiation absorbed dose associated with the observed effect on cancer cell DNA proliferation. Structures of N 2 S 2 -Tat-Bn and Tc/Re(O)N 2 S 2 -Tat-Bn were calculated by an Mm procedure. 99m Tc-Tat-Bn and 188 Re-Tat-Bn were synthesized and stability studies carried out by HPLC and I TLC-Sg analyses in serum and cysteine solutions. In vitro internalization was tested using human prostate cancer Pc 3 cells and breast carcinoma cell lines MDA-Mb 231 and MCF 7. Nuclei from cells were isolated using a nuclear extraction kit. Total disintegrations in each subcellular compartment were calculated by integration of experimental time activity kinetic curves. Nucleus internalization was corroborated by con focal microscopy images using immunofluorescent labelled Tat-Bn. Biodistribution was determined in Pc 3 tumor-bearing nude mice. The Penelope code was used to simulate and calculate the absorbed dose by contribution of β, Auger and I C electrons in the cytoplasm and nucleus using geometric models built from immunofluorescent cell images. A cell proliferation

HIV-1 tat promotes integrin-mediated HIV transmission to dendritic cells by binding Env spikes and competes neutralization by anti-HIV antibodies.

Directory of Open Access Journals (Sweden)

Paolo Monini

Full Text Available Use of Env in HIV vaccine development has been disappointing. Here we show that, in the presence of a biologically active Tat subunit vaccine, a trimeric Env protein prevents in monkeys virus spread from the portal of entry to regional lymph nodes. This appears to be due to specific interactions between Tat and Env spikes that form a novel virus entry complex favoring R5 or X4 virus entry and productive infection of dendritic cells (DCs via an integrin-mediated pathway. These Tat effects do not require Tat-transactivation activity and are blocked by anti-integrin antibodies (Abs. Productive DC infection promoted by Tat is associated with a highly efficient virus transmission to T cells. In the Tat/Env complex the cysteine-rich region of Tat engages the Env V3 loop, whereas the Tat RGD sequence remains free and directs the virus to integrins present on DCs. V2 loop deletion, which unshields the CCR5 binding region of Env, increases Tat/Env complex stability. Of note, binding of Tat to Env abolishes neutralization of Env entry or infection of DCs by anti-HIV sera lacking anti-Tat Abs, which are seldom present in natural infection. This is reversed, and neutralization further enhanced, by HIV sera containing anti-Tat Abs such as those from asymptomatic or Tat-vaccinated patients, or by sera from the Tat/Env vaccinated monkeys. Thus, both anti-Tat and anti-Env Abs are required for efficient HIV neutralization. These data suggest that the Tat/Env interaction increases HIV acquisition and spreading, as a mechanism evolved by the virus to escape anti-Env neutralizing Abs. This may explain the low effectiveness of Env-based vaccines, which are also unlikely to elicit Abs against new Env epitopes exposed by the Tat/Env interaction. As Tat also binds Envs from different clades, new vaccine strategies should exploit the Tat/Env interaction for both preventative and therapeutic interventions.

TAT-Mediated Delivery of Tousled Protein to Salivary Glands Protects Against Radiation-Induced Hypofunction

Energy Technology Data Exchange (ETDEWEB)

Sunavala-Dossabhoy, Gulshan, E-mail: gsunav@lsuhsc.edu [Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Palaniyandi, Senthilnathan; Richardson, Charles; De Benedetti, Arrigo [Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Schrott, Lisa [Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Caldito, Gloria [Department of Bioinformatics and Computational Biology, Louisiana State University Health Sciences Center, Shreveport, LA (United States)

2012-09-01

Purpose: Patients treated with radiotherapy for head-and-neck cancer invariably suffer its deleterious side effect, xerostomia. Salivary hypofunction ensuing from the irreversible destruction of glands is the most common and debilitating oral complication affecting patients undergoing regional radiotherapy. Given that the current management of xerostomia is palliative and ineffective, efforts are now directed toward preventive measures to preserve gland function. The human homolog of Tousled protein, TLK1B, facilitates chromatin remodeling at DNA repair sites and improves cell survival against ionizing radiation (IR). Therefore, we wanted to determine whether a direct transfer of TLK1B protein to rat salivary glands could protect against IR-induced salivary hypofunction. Methods: The cell-permeable TAT-TLK1B fusion protein was generated. Rat acinar cell line and rat salivary glands were pretreated with TAT peptide or TAT-TLK1B before IR. The acinar cell survival in vitro and salivary function in vivo were assessed after radiation. Results: We demonstrated that rat acinar cells transduced with TAT-TLK1B were more resistant to radiation (D{sub 0} = 4.13 {+-} 1.0 Gy; {alpha}/{beta} = 0 Gy) compared with cells transduced with the TAT peptide (D{sub 0} = 4.91 {+-} 1.0 Gy; {alpha}/{beta} = 20.2 Gy). Correspondingly, retroductal instillation of TAT-TLK1B in rat submandibular glands better preserved salivary flow after IR (89%) compared with animals pretreated with Opti-MEM or TAT peptide (31% and 39%, respectively; p < 0.01). Conclusions: The results demonstrate that a direct transfer of TLK1B protein to the salivary glands effectively attenuates radiation-mediated gland dysfunction. Prophylactic TLK1B-protein therapy could benefit patients undergoing radiotherapy for head-and-neck cancer.

Changing Incidence and Risk Factors for Kaposi Sarcoma by Time Since Starting Antiretroviral Therapy

DEFF Research Database (Denmark)

Wyss, Natascha; Zwahlen, Marcel; Bohlius, Julia

2016-01-01

BACKGROUND:  Kaposi sarcoma (KS) remains a frequent cancer in human immunodeficiency virus (HIV)-positive patients starting combination antiretroviral therapy (cART). We examined incidence rates and risk factors for developing KS in different periods after starting cART in patients from European...

Improved intracellular delivery of glucocerebrosidase mediated by the HIV-1 TAT protein transduction domain

International Nuclear Information System (INIS)

Lee, Kyun Oh; Luu, Nga; Kaneski, Christine R.; Schiffmann, Raphael; Brady, Roscoe O.; Murray, Gary J.

2005-01-01

Enzyme replacement therapy (ERT) for Gaucher disease designed to target glucocerebrosidase (GC) to macrophages via mannose-specific endocytosis is very effective in reversing hepatosplenomegaly, and normalizing hematologic parameters but is less effective in improving bone and lung involvement and ineffective in brain. Recombinant GCs containing an in-frame fusion to the HIV-1 trans-activator protein transduction domain (TAT) were expressed in eukaryotic cells in order to obtain active, normally glycosylated GC fusion proteins for enzyme uptake studies. Despite the absence of mannose-specific endocytic receptors on the plasma membranes of various fibroblasts, the recombinant GCs with C-terminal TAT fusions were readily internalized by these cells. Immunofluorescent confocal microscopy demonstrated the recombinant TAT-fusion proteins with a mixed endosomal and lysosomal localization. Thus, TAT-modified GCs represent a novel strategy for a new generation of therapeutic enzymes for ERT for Gaucher disease

Value of conventionally fractionated radiotherapy for the local treatment of HIV associated Kaposi's sarcoma

International Nuclear Information System (INIS)

Saran, F.; Adamietz, I.A.; Mose, S.; Thilmann, C.; Boettcher, H.D.

1995-01-01

From June 1991 to June 1993, 43 patients with 111 HIV-associated Kaposi's sarcoma of the skin or oral cavity were treated. Lesions were irradiated with 5 to 12 MeV electrons or 60Co gamma-rays. The fractionation scheme was 5 times 2 Gy/week for skin and enoral lesions with a total reference dosage of up to 20 Gy. Side effects were assessed during therapy and the therapeutic result 6 weeks after end of treatment. Thirty-eight out of 111 lesions were judged as complete response (CR) (34%), 61/111 as partial response (PR) (55%) and 12/111 were judged as no change (NC) (11%). Overall response (CR + PR) was 89%. Two patients with lesions of oral cavity suffered from RTOG grade-IV mucositis after 10 and 14 Gy. In 71/106 skin lesions (67%), radiation induced RTOG grade-I reactions were observed. Conclusion: In patients with HIV associated Kaposi's sarcoma effective palliation can be achieved by means of radiotherapy with an overall dose of 20 Gy in conventional fractionation. Yet, the fraction of patients with complete responses is with 34 to 47% lower compared with doses above 20 Gy (66 to 100%). With reference to the reported data our results point to a dose-response relationship for Kaposi's sarcoma. Therefore higher total reference doses, e.g. 30 Gy with weekly 5 times 2 Gy or 24 Gy with 5 times 1.6 Gy for mucous lesions, respectively, are suggested as by this mean the complete response rate can be coubled. (orig./MG) [de

Thoracic manifestations of Kaposi's sarcoma in AIDS: radiological findings

International Nuclear Information System (INIS)

Marchiori, Edson; Baptista, Maria Ines Garcia; Cardenas, Gloria Pamela; Costa Praxedes, Marcia da; Boechat, Lucia de Fatima; Quaresma, Patricia Souto Maior

1995-01-01

The radiological findings of 189 cases of Kaposi's sarcoma occurring in patients with AIDS were studied. There was also made pathological correlations in these patients. Interstitial reticular infiltrations were frequently detected on thoracic examination showing paracardiac confluent areas. There was also lymphadenopathy, gross nodules and pleural fluid accumulation. Although there was no detection of any pathognomonic aspect, the interstitial reticular infiltration finding together with the paracardiac confluent areas and associated with gross nodules, is highly indicative to thoracic involvement by the disease. (author). 32 refs., 5 figs., 2 tabs

Human Immunodeficiency Virus Tat-Activated Expression of Poliovirus Protein 2A Inhibits mRNA Translation

Science.gov (United States)

Sun, Xiao-Hong; Baltimore, David

1989-04-01

To study the effect of poliovirus protein 2A on cellular RNA translation, the tat control system of human immunodeficiency virus (HIV) was used. Protein 2A was expressed from a plasmid construct (pHIV/2A) incorporating the HIV long terminal repeat. Protein synthesis was measured by using chloramphenicol acetyltransferase as a reporter gene driven by the Rous sarcoma virus long terminal repeat. When HIV/2A was contransfected with the reporter, addition of a tat-producing plasmid caused at least a 50-fold drop in chloramphenicol acetyltransferase synthesis. A HeLa cell line carrying HIV/2A was established. In it, tat expression caused more than a 10-fold drop in chloramphenicol acetyltransferase synthesis from the reporter plasmid. Furthermore, 2A induction by tat caused cleavage of the cellular translation factor P220, a part of eukaryotic translation initiation factor 4F. Thus protein 2A can, by itself, carry out the inhibition of cellular protein synthesis characteristic of a poliovirus infection. Also, the HIV tat activation provides a very effective method to control gene expression in mammalian cells.

HIV-1 tat protein recruits CIS to the cytoplasmic tail of CD127 to induce receptor ubiquitination and proteasomal degradation

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Sugden, Scott, E-mail: scott.sugden@ircm.qc.ca [The Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6 (Canada); Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5 (Canada); Ghazawi, Feras [The Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6 (Canada); Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5 (Canada); MacPherson, Paul, E-mail: pmacpherson@toh.on.ca [The Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6 (Canada); Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5 (Canada); Division of Infectious Diseases, The Ottawa Hospital General Campus, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6 (Canada)

2016-11-15

HIV-1 Tat protein down regulates expression of the IL-7 receptor alpha-chain (CD127) from the surface of CD8 T cells resulting in impaired T cell proliferation and cytolytic capacity. We have previously shown that soluble Tat protein is taken up by CD8 T cells and interacts with the cytoplasmic tail of CD127 to induce receptor degradation. The N-terminal domain of Tat interacts with CD127 while the basic domain directs CD127 to the proteasome. We have also shown that upon IL-7 binding to its receptor, CD127 is phosphorylated resulting in CIS-mediated proteasomal degradation. Here, we show that Tat mimics this process by recruiting CIS to CD127 in the absence of IL-7 and receptor phosphorylation, leading to CD127 ubiquitination and degradation. Tat therefore acts as an adapter to induce cellular responses under conditions where they may not otherwise occur. Thusly, Tat reduces IL-7 signaling and impairs CD8 T cell survival and function. -- Highlights: •Soluble HIV-1 Tat decreases CD127 expression on CD8 T cells, causing dysfunction. •Tat induces CD127 ubiquitination without activating IL-7 signaling. •Tat binds CD127 and recruits the E3 ubiquitin ligase CIS via its basic domain. •Tat hijacks a normal cellular mechanism to degrade CD127 without IL-7 signaling.

HIV-1 tat protein recruits CIS to the cytoplasmic tail of CD127 to induce receptor ubiquitination and proteasomal degradation

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Sugden, Scott; Ghazawi, Feras; MacPherson, Paul

2016-01-01

HIV-1 Tat protein down regulates expression of the IL-7 receptor alpha-chain (CD127) from the surface of CD8 T cells resulting in impaired T cell proliferation and cytolytic capacity. We have previously shown that soluble Tat protein is taken up by CD8 T cells and interacts with the cytoplasmic tail of CD127 to induce receptor degradation. The N-terminal domain of Tat interacts with CD127 while the basic domain directs CD127 to the proteasome. We have also shown that upon IL-7 binding to its receptor, CD127 is phosphorylated resulting in CIS-mediated proteasomal degradation. Here, we show that Tat mimics this process by recruiting CIS to CD127 in the absence of IL-7 and receptor phosphorylation, leading to CD127 ubiquitination and degradation. Tat therefore acts as an adapter to induce cellular responses under conditions where they may not otherwise occur. Thusly, Tat reduces IL-7 signaling and impairs CD8 T cell survival and function. -- Highlights: •Soluble HIV-1 Tat decreases CD127 expression on CD8 T cells, causing dysfunction. •Tat induces CD127 ubiquitination without activating IL-7 signaling. •Tat binds CD127 and recruits the E3 ubiquitin ligase CIS via its basic domain. •Tat hijacks a normal cellular mechanism to degrade CD127 without IL-7 signaling.

Cloning, Expression and Purification of the Recombinant HIV-1 Tat-Nef Fusion Protein in Prokaryotic Expression System

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Somayeh Kadkhodayan

2016-07-01

Full Text Available Abstract Background: Nef is one of the HIV-1 critical proteins, because it is essential for viral replication and AIDS disease progression and induction of immune response against it can partially inhibit viral infection. Moreover, a domain of the HIV-1 Trans-Activator of Transcription (Tat, 48-60 aa could act as a cell penetrating peptide (CPP. In current study, cloning and expression of Tat-Nef fusion protein was performed in E. coli for the first time. The protein expression was confirmed by western blot analysis and was purified using reverse staining method. Materials and Methods: In this experimental study, primarily, cloning of Tat-Nef fusion gene was done in pGEX6p2 expression vector. Then, the expression of Tat-Nef recombinat protein in E.coli BL21 (DE3 strain was performed by using IPTG inducer. The protein expression was confirmed by SDS-PAGE and western blotting using anti-Nef monoclonal antibody. Then, the recombinant fusion protein was purified from gel using reverse staining method. Results: The results of PCR analysis and enzyme digestion showed a clear band of ~ 726 bp in agarose gel indicating the correct Tat-Nef fusion cloning in pGEX6p2 prokaryotic expression vector. In addition, a 54 kDa band of Tat-Nef on SDS-PAGE revealed Tat-Nef protein expression that western blot analysis using anti-Nef monoclonal antibody confirmed it. Conclusion: The purified Tat-Nef recombinant fusion protein will be used as an antigen for protein vaccine design against HIV infection.

Crosstalk between HDAC6 and Nox2-based NADPH oxidase mediates HIV-1 Tat-induced pro-inflammatory responses in astrocytes

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Gi Soo Youn

2017-08-01

Full Text Available Histone deacetylase 6 (HDAC6 likely is important in inflammatory diseases. However, how HDAC6 exerts its effect on inflammatory processes remains unclear. HIV-1 transactivator of transcription (Tat activates NADPH oxidase resulting in generation of reactive oxygen species (ROS, leading to extensive neuro-inflammation in the central nervous system. We investigated the correlation of HDAC6 and NADPH oxidase in HIV-1 Tat-stimulated astrocytes. HDAC6 knockdown attenuated HIV-1 Tat-induced ROS generation and NADPH oxidase activation. HDAC6 knockdown suppressed HIV-1 Tat-induced expression of NADPH oxidase subunits, such as Nox2, p47phox, and p22phox. Specific inhibition of HDAC6 using tubastatin A suppressed HIV-1 Tat-induced ROS generation and activation of NADPH oxidase. N-acetyl cysteine, diphenyl iodonium, and apocynin suppressed HIV-1 Tat-induced expression of HDAC6 and the pro-inflammatory chemokines CCL2, CXCL8, and CXCL10. Nox2 knockdown attenuated HIV-1 Tat-induced HDAC6 expression and subsequent expression of chemokines. The collective results point to the potential crosstalk between HDAC6 and NADPH oxidase, which could be a combined therapeutic target for relief of HIV-1 Tat-mediated neuro-inflammation. Keywords: HIV-1 Tat, HDAC6, NADPH oxidase, ROS, Inflammation, Astrocytes

Conjugation to the cell-penetrating peptide TAT potentiates the photodynamic effect of carboxytetramethylrhodamine.

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Divyamani Srinivasan

2011-03-01

Full Text Available Cell-penetrating peptides (CPPs can transport macromolecular cargos into live cells. However, the cellular delivery efficiency of these reagents is often suboptimal because CPP-cargo conjugates typically remain trapped inside endosomes. Interestingly, irradiation of fluorescently labeled CPPs with light increases the release of the peptide and its cargos into the cytosol. However, the mechanism of this phenomenon is not clear. Here we investigate the molecular basis of the photo-induced endosomolytic activity of the prototypical CPPs TAT labeled to the fluorophore 5(6-carboxytetramethylrhodamine (TMR.We report that TMR-TAT acts as a photosensitizer that can destroy membranes. TMR-TAT escapes from endosomes after exposure to moderate light doses. However, this is also accompanied by loss of plasma membrane integrity, membrane blebbing, and cell-death. In addition, the peptide causes the destruction of cells when applied extracellularly and also triggers the photohemolysis of red blood cells. These photolytic and photocytotoxic effects were inhibited by hydrophobic singlet oxygen quenchers but not by hydrophilic quenchers.Together, these results suggest that TAT can convert an innocuous fluorophore such as TMR into a potent photolytic agent. This effect involves the targeting of the fluorophore to cellular membranes and the production of singlet oxygen within the hydrophobic environment of the membranes. Our findings may be relevant for the design of reagents with photo-induced endosomolytic activity. The photocytotoxicity exhibited by TMR-TAT also suggests that CPP-chromophore conjugates could aid the development of novel Photodynamic Therapy agents.

The HIV-1 viral protein Tat increases glutamate and decreases GABA exocytosis from human and mouse neocortical nerve endings.

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Musante, Veronica; Summa, Maria; Neri, Elisa; Puliti, Aldamaria; Godowicz, Tomasz T; Severi, Paolo; Battaglia, Giuseppe; Raiteri, Maurizio; Pittaluga, Anna

2010-08-01

Human immunodeficiency virus-1 (HIV-1)-encoded transactivator of transcription (Tat) potentiated the depolarization-evoked exocytosis of [(3)H]D-aspartate ([(3)H]D-ASP) from human neocortical terminals. The metabotropic glutamate (mGlu) 1 receptor antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) prevented this effect, whereas the mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl) pyridine hydrochloride (MPEP) was ineffective. Western blot analysis showed that human neocortex synaptosomes possess mGlu1 and mGlu5 receptors. Tat potentiated the K(+)-evoked release of [(3)H]D-ASP or of endogenous glutamate from mouse neocortical synaptosomes in a CPCCOEt-sensitive and MPEP-insensitive manner. Deletion of mGlu1 receptors (crv4/crv4 mice) or mGlu5 receptors (mGlu5(-/-)mouse) silenced Tat effects. Tat enhanced inositol 1,4,5-trisphosphate production in human and mouse neocortical synaptosomes, consistent with the involvement of group I mGlu receptors. Tat inhibited the K(+)-evoked release of [(3)H]gamma-aminobutyric acid ([(3)H]GABA) from human synaptosomes and that of endogenous GABA or [(3)H]GABA from mouse nerve terminals; the inhibition was insensitive to CPCCOEt or MPEP. Tat-induced effects were retained by Tat(37-72) but not by Tat(48-85). In mouse neocortical slices, Tat facilitated the K(+)- and the veratridine-induced release of [(3)H]D-ASP in a CPCCOEt-sensitive manner and was ineffective in crv4/crv4 mouse slices. These observations are relevant to the comprehension of the pathophysiological effects of Tat in central nervous system and may suggest new potential therapeutic approaches to the cure of HIV-1-associated dementia.

LRRK2 kinase inhibition prevents pathological microglial phagocytosis in response to HIV-1 Tat protein

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Marker Daniel F

2012-11-01

Full Text Available Abstract Background Human Immunodeficiency Virus-1 (HIV-1 associated neurocognitive disorders (HANDs are accompanied by significant morbidity, which persists despite the use of combined antiretroviral therapy (cART. While activated microglia play a role in pathogenesis, changes in their immune effector functions, including phagocytosis and proinflammatory signaling pathways, are not well understood. We have identified leucine-rich repeat kinase 2 (LRRK2 as a novel regulator of microglial phagocytosis and activation in an in vitro model of HANDs, and hypothesize that LRRK2 kinase inhibition will attenuate microglial activation during HANDs. Methods We treated BV-2 immortalized mouse microglia cells with the HIV-1 trans activator of transcription (Tat protein in the absence or presence of LRRK2 kinase inhibitor (LRRK2i. We used Western blot, qRT-PCR, immunocytochemistry and latex bead engulfment assays to analyze LRRK2 protein levels, proinflammatory cytokine and phagocytosis receptor expression, LRRK2 cellular distribution and phagocytosis, respectively. Finally, we utilized ex vivo microfluidic chambers containing primary hippocampal neurons and BV-2 microglia cells to investigate microglial phagocytosis of neuronal axons. Results We found that Tat-treatment of BV-2 cells induced kinase activity associated phosphorylation of serine 935 on LRRK2 and caused the formation of cytoplasmic LRRK2 inclusions. LRRK2i decreased Tat-induced phosphorylation of serine 935 on LRRK2 and inhibited the formation of Tat-induced cytoplasmic LRRK2 inclusions. LRRK2i also decreased Tat-induced process extension in BV-2 cells. Furthermore, LRRK2i attenuated Tat-induced cytokine expression and latex bead engulfment. We examined relevant cellular targets in microfluidic chambers and found that Tat-treated BV-2 microglia cells cleared axonal arbor and engulfed neuronal elements, whereas saline treated controls did not. LRRK2i was found to protect axons in the presence

Immune reconstitution and risk of Kaposi sarcoma and non-Hodgkin lymphoma in HIV-infected adults

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Jaffe, Harold W.; de Stavola, Bianca L.; Carpenter, Lucy M.; Porter, Kholoud; Cox, David R.; del Amo, Julia; Meyer, Laurence; Bucher, Heiner C.; Chêne, Geneviève; Hamouda, Osamah; Pillay, Deenan; Prins, Maria; Rosinska, Magda; Sabin, Caroline; Touloumi, Giota; Lodi, Sara; Coughlin, Kate; Walker, Sarah; Babiker, Abdel; de Luca, Andrea; Fisher, Martin; Muga, Roberto; Zangerle, Robert; Kelleher, A. D.; Cooper, D. A.; Grey, Pat; Finlayson, Robert; Bloch, Mark; Kelleher, Tony; Ramacciotti, Tim; Gelgor, Linda; Cooper, David; Gill, John; Jørgensen, Louise B.; Tartu, U.; Lutsar, Irja; Dabis, Francois; Thiebaut, Rodolphe; Masquelier, Bernard; Costagliola, Dominique; Guiguet, Marguerite; Vanhems, Philippe; Chaix, Marie-Laure; Ghosn, Jade; Boufassa, Faroudy; Kücherer, Claudia; Bartmeyer, Barbara; Geskus, Ronald; van der Helm, Jannie; Schuitemaker, Hanneke

2011-01-01

Given the well documented occurrence of immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients who recently started combination antiretroviral therapy (cART), we examined whether cART initiation increased the risk of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) using data from

Clinical Features, Presence of Human Herpesvirus-8 and Treatment Results in Classic Kaposi Sarcoma

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Özlem Su

2008-12-01

Full Text Available Background and Design: Classic Kaposi sarcoma (KS occurs predominantly among the elderly, with Jews, Italians and Greeks. Classic KS has been seen relatively frequently in Turkey. Our aim was to evaluate the demographic, clinical features of Kaposi sarcoma and etiopathological role of human herpesvirus-8 (HHV-8. Treatment results of 18 classic Kaposi’s sarcoma were also concluded.Material and Method: Eighteen cases of classic Kaposi sarcoma diagnosed as clinically and histopathologically between January 2001 and August 2008 in our dermatology department were taken to this study. Demographic, clinical features and treatment results were reviewed retrospectively in all patients. HHV-8 was investigated in the lesional skin of 7 patients.Results: A male/female ratio of 2/1 was found. Mean age at diagnosis was 67.2 (37-94 years. Bilaterally lower extremities were involved in 15 patients (83.3%, the trunk was involved in 3 patients (16.6%. Plaques and nodules were the common type of lesions (66.6% and 55.5%. Nine patients had no symptoms (50%. Edema was the most common symptom (38.8%. A second primary malignancy was found in 2 patients (11.1%. HHV-8 was detected in 6 of the 7 patients(85.7%. Majority of the patients were treated with interferon alfa (subcutaneously and cryotherapy as a monotherapy or a combination therapy. Imiquimod was the second agent in combined treatment (27.7%. Conclusion: We suggest that interferon alfa and imiquimod can be used as first line therapy agents with their antiviral and immunmodulatuar features in the treatment of KKS. (Turkderm 2008; 42: 122-6

Targeted PEG-based bioconjugates enhance the cellular uptake and transport of a HIV-1 TAT nonapeptide.

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Ramanathan, S; Qiu, B; Pooyan, S; Zhang, G; Stein, S; Leibowitz, M J; Sinko, P J

2001-12-13

We previously described the enhanced cell uptake and transport of R.I-K(biotin)-Tat9, a large ( approximately 1500 Da) peptidic inhibitor of HIV-1 Tat protein, via SMVT, the intestinal biotin transporter. The aim of the present study was to investigate the feasibility of targeting biotinylated PEG-based conjugates to SMVT in order to enhance cell uptake and transport of Tat9. The 29 kDa peptide-loaded bioconjugate (PEG:(R.I-Cys-K(biotin)-Tat9)8) used in these studies contained eight copies of R.I-K(biotin)-Tat9 appended to PEG by means of a cysteine linkage. The absorptive transport of biotin-PEG-3400 (0.6-100 microM) and the bioconjugate (0.1-30 microM) was studied using Caco-2 cell monolayers. Inhibition of biotin-PEG-3400 by positive controls (biotin, biocytin, and desthiobiotin) was also determined. Uptake of these two compounds was also determined in CHO cells transfected with human SMVT (CHO/hSMVT) and control cells (CHO/pSPORT) over the concentration ranges of 0.05-12.5 microM and 0.003-30 microM, respectively. Nonbiotinylated forms of these two compounds, PEG-3350 and PEG:(R.I-Cys-K-Tat9)8, were used in the control studies. Biotin-PEG-3400 transport was found to be concentration-dependent and saturable in Caco-2 cells (K(m)=6.61 microM) and CHO/hSMVT cells (K(m)=1.26 microM). Transport/uptake was significantly inhibited by positive control substrates of SMVT. PEG:(R.I-Cys-K(biotin)Tat9)8 also showed saturable transport kinetics in Caco-2 cells (K(m)=6.13 microM) and CHO/hSMVT cells (K(m)=8.19 microM). Maximal uptake in molar equivalents of R.I-Cys-K(biotin)Tat9 was 5.7 times greater using the conjugate versus the biotinylated peptide alone. Transport of the nonbiotinylated forms was significantly lower (PPEG-3400 and PEG:(R.I-Cys-K(biotin)Tat9)8 interact with human SMVT to enhance the cellular uptake and transport of these larger molecules and that targeted bioconjugates may have potential for enhancing the cellular uptake and transport of small peptide

Lichen planus-like keratosis: Another differential diagnosis for kaposi sarcoma

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Marcela Clavellina-Miller

2015-01-01

Full Text Available Epidemic Kaposi sarcoma is a common finding among HIV/AIDS patients that are not under antiretroviral treatment, and sometimes it is the first sign of the disease. However, it can be seen even in patients with undetectable viral load and high CD 4 cell count. Under these circumstances, the clinical presentation can be atypical in location or number. For this reason, the number of differential diagnosis is increased and biopsy of the suspicious lesions is essential for an accurate diagnosis and further apropiate treatment.

Absolute dose measurement Gafchromic R EBT2 movies. Case Study of Kaposis sarcoma; Medida de dosis absoluta con peliculas Gafchromic EBT2. Caso practico de un sarcoma de Kaposi

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Pereira, L.; Moral, F. del; Meilan, E.; Azevedo Gomes, J. C. de; Tejeiro Garcia, A. G.; Andrade Alvarez, B.; Vazquez, J.; Nieto, I.; Medal, D.; Lopez Medina, A.; Francisco, S.; Salgado, M.; Munoz, V.

2011-07-01

Because of its high spatial resolution, low energy dependence and good response over a wide energy range, EBT2 Gafchromic films are widely used in many applications in radiotherapy for measuring relative dose. Despite being the most common use can be used to measure absolute dose. This text is an example of using films as EBT2 for in vivo absolute dose in a Kaposis sarcoma.

TAT-Gap19 and Carbenoxolone Alleviate Liver Fibrosis in Mice

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Sara Crespo Yanguas

2018-03-01

Full Text Available Although a plethora of signaling pathways are known to drive the activation of hepatic stellate cells in liver fibrosis, the involvement of connexin-based communication in this process remains elusive. Connexin43 expression is enhanced in activated hepatic stellate cells and constitutes the molecular building stone of hemichannels and gap junctions. While gap junctions support intercellular communication, and hence the maintenance of liver homeostasis, hemichannels provide a circuit for extracellular communication and are typically opened by pathological stimuli, such as oxidative stress and inflammation. The present study was set up to investigate the effects of inhibition of connexin43-based hemichannels and gap junctions on liver fibrosis in mice. Liver fibrosis was induced by administration of thioacetamide to Balb/c mice for eight weeks. Thereafter, mice were treated for two weeks with TAT-Gap19, a specific connexin43 hemichannel inhibitor, or carbenoxolone, a general hemichannel and gap junction inhibitor. Subsequently, histopathological analysis was performed and markers of hepatic damage and functionality, oxidative stress, hepatic stellate cell activation and inflammation were evaluated. Connexin43 hemichannel specificity of TAT-Gap19 was confirmed in vitro by fluorescence recovery after photobleaching analysis and the measurement of extracellular release of adenosine-5′-triphosphate. Upon administration to animals, both TAT-Gap19 and carbenoxolone lowered the degree of liver fibrosis accompanied by superoxide dismutase overactivation and reduced production of inflammatory proteins, respectively. These results support a role of connexin-based signaling in the resolution of liver fibrosis, and simultaneously demonstrate the therapeutic potential of TAT-Gap19 and carbenoxolone in the treatment of this type of chronic liver disease.

Improving ED specimen TAT using Lean Six Sigma.

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Sanders, Janet H; Karr, Tedd

2015-01-01

Lean and Six Sigma are continuous improvement methodologies that have garnered international fame for improving manufacturing and service processes. Increasingly these methodologies are demonstrating their power to also improve healthcare processes. The purpose of this paper is to discuss a case study for the application of Lean and Six Sigma tools in the reduction of turnaround time (TAT) for Emergency Department (ED) specimens. This application of the scientific methodologies uncovered opportunities to improve the entire ED to lab system for the specimens. This case study provides details on the completion of a Lean Six Sigma project in a 1,000 bed tertiary care teaching hospital. Six Sigma's Define, Measure, Analyze, Improve, and Control methodology is very similar to good medical practice: first, relevant information is obtained and assembled; second, a careful and thorough diagnosis is completed; third, a treatment is proposed and implemented; and fourth, checks are made to determine if the treatment was effective. Lean's primary goal is to do more with less work and waste. The Lean methodology was used to identify and eliminate waste through rapid implementation of change. The initial focus of this project was the reduction of turn-around-times for ED specimens. However, the results led to better processes for both the internal and external customers of this and other processes. The project results included: a 50 percent decrease in vials used for testing, a 50 percent decrease in unused or extra specimens, a 90 percent decrease in ED specimens without orders, a 30 percent decrease in complete blood count analysis (CBCA) Median TAT, a 50 percent decrease in CBCA TAT Variation, a 10 percent decrease in Troponin TAT Variation, a 18.2 percent decrease in URPN TAT Variation, and a 2-5 minute decrease in ED registered nurses rainbow draw time. This case study demonstrated how the quantitative power of Six Sigma and the speed of Lean worked in harmony to improve

HIV-1 Tat reduces nephrin in human podocytes: a potential mechanism for enhanced glomerular permeability in HIV-associated nephropathy.

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Doublier, Sophie; Zennaro, Cristina; Spatola, Tiziana; Lupia, Enrico; Bottelli, Antonella; Deregibus, Maria Chiara; Carraro, Michele; Conaldi, Pier Giulio; Camussi, Giovanni

2007-02-19

To determine whether HIV-1 Tat may directly alter glomerular permeability in HIV-associated nephropathy (HIVAN). Heavy proteinuria is a hallmark of HIVAN. The slit diaphragm is the ultimate glomerular filtration barrier critical for maintaining the efficiency of the ultrafiltration unit of the kidney. In this study, we evaluated the direct effect of Tat protein on the permeability of isolated glomeruli and on the expression of nephrin, the main slit diaphragm component, by human cultured podocytes. Permeability was studied by measuring the permeability to albumin in isolated rat glomeruli. We also evaluated the expression of nephrin in human cultured podocytes by using immunofluorescence and Western blot. We found that Tat increased albumin permeability in isolated glomeruli, and rapidly induced the redistribution and loss of nephrin in cultured podocytes. Pretreatment of glomeruli and podocytes with blocking antibodies showed that Tat reduced nephrin expression by engaging vascular endothelial growth factor receptors types 2 and 3 and the integrin alphavbeta3. Pre-incubation of podocytes with two platelet-activating factor (PAF) receptor antagonists prevented the loss and redistribution of nephrin induced by Tat, suggesting that PAF is an intracellular mediator of Tat action. Tat induced a rapid PAF synthesis by podocytes. When podocytes transfected to overexpress PAF-acetylhydrolase, the main catabolic enzyme of PAF, were stimulated with Tat, the redistribution and loss of nephrin was abrogated. The present results define a mechanism by which Tat may reduce nephrin expression in podocytes, thus increasing glomerular permeability. This provides new insights in the understanding of HIVAN pathogenesis.

Anti-inflammatory effects of Tat-Annexin protein on ovalbumin-induced airway inflammation in a mouse model of asthma

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Lee, Sun Hwa; Kim, Dae Won; Kim, Hye Ri; Woo, Su Jung; Kim, So Mi; Jo, Hyo Sang [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Jeon, Seong Gyu [Department of Life Science, Pohang University of Science and Technology, Pohang 790-784 (Korea, Republic of); Cho, Sung-Woo [Department of Biochemistry and Molecular Biology, University of Ulsan, College of Medicine, Seoul 138-736 (Korea, Republic of); Park, Jong Hoon [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Won, Moo Ho [Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Park, Jinseu [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Eum, Won Sik, E-mail: wseum@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Choi, Soo Young, E-mail: sychoi@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of)

2012-01-20

Highlights: Black-Right-Pointing-Pointer We construct a cell permeable Tat-ANX1 fusion protein. Black-Right-Pointing-Pointer We examined the protective effects of Tat-ANX1 protein on OVA-induced asthma in animal models. Black-Right-Pointing-Pointer Transduced Tat-ANX1 protein protects from the OVA-induced production of cytokines and eosinophils in BAL fluid. Black-Right-Pointing-Pointer Tat-ANX1 protein markedly reduced OVA-induced MAPK in lung tissues. Black-Right-Pointing-Pointer Tat-ANX1 protein could be useful as a therapeutic agent for lung disorders including asthma. -- Abstract: Chronic airway inflammation is a key feature of bronchial asthma. Annexin-1 (ANX1) is an anti-inflammatory protein that is an important modulator and plays a key role in inflammation. Although the precise action of ANX1 remains unclear, it has emerged as a potential drug target for inflammatory diseases such as asthma. To examine the protective effects of ANX1 protein on ovalbumin (OVA)-induced asthma in animal models, we used a cell-permeable Tat-ANX1 protein. Mice sensitized and challenged with OVA antigen had an increased amount of cytokines and eosinophils in their bronchoalveolar lavage (BAL) fluid. However, administration of Tat-ANX1 protein before OVA challenge significantly decreased the levels of cytokines (interleukin (IL)-4, IL-5, and IL-13) and BAL fluid in lung tissues. Furthermore, OVA significantly increased the activation of mitogen-activated protein kinase (MAPK) in lung tissues, whereas Tat-ANX1 protein markedly reduced phosphorylation of MAPKs such as extracellular signal-regulated protein kinase, p38, and stress-activated protein kinase/c-Jun N-terminal kinase. These results suggest that transduced Tat-ANX1 protein may be a potential protein therapeutic agent for the treatment of lung disorders including asthma.

TAT improves in vitro transportation of fortilin through midgut and into hemocytes of white shrimp Litopenaeus vannamei

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Zhou, Yi; Zhang, Wenbing; Mai, Kangsen; Xu, Wei; Zhang, Yanjiao; Ai, Qinghui; Wang, Xiaojie

2012-06-01

Fortilin is a multifunctional protein implicated in many important cellular processes. Since injection of Pm-fortilin reduces shrimp mortality caused by white spot syndrome virus (WSSV), there is potential application of fortilin in shrimp culture. In the present study, in order to improve trans-membrane transportation efficiency, the protein transduction domain of the transactivator of transcription (TAT) peptide was fused to fortilin. The Pichia pastoris yeast expression system, which is widely accepted in animal feeds, was used for production of recombinant fusion protein. Green fluorescence protein (GFP) was selected as a reporter because of its intrinsic visible fluorescence. The fortilin, TAT and GFP fusion protein were constructed. Their trans-membrane transportation efficiency and effects on immune response of shrimp were analyzed in vitro. Results showed that TAT peptide improved in vitro uptake of fortilin into the hemocytes and midgut of Litopenaeus vannamei. The phenoloxidase (PO) activity of hemocytes incubated with GFP-Fortilin or GFP-Fortilin-TAT was significantly increased compared with that in the control without expressed fortilin. The PO activity of hemocytes incubated with 200 μg mL-1 GFP-Fortilin-TAT was significantly higher than that in the group with the same concentration of GFP-Fortilin. Hemocytes incubated with GFP-Fortilin-TAT at all concentrations showed significantly higher nitric oxide synthase (NOS) activity than those in the control or in the GFP-Fortilin treatment. The present in vitro study indicated that TAT fusion protein improved the immune effect of fortilin.

Use of X-Chromosome Inactivation Pattern to Analyze the Clonality of 14 Female Cases of Kaposi Sarcoma.

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Yuan, Ding; XiuJuan, Wu; Yan, Zhang; JunQin, Liang; Fang, Xiang; Shirong, Yu; Xiaojing, Kang; Yanyan, Feng; Weidong, Wu; Dong, Luo; Qingli, Lu; DeZhi, Zhang; XiongMing, Pu

2015-06-16

Kaposi sarcoma (KS) has features of both neoplastic growth and hyperplastic proliferation. It is the most common tumor seen in patients with HIV infection. Whether KS is a real tumor or a benign hyperplastic disease is not known. Tissues from KS and cutaneous hemangioma lesion DNA were extracted, and then digested with methylation-sensitive restriction endonuclease HpaII. Human androgen receptor gene (HUMARA) was amplified with PCR method and the product was separated on 10% denaturing polyacrylamide gels and stained with ethylene dibromide (EB) to show the polymorphism of HUMARA. Phosphoglycerate kinase (PGK) was amplified and the product was digested by BStXI, agarose gel and EB stained to show the polymorphism of PGK. Finally, we analyzed the clonality of KS. In the 14 patients with KS, heterozygosity of the HUMARA gene was observed in 12 (85.7%) cases. Loss of heterozygosity of HUMARA gene on X-chromosome (without HpaII digestion there were 2 bands, after HpaII digestion there were just 1 of the bands), representing monoclonal origin, was present in 11 cases of Kaposi sarcoma. Heterozygosity of the PGK gene was observed in 5 (35.7%) cases, which all represent monoclonal origin. There was no significant difference according to country, stage, or HIV and HHV-8 (P>0.05). The current findings suggest that Kaposi sarcoma is a clonal neoplasm, not a reactive proliferation.

Tit-For-Tat Strategy for Increasing Medical Student Evaluation Response Rates

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Matthew G. Malone

2017-12-01

Full Text Available Introducation It is essential for faculty to receive feedback on their teaching for the purpose of improvement as well as promotion. It can be challenging to motivate students to provide feedback to preceptors and fill out evaluation forms when not a clerkship requirement. Furthermore, there is concern that making the evaluations a requirement can compromise the quality of the feedback. The objective of this study was to identify an increase in the number of faculty and resident evaluations completed by students rotating through their Emergency Medicine clerkship following the implementation of a tit-for-tat incentive strategy. Method Prior to the implementation of Tit-for-Tat, students rotating through their emergency medicine clerkship were asked to fill out evaluations of residents and faculty members with whom they worked. These were encouraged but voluntary. Beginning in the 2014–2015 academic year, a tit-for-tat strategy was employed whereby students had to complete a resident or faculty evaluation in order to view the student assessment completed by that resident or faculty preceptor. Results Students submitted 1101 evaluations in the control, with a mean of 3.60 evaluations completed per student and 3.77 evaluations received per preceptor. Following the implementation of tit-for-tat, students submitted 2736 evaluations, with a mean of 8.19 evaluations completed per student and 7.52 evaluations received per preceptor. Both the increase in evaluations completed per student and evaluations received per preceptor were statistically significant with p-value <0.001. Conclusion The tit-for-tat strategy significantly increased the number of evaluations submitted by students rotating through their emergency medicine clerkship. This has served as an effective tool to increase the overall number of evaluations completed, the number of evaluations each instructor received on average and the proportion of students that completed evaluations

AIDS Kaposi sarcoma-derived cells produce and respond to interleukin 6

International Nuclear Information System (INIS)

Miles, S.A.; Rezai, A.R.; Salazar-Gonzalez, J.F.; Meyden, M.V.; Stevens, R.H.; Mitsuyasu, R.T.; Martinez-Maza, O.; Logan, D.M.; Taga, Tetsuya; Hirano, Toshio; Kishimoto, Tadamitsu

1990-01-01

Cell lines derived from Kaposi sarcoma lesions of patients with AIDS (AIDS-KS cells) produce several cytokines, including an endothelial cell growth factor, interleukin 1β, and basic fibroblast growth factor. Since exposure to human immunodeficiency virus increases interleukin 6 (IL-6) production in monocytes and endothelial cells produce IL-6, the authors examined IL-6 expression and response in AIDS-KS cell lines and IL-6 expression in AIDS Kaposi sarcoma tissue. The AIDS-KS cell lines (N521J and EKS3) secreted large amounts of immunoreactive and biologically active IL-6. The authors found both IL-6 and IL-6 receptor (IL-6-R) RNA by slot blot hybridization analysis of AIDS-KS cells. The IL-6-R was functional, as [ 3 H]thymidine incorporation by AIDS-KS cells increased significantly after exposure to human recombinant IL-6 (hrIL-6) at >10 units/ml. When AIDS-KS cells (EKS3) were exposed to IL-6 antisense oligonucleotide, cellular proliferation decreased by nearly two-thirds, with a corresponding decrease in the production of IL-6. These results show that both IL-6 and IL-6-R are produced by AIDS-KS cells and that IL-6 is required for optimal AIDS-KS cell proliferation, and they suggest that IL-6 is an autocrine growth factor for AIDS-KS cells

Evidence for conformational flexibility in the Tat-TAR recognition motif of cyclin T1

International Nuclear Information System (INIS)

Das, Chandreyee; Edgcomb, Stephen P.; Peteranderl, Ralph; Chen, Lily; Frankel, Alan D.

2004-01-01

Cyclin T1 (CycT1) is a cellular transcription elongation factor that also participates in Tat-mediated activation of several lentiviral promoters. In human immunodeficiency virus (HIV), CycT1 is required for Tat to bind tightly to TAR and interacts in the ternary complex via its Tat-TAR recognition motif (TRM). In the related bovine immunodeficiency virus (BIV), Tat recognizes its cognate TAR element with high affinity and specificity in the absence of CycT1. At both promoters, CycT1 recruits the Cdk9 kinase, which phosphorylates RNA polymerase II to generate processive transcription complexes. To examine the physical properties of CycT1, we purified a functional domain corresponding to residues 1-272 and found that it possesses a stably folded core, as judged by partial proteolysis and circular dichroism experiments. Interestingly, the C-terminal 20 residues corresponding to the TRM appear conformationally flexible or disordered. The TRM of the bovine CycT1 (bCycT1) is similarly sensitive to proteolysis yet differs in sequence from the human protein. In particular, bCycT1 lacks a cysteine at residue 261 known to be critical for HIV but not BIV ternary complex formation, and mutagenesis data are consistent with a proposed role for this cysteine in metal binding. The apparent flexibility of the TRM suggests that conformational rearrangements may accompany formation of CycT1-Tat-TAR ternary complexes and may contribute to different TAR recognition strategies in different lentiviruses

Disseminated Kaposi's sarcoma-a missed diagnosis.

Science.gov (United States)

Armstrong, Marc B; Thurber, Jalil

2014-11-01

Kaposi's sarcoma is significantly prevalent among men infected with the human immunodeficiency virus, accounting for >90% of all cases. The early presentation of KS typically involves mucocutaneous lesions and lymphadenopathy, and more advanced disease can affect the lungs and other organs. Our aim was to remind emergency physicians to remain suspicious of clinical presentations despite previous diagnoses or patient statements, particularly in patients with risk factors. We present a case of a young man having skin lesions and respiratory problems remaining undiagnosed, despite, and possibly due to, multiple recent physician contacts. Respiratory illnesses are common presentations in the emergency department and are typically benign and attributed to viral causes. However, the emergency physician must always be on the look out for more dangerous causes of respiratory complaints, especially in patients with risk factors and in those found to be refractory to recent treatment for more common illnesses. Copyright © 2014 Elsevier Inc. All rights reserved.

TERBİNAFİNE KULLANIMINA BAĞLI TAT DUYUSU BOZUKLUĞU: BİR OLGU SUNUMU

OpenAIRE

Bayar, Özlem Filiz; Şenol Güven, Gamze; Ak, Gülsüm

2015-01-01

Amaç: Terbinafine Alilamin grubunda yer alan bir antifungal ajandır. 1991 yılında üretilmiş olup, topikal ve sistemik olarak geniş bir kullanıma sahiptir. Oral formunun kullanımıyla % 0.6 ile 2.8 oranlarında nadir görülen bir yan etki olan tat duyusu bozukluğu meydana gelmektedir. Bu olgu sunumunda, nadir görülen oral Terbinafine kullanımına bağlı tat duyusu bozukluğu gelişen bir hastayı sunmaktayız.Gereç ve yöntem: 43 yaşında erkek hasta oral Terbinafine kullanımı sonucu gelişen tat duyusu b...

Absolute dose measurement Gafchromic R EBT2 movies. Case Study of Kaposis sarcoma

International Nuclear Information System (INIS)

Pereira, L.; Moral, F. del; Meilan, E.; Azevedo Gomes, J. C. de; Tejeiro Garcia, A. G.; Andrade Alvarez, B.; Vazquez, J.; Nieto, I.; Medal, D.; Lopez Medina, A.; Francisco, S.; Salgado, M.; Munoz, V.

2011-01-01

Because of its high spatial resolution, low energy dependence and good response over a wide energy range, EBT2 Gafchromic films are widely used in many applications in radiotherapy for measuring relative dose. Despite being the most common use can be used to measure absolute dose. This text is an example of using films as EBT2 for in vivo absolute dose in a Kaposis sarcoma.

Primary Kaposi sarcoma of the subcutaneous tissue

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Dezube Bruce J

2008-09-01

Full Text Available Abstract Background Involvement of the subcutis by Kaposi sarcoma (KS occurs primarily when cutaneous KS lesions evolve into deep penetrating nodular tumors. Primary KS of the subcutaneous tissue is an exceptional manifestation of this low-grade vascular neoplasm. Case presentation We present a unique case of acquired immune deficiency syndrome (AIDS-associated KS manifesting primarily in the subcutaneous tissue of the anterior thigh in a 43-year-old male, which occurred without overlying visible skin changes or concomitant KS disease elsewhere. Radiological imaging and tissue biopsy confirmed the diagnosis of KS. Conclusion This is the first documented case of primary subcutaneous KS occurring in the setting of AIDS. The differential diagnosis of an isolated subcutaneous lesion in an human immunodeficiency virus (HIV-infected individual is broad, and requires both imaging and a histopathological diagnosis to guide appropriate therapy.

Tat-antioxidant 1 protects against stress-induced hippocampal HT-22 cells death and attenuate ischaemic insult in animal model.

Science.gov (United States)

Kim, So Mi; Hwang, In Koo; Yoo, Dae Young; Eum, Won Sik; Kim, Dae Won; Shin, Min Jea; Ahn, Eun Hee; Jo, Hyo Sang; Ryu, Eun Ji; Yong, Ji In; Cho, Sung-Woo; Kwon, Oh-Shin; Lee, Keun Wook; Cho, Yoon Shin; Han, Kyu Hyung; Park, Jinseu; Choi, Soo Young

2015-06-01

Oxidative stress-induced reactive oxygen species (ROS) are responsible for various neuronal diseases. Antioxidant 1 (Atox1) regulates copper homoeostasis and promotes cellular antioxidant defence against toxins generated by ROS. The roles of Atox1 protein in ischaemia, however, remain unclear. In this study, we generated a protein transduction domain fused Tat-Atox1 and examined the roles of Tat-Atox1 in oxidative stress-induced hippocampal HT-22 cell death and an ischaemic injury animal model. Tat-Atox1 effectively transduced into HT-22 cells and it protected cells against the effects of hydrogen peroxide (H2O2)-induced toxicity including increasing of ROS levels and DNA fragmentation. At the same time, Tat-Atox1 regulated cellular survival signalling such as p53, Bad/Bcl-2, Akt and mitogen-activate protein kinases (MAPKs). In the animal ischaemia model, transduced Tat-Atox1 protected against neuronal cell death in the hippocampal CA1 region. In addition, Tat-Atox1 significantly decreased the activation of astrocytes and microglia as well as lipid peroxidation in the CA1 region after ischaemic insult. Taken together, these results indicate that transduced Tat-Atox1 protects against oxidative stress-induced HT-22 cell death and against neuronal damage in animal ischaemia model. Therefore, we suggest that Tat-Atox1 has potential as a therapeutic agent for the treatment of oxidative stress-induced ischaemic damage. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Neuroprotective effect of TAT-14-3-3ε fusion protein against cerebral ischemia/reperfusion injury in rats.

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Yuanjun Zhu

Full Text Available Stroke is the major cause of death and disability worldwide, and the thrombolytic therapy currently available was unsatisfactory. 14-3-3ε is a well characterized member of 14-3-3 family, and has been reported to protect neurons against apoptosis in cerebral ischemia. However, it cannot transverse blood brain barrier (BBB due to its large size. A protein transduction domain (PTD of HIV TAT protein, is capable of delivering a large variety of proteins into the brain. In this study, we generated a fusion protein TAT-14-3-3ε, and evaluated its potential neuroprotective effect in rat focal ischemia/reperfusion (I/R model. Western blot analysis validated the efficient transduction of TAT-14-3-3ε fusion protein into brain via a route of intravenous injection. TAT-14-3-3ε pre-treatment 2 h before ischemia significantly reduced cerebral infarction volume and improved neurologic score, while post-treatment 2 h after ischemia was less effective. Importantly, pre- or post-ischemic treatment with TAT-14-3-3ε significantly increased the number of surviving neurons as determined by Nissl staining, and attenuated I/R-induced neuronal apoptosis as showed by the decrease in apoptotic cell numbers and the inhibition of caspase-3 activity. Moreover, the introduction of 14-3-3ε into brain by TAT-mediated delivering reduced the formation of autophagosome, attenuated LC3B-II upregulation and reversed p62 downregulation induced by ischemic injury. Such inhibition of autophagy was reversed by treatment with an autophagy inducer rapamycin (RAP, which also attenuated the neuroprotective effect of TAT-14-3-3ε. Conversely, autophagy inhibitor 3-methyladenine (3-MA inhibited I/R-induced the increase in autophagic activity, and attenuated I/R-induced brain infarct. These results suggest that TAT-14-3-3ε can be efficiently transduced into brain and exert significantly protective effect against brain ischemic injury through inhibiting neuronal apoptosis and autophagic

Interaction of the protein transduction domain of HIV-1 TAT with heparan sulfate: binding mechanism and thermodynamic parameters.

Science.gov (United States)

Ziegler, André; Seelig, Joachim

2004-01-01

The positively charged protein transduction domain of the HIV-1 TAT protein (TAT-PTD; residues 47-57 of TAT) rapidly translocates across the plasma membrane of living cells. This property is exploited for the delivery of proteins, drugs, and genes into cells. The mechanism of this translocation is, however, not yet understood. Recent theories for translocation suggest binding of the protein transduction domain (PTD) to extracellular glycosaminoglycans as a possible mechanism. We have studied the binding equilibrium between TAT-PTD and three different glycosaminoglycans with high sensitivity isothermal titration calorimetry and provide the first quantitative thermodynamic description. The polysulfonated macromolecules were found to exhibit multiple identical binding sites for TAT-PTD with only small differences between the three species as far as the thermodynamic parameters are concerned. Heparan sulfate (HS, molecular weight, 14.2 +/- 2 kDa) has 6.3 +/- 1.0 independent binding sites for TAT-PTD which are characterized by a binding constant K0 = (6.0 +/- 0.6) x 10(5) M(-1) and a reaction enthalpy deltaHpep0 = -4.6 +/- 1.0 kcal/mol at 28 degrees C. The binding affinity, deltaGpep0, is determined to equal extent by enthalpic and entropic contributions. The HS-TAT-PTD complex formation entails a positive heat capacity change of deltaCp0 = +135 cal/mol peptide, which is characteristic of a charge neutralization reaction. This is in contrast to hydrophobic binding reactions which display a large negative heat capacity change. The stoichiometry of 6-7 TAT-PTD molecules per HS corresponds to an electric charge neutralization. Light scattering data demonstrate a maximum scattering intensity at this stoichiometric ratio, the intensity of which depends on the order of mixing of the two components. The data suggest cross-linking and/or aggregation of HS-TAT-PTD complexes. Two other glycosaminoglycans, namely heparin and chondroitin sulfate B, were also studied with isothermal

Building Capacity in Using Earth Observations Under the GOFC-GOLD and TAT Programs

Science.gov (United States)

Gutman, G.

2015-12-01

The Global Observation of Forest and Land Cover Dynamics (GOFC-GOLD) is a coordinated international effort to provide ongoing space-based and in-situ observations of forests and other vegetation cover. The main goal of GOFC/GOLD is to support a forum for international information exchange, observation and data coordination, and a framework for establishing the necessary long-term monitoring systems. GOFC-GOLD has two Implementation Teams: Land Cover Characteristics and Change, and Fire Monitoring and Mapping. Additionally, it includes two working groups: the Working Group on Biomass Monitoring and the Working group on Reducing Emissions from Deforestation and Forest Degradation (REDD), the latter being aligned with the United Nations Framework Convention on Climate Change. Regional networks are an integral part of the GOFC-GOLD program, with some networks fully developed and some still emerging. GOFC-GOLD provides training workshops to build capacity in the regions. Capacity building in using Earth Observation techniques and applications is also promoted by cooperation of NASA and ESA under the Trans-Atlantic Training (TAT) program. The main objective of TAT is training of early career scientists and students in East European and Baltic countries emphasizing outstanding technical issues in remote sensing of land-cover/land-use change and ecosystems processes. TAT promotes data sharing and advanced research methods and technologies through series of training sessions. Three TAT sessions have been held until now, each session consisting of 5-10 tutors and about 30 early career scientists and students from Eastern Europe. The sessions include lectures on remote sensing covering the full solar spectrum and hands-on practice. The experience obtained in capacity building activities under GOFC-GOLD and TAT will be shared with the audience.

Celastrol ameliorates HIV-1 Tat-induced inflammatory responses via NF-kappaB and AP-1 inhibition and heme oxygenase-1 induction in astrocytes

International Nuclear Information System (INIS)

Youn, Gi Soo; Kwon, Dong-Joo; Ju, Sung Mi; Rhim, Hyangshuk; Bae, Yong Soo; Choi, Soo Young; Park, Jinseu

2014-01-01

HIV-1 Tat causes extensive neuroinflammation that may progress to AIDS-related encephalitis and dementia. Celastrol possesses various biological activities such as anti-oxidant, anti-tumor, and anti-inflammatory activities. In this study, we investigated the modulatory effects of celastrol on HIV-1 Tat-induced inflammatory responses and the molecular mechanisms underlying its action in astrocytes. Pre-treatment of CRT-MG human astroglioma cells with celastrol significantly inhibited HIV-1 Tat-induced expression of ICAM-1/VCAM-1 and subsequent monocyte adhesiveness in CRT-MG cells. In addition, celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory chemokines, such as CXCL10, IL-8, and MCP-1. Celastrol decreased HIV-1 Tat-induced activation of JNK MAPK, AP-1, and NF-κB. Furthermore, celastrol induced mRNA and protein expression of HO-1 as well as Nrf2 activation. Blockage of HO-1 expression using siRNA reversed the inhibitory effect of celastrol on HIV-1 Tat-induced inflammatory responses. These results suggest that celastrol has regulatory effects on HIV-1 Tat-induced inflammatory responses by blocking the JNK MAPK-AP-1/NF-κB signaling pathways and inducing HO-1 expression in astrocytes. - Highlights: • Celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory genes. • Celastrol inhibited HIV-1 Tat -induced activation of JNK MAPK. • Celastrol inhibited HIV-1 Tat-induced activation of both NF-κB and AP-1. • Celastrol inhibited HIV-1 Tat-induced inflammatory responses via HO-1 induction

Celastrol ameliorates HIV-1 Tat-induced inflammatory responses via NF-kappaB and AP-1 inhibition and heme oxygenase-1 induction in astrocytes

Energy Technology Data Exchange (ETDEWEB)

Youn, Gi Soo; Kwon, Dong-Joo; Ju, Sung Mi [Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Rhim, Hyangshuk [Department of Biomedical Sciences, Department of Medical Life Sciences, College of Medicine, the Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Bae, Yong Soo [Department of Biological Science, College of Natural Sciences, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Choi, Soo Young [Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Park, Jinseu, E-mail: jinpark@hallym.ac.kr [Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of)

2014-10-01

HIV-1 Tat causes extensive neuroinflammation that may progress to AIDS-related encephalitis and dementia. Celastrol possesses various biological activities such as anti-oxidant, anti-tumor, and anti-inflammatory activities. In this study, we investigated the modulatory effects of celastrol on HIV-1 Tat-induced inflammatory responses and the molecular mechanisms underlying its action in astrocytes. Pre-treatment of CRT-MG human astroglioma cells with celastrol significantly inhibited HIV-1 Tat-induced expression of ICAM-1/VCAM-1 and subsequent monocyte adhesiveness in CRT-MG cells. In addition, celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory chemokines, such as CXCL10, IL-8, and MCP-1. Celastrol decreased HIV-1 Tat-induced activation of JNK MAPK, AP-1, and NF-κB. Furthermore, celastrol induced mRNA and protein expression of HO-1 as well as Nrf2 activation. Blockage of HO-1 expression using siRNA reversed the inhibitory effect of celastrol on HIV-1 Tat-induced inflammatory responses. These results suggest that celastrol has regulatory effects on HIV-1 Tat-induced inflammatory responses by blocking the JNK MAPK-AP-1/NF-κB signaling pathways and inducing HO-1 expression in astrocytes. - Highlights: • Celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory genes. • Celastrol inhibited HIV-1 Tat -induced activation of JNK MAPK. • Celastrol inhibited HIV-1 Tat-induced activation of both NF-κB and AP-1. • Celastrol inhibited HIV-1 Tat-induced inflammatory responses via HO-1 induction.

Clinical and virological effects of high-dose recombinant interferon-alpha in disseminated AIDS-related Kaposi's sarcoma

NARCIS (Netherlands)

de Wit, R.; Schattenkerk, J. K.; Boucher, C. A.; Bakker, P. J.; Veenhof, K. H.; Danner, S. A.

1988-01-01

The effectiveness and antiretroviral activities of interferon-alpha in AIDS-related Kaposi's sarcoma was assessed in a non-randomised, phase-II clinical trial. 28 patients were treated with high-dose (27-36 MU) human recombinant interferon-alpha 2a subcutaneously every day for 8 weeks. In patients

Topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles

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Chu YC

2017-02-01

Full Text Available Yongchao Chu,1,* Ning Chen,2,* Huajun Yu,2,* Hongjie Mu,1 Bin He,1 Hongchen Hua,1 Aiping Wang,1 Kaoxiang Sun1 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, Shandong, People’s Republic of China; 2Department of Ophthalmology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, People’s Republic of China *These authors contributed equally to this work Abstract: A nanoparticle (NP was developed to target choroidal neovascularization (CNV via topical ocular administration. The NPs were prepared through conjugation of internalizing arginine-glycine-aspartic acid RGD (iRGD; Ac-CCRGDKGPDC and transactivated transcription (TAT (RKKRRQRRRC peptide to polymerized ethylene glycol and lactic-co-glycolic acid. The iRGD sequence can specifically bind with integrin αvβ3, while TAT facilitates penetration through the ocular barrier. 1H nuclear magnetic resonance and high-performance liquid chromatography demonstrated that up to 80% of iRGD and TAT were conjugated to poly(ethylene glycol–poly(lactic-co-glycolic acid. The resulting particle size was 67.0±1.7 nm, and the zeta potential of the particles was −6.63±0.43 mV. The corneal permeation of iRGD and TAT NPs increased by 5.50- and 4.56-fold compared to that of bare and iRGD-modified NPs, respectively. Cellular uptake showed that the red fluorescence intensity of iRGD and TAT NPs was highest among primary NPs and iRGD- or TAT-modified NPs. CNV was fully formed 14 days after photocoagulation in Brown Norway (BN rats as shown by optical coherence tomography and fundus fluorescein angiography analyses. Choroidal flat mounts in BN rats showed that the red fluorescence intensity of NPs followed the order of iRGD and TAT NPs > TAT-modified NPs > iRGD-modified NPs

Tat-PRAS40 prevent hippocampal HT-22 cell death and oxidative stress induced animal brain ischemic insults.

Science.gov (United States)

Shin, Min Jea; Kim, Dae Won; Jo, Hyo Sang; Cho, Su Bin; Park, Jung Hwan; Lee, Chi Hern; Yeo, Eun Ji; Choi, Yeon Joo; Kim, Ji An; Hwang, Jung Soon; Sohn, Eun Jeong; Jeong, Ji-Heon; Kim, Duk-Soo; Kwon, Hyeok Yil; Cho, Yong-Jun; Lee, Keunwook; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

2016-08-01

Proline rich Akt substrate (PRAS40) is a component of mammalian target of rapamycin complex 1 (mTORC1) and is known to play an important role against reactive oxygen species-induced cell death. However, the precise function of PRAS40 in ischemia remains unclear. Thus, we investigated whether Tat-PRAS40, a cell-permeable fusion protein, has a protective function against oxidative stress-induced hippocampal neuronal (HT-22) cell death in an animal model of ischemia. We showed that Tat-PRAS40 transduced into HT-22 cells, and significantly protected against cell death by reducing the levels of H2O2 and derived reactive species, and DNA fragmentation as well as via the regulation of Bcl-2, Bax, and caspase 3 expression levels in H2O2 treated cells. Also, we showed that transduced Tat-PARS40 protein markedly increased phosphorylated RRAS40 expression levels and 14-3-3σ complex via the Akt signaling pathway. In an animal ischemia model, Tat-PRAS40 effectively transduced into the hippocampus in animal brain and significantly protected against neuronal cell death in the CA1 region. We showed that Tat-PRAS40 protein effectively transduced into hippocampal neuronal cells and markedly protected against neuronal cell damage. Therefore, we suggest that Tat-PRAS40 protein may be used as a therapeutic protein for ischemia and oxidative stress-induced brain disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Kaposi's Sarcoma: clinical and pathological aspects in patients seen at the Hospital Universitário Cassiano Antônio Moraes - Vitória - Espírito Santo - Brazil Sarcoma de Kaposi: achados clínico-patológicos nos pacientes atendidos no Hospital Universitário Cassiano Antônio Moraes - Vitória - Espírito Santo - Brazil

Directory of Open Access Journals (Sweden)

Ricardo Montibeler Tiussi

2012-04-01

Full Text Available BACKGROUND: Kaposi's sarcoma is a neoplasm of endothelial origin that is divided into four distinct types according to the clinical characteristics and the affected population: Classic (in elder men of Jewish or Mediterranean origin; Epidemic (in patients affected by AIDS; Endemic (in black African men and Iatrogenic (in patients under immunosuppressive regimens. Human herpesvirus 8 infection is essential but not sufficient for the sarcoma development. OBJECTIVE: To describe the epidemiological, clinical and histopathological aspects of patients with KS seen at the Dermatology Clinic -Cassiano Antônio Moraes University Hospital - Federal University of Espirito Santo, Vitória - ES. METHODS: A descriptive and retrospective study based on clinical charts of patients with KS seen at the Dermatology Clinic from 1986 to 2009. RESULTS: The majority of the 15 cases were male patients (93,3% and white (60%. Epidemic Kaposi's sarcoma occurred in 80%, and the Classic form in 20%, with no cases in the Endemic or Iatrogenic groups. All the histopatho logical exams of the cutaneous lesions were reviewed and a proliferation of fusiform cells, extravasated erythrocytes and vascular rifts among the largest vessels, assuming the "vessels in vessels" typical aspect, were seen. CONCLUSION: The number of cases of Kaposi's Sarcoma was linear throughout the years of the study, especially of the epidemic form, although the incidence and prevalence of AIDS increased in the state of Espírito Santo. Therefore, if we consider the relation between KS and AIDS, a decreasing line of Kaposi's sarcoma could be seen, especially after the introduction of HAART.FUNDAMENTOS: O Sarcoma de Kaposi é neoplasia de origem endotelial, dividida em quatro formas clínicas: clássica (homens idosos de origem judaica e mediterrânea, epidêmica (associada ao HIV, endêmica (negros africanos e iatrogênica (relacionada à imunossupressão. A infecção pelo herpes vírus humano tipo 8 (HHV

Productively infected murine Kaposi's sarcoma-like tumors define new animal models for studying and targeting KSHV oncogenesis and replication.

Directory of Open Access Journals (Sweden)

Brittany M Ashlock

Full Text Available Kaposi's sarcoma (KS is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV. KS tumors are composed of KSHV-infected spindle cells of vascular origin with aberrant neovascularization and erythrocyte extravasation. KSHV genes expressed during both latent and lytic replicative cycles play important roles in viral oncogenesis. Animal models able to recapitulate both viral and host biological characteristics of KS are needed to elucidate oncogenic mechanisms, for developing targeted therapies, and to trace cellular components of KS ontogeny. Herein, we describe two new murine models of Kaposi's sarcoma. We found that murine bone marrow-derived cells, whether established in culture or isolated from fresh murine bone marrow, were infectable with rKSHV.219, formed KS-like tumors in immunocompromised mice and produced mature herpesvirus-like virions in vivo. Further, we show in vivo that the histone deacetylase (HDAC inhibitor suberoylanilide hydroxamic acid (SAHA/Vorinostat enhanced viral lytic reactivation. We propose that these novel models are ideal for studying both viral and host contributions to KSHV-induced oncogenesis as well as for testing virally-targeted antitumor strategies for the treatment of Kaposi's sarcoma. Furthermore, our isolation of bone marrow-derived cell populations containing a cell type that, when infected with KSHV, renders a tumorigenic KS-like spindle cell, should facilitate systematic identification of KS progenitor cells.

The human immunodeficiency virus-1 protein Tat and its discrete fragments evoke selective release of acetylcholine from human and rat cerebrocortical terminals through species-specific mechanisms.

Science.gov (United States)

Feligioni, Marco; Raiteri, Luca; Pattarini, Roberto; Grilli, Massimo; Bruzzone, Santina; Cavazzani, Paolo; Raiteri, Maurizio; Pittaluga, Anna

2003-07-30

The effect of the human immunodeficiency virus-1 protein Tat was investigated on neurotransmitter release from human and rat cortical nerve endings. Tat failed to affect the release of several neurotransmitters, such as glutamate, GABA, norepinephrine, and others, but it evoked the release of [3H]ACh via increase of cytosolic [Ca2+]. In human nerve terminals, the Tat effect partly depends on Ca2+ entry through voltage-sensitive Ca2+ channels, because Cd2+ halved the Tat-evoked release. Activation of group I metabotropic glutamate receptors (mGluR) and mobilization of Ca2+ from IP3-sensitive intraterminal stores are also involved, because the Tat effect was prevented by mGluR antagonists 2-methyl-6-(phenylethynyl)pyridine hydrochloride and 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester and by the IP3 receptor antagonists heparin and xestospongin C. Furthermore, the group I selective mGlu agonist (RS)-3,5-dihydroxyphenylglycine enhanced [3H]ACh release. In rat nerve terminals, the Tat-evoked release neither depends on external Ca2+ ions entry nor on IP3-mediated mechanisms. Tat seems to cause mobilization of Ca2+ from ryanodine-sensitive internal stores because its effect was prevented by both 8-bromo-cyclic adenosine diphosphate-ribose and dantrolene. The Tat-evoked release from human synaptosomes was mimicked by the peptide sequences Tat 32-62, Tat 49-86, and Tat 41-60. In contrast, the Tat 49-86 and Tat 61-80 fragments, but not the Tat 32-62 fragment, were active in rat synaptosomes. In conclusion, Tat elicits Ca2+-dependent [3H]ACh release by species-specific intraterminal mechanisms by binding via discrete amino acid sequences to different receptive sites on human and rat cholinergic terminals.

Human herpes virus-8 DNA in bronchoalveolar lavage samples from patients with AIDS-associated pulmonary Kaposi's sarcoma

DEFF Research Database (Denmark)

Benfield, T L; Dodt, K K; Lundgren, Jens Dilling

1997-01-01

Kaposi's sarcoma (KS) is the most frequent AIDS-associated neoplasm, and often disseminates to visceral organs, including the lungs. An ante-mortem diagnosis of pulmonary KS is difficult. Recently, DNA sequences resembling a new human herpes virus (HHV-8), have been identified in various forms...

Contribution of nonneutralizing vaccine-elicited antibody activities to improved protective efficacy in rhesus macaques immunized with Tat/Env compared with multigenic vaccines.

Science.gov (United States)

Florese, Ruth H; Demberg, Thorsten; Xiao, Peng; Kuller, LaRene; Larsen, Kay; Summers, L Ebonita; Venzon, David; Cafaro, Aurelio; Ensoli, Barbara; Robert-Guroff, Marjorie

2009-03-15

Previously, chronic-phase protection against SHIV(89.6P) challenge was significantly greater in macaques primed with replicating adenovirus type 5 host range mutant (Ad5hr) recombinants encoding HIVtat and env and boosted with Tat and Env protein compared with macaques primed with multigenic adenovirus recombinants (HIVtat, HIVenv, SIVgag, SIVnef) and boosted with Tat, Env, and Nef proteins. The greater protection was correlated with Tat- and Env-binding Abs. Because the macaques lacked SHIV(89.6P)-neutralizing activity prechallenge, we investigated whether Ab-dependent cellular cytotoxicity (ADCC) and Ab-dependent cell-mediated viral inhibition (ADCVI) might exert a protective effect. We clearly show that Tat can serve as an ADCC target, although the Tat-specific activity elicited did not correlate with better protection. However, Env-specific ADCC activity was consistently higher in the Tat/Env group, with sustained cell killing postchallenge exhibited at higher levels (p vaccine regimens.

Progesterone protects normative anxiety-like responding among ovariectomized female mice that conditionally express the HIV-1 regulatory protein, Tat, in the CNS.

Science.gov (United States)

Paris, Jason J; Fenwick, Jason; McLaughlin, Jay P

2014-05-01

Increased anxiety is co-morbid with human immunodeficiency virus (HIV) infection. Actions of the neurotoxic HIV-1 regulatory protein, Tat, may contribute to affective dysfunction. We hypothesized that Tat expression would increase anxiety-like behavior of female GT-tg bigenic mice that express HIV-1 Tat protein in the brain in a doxycycline-dependent manner. Furthermore, given reports that HIV-induced anxiety may occur at lower rates among women, and that the neurotoxic effects of Tat are ameliorated by sex steroids in vitro, we hypothesized that 17β-estradiol and/or progesterone would ameliorate Tat-induced anxiety-like effects. Among naturally-cycling proestrous and diestrous mice, Tat-induction via 7days of doxycycline treatment significantly increased anxiety-like responding in an open field, elevated plus maze and a marble-burying task, compared to treatment with saline. Proestrous mice demonstrated less anxiety-like behavior than diestrous mice in the open field and elevated plus maze, but these effects did not significantly interact with Tat-induction. Among ovariectomized mice, doxycycline-induced Tat protein significantly increased anxiety-like behavior in an elevated plus maze and a marble burying task compared to saline-treated mice, but not an open field (where anxiety-like responding was already maximal). Co-administration of progesterone (4mg/kg), but not 17β-estradiol (0.09mg/kg), with doxycycline significantly ameliorated anxiety-like responding in the elevated plus maze and marble burying tasks. When administered together, 17β-estradiol partially antagonized the protective effects of progesterone on Tat-induced anxiety-like behavior. These findings support evidence of steroid-protection over HIV-1 proteins, and extend them by demonstrating the protective capacity of progesterone on Tat-induced anxiety-like behavior of ovariectomized female mice. Copyright © 2014 Elsevier Inc. All rights reserved.

Temporary increase in serum beta 2-microglobulin during treatment with interferon-alpha for AIDS-associated Kaposi's sarcoma

NARCIS (Netherlands)

de Wit, R.; Bakker, P. J.; Reiss, P.; Hoek, F. J.; Lange, J. M.; Goudsmit, J.; Veenhof, K. H.

1990-01-01

Beta 2-microglobulin (beta 2-M) levels were determined in the serum of 24 patients treated with high-dose human recombinant interferon-alpha (IFN alpha) for AIDS-associated Kaposi's sarcoma. There was a significant increase in serum beta 2-M levels, irrespective of the response to treatment.

Subtypes of coups d’état: recent transformations of a 17th century concept

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Rafael Martínez

2014-12-01

Full Text Available Ostensibly, the coup d’état as a practice has been virtually eradicated, or confined, at least, to failed African states. Nevertheless, in recent years various changes of government in Latin America (and even Europe have provoked serious doubts to be raised as to their legality and legitimacy, and they have come to be regarded as coups d’état. In light of this reality, this study attempts to go deeper into the concept of the coup d’état, right through from its creation in the 17th century to our times, in order to determine the evolutionary changes that the concept has undergone and to extract the lowest common denominator that has remained unchanged. With these premises established, the presumed evolutionary course of the concept in the 21st century is plotted and the typologies it might generate are proposed.

Ex vivo expansion of hematopoietic stem cell by fusion protein TAT-Zfx

International Nuclear Information System (INIS)

Xu Chong; Zhang Yanbing; Jiang Hua

2009-01-01

The relative inability of hemopoietic stem cells (HSCs) to reproduce themselves (self-renew) ex vivo imposes substantial limitations on the current use of HSC transplantation. Recently, the transcription factor Zfx has been demonstrated that played an important in controlling the self-renewal of hematopoietic stem cells. Here, we reported that Zfx could enable high-level expansion of HSCs in vitro, by combination of protein transduction domain, TAT. Furthermore, we also demonstrated that expanded HSCs population retains their normal in vivo potential of pluripotency. It is thus that TAT-Zfx has the potential to expand HSCs significantly in vitro, and will have enormous clinical potentials.

The cross-talk of HIV-1 Tat and methamphetamine in HIV-associated neurocognitive disorders

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Susana T Valente

2015-10-01

Full Text Available Antiretroviral therapy (ART has dramatically improved the lives of HIV-1 infected individuals. Nonetheless, HIV associated neurocognitive disorders (HAND, which range from undetectable neurocognitive impairments to severe dementia, still affect approximately 50% of the infected population, hampering their quality of life.The persistence of HAND is promoted by several factors, including longer life expectancies, the residual levels of virus in the central nervous system and the continued presence of HIV-1 regulatory proteins such as the transactivator of transcription (Tat in the brain. Tat is a secreted viral protein that crosses the blood brain barrier into the central nervous system, where it has the ability to directly act on neurons and non-neuronal cells alike. These actions result in the release of soluble factors involved in inflammation, oxidative stress and excitotoxicity, ultimately resulting in neuronal damage. The percentage of methamphetamine abusers is high among the HIV-1-positive population compared to the general population. On the other hand, methamphetamine abuse is correlated with increased viral replication, enhanced Tat-mediated neurotoxicity and neurocognitive impairments. Although several strategies have been investigated to reduce HAND and methamphetamine use, no clinically approved treatment is currently available. Here, we review the latest findings of the effects of Tat and methamphetamine in HAND and discuss a few promising potential therapeutic developments.

Assessment of the chemosensitizing activity of TAT-RasGAP317-326 in childhood cancers.

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Nadja Chevalier

Full Text Available Although current anti-cancer protocols are reasonably effective, treatment-associated long-term side effects, induced by lack of specificity of the anti-cancer procedures, remain a challenging problem in pediatric oncology. TAT-RasGAP317-326 is a RasGAP-derived cell-permeable peptide that acts as a sensitizer to various anti-cancer treatments in adult tumor cells. In the present study, we assessed the effect of TAT-RasGAP317-326 in several childhood cancer cell lines. The RasGAP-derived peptide-induced cell death was analyzed in several neuroblastoma, Ewing sarcoma and leukemia cell lines (as well as in normal lymphocytes. Cell death was evaluated using flow cytometry methods in the absence or in the presence of the peptide in combination with various genotoxins used in the clinics (4-hydroperoxycyclophosphamide, etoposide, vincristine and doxorubicin. All tested pediatric tumors, in response to at least one genotoxin, were sensitized by TAT-RasGAP317-326. The RasGAP-derived peptide did not increase cell death of normal lymphocytes, alone or in combination with the majority of the tested chemotherapies. Consequently, TAT-RasGAP317-326 may benefit children with tumors by increasing the efficacy of anti-cancer therapies notably by allowing reductions in anti-cancer drug dosage and the associated drug-induced side effects.

Palliative radiation therapy for AIDS-associated Kaposi's sarcoma by using a single fraction of 800 cGy

NARCIS (Netherlands)

de Wit, R.; Smit, W. G.; Veenhof, K. H.; Bakker, P. J.; Oldenburger, F.; González, D. G.

1990-01-01

A single radiation fraction of 800 cGy was used in the treatment of acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS). A total of 74 radiation treatments was given to a total of 31 patients. Of all 74 evaluable treatments, there were 25 objective major responses (6 complete,

Genetic disruption of tubulin acetyltransferase, αTAT1, inhibits proliferation and invasion of colon cancer cells through decreases in Wnt1/β-catenin signaling

International Nuclear Information System (INIS)

Oh, Somi; You, Eunae; Ko, Panseon; Jeong, Jangho; Keum, Seula; Rhee, Sangmyung

2017-01-01

Microtubules are required for diverse cellular processes, and abnormal regulation of microtubule dynamics is closely associated with severe diseases including malignant tumors. In this study, we report that α-tubulin N-acetyltransferase (αTAT1), a regulator of α-tubulin acetylation, is required for colon cancer proliferation and invasion via regulation of Wnt1 and its downstream genes expression. Public transcriptome analysis showed that expression of ATAT1 is specifically upregulated in colon cancer tissue. A knockout (KO) of ATAT1 in the HCT116 colon cancer cell line, using the CRISPR/Cas9 system showed profound inhibition of proliferative and invasive activities of these cancer cells. Overexpression of αTAT1 or the acetyl-mimic K40Q α-tubulin mutant in αTAT1 KO cells restored the invasiveness, indicating that microtubule acetylation induced by αTAT1 is critical for HCT116 cell invasion. Analysis of colon cancer-related gene expression in αTAT1 KO cells revealed that the loss of αTAT1 decreased the expression of WNT1. Mechanistically, abrogation of tubulin acetylation by αTAT1 knockout inhibited localization of β-catenin to the plasma membrane and nucleus, thereby resulting in the downregulation of Wnt1 and of its downstream genes including CCND1, MMP-2, and MMP-9. These results suggest that αTAT1-mediated Wnt1 expression via microtubule acetylation is important for colon cancer progression. - Highlights: • Ablation of αTAT1 inhibits HCT116 colon cancer cell invasion. • αTAT1/acetylated microtubules regulate expression of Wnt1/β-catenin target genes. • Acetylated microtubules regulate cellular localization of β-catenin. • Loss of αTAT1 prevents Wnt1 from inducing β-catenin-dependent and -independent pathways.

Epitopes of human immunodeficiency virus regulatory proteins tat, nef, and rev are expressed in normal human tissue

NARCIS (Netherlands)

Parmentier, H. K.; van Wichen, D. F.; Meyling, F. H.; Goudsmit, J.; Schuurman, H. J.

1992-01-01

The expression of regulatory proteins tat, rev, and nef of human immunodeficiency virus type-1 (HIV-1) and tat of HIV-2 was studied in frozen sections of lymph nodes from HIV-1-infected individuals, and various tissues from uninfected persons. In HIV-1-positive lymph nodes, monoclonal antibodies to

High incidence of Kaposi sarcoma-associated herpesvirus infection in HIV-related solid immunoblastic/plasmablastic diffuse large B-cell lymphoma

NARCIS (Netherlands)

Deloose, S. T. P.; Smit, L. A.; Pals, F. T.; Kersten, M.-J.; van Noesel, C. J. M.; Pals, S. T.

2005-01-01

Kaposi sarcoma-associated herpesvirus ( KSHV) is known to be associated with two distinct lymphoproliferative disorders: primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD)/MCD-associated plasmablastic lymphoma. We here report a high incidence of KSHV infection in solid

Tat-CBR1 inhibits inflammatory responses through the suppressions of NF-κB and MAPK activation in macrophages and TPA-induced ear edema in mice

Energy Technology Data Exchange (ETDEWEB)

Kim, Young Nam [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Kim, Dae Won [Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangnung-Wonju National University, Kangneung 210-702 (Korea, Republic of); Jo, Hyo Sang; Shin, Min Jea; Ahn, Eun Hee; Ryu, Eun Ji; Yong, Ji In; Cha, Hyun Ju; Kim, Sang Jin; Yeo, Hyeon Ji; Youn, Jong Kyu; Hwang, Jae Hyeok [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Jeong, Ji-Heon; Kim, Duk-Soo [Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 330-090 (Korea, Republic of); Cho, Sung-Woo [Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Park, Jinseu [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Eum, Won Sik, E-mail: wseum@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Choi, Soo Young, E-mail: sychoi@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of)

2015-07-15

Human carbonyl reductase 1 (CBR1) plays a crucial role in cell survival and protects against oxidative stress response. However, its anti-inflammatory effects are not yet clearly understood. In this study, we examined whether CBR1 protects against inflammatory responses in macrophages and mice using a Tat-CBR1 protein which is able to penetrate into cells. The results revealed that purified Tat-CBR1 protein efficiently transduced into Raw 264.7 cells and inhibited lipopolysaccharide (LPS)-induced cyclooxygenase-2 (COX-2), nitric oxide (NO) and prostaglandin E{sub 2} (PGE{sub 2}) expression levels. In addition, Tat-CBR1 protein leads to decreased pro-inflammatory cytokine expression through suppression of nuclear transcription factor-kappaB (NF-κB) and mitogen activated protein kinase (MAPK) activation. Furthermore, Tat-CBR1 protein inhibited inflammatory responses in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation when applied topically. These findings indicate that Tat-CBR1 protein has anti-inflammatory properties in vitro and in vivo through inhibition of NF-κB and MAPK activation, suggesting that Tat-CBR1 protein may have potential as a therapeutic agent against inflammatory diseases. - Highlights: • Transduced Tat-CBR1 reduces LPS-induced inflammatory mediators and cytokines. • Tat-CBR1 inhibits MAPK and NF-κB activation. • Tat-CBR1 ameliorates inflammation response in vitro and in vivo. • Tat-CBR1 may be useful as potential therapeutic agent for inflammation.

Solitary Kaposi's sarcoma in retromolar region of an HIV positive patient: case report Sarcoma de Kaposi em região retromolar de um paciente HIV positivo: relato de caso

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Maiara de Moraes

2012-02-01

Full Text Available Kaposi's sarcoma is a malignant neoplasm of vascular origin. It occurs mainly among immune deficient individuals, thus it is the most common neoplasm among HIV- positive patients. Its pathogenesis is complex and has not been fully clarified. This case arouses particular interest due to its anatomic location in the retromolar region of a 39-year-old male HIV- positive patient, who presented low white blood cell count and was not undergoing antiretroviral therapy. The emergence of this lesion may be associated with highly active antiretroviral therapy (HAART discontinuation and leukopenia. Hence, the reestablishment of therapy allows a suitable therapeutic approach and contributes to prognosis and survival rates.Sarcoma de Kaposi é uma neoplasia maligna de origem vascular que ocorre principalmente em indivíduos com deficiência imunológica, sendo a neoplasia mais comum em pacientes HIV positivos. Sua patogênese é complexa e não está bem estabelecida. Este caso é de interesse pela localização anatômica em região retromolar de paciente soropositivo, que apresentou baixa contagem de células brancas do sangue e que não realizava terapia antirretroviral. O surgimento da lesão pode estar associado à interrupção da terapia antirretroviral altamente ativa (HAART e à baixa contagem leucocitária. Assim, o restabelecimento da terapia pode permitir a abordagem terapêutica e contribuir para o prognóstico e a sobrevida.

The epigenetic landscape of latent Kaposi sarcoma-associated herpesvirus genomes.

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Thomas Günther

Full Text Available Herpesvirus latency is generally thought to be governed by epigenetic modifications, but the dynamics of viral chromatin at early timepoints of latent infection are poorly understood. Here, we report a comprehensive spatial and temporal analysis of DNA methylation and histone modifications during latent infection with Kaposi Sarcoma-associated herpesvirus (KSHV, the etiologic agent of Kaposi Sarcoma and primary effusion lymphoma (PEL. By use of high resolution tiling microarrays in conjunction with immunoprecipitation of methylated DNA (MeDIP or modified histones (chromatin IP, ChIP, our study revealed highly distinct landscapes of epigenetic modifications associated with latent KSHV infection in several tumor-derived cell lines as well as de novo infected endothelial cells. We find that KSHV genomes are subject to profound methylation at CpG dinucleotides, leading to the establishment of characteristic global DNA methylation patterns. However, such patterns evolve slowly and thus are unlikely to control early latency. In contrast, we observed that latency-specific histone modification patterns were rapidly established upon a de novo infection. Our analysis furthermore demonstrates that such patterns are not characterized by the absence of activating histone modifications, as H3K9/K14-ac and H3K4-me3 marks were prominently detected at several loci, including the promoter of the lytic cycle transactivator Rta. While these regions were furthermore largely devoid of the constitutive heterochromatin marker H3K9-me3, we observed rapid and widespread deposition of H3K27-me3 across latent KSHV genomes, a bivalent modification which is able to repress transcription in spite of the simultaneous presence of activating marks. Our findings suggest that the modification patterns identified here induce a poised state of repression during viral latency, which can be rapidly reversed once the lytic cycle is induced.

Iran : l’État islamique entre structures monopolistiques et modèle de l’État social

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Azadeh Kian-Thiébaut

2012-01-01

Full Text Available Dans l’Iran post-révolutionnaire, la segmentation de la société s’est amplifiée, l’économie est demeurée rentière et l’État, privatisé, sert avant tout les intérêts des structures monopolistiques, formées à la suite de la création des fondations révolutionnaires, de l’étatisation de l’économie et de sa réorientation vers le secteur de distribution. Le poids de ces fondations, dirigées par les conservateurs, qui jouissent d’un statut autonome et contrôlent une partie importante du PIB s’étend aussi à la sphère politique. D’où l’échec des tentatives d’une réforme structurelle profonde, en dépit de l’évolution de l’économie stato-centrée des dix premières années, établie sous l’impulsion des acteurs sociaux et économiques radicaux, vers une économie de marché. Face à la crise économique et au chômage massif, le gouvernement, soucieux de la fragilisation de la cohésion sociale, se rapproche du modèle de l’État social en optant pour une politique sociale dont les dépenses sont financées par les revenus pétroliers et non par la taxation et la solidarité. Ce qui risque d’entraver l’autonomisation de la population assistée et d’amoindrir l’influence qu’elle peut exercer sur l’État.Confrontée au verrouillage du système politique et animée par une volonté de participation sociale visant à introduire un changement par le bas, la société civile émergente, en particulier les classes moyennes, s’engage davantage dans l’activité sociale à travers des réseaux traditionnels et modernes d’entraide. Cette participation sociale est susceptible d’assurer, à terme, les conditions de développement des sphères de l’autonomie sociale.

Comparison of the distribution of non-AIDS Kaposi's sarcoma and non-Hodgkin's lymphoma in Europe

Science.gov (United States)

Maso, L Dal; Franceschi, S; Re, A Lo; Vecchia, C La

1999-01-01

To evaluate whether some form of mild immunosuppression may influence the geographical distribution of non-AIDS Kaposi's sarcoma (KS), we correlated incidence rates of KS and non-Hodgkin's lymphoma in individuals aged 60 or more in 18 European countries and Israel. Significant positive correlations emerged but, within highest risk countries (i.e.Italy and Israel), internal correlations were inconsistent. © 1999 Cancer Research Campaign PMID:10408708

Human herpesvirus-8 positive iatrogenic Kaposi's sarcoma in the setting of refractory ulcerative colitis

OpenAIRE

Duh, Erica; Fine, Sean

2017-01-01

Although Kaposi sarcoma (KS) has been more traditionally considered an AIDS-defining illness, it may also be seen in individuals on immunosuppresive therapy. We report a case of a patient who presented to the hospital in the setting of increasingly refractory ulcerative colitis. Computed tomography scan of the abdomen was consistent with sigmoid diverticulititis and blood cultures were positive for Klebsiella. After a course of antibiotics with resolution of infection, a colonoscopy was perfo...

Seroprevalence of Kaposi's sarcoma-associated herpesvirus in various populations in Cuba Seroprevalencia del herpesvirus asociado con el sarcoma de Kaposi en diversas poblaciones en Cuba

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Vivian Kourí

2004-05-01

Full Text Available OBJECTIVE: Little is known about the prevalence and distribution of Kaposi's sarcoma-associated herpesvirus (KSHV infection in the Caribbean. The aim of this study was to determine rates of KSHV seropositivity in various populations in Cuba. METHODS: During the years 1998 to 2002 we screened serum samples from 410 subjects in Cuba. Serologic screening for KSHV antibodies was a two-step process using (1 indirect immunofluorescence assay (IFA specifically reactive to the KSHV latency-associated nuclear antigen (LANA encoded by open reading frame 73 (ORF73, and (2 confirmatory immunoblot using recombinant KSHV ORF65.2, a lytically expressed, 20-kilodalton protein as the target antigen. Five different populations were studied: (1 45 AIDS patients with Kaposi's sarcoma (AIDS-KS, (2 154 HIV-1-infected patients without clinical evidence of KS, (3 171 HIV-negative blood donors, (4 27 consecutive kidney transplant recipients, who were HIV-negative, and (5 13 contacts (sexual contacts or relatives of the AIDS-KS-affected patients. RESULTS: Among the 45 AIDS-KS subjects, 35 of them (77.8% were KSHV-seropositive. Thirty-two of the 154 HIV-positive patients without KS (20.8% of them were KSHV-seropositive, and 6 of the 13 contacts of KS-affected patients (46.2% of them were infected with KSHV. In contrast to other researchers, we did not find in the populations that we studied in Cuba that KSHV seropositivity was associated with male homosexual or bisexual activity. We found high KSHV seropositivity rates among women reporting sexual contact with bisexual men and among men who had acquired an HIV infection in Africa. There were low rates of KSHV infection among the blood donors (1.2% and the renal transplant recipients (0.0%. The low rates of KSHV infection that we found among the non-HIV-infected populations in Cuba are similar to patterns found in populations in Europe and in the United States. CONCLUSIONS: Together with similar results from Brazil

Structural map of Kaposi sarcoma-associated herpesvirus RNA provides clues to molecular interactions | Center for Cancer Research

Science.gov (United States)

Scientists from CCR have generated a comprehensive structural map of Kaposi sarcoma-associated herpesvirus polyadenylated nuclear (PAN) RNA, a long non-coding RNA that helps the virus evade detection by its host’s immune system. The findings open new oppportunites to study the life cycle of this cancer-causing virus.  Learn more...

PDGF-mediated protection of SH-SY5Y cells against Tat toxin involves regulation of extracellular glutamate and intracellular calcium

International Nuclear Information System (INIS)

Zhu Xuhui; Yao Honghong; Peng Fuwang; Callen, Shannon; Buch, Shilpa

2009-01-01

The human immunodeficiency virus (HIV-1) protein Tat has been implicated in mediating neuronal apoptosis, one of the hallmark features of HIV-associated dementia (HAD). Mitigation of the toxic effects of Tat could thus be a potential mechanism for reducing HIV toxicity in the brain. In this study we demonstrated that Tat-induced neurotoxicity was abolished by NMDA antagonist-MK801, suggesting the role of glutamate in this process. Furthermore, we also found that pretreatment of SH-SY5Y cells with PDGF exerted protection against Tat toxicity by decreasing extracellular glutamate levels. We also demonstrated that extracellular calcium chelator EGTA was able to abolish PDGF-mediated neuroprotection, thereby underscoring the role of calcium signaling in PDGF-mediated neuroprotection. We also showed that Erk signaling pathway was critical for PDGF-mediated protection of cells. Additionally, blocking calcium entry with EGTA resulted in suppression of PDGF-induced Erk activation. These findings thus underscore the role of PDGF-mediated calcium signaling and Erk phosphorylation in the protection of cells against HIV Tat toxicity.

Negotiation of intracellular membrane barriers by TAT-modified gold nanoparticles.

Science.gov (United States)

Krpetić, Zeljka; Saleemi, Samia; Prior, Ian A; Sée, Violaine; Qureshi, Rumana; Brust, Mathias

2011-06-28

This paper contributes to the debate on how nanosized objects negotiate membrane barriers inside biological cells. The uptake of peptide-modified gold nanoparticles by HeLa cells has been quantified using atomic emission spectroscopy. The TAT peptide from the HIV virus was singled out as a particularly effective promoter of cellular uptake. The evolution of the intracellular distribution of TAT-modified gold nanoparticles with time has been studied in detail by TEM and systematic image analysis. An unusual trend of particles disappearing from the cytosol and the nucleus and accumulating massively in vesicular bodies was observed. Subsequent release of the particles, both by membrane rupture and by direct transfer across the membrane boundary, was frequently found. Ultimately, near total clearing of particles from the cells occurred. This work provides support for the hypothesis that cell-penetrating peptides can enable small objects to negotiate membrane barriers also in the absence of dedicated transport mechanisms.

Recombinant TAT-BMI-1 fusion protein induces ex vivo expansion of human umbilical cord blood-derived hematopoietic stem cells.

Science.gov (United States)

Codispoti, Bruna; Rinaldo, Nicola; Chiarella, Emanuela; Lupia, Michela; Spoleti, Cristina Barbara; Marafioti, Maria Grazia; Aloisio, Annamaria; Scicchitano, Stefania; Giordano, Marco; Nappo, Giovanna; Lucchino, Valeria; Moore, Malcolm A S; Zhou, Pengbo; Mesuraca, Maria; Bond, Heather Mandy; Morrone, Giovanni

2017-07-04

Transplantation of hematopoietic stem cells (HSCs) is a well-established therapeutic approach for numerous disorders. HSCs are typically derived from bone marrow or peripheral blood after cytokine-induced mobilization. Umbilical cord blood (CB) represents an appealing alternative HSC source, but the small amounts of the individual CB units have limited its applications. The availability of strategies for safe ex vivo expansion of CB-derived HSCs (CB-HSCs) may allow to extend the use of these cells in adult patients and to avoid the risk of insufficient engraftment or delayed hematopoietic recovery.Here we describe a system for the ex vivo expansion of CB-HSCs based on their transient exposure to a recombinant TAT-BMI-1 chimeric protein. BMI-1 belongs to the Polycomb family of epigenetic modifiers and is recognized as a central regulator of HSC self-renewal. Recombinant TAT-BMI-1 produced in bacteria was able to enter the target cells via the HIV TAT-derived protein transduction peptide covalently attached to BMI-1, and conserved its biological activity. Treatment of CB-CD34+ cells for 3 days with repeated addition of 10 nM purified TAT-BMI-1 significantly enhanced total cell expansion as well as that of primitive hematopoietic progenitors in culture. Importantly, TAT-BMI-1-treated CB-CD34+ cells displayed a consistently higher rate of multi-lineage long-term repopulating activity in primary and secondary xenotransplants in immunocompromised mice. Thus, recombinant TAT-BMI-1 may represent a novel, effective reagent for ex vivo expansion of CB-HSC for therapeutic purposes.

Sarcoma de Kaposi en paciente con SIDA

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Jesús Ramón León Polanco

2015-01-01

Full Text Available Se presenta el caso de un paciente masculino de 33 años de edad, con antecedentes de VIH-SIDA desde hace 10 años, que se mantiene en tratamiento con antirretrovirales. Durante todo este tiempo ha presentado varios episodios de infecciones respiratorias, incluyendo tuberculosis pulmonar 5 años atrás. Acude a consulta refiriendo edemas en miembros inferiores acompañado de lesiones en piel de color violáceo de un año de evolución, previamente interpretado como linfangitis rebelde al tratamiento y que se extendió a la cara interna de los muslos y a los miembros inferiores. Con pérdida de peso, no prurito en las lesiones, fiebre, lesiones en la mucosa oral. Se determinó hemoglobina 89 g/L, leucocitos 4,5 x 109 /L, se estudiaron las funciones hepática y renales resultando normales. Radiografías de tórax y ultrasonido abdominal normales. Se realizó estudio anatomopatológico de piel que informó Sarcoma de Kaposi. Se impuso tratamiento con quimioterapia

The human herpes virus 8-encoded chemokine receptor is required for angioproliferation in a murine model of Kaposi's sarcoma

DEFF Research Database (Denmark)

Jensen, Kristian K; Manfra, Denise J; Grisotto, Marcos G

2005-01-01

Kaposi's sarcoma (KS)-associated herpesvirus or human herpes virus 8 is considered the etiological agent of KS, a highly vascularized neoplasm that is the most common tumor affecting HIV/AIDS patients. The KS-associated herpesvirus/human herpes virus 8 open reading frame 74 encodes a constitutively...

Structure-based design of ligands for protein basic domains: Application to the HIV-1 Tat protein

Science.gov (United States)

Filikov, Anton V.; James, Thomas L.

1998-05-01

A methodology has been developed for designing ligands to bind a flexible basic protein domain where the structure of the domain is essentially known. It is based on an empirical binding free energy function developed for highly charged complexes and on Monte Carlo simulations in internal coordinates with both the ligand and the receptor being flexible. HIV-1 encodes a transactivating regulatory protein called Tat. Binding of the basic domain of Tat to TAR RNA is required for efficient transcription of the viral genome. The structure of a biologically active peptide containing the Tat basic RNA-binding domain is available from NMR studies. The goal of the current project is to design a ligand which will bind to that basic domain and potentially inhibit the TAR-Tat interaction. The basic domain contains six arginine and two lysine residues. Our strategy was to design a ligand for arginine first and then a superligand for the basic domain by joining arginine ligands with a linker. Several possible arginine ligands were obtained by searching the Available Chemicals Directory with DOCK 3.5 software. Phytic acid, which can potentially bind multiple arginines, was chosen as a building block for the superligand. Calorimetric binding studies of several compounds to methylguanidine and Arg-/Lys-containing peptides were performed. The data were used to develop an empirical binding free energy function for prediction of affinity of the ligands for the Tat basic domain. Modeling of the conformations of the complexes with both the superligand and the basic domain being flexible has been carried out via Biased Probability Monte Carlo (BPMC) simulations in internal coordinates (ICM 2.6 suite of programs). The simulations used parameters to ensure correct folding, i.e., consistent with the experimental NMR structure of a 25-residue Tat peptide, from a random starting conformation. Superligands for the basic domain were designed by joining together two molecules of phytic acid with

Backbone dynamics of the EIAV-Tat protein from 15N relaxation studies

International Nuclear Information System (INIS)

Ejchart, A.; Herrmann, F.; Roesch, P.; Sticht, H.; Willbold, D.

1994-01-01

The work investigates the mobility of EIAV-Tat protein backbone by measuring the relaxation parameters of the 15 N nitrogens. High degree of the flexibility, non-typical of rigid, well structured proteins was shown

Sarcoma de Kaposi en conjuntiva bulbar

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Ileana Agramonte Centelles

Full Text Available Paciente masculino de 29 años de edad, raza blanca, soltero, profesor universitario, con antecedentes de padecer crisis de epilepsia tratado con fenitoína y actualmente controlado, menciona que desde hace aproximadamente 4 semanas comenzó con ojo rojo y molestias oculares del ojo derecho, por lo cual acudió a su área de salud donde fue tratado como cuadro de conjuntivitis. No mostró mejoría alguna, sino empeoramiento del cuadro clínico, y observó un enrojecimiento ocular intenso en el ángulo interno de dicho ojo que se fue extendiendo, acompañado de ligera fotofobia. Por la tórpida evolución del cuadro decidió acudir a nuestra institución por lo cual fue remitido a la Consulta de Oculoplastia. También refirió que desde hacía dos meses había presentado anorexia, dificultad al comer, así como pérdida de peso, por lo cual se decidió comenzar estudio y tratamiento. Se decidió realizar la resección de la masa tumoral en conjuntiva bulbar y se envió para estudio anatomopatológico. El resultado fue compatible con un sarcoma de Kaposi.

Secretory TAT-peptide-mediated protein transduction of LIF receptor α-chain distal cytoplasmic motifs into human myeloid HL-60 cells

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Q. Sun

2012-10-01

Full Text Available The distal cytoplasmic motifs of leukemia inhibitory factor receptor α-chain (LIFRα-CT3 can independently induce intracellular myeloid differentiation in acute myeloid leukemia (AML cells by gene transfection; however, there are significant limitations in the potential clinical use of these motifs due to liposome-derived genetic modifications. To produce a potentially therapeutic LIFRα-CT3 with cell-permeable activity, we constructed a eukaryotic expression pcDNA3.0-TAT-CT3-cMyc plasmid with a signal peptide (ss inserted into the N-terminal that codes for an ss-TAT-CT3-cMyc fusion protein. The stable transfection of Chinese hamster ovary (CHO cells via this vector and subsequent selection by Geneticin resulted in cell lines that express and secrete TAT-CT3-cMyc. The spent medium of pcDNA3.0-TAT-CT3-cMyc-transfected CHO cells could be purified using a cMyc-epitope-tag agarose affinity chromatography column and could be detected via SDS-PAGE, with antibodies against cMyc-tag. The direct administration of TAT-CT3-cMyc to HL-60 cell culture media caused the enrichment of CT3-cMyc in the cytoplasm and nucleus within 30 min and led to a significant reduction of viable cells (P < 0.05 8 h after exposure. The advantages of using this mammalian expression system include the ease of generating TAT fusion proteins that are adequately transcripted and the potential for a sustained production of such proteins in vitro for future AML therapy.

Secretory TAT-peptide-mediated protein transduction of LIF receptor α-chain distal cytoplasmic motifs into human myeloid HL-60 cells

International Nuclear Information System (INIS)

Sun, Q.; Xiong, J.; Lu, J.; Xu, S.; Li, Y.; Zhong, X.P.; Gao, G.K.; Liu, H.Q.

2012-01-01

The distal cytoplasmic motifs of leukemia inhibitory factor receptor α-chain (LIFRα-CT3) can independently induce intracellular myeloid differentiation in acute myeloid leukemia (AML) cells by gene transfection; however, there are significant limitations in the potential clinical use of these motifs due to liposome-derived genetic modifications. To produce a potentially therapeutic LIFRα-CT3 with cell-permeable activity, we constructed a eukaryotic expression pcDNA3.0-TAT-CT3-cMyc plasmid with a signal peptide (ss) inserted into the N-terminal that codes for an ss-TAT-CT3-cMyc fusion protein. The stable transfection of Chinese hamster ovary (CHO) cells via this vector and subsequent selection by Geneticin resulted in cell lines that express and secrete TAT-CT3-cMyc. The spent medium of pcDNA3.0-TAT-CT3-cMyc-transfected CHO cells could be purified using a cMyc-epitope-tag agarose affinity chromatography column and could be detected via SDS-PAGE, with antibodies against cMyc-tag. The direct administration of TAT-CT3-cMyc to HL-60 cell culture media caused the enrichment of CT3-cMyc in the cytoplasm and nucleus within 30 min and led to a significant reduction of viable cells (P < 0.05) 8 h after exposure. The advantages of using this mammalian expression system include the ease of generating TAT fusion proteins that are adequately transcripted and the potential for a sustained production of such proteins in vitro for future AML therapy

Secretory TAT-peptide-mediated protein transduction of LIF receptor α-chain distal cytoplasmic motifs into human myeloid HL-60 cells

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Sun, Q. [Department of Hyperbaric Medicine, No. 401 Hospital of PLA, Qingdao (China); Department of Histology and Embryology, Faculty of Basic Medical Sciences, Second Military Medical University, Shanghai (China); Xiong, J. [Department of Histology and Embryology, Faculty of Basic Medical Sciences, Second Military Medical University, Shanghai (China); Lu, J. [Office of Medical Education, Training Department, Second Military Medical University, Shanghai (China); Xu, S. [Department of Histology and Embryology, Faculty of Basic Medical Sciences, Second Military Medical University, Shanghai (China); Li, Y. [State Food and Drug Administration of China,Huangdao Branch, Qingdao (China); Zhong, X.P.; Gao, G.K. [Department of Hyperbaric Medicine, No. 401 Hospital of PLA, Qingdao (China); Liu, H.Q. [2Department of Histology and Embryology, Faculty of Basic Medical Sciences, Second Military Medical University, Shanghai (China)

2012-06-22

The distal cytoplasmic motifs of leukemia inhibitory factor receptor α-chain (LIFRα-CT3) can independently induce intracellular myeloid differentiation in acute myeloid leukemia (AML) cells by gene transfection; however, there are significant limitations in the potential clinical use of these motifs due to liposome-derived genetic modifications. To produce a potentially therapeutic LIFRα-CT3 with cell-permeable activity, we constructed a eukaryotic expression pcDNA3.0-TAT-CT3-cMyc plasmid with a signal peptide (ss) inserted into the N-terminal that codes for an ss-TAT-CT3-cMyc fusion protein. The stable transfection of Chinese hamster ovary (CHO) cells via this vector and subsequent selection by Geneticin resulted in cell lines that express and secrete TAT-CT3-cMyc. The spent medium of pcDNA3.0-TAT-CT3-cMyc-transfected CHO cells could be purified using a cMyc-epitope-tag agarose affinity chromatography column and could be detected via SDS-PAGE, with antibodies against cMyc-tag. The direct administration of TAT-CT3-cMyc to HL-60 cell culture media caused the enrichment of CT3-cMyc in the cytoplasm and nucleus within 30 min and led to a significant reduction of viable cells (P < 0.05) 8 h after exposure. The advantages of using this mammalian expression system include the ease of generating TAT fusion proteins that are adequately transcripted and the potential for a sustained production of such proteins in vitro for future AML therapy.

Fractalkine/CX3CL1 protects striatal neurons from synergistic morphine and HIV-1 Tat-induced dendritic losses and death

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Suzuki Masami

2011-11-01

Full Text Available Abstract Background Fractalkine/CX3CL1 and its cognate receptor CX3CR1 are abundantly expressed in the CNS. Fractalkine is an unusual C-X3-C motif chemokine that is important in neuron-microglial communication, a co-receptor for HIV infection, and can be neuroprotective. To assess the effects of fractalkine on opiate-HIV interactive neurotoxicity, wild-type murine striatal neurons were co-cultured with mixed glia from the striata of wild-type or Cx3cr1 knockout mice ± HIV-1 Tat and/or morphine. Time-lapse digital images were continuously recorded at 20 min intervals for up to 72 h using computer-aided microscopy to track the same cells repeatedly. Results Co-exposure to Tat and morphine caused synergistic increases in neuron death, dendritic pruning, and microglial motility as previously reported. Exogenous fractalkine prevented synergistic Tat and morphine-induced dendritic losses and neuron death even though the inflammatory mediator TNF-α remained significantly elevated. Antibody blockade of CX3CR1 mimicked the toxic effects of morphine plus Tat, but did not add to their toxicity; while fractalkine failed to protect wild-type neurons co-cultured with Cx3cr1-/--null glia against morphine and Tat toxicity. Exogenous fractalkine also normalized microglial motility, which is elevated by Tat and morphine co-exposure, presumably limiting microglial surveillance that may lead to toxic effects on neurons. Fractalkine immunofluorescence was expressed in neurons and to a lesser extent by other cell types, whereas CX3CR1 immunoreactivity or GFP fluorescence in cells cultured from the striatum of Cx3cr1-/- (Cx3cr1GFP/GFP mice were associated with microglia. Immunoblotting shows that fractalkine levels were unchanged following Tat and/or morphine exposure and there was no increase in released fractalkine as determined by ELISA. By contrast, CX3CR1 protein levels were markedly downregulated. Conclusions The results suggest that deficits in fractalkine

HIV-1 Tat C-mediated regulation of tumor necrosis factor receptor-associated factor-3 by microRNA 32 in human microglia

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Mishra Ritu

2012-06-01

Full Text Available Abstract Background HIV-1 Tat protein is known to be associated with neuroinflammation, a condition that develops in almost half of patients infected with HIV-1. HIV-1 Tat can alter glial neuroprotective functions, leading to neurotoxicity within the CNS. HIV-1 Tat is known to be secreted from productively infected cells and can affect neighboring uninfected cells by modulating cellular gene expression in a bystander fashion. Methods We were interested to study whether exogenous exposure to HIV-1 Tat-C protein perturbs the microRNA (miRNA expression profile of human microglial cells, leading to altered protein expression. We used protein expression and purification, miRNA overexpression, miRNA knockdown, transfection, site-directed mutagenesis, real-time PCR, luciferase assay and western blotting techniques to perform our study. Results HIV-1 Tat-C treatment of human microglial cells resulted in a dose-dependent increase in miR-32 expression. We found that tumor necrosis factor-receptor–associated factor 3 TRAF3 is a direct target for miR-32, and overexpression of miR-32 in CHME3 cells decreased TRAF3 both at the mRNA and the protein level. Recovery of TRAF3 protein expression after transfection of anti-miR-32 and the results of the luciferase reporter assay provided direct evidence of TRAF3 regulation by miR-32. We found that the regulation of interferon regulatory factor 3 (IRF3 and IRF7 is controlled by cellular levels of TRAF3 protein in microglial cells, as after overexpression of miR-32 and application of anti-miR-32, expression levels of IRF3 and IRF7 were inversely regulated by expression levels of TRAF3. Thus, our results suggest a novel miRNA mediated mechanism for regulation of TRAF3 in human microglial cells exposed to HIV-1 Tat C protein. These results may help to elucidate the detrimental neuroinflammatory consequences of HIV-1 Tat C protein in bystander fashion. Conclusion HIV-1 Tat protein can modulate TRAF3 expression through

Combined metabonomic and quantitative real-time PCR analyses reveal systems metabolic changes in Jurkat T-cells treated with HIV-1 Tat protein.

Science.gov (United States)

Liao, Wenting; Tan, Guangguo; Zhu, Zhenyu; Chen, Qiuli; Lou, Ziyang; Dong, Xin; Zhang, Wei; Pan, Wei; Chai, Yifeng

2012-11-02

HIV-1 Tat protein is released by infected cells and can affect bystander uninfected T cells and induce numerous biological responses which contribute to its pathogenesis. To elucidate the complex pathogenic mechanism, we conducted a comprehensive investigation on Tat protein-related extracellular and intracellular metabolic changes in Jurkat T-cells using combined gas chromatography-mass spectrometry (GC-MS), reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) and a hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS)-based metabonomics approach. Quantitative real-time PCR (qRT-PCR) analyses were further employed to measure expressions of several relevant enzymes together with perturbed metabolic pathways. Combined metabonomic and qRT-PCR analyses revealed that HIV-1 Tat caused significant and comprehensive metabolic changes, as represented by significant changes of 37 metabolites and 10 relevant enzymes in HIV-1 Tat-treated cells. Using MetaboAnalyst 2.0, it was found that 11 pathways (Impact-value >0.10) among the regulated pathways were acutely perturbed, including sphingolipid metabolism, glycine, serine and threonine metabolism, pyruvate metabolism, inositol phosphate metabolism, arginine and proline metabolism, citrate cycle, phenylalanine metabolism, tryptophan metabolism, pentose phosphate pathway, glycerophospholipid metabolism, glycolysis or gluconeogenesis. These results provide metabolic evidence of the complex pathogenic mechanism of HIV-1 Tat protein as a "viral toxin", and would help obligate Tat protein as "an important target" for therapeutic intervention and vaccine development.

Sarcoma de Kaposi por virus del herpes humano de tipo 8 en un receptor de trasplante hepático pediátrico: Caso clínico

OpenAIRE

Malla, Ivone; Pérez, Celeste; Cheang, Yu; Silva, Marcelo

2013-01-01

Los pacientes que reciben tratamiento inmunosupresor están en riesgo de desarrollar tumores malignos. La infección primaria o reactivación del virus del herpes humano de tipo 8 (HHV-8) puede predisponer al sarcoma de Kaposi después del trasplante de un órgano sólido. En los receptores de trasplantes pediátricos, este sarcoma tiene baja incidencia y mal pronóstico. Se informa la presentación clínica de un sarcoma de Kaposi en un ganglio linfático luego de una infección por HHV-8 en un niño a l...

Changing Incidence and Risk Factors for Kaposi Sarcoma by Time Since Starting Antiretroviral Therapy: Collaborative Analysis of 21 European Cohort Studies

NARCIS (Netherlands)

Wyss, Natascha; Zwahlen, Marcel; Clifford, Gary; Campbell, Maria; Chakraborty, Rana; Bonnet, Fabrice; Chene, Geneviève; Bani-Sadr, Firouze; Verbon, Annelies; Zangerle, Robert; Paparizos, Vassilios; Prins, Maria; Dronda, Fernando; Le Moing, Vincent; Antinori, Andrea; Quiros-Roldan, Eugenia; Mussini, Cristina; Miro, Jose M.; Meyer, Laurence; Vehreschild, Janne; Obel, Niels; Mocroft, Amanda; Brockmeyer, Norbert; Boue, François; Sabin, Caroline; Spagnuolo, Vincenzo; Hasse, Barbara; de Wit, Stéphane; Roca, Bernardino; Egger, Matthias; Bohlius, Julia

2016-01-01

Kaposi sarcoma (KS) remains a frequent cancer in human immunodeficiency virus (HIV)-positive patients starting combination antiretroviral therapy (cART). We examined incidence rates and risk factors for developing KS in different periods after starting cART in patients from European observational

Multiplexed colorimetric detection of Kaposi's sarcoma associated herpesvirus and Bartonella DNA using gold and silver nanoparticles

Science.gov (United States)

Mancuso, Matthew; Jiang, Li; Cesarman, Ethel; Erickson, David

2013-01-01

Kaposi's sarcoma (KS) is an infectious cancer occurring most commonly in human immunodeficiency virus (HIV) positive patients and in endemic regions, such as Sub-Saharan Africa, where KS is among the top four most prevalent cancers. The cause of KS is the Kaposi's sarcoma-associated herpesvirus (KSHV, also called HHV-8), an oncogenic herpesvirus that while routinely diagnosed in developed nations, provides challenges to developing world medical providers and point-of-care detection. A major challenge in the diagnosis of KS is the existence of a number of other diseases with similar clinical presentation and histopathological features, requiring the detection of KSHV in a biopsy sample. In this work we develop an answer to this challenge by creating a multiplexed one-pot detection system for KSHV DNA and DNA from a frequently confounding disease, bacillary angiomatosis. Gold and silver nanoparticle aggregation reactions are tuned for each target and a multi-color change system is developed capable of detecting both targets down to levels between 1 nM and 2 nM. The system developed here could later be integrated with microfluidic sample processing to create a final device capable of solving the two major challenges in point-of-care KS detection.

Pomalidomide for Symptomatic Kaposi's Sarcoma in People With and Without HIV Infection: A Phase I/II Study

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Polizzotto, Mark N.; Uldrick, Thomas S.; Wyvill, Kathleen M.; Aleman, Karen; Peer, Cody J.; Bevans, Margaret; Sereti, Irini; Maldarelli, Frank; Whitby, Denise; Marshall, Vickie; Goncalves, Priscila H.; Khetani, Vikram; Figg, William D.; Steinberg, Seth M.; Zeldis, Jerome B.

2016-01-01

Purpose Kaposi's sarcoma (KS) is a multicentric tumor caused by Kaposi's sarcoma–associated herpesvirus. Unmet needs include therapies that are oral, anthracycline sparing, and deliverable in resource-limited settings. We evaluated pomalidomide, an oral immune modulatory agent, in patients with symptomatic KS. Methods The primary objectives were to assess tolerability, pharmacokinetics, and activity. Initial dosage level was 5 mg once per day for 21 days per 28-day cycle, with a de-escalated level of 3 mg if not tolerable, and aspirin 81 mg once per day thromboprophylaxis. HIV-infected patients required controlled viremia with either persistent KS despite 3 months of antiretroviral therapy (ART) or progressive KS despite 2 months of ART. Evaluations included tumor response and health-related quality of life (HRQL). Results Twenty-two patients were treated; 15 (68%) were HIV infected, 17 (77%) had advanced (T1) disease, and 19 (86%) previous KS therapy excluding ART. All were treated with 5 mg because no dose-limiting toxicities occurred. Over 156 cycles, the grade 3/4 adverse events possibly attributable to therapy were neutropenia (23 cycles, 10 patients), infection (1 cycle), and edema (1 cycle). Sixteen patients responded (73%; 95% CI, 50% to 89%): nine of 15 HIV-infected patients (60%; 95% CI, 32% to 84%) and all seven HIV-uninfected patients (100%; 95% CI, 59% to 100%). Median time to response was 4 weeks (range, 4 to 36 weeks). HRQL showed no impairment during therapy and improved satisfaction with appearance at end therapy (P = .03). Significant increases in CD4+ and CD8+ cells were seen in patients with and without HIV, together with a transient increase in Kaposi's sarcoma–associated herpesvirus viral load at week 4 (P = .05). Conclusion Pomalidomide is well tolerated and active in KS regardless of HIV status. Responses were rapid, with improved self-reported outcomes, and occurred in advanced and heavily pretreated disease. Correlative studies support

Inhibition of GABAergic Neurotransmission by HIV-1 Tat and Opioid Treatment in the Striatum Involves ?-Opioid Receptors

OpenAIRE

Xu, Changqing; Fitting, Sylvia

2016-01-01

Due to combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is considered a chronic disease with high prevalence of mild forms of neurocognitive impairments, also referred to as HIV-associated neurocognitive disorders (HAND). Although opiate drug use can exacerbate HIV-1 Tat-induced neuronal damage, it remains unknown how and to what extent opioids interact with Tat on the GABAergic system. We conducted whole-cell recordings in mouse striatal slices and examined...

Palatal Actinomycosis and Kaposi Sarcoma in an HIV-Infected Subject with Disseminated Mycobacterium avium-intracellulare Infection

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Yuria Ablanedo-Terrazas

2012-01-01

Full Text Available Actinomyces and Mycobacterium avium-intracellulare are facultative intracellular organisms, members of the bacterial order actinomycetales. Although Actinomyces can behave as copathogen when anatomic barriers are compromised, its coinfection with Mycobacterium avium-intracellulare has not previously been reported. We present the first reported case of palatal actinomycosis co-infection with disseminated MAC, in an HIV-infected subject with Kaposi sarcoma and diabetes. We discuss the pathogenesis of the complex condition of this subject.

Ireland's Preparedness for Nuclear Emergencies - Development of a Handbook for the Technical Assessment Team (TAT)

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Organo, Catherine; Smith, Kilian; Smith, Veronica; O' Connor, Collette; McMahon, Ciara [Environmental Protection Agency, Office of Radiological Protection, 3 Clonskeagh Square, Clonskeagh Road, Dublin 14 (Ireland)

2014-07-01

In Ireland, the National Emergency Plan for Nuclear Accidents (NEPNA) provides a framework for the national response to a large scale nuclear incident with the potential to contaminate a wide area. Under this plan, the Radiological Protection Institute of Ireland (RPII) has been assigned a major role covering a range of responsibilities. One of these is to carry out a radiological assessment of the situation. The RPII Technical Assessment Team (TAT) is activated in such circumstances, and is tasked with delivering this radiological assessment. Broadly speaking, the role of the TAT is to gather together all of the available information relevant to the event and to use this information to assess the radiological consequences for Ireland so as to formulate advice regarding subsequent precautionary actions, particular regarding food controls and preventive measures for the agricultural sectors. The TAT could also be asked to assess the radiological consequences for Irish citizens abroad, living in any location potentially affected by radioactive contamination. The arrangements for the running of the TAT are set out in the TAT handbook. This document has been under developed for a number of years and is now undergoing a major revision. A large number of additional documents have been developed since the original draft version was produced and, in conjunction with RPII's experience in responding to real events and exercises these need to be integrated and taken into account to produce an updated version. This poster will explain the rationale behind the review; it will outline the planning process and describe the various implementation phases, from the inventory of the existing documents and procedures to the integration of the new information that need to be considered during the response to an emergency. An outline of some of the key procedures being developed will also be given. (authors)

Functional analysis of human aromatic amino acid transporter MCT10/TAT1 using the yeast Saccharomyces cerevisiae.

Science.gov (United States)

Uemura, Satoshi; Mochizuki, Takahiro; Kurosaka, Goyu; Hashimoto, Takanori; Masukawa, Yuki; Abe, Fumiyoshi

2017-10-01

Tryptophan is an essential amino acid in humans and an important serotonin and melatonin precursor. Monocarboxylate transporter MCT10 is a member of the SLC16A family proteins that mediates low-affinity tryptophan transport across basolateral membranes of kidney, small intestine, and liver epithelial cells, although the precise transport mechanism remains unclear. Here we developed a simple functional assay to analyze tryptophan transport by human MCT10 using a deletion mutant for the high-affinity tryptophan permease Tat2 in Saccharomyces cerevisiae. tat2Δtrp1 cells are defective in growth in YPD medium because tyrosine present in the medium competes for the low-affinity tryptophan permease Tat1 with tryptophan. MCT10 appeared to allow growth of tat2Δtrp1 cells in YPD medium, and accumulate in cells deficient for Rsp5 ubiquitin ligase. These results suggest that MCT10 is functional in yeast, and is subject to ubiquitin-dependent quality control. Whereas growth of Tat2-expressing cells was significantly impaired by neutral pH, that of MCT10-expressing cells was nearly unaffected. This property is consistent with the transport mechanism of MCT10 via facilitated diffusion without a need for pH gradient across the plasma membrane. Single-nucleotide polymorphisms (SNPs) are known to occur in the human MCT10 coding region. Among eight SNP amino acid changes in MCT10, the N81K mutation completely abrogated tryptophan import without any abnormalities in the expression or localization. In the MCT10 modeled structure, N81 appeared to protrude into the putative trajectory of tryptophan. Plasma membrane localization of MCT10 and the variant proteins was also verified in human embryonic kidney 293T cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative analysis of twin-arginine (Tat)-dependent protein secretion of a heterologous model protein (GFP) in three different Gram-positive bacteria

NARCIS (Netherlands)

Meissner, Daniel; Vollstedt, Angela; van Dijl, Jan Maarten; Freudl, Roland

In contrast to the general protein secretion (Sec) system, the twin-arginine translocation (Tat) export pathway allows the translocation of proteins across the bacterial plasma membrane in a fully folded conformation. Due to this feature, the Tat pathway provides an attractive alternative to the

Cloning, Expression and Purification of the Recombinant HIV-1 Tat-Nef Fusion Protein in Prokaryotic Expression System

OpenAIRE

Somayeh Kadkhodayan; Shiva Irani; Seyed Mehdi Sadat; Fatemeh Fotouhi; Azam Bolhassani

2016-01-01

Abstract Background: Nef is one of the HIV-1 critical proteins, because it is essential for viral replication and AIDS disease progression and induction of immune response against it can partially inhibit viral infection. Moreover, a domain of the HIV-1 Trans-Activator of Transcription (Tat, 48-60 aa) could act as a cell penetrating peptide (CPP). In current study, cloning and expression of Tat-Nef fusion protein was performed in E. coli for the first time. The protein expression was confi...

Interplay between Structure and Charge as a Key to Allosteric Modulation of Human 20S Proteasome by the Basic Fragment of HIV-1 Tat Protein.

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Przemysław Karpowicz

Full Text Available The proteasome is a giant protease responsible for degradation of the majority of cytosolic proteins. Competitive inhibitors of the proteasome are used against aggressive blood cancers. However, broadening the use of proteasome-targeting drugs requires new mechanistic approaches to the enzyme's inhibition. In our previous studies we described Tat1 peptide, an allosteric inhibitor of the proteasome derived from a fragment of the basic domain of HIV-Tat1 protein. Here, we attempted to dissect the structural determinants of the proteasome inhibition by Tat1. Single- and multiple- alanine walking scans were performed. Tat1 analogs with stabilized beta-turn conformation at positions 4-5 and 8-9, pointed out by the molecular dynamics modeling and the alanine scan, were synthesized. Structure of Tat1 analogs were analyzed by circular dichroism, Fourier transform infrared and nuclear magnetic resonance spectroscopy studies, supplemented by molecular dynamics simulations. Biological activity tests and structural studies revealed that high flexibility and exposed positive charge are hallmarks of Tat1 peptide. Interestingly, stabilization of a beta-turn at the 8-9 position was necessary to significantly improve the inhibitory potency.

RNA-Seq of Kaposi's sarcoma reveals alterations in glucose and lipid metabolism.

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For Yue Tso

2018-01-01

Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is the etiologic agent of Kaposi's sarcoma (KS. It is endemic in a number of sub-Saharan African countries with infection rate of >50%. The high prevalence of HIV-1 coupled with late presentation of advanced cancer staging make KS the leading cancer in the region with poor prognosis and high mortality. Disease markers and cellular functions associated with KS tumorigenesis remain ill-defined. Several studies have attempted to investigate changes of the gene profile with in vitro infection of monoculture models, which are not likely to reflect the cellular complexity of the in vivo lesion environment. Our approach is to characterize and compare the gene expression profile in KS lesions versus non-cancer tissues from the same individual. Such comparisons could identify pathways critical for KS formation and maintenance. This is the first study that utilized high throughput RNA-seq to characterize the viral and cellular transcriptome in tumor and non-cancer biopsies of African epidemic KS patients. These patients were treated anti-retroviral therapy with undetectable HIV-1 plasma viral load. We found remarkable variability in the viral transcriptome among these patients, with viral latency and immune modulation genes most abundantly expressed. The presence of KSHV also significantly affected the cellular transcriptome profile. Specifically, genes involved in lipid and glucose metabolism disorder pathways were substantially affected. Moreover, infiltration of immune cells into the tumor did not prevent KS formation, suggesting some functional deficits of these cells. Lastly, we found only minimal overlaps between our in vivo cellular transcriptome dataset with those from in vitro studies, reflecting the limitation of in vitro models in representing tumor lesions. These findings could lead to the identification of diagnostic and therapeutic markers for KS, and will provide bases for further mechanistic

Kaposi's sarcoma-associated herpesvirus-encoded LANA associates with glucocorticoid receptor and enhances its transcriptional activities

International Nuclear Information System (INIS)

Togi, Sumihito; Nakasuji, Misa; Muromoto, Ryuta; Ikeda, Osamu; Okabe, Kanako; Kitai, Yuichi; Kon, Shigeyuki; Oritani, Kenji; Matsuda, Tadashi

2015-01-01

Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA), which interacts with cellular proteins, plays a central role in modification of viral and/or cellular gene expression. Here, we show that LANA associates with glucocorticoid receptor (GR), and that LANA enhances the transcriptional activity of GR. Co-immunoprecipitation revealed a physical interaction between LANA and GR in transiently transfected 293T and HeLa cells. In human B-lymphoma cells, LANA overexpression enhanced GR activity and cell growth suppression following glucocorticoid stimulation. Furthermore, confocal microscopy showed that activated GR was bound to LANA and accumulated in the nucleus, leading to an increase in binding of activated GR to the glucocorticoid response element of target genes. Taken together, KSHV-derived LANA acts as a transcriptional co-activator of GR. Our results might suggest a careful use of glucocorticoids in the treatment of patients with KSHV-related malignancies such as Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. - Highlights: • KSHV-LANA enhances the transcriptional activity of GR in 293T and HeLa cells. • KSHV-LANA physically associates with GR. • KSHV-LANA enhances GR activation and cell growth suppression in human B-lymphocytes. • KSHV-LANA influences the nuclear retention and DNA binding activity of GR

Kaposi's sarcoma-associated herpesvirus-encoded LANA associates with glucocorticoid receptor and enhances its transcriptional activities

Energy Technology Data Exchange (ETDEWEB)

Togi, Sumihito; Nakasuji, Misa; Muromoto, Ryuta; Ikeda, Osamu; Okabe, Kanako; Kitai, Yuichi; Kon, Shigeyuki [Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo 060-0812 (Japan); Oritani, Kenji [Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Matsuda, Tadashi, E-mail: tmatsuda@pharm.hokudai.ac.jp [Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo 060-0812 (Japan)

2015-07-31

Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA), which interacts with cellular proteins, plays a central role in modification of viral and/or cellular gene expression. Here, we show that LANA associates with glucocorticoid receptor (GR), and that LANA enhances the transcriptional activity of GR. Co-immunoprecipitation revealed a physical interaction between LANA and GR in transiently transfected 293T and HeLa cells. In human B-lymphoma cells, LANA overexpression enhanced GR activity and cell growth suppression following glucocorticoid stimulation. Furthermore, confocal microscopy showed that activated GR was bound to LANA and accumulated in the nucleus, leading to an increase in binding of activated GR to the glucocorticoid response element of target genes. Taken together, KSHV-derived LANA acts as a transcriptional co-activator of GR. Our results might suggest a careful use of glucocorticoids in the treatment of patients with KSHV-related malignancies such as Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. - Highlights: • KSHV-LANA enhances the transcriptional activity of GR in 293T and HeLa cells. • KSHV-LANA physically associates with GR. • KSHV-LANA enhances GR activation and cell growth suppression in human B-lymphocytes. • KSHV-LANA influences the nuclear retention and DNA binding activity of GR.

Chemical Composition of Essential Oils from Thymus vulgaris, Cymbopogon citratus, and Rosmarinus officinalis, and Their Effects on the HIV-1 Tat Protein Function.

Science.gov (United States)

Feriotto, Giordana; Marchetti, Nicola; Costa, Valentina; Beninati, Simone; Tagliati, Federico; Mischiati, Carlo

2018-02-01

New drugs would be beneficial to fight resistant HIV strains, in particular those capable of interfering with essential viral functions other than those targeted by highly active antiretroviral therapy drugs. Despite the central role played by Tat protein in HIV transcription, a search for vegetable extracts able to hamper this important viral function was never carried out. In this work, we evaluated the chemical composition and possible interference of essential oil from Thymus vulgaris, Cananga odorata, Cymbopogon citratus, and Rosmarinus officinalis with the Tat/TAR-RNA interaction and with Tat-induced HIV-1 LTR transcription. GC/MS Analysis demonstrated the biodiversity of herbal species translated into essential oils composed of different blends of terpenes. In all of them, 4 - 6 constituents represent from 81.63% to 95.19% of the total terpenes. Essential oils of Thymus vulgaris, Cymbopogon citratus, and Rosmarinus officinalis were active in interfering with Tat functions, encouraging further studies to identify single terpenes responsible for the antiviral activity. In view of the quite different composition of these essential oils, we concluded that their interference on Tat function depends on specific terpene or a characteristic blend. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

Sarcoma de Kaposi en una paciente de Santo Tomé y Príncipe

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Melba Elers Bandera

2013-10-01

Full Text Available Se presenta el caso clínico de una paciente que fue asistida en el Hospital General "Dr. Ayres Menezes" de la República Democrática de Santo Tomé y Príncipe, por presentar fiebre y lesiones en la piel, a la cual se le diagnosticó sarcoma de Kaposi asociado a la infección por el virus de inmunodeficiencia humana/sida. La evolución tórpida y el estadio tan avanzado de la enfermedad, así como la resistencia a los fármacos antirretrovirales, ocasionaron la muerte de la fémina

Aqueous immersion technique for the irradiation with photons Kaposi's sarcoma multiple foot and ankle

International Nuclear Information System (INIS)

Velazquez Miranda, S.; Munoz Carmona, D. M.; Ortyiz Seidel, M.; Gomez-Millan Barrachina, J.; Delgado Gil, M. M.; Ortega Rodriguez, M. J.; Dominguez Rodriguez, M.; Marquez Garcia Salazar, M.; Bayo Lozano, E.

2011-01-01

Classic Kaposi sarcoma presents as asymptomatic red-violaceus plaques, usually on the legs below the knees, ankles and soles preferentially. When the disease is spread on the skin preferential treatment is radiation therapy at low doses. Homogeneous irradiation of the various lesions could be very complex due to the irregular geometry of the feet, interdigital lesions on different planes. To overcome this problem, and in the case of disseminated disease and low doses, we propose the technique of dipping the tip in Cuba expanded polystyrene filled with saline with a methacrylate plate 2 cm in depth and irradiation with parallel opposed fields.

PSD-95 uncoupling from NMDA receptors by Tat-N-dimer ameliorates neuronal depolarisation in cortical spreading depression

DEFF Research Database (Denmark)

Kucharz, Krzysztof; Søndergaard Rasmussen, Ida; Bach, Anders

2017-01-01

during the first hour after i.v. injection. The Tat-N-dimer suppressed stimulation-evoked synaptic activity by 2-20%, while cortical blood flow and cerebral oxygen metabolic (CMRO2) responses were preserved. During cortical spreading depression, the Tat-N-dimer reduced the average amplitude...... depression on cortical blood flow and CMRO2 We suggest that uncoupling of PSD-95 from NMDA receptors reduces overall neuronal excitability and the amplitude of the spreading depolarisation wave. These findings may be of interest for understanding the neuroprotective effects of the nNOS/PSD-95 uncoupling...

On the role of the second coding exon of the HIV-1 Tat protein in virus replication and MHC class I downregulation

NARCIS (Netherlands)

Verhoef, K.; Bauer, M.; Meyerhans, A.; Berkhout, B.

1998-01-01

Tat is an essential protein of human immunodeficiency virus type 1 (HIV-1) and activates transcription from the viral long terminal repeat (LTR) promoter. The tat gene is composed of two coding exons of which the first, corresponding to the N-terminal 72 amino acid residues, has been reported to be

"cART intensification by the HIV-1 Tat B clade vaccine: progress to phase III efficacy studies".

Science.gov (United States)

Cafaro, Aurelio; Sgadari, Cecilia; Picconi, Orietta; Tripiciano, Antonella; Moretti, Sonia; Francavilla, Vittorio; Pavone Cossut, Maria Rosaria; Buttò, Stefano; Cozzone, Giovanni; Ensoli, Fabrizio; Monini, Paolo; Ensoli, Barbara

2018-02-01

In spite of its success at suppressing HIV replication, combination antiretroviral therapy (cART) only partially reduces immune dysregulation and loss of immune functions. These cART-unmet needs appear to be due to persistent virus replication and cell-to-cell transmission in reservoirs, and are causes of increased patients' morbidity and mortality. Up to now, therapeutic interventions aimed at cART-intensification by attacking the virus reservoir have failed. Areas covered: We briefly review the rationale and clinical development of Tat therapeutic vaccine in cART-treated subjects in Italy and South Africa (SA). Vaccination with clade-B Tat induced cross-clade neutralizing antibodies, immune restoration, including CD4 + T cell increase particularly in low immunological responders, and reduction of proviral DNA. Phase III efficacy trials in SA are planned both in adult and pediatric populations. Expert commentary: We propose the Tat therapeutic vaccine as a pathogenesis-driven intervention that effectively intensifies cART and may lead to a functional cure and provide new perspectives for prevention and virus eradication strategies.

Evaluation of the internalization kinetics of the radiopharmaceutical 99mTc-N2S2-Tat(49-57)Lys3-Bn with diagnostic purposes, using comet assay

International Nuclear Information System (INIS)

Luna G, M. A.

2011-01-01

Gastrin-rea leasing peptide receptors (GRP-r) are over expressed in breast and prostate cancer cells. Bombesin (Bn) binds specifically and strongly to GRP-r and this is the base for to label the Bn with radionuclides by gamma rays. Tat (49-57) is a peptide that across the cell membrane easily so that, when it is conjugated to different proteins, it can works as a Trojan horse, facilitating the drug internalization to the cells. The radiopharmaceutical 99m Tc-N 2 S 2 -Tat(49-57)-Lys 3 -Bn was prepared for diagnosis and therapy at early stage of breast cancer. The objective of this study was to determine the role of Tat in the internalization kinetics of radiopharmaceuticals measured by DNA damage induced by means of comet assay. Human lymphocytes were treated with the following protocols: a) Tat-Bn, b) 99m Tc-Bn, or c) 99m Tc-N 2 S 2 -Tat(49-57)-Lys 3 -Bn, also an untreated group was conformed. The internalization was evaluated at 0, 5, 10, 15, 30 and 60 min after exposure with three repetitions each one, and for radiopharmaceuticals with 2.9, 6.6, 9.0 and 14.8 MBq activities. DNA damage was scored in 100 cells per time and treatment, as tail length and tail moment. A Kruskal-Wallis variance analysis with p≤ 0.05 was applied for comparison between treatments. The results showed that the damage caused by 99m Tc-N 2 S 2 -Tat(49-57)-Lys 3 -Bn is significantly higher than that caused by 99m Tc-Bn and Tat-Bn, showing that Tat favors the internalization of the radiopharmaceutical. (Author)

Aqueous immersion technique for the irradiation with photons Kaposi's sarcoma multiple foot and ankle; Tecnica de inmersion acuosa para la irradiacion con fotones del sarcoma de Kaposi multiple en pies y tobillos

Energy Technology Data Exchange (ETDEWEB)

Velazquez Miranda, S.; Munoz Carmona, D. M.; Ortyiz Seidel, M.; Gomez-Millan Barrachina, J.; Delgado Gil, M. M.; Ortega Rodriguez, M. J.; Dominguez Rodriguez, M.; Marquez Garcia Salazar, M.; Bayo Lozano, E.

2011-07-01

Classic Kaposi sarcoma presents as asymptomatic red-violaceus plaques, usually on the legs below the knees, ankles and soles preferentially. When the disease is spread on the skin preferential treatment is radiation therapy at low doses. Homogeneous irradiation of the various lesions could be very complex due to the irregular geometry of the feet, interdigital lesions on different planes. To overcome this problem, and in the case of disseminated disease and low doses, we propose the technique of dipping the tip in Cuba expanded polystyrene filled with saline with a methacrylate plate 2 cm in depth and irradiation with parallel opposed fields.

Local measures in HIV-associated Kaposi's sarcoma - importance of radiation therapy

International Nuclear Information System (INIS)

Plettenberg, A.; Meigel, W.; Janik, I.; Kolb, H.

1991-01-01

In 23 patients with HIV-associated Kaposi's sarcoma 53 tumor lesions were treated with fractional radiotherapy. Indication for the radiotherapy were mostly cosmetic reasons in stigmatising tumors, but also in several cases pain, oedema or functional deficits as a result of the tumor lesions. 21 patients received orthovoltage irradiation, the remaining four patients were treated with telecobalt therapy. A complete response was observed in 17%, a partial response in 76% and unchanged lesions in 4%. In two cases (4%), both were treated with telecobalt-therapy by large tumor masses, there occurred a further tumor progression inspite of the radiotherapy. In ten lesions, all with partial remission, we later observed a repeated tumor progression. Important side effects were signs of inflammation as mucositis and edema or hyperpigmentation. The occurrence of acute side effects can be reduced by fractionating of the radiotherapy. (orig.) [de

Kaposi sarcoma and lymphadenopathy syndrome: limitations of abdominal CT in acquired immunodeficiency syndrome

International Nuclear Information System (INIS)

Moon, K.L. Jr.; Federle, M.P.; Abrams, D.I.; Volberding, P.; Lewis, B.J.

1984-01-01

Abdominal computed tomography (CT) was performed in 31 patients with Kaposi sarcoma (KS) related to acquired immunodeficiency syndrome (AIDS), three patients with classic KS, and 12 patients with the newly described lymphadenopathy syndrome (LNS). The frequency, distribution, and appearance of lymphadenopathy and splenomegaly were similar in the AIDS-related KS and LNS groups. Rectal and perirectal disease was identified in 86% of homosexual men studied; rectal KS could not be distinguished from proctitis on CT criteria alone. No CT abnormalities were seen in patients with classic KS. The CT demonstration of retroperitoneal, mesenteric, or pelvic adenopathy or of rectal or perirectal disease in patients with AIDS-related KS is not necessarily indicative of widespread involvement with the disease

Parasite infection is associated with Kaposi's sarcoma associated herpesvirus (KSHV in Ugandan women

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Ndibazza Juliet

2011-09-01

Full Text Available Abstract Background Immune modulation by parasites may influence susceptibility to bacteria and viruses. We examined the association between current parasite infections, HIV and syphilis (measured in blood or stool samples using standard methods and antibodies against Kaposi's sarcoma herpesvirus (KSHV, measured by ELISA, in 1915 stored plasma samples from pregnant women in Entebbe, Uganda. Results Seroprevalence of KSHV was higher in women with malaria parasitaemia (73% vs 60% p = 0.01, hookworm (67% vs 56% p = 0.001 and Mansonella perstans (69% vs 59% p = 0.05; seroprevalence increased with increasing intensity of hookworm infection (p Conclusions Specific parasite infections are associated with presence of antibodies against KSHV, perhaps mediated via their effect on immune function.

Late diagnosis of positive HIV serology in pregnancy incidentally discovered by the widespread appearance of Kaposi's sarcoma.

Science.gov (United States)

Mian, D B; Itoua, C; Angoi, V; Gbary, E; Nguessan, K L P; Iloki, H; Boni, S

2015-01-01

The authors report a case of Kaposi's sarcoma (KS) found in a pregnant woman. On discovery, the condition had spread throughout her body as is characteristic in some cases of individuals with HIV-positive serology. She was unaware of her HIV positive status. Her HIV infection had been diagnosed at the same time as KS at her last prenatal consultation. The newborn was delivered by an uncomplicated cesarean section. Appropriate treatment and multidisciplinary management after childbirth resulted in complete remission.

DmsD, a Tat system specific chaperone, interacts with other general chaperones and proteins involved in the molybdenum cofactor biosynthesis

OpenAIRE

Li, Haiming; Chang, Limei; Howell, Jenika M.; Turner, Raymond J.

2010-01-01

Many bacterial oxidoreductases depend on the Tat translocase for correct cell localization. Substrates for the Tat translocase possess twin-arginine leaders. System specific chaperones or redox enzyme maturation proteins (REMPs) are a group of proteins implicated in oxidoreductase maturation. DmsD is a REMP discovered in Escherichia coli, which interacts with the twin-arginine leader sequence of DmsA, the catalytic subunit of DMSO reductase. In this study, we identified several potential inte...

Um caso de organização limite da personalidade: Um estudo comparativo da projeção no Rorschach e no TAT

OpenAIRE

Fernandez, Isabel Bernardo

1994-01-01

Apresenta-se um estudo comparativo dos protocolos do Rorschach e do TAT de uma jovem de quase 20 anos, diagnosticada como organização limite da personalidade, procurando mostrar como ambos se elucidam entre o Rorschach e o TAT.e completam num esclarecimento relativo aos «como» e

Evaluation of the internalization kinetics of the radiopharmaceutical {sup 99m}Tc-N{sub 2}S{sub 2}-Tat(49-57)Lys{sup 3}-Bn with diagnostic purposes, using comet assay; Evaluacion de la cinetica de internalizacion del radiofarmaco {sup 99m}Tc-N{sub 2}S{sub 2}-TAT(49-57)Lys{sup 3}-BN con fines diagnosticos, empleando ensayo cometa

Energy Technology Data Exchange (ETDEWEB)

Luna G, M. A.

2011-07-01

Gastrin-rea leasing peptide receptors (GRP-r) are over expressed in breast and prostate cancer cells. Bombesin (Bn) binds specifically and strongly to GRP-r and this is the base for to label the Bn with radionuclides by gamma rays. Tat (49-57) is a peptide that across the cell membrane easily so that, when it is conjugated to different proteins, it can works as a Trojan horse, facilitating the drug internalization to the cells. The radiopharmaceutical {sup 99m}Tc-N{sub 2}S{sub 2}-Tat(49-57)-Lys{sup 3}-Bn was prepared for diagnosis and therapy at early stage of breast cancer. The objective of this study was to determine the role of Tat in the internalization kinetics of radiopharmaceuticals measured by DNA damage induced by means of comet assay. Human lymphocytes were treated with the following protocols: a) Tat-Bn, b) {sup 99m}Tc-Bn, or c) {sup 99m}Tc-N{sub 2}S{sub 2}-Tat(49-57)-Lys{sup 3}-Bn, also an untreated group was conformed. The internalization was evaluated at 0, 5, 10, 15, 30 and 60 min after exposure with three repetitions each one, and for radiopharmaceuticals with 2.9, 6.6, 9.0 and 14.8 MBq activities. DNA damage was scored in 100 cells per time and treatment, as tail length and tail moment. A Kruskal-Wallis variance analysis with p{<=} 0.05 was applied for comparison between treatments. The results showed that the damage caused by {sup 99m}Tc-N{sub 2}S{sub 2}-Tat(49-57)-Lys{sup 3}-Bn is significantly higher than that caused by {sup 99m}Tc-Bn and Tat-Bn, showing that Tat favors the internalization of the radiopharmaceutical. (Author)

Development and characterization of chitosan-PEG-TAT nanoparticles for the intracellular delivery of siRNA

Directory of Open Access Journals (Sweden)

Malhotra M

2013-05-01

Full Text Available Meenakshi Malhotra,1 Catherine Tomaro-Duchesneau,1 Shyamali Saha,2 Imen Kahouli,3 Satya Prakash11Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, 2Faculty of Dentistry, 3Department of Experimental Medicine, McGill University, Montreal, QC, CanadaAbstract: Recently, cell-penetrating peptides have been proposed to translocate antibodies, proteins, and other molecules in targeted drug delivery. The proposed study presents the synthesis and characterization of a peptide-based chitosan nanoparticle for small interfering RNA (siRNA delivery, in-vitro. Specifically, the synthesis included polyethylene glycol (PEG, a hydrophilic polymer, and trans-activated transcription (TAT peptide, which were chemically conjugated on the chitosan polymer. The conjugation was achieved using N-Hydroxysuccinimide-PEG-maleimide (heterobifunctional PEG as a cross-linker, with the bifunctional PEG facilitating the amidation reaction through its N-Hydroxysuccinimide group and reacting with the amines on chitosan. At the other end of PEG, the maleimide group was chemically conjugated with the cysteine-modified TAT peptide. The degree of substitution on chitosan with PEG and on PEG with TAT was confirmed using colorimetric assays. The resultant polymer was used to form nanoparticles complexing siRNA, which were then characterized for particle size, morphology, cellular uptake, and cytotoxicity. The nanoparticles were tested in-vitro on mouse neuroblastoma cells (Neuro2a. Particle size and surface charge were characterized and an optimal pH condition and PEG molecular weight were determined to form sterically stable nanoparticles. Results indicate 7.5% of the amines in chitosan polymer were conjugated to the PEG and complete conjugation of TAT peptide was observed on the synthesized PEGylated chitosan polymer. Compared with unmodified chitosan nanoparticles, the nanoparticles formed at pH 6 were

Overproduction of a Model Sec- and Tat-Dependent Secretory Protein Elicits Different Cellular Responses in Streptomyces lividans.

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Sonia Gullón

Full Text Available Streptomyces lividans is considered an efficient host for the secretory production of homologous and heterologous proteins. To identify possible bottlenecks in the protein production process, a comparative transcriptomic approach was adopted to study cellular responses during the overproduction of a Sec-dependent model protein (alpha-amylase and a Tat-dependent model protein (agarase in Streptomyces lividans. The overproduction of the model secretory proteins via the Sec or the Tat route in S. lividans does elicit a different major cell response in the bacterium. The stringent response is a bacterial response to nutrients' depletion, which naturally occurs at late times of the bacterial cell growth. While the induction of the stringent response at the exponential phase of growth may limit overall productivity in the case of the Tat route, the induction of that response does not take place in the case of the Sec route, which comparatively is an advantage in secretory protein production processes. Hence, this study identifies a potential major drawback in the secretory protein production process depending on the secretory route, and provides clues to improving S. lividans as a protein production host.

A Yersinia pestis tat mutant is attenuated in bubonic and small-aerosol pneumonic challenge models of infection but not as attenuated by intranasal challenge.

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Joel Bozue

Full Text Available Bacterial proteins destined for the Tat pathway are folded before crossing the inner membrane and are typically identified by an N-terminal signal peptide containing a twin arginine motif. Translocation by the Tat pathway is dependent on the products of genes which encode proteins possessing the binding site of the signal peptide and mediating the actual translocation event. In the fully virulent CO92 strain of Yersinia pestis, the tatA gene was deleted. The mutant was assayed for loss of virulence through various in vitro and in vivo assays. Deletion of the tatA gene resulted in several consequences for the mutant as compared to wild-type. Cell morphology of the mutant bacteria was altered and demonstrated a more elongated form. In addition, while cultures of the mutant strain were able to produce a biofilm, we observed a loss of adhesion of the mutant biofilm structure compared to the biofilm produced by the wild-type strain. Immuno-electron microscopy revealed a partial disruption of the F1 antigen on the surface of the mutant. The virulence of the ΔtatA mutant was assessed in various murine models of plague. The mutant was severely attenuated in the bubonic model with full virulence restored by complementation with the native gene. After small-particle aerosol challenge in a pneumonic model of infection, the mutant was also shown to be attenuated. In contrast, when mice were challenged intranasally with the mutant, very little difference in the LD50 was observed between wild-type and mutant strains. However, an increased time-to-death and delay in bacterial dissemination was observed in mice infected with the ΔtatA mutant as compared to the parent strain. Collectively, these findings demonstrate an essential role for the Tat pathway in the virulence of Y. pestis in bubonic and small-aerosol pneumonic infection but less important role for intranasal challenge.

Effects of x-rays or aseptic inflammatory reaction on the circadian rythm of tyrosine aminotransferase in mouse liver (TAT activity of mouse liver)

International Nuclear Information System (INIS)

Jungowska-Klin, B.

1979-01-01

The circadian rhythm of tyrosine aminotransferase (TAT) was investigated during 48 hours in the liver of mice subjected to: a/ subcutaneous inflammatory reaction, b/ ionizing radiation. The cyclic changes in the circadian enzyme activity were described with a harmonic function. In relation to the control mice in the experimental mice statistically significant changes were demonstrated in the activity of tyrosine aminotransferase associated with desynchronization of the circadian TAT rhythm, particularly evident in the first hours of the first day of the experiment. The functions of enzyme activity changed in the second 24-hours period showed, both qualitatively and quantitatively, a tendency for a gradual return of normal TAT activity in the 24-hour periods. (author)

HIV-1 Tat affects the programming and functionality of human CD8⁺ T cells by modulating the expression of T-box transcription factors.

Science.gov (United States)

Sforza, Fabio; Nicoli, Francesco; Gallerani, Eleonora; Finessi, Valentina; Reali, Eva; Cafaro, Aurelio; Caputo, Antonella; Ensoli, Barbara; Gavioli, Riccardo

2014-07-31

HIV infection is characterized by several immune dysfunctions of both CD8⁺ and CD4⁺ T cells as hyperactivation, impairment of functionality and expansion of memory T cells. CD8⁺ T-cell dysfunctions have been associated with increased expression of T-bet, Eomesdermin and pro-inflammatory cytokines, and with down-regulation of CD127. The HIV-1 trans-activator of transcription (Tat) protein, which is released by infected cells and detected in tissues of HIV-positive individuals, is known to contribute to the dysregulation of CD4⁺ T cells; however, its effects on CD8⁺ T cells have not been investigated. Thus, in this study, we sought to address whether Tat may affect CD8⁺ T-cell functionality and programming. CD8⁺ T cells were activated by T-cell receptor engagement in the presence or absence of Tat. Cytokine production, killing capacity, surface phenotype and expression of transcription factors important for T-cell programming were evaluated. Tat favors the secretion of interleukin-2, interferon-γ and granzyme B in CD8⁺ T cells. Behind this functional modulation we observed that Tat increases the expression of T-bet, Eomesdermin, Blimp-1, Bcl-6 and Bcl-2 in activated but not in unstimulated CD8⁺ T lymphocytes. This effect is associated with the down-regulation of CD127 and the up-regulation of CD27. Tat deeply alters the programming and functionality of CD8⁺ T lymphocytes.

Mesenchymal-to-endothelial transition in Kaposi sarcoma: a histogenetic hypothesis based on a case series and literature review.

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Simona Gurzu

Full Text Available OBJECTIVES: Although several studies have been conducted regarding Kaposi sarcoma (KS, its histogenesis still remains to be elucidated. The aim of our study was to analyze the immunophenotype of Kaposi sarcoma and to present a hypothesis about the histogenesis of this tumor, based on a case series and a review of relevant literature. METHODS: In 15 cases of KSs diagnosed during 2000-2011, the clinicopathological features were correlated with the immunoexpression of c-Kit, SMA, CD34, CD31, vascular endothelial growth factor (VEGF, COX-2, c-KIT, smooth muscle antigen (SMA, and stem cell surface marker CD105. RESULTS: Both CD105 and c-KIT rate of the spindle-shaped tumor cell positivity increased in parallel to the pathological stage. All cases displayed CD105 and weak c-KIT positivity in the endothelial cells. SMA, VEGF, and COX-2 were focally expressed in all cases. CD34 marked both endothelium and spindle-shaped tumor cells. No c-KIT expression was noticed in KS of the internal organs. CONCLUSIONS: KS seems to be a variant of myofibroblastic tumors that originates from the viral modified pluripotent mesenchymal cells of the connective tissue transformed in spindle-shaped KS cells, followed by a mesenchymal-endothelial transition and a myofibroblastic-like differentiation. This paper mailnly showed that KS cannot be considered a pure vascular tumor.

Les réserves extractivistes, état des lieux

OpenAIRE

Aubertin, Catherine

2014-01-01

La lutte des seringueiros a popularisé la notion de réserves extractivistes. Au départ calquée sur le modèle de la réserve indigène, la réserve extractiviste devait apporter une solution foncière aux conflits avec les patrons en garantissant, grâce à des expropriations menées par l’État, un droit d’usage collectif aux seringueiros et le maintien de leur outil de production, la forêt. L’histoire des réserves extractivistes est significative des modifications politiques enregistrées ces dix der...

Novel PI3K/Akt Inhibitors Screened by the Cytoprotective Function of Human Immunodeficiency Virus Type 1 Tat

Science.gov (United States)

Kim, Dong-Hyun; Kim, Baek

2011-01-01

The PI3K/Akt pathway regulates various stress-related cellular responses such as cell survival, cell proliferation, metabolism and protein synthesis. Many cancer cell types display the activation of this pathway, and compounds inhibiting this cell survival pathway have been extensively evaluated as anti-cancer agents. In addition to cancers, several human viruses, such as HTLV, HPV, HCV and HIV-1, also modulate this pathway, presumably in order to extend the life span of the infected target cells for productive viral replication. The expression of HIV-1 Tat protein exhibited the cytoprotective effect in macrophages and a human microglial cell line by inhibiting the negative regulator of this pathway, PTEN. This cytoprotective effect of HIV-1 appears to contribute to the long-term survival and persistent HIV-1 production in human macrophage reservoirs. In this study we exploited the PI3K/Akt dependent cytoprotective effect of Tat-expressing CHME5 cells. We screened a collection of compounds known to modulate inflammation, and identified three novel compounds: Lancemaside A, Compound K and Arctigenin that abolished the cytoprotective phenotype of Tat-expressing CHME5 cells. All three compounds antagonized the kinase activity of Akt. Further detailed signaling studies revealed that each of these three compounds targeted different steps of the PI3K/Akt pathway. Arctigenin regulates the upstream PI3K enzyme from converting PIP2 to PIP3. Lancemaside A1 inhibited the movement of Akt to the plasma membrane, a critical step for Akt activation. Compound K inhibited Akt phosphorylation. This study supports that Tat-expressing CHME5 cells are an effective model system for screening novel PI3K/Akt inhibitors. PMID:21765914

Novel PI3K/Akt inhibitors screened by the cytoprotective function of human immunodeficiency virus type 1 Tat.

Directory of Open Access Journals (Sweden)

Yuri Kim

Full Text Available The PI3K/Akt pathway regulates various stress-related cellular responses such as cell survival, cell proliferation, metabolism and protein synthesis. Many cancer cell types display the activation of this pathway, and compounds inhibiting this cell survival pathway have been extensively evaluated as anti-cancer agents. In addition to cancers, several human viruses, such as HTLV, HPV, HCV and HIV-1, also modulate this pathway, presumably in order to extend the life span of the infected target cells for productive viral replication. The expression of HIV-1 Tat protein exhibited the cytoprotective effect in macrophages and a human microglial cell line by inhibiting the negative regulator of this pathway, PTEN. This cytoprotective effect of HIV-1 appears to contribute to the long-term survival and persistent HIV-1 production in human macrophage reservoirs. In this study we exploited the PI3K/Akt dependent cytoprotective effect of Tat-expressing CHME5 cells. We screened a collection of compounds known to modulate inflammation, and identified three novel compounds: Lancemaside A, Compound K and Arctigenin that abolished the cytoprotective phenotype of Tat-expressing CHME5 cells. All three compounds antagonized the kinase activity of Akt. Further detailed signaling studies revealed that each of these three compounds targeted different steps of the PI3K/Akt pathway. Arctigenin regulates the upstream PI3K enzyme from converting PIP2 to PIP3. Lancemaside A1 inhibited the movement of Akt to the plasma membrane, a critical step for Akt activation. Compound K inhibited Akt phosphorylation. This study supports that Tat-expressing CHME5 cells are an effective model system for screening novel PI3K/Akt inhibitors.

La digestion anaérobie des boues de stations d'épuration urbaines :état des lieux - état de l'art

OpenAIRE

Reverdy, A.L; Baudez, J.C.; Dieudé-Fauvel, E.

2011-01-01

/ Avec le protocole de Kyoto et le Grenelle de l'environnement, les politiques actuelles prônent le développement des énergies renouvelables. La digestion anaérobie des boues de stations d'épuration urbaines est un procédé permettant de répondre à cette exigence. L'étude présentée dans ce rapport offre dans un premier temps un descriptif du procédé de méthanisation. Dans une deuxième partie, un état des lieux de la digestion anaérobie des boues d'épuration urbaines est réalisé en France...

La gouvernance de la sécurité dans les États faibles et défaillants The Governance of Security in Weak and Failing State

OpenAIRE

Samuel Tanner; Benoît Dupont; Peter Grabosky; Clifford Shearing

2009-01-01

Cet article vise à identifier des moyens permettant le renforcement des mécanismes de contrôle social et de résolution des conflits dans les États faibles et défaillants. Après avoir examiné la gouvernance de la sécurité telle qu’elle se développe dans les États forts, nous montrons que certaines configurations institutionnelles peuvent être transposées dans un contexte d’État faible, où les institutions étatiques en charge de la sécurité sont défaillantes ou inexistantes. Nous identifions de...

Design and biological evaluation of 99mTc-N2S2-Tat(49–57)-c(RGDyK): A hybrid radiopharmaceutical for tumors expressing α(v)β(3) integrins

International Nuclear Information System (INIS)

Ocampo-García, Blanca E.; Santos-Cuevas, Clara L.; De León-Rodríguez, Luis M.; García-Becerra, Rocío; Ordaz-Rosado, David; Luna-Guitiérrez, Myrna A.; Jiménez-Mancilla, Nallely P.; Romero-Piña, Mario E.; Ferro-Flores, Guillermina

2013-01-01

The α(ν)β(3) integrin is over-expressed in the tumor neovasculature and the tumor cells of glioblastomas. The HIV Tat-derived peptide has been used to deliver various cargos into cells. The aim of this research was to synthesize and assess the in vitro and in vivo uptake of 99m Tc-N 2 S 2 -Tat(49–57)-c(RGDyK) ( 99m Tc-Tat-RGD) in α(ν)β(3) integrin positive cancer cells and compare it to that of a conventional 99m Tc-RGD peptide ( 99m Tc-EDDA/HYNIC-E-[c(RGDfK)] 2 ). Methods: The c(RGDyK) peptide was conjugated to a maleimidopropionyl (MP) moiety through Lys, and the MP group was used as the branch position to form a thioether with the Cys 12 side chain of the Tat(49–57)-spacer-N 2 S 2 peptide. 99m Tc-Tat-RGD was prepared, and stability studies were carried out by size exclusion HPLC analyses in human serum. The in vitro affinity for α(v)β(3) integrin was determined by a competitive binding assay. In vitro internalization was determined using glioblastoma C6 cells. Biodistribution studies were accomplished in athymic mice with C6 induced tumors that had blocked and unblocked receptors. Images were obtained using a micro-SPECT/CT. Results: 99m Tc-Tat-RGD was obtained with a radiochemical purity higher than 95%, as determined by radio-HPLC and ITLC-SG analyses. Protein binding was 15.7% for 99m Tc-Tat-RGD and 5.6% for 99m Tc-RGD. The IC 50 values were 6.7 nM ( 99m Tc-Tat-RGD) and 4.6 nM ( 99m Tc-RGD). Internalization in C6 cells was higher in 99m Tc-Tat-RGD (37.5%) than in 99m Tc-RGD (10%). Biodistribution studies and in vivo micro-SPECT/CT images in mice showed higher tumor uptake for 99m Tc-Tat-RGD (6.98% ± 1.34% ID/g at 3 h) than that of 99m Tc-RGD (3.72% ± 0.52% ID/g at 3 h) with specific recognition for α(v)β(3) integrins. Conclusions: Because of the significant cell internalization (Auger and internal conversion electrons) and specific recognition for α(v)β(3) integrins, the hybrid 99m Tc-N 2 S 2 -Tat(49–57)-c(RGDyK) radiopharmaceutical is

The Politics of Religion in the United States Manifestations politiques de la religion aux États-Unis

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Josef Braml

2011-04-01

Full Text Available Aux États-Unis, les attitudes religieuses ont plus d’influence sur les choix politiques que dans n’importe quelle autre démocratie occidentale. L’engagement religieux/moral de la droite chrétienne polarise les États-Unis, ce qui a des conséquences sur le plan électoral mais aussi sur les choix politiques réels. L’importance de la droite chrétienne dans la coalition électorale du Parti républicain oblige celui-ci à mettre l’accent sur les questions liées à la sécurité nationale, en particulier la lutte anti-terroriste, afin de mieux souder une coalition électorale hétérogène.

De novo Renal Transplantation after Kaposi Sarcoma: Favorable Outcome in a Patient Receiving Sirolimus and Mycophenolate-Based Immunosuppression

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F. Friedersdorff

2010-04-01

Full Text Available Immunosuppressive treatment increases the risk of infection and malignancy in organ transplant recipients. We report on a 42-year-old male renal transplant recipient who lost his first graft after reduction of immunosuppressive treatment due to Kaposi sarcoma and who successfully underwent a second renal transplant 10 years later. The patient’s current treatment consists of low-dose prednisone, and the two antiproliferative immunosuppressants mycophenolate mofetil and rapamycin. 4.5 years after his second transplant, the serum creatinine is 1 mg/dl and the patient has no signs of recurrent disease.

The neuroprotective efficacy of cell-penetrating peptides TAT, penetratin, Arg-9, and Pep-1 in glutamic acid, kainic acid, and in vitro ischemia injury models using primary cortical neuronal cultures.

Science.gov (United States)

Meloni, Bruno P; Craig, Amanda J; Milech, Nadia; Hopkins, Richard M; Watt, Paul M; Knuckey, Neville W

2014-03-01

Cell-penetrating peptides (CPPs) are small peptides (typically 5-25 amino acids), which are used to facilitate the delivery of normally non-permeable cargos such as other peptides, proteins, nucleic acids, or drugs into cells. However, several recent studies have demonstrated that the TAT CPP has neuroprotective properties. Therefore, in this study, we assessed the TAT and three other CPPs (penetratin, Arg-9, Pep-1) for their neuroprotective properties in cortical neuronal cultures following exposure to glutamic acid, kainic acid, or in vitro ischemia (oxygen-glucose deprivation). Arg-9, penetratin, and TAT-D displayed consistent and high level neuroprotective activity in both the glutamic acid (IC50: 0.78, 3.4, 13.9 μM) and kainic acid (IC50: 0.81, 2.0, 6.2 μM) injury models, while Pep-1 was ineffective. The TAT-D isoform displayed similar efficacy to the TAT-L isoform in the glutamic acid model. Interestingly, Arg-9 was the only CPP that displayed efficacy when washed-out prior to glutamic acid exposure. Neuroprotection following in vitro ischemia was more variable with all peptides providing some level of neuroprotection (IC50; Arg-9: 6.0 μM, TAT-D: 7.1 μM, penetratin/Pep-1: >10 μM). The positive control peptides JNKI-1D-TAT (JNK inhibitory peptide) and/or PYC36L-TAT (AP-1 inhibitory peptide) were neuroprotective in all models. Finally, in a post-glutamic acid treatment experiment, Arg-9 was highly effective when added immediately after, and mildly effective when added 15 min post-insult, while the JNKI-1D-TAT control peptide was ineffective when added post-insult. These findings demonstrate that different CPPs have the ability to inhibit neurodamaging events/pathways associated with excitotoxic and ischemic injuries. More importantly, they highlight the need to interpret neuroprotection studies when using CPPs as delivery agents with caution. On a positive note, the cytoprotective properties of CPPs suggests they are ideal carrier molecules to

NF90 una proteína celular que se une a RNAds inhibe la transactivación del LTR del HIV-1 mediada por TAT

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Silvio Urcuqui Inchima

2001-04-01

Full Text Available

La transactivación del LTR de HIV-1 requiere la interacción de la proteína Tat ( trans-activation transcription con la estructura TAR ( trans-activation response, que se encuentra localizada en el extremo 5’ de todos los transcriptos virales. La interacción de la proteína Tat con TAR forma un precomplejo transcripcional indispensable para la eficiente transcripción del genoma viral.
La interacción de diferentes factores celulares (cdk9 y ciclina T, entre otros con el precomplejo Tat-TAR, constituye un complejo estable que facilita la fosforilación de la subunidad mayor de la RNA polimerasa II, asegurando una eficiente elongación de los transcriptos virales. No se han descripto proteínas capaces de regular negativamente la función de Tat con resultados nefastos para la replicación viral. También se ha descrito otro tipo de proteínas celulares con capacidad de interactuar con TAR. El ejemplo mejor caracterizado es la proteína-kinasa dependiente de RNA (PKR, se autofosforila y mediante fosforilación del factor eIF2, inhibe la síntesis de proteínas. Con el presente trabajo se
pretendió aislar y caracterizar otras proteínas celulares capaces de interactuar con la estructura TAR y estudiar su efecto en la función de Tat.

Cell Type Preference of a Novel Human Derived Cell-Permeable Peptide dNP2 and TAT in Murine Splenic Immune Cells.

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Sangho Lim

Full Text Available Cell-permeable peptides (CPPs have been widely studied as an attractive drug delivery system to deliver therapeutic macromolecules such as DNA, RNA, and protein into cells. However, its clinical application is still limited and controversial due to the lack of a complete understanding of delivery efficiency in target cells. Previously we identified and characterized the novel and superior CPP, named dNP2, and here we comparatively analyzed intracellular delivery efficiency of dNP2 and TAT in various immune cells of mouse spleen to demonstrate their cell type preference. dNP2- or TAT-conjugated fluorescent proteins were most efficiently taken up by phagocytic cells such as dendritic cells and macrophages while little protein uptake was seen by lymphocytes including T cells, B cells, and NK cells. Interestingly CD8+ lymphoid dendritic cells and CD62LloCD44hi memory like T cell subsets showed significantly better uptake efficiency in vitro and in vivo relative to other dendritic cells or T cells, respectively. In addition, activated macrophages, T cells, and B cells took up the proteins more efficiently relative to when in the resting state. Importantly, only dNP2, not TAT, shows significant intracellular protein delivery efficiency in vivo. Collectively, this study provides important information regarding heterogeneous intracellular delivery efficiency of CPPs such as dNP2 and TAT with cell type preference in the spleen needed for its application in phagocytic cells or activated immune cells.

An attenuated herpes simplex virus type 1 (HSV1 encoding the HIV-1 Tat protein protects mice from a deadly mucosal HSV1 challenge.

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Mariaconcetta Sicurella

Full Text Available Herpes simplex virus types 1 and 2 (HSV1 and HSV2 are common infectious agents in both industrialized and developing countries. They cause recurrent asymptomatic and/or symptomatic infections, and life-threatening diseases and death in newborns and immunocompromised patients. Current treatment for HSV relies on antiviral medications, which can halt the symptomatic diseases but cannot prevent the shedding that occurs in asymptomatic patients or, consequently, the spread of the viruses. Therefore, prevention rather than treatment of HSV infections has long been an area of intense research, but thus far effective anti-HSV vaccines still remain elusive. One of the key hurdles to overcome in anti-HSV vaccine development is the identification and effective use of strategies that promote the emergence of Th1-type immune responses against a wide range of epitopes involved in the control of viral replication. Since the HIV1 Tat protein has several immunomodulatory activities and increases CTL recognition of dominant and subdominant epitopes of heterologous antigens, we generated and assayed a recombinant attenuated replication-competent HSV1 vector containing the tat gene (HSV1-Tat. In this proof-of-concept study we show that immunization with this vector conferred protection in 100% of mice challenged intravaginally with a lethal dose of wild-type HSV1. We demonstrate that the presence of Tat within the recombinant virus increased and broadened Th1-like and CTL responses against HSV-derived T-cell epitopes and elicited in most immunized mice detectable IgG responses. In sharp contrast, a similarly attenuated HSV1 recombinant vector without Tat (HSV1-LacZ, induced low and different T cell responses, no measurable antibody responses and did not protect mice against the wild-type HSV1 challenge. These findings strongly suggest that recombinant HSV1 vectors expressing Tat merit further investigation for their potential to prevent and/or contain HSV1

An attenuated herpes simplex virus type 1 (HSV1) encoding the HIV-1 Tat protein protects mice from a deadly mucosal HSV1 challenge.

Science.gov (United States)

Sicurella, Mariaconcetta; Nicoli, Francesco; Gallerani, Eleonora; Volpi, Ilaria; Berto, Elena; Finessi, Valentina; Destro, Federica; Manservigi, Roberto; Cafaro, Aurelio; Ensoli, Barbara; Caputo, Antonella; Gavioli, Riccardo; Marconi, Peggy C

2014-01-01

Herpes simplex virus types 1 and 2 (HSV1 and HSV2) are common infectious agents in both industrialized and developing countries. They cause recurrent asymptomatic and/or symptomatic infections, and life-threatening diseases and death in newborns and immunocompromised patients. Current treatment for HSV relies on antiviral medications, which can halt the symptomatic diseases but cannot prevent the shedding that occurs in asymptomatic patients or, consequently, the spread of the viruses. Therefore, prevention rather than treatment of HSV infections has long been an area of intense research, but thus far effective anti-HSV vaccines still remain elusive. One of the key hurdles to overcome in anti-HSV vaccine development is the identification and effective use of strategies that promote the emergence of Th1-type immune responses against a wide range of epitopes involved in the control of viral replication. Since the HIV1 Tat protein has several immunomodulatory activities and increases CTL recognition of dominant and subdominant epitopes of heterologous antigens, we generated and assayed a recombinant attenuated replication-competent HSV1 vector containing the tat gene (HSV1-Tat). In this proof-of-concept study we show that immunization with this vector conferred protection in 100% of mice challenged intravaginally with a lethal dose of wild-type HSV1. We demonstrate that the presence of Tat within the recombinant virus increased and broadened Th1-like and CTL responses against HSV-derived T-cell epitopes and elicited in most immunized mice detectable IgG responses. In sharp contrast, a similarly attenuated HSV1 recombinant vector without Tat (HSV1-LacZ), induced low and different T cell responses, no measurable antibody responses and did not protect mice against the wild-type HSV1 challenge. These findings strongly suggest that recombinant HSV1 vectors expressing Tat merit further investigation for their potential to prevent and/or contain HSV1 infection and

High-dose interferon-alpha2a exerts potent activity against human immunodeficiency virus type 1 not associated with antitumor activity in subjects with Kaposi's sarcoma

NARCIS (Netherlands)

Frissen, P. H.; de Wolf, F.; Reiss, P.; Bakker, P. J.; Veenhof, C. H.; Danner, S. A.; Goudsmit, J.; Lange, J. M.

1997-01-01

Anti-human immunodeficiency virus type 1 (HIV-1) activity was assessed in HIV-1-infected homosexual and bisexual men receiving 18-36 MIU/day of recombinant interferon (IFN)-alpha2a for Kaposi's sarcoma (KS). The median baseline HIV-1 RNA level was 4.99 log10 copies/mL. Seventeen subjects (68%)

Human retroviruses: their role in cancer.

Science.gov (United States)

Blattner, W A

1999-01-01

Viruses are etiologically linked to approximately 20% of all malignancies worldwide. Retroviruses account for approximately 8%-10% of the total. For human T-cell leukemia virus 1 (HTLV-I), the viral regulatory tax gene product is responsible for enhanced transcription of viral and cellular genes that promote cell growth by stimulating various growth factors and through dysregulation of cellular regulatory suppressor genes, such as p53. After a long latent period, adult T-cell leukemia/lymphoma (ATL) occurs in 1 per 1000 carriers per year, resulting in 2500-3000 cases per year worldwide and over half of the adult lymphoid malignancies in endemic areas. Human immunodeficiency virus 1 (HIV-1) accounts for a significant cancer burden, and its transactivating regulatory protein Tat enhances direct and indirect cytokine and immunological dysregulation to cause diverse cancers. Kaposi's sarcoma (KS) is a very rare tumor except after HIV-1 infection, when its incidence is greatly amplified reaching seventy thousand-fold in HIV-infected homosexual men. Human herpesvirus 8 (HHV-8), which is also known as Kaposi's sarcoma-associated virus (KSHV), is a necessary but not sufficient etiological factor in KS. The dramatic decline of KS since the introduction of highly active antiretroviral therapy (HAART) could be due to suppression of HIV-1 tat. B-cell non-Hodgkin's lymphoma occurs as their first acquired immunodeficiency syndrome-defining diagnosis in 3%-4% of HIV-infected patients. Hodgkin's lymphoma is also associated with HIV infection but at a lower risk. Human papillomaviruses are linked to invasive cervical cancer and anogenital cancers among HIV-infected patients. Human retroviruses cause malignancy via direct effects as well as through interactions with other oncogenic herpesviruses and other viruses.

Sarcoma de kaposi endemico en un paciente VIH negativo

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José Revilla-López

Full Text Available El sarcoma de Kaposi (SK es un cáncer angioproliferativo inflamatorio multifocal asociado a herpes virus 8 (VHH-8. Se han descrito cuatro variantes clínico-epidemiológicas: clásico, endémico, iatrogénico y epidémico o asociado a VIH. Clínicamente puede ser indolente o agresivo, afecta principalmente áreas mucocutáneas con eventual compromiso visceral y de ganglios linfáticos. Se presenta frecuentemente y de forma más agresiva en la población VIH positiva. Presentamos un caso de un paciente varón de 27 años VIH negativo con lesión tumoral sangrante en el anillo de Waldeyer, múltiples adenopatías y lesiones exofíticas en pie que remiten con quimioterapia de emergencia basada en antraciclinas. El SK VIH negativo es una condición poco frecuente. Es importante tener en cuenta al Perú como región endémica para el VHH-8. La afectación oral del SK es una manifestación rara y de mal pronóstico, sin embargo, el factor VIH negativo podría conferirle un buen pronóstico

Evaluation of Psychoanalytic Oriented Psychotherapy Outcome Using Rorschach and TAT: A Case Study

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Zihniye OKRAY

2017-12-01

Full Text Available Projective techniques especially Rorschach and TAT ( Thematic Apperception Test have a wide variety of assestment areas. These techniques have been used from selection of staff for a appropriate job, giving diagnosis to psychiatric patients, in child services for counseling, selection and evaluation of military personel. Apart from these uses they also have valuable contributions to the efficiency of a certain treatment programs with helping clinicans to evaluate the psychodynamic properties of a client to decide the type, duration and specific issues in the treatment programme (Deabler, 1947, Weiner, 1997, Tunaboylu-İkiz, 2001, 2002, 2010,2011, Anzieu & Chabert, 2011. In this study a case who was treated with psychodynamic oriented psychotherapy for 2 years the outcome of the threapy evaluated with Rorschach and TAT. In the first assestment before the psychothreapy began the Detail responses given by the patient was to much inorder to protect himself from the dangers coming from the real world.The content of the responses also showed the same charasteristic with using the same theme all over the full protocol.Case’s problems around his self-representaion, self, identification- differences between gender and object relations was evaluated with TAT that showed object loss was the main problematic. After 2 years with the termination of the threapy the second evaluation was done. In this second evaluation the case led himself more freely to the test material with less resistance. In the second evaluation; the case’s cognitive processes and using of words are more rich wch represents high cognitive and entellectual capacities. He is less resistant to unconscious material, sexual contents coming up in responses with more intellectual ways. With these two assestment the efficiency of psychodynamic oriented psychothreapy was proved. Although the case’s perception of the real world still contains some aspects of threads the second evaluation

A dose-response analysis for classical Kaposi's sarcoma management by radiotherapy

International Nuclear Information System (INIS)

Oysul, K.; Beyzadeoglu, M.; Surenkok, S.; Ozyigit, G.; Dirican, B.

2008-01-01

Objective was to evaluate the dose-response relationship in classical Kaposi's sarcoma CKS patients treated with external beam radiotherapy. Between 1993 and 2004, patients with CKS treated at the Department of Radiation Oncology, Gulhane Military Medical School, Ankara, Turkey were evaluated in this retrospective study. The median age at initial presentation was 60 years. First we analyzed the overall response rates for normalized total dose2Gy NTD2Gy of 20Gy. Secondly we searched for whether better response rates could be obtained with the NTD2Gy of >/=20Gy compared to the NTD2Gy of /20Gy and 64% and 24%for NDT2Gyof 20< Gy and these were statistically different p=0.001. Late side effects of radiation therapy were acceptable in all but 4 patients with fibrosis and edema. This retrospective analysis showed that radiotherapy schedules with an NDT2Gy of 20 Gy and above by using local irradiation fields are effective in terms of complete response rates in the management of CKS compared to NDT2Gy of < 20 Gy. (author)

Immunophenotypic analysis of the Kaposi sarcoma herpesvirus (KSHV; HHV-8)-infected B cells in HIV+ multicentric Castleman disease (MCD).

Science.gov (United States)

Chadburn, A; Hyjek, E M; Tam, W; Liu, Y; Rengifo, T; Cesarman, E; Knowles, D M

2008-11-01

Kaposi sarcoma herpesvirus (KSHV) is aetiologically related to Kaposi sarcoma, classical and extracavitary primary effusion lymphoma (PEL; EC-PEL) and multicentric Castleman disease (MCD), entities preferentially occurring in HIV-infected individuals. Characterization of HIV-associated PELs/EC-PELs suggests that the KSHV-infected malignant cells originate from a pre-terminal stage of B-cell differentiation. However, only limited phenotypic studies have been performed on HIV+ MCD, including for PR domain containing 1 with zinc finger domain/B lymphocyte-induced maturation protein 1 (PRDM1/BLIMP1), a key regulator of terminal B-cell differentiation. The aim was to characterize KSHV-infected cells in 17 cases of HIV+ MCD. Double immunohistochemistry and immunohistochemistry-in situ hybridization were used to characterize the KSHV-infected cells in MCD; the results were compared with the phenotypic profiles of 39 PELs/EC-PELs and seven PEL cell lines. Whereas the immunophenotype of KSHV-infected cells in MCD and malignant KSHV+ PEL cells was similar (PAX5, Bcl-6-; PRDM1/BLIMP1, IRF4/MUM1+; Ki67+), the MCD KSHV-infected cells differed, as they expressed OCT2, cytoplasmic lambda immunoglobulin; variably expressed CD27; lacked CD138; and were Epstein-Barr virus negative. Although both PEL and MCD originate from KSHV-infected pre-terminally differentiated B cells, these findings, with previously reported genetic studies, indicate HIV+ MCD may arise from extrafollicular B cells, whereas PELs may originate from cells that have traversed the germinal centre.

The Crystal Structure of PF-8, the DNA Polymerase Accessory Subunit from Kaposi's Sarcoma-Associated Herpesvirus

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Baltz, Jennifer L.; Filman, David J.; Ciustea, Mihai; Silverman, Janice Elaine Y.; Lautenschlager, Catherine L.; Coen, Donald M.; Ricciardi, Robert P.; Hogle, James M.; (UPENN)

2009-12-01

Kaposi's sarcoma-associated herpesvirus is an emerging pathogen whose mechanism of replication is poorly understood. PF-8, the presumed processivity factor of Kaposi's sarcoma-associated herpesvirus DNA polymerase, acts in combination with the catalytic subunit, Pol-8, to synthesize viral DNA. We have solved the crystal structure of residues 1 to 304 of PF-8 at a resolution of 2.8 {angstrom}. This structure reveals that each monomer of PF-8 shares a fold common to processivity factors. Like human cytomegalovirus UL44, PF-8 forms a head-to-head dimer in the form of a C clamp, with its concave face containing a number of basic residues that are predicted to be important for DNA binding. However, there are several differences with related proteins, especially in loops that extend from each monomer into the center of the C clamp and in the loops that connect the two subdomains of each protein, which may be important for determining PF-8's mode of binding to DNA and to Pol-8. Using the crystal structures of PF-8, the herpes simplex virus catalytic subunit, and RB69 bacteriophage DNA polymerase in complex with DNA and initial experiments testing the effects of inhibition of PF-8-stimulated DNA synthesis by peptides derived from Pol-8, we suggest a model for how PF-8 might form a ternary complex with Pol-8 and DNA. The structure and the model suggest interesting similarities and differences in how PF-8 functions relative to structurally similar proteins.

Amélioration de l'état nutritionnel des enfants au Ghana, au Kenya ...

International Development Research Centre (IDRC) Digital Library (Canada)

Les chercheurs ont déterminé que les changements sur le plan de la nutrition en Afrique sont l'une des principales causes de l'épidémie croissante de maladies non transmissibles (MNT). Ce projet de recherche évaluera les habitudes alimentaires et l'état nutritionnel des enfants pour jeter les bases d'un projet de ...

Tat protein vaccination of cynomolgus macaques influences SHIV-89.6P cy243 epitope variability.

Science.gov (United States)

Ridolfi, Barbara; Genovese, Domenico; Argentini, Claudio; Maggiorella, Maria Teresa; Sernicola, Leonardo; Buttò, Stefano; Titti, Fausto; Borsetti, Alessandra; Ensoli, Barbara

2008-02-01

In a previous study we showed that vaccination with the native Tat protein controlled virus replication in five out of seven monkeys against challenge with the simian human immunodeficiency virus (SHIV)-89.6P cy243 and that this protection correlated with T helper (Th)-1 response and cytotoxic T lymphocyte (CTL) activity. To address the evolution of the SHIV-89.6P cy243 both in control and vaccinated infected monkeys, the sequence of the human immunodeficiency virus (HIV)-1 Tat protein and the C2-V3 Env region of the proviral-DNA-derived clones were analyzed in both control and vaccinated but unprotected animals. We also performed analysis of the T cell epitope using a predictive epitope model taking into consideration the phylogeny of the variants. Our results suggest that even though the viral evolution observed in both groups of monkeys was directed toward variations in the major histocompatibility complex (MHC)-I epitopes, in the control animals it was associated with mutational escape of such epitopes. On the contrary, it is possible that viral evolution in the vaccinated monkeys was linked to mutations that arose to keep high the viral fitness. In the vaccinated animals the reduction of epitope variability, obtained prompting the immune system by vaccination and inducing a specific immunological response against virus, was able to reduce the emergence of escape mutants. Thus the intervention of host's selective forces in driving CTL escape mutants and in modulating viral fitness appeared to be different in the two groups of monkeys. We concluded that in the vaccinated unprotected animals, vaccination with the Tat protein induced a broad antiviral response, as demonstrated by the reduced ability to develop escape mutants, which is known to help in the control of viral replication.

Sécurité d'État et insécurité nationale au Mali : les logiques ...

African Journals Online (AJOL)

PhD, Socio économiste, Directeur, CERNES, Bamako, Mali. .... Au regard de la référence que constitue la définition sécuritaire régalienne de l'État et de son monopole .... Sur le plan économique, le cycle accumulation, rupture et reconstitution.

Comparison of Kaposi Sarcoma risk in human immunodeficiency virus-positive adults across 5 continents

DEFF Research Database (Denmark)

Rohner, Eliane; Bütikofer, Lukas; Schmidlin, Kurt

2017-01-01

Background: We compared Kaposi sarcoma (KS) risk in adults who started antiretroviral therapy (ART) across the Asia-Pacific, South Africa, Europe, Latin, and North America. Methods: We included cohort data of human immunodeficiency virus (HIV)-positive adults who started ART after 1995 within...... KS risk was 6 times higher in men who have sex with men (aHR, 5.95; 95% CI, 5.09-6.96) than in women. Comparing patients with current CD4 cell counts ≥700 cells/μL with those whose counts were ...% in other regions. Conclusions. Despite important ART-related declines in KS incidence, men and women in South Africa and men who have sex with men remain at increased KS risk, likely due to high human herpesvirus 8 coinfection rates. Early ART initiation and maintenance of high CD4 cell counts...

Incidentally Detected Kaposi Sarcoma of Adrenal Gland with Anaplastic Features in an HIV Negative Patient

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Zeliha Esin Celik

2016-01-01

Full Text Available Kaposi sarcoma (KS, a vascular tumor caused by infection with human herpesvirus 8 (HHV8, is a systemic disease that can present with cutaneous lesions with or without visceral involvement. Very few cases of KS, most of which were associated with AIDS, have been reported in the adrenal gland. Anaplastic transformation of KS is a rare clinical presentation known as an aggressive disease with local recurrence and metastatic potential. We report here a 47-year-old HIV negative male presented with extra-adrenal symptoms and had an incidentally detected anaplastic adrenal KS exhibited aggressive clinical course. To the best of our knowledge, this is the first case of anaplastic primary adrenal KS without mucocutaneous involvement but subsequently developed other side adrenal metastases in an HIV negative patient.

Tat-dependent repression of human immunodeficiency virus type 1 long terminal repeat promoter activity by fusion of cellular transcription factors

International Nuclear Information System (INIS)

Zhao Cunyou; Chen Yali; Park, Jiyoung; Kim, Jae Bum; Tang Hong

2004-01-01

Transcription initiation from HIV-1 long terminal repeat (LTR) promoter requires the virally encoded transactivator, Tat, and several cellular co-factors to accomplish the Tat-dependent processive transcription elongation. Individual cellular transcription activators, LBP-1b and Oct-1, on the other hand, have been shown to inhibit LTR promoter activities probably via competitive binding against TFIID to the TATA-box in LTR promoter. To explore the genetic interference strategies against the viral replication, we took advantage of the existence of the bipartite DNA binding domains and the repression domains of LBP-1b and Oct-1 factors to generate a chimeric transcription repressor. Our results indicated that the fusion protein of LBP-1b and Oct-1 exhibited higher DNA binding affinity to the viral promoter than the individual factors, and little interference with the host cell gene expression due to its anticipated rare cognate DNA sites in the host cell genome. Moreover, the chimera exerted increased Tat-dependent repression of transcription initiation at the LTR promoter both in vitro and in vivo compared to LBP-1b, Oct-1 or combination of LBP-1b and Oct-1. These results might provide the lead in generating a therapeutic reagent useful to suppress HIV-1 replication

Sarcoma de Kaposi bucal en pacientes con trasplante de riñón

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Gladys Aída Estrada Pereira

2015-02-01

Full Text Available Se realizó un estudio descriptivo y transversal de 25 pacientes con trasplante renal y sarcoma de Kaposi bucal, atendidos en la consulta estomatológica del Policlínico de Especialidades del Hospital Clinicoquirúrgico Docente "Saturnino Lora Torres" de Santiago de Cuba, desde marzo de 2008 hasta igual mes de 2013, para describir los resultados clínicos e histopatológicos. Entre los hallazgos principales predominaron el sexo masculino, el grupo etario de 40-49 años y los afectados de piel negra. Por otra parte, como alteraciones hísticas sobresalieron los espacios vasculares atípicos, los cuerpos eosinófilos y la extravasación de hematíes; asimismo, la mayoría de las lesiones correspondieron al paladar duro y a la encía. La biopsia resultó ser un medio de diagnóstico valioso para confirmar esta enfermedad

Systematic identification of cellular signals reactivating Kaposi sarcoma-associated herpesvirus.

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Fuqu Yu

2007-03-01

Full Text Available The herpesvirus life cycle has two distinct phases: latency and lytic replication. The balance between these two phases is critical for viral pathogenesis. It is believed that cellular signals regulate the switch from latency to lytic replication. To systematically evaluate the cellular signals regulating this reactivation process in Kaposi sarcoma-associated herpesvirus, the effects of 26,000 full-length cDNA expression constructs on viral reactivation were individually assessed in primary effusion lymphoma-derived cells that harbor the latent virus. A group of diverse cellular signaling proteins were identified and validated in their effect of inducing viral lytic gene expression from the latent viral genome. The results suggest that multiple cellular signaling pathways can reactivate the virus in a genetically homogeneous cell population. Further analysis revealed that the Raf/MEK/ERK/Ets-1 pathway mediates Ras-induced reactivation. The same pathway also mediates spontaneous reactivation, which sets the first example to our knowledge of a specific cellular pathway being studied in the spontaneous reactivation process. Our study provides a functional genomic approach to systematically identify the cellular signals regulating the herpesvirus life cycle, thus facilitating better understanding of a fundamental issue in virology and identifying novel therapeutic targets.

Therapeutic immunization with HIV-1 Tat reduces immune activation and loss of regulatory T-cells and improves immune function in subjects on HAART.

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Barbara Ensoli

2010-11-01

Full Text Available Although HAART suppresses HIV replication, it is often unable to restore immune homeostasis. Consequently, non-AIDS-defining diseases are increasingly seen in treated individuals. This is attributed to persistent virus expression in reservoirs and to cell activation. Of note, in CD4(+ T cells and monocyte-macrophages of virologically-suppressed individuals, there is continued expression of multi-spliced transcripts encoding HIV regulatory proteins. Among them, Tat is essential for virus gene expression and replication, either in primary infection or for virus reactivation during HAART, when Tat is expressed, released extracellularly and exerts, on both the virus and the immune system, effects that contribute to disease maintenance. Here we report results of an ad hoc exploratory interim analysis (up to 48 weeks on 87 virologically-suppressed HAART-treated individuals enrolled in a phase II randomized open-label multicentric clinical trial of therapeutic immunization with Tat (ISS T-002. Eighty-eight virologically-suppressed HAART-treated individuals, enrolled in a parallel prospective observational study at the same sites (ISS OBS T-002, served for intergroup comparison. Immunization with Tat was safe, induced durable immune responses, and modified the pattern of CD4(+ and CD8(+ cellular activation (CD38 and HLA-DR together with reduction of biochemical activation markers and persistent increases of regulatory T cells. This was accompanied by a progressive increment of CD4(+ T cells and B cells with reduction of CD8(+ T cells and NK cells, which were independent from the type of antiretroviral regimen. Increase in central and effector memory and reduction in terminally-differentiated effector memory CD4(+ and CD8(+ T cells were accompanied by increases of CD4(+ and CD8(+ T cell responses against Env and recall antigens. Of note, more immune-compromised individuals experienced greater therapeutic effects. In contrast, these changes were opposite

Labeling Efficacy of Superparamagnetic Iron Oxide Nanoparticles to Human Neural Stem Cells: Comparison of Ferumoxides, Monocrystalline Iron Oxide, Cross-linked Iron Oxide (CLIO)-NH2 and tat-CLIO

International Nuclear Information System (INIS)

Song, Mi Yeoun; Moon, Woo Kyung; Kim, Yun Hee; Song, In Chan; Yoon, Byung Woo; Lim, Dong Yeol

2007-01-01

We wanted to compare the human neural stem cell (hNSC) labeling efficacy of different superparamagnetic iron oxide nanoparticles (SPIONs), namely, ferumoxides, monocrystalline iron oxide (MION), cross-linked iron oxide (CLIO)-NH 2 and tat-CLIO. The hNSCs (5x10 5 HB1F3 cells/ml) were incubated for 24 hr in cell culture media that contained 25 μg/ml of ferumoxides, MION or CLIO-NH 2 , and with or without poly-L-lysine (PLL) and tat-CLIO. The cellular iron uptake was analyzed qualitatively with using a light microscope and this was quantified via atomic absorption spectrophotometry. The visibility of the labeled cells was assessed with MR imaging. The incorporation of SPIONs into the hNSCs did not affect the cellular proliferations and viabilities. The hNSCs labeled with tat-CLIO showed the longest retention, up to 72 hr, and they contained 2.15± 0.3 pg iron/cell, which are 59 fold, 430 fold and six fold more incorporated iron than that of the hNSCs labeled with ferumoxides, MION or CLIO-NH 2 , respectively. However, when PLL was added, the incorporation of ferumoxides, MION or CLIO-NH 2 into the hNSCs was comparable to that of tat-CLIO. For MR imaging, hNSCs can be efficiently labeled with tat-CLIO alone or with a combination of ferumoxides, MION, CLIO-NH 2 and the transfection agent PLL

Labeling Efficacy of Superparamagnetic Iron Oxide Nanoparticles to Human Neural Stem Cells: Comparison of Ferumoxides, Monocrystalline Iron Oxide, Cross-linked Iron Oxide (CLIO)-NH2 and tat-CLIO

Science.gov (United States)

Song, Miyeoun; Kim, Yunhee; Lim, Dongyeol; Song, In-Chan; Yoon, Byung-Woo

2007-01-01

Objective We wanted to compare the human neural stem cell (hNSC) labeling efficacy of different superparamagnetic iron oxide nanoparticles (SPIONs), namely, ferumoxides, monocrystalline iron oxide (MION), cross-linked iron oxide (CLIO)-NH2 and tat-CLIO. Materials and Methods The hNSCs (5 × 105 HB1F3 cells/ml) were incubated for 24 hr in cell culture media that contained 25 µg/ml of ferumoxides, MION or CLIO-NH2, and with or without poly-L-lysine (PLL) and tat-CLIO. The cellular iron uptake was analyzed qualitatively with using a light microscope and this was quantified via atomic absorption spectrophotometry. The visibility of the labeled cells was assessed with MR imaging. Results The incorporation of SPIONs into the hNSCs did not affect the cellular proliferations and viabilities. The hNSCs labeled with tat-CLIO showed the longest retention, up to 72 hr, and they contained 2.15 ± 0.3 pg iron/cell, which are 59 fold, 430 fold and six fold more incorporated iron than that of the hNSCs labeled with ferumoxides, MION or CLIO-NH2, respectively. However, when PLL was added, the incorporation of ferumoxides, MION or CLIO-NH2 into the hNSCs was comparable to that of tat-CLIO. Conclusion For MR imaging, hNSCs can be efficiently labeled with tat-CLIO alone or with a combination of ferumoxides, MION, CLIO-NH2 and the transfection agent PLL. PMID:17923778

Tat-haFGF14–154 Upregulates ADAM10 to Attenuate the Alzheimer Phenotype of APP/PS1 Mice through the PI3K-CREB-IRE1α/XBP1 Pathway

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Tian Meng

2017-06-01

Full Text Available Acid fibroblast growth factor (aFGF has shown neuroprotection in Alzheimer’s disease (AD models in previous studies, yet its mechanism is still uncertain. Here we report that the efficacy of Tat-haFGF14–154 is markedly increased when loaded cationic liposomes for intranasal delivery are intranasally administered to APP/PS1 mice. Our results demonstrated that liposomal Tat-haFGF14–154 treatment significantly ameliorated behavioral deficits, relieved brain Aβ burden, and increased the expression and activity of disintegrin and metalloproteinase domain-containing protein 10 (ADAM10 in the brain. Tat-haFGF14–154 antagonized Aβ1–42-induced cell death and structural damage in rat primary neurons in an ADAM10-dependent manner, which, in turn, was promoted by the activation of XBP1 splicing and modulated by the PI3K-CREB pathway. Both knockdown of ADAM10 and inhibition of PI3K (LY294002 negated Tat-haFGF14–154 rescue. Thus, Tat-haFGF14–154 activates the IRE1α/XBP1 pathway of the unfolded protein response (UPR against the endoplasmic reticulum (ER stress induced by Aβ, and, subsequently, the nuclear translocation of spliced XBP1 (XBP1s promotes transcription of ADAM10. These results highlight the important role of ADAM10 and its activation through the PI3K-CREB-IRE1α/XBP1 pathway as a key factor in the mechanism of neuroprotection for Tat-haFGF14–154.

Enhanced Cellular Uptake of Albumin-Based Lyophilisomes when Functionalized with Cell-Penetrating Peptide TAT in HeLa Cells

NARCIS (Netherlands)

van Bracht, Etienne; Versteegden, Luuk R. M.; Stolle, Sarah; Verdurmen, Wouter P. R.; Woestenenk, Rob; Raave, Rene; Hafmans, Theo; Oosterwijk, Egbert; Brock, Roland; van Kuppevelt, Toin H.; Daamen, Willeke F.

2014-01-01

Lyophilisomes are a novel class of biodegradable proteinaceous nano/micrometer capsules with potential use as drug delivery carrier. Cell-penetrating peptides (CPPs) including the TAT peptide have been successfully implemented for intracellular delivery of a broad variety of cargos including various

Alternative Mechanisms for the Interaction of the Cell-Penetrating Peptides Penetratin and the TAT Peptide with Lipid Bilayers

NARCIS (Netherlands)

Yesylevskyy, Semen; Marrink, Siewert-Jan; Mark, Alan E.

2009-01-01

Cell-penetrating peptides (CPPs) have recently attracted much interest due to their apparent ability to penetrate cell membranes in an energy-independent manner. Here molecular-dynamics simulation techniques were used to study the interaction of two CPPs: penetratin and the TAT peptide with

Trans-activation of the JC virus late promoter by the tat protein of type 1 human immunodeficiency virus in glial cells

International Nuclear Information System (INIS)

Tada, Hiroomi; Lashgari, M.; Amini, S.; Khalili, K.; Rappaport, J.; Wong-Staal, F.

1990-01-01

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the JC virus (JCV), a human papovavirus. PML is a relatively rare disease seen predominantly in immunocompromised individuals and is a frequent complication observed in AIDS patients. The significantly higher incidence of PML in AIDS patients than in other immunosuppressive disorders has suggested that the presence of human immunodeficiency virus type 1 (HIV-1) in the brain may directly or indirectly contribute to the pathogenesis of this disease. In the present study the authors have examined the expression of the JCV genome in both glial and non-glial cells in the presence of HIV-1 regulatory proteins. They find that the HIV-1-encoded trans-regulatory protein tat increases the basal activity of the JCV late promoter, JCV L , in glial cells. They conclude that the presence of the HIV-1-encoded tat protein may positively affect the JCV lytic cycle in glial cells by stimulating JCV gene expression. The results suggest a mechanism for the relatively high incidence of PML in AIDS patients than in other immunosuppressive disorders. Furthermore, the findings indicate that the HIV-1 regulatory protein tat may stimulate other viral and perhaps cellular promoters, in addition to its own

Tat proteins as novel thylakoid membrane anchors organize a biosynthetic pathway in chloroplasts and increase product yield 5-fold

DEFF Research Database (Denmark)

Henriques de Jesus, Maria Perestrello Ramos; Nielsen, Agnieszka Janina Zygadlo; Mellor, Silas Busck

2017-01-01

to their complex structures. Some of the crucial enzymes catalyzing their biosynthesis are the cytochromes P450 (P450s) situated in the endoplasmic reticulum (ER), powered by electron transfers from NADPH. Dhurrin is a cyanogenic glucoside and its biosynthesis involves a dynamic metabolon formed by two P450s....... Nevertheless, translocation of the pathway from the ER to the chloroplast creates other difficulties, such as the loss of metabolon formation and intermediate diversion into other metabolic pathways. We show here that co-localization of these enzymes in the thylakoid membrane leads to a significant increase...... in product formation, with a concomitant decrease in off-pathway intermediates. This was achieved by exchanging the membrane anchors of the dhurrin pathway enzymes to components of the Twin-arginine translocation pathway, TatB and TatC, which have self-assembly properties. Consequently, we show 5-fold...

Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen prolongs the life span of primary human umbilical vein endothelial cells.

Science.gov (United States)

Watanabe, Takahiro; Sugaya, Makoto; Atkins, April M; Aquilino, Elisabeth A; Yang, Aparche; Borris, Debra L; Brady, John; Blauvelt, Andrew

2003-06-01

Tumor spindle cells in all clinical types of Kaposi's sarcoma (KS) are infected with Kaposi's sarcoma-associated herpesvirus (KSHV). Although KSHV contains more than 80 genes, only a few are expressed in tumor spindle cells, including latency-associated nuclear antigen (LANA) and k-cyclin (kCYC). To assess the oncogenic potential of LANA and kCYC, primary human umbilical vein endothelial cells (HUVEC) and murine NIH 3T3 cells were stably transduced by using recombinant retroviruses expressing these genes or the known viral oncogene simian virus 40 large T antigen (LTAg). Interestingly, LANA-transduced HUVEC proliferated faster and demonstrated a greatly prolonged life span (mean +/- standard deviation, 38.3 +/- 11.0 passages) than untransduced cells and vector-transduced cells (<20 passages). By contrast, kCYC-transduced HUVEC did not proliferate faster or live longer than control cells. LANA- and kCYC-transduced HUVEC, but not LTAg-transduced HUVEC, retained the ability to form normal vessel-like structures in an in vitro model of angiogenesis. In cellular assays of transformation, LANA- and kCYC-transduced NIH 3T3 cells demonstrated minimal or no anchorage-independent growth in soft agar and no tumorigenicity when injected into nude mice, unlike LTAg-transduced NIH 3T3 cells. Lastly, gene expression profiling revealed down-regulation, or silencing, of a number of genes within LANA-transduced HUVEC. Taken together, these results suggest that KSHV LANA is capable of inducing prolonged life span, but not transformation, in primary human cells. These findings may explain why LANA-expressing spindle cells proliferate within KS tumors, yet most often do not demonstrate biologic characteristics of transformation or true malignant conversion.

Broad target cell selectivity of Kaposi's sarcoma-associated herpesvirus glycoprotein-mediated cell fusion and virion entry

International Nuclear Information System (INIS)

Kaleeba, Johnan A.R.; Berger, Edward A.

2006-01-01

The molecular mechanism of Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus 8) entry is poorly understood. We tested a broad variety of cell types of diverse species and tissue origin for their ability to function as targets in a quantitative reporter gene assay for KSHV-glycoprotein-mediated cell fusion. Several human, non-human primate, and rabbit cell lines were efficient targets, whereas rodent and all human lymphoblastoid cell lines were weak targets. Parallel findings were obtained with a virion entry assay using a recombinant KSHV encoding a reporter gene. No correlation was observed between target cell activity and surface expression of α3β1 integrin, a proposed KSHV receptor. We hypothesize that target cell permissiveness in both the cell fusion and virion entry assays reflects the presence of a putative KSHV fusion-entry receptor

Seroprevalence and risk factors of Kaposi's sarcoma-associated herpesvirus infection among the general Uygur population from south and north region of Xinjiang, China

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Wang Hui

2011-12-01

Full Text Available Abstract Background Kaposi sarcoma (KS is a complex multifocal neoplasm and is the major cause of death for about 50% of acquired immunodeficiency syndrome (AIDS patients. Kaposi's sarcoma-associated herpesvirus (KSHV is an oncogenic virus with a causal role in the development of all types of KS. KS is prevalent among the Uygur people in Xinjiang, especially in south area. Here we carried out a cross-sectional study among 1534 general Uygur individuals from south and north region of Xinjiang to assess the seroprevalence of KSHV and to identify the potential correlation between KSHV seroprevalence and KS incidence. Results Seroprevalence of KSHV in South and North Xinjiang was 23.1% and 25.9%, respectively. Older age was independently associated with higher KSHV seroprevalence. In subjects from South Xinjiang, lower educational level and reported drinking were each independently associated with higher KSHV seroprevalence. Furthermore, the antibody titer was significantly lower in both south and north KSHV seropositive individuals compared with KS patients, as analyzed by gradient dilution (P Conclusion KSHV is highly prevalent in the general Uygur population in both South and North Xinjiang. Interestingly, the infection rate of KSHV in these two geographical areas did not correlate well with KS incidence. Perhaps unknown factors exist that promote the progression of KSHV infection to KS development in the local minority groups.

Gastric and Peritoneal Involvement of Human Herpes Virus 8 Related Kaposi Sarcoma in a Patient with Acquired Immunodeficiency Syndrome

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Nuno Ribeiro Ferreira

2015-09-01

Full Text Available Kaposi's sarcoma (KS is one of the most frequent neoplastic diseases in patients infected with human immunodeficiency virus (HIV. The authors report the case of a 40-year-old male with ascites, peripheral edema and peritoneal carcinomatosis secondary to a gastric KS related to human herpes virus type 8 (HHV-8. The patient had severe immunodeficiency, with a TCD4+ count of 86 cells/µl and newly diagnosed acquired immunodeficiency syndrome. His clinical condition rapidly deteriorated, with multiorgan failure, and he died without the possibility of initiating antiretroviral therapy or chemotherapy. To the authors’ knowledge, carcinomatosis is a rare feature in KS.

DNA-PK/Ku complex binds to latency-associated nuclear antigen and negatively regulates Kaposi's sarcoma-associated herpesvirus latent replication

International Nuclear Information System (INIS)

Cha, Seho; Lim, Chunghun; Lee, Jae Young; Song, Yoon-Jae; Park, Junsoo; Choe, Joonho; Seo, Taegun

2010-01-01

During latent infection, latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays important roles in episomal persistence and replication. Several host factors are associated with KSHV latent replication. Here, we show that the catalytic subunit of DNA protein kinase (DNA-PKcs), Ku70, and Ku86 bind the N-terminal region of LANA. LANA was phosphorylated by DNA-PK and overexpression of Ku70, but not Ku86, impaired transient replication. The efficiency of transient replication was significantly increased in the HCT116 (Ku86 +/-) cell line, compared to the HCT116 (Ku86 +/+) cell line, suggesting that the DNA-PK/Ku complex negatively regulates KSHV latent replication.

TAT – Thematic Apperception Test (Murray test as Cross-cultural Studies Tool

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Dan Ungureanu

2011-05-01

Full Text Available Three images of the TAT were used to elicit answers from a sample of around one hundred teenagers from different countries and cultural backgrounds. The goal of the research was to identify possible cultural differences in perception of social and family relationships, differences in associating emotions with a social context. Our study was inspired by the ones conducted by Bert Kaplan in Kansas and Ivano Rinaldi in rural Lucania, at the request of Edward Banfield (The Moral Basis of a Backward Society, 1958. It was the first one to use the Thematic Apperception Test for a cross-cultural comparison.

Human herpesvirus-8 positive iatrogenic Kaposi's sarcoma in the setting of refractory ulcerative colitis.

Science.gov (United States)

Duh, Erica; Fine, Sean

2017-12-16

Although Kaposi sarcoma (KS) has been more traditionally considered an AIDS-defining illness, it may also be seen in individuals on immunosuppresive therapy. We report a case of a patient who presented to the hospital in the setting of increasingly refractory ulcerative colitis. Computed tomography scan of the abdomen was consistent with sigmoid diverticulititis and blood cultures were positive for Klebsiella. After a course of antibiotics with resolution of infection, a colonoscopy was performed to evaluate his diverticulitis and incidentally revealed a new rectal tumor. Immunohistochemistry showed the tumor was consistent with KS, with cells staining strongly positive for human herpesvirus-8. This case not only illustrates a rare case of KS found in an HIV-negative individual, but it also highlights the importance of considering an alternative diagnosis in a patient refractory to medical treatment. We discuss the management and care of an ulcerative colitis patient diagnosed with KS on immunosuppressive therapy.

Inhibition of both HIV-1 reverse transcription and gene expression by a cyclic peptide that binds the Tat-transactivating response element (TAR RNA.

Directory of Open Access Journals (Sweden)

Matthew S Lalonde

2011-05-01

Full Text Available The RNA response element TAR plays a critical role in HIV replication by providing a binding site for the recruitment of the viral transactivator protein Tat. Using a structure-guided approach, we have developed a series of conformationally-constrained cyclic peptides that act as structural mimics of the Tat RNA binding region and block Tat-TAR interactions at nanomolar concentrations in vitro. Here we show that these compounds block Tat-dependent transcription in cell-free systems and in cell-based reporter assays. The compounds are also cell permeable, have low toxicity, and inhibit replication of diverse HIV-1 strains, including both CXCR4-tropic and CCR5-tropic primary HIV-1 isolates of the divergent subtypes A, B, C, D and CRF01_AE. In human peripheral blood mononuclear cells, the cyclic peptidomimetic L50 exhibited an IC(50 ∼250 nM. Surprisingly, inhibition of LTR-driven HIV-1 transcription could not account for the full antiviral activity. Timed drug-addition experiments revealed that L-50 has a bi-phasic inhibition curve with the first phase occurring after HIV-1 entry into the host cell and during the initiation of HIV-1 reverse transcription. The second phase coincides with inhibition of HIV-1 transcription. Reconstituted reverse transcription assays confirm that HIV-1 (- strand strong stop DNA synthesis is blocked by L50-TAR RNA interactions in-vitro. These findings are consistent with genetic evidence that TAR plays critical roles both during reverse transcription and during HIV gene expression. Our results suggest that antiviral drugs targeting TAR RNA might be highly effective due to a dual inhibitory mechanism.

Calcul de la distribution d'états de charge du néon dans un plasma coronal chaud en équilibre d'ionisation

OpenAIRE

BENTOTOCHE, Mohamed Sadek; MERABTI, Karim Elhadj

2011-01-01

L'abondance relative des di érents états de charge d'un même élément constitue l'un des paramètres les plus importants d'un plasma. La connaissance de cette abondance relative est nécessaire dans les calculs de rapports d'intensité des raies émises par di érents ions, qui peuvent servir d'outils de diagnostic des conditions physiques régnant dans le plasma émissif. Dans ce mémoire, nous avons e ectué des calculs détaillés de l'abondance relative d'ions de néon dans les six états d...

Gastrointestinal Bleeding and Diffuse Skin Thickening as Kaposi Sarcoma Clinical Presentation

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Sara Querido

2015-01-01

Full Text Available A 56-year-old African patient received a kidney from a deceased donor with 4 HLA mismatches in April 2013. He received immunosuppression with basiliximab, tacrolimus, mycophenolate mofetil, and prednisone. Immediate diuresis and a good allograft function were soon observed. Six months later, the serum creatinine level increased to 2.6 mg/dL. A renal allograft biopsy revealed interstitial fibrosis and tubular atrophy grade II. Toxicity of calcineurin inhibitor was assumed and, after a switch for everolimus, renal function improved. However, since March 2014, renal function progressively deteriorated. A second allograft biopsy showed no new lesions. Two months later, the patient was admitted due to anuria, haematochezia with anaemia, requiring 5 units of packed red blood cells, and diffuse skin thickening. Colonoscopy showed haemorrhagic patches in the colon and the rectum; histology diagnosis was Kaposi sarcoma (KS. A skin biopsy revealed cutaneous involvement of KS. Rapid clinical deterioration culminated in death in June 2014. This case is unusual as less than 20 cases of KS with gross gastrointestinal bleeding have been reported and only 6 cases had the referred bleeding originating in the lower gastrointestinal tract. So, KS should be considered in differential diagnosis of gastrointestinal bleeding in some kidney transplant patients.

Effect of PEG biofunctional spacers and TAT peptide on dsRNA loading on gold nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Sanz, Vanesa; Conde, Joao; Hernandez, Yulan [Universidad de Zaragoza, Instituto de Nanociencia de Aragon (Spain); Baptista, Pedro V. [Universidade Nova de Lisboa, Departamento de Ciencias da Vida, Faculdade de Ciencias e Tecnologia, Centro de Investigacao em Genetica Molecular Humana (Portugal); Ibarra, M. R.; Fuente, Jesus M. de la, E-mail: jmfuente@unizar.es [Universidad de Zaragoza, Instituto de Nanociencia de Aragon (Spain)

2012-06-15

The surface chemistry of gold nanoparticles (AuNPs) plays a critical role in the self-assembly of thiolated molecules and in retaining the biological function of the conjugated biomolecules. According to the well-established gold-thiol interaction the undefined ionic species on citrate-reduced gold nanoparticle surface can be replaced with a self-assembled monolayer of certain thiolate derivatives and other biomolecules. Understanding the effect of such derivatives in the functionalization of several types of biomolecules, such as PEGs, peptides or nucleic acids, has become a significant challenge. Here, an approach to attach specific biomolecules to the AuNPs ({approx}14 nm) surface is presented together with a study of their effect in the functionalization with other specific derivatives. The effect of biofunctional spacers such as thiolated poly(ethylene glycol) (PEG) chains and a positive peptide, TAT, in dsRNA loading on AuNPs is reported. Based on the obtained data, we hypothesize that loading of oligonucleotides onto the AuNP surface may be controlled by ionic and weak interactions positioning the entry of the oligo through the PEG layer. We demonstrate that there is a synergistic effect of the TAT peptide and PEG chains with specific functional groups on the enhancement of dsRNA loading onto AuNPs.

Effect of PEG biofunctional spacers and TAT peptide on dsRNA loading on gold nanoparticles

International Nuclear Information System (INIS)

Sanz, Vanesa; Conde, João; Hernández, Yulán; Baptista, Pedro V.; Ibarra, M. R.; Fuente, Jesús M. de la

2012-01-01

The surface chemistry of gold nanoparticles (AuNPs) plays a critical role in the self-assembly of thiolated molecules and in retaining the biological function of the conjugated biomolecules. According to the well-established gold–thiol interaction the undefined ionic species on citrate-reduced gold nanoparticle surface can be replaced with a self-assembled monolayer of certain thiolate derivatives and other biomolecules. Understanding the effect of such derivatives in the functionalization of several types of biomolecules, such as PEGs, peptides or nucleic acids, has become a significant challenge. Here, an approach to attach specific biomolecules to the AuNPs (∼14 nm) surface is presented together with a study of their effect in the functionalization with other specific derivatives. The effect of biofunctional spacers such as thiolated poly(ethylene glycol) (PEG) chains and a positive peptide, TAT, in dsRNA loading on AuNPs is reported. Based on the obtained data, we hypothesize that loading of oligonucleotides onto the AuNP surface may be controlled by ionic and weak interactions positioning the entry of the oligo through the PEG layer. We demonstrate that there is a synergistic effect of the TAT peptide and PEG chains with specific functional groups on the enhancement of dsRNA loading onto AuNPs.

The HIV-1 Tat protein modulates CD4 expression in human T cells through the induction of miR-222.

Science.gov (United States)

Orecchini, Elisa; Doria, Margherita; Michienzi, Alessandro; Giuliani, Erica; Vassena, Lia; Ciafrè, Silvia Anna; Farace, Maria Giulia; Galardi, Silvia

2014-01-01

Several cellular microRNAs show substantial changes in expression during HIV-1 infection and their active role in the viral life cycle is progressively emerging. In the present study, we found that HIV-1 infection of Jurkat T cells significantly induces the expression of miR-222. We show that this induction depends on HIV-1 Tat protein, which is able to increase the transcriptional activity of NFkB on miR-222 promoter. Moreover, we demonstrate that miR-222 directly targets CD4, a key receptor for HIV-1, thus reducing its expression. We propose that Tat, by inducing miR-222 expression, complements the CD4 downregulation activity exerted by other viral proteins (i.e., Nef, Vpu, and Env), and we suggest that this represents a novel mechanism through which HIV-1 efficiently represses CD4 expression in infected cells.

Acroangiodermatite (pseudossarcoma de Kaposi: uma condição raramente reconhecida. Um caso na planta do pé associado a insuficiência venosa crônica Acroangiodermatitis (pseudo-Kaposi sarcoma: a rarely-recognized condition. A case on the plantar aspect of the foot associated with chronic venous insufficiency

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Maria Inês Fernandes Pimentel

2011-08-01

Full Text Available A acroangiodermatite ou pseudossarcoma de Kaposi é entidade angioproliferativa incomum relacionada a insuficiência venosa crônica, fístulas arteriovenosas, membros paralisados, cotos de amputação, síndromes vasculares e condições trombóticas. Apresenta-se, em geral, como máculas, pápulas ou placas purpúricas no dorso dos pés (especialmente hálux e maléolos. Relatamos um caso de acroangiodermatite afetando a região plantar, por dois anos sem diagnóstico, para o qual a coloração histológica por hematoxilina-eosina e a marcação imuno-histoquímica com CD34 foram decisivas. A paciente tinha insuficiência venosa crônica e a lesão respondeu bem ao uso de bandagens elásticas e repouso com a perna elevadaAcroangiodermatitis, often known as pseudo-Kaposi sarcoma, is an uncommon angioproliferative entity related to chronic venous insufficiency, arteriovenous fistulae, paralysed limbs, amputation stumps, vascular syndromes and conditions associated with thrombosis. It presents most frequently as purple macules, papules or plaques in the dorsal aspects of the feet, especially the toes, and the malleoli. We report a case of acroangiodermatitis in the plantar aspect of the foot, misdiagnosed for two years, in which haematoxylin-eosin hystopathological stain and immunolabeling with CD34 histochemistry examination were decisive for diagnosis. Patient had chronic venous insufficiency. The lesion responded well to the treatment with a combination of leg elevation and compression

L'état de l'environnement industriel français est-il objectivement mesurable ?

OpenAIRE

Gotteland, David; Boulé, Jean-Marie

2004-01-01

Working paper serie RMT (WPS 04-07); the environmental state is a frequently modelized variable in marketing research. This paper proposes updated scales and panorama of the objective state of 58 industrial branches defined by INSEE based on three characteristic dimensions: dynamism, complexity and capacity.; l'état de l'environnement est une variable fréquemment modélisée dans la recherche en marketing. A partir de ce constat, cet article propose une échelle de mesure et un panorama actualis...

The HIV-1 Tat protein modulates CD4 expression in human T cells through the induction of miR-222

Science.gov (United States)

Orecchini, Elisa; Doria, Margherita; Michienzi, Alessandro; Giuliani, Erica; Vassena, Lia; Ciafrè, Silvia Anna; Farace, Maria Giulia; Galardi, Silvia

2014-01-01

Several cellular microRNAs show substantial changes in expression during HIV-1 infection and their active role in the viral life cycle is progressively emerging. In the present study, we found that HIV-1 infection of Jurkat T cells significantly induces the expression of miR-222. We show that this induction depends on HIV-1 Tat protein, which is able to increase the transcriptional activity of NFkB on miR-222 promoter. Moreover, we demonstrate that miR-222 directly targets CD4, a key receptor for HIV-1, thus reducing its expression. We propose that Tat, by inducing miR-222 expression, complements the CD4 downregulation activity exerted by other viral proteins (i.e., Nef, Vpu, and Env), and we suggest that this represents a novel mechanism through which HIV-1 efficiently represses CD4 expression in infected cells. PMID:24717285

Plan de ventas para el cumplimiento de metas y presupuestos de SUMARC TAT

OpenAIRE

Carvajal Londoño, Paula Carolina; Martínez Rojas, Natalia Camila

2015-01-01

La empresa SUMARC TATS.A.S se ha desempeñado desde su fundación como distribuidor de los productos de NUTRESA en el canal tradicional y durante los últimos ocho años se ha mantenido en el mercado enfrentando retos y desafíos que le permiten hoy en día tener un amplio conocimiento del canal. Sin embargo, en los últimos meses se han detectado falencias en términos de cumplimiento de metas y presupuestos, lo cual implica que la empresa debe diseñar un nuevo esquema comercial que le permita cumpl...

Le syndrome de fatigue chronique et la fibromyalgie au Canada : prévalence et associations avec six indicateurs de l'état de santé

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C. Rusu

2015-01-01

Full Text Available Introduction : Peu d'études ont traité, à l'aide de données populationnelles, des facteurs associés de façon indépendante au syndrome de fatigue chronique (SFC et à la fibromyalgie (FM ou des répercussions de ces affections sur l'état de santé. Méthodologie : Nous avons utilisé les données de l'Enquête sur la santé dans les collectivités canadiennes de 2010 (n=59 101, représentative de la population à l'échelle nationale, pour décrire les cas autodéclarés de SFC et de FM diagnostiqués par un professionnel de la santé et pour déterminer les associations de ces affections avec six indicateurs de l'état de santé. Résultats : En 2010, 1,4 % (intervalle de confiance [IC] à 95 % : 1,3 % à 1,6 % des Canadiens de 12 ans ou plus vivant à domicile ont déclaré avoir reçu un diagnostic de SFC,1,5 % (IC à 95 %: 1,4 % à 1,7 % de FM, et 0,3 % (IC à 95 %: 0,3 % à 0,4 % a déclaré être atteinte à la fois de SFC et de FM. Les cas de SFC comme ceux de FM étaient plus fréquents chez les femmes, les adultes de 40 ans ou plus, les personnes à faible revenu et les personnes présentant certains facteurs de risque de maladie chronique (obésité, sédentarité et tabagisme. Après ajustement en fonction des différences existant entre les groupes, les personnes ayant déclaré être atteintes du SFC ou de FM ou des deux avaient un moins bon état de santé que les personnes atteintes d'aucune de ces affections pour cinq indicateurs de l'état de santé, mais aucune différence n'a été trouvée entre ces groupes par rapport à l'indicateur de santé mentale. Le fait d'être atteint à la fois du SFC et de FM et de présenter de multiples affections comorbides était associé à un moins bon état de santé. Conclusion : La présence concomitante du SFC, de la FM et d'autres affections chroniques était étroitement associée au fait d'avoir un moins bon état de santé, et les différences relatives à l'état de santé �

Radiation therapy for the treatment of skin Kaposi sarcoma.

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Tsao, May N; Sinclair, Emily; Assaad, Dalal; Fialkov, Jeff; Antonyshyn, Oleh; Barnes, Elizabeth

2016-10-01

Kaposi sarcoma (KS) lesions are purplish, reddish blue or dark brown/black macules, plaques or nodules which involve the skin and occasionally internal organs. Most patients with KS have a long indolent chronic course. A retrospective review was undertaken for all KS skin patients treated with radiotherapy at a tertiary cancer centre from Jan. 2, 1999 to Dec. 31, 2014 (inclusive). A total of 47 patients with KS (43 classical, 0 African, 1 iatrogenic, 3 AIDS related) were seen in the multidisciplinary clinic. Out of this group, 17 patients (5 females and 12 males, 14 classical, 0 African, 0 iatrogenic, 3 AIDS related) with 97 KS skin sites were treated with local external beam radiotherapy. An additional 18 skin sites were treated with repeat radiotherapy. The radiotherapy dose ranged from 6 Gy in 1 fraction to 30 Gy in 10 fractions with the most common dose fractionation scheme being 8 Gy in 1 fraction or 20 Gy in 5 daily fractions. For the previously untreated KS sites, 87% responded to radiation [30% complete response (CR) and 57% partial response (PR)]. Thirteen percent of KS sites treated with radiation progressed. For the skin sites which were treated with repeat radiotherapy, 0% showed CRs, 50% PRs and 50% had continued progression. The majority of KS skin lesions (87%) responded to radiotherapy. Patients experience minimal side effects from the palliative radiation regimens used. KS skin lesions which progress despite radiation are unlikely to show CR with repeat radiotherapy. In our experience 50% of skin KS will have partial regression with repeat radiotherapy and 50% will have continued progression.

Staining for factor VIII related antigen and Ulex europaeus agglutinin I (UEA-I) in 230 tumours. An assessment of their specificity for angiosarcoma and Kaposi's sarcoma.

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Leader, M; Collins, M; Patel, J; Henry, K

1986-11-01

In this study we examined the staining reactivity of commercially available antisera to factor VIII related antigen (F VIII RAg) and Ulex europaeus agglutinin I (UEA-I) on sections from 230 formalin fixed paraffin embedded tumours. These included 196 sarcomas, 20 carcinomas and 14 angiomas. All angiomas showed positive staining for F VIII RAg; all carcinomas showed negative staining; the vasoformative areas of all angiosarcomas stained positively but only four of six angiosarcomas showed positive staining of their solid areas; of seven Kaposi's sarcomas, all showed positive staining of vessels and six showed positive staining of the spindle cell component. In the remaining 181 non-vascular sarcomas there was a false positive result in four tumours (2.2%), three of which had a history of irradiation. Pre-radiotherapy biopsies of these three tumours stained negatively with anti-F VIII RAg. UEA-I was demonstrated in all the angiomas studied, in all angiosarcomas (including the solid components) and in well-formed vessels of all Kaposi's sarcomas, but only in the spindle cell component of 3/6. However, there was an unacceptably high rate of false positive staining amongst the carcinomas and non-vascular sarcomas. In conclusion, F VIII RAg is a specific but not a sensitive marker of angiosarcomas; UEA-I is a sensitive but not a specific marker of angiosarcomas.

D2-40 negative pyogenic granuloma-like Kaposi's sarcoma: Diagnostic features and histogenetic hypothesis of an uncommon skin tumor in HIV-negative patients.

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Cabibi, D; Giannone, A G; Guarnotta, C; Schillaci, O; Franco, V

2015-07-01

Pyogenic granuloma-like Kaposi's sarcoma (PGLKS) is a recently described skin tumor showing features both of pyogenic granuloma (PG) and Kaposi's sarcoma (KS). The differential diagnosis is often challenging. We reviewed a series of 50 PG and 23 Ks located on distal extremities with the aid of an immunohistochemical panel comprising CD34, CD31, FVIII, SMA, D2-40, HHV8. After revision, 6/50 PG lesions previously diagnosed as PG, showed positive immunostaining for LNA1-HHV8 and focal positivity for CD31 and FVIII in the endothelial cells of the proliferating vessels, with some SMA positive pericytes. D2-40, a marker of lymphatic endothelium positive in KS, stained negatively. These lesions were renamed PGLKS. Of note, in our series, PGLKS represented the only form of KS localized in the hand; all the patients were HIV-negative, older than PG patients, with a prevalence for male gender. PGLKS and PG need a different management and a follow-up is advisable for PGLKS, as for the other variants of KS. To date, D2-40 negative immunostaining has not yet been reported in PGLKS and should not lead to a misdiagnosis of PG. The morphological similarities with PG and the immunohistochemical findings, showing a defective phenotype of the neoplastic cells, suggest a histogenetic hypothesis in which D2-40 negative PGLKS could represent an early stage of HHV8 infection of a pre-existing PG, whose vessels loose progressively their blood vascular markers but have not still acquired the lymphatic ones. Copyright © 2015 Elsevier GmbH. All rights reserved.

A case of exogenous corticosteroid-induced Kaposi's sarcoma that developed after a cure of endogenous hypercortisolism.

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Yoo, Soyeon; Moon, Shinhang; Chin, Sang-Ouk; Lee, Sang-Ah; Hyun, Changlim; Koh, Gwanpyo

2015-12-01

Case Kaposi's sarcoma (KS) is a malignant vascular tumor that occurs commonly in patients with acquired immunodeficiency syndrome. KS associated with Cushing's syndrome (CS) is unusual, especially in endogenous CS. Here, we report a case of KS associated with glucocorticoid-replacement therapy after surgical treatment for adrenal CS. A 70-year-old man presented with symptoms and signs of CS with a left adrenal mass. Adrenal CS was confirmed by biochemical studies. After left adrenalectomy, he took oral prednisolone (15 mg/day) to prevent adrenal insufficiency. Ten weeks later, numerous raised purple plaques on the lower extremities were newly detected. The biopsy findings were compatible with KS, but anti-HIV antibodies were negative. After withdrawal of glucocorticoid therapy, the skin lesions regressed completely. In this case, KS developed after the use of exogenous corticosteroid but not during endogenous hypercortisolism. This finding suggests that endogenous and exogenous corticosteroid play different roles in the development of KS.

Étude sur l'état de la démocratie et de la gouvernance au Sri Lanka ...

International Development Research Centre (IDRC) Digital Library (Canada)

Étude sur l'état de la démocratie et de la gouvernance au Sri Lanka. Ce projet de recherche aidera la Social Scientists' Association (SSA) du Sri Lanka à contribuer à la deuxième phase du projet State of Democracy and Human Security in South Asia (SDSA). Des chercheurs chevronnés de la SSA et du programme Lokniti ...

DNA-PK/Ku complex binds to latency-associated nuclear antigen and negatively regulates Kaposi's sarcoma-associated herpesvirus latent replication

Energy Technology Data Exchange (ETDEWEB)

Cha, Seho [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of); Lim, Chunghun [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Lee, Jae Young [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of); Song, Yoon-Jae [Department of Life Science, Kyungwon University, Seongnam-Si, Kyeonggi-Do 461-701 (Korea, Republic of); Park, Junsoo [Division of Biological Science and Technology, Yonsei University, Wonju 220-100 (Korea, Republic of); Choe, Joonho [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Seo, Taegun, E-mail: tseo@dongguk.edu [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of)

2010-04-16

During latent infection, latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays important roles in episomal persistence and replication. Several host factors are associated with KSHV latent replication. Here, we show that the catalytic subunit of DNA protein kinase (DNA-PKcs), Ku70, and Ku86 bind the N-terminal region of LANA. LANA was phosphorylated by DNA-PK and overexpression of Ku70, but not Ku86, impaired transient replication. The efficiency of transient replication was significantly increased in the HCT116 (Ku86 +/-) cell line, compared to the HCT116 (Ku86 +/+) cell line, suggesting that the DNA-PK/Ku complex negatively regulates KSHV latent replication.

First application of hemi-body electron beam irradiation for Kaposi sarcoma at the lower extremities.

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Platoni, Kalliopi; Diamantopoulos, Stefanos; Dilvoi, Maria; Delinikolas, Panagiotis; Kypraiou, Efrosyni; Efstathopoulos, Efstathios; Kouloulias, Vassilis

2018-01-01

Kaposi's sarcoma (KS) is a systemic neoplastic disease that can present cutaneous symptoms and is usually treated with a systematic approach due to its extent. Due to its radiosensitivity, radiotherapy is considered one of its main treatments, for palliation and local control of the skin and mucosal lesions. The aim of this paper was to report the first case of KS treated by hemi-body electron irradiation protocol in Greece. A fractionated 40 Gy hemi-body electron irradiation was prescribed to a 60-year-old male patient with KS at his legs. Dose uniformity was verified on a daily basis by thermoluminescence dosimetry (TLD). The treatment resulted to complete clinical response. Limited irradiation-derived side effects appeared. This is the first case ever to be treated with hemi-body electron irradiation protocol in Greece. To the best of our knowledge, this is also the first time that a single field hemi-body electron beam irradiation at a total skin electron beam (TSEB)-like configuration is reported to be used for KS.

Short-Chain Fatty Acids from Periodontal Pathogens Suppress Histone Deacetylases, EZH2, and SUV39H1 To Promote Kaposi's Sarcoma-Associated Herpesvirus Replication

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Yu, Xiaolan; Shahir, Abdel-Malek; Sha, Jingfeng; Feng, Zhimin; Eapen, Betty; Nithianantham, Stanley; Das, Biswajit; Karn, Jonathan; Weinberg, Aaron; Bissada, Nabil F.

2014-01-01

ABSTRACT Periodontal pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum produce five different short-chain fatty acids (SCFAs) as metabolic by-products. We detect significantly higher levels of SCFAs in the saliva of patients with severe periodontal disease. The different SCFAs stimulate lytic gene expression of Kaposi's sarcoma-associated herpesvirus (KSHV) dose dependently and synergistically. SCFAs inhibit class-1/2 histone deacetylases (HDACs) and downregulate expression of silent information regulator-1 (SIRT1). SCFAs also downregulate expression of enhancer of zeste homolog2 (EZH2) and suppressor of variegation 3-9 homolog1 (SUV39H1), which are two histone N-lysine methyltransferases (HLMTs). By suppressing the different components of host epigenetic regulatory machinery, SCFAs increase histone acetylation and decrease repressive histone trimethylations to transactivate the viral chromatin. These new findings provide mechanistic support that SCFAs from periodontal pathogens stimulate KSHV replication and infection in the oral cavity and are potential risk factors for development of oral Kaposi's sarcoma (KS). IMPORTANCE About 20% of KS patients develop KS lesions first in the oral cavity, while other patients never develop oral KS. It is not known if the oral microenvironment plays a role in oral KS tumor development. In this work, we demonstrate that a group of metabolic by-products, namely, short-chain fatty acids, from bacteria that cause periodontal disease promote lytic replication of KSHV, the etiological agent associated with KS. These new findings provide mechanistic support that periodontal pathogens create a unique microenvironment in the oral cavity that contributes to KSHV replication and development of oral KS. PMID:24501407

Sarcoma de Kaposi y linfomas no hodgkinianos asociados con infección por el virus de inmunodeficiencia humana HIV associated to Kaposi's sarcoma and non-Hodgkin lymphomas

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Bertha Beatriz Socarrás Ferrer

2004-04-01

Full Text Available El SIDA es producido por el virus de la inmunodeficiencia humana, tiene la particularidad de infectar y destruir las células del sistema inmune, lo que producen un estado de inmunosupresión irreversible y progresivo en el organismo que se hace susceptible a múltiples infecciones virales, micóticas y bacterianas. Se describen múltiples neoplasias en estos pacientes, pero solo algunos muestran directa relación con el virus de la inmunodeficiencia humana, y su aparición implica el diagnóstico del SIDA: sarcoma de Kaposi, linfomas no hodgkinianos, linfoma cerebral primario y carcinoma de cérvix uterino. El tratamiento de estos pacientes es difícil debido a los problemas provocados por la infección del virus de inmunodeficiencia humana que debilita el sistema inmunitarioAIDS is produced by HIV. It has the particularity of infecting and destroying the immune system cells, producing an irreversible and progressive immunodepression state in the organism, which makes it susceptible to multiple viral, mycotic and bacterial infections. Several neoplasias are described in these patients, but only some of them show a direct relation to the HIV and its appearance implies the AIDS diagnosis: Kaposi’s sarcoma, non-hodgkin lymphomas, primary brain lymphoma and uterine cervix carcinoma. The treatment of these patients is difficult due to the problems provoked by the HIV infection that weakens the immunity system

Appréhender le probléme historique de l'État sous l'approche de la culture politique. Éléments de réflexion

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Martin Pâquet

1998-01-01

Full Text Available "Histoire-carrefour", l'étudedel' État se glisse entre les césures des spécialités. Souventefois on adéploré, ál´instar du moderniste Richard Bonney, que "les zones de l'histoire qui ont été le plus négligées" soient "les zones-frontiéres' Dans un article récent, Jean-Marie Fecteau a renchéri dans le même  sens, soulignant la négligence de l'État et du Droit par l'historiographie contemporaine, malgré le renouveau de l'histoire politique.

Azidothymidine Sensitizes Primary Effusion Lymphoma Cells to Kaposi Sarcoma-Associated Herpesvirus-Specific CD4+ T Cell Control and Inhibits vIRF3 Function.

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Samantha J Williamson

2016-11-01

Full Text Available Kaposi sarcoma-associated herpesvirus (KSHV is linked with the development of Kaposi sarcoma and the B lymphocyte disorders primary effusion lymphoma (PEL and multi-centric Castleman disease. T cell immunity limits KSHV infection and disease, however the virus employs multiple mechanisms to inhibit efficient control by these effectors. Thus KSHV-specific CD4+ T cells poorly recognize most PEL cells and even where they can, they are unable to kill them. To make KSHV-infected cells more sensitive to T cell control we treated PEL cells with the thymidine analogue azidothymidine (AZT, which sensitizes PEL lines to Fas-ligand and TRAIL challenge; effector mechanisms which T cells use. PELs co-cultured with KSHV-specific CD4+ T cells in the absence of AZT showed no control of PEL outgrowth. However in the presence of AZT PEL outgrowth was controlled in an MHC-restricted manner. To investigate how AZT sensitizes PELs to immune control we first examined BJAB cells transduced with individual KSHV-latent genes for their ability to resist apoptosis mediated by stimuli delivered through Fas and TRAIL receptors. This showed that in addition to the previously described vFLIP protein, expression of vIRF3 also inhibited apoptosis delivered by these stimuli. Importantly vIRF3 mediated protection from these apoptotic stimuli was inhibited in the presence of AZT as was a second vIRF3 associated phenotype, the downregulation of surface MHC class II. Although both vFLIP and vIRF3 are expressed in PELs, we propose that inhibiting vIRF3 function with AZT may be sufficient to restore T cell control of these tumor cells.

La Somalie en mauvais État

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Alain Gascon

2008-05-01

Full Text Available La Somalie a sombré depuis 1988 dans une guerre civile que rien ne semble pouvoir arrêter. Les chefs de guerre se disputent des portions du territoire en autant de repaires pour y organiser leurs trafics criminels. Expulsés de Mogadiscio par les milices des tribunaux islamiques, ils y sont revenus avec le gouvernement provisoire, réinstallé par l’Éthiopie. Toutefois, au Somaliland, au Nord, les autorités séparatistes ont rétabli la paix sur tout leur territoire, reconstruit les infrastructures et organisé des élections que personne n’a contestées, mais l’ONU, sous la pression conjuguée de la Ligue Arabe et de l’Union africaine, refuse de reconnaître l’indépendance de l’ex-colonie britannique. Après vingt ans d’indifférence à ce lointain conflit, l’État somalien est menacé de disparition.Since 1988 Somalia has sunk into an endless civil war. Warlords have been fighting over parts of the national territory in order to expand their criminal traffics. They were expelled from the capital by the Islamic court militias but they have returned to it when the Provisionnal Government of Somalia was restored by Ethiopia in Mogadisico. Under the pressures of the Arab League and of the African Union the United Nations have constantly refused to recognize the independence of Somaliland, a former British colony, despite its separatist government has brought peace on all their territory, rebuilt equipments and held fair elections. Twenty years of indifference to this remote conflict have threatened the Somalian state to death.

Y. Laberge on Frédéric Salmon's Atlas historique des États-Unis.

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2010-06-01

Full Text Available Frédéric Salmon, Atlas historique des États-Unis de 1783 à nos jours. Paris: Armand Colin, 2008. Pp.127. ISBN-13: 978-2200347604  This new, cultural, historical atlas of United States was entirely conceived by a French geographer named Frédéric Salmon; this is not a mere collection of old or already existing maps, but rather a brand new group of unique maps related to the geography, history and demographics of the USA, from the late 18th century to the early 21st century. It should not be mix...

On the Sidelines of the Failed Coup d’ État in Turkey : Can Greece Extradite the Eight Turkish Military Officers to Turkey?

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Rachovitsa, Adamantia

2016-01-01

The article discusses the pending extradition case of eight Turkish military officers who, on the night of the recent failed coup d’ état in Turkey, defected and resorted to Greece. The analysis addresses the public emergency in Turkey, insofar it is relevant for the extradition case, against the

Key Performance Indicators to Measure Improvement After Implementation of Total Laboratory Automation Abbott Accelerator a3600.

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Miler, Marijana; Nikolac Gabaj, Nora; Dukic, Lora; Simundic, Ana-Maria

2017-12-27

The aim of the study was to estimate improvement of work efficiency in the laboratory after implementation of total laboratory automation (TLA) by Abbott Accelerator a3600 in the laboratory with measuring different key performance indicators (KPIs) before and after TLA implementation. The objective was also to recommend steps for defining KPIs in other laboratories. For evaluation of improvement 10 organizational and/or technical KPIs were defined for all phases of laboratory work and measured before (November 2013) and after (from 2015 to 2017) TLA implementation. Out of 10 defined KPIs, 9 were successfully measured and significantly improved. Waiting time for registration of samples in the LIS was significantly reduced from 16 (9-28) to 9 (6-16) minutes after TLA (P performed at core biochemistry analyzers which significantly reduced walking distance for sample management (for more than 800 m per worker) and number of tube touches (for almost 50%). Analyzers downtime and engagement time for analyzers maintenance was reduced for 50 h and 28 h per month, respectively. TLA eliminated manual dilution of samples with extreme results with sigma values increment from 3.4 to >6 after TLA. Although median turnaround time TAT for potassium and troponin was higher (for approximately 20 min), number of outliers with TAT >60 min expressed as sigma values were satisfying (>3). Implementation of the TLA improved the most of the processes in our laboratory with 9 out of 10 properly defined and measured KPIs. With proper planning and defining of KPIs, every laboratory could measure changes in daily workflow.

Les «États point-champ» phéniciens et l’empire carthaginois dans l’espace méditerranéen (IXe-IIe siècles avant J.-C.

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Philippe Moyen

2006-03-01

Full Text Available De la prospérité des cités-États phéniciennes à la disparition de l’empire carthaginois, la Méditerranée, entre le IXe et le IIe siècle, constitue un champ d’analyse privilégié pour étudier, dans la longue durée, l’évolution des «États point-champ» et mettre en évidence la diversité des modalités de territorialisation dans la production des aires géopolitiques supports de la trame évènementielle de l’Histoire.

Human herpesvirus-8 (HHV-8 sero-detection and HIV association in Kaposi's sarcoma (KS, non-KS tumors and non-neoplastic conditions

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Pak Fatemeh

2008-06-01

Full Text Available Abstract Background The association of the human herpesvirus-8/Kaposi's sarcoma (KS-associated herpesvirus (HHV-8/KSHV serology with various malignancies in Tanzania is not currently well established while previous studies were based on either PCR or immunofluorescence assays [IFA] but not with a sensitive enzyme-linked immunosorbent assay (ELISA. Selected archival diagnostic biopsies (n = 184 and sera from indigenous patients with KS (n = 120, non-KS tumors (n = 24 and non-neoplastic lesions (n = 40 at Muhimbili National Hospital (MNH, Tanzania, were evaluated by diagnostic histopathology, immunohistology [anti-HHV-8 latency-associated nuclear antigen (LANA] and serology for HIV (ELISA and HHV-8 (IFA and ELISA. Results About 66.3% (n = 122 cases including AIDS-associated Kaposi's sarcoma (AKS (n = 93, reactive conditions (n = 28 and only one non-KS tumour were HIV positive. Endemic KS (EKS patients were mostly males (96.3%, 26/27 who were less (69.9%, 65/93 predominant in AIDS-associated (AKS. A high (89% percentage of patients with anti-HHV-8 antibodies was found in the cohort including the HIV positive (92% cases, males (81.2%, KS patients (93%, non-KS tumors (92%, and reactive conditions (75%. All HHV-8 seronegative KS cases were nodular stage whereas both sera and corresponding biopsies from early stage KS were HHV-8+. Assay sensitivity, positive predictive value (PPV and specificity were 98.6%, 93.5% and 16.7% for IFA and 93.5%, 98.6% and 50.0% for ELISA respectively. Conclusion HHV-8 seroprevalence at MNH appears high as expected among AKS cases and males but also in non-KS patients. ELISA showed a combination of high HHV-8 sensitivity as well as higher PPV and specificity than IFA which however, showed higher sensitivity. The apparent stage-dependent, inverted serum HHV-8 immunoreactivity supports a notion of viral immune-segregation during KS development. Routine HHV-8 screening should be considered particularly in patients at risk of

HITS-CLIP analysis uncovers a link between the Kaposi's sarcoma-associated herpesvirus ORF57 protein and host pre-mRNA metabolism.

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Emi Sei

2015-02-01

Full Text Available The Kaposi's sarcoma associated herpesvirus (KSHV is an oncogenic virus that causes Kaposi's sarcoma, primary effusion lymphoma (PEL, and some forms of multicentric Castleman's disease. The KSHV ORF57 protein is a conserved posttranscriptional regulator of gene expression that is essential for virus replication. ORF57 is multifunctional, but most of its activities are directly linked to its ability to bind RNA. We globally identified virus and host RNAs bound by ORF57 during lytic reactivation in PEL cells using high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP. As expected, ORF57-bound RNA fragments mapped throughout the KSHV genome, including the known ORF57 ligand PAN RNA. In agreement with previously published ChIP results, we observed that ORF57 bound RNAs near the oriLyt regions of the genome. Examination of the host RNA fragments revealed that a subset of the ORF57-bound RNAs was derived from transcript 5' ends. The position of these 5'-bound fragments correlated closely with the 5'-most exon-intron junction of the pre-mRNA. We selected four candidates (BTG1, EGR1, ZFP36, and TNFSF9 and analyzed their pre-mRNA and mRNA levels during lytic phase. Analysis of both steady-state and newly made RNAs revealed that these candidate ORF57-bound pre-mRNAs persisted for longer periods of time throughout infection than control RNAs, consistent with a role for ORF57 in pre-mRNA metabolism. In addition, exogenous expression of ORF57 was sufficient to increase the pre-mRNA levels and, in one case, the mRNA levels of the putative ORF57 targets. These results demonstrate that ORF57 interacts with specific host pre-mRNAs during lytic reactivation and alters their processing, likely by stabilizing pre-mRNAs. These data suggest that ORF57 is involved in modulating host gene expression in addition to KSHV gene expression during lytic reactivation.

Kaposi's sarcoma herpesvirus C-terminal LANA concentrates at pericentromeric and peri-telomeric regions of a subset of mitotic chromosomes

International Nuclear Information System (INIS)

Kelley-Clarke, Brenna; Ballestas, Mary E.; Komatsu, Takashi; Kaye, Kenneth M.

2007-01-01

The Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) tethers KSHV terminal repeat (TR) DNA to mitotic chromosomes to efficiently segregate episomes to progeny nuclei. LANA contains N- and C-terminal chromosome binding regions. We now show that C-terminal LANA preferentially concentrates to paired dots at pericentromeric and peri-telomeric regions of a subset of mitotic chromosomes through residues 996-1139. Deletions within C-terminal LANA abolished both self-association and chromosome binding, consistent with a requirement for self-association to bind chromosomes. A deletion abolishing TR DNA binding did not affect chromosome targeting, indicating LANA's localization is not due to binding its recognition sequence in chromosomal DNA. LANA distributed similarly on human and non-human mitotic chromosomes. These results are consistent with C-terminal LANA interacting with a cell factor that concentrates at pericentromeric and peri-telomeric regions of mitotic chromosomes

La chaîne de froid en amont de la filière pêche artisanale au Sénégal: état des lieux et mise à niveau

OpenAIRE

Sarr, S. L.

2009-01-01

La présente étude porte sur l’état des lieux et la mise à niveau de la chaîne de froid en Amont de la filière pêche artisanale au Sénégal, notamment dans les régions de Thiès et de Dakar. L’objectif de cette étude est d’une part, de faire l’état des lieux des infrastructures de froid dans les pirogues, les quais pilotes de débarquement, les véhicules de transport et le Marché Central au Poisson de Dakar, d’autre part de formuler un programme de mise à niveau visant à solutionner les insuffisa...

L'état de santé de la population de la ville de Suceava.

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Maria-Magdalena LUPCHIAN

2009-01-01

Full Text Available La structure de la morbidité d’après les causes des maladies à Suceava relève quelques aspects qui montrent que lapopulation de la ville a connu un processus de la transition épidémiologique, manifesté par lacroissance du pourcentage des maladies chroniques et dégénératives, par la réduction dupourcentage des maladies infectieuses et parasitaires, par le remplacement des taux élevés dela mortalité par des taux élevés de la morbidité et par des taux élevés de la mortalité despersonnes âgées. La structure de la morbidité au niveau de la ville de Suceava reflète la grandeimportance des maladies de l’appareil respiratoire (46,6% dans la totalité des maladies quiaffectent les citadins. L’analyse des malades chroniques donne une image plus claire de l’étatde santé de la population. Les malades chroniques sont les personnes les plus touchées par lesmaladies qui ont un caractère permanent ; la maladie chronique implique la permanence de lasurveillance médicale, le traitement médicamenteux permanent et diminue la capacité detravail temporairement ou définitivement. Au niveau de la population de la ville, les maladeschroniques représentent presque 40% avec des variations entre 53,8% dans les quartierspéricentraux et 24% dans le quartier Obcine, en relation avec l’âge moyen de la population.On peut tirer la conclusion que l’état de santé de la population de la ville est clairementinfluencé par l’âge et par le style de vie des citadins, un style de vie qui a connu deschangements importants après 1989. Le fait que les citadins bénéficient d’un meilleur accèsaux services sanitaires peut être mis en évidence par la comparaison de l’état de santé descitadins et des citoyens du milieu rural mais cette approche n’est pas caractéristique pour notreétude. Les mêmes facteurs déterminent aussi les différences intra urbaines ; on peutindividualiser le quartier central et les quartiers p

Le Dix-huit Brumaire de Napoléon Bonaparte : retour sur un coup d'État [Review of: P. Gueniffey. Le Dix-huit Brumaire : l’épilogue de la Révolution française, 9-10 novembre 1799

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Jourdan, A.

2008-01-01

Patrice Gueniffey propose une nouvelle histoire du Dix-huit Brumaire, coup d’État par lequel Napoléon Bonaparte prit le pouvoir le 9 novembre 1799. Il voit dans cet évènement « une manière un peu tendue de résoudre les crises graves de l’État » et dresse un parallèle avec la journée du 13 mai 1958

Cytoplasmic isoforms of Kaposi sarcoma herpesvirus LANA recruit and antagonize the innate immune DNA sensor cGAS.

Science.gov (United States)

Zhang, Guigen; Chan, Baca; Samarina, Naira; Abere, Bizunesh; Weidner-Glunde, Magdalena; Buch, Anna; Pich, Andreas; Brinkmann, Melanie M; Schulz, Thomas F

2016-02-23

The latency-associated nuclear antigen (LANA) of Kaposi sarcoma herpesvirus (KSHV) is mainly localized and functions in the nucleus of latently infected cells, playing a pivotal role in the replication and maintenance of latent viral episomal DNA. In addition, N-terminally truncated cytoplasmic isoforms of LANA, resulting from internal translation initiation, have been reported, but their function is unknown. Using coimmunoprecipitation and MS, we found the cGMP-AMP synthase (cGAS), an innate immune DNA sensor, to be a cellular interaction partner of cytoplasmic LANA isoforms. By directly binding to cGAS, LANA, and particularly, a cytoplasmic isoform, inhibit the cGAS-STING-dependent phosphorylation of TBK1 and IRF3 and thereby antagonize the cGAS-mediated restriction of KSHV lytic replication. We hypothesize that cytoplasmic forms of LANA, whose expression increases during lytic replication, inhibit cGAS to promote the reactivation of the KSHV from latency. This observation points to a novel function of the cytoplasmic isoforms of LANA during lytic replication and extends the function of LANA from its role during latency to the lytic replication cycle.

Promoter switching allows simultaneous transcription of LANA and K14/vGPCR of Kaposi's sarcoma-associated herpesvirus

International Nuclear Information System (INIS)

Staudt, Michelle R.; Dittmer, Dirk P.

2006-01-01

Latent transcription of the latency-associated nuclear antigen (LANA/ORF73) of Kaposi's sarcoma-associated herpesvirus is driven by the LANAp-c. Complexity arises during lytic reactivation, however, as the bicistronic K14/vGPCR transcript initiates 32 bp downstream of LANAp-c in the opposite orientation. We identify an Rta/ORF50-inducible LANA promoter (LANAp-i) that is distinct from the LANAp-c. LANAp-c is unaffected by Rta/ORF50. Utilization of the second, downstream LANAp-i explains how LANA and K14/vGPCR are simultaneously transcribed during de novo infection or lytic reactivation. Transactivation of LANAp-i and K14/vGPCRp requires the C-terminal activation domain of Rta/ORF50 and is mediated by DNA-binding-dependent and -independent Rta/ORF50 mechanisms. Transcriptional profiling following viral reactivation support promoter reporter phenotypes. In sum, cis-elements within the LANAp were selected to ensure faithful expression of LANA and other genes regulated by LANAp during all stages of the KSHV lifecycle despite potential interference from K14/vGPCRp activity

Intracellular-activated Notch1 can reactivate Kaposi's sarcoma-associated herpesvirus from latency

International Nuclear Information System (INIS)

Lan, Ke; Murakami, Masanao; Choudhuri, Tathagata; Kuppers, Daniel A.; Robertson, Erle S.

2006-01-01

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a predominantly latent infection in the infected host. Importantly, during latency, only a small number of viral encoded genes are expressed. This viral gene expression pattern contributes to the establishment of long-term infection as well as the ability of the virus to evade the immune system. Previous studies have been shown that the replication and transcription activator (RTA) encoded by ORF50 activates it downstream genes and initiates viral lytic reactivation through functional interaction with RBP-Jκ, the major downstream effector of the Notch signaling pathway. This indicates that RTA can usurp the conserved Notch signaling pathway and mimic the activities of intracellular Notch1 to modulate gene expression. In this report, we show that the activated intracellular domain of Notch1 (ICN) is aberrantly accumulated in KSHV latently infected pleural effusion lymphoma (PEL) cells. ICN activated the RTA promoter in a dose-dependent manner, and forced expression of ICN in latently infected KSHV-positive cells initiated full blown lytic replication with the production of infectious viral progeny. However, latency-associated nuclear antigen (LANA) which is predominantly expressed during latency can specifically down-modulate ICN-mediated transactivation of RTA and so control KSHV for lytic reactivation. These results demonstrate that LANA can inhibit viral lytic replication by antagonizing ICN function and suggest that LANA is a critical component of the regulatory control mechanism for switching between viral latent and lytic replication by directly interacting with effectors of the conserved cellular Notch1 pathway

The CD8 and CD4 T-cell response against Kaposi's sarcoma-associated herpesvirus is skewed towards early and late lytic antigens.

Directory of Open Access Journals (Sweden)

Rebecca C Robey

Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is causally related to Kaposi's sarcoma (KS, the most common malignancy in untreated individuals with HIV/AIDS. The adaptive T-cell immune response against KSHV has not been fully characterized. To achieve a better understanding of the antigenic repertoire of the CD8 and CD4 T-cell responses against KSHV, we constructed a library of lentiviral expression vectors each coding for one of 31 individual KSHV open reading frames (ORFs. We used these to transduce monocyte-derived dendritic cells (moDCs isolated from 14 KSHV-seropositive (12 HIV-positive and 7 KSHV-seronegative (4 HIV-positive individuals. moDCs were transduced with up to 3 KSHV ORFs simultaneously (ORFs grouped according to their expression during the viral life cycle. Transduced moDCs naturally process the KSHV genes and present the resulting antigens in the context of MHC class I and II. Transduced moDCs were cultured with purified autologous T cells and the CD8 and CD4 T-cell proliferative responses to each KSHV ORF (or group was assessed using a CFSE dye-based assay. Two pools of early lytic KSHV genes ([ORF8/ORF49/ORF61] and [ORF59/ORF65/K4.1] were frequently-recognized targets of both CD8 and CD4 T cells from KSHV seropositive individuals. One pool of late lytic KSHV genes ([ORF28/ORF36/ORF37] was a frequently-recognized CD8 target and another pool of late genes ([ORF33/K1/K8.1] was a frequently-recognized CD4 target. We report that both the CD8 and CD4 T-cell responses against KSHV are skewed towards genes expressed in the early and late phases of the viral lytic cycle, and identify some previously unknown targets of these responses. This knowledge will be important to future immunological investigations into KSHV and may eventually lead to the development of better immunotherapies for KSHV-related diseases.

A viral transcriptional activator of Kaposi's sarcoma-associated herpesvirus (KSHV) induces apoptosis, which is blocked in KSHV-infected cells

International Nuclear Information System (INIS)

Nishimura, Ken; Ueda, Keiji; Sakakibara, Shuhei; Do, Eunju; Ohsaki, Eriko; Okuno, Toshiomi; Yamanishi, Koichi

2003-01-01

Replication and transcription activator (RTA), mostly encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame 50, is expressed in the immediate-early phase of reactivation and plays a critical role in inducing the viral lytic cycle in KSHV-infected cells. We established cell clones from BJAB cells and replication-deficient BCBL-1 cells in which KSHV RTA expression was controlled by an inducible promoter of the tetracycline-based Tet-Off expression system. In RTA-inducible BJAB cells, tetracycline removal induced the synthesis of RTA, resulting in cell death. DNA fragmentation, structural changes in the cell membrane, and poly(ADP-ribose) polymerase (PARP) cleavage were observed in the RTA-induced BJAB cells, indicating that RTA expression induced caspase activation and cell death by apoptosis. However, expression of RTA in RTA-inducible BCBL-1 cells did not undergo apoptosis and cell death. These results suggested that KSHV RTA is an apoptosis inducer that is opposed by an antiapoptotic pathway in infected cells

Markers to differentiate between Kaposi's sarcoma and tuberculous pleural effusions in HIV-positive patients.

Science.gov (United States)

Coleman, M; Finney, L J; Komrower, D; Chitani, A; Bates, J; Chipungu, G A; Corbett, E; Allain, T J

2015-02-01

Kaposi's sarcoma (KS) and tuberculosis (TB) commonly cause pleural effusions in high human immunodeficiency virus (HIV) burden resource-limited countries. Differentiating between them is challenging, as pleural biopsy and TB culture are rarely available. To identify markers to differentiate between TB effusions and KS effusions in HIV-positive patients, and to compare liquid culture and Xpert MTB/RIF in pleural fluid. Fifty HIV-positive patients with pleural effusions recruited in Malawi underwent pleural ultrasound and aspiration. Fluid visual inspection, cell count, bacterial culture, glucose/protein, solid and liquid TB culture and Xpert were performed. The mean age of the patients was 32 years; 30/50 (60%) were male and 29 (58%) had cutaneous/oral KS. Thirteen (26%) pleural fluid samples were liquid culture-positive for TB, while 9/13 (69%) were Xpert-positive. Three (10.3%) KS patients had culture-positive TB effusions; 17 (58.6%) had KS effusions. The relative risk of TB in KS patients increased with limited KS, loculated fluid and low glucose. Eleven (52.3%) non-KS patients had culture-positive TB effusions associated with male sex, straw-coloured fluid and fibrin stranding on ultrasound. KS patients were most likely to have KS effusion, but TB should be considered. Most non-KS patients had TB, supporting the use of World Health Organization guidelines. Xpert identified two thirds of liquid culture-positive results.

RNA Sequencing Reveals that Kaposi Sarcoma-Associated Herpesvirus Infection Mimics Hypoxia Gene Expression Signature

Science.gov (United States)

Viollet, Coralie; Davis, David A.; Tekeste, Shewit S.; Reczko, Martin; Pezzella, Francesco; Ragoussis, Jiannis

2017-01-01

Kaposi sarcoma-associated herpesvirus (KSHV) causes several tumors and hyperproliferative disorders. Hypoxia and hypoxia-inducible factors (HIFs) activate latent and lytic KSHV genes, and several KSHV proteins increase the cellular levels of HIF. Here, we used RNA sequencing, qRT-PCR, Taqman assays, and pathway analysis to explore the miRNA and mRNA response of uninfected and KSHV-infected cells to hypoxia, to compare this with the genetic changes seen in chronic latent KSHV infection, and to explore the degree to which hypoxia and KSHV infection interact in modulating mRNA and miRNA expression. We found that the gene expression signatures for KSHV infection and hypoxia have a 34% overlap. Moreover, there were considerable similarities between the genes up-regulated by hypoxia in uninfected (SLK) and in KSHV-infected (SLKK) cells. hsa-miR-210, a HIF-target known to have pro-angiogenic and anti-apoptotic properties, was significantly up-regulated by both KSHV infection and hypoxia using Taqman assays. Interestingly, expression of KSHV-encoded miRNAs was not affected by hypoxia. These results demonstrate that KSHV harnesses a part of the hypoxic cellular response and that a substantial portion of hypoxia-induced changes in cellular gene expression are induced by KSHV infection. Therefore, targeting hypoxic pathways may be a useful way to develop therapeutic strategies for KSHV-related diseases. PMID:28046107

Hypofractionated radiation therapy in the treatment of epidemic Kaposi sarcoma - A prospective randomized trial

International Nuclear Information System (INIS)

Singh, Niveditha B.; Lakier, Roy H.; Donde, Bernard

2008-01-01

Purpose: To compare a conventional fractionation regimen with a hypofractionated regimen in the treatment of Epidemic Kaposi sarcoma with radiation therapy. Materials and methods: Sixty patients were randomized to receive a standard regimen of 24 Gy in 12 fractions (ARM A) or the study regimen of 20 Gy in five fractions (ARM B). Radiation technique was individualized. Treatment response, local control and toxicity were recorded. Results: Thirty five sites were treated in ARM A and 30 sites in ARM B. Treatment arms were similar for gender, ECOG performance score, treated site, antiretroviral therapy usage, T stage, I stage and S stage. The overall survival using the Kaplan Meier method was 37% at 1 year. Complete responses were recorded at 28 sites (13 Arm A, 15 Arm B), partial responses at 19 sites (8 Arm A, 11 Arm B) and stable disease at three sites (2 Arm A, 1 Arm B). The mean time to maximum objective response was 3 months (range: 1-14 months). Response rates and local control were equal in the two arms (p = 0.73 and 0.77, respectively, log rank test). Acute skin toxicity (p = 0.77) and late skin toxicity (p = 0.24) were equal in the two arms. Conclusion: The two treatment regimens produced equivalent results for treatment response, local recurrence-free survival and toxicity

Dispositifs permanents pour le suivi des forêts en Afrique Centrale : un état des lieux

OpenAIRE

Picard , Nicolas

2007-01-01

38 p.; Cette étude, réalisée dans le cadre d'une convention entre la Commission des Forêts d'Afrique Centrale (COMIFAC) et le Centre de Coopération Internationale en Recherche Argonomique pour le Développement (CIRAD), département Environnements et Sociétés, vise à faire un état des lieux en matière de dispositifs permanents de suivi de la dynamique forestière dans les forêts du bassin du Congo. Elle est la première étape d'une étude visant à définir un protocole de mise en place de dispositi...

Use of the TAT in the assessment of DSM-IV cluster B personality disorders.

Science.gov (United States)

Ackerman, S J; Clemence, A J; Weatherill, R; Hilsenroth, M J

1999-12-01

The Social Cognition and Object Relations Scale (SCORS), developed by Western, Lohr, Silk, Kerber, and Goodrich (1985), is a diagnostic instrument used to assess an array of psychological functioning by using clinical narratives such as the Thematic Apperception Test (TAT; Murray, 1943) stories. This study investigated the utility of the SCORS to differentiate between Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994) antisocial personality disorder (ANPD), borderline personality disorder (BPD), narcissistic personality disorder (NPD), and Cluster C personality disorder (CPD). A sample of 58 patients was separated into four groups: ANPD (n = 9), BPD (n = 21; 18 with a primary BPD diagnosis and 3 with prominent borderline traits who met 4 of the 5 DSM-IV criteria necessary for a BPD diagnosis), NPD (n = 16; 8 with a primary NPD diagnosis and 8 with prominent narcissistic traits who met 4 of the 5 DSM-IV criteria necessary for a NPD diagnosis), and CPD (n = 12). These groups were then compared on the 8 SCORS variables by using 5 TAT cards (1, 2, 3BM, 4, and 13MF). Spearman-Brown correction for 2-way mixed effects model of reliability for the 8 SCORS variables ranged from .70 to .95. The results of categorical and dimensional analyses indicate that (a) SCORS variables can be used to differentiate ANPD, BPD, and NPD; (b) the BPD group scored significantly lower (greater maladjustment) than did the CPD group on certain variables; (c) the BPD group scored significantly lower (greater maladjustment) than did the NPD group on all 8 SCORS variables; (d) the ANPD group scored significantly lower than did the NPD group on certain variables; (e) certain variables were found to be empirically related to the total number of DSM-IV ANPD, BPD, and NPD criteria; and (f) certain variables were found to be empirically related to Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen

A new fluorescence/PET probe for targeting intracellular human telomerase reverse transcriptase (hTERT) using Tat peptide-conjugated IgM

International Nuclear Information System (INIS)

Jung, Kyung oh; Youn, Hyewon; Kim, Seung Hoo; Kim, Young-Hwa; Kang, Keon Wook; Chung, June-Key

2016-01-01

Despite an increasing need for methods to visualize intracellular proteins in vivo, the majority of antibody-based imaging methods available can only detect membrane proteins. The human telomerase reverse transcriptase (hTERT) is an intracellular target of great interest because of its high expression in several types of cancer. In this study, we developed a new probe for hTERT using the Tat peptide. An hTERT antibody (IgG or IgM) was conjugated with the Tat peptide, a fluorescence dye and "6"4Cu. HT29 (hTERT+) and U2OS (hTERT−) were used to visualize the intracellular hTERT. The hTERT was detected by RT-PCR and western blot. Fluorescence signals for hTERT were obtained by confocal microscopy, live cell imaging, and analyzed by Tissue-FAXS. In nude mice, tumors were visualized using the fluorescence imaging devices Maestro™ and PETBOX. In RT-PCR and western blot, the expression of hTERT was detected in HT29 cells, but not in U2OS cells. Fluorescence signals were clearly observed in HT29 cells and in U2OS cells after 1 h of treatment, but signals were only detected in HT29 cells after 24 h. Confocal microscopy showed that 9.65% of U2OS and 78.54% of HT29 cells had positive hTERT signals. 3D animation images showed that the probe could target intranuclear hTERT in the nucleus. In mice models, fluorescence and PET imaging showed that hTERT in HT29 tumors could be efficiently visualized. In summary, we developed a new method to visualize intracellular and intranuclear proteins both in vitro and in vivo. - Highlights: • We developed new probes for imaging hTERT using Tat-conjugated IgM antibodies labeled with a fluorescent dye and radioisotope. • This probes could be used to overcome limitation of conventional antibody imaging system in live cell imaging. • This system could be applicable to monitor intracellular and intranuclear proteins in vitro and in vivo.

A new fluorescence/PET probe for targeting intracellular human telomerase reverse transcriptase (hTERT) using Tat peptide-conjugated IgM

Energy Technology Data Exchange (ETDEWEB)

Jung, Kyung oh [Department of Nuclear Medicine, Seoul National University College of Medicine (Korea, Republic of); Biomedical Sciences, Seoul National University College of Medicine (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine (Korea, Republic of); Tumor Microenvironment Global Core Research Center, Seoul National University (Korea, Republic of); Youn, Hyewon, E-mail: hwyoun@snu.ac.kr [Department of Nuclear Medicine, Seoul National University College of Medicine (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine (Korea, Republic of); Tumor Microenvironment Global Core Research Center, Seoul National University (Korea, Republic of); Cancer Imaging Center, Seoul National University Hospital, Seoul (Korea, Republic of); Kim, Seung Hoo [Department of Nuclear Medicine, Seoul National University College of Medicine (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine (Korea, Republic of); Kim, Young-Hwa [Department of Nuclear Medicine, Seoul National University College of Medicine (Korea, Republic of); Biomedical Sciences, Seoul National University College of Medicine (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine (Korea, Republic of); Kang, Keon Wook [Department of Nuclear Medicine, Seoul National University College of Medicine (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine (Korea, Republic of); Chung, June-Key, E-mail: jkchung@snu.ac.kr [Department of Nuclear Medicine, Seoul National University College of Medicine (Korea, Republic of); Biomedical Sciences, Seoul National University College of Medicine (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine (Korea, Republic of); Tumor Microenvironment Global Core Research Center, Seoul National University (Korea, Republic of)

2016-08-26

Despite an increasing need for methods to visualize intracellular proteins in vivo, the majority of antibody-based imaging methods available can only detect membrane proteins. The human telomerase reverse transcriptase (hTERT) is an intracellular target of great interest because of its high expression in several types of cancer. In this study, we developed a new probe for hTERT using the Tat peptide. An hTERT antibody (IgG or IgM) was conjugated with the Tat peptide, a fluorescence dye and {sup 64}Cu. HT29 (hTERT+) and U2OS (hTERT−) were used to visualize the intracellular hTERT. The hTERT was detected by RT-PCR and western blot. Fluorescence signals for hTERT were obtained by confocal microscopy, live cell imaging, and analyzed by Tissue-FAXS. In nude mice, tumors were visualized using the fluorescence imaging devices Maestro™ and PETBOX. In RT-PCR and western blot, the expression of hTERT was detected in HT29 cells, but not in U2OS cells. Fluorescence signals were clearly observed in HT29 cells and in U2OS cells after 1 h of treatment, but signals were only detected in HT29 cells after 24 h. Confocal microscopy showed that 9.65% of U2OS and 78.54% of HT29 cells had positive hTERT signals. 3D animation images showed that the probe could target intranuclear hTERT in the nucleus. In mice models, fluorescence and PET imaging showed that hTERT in HT29 tumors could be efficiently visualized. In summary, we developed a new method to visualize intracellular and intranuclear proteins both in vitro and in vivo. - Highlights: • We developed new probes for imaging hTERT using Tat-conjugated IgM antibodies labeled with a fluorescent dye and radioisotope. • This probes could be used to overcome limitation of conventional antibody imaging system in live cell imaging. • This system could be applicable to monitor intracellular and intranuclear proteins in vitro and in vivo.

Gene expression profile of AIDS-related Kaposi's sarcoma

International Nuclear Information System (INIS)

Cornelissen, Marion; Kuyl, Antoinette C van der; Burg, Remco van den; Zorgdrager, Fokla; Noesel, Carel JM van; Goudsmit, Jaap

2003-01-01

Kaposi's Sarcoma (KS) is a proliferation of aberrant vascular structures lined by spindle cells, and is caused by a gammaherpes virus (HHV8/KSHV). Its course is aggravated by co-infection with HIV-1, where the timing of infection with HIV-1 and HHV8 is important for the clinical outcome. In order to better understand the pathogenesis of KS, we have analysed tissue from two AIDS-KS lesions, and from normal skin by serial analysis of gene expression (SAGE). Semi-quantitative RT-PCR was then used to validate the results. The expression profile of AIDS-related KS (AIDS-KS) reflects an active process in the skin. Transcripts of HHV8 were found to be very low, and HIV-1 mRNA was not detected by SAGE, although it could be found using RT-PCR. Comparing the expression profile of AIDS-KS tissue with publicly available SAGE libraries suggested that AIDS-KS mRNA levels are most similar to those in an artificially mixed library of endothelial cells and leukocytes, in line with the description of KS lesions as containing spindle cells with endothelial characteristics, and an inflammatory infiltrate. At least 64 transcripts were found to be significantly elevated, and 28 were statistically downregulated in AIDS-KS compared to normal skin. Five of the upregulated mRNAs, including Tie 1 and sialoadhesin/CD169, were confirmed by semi-quantitative PCR to be elevated in additional AIDS-KS biopsies. Antibodies to sialoadhesin/CD169, a known marker of activated macrophages, were shown to specifically label tumour macrophages. The expression profile of AIDS-KS showed 64 genes to be significantly upregulated, and 28 genes downregulated, compared with normal skin. One of the genes with increased expression was sialoadhesin (CD169). Antibodies to sialoadhesin/CD169 specifically labelled tumour-associated macrophages, suggesting that macrophages present in AIDS-KS lesions belong to a subset of human CD169+ macrophages

Kaposi Sarcoma Risk in HIV-Infected Children and Adolescents on Combination Antiretroviral Therapy From Sub-Saharan Africa, Europe, and Asia

DEFF Research Database (Denmark)

Rohner, Eliane; Schmidlin, Kurt; Zwahlen, Marcel

2016-01-01

. RESULTS:  We included 24 991 children from eastern Africa, southern Africa, Europe and Asia; 26 developed KS after starting cART. Incidence rates per 100 000 person-years (PYs) were 86 in eastern Africa (95% confidence interval [CI], 55-133), 11 in southern Africa (95% CI, 4-35), and 81 (95% CI, 26......HR, 3.4; 95% CI, 1.2-10.1) and advanced HIV/AIDS stage (CDC stage C vs A/B; aHR, 2.4; 95% CI, .8-7.3) at cART initiation. CONCLUSIONS:  HIV-infected children from SSA but not those from other regions, have a high risk of developing KS after cART initiation. Early cART initiation in these children might......BACKGROUND:  The burden of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected children and adolescents on combination antiretroviral therapy (cART) has not been compared globally. METHODS:  We analyzed cohort data from the International Epidemiologic Databases to Evaluate AIDS...

Clinical and Endoscopic Features of Gastrointestinal Kaposi Sarcoma: A Single-Center Portuguese Experience over the Last Decade

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Joana Carmo

2017-04-01

Full Text Available Background: Kaposi sarcoma (KS is an angioproliferative tumor caused by human herpesvirus 8 (HHV-8. Gastrointestinal (GI involvement by KS is a rare endoscopic finding, scarcely characterized in the literature. Objective: To characterize clinical and endoscopic features of patients with GI KS. Methods: This is a single-center retrospective study of GI KS cases confirmed by immunohistochemistry in the last decade (2006-2015. The following variables were analyzed: demographic data; clinical data (extraintestinal involvement, symptoms, presence and stage of HIV infection, immunosuppressive therapy; endoscopic data; stage-stratified therapeutic approach; and mortality (at 3 and 6 months. Results: Thirteen patients with GI KS were identified: 77% were men, the mean age was 55 years, and 62% of them were Native Africans. In most cases (n = 10, 77%, KS was associated with HIV. A total of 90% of the HIV patients had a CD4+ count of Conclusion: GI KS is mostly found in nontreated, stage 3, HIV patients, and particularly in men from areas where HHV-8 is endemic. Involvement of the upper digestive tract is often asymptomatic. The endoscopic appearance is variable and these patients have a poor prognosis.

Fédéralisme et droits des LGBT aux États-Unis et au Canada : analyse comparatives des politiques

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Miriam Smith

2014-12-01

Full Text Available L’article examine le militantisme LGBT et les résultats des politiques en matière de droit pénal et du mariage entre personnes de même sexe de 1969 à aujourd’hui, dans le cadre d’une analyse comparée du fédéralisme aux États-Unis et au Canada. Nous soutiendrons que le fédéralisme a grandement façonné les politiques publiques relatives aux droits des LGBT. Dans le régime américain, le potentiel d’expansion du fédéralisme a favorisé les changements graduels de politiques dans les États et, parallèlement, les multiples points de véto créés par le système de séparation des pouvoirs conjugués aux compétences conférés aux États dans d’importants domaines de politiques ont entravé ces changements de politiques. Dans le régime canadien, la centralisation des mécanismes de protection des droits de la personne dans la Charte de même que la dynamique descendante de l’exercice du pouvoir dans le régime parlementaire de type Westminster ont facilité les changements de politiques. Le fédéralisme est souvent perçu comme un obstacle à l’adoption de politiques progressistes. La répartition des pouvoirs entrave l’élaboration de politiques cohérentes et prête le flanc à la prolifération de vétos dont peuvent se prévaloir des groupes influents pour freiner le changement. Les critiques de cette perspective arguent depuis longtemps que, même si le fédéralisme multiplie les points de véto, il présente aussi de nombreuses possibilités d’innovation. Ils font valoir que les groupes ont plus de poids dans les régimes fédéraux puisqu’ils peuvent exercer leur influence à deux paliers de gouvernement plutôt qu’à un. Ainsi, un groupe qui ne réussit pas à se faire entendre à l’un des paliers pourra tenter sa chance au second et pourra même dresser un palier contre l’autre pour atteindre ses objectifs stratégiques.

A desvinculação do TAT do conceito de "projeção" e a ampliação de seu uso Disconection of TAT from the "projective" concept and its use enlargement

Directory of Open Access Journals (Sweden)

Vera Stela Telles

2000-01-01

Full Text Available Crítica à designação de "projetivo" referente aos fenômenos implicados no material do TAT. Procurou-se mostrar que tal designação levou historicamente o teste a ser amarrado às teorias psicanalíticas, sem que nada, nos fenômenos registrados, obrigasse a tal leitura. Ao contrário, a nosso ver, a maior parte da problemática de seu uso em pesquisa e da possibilidade de um consenso geral referente à sua interpretação, deve-se aos problemas inerentes à próprias teorias psicanalíticas. Sugerimos então sua desvinculação desse termo que o remete a um sistema teórico fechado que como tal, impede a verdadeira observação do material obtido pelo teste. Essa observação dos fenômenos permitiria a superação dos impasses e consequentemente a ampliação de seu uso, já que o consenso seria procurado no material, para além de qualquer postura teórica prévia do observador.It criticises the "projective" designation, which refers itself to implicit phenomena on TAT material. It was intended to show that the "projective" led, in historical means, the test to be tied up to psychoanalytic theories, though nothing on those phenomena obliged this interpretation to be made. On the contrary, the largest part from the problematical of its research using and from the possibility of a general consensus, concerning its interpretation, are due to inherent problems of psychoanalysis theories themselves. We suggest, then, its disconnection from this term, which prevents a real remark of the material obtained by the test. The phenomena observation would allow the impasses overcoming and, consequently, the enlargement of its use, since consensus would be searched in the material, beyond any previous theoretical posture from the observer.

Politiques culturelles des États européens : pour une nécessaire refondation.

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Anne-Marie Autissier

2006-03-01

Full Text Available Bien que les politiques culturelles nationales varient considérablement d’un pays européen à l’autre, en fonction des histoires, des sociétés et de la relation entre les États et les milieux professionnels de la culture, l’on peut identifier en Europe occidentale, quelques principes plus ou moins amplement appliqués : la nécessaire liberté artistique, la culture comme objet de politique publique, la nécessité de préserver et de restaurer le patrimoine bâti et les œuvres du répertoire national, comme autant de garants de l’exercice démocratique. Malgré des évolutions asynchrones, les gouvernements européens se sont tous dotés d’administrations en charge de la culture, soit directement liées à l’État, soit agissant dans une certaine marge d’autonomie. Inégalement, la création contemporaine a été soutenue. Enfin, la reconnaissance des cultures et langues régionales a donné lieu à la mise en place de régions jouissant d’une autonomie relative ou importante. Dernier trait commun aux pays d’Europe occidentale, les communes apparaissent partout comme les premiers financeurs des activités culturelles, entendues dans une acception large : de l’art contemporain aux initiatives socio-culturelles. Ce relatif parallélisme a d’ailleurs un impact dans les pays issus du communisme d’État — membres de l’Union ou nouveaux voisins de cette dernière. Les gouvernements de ces pays se sont dotés d’instances et de dispositifs souvent inspirés des politiques européennes occidentales. Depuis les années 1980, la montée en charge des services, la mondialisation des activités financières, les concentrations opérées dans les industries culturelles, obligent les politiques culturelles nationales à trouver de nouvelles réponses. L’on a pu ainsi parler de « politiques culturelles de plus en plus instables », car obligées d’arbitrer entre des marges financières de plus en plus réduites et

Thermodynamic studies of a series of homologous HIV-1 TAR RNA ligands reveal that loose binders are stronger Tat competitors than tight ones.

Science.gov (United States)

Pascale, Lise; Azoulay, Stéphane; Di Giorgio, Audrey; Zenacker, Laura; Gaysinski, Marc; Clayette, Pascal; Patino, Nadia

2013-06-01

RNA is a major drug target, but the design of small molecules that modulate RNA function remains a great challenge. In this context, a series of structurally homologous 'polyamide amino acids' (PAA) was studied as HIV-1 trans-activating response (TAR) RNA ligands. An extensive thermodynamic study revealed the occurence of an enthalpy-entropy compensation phenomenon resulting in very close TAR affinities for all PAA. However, their binding modes and their ability to compete with the Tat fragment strongly differ according to their structure. Surprisingly, PAA that form loose complexes with TAR were shown to be stronger Tat competitors than those forming tight ones, and thermal denaturation studies demonstrated that loose complexes are more stable than tight ones. This could be correlated to the fact that loose and tight ligands induce distinct RNA conformational changes as revealed by circular dichroism experiments, although nuclear magnetic resonance (NMR) experiments showed that the TAR binding site is the same in all cases. Finally, some loose PAA also display promising inhibitory activities on HIV-infected cells. Altogether, these results lead to a better understanding of RNA interaction modes that could be very useful for devising new ligands of relevant RNA targets.

Les Murchidât au Maroc. Entre islam d’État et islam au féminin

OpenAIRE

Dirèche, Karima

2013-01-01

Avec l’émergence des murchidât dans l’espace religieux marocain, c’est la reconnaissance inédite du rôle religieux d’éducatrice des femmes dans la sphère publique. Elles sont  présentées, par l’État et relayé en cela par la presse nationale, comme un des vecteurs de diffusion d’un islam marocain moderne et féministe. Ces nouvelles prédicatrices, soumises à une formation endroit musulman et en sciences sociales sont actives dans le cadre des prisons, des hôpitaux, des lieux de travail et des e...

Identification and characterization of Kaposi's sarcoma-associated herpesvirus open reading frame 11 promotor activation

Energy Technology Data Exchange (ETDEWEB)

Chen, Lei [Los Alamos National Laboratory

2008-01-01

Open reading frame 11 (ORF11) of Kaposi's sarcoma-associated herpesvirus belongs to a herpesviral homologous protein family shared by some members of the gamma- herpesvirus subfamily. Little is known about this ORF11 homologous protein family. We have characterized an unknown open reading frame, ORF11, located adjacent and in the opposite orientation to a well-characterized viral IL-6 gene. Northern blot analysis reveals that ORF11 is expressed during the KSHV lytic cycle with delayed-early transcription kinetics. We have determined the 5{prime} and 3{prime} untranslated region of the unspliced ORF11 transcript and identified both the transcription start site and the transcription termination site. Core promoter region, representing ORF11 promoter activity, was mapped to a 159nt fragment 5{prime} most proximal to the transcription start site. A functional TATA box was identified in the core promoter region. Interestingly, we found that ORF11 transcriptional activation is not responsive to Rta, the KSHV lytic switch protein. We also discovered that part of the ORF11 promoter region, the 209nt fragment upstream of the transcription start site, was repressed by phorbol esters. Our data help to understand transcription regulation of ORF11 and to elucidate roles of ORF11 in KSHV pathogenesis and life cycle.

Identification and Partial Characterization of an L-Tyrosine Aminotransferase (TAT from Arabidopsis thaliana

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Pranav R. Prabhu

2010-01-01

Full Text Available The aminotransferase gene family in the model plant Arabidopsis thaliana consists of 44 genes. Twenty six of these enzymes are classified as characterized meaning that the reaction(s that the enzyme catalyzes are documented using experimental means. The remaining 18 enzymes are uncharacterized and are therefore deemed putative. Our laboratory is interested in elucidating the function(s of the remaining putative aminotransferase enzymes. To this end, we have identified and partially characterized an aminotransferase (TAT enzyme from Arabidopsis annotated by the locus tag At5g36160. The full-length cDNA was cloned and the purified recombinant enzyme was characterized using in vitro and in vivo experiments. In vitro analysis showed that the enzyme is capable of interconverting L-Tyrosine and 4-hydroxyphenylpyruvate, and L-Phenylalanine and phenylpyruvate. In vivo analysis by functional complementation showed that the gene was able to complement an E. coli with a background of aminotransferase mutations that confers auxotrophy for L-Tyrosine and L-Phenylalanine.

Preliminary X-ray diffraction analysis of YcdB from Escherichia coli: a novel haem-containing and Tat-secreted periplasmic protein with a potential role in iron transport

International Nuclear Information System (INIS)

Cartron, Michaël L.; Mitchell, Sue A.; Woodhall, Mark R.; Andrews, Simon C.; Watson, Kimberly A.

2006-01-01

The crystallization and structure determination of the apo form of a novel haem-containing Tat substrate, YcdB from E. coli, has been solved to 2.0 Å resolution. The preliminary structure shows similarity to other haem-dependent peroxidases, despite low sequence homology. YcdB is a periplasmic haem-containing protein from Escherichia coli that has a potential role in iron transport. It is currently the only reported haem-containing Tat-secreted substrate. Here, the overexpression, purification, crystallization and structure determination at 2.0 Å resolution are reported for the apo form of the protein. The apo-YcdB structure resembles those of members of the haem-dependent peroxidase family and thus confirms that YcdB is also a member of this family. Haem-soaking experiments with preformed apo-YcdB crystals have been optimized to successfully generate haem-containing YcdB crystals that diffract to 2.9 Å. Completion of model building and structure refinement are under way

Selective Preference of Parallel DNA Triplexes Is Due to the Disruption of Hoogsteen Hydrogen Bonds Caused by the Severe Nonisostericity between the G*GC and T*AT Triplets.

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Gunaseelan Goldsmith

Full Text Available Implications of DNA, RNA and RNA.DNA hybrid triplexes in diverse biological functions, diseases and therapeutic applications call for a thorough understanding of their structure-function relationships. Despite exhaustive studies mechanistic rationale for the discriminatory preference of parallel DNA triplexes with G*GC & T*AT triplets still remains elusive. Here, we show that the highest nonisostericity between the G*GC & T*AT triplets imposes extensive stereochemical rearrangements contributing to context dependent triplex destabilisation through selective disruption of Hoogsteen scheme of hydrogen bonds. MD simulations of nineteen DNA triplexes with an assortment of sequence milieu reveal for the first time fresh insights into the nature and extent of destabilization from a single (non-overlapping, double (overlapping and multiple pairs of nonisosteric base triplets (NIBTs. It is found that a solitary pair of NIBTs, feasible either at a G*GC/T*AT or T*AT/G*GC triplex junction, does not impinge significantly on triplex stability. But two overlapping pairs of NIBTs resulting from either a T*AT or a G*GC interruption disrupt Hoogsteen pair to a noncanonical mismatch destabilizing the triplex by ~10 to 14 kcal/mol, implying that their frequent incidence in multiples, especially, in short sequences could even hinder triplex formation. The results provide (i an unambiguous and generalised mechanistic rationale for the discriminatory trait of parallel triplexes, including those studied experimentally (ii clarity for the prevalence of antiparallel triplexes and (iii comprehensive perspectives on the sequence dependent influence of nonisosteric base triplets useful in the rational design of TFO's against potential triplex target sites.

Étude théorique et expérimentale de superpositions quantiques cohérentes et d'états intriqués non-gaussiens de la lumière

Science.gov (United States)

Ourjoumtsev, A.

In this thesis, we develop new methods to generate and analyse non-classical states of the light for quantum information processing. We show that the tools of discrete variables, where light is described in terms of photons, can be combined with a continuous approach, where one considers the quadratures of the electromagnetic field, to efficiently create, transform and analyze complex quantum states. Using ultrashort light pulses, we prepared optical “Schrödinger cats”, defined as quantum superpositions of coherent states. In this case the Wigner function, describing the quantum statistics of the electromagnetic field, differs from a classical probability distribution and takes negative values. Time-resolved homodyne tomography allowed us to realize the first experimental observation of this negativity for small free-propagating “Schrödinger kittens”. Furthermore, we developped and experimentally demonstrated a protocol to prepare arbitrarily large “Schrödinger cat” states, opening a way towards numerous quantum information processing protocols. We have shown experimentally that contitional photon subtraction allows one to increase the entanglement of gaussian states. We used this method to entangle two initially independent distant light pulses, using a low-transmission quantum channel. This approach allows one to prepare strongly entangled states with negative Wigner functions between distant sites, as required for entanglement distillation and long-distance quantum communications. Cette thèse porte sur la manipulation d'états non-classiques de la lumière, et leurs applications à l'information quantique. Nous montrons que les outils propres à une description discrète, où la lumière est considérée comme un ensemble de photons, peuvent être efficacement combinés avec une approche continue, où l'on s'intéresse aux quadratures de l'onde électromagnétique, pour créer, transformer et analyser des états quantiques complexes. Nous

HHV-8 infection in patients with AIDS-related Kaposi's sarcoma in Brazil

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Keller R.

2001-01-01

Full Text Available The aims of the present study were to determine the prevalence of human herpesvirus type 8 (HHV-8 in HIV-positive Brazilian patients with (HIV+/KS+ and without Kaposi's sarcoma (HIV+/KS- using PCR and immunofluorescence assays, to assess its association with KS disease, to evaluate the performance of these tests in detecting HHV-8 infection, and to investigate the association between anti-HHV-8 antibody titers, CD4 counts and staging of KS disease. Blood samples from 66 patients, 39 HIV+/KS+ and 27 HIV+/KS-, were analyzed for HHV-8 viremia in peripheral blood mononuclear cells by PCR and HHV-8 antigenemia for latent and lytic infection by immunofluorescence assay. Positive samples for latent nuclear HHV-8 antigen (LNA antibodies were titrated out from 1/100 to 1/409,600 dilution. Clinical information was collected from medical records and risk behavior was assessed through an interview. HHV-8 DNA sequences were detected by PCR in 74.3% of KS+ patients and in 3.7% of KS- patients. Serological assays were similar in detecting anti-LNA antibodies and anti-lytic antigens in sera from KS+ patients (79.5% and KS- patients (18.5%. HHV-8 was associated with KS whatever the method used, i.e., PCR (odds ratio (OR = 7.4, 95% confidence interval (CI = 2.16-25.61 or anti-LNA and anti-lytic antibodies (OR = 17.0, 95%CI = 4.91-59.14. Among KS+ patients, HHV-8 titration levels correlated positively with CD4 counts (rho 0.48, P = 0.02, but not with KS staging. HHV-8 is involved in the development of KS in different geographic areas worldwide, as it is in Brazil, where HHV-8 is more frequent among HIV+ patients. KS severity was associated with immunodeficiency, but no correlation was found between HHV-8 antibody titers and KS staging.

Surface applicators for high dose rate brachytherapy in AIDS-related kaposi's sarcoma

International Nuclear Information System (INIS)

Evans, Michael D.C.; Yassa, Mariam; Podgorsak, Ervin B.; Roman, Ted N.; Schreiner, L. John; Souhami, Luis

1997-01-01

Purpose: The development of commercially available surface applicators using high dose rate remote afterloading devices has enabled radiotherapy centers to treat selected superficial lesions using a remote afterloading brachytherapy unit. The dosimetric parameters of these applicators, the clinical implementation of this technique, and a review of the initial patient treatment regimes are presented. Methods and Materials: A set of six fixed-diameter (1, 2, and 3 cm), tungsten/steel surface applicators is available for use with a single stepping-source (Ir-192, 370 GBq) high dose rate afterloader. The source can be positioned either in a parallel or perpendicular orientation to the treatment plane at the center of a conical aperture that sits at an SSD of approximately 15 mm and is used with a 1-mm thick removable plastic cap. The surface dose rates, percent depth dose, and off-axis ratios were measured. A custom-built, ceiling-mounted immobilization device secures the applicator on the surface of the patient's lesion during treatment. Results: Between November 1994, and September 1996, 16 AIDS-related Kaposi's sarcoma patients having a total of 120 lesions have been treated with palliative intent. Treatment sites were distributed between the head and neck, extremity, and torso. Doses ranged from 8 to 20 Gy, with a median dose of 10 Gy delivered in a single fraction. Treatments were well tolerated with minimal skin reaction, except for patients with lesions treated to 20 Gy who developed moderate/severe desquamation. Conclusion: Radiotherapy centers equipped with a high dose rate remote afterloading unit may treat small selected surface lesions with commercially available surface applicators. These surface applicators must be used with a protective cap to eliminate electron contamination. The optimal surface dose appears to be either 10 or 15 Gy depending upon the height of the lesion

Efficacy of a Film-Forming Medical Device Containing Piroxicam and Sun Filters in the Treatment of Multiple Actinic Keratosis Lesions in a Subject with a History of Kaposi Sarcoma

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Elisabetta Scotti

2016-10-01

Full Text Available Actinic keratosis (AK is considered a premalignant form of skin cancer due to chronic sun exposure. In addition, human papilloma virus (HPV has been advocated a role in the pathogenesis of this clinical condition. HPV proteins (mainly E6 and E7 seem to act synergistically with ultraviolet (UV radiation in reducing the defensive mechanisms of keratinocyte apoptosis after UV damage. Data regarding the involvement of other viruses, i.e. human herpes viruses (HHV, in the pathogenesis of AK are so far controversial. HHV8 is considered the infective agent involved in the development of Kaposi sarcoma. Some experimental data have shown that AK lesions carry HHV8 in more than 30% of the bioptic samples. Topical piroxicam was shown to be effective in the treatment of AK. In addition, the molecule shows antiviral action against HPV and HHV8. Here, we report the efficacy of a medical device containing a film-forming substance (polyvinyl alcohol, chemical and physical sun filters (SPF 50+, and 0.8% piroxicam (ActixicamTM, Difa Cooper; ACTX in the treatment of multiple scalp AK lesions, unresponsive to other treatments, in a subject with Kaposi sarcoma and a history of severe contact dermatitis. The subject presented with severe involvement of the scalp, with multiple hypertrophic AK lesions. Previous lesion-directed and field-targeted treatments have not been effective. The subject was treated with ACTX applied twice daily on the affected scalp. Relevant clinical improvement was observed as soon as 1 month of therapy. Complete clinical resolution of all scalp lesions was observed after 3 months of treatment. The product was well tolerated.

Cas pratique : État de la retenue d’El Golfo dans l’île d’El Hierro (îles Canaries

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BLANCO, Manuel

2012-08-01

Full Text Available La pérennité des matériaux géosynthétiques garantit la mise en place d'un système de protection efficace et durable pour l'environnement. Cet article présente le comportement sur douze ans d’une géomembrane en caoutchouc synthétique installée dans la retenue d'eau d’El Golfo aux îles Canaries : des résultats encourageants qui montrent un bon état de conservation de la géomembrane face aux aléas climatiques.

Risk factors for Kaposi's sarcoma in human immunodeficiency virus patients after initiation of antiretroviral therapy: A nested case–control study in Kenya

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Rodgers Lupia

2017-12-01

Full Text Available Background/Purpose: This study aimed to evaluate the association between highly active antiretroviral therapy (HAART adherence and development of Kaposi's sarcoma (KS in human immunodeficiency virus (HIV/AIDS patients. Methods: We conducted a retrospective nested case–control study of 165 participants (33 cases and 132 controls receiving HAART care at Maseno Hospital, Kenya, from January 2005 to October 2013. Cases were HIV-positive adults with KS, who were matched with controls in a ratio of 1:4 based on age (±5 years of each case, sex, and KS diagnosis date. Perfect adherence to HAART was assessed on every clinic visit by patients' self-reporting and pill counts. Chi-square tests were performed to compare socioeconomic and clinical statuses between cases and controls. A conditional logistic regression was used to assess the effects of perfect adherence to HAART, the latest CD4 count, education level, distance to health-care facility, initial World Health Organization stage, and number of regular sexual partners on the development of KS. Results: Only 63.6% participants reported perfect adherence, and the control group had a significantly higher percentage of perfect adherence (75.0% than did cases (18.2%. After adjustment for potential imbalances in the baseline and clinical characteristics, patients with imperfect HAART adherence had 20-times greater risk of developing KS than patients with perfect HAART adherence [hazard ratios: 21.0, 95% confidence interval: 4.2–105.1]. Patients with low latest CD4 count (≤350 cells/mm3 had a seven-times greater risk of developing KS than did their counterparts (HRs: 7.1, 95% CI: 1.4–36.2. Conclusion: Imperfect HAART adherence and low latest CD4 count are significantly associated with KS development. Keywords: antiretroviral therapy, highly active antiretroviral therapy, human immunodeficiency virus/AIDS treatment, Kaposi's sarcoma, Kenya, Maseno

Cellular Uptake and Photo-Cytotoxicity of a Gadolinium(III-DOTA-Naphthalimide Complex “Clicked” to a Lipidated Tat Peptide

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William I. O’Malley

2016-02-01

Full Text Available A new bifunctional macrocyclic chelator featuring a conjugatable alkynyl-naphthalimide fluorophore pendant group has been prepared and its Gd(III complex coupled to a cell-penetrating lipidated azido-Tat peptide derivative using Cu(I-catalysed “click” chemistry. The resulting fluorescent conjugate is able to enter CAL-33 tongue squamous carcinoma cells, as revealed by confocal microscopy, producing a very modest anti-proliferative effect (IC50 = 93 µM. Due to the photo-reactivity of the naphthalimide moiety, however, the conjugate’s cytotoxicity is significantly enhanced (IC50 = 16 µM upon brief low-power UV-A irradiation.

Spécification géométrique des produits (GPS) -- Indication des états de surface dans la documentation technique de produits

CERN Document Server

International Organization for Standardization. Geneva

2002-01-01

La présente Norme internationale spécifie les règles pour l'indication des états de surface dans la documentation technique de produits (par exemple dessins, spécifications, contrats, rapports) au moyen de symboles graphiques et d'indications textuelles. Elle est applicable à l'indication des exigences sur les surfaces au moyen de paramètres de profil conformément à l'ISO 4287, relatifs au profil R (paramètres de rugosité), au profil W (paramètres d'ondulation) et au profil P (paramètres de structure), de paramètres liés aux motifs conformément à l'ISO 12085, relatifs au motif de rugosité et au motif d'ondulation, et de paramètres relatifs à la courbe du taux de longueur portante conformément à l'ISO 13565-2 et à l'ISO 13565-3. NOTE Quant à l'indication des exigences concernant les imperfections de surface (pores, stries, etc.), qui ne peuvent pas être spécifiées à l'aide des paramètres d'état de surface, référence est faite à l'ISO 8785 qui couvre les imperfections de surface...

Differentially regulated splice variants and systems biology analysis of Kaposi's sarcoma-associated herpesvirus-infected lymphatic endothelial cells.

Science.gov (United States)

Chang, Ting-Yu; Wu, Yu-Hsuan; Cheng, Cheng-Chung; Wang, Hsei-Wei

2011-09-01

Alternative RNA splicing greatly increases proteome diversity, and the possibility of studying genome-wide alternative splicing (AS) events becomes available with the advent of high-throughput genomics tools devoted to this issue. Kaposi's sarcoma associated herpesvirus (KSHV) is the etiological agent of KS, a tumor of lymphatic endothelial cell (LEC) lineage, but little is known about the AS variations induced by KSHV. We analyzed KSHV-controlled AS using high-density microarrays capable of detecting all exons in the human genome. Splicing variants and altered exon-intron usage in infected LEC were found, and these correlated with protein domain modification. The different 3'-UTR used in new transcripts also help isoforms to escape microRNA-mediated surveillance. Exome-level analysis further revealed information that cannot be disclosed using classical gene-level profiling: a significant exon usage difference existed between LEC and CD34(+) precursor cells, and KSHV infection resulted in LEC-to-precursor, dedifferentiation-like exon level reprogramming. Our results demonstrate the application of exon arrays in systems biology research, and suggest the regulatory effects of AS in endothelial cells are far more complex than previously observed. This extra layer of molecular diversity helps to account for various aspects of endothelial biology, KSHV life cycle and disease pathogenesis that until now have been unexplored.

Seroprevalence of Human herpesvirus 8 (HHV-8 and incidence of Kaposi's sarcoma in Iran

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Nategh Rakhshandeh

2011-04-01

Full Text Available Abstract Seroepidemiological surveys show that the prevalence of human herpesvirus 8 (HHV-8 infection mostly varies in various geographical areas and reflects the local incidence of classic and endemic KS, being widespread in sub-Saharan Africa and Mediterranean countries and uncommon in the USA and Northern Europe. In the Middle East only few populations, such as Ashkenazi and Sephardic groups in Israel, have been adequately evaluated for HHV-8 seroprevalence. Among Iranian population a striking higher seroprevalence of HHV8 has been reported among haemodialysis (16.9%, renal transplant recipients (25% and HIV (45.7% patients compared to blood donors (2%. Kaposi's sarcoma (KS is the rarest cancer in Iran, with an annual age-standardized incidence varying from 0.10 to 0.17 per 100,000 in males and from 0.06 to 0.08 per 100,000 in females. KS, however, is one of the most important malignancies in Iranian renal transplanted patients affecting up to 2.4% of organ recipients. The epidemiology of HHV8 and KS in Iran needs further evaluation. While the high prevalence of HHV-8 antibodies in HIV positive and haemodialysis individuals may be attributed to high-risk sexual behavior and polytransfusions, respectively, unknown determinants may be responsible for high seroprevalence of HHV8 and high incidence of KS in solid organ recipients. A global survey on HHV8 seroprevalence in Iran is mandatory to define co-factors associated with HHV8 infection and KS risk in the general Iranian population and in specific patient groups.

Recreational Drug Use and Risk of Kaposi's Sarcoma in HIV- and HHV-8-Coinfected Homosexual Men

Science.gov (United States)

Chao, Chun; Jacobson, Lisa P.; Jenkins, Frank J.; Tashkin, Donald; Martínez-Maza, Otoniel; Roth, Michael D.; Ng, Leslie; Margolick, Joseph B.; Chmiel, Joan S.; Detels, Roger

2009-01-01

Abstract Experimental data suggested that exposure to recreational drugs might adversely affect antitumor immunity, which led us to examine the hypothesis that use of marijuana, cocaine, poppers, and amphetamines might increase the risk of Kaposi's Sarcoma (KS) in HIV- and HHV-8-coinfected homosexual men. We analyzed data prospectively collected from the Multicenter AIDS Cohort Study (MACS) between 1984 and 2002. Among the 1335 HIV- and HHV-8-coinfected white men, 401 KS cases were identified. Multivariable Cox regression models were used to estimate the effects of time-varying recreational drug use on KS risk adjusting for potential confounders. The effects of both recent use (6 months prior) of recreational drugs and lagged exposure (i.e., use from 3 and 5 years prior) were examined. We did not observe any clear association with KS for recent use of any of the four drugs. In the analyses using lagged exposures, KS risk was associated with use of poppers 3–5 years prior [hazard ratio (HR)3 years prior = 1.27, 95% CI (0.97–1.67), HR5 years prior = 1.46 (1.01–2.13)]. However, no clear dose-response relationship was observed. These findings do not support a biological association between use of these substances and KS development in HIV- and HHV-8-coinfected homosexual men. PMID:19108691

Seroprevalence and determinants of Kaposi sarcoma-associated human herpesvirus 8 in Indian HIV-infected males.

Science.gov (United States)

Munawwar, Arshi; Sharma, Surendra K; Gupta, Somesh; Singh, Sarman

2014-12-01

In India Kaposi's sarcoma is rarely seen in AIDS patients. Hence the current belief is that the incidence of human herpesvirus-8 (HHV-8) is very low in this subcontinent, most probably due to the heterosexual route of HIV transmission. However, there is a scarcity of data on the prevalence of HHV-8 in India. In India the primary mode of HIV transmission is the heterosexual route. Therefore we aimed to determine the prevalence of antibodies against HHV-8 in North Indian HIV-infected men naive of antiretroviral therapy (ART). In a prospective study, 165 Indian adult males were recruited from an ART clinic. Blood samples were collected before administering any antiretroviral drug. The sera were tested for antibodies against HHV-8 using a commercial enzyme-linked immunosorbent assay (ELISA) kit, which detects IgG antibodies to lytic antigens of HHV-8. All positive samples were confirmed for the presence of anti-HHV-8 antibodies using an indirect immunofluorescence assay (IFA). The IFA kit is intended to detect primary, latent, persistent, or reactivated infection of HHV-8. Of the 165 males, 43 (26.06%) were positive by ELISA while 26 (15.8%) were also positive by IFA. Seroprevalence decreased with increasing age (p<0.05). Factors independently associated with HHV-8 infection were younger age group and alcohol consumption. These findings suggest that even in a heterosexual population, HHV-8 can be transmitted frequently.

In vivo growth-restricted and reversible malignancy induced by Human Herpesvirus-8/ KSHV: a cell and animal model of virally induced Kaposi's sarcoma

Science.gov (United States)

Mutlu, Agata D'Agostino; Cavallin, Lucas E.; Vincent, Loïc; Chiozzini, Chiara; Eroles, Pilar; Duran, Elda M.; Asgari, Zahra; Hooper, Andrea T.; La Perle, Krista M. D.; Hilsher, Chelsey; Gao, Shou-Jiang; Dittmer, Dirk P.; Rafii, Shahin; Mesri, Enrique A.

2007-01-01

Transfection of a Kaposi's sarcoma (KS) herpesvirus (KSHV) Bacterial Artificial Chromosome (KSHVBac36) into mouse bone marrow endothelial lineage cells generates a cell (mECK36) that forms KS-like tumors in mice. mECK36 expressed most KSHV genes and were angiogenic, but didn't form colonies in soft agar. In nude mice, mECK36 formed KSHV-harboring vascularized spindle-cell sarcomas that were LANA+/podoplanin+, overexpressed VEGF and Angiopoietin ligands and receptors, and displayed KSHV and host transcriptomes reminiscent of KS. mECK36 that lost the KSHV episome reverted to non-tumorigenicity. siRNA suppression of KSHV vGPCR, an angiogenic gene up-regulated in mECK36 tumors, inhibited angiogenicity and tumorigenicity. These results show that KSHV malignancy is in vivo growth-restricted and reversible, defining mECK36 as a biologically sensitive animal model of KSHV-dependent KS. PMID:17349582

You mob my owl, I'll mob yours: birds play tit-for-tat game

Science.gov (United States)

Krama, Tatjana; Vrublevska, Jolanta; Freeberg, Todd M.; Kullberg, Cecilia; Rantala, Markus J.; Krams, Indrikis

2012-01-01

Reciprocity is fundamental to cooperative behaviour and has been verified in theoretical models. However, there is still limited experimental evidence for reciprocity in non-primate species. Our results more decisively clarify that reciprocity with a tit-for-tat enforcement strategy can occur among breeding pied flycatchers Ficedula hypoleuca separate from considerations of byproduct mutualism. Breeding pairs living in close proximity (20–24 m) did exhibit byproduct mutualism and always assisted in mobbing regardless of their neighbours' prior actions. However, breeding pairs with distant neighbours (69–84 m) either assisted or refused to assist in mobbing a predatory owl based on whether or not the distant pair had previously helped them in their own nest defense against the predator. Clearly, these birds are aware of their specific spatial security context, remember their neighbours' prior behaviour, and choose a situation-specific strategic course of action, which could promote their longer-term security, a capacity previously thought unique to primates. PMID:23150772

2018-05-05T10:34:30Z https://www.ajol.info/index.php/all/oai oai:ojs ...

African Journals Online (AJOL)

article/11400 2018-05-05T10:34:30Z njcp:ART AIDS-associated Kaposi\\'s Sarcoma in Sokoto, Nigeria. Mbah, N Abdulkareem, IH Panti, A Kaposi\\'s sarcoma, Prevalence, Northwestern Nigeria, HIV/AIDS. Background: Since the advent of the ...

Activation of PI3K/AKT and ERK MAPK signal pathways is required for the induction of lytic cycle replication of Kaposi's Sarcoma-associated herpesvirus by herpes simplex virus type 1

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Lv Zhigang

2011-10-01

Full Text Available Abstract Background Kaposi's sarcoma-associated herpesvirus (KSHV is causally linked to several acquired immunodeficiency syndrome-related malignancies, including Kaposi's sarcoma (KS, primary effusion lymphoma (PEL and a subset of multicentric Castleman's disease. Regulation of viral lytic replication is critical to the initiation and progression of KS. Recently, we reported that herpes simplex virus type 1 (HSV-1 was an important cofactor that activated lytic cycle replication of KSHV. Here, we further investigated the possible signal pathways involved in HSV-1-induced reactivation of KSHV. Results By transfecting a series of dominant negative mutants and protein expressing constructs and using pharmacologic inhibitors, we found that either Janus kinase 1 (JAK1/signal transducer and activator of transcription 3 (STAT3 or JAK1/STAT6 signaling failed to regulate HSV-1-induced KSHV replication. However, HSV-1 infection of BCBL-1 cells activated phosphatidylinositol 3-kinase (PI3K/protein kinase B (PKB, also called AKT pathway and inactivated phosphatase and tensin homologue deleted on chromosome ten (PTEN and glycogen synthase kinase-3β (GSK-3β. PTEN/PI3K/AKT/GSK-3β pathway was found to be involved in HSV-1-induced KSHV reactivation. Additionally, extracellular signal-regulated protein kinase (ERK mitogen-activated protein kinase (MAPK pathway also partially contributed to HSV-1-induced KSHV replication. Conclusions HSV-1 infection stimulated PI3K/AKT and ERK MAPK signaling pathways that in turn contributed to KSHV reactivation, which provided further insights into the molecular mechanism controlling KSHV lytic replication, particularly in the context of HSV-1 and KSHV co-infection.

Political and economic conjuncture in Brazil (1950-1964: a fertile land for the 1964 coup d'État

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FABIANO FARIAS DE SOUZA

2013-01-01

Full Text Available The years preceding the 1964 coup d’état in Brazil were marked by turbulent political moments that contributed to the accomplishment of joints and conspiracies that were plotting the overthrow of President João Goulart, seen as a solution to the end of the economic, political and social crises taking place successively in the country. In this period, society was divided between the proposals of the left and right of the political debate in effect at that time. Thus, we analyze the circumstances that forged an enabling environment for identified civil and military that communed common interest in replacing the ruling power by taking control of the Brazilian State.

Imaging Dose-dependent Pharmacokinetics of an RGD-Fluorescent Dye Conjugate Targeted to αvβ3 Receptor Expressed in Kaposi's Sarcoma

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Sunkuk Kwon

2005-04-01

Full Text Available Dynamic fluorescence images were obtained from xenografts bearing a subcutaneous human Kaposi's sarcoma (KS1767 immediately following the intravenous injection of an integrin-receptor targeting Cy5.5-c(KRGDf at a dose ranging from 0.75 to 6 nmol/mouse. The fluorescence images were acquired using an intensified charge-coupled device system and were analyzed with a three-compartment pharmacokinetic (PK model to determine uptake parameters in the tumor and normal tissue regions of interest as a function of administered dose. Our results show that the uptake of Cy5.5-c(KRGDf in tumor regions were: (i significantly greater than the contralateral normal tissue regions; (ii linearly increased with dose of Cy5.5-c(KRGDf up to 1.5 nmol/mouse; and (iii blocked by preinjection of c(KRGDf. Above doses of 1.5 nmol/mouse, the uptake no longer increased with dose, suggesting integrin receptor saturation. In normal tissues, the PK uptake parameters were not influenced by Cy5.5-c(KRGDf dose nor by the preadministration of c(KRGDf.

Kaposi Sarcoma among HIV Infected Patients in Lagos University Teaching Hospital, Nigeria: A 14-Year Retrospective Clinicopathological Study

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Olakanmi Akinde

2016-01-01

Full Text Available Background. Despite the increased incidence of Kaposi sarcoma (KS resulting from the Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS pandemic, there is still significant underreporting of KS in this environment. Objectives. This study was aimed at determining the incidence and clinicopathologic patterns of KS among HIV infected patients in Lagos University Teaching Hospital (LUTH, Nigeria, over a 14-year period: January 2000 to December 2013. Methodology. The materials for this study included patients’ hospital clinical files, duplicate copies of histopathologic reports, and tissue blocks and corresponding archival slides in the Anatomic and Molecular Pathology Department and the HIV/AIDS unit of the Department of Haematology. Results. Within the study period, 182 cases of KS were diagnosed, accounting for 1.2% of all patients managed for HIV/AIDS and 2.99% of solid malignant tumours. The male-to-female ratio and modal age group were 1 : 1.3 and 5th decade, respectively. Most cases (90% had purely mucocutaneous involvement with the lower limb being the commonest site (65.8%. The majority of lesions were plaques (65.8%. Vascular formation was the predominant histologic type seen (43.5%. Conclusion. KS in Lagos followed the same epidemiologic trend as other centers in Nigeria, with an increasing incidence in this era of HIV/AIDS.

Marketers as Innovators: how ethnic marketing revisits ethnicity Marketing ethnique et innovation aux États-Unis

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Marie-Christine Pauwels

2009-10-01

Full Text Available L’innovation aux États-Unis est ici vue sous un angle social et culturel. Il ne s’agit plus d’étudier l’innovation technologique, mais l’innovation en matière de produit. L’article aborde la création de valeur à travers la variable ethnique dans le domaine de la vente, du marketing et de la publicité. Les nouvelles tendances en matière d’ethno-marketing sont analysées, en particulier la manière dont les professionnels utilisent la notion d’ethnicité pour vendre des produits de consommation courante à un marché de consommateurs de plus en plus exigeants, soit en ayant recours à une segmentation de ces consommateurs en micro-marchés toujours plus étroits, soit en privilégiant un marketing multi- ou trans-culturel.

RGDS- and TAT-conjugated upconversion of NaYF4:Yb3+/Er3+&SiO2 nanoparticles: in vitro human epithelioid cervix carcinoma cellular uptake, imaging, and targeting

Czech Academy of Sciences Publication Activity Database

Kostiv, Uliana; Kotelnikov, Ilya; Proks, Vladimír; Šlouf, Miroslav; Kučka, Jan; Engstová, Hana; Ježek, Petr; Horák, Daniel

2016-01-01

Roč. 8, č. 31 (2016), s. 20422-20431 ISSN 1944-8244 R&D Projects: GA ČR(CZ) GA15-01897S; GA ČR(CZ) GA16-02702S Institutional support: RVO:61389013 ; RVO:67985823 Keywords : upconversion, nanoparticles * RGDS peptide * TAT peptide Subject RIV: CD - Macromolecular Chemistry; BO - Biophysics (FGU-C) Impact factor: 7.504, year: 2016

Geographic variation in the prevalence of Kaposi sarcoma-associated herpesvirus and risk factors for transmission.

Science.gov (United States)

de Sanjose, Silvia; Mbisa, Georgina; Perez-Alvarez, Susana; Benavente, Yolanda; Sukvirach, Sukhon; Hieu, Nguyen Trong; Shin, Hai-Rim; Anh, Pham Thi Hoang; Thomas, Jaiyeola; Lazcano, Eduardo; Matos, Elena; Herrero, Rolando; Muñoz, Nubia; Molano, Monica; Franceschi, Silvia; Whitby, Denise

2009-05-15

The aim of the present study was to estimate the prevalence of Kaposi sarcoma-associated herpesvirus (KSHV) in the female general population, to define geographic variation in and heterosexual transmission of the virus. The study included 10,963 women from 9 countries for whom information on sociodemographic characteristics and reproductive, sexual, and smoking behaviors were available. Antibodies against KSHV that encoded lytic antigen K8.1 and latent antigen ORF73 were determined. The range of prevalence of KSHV (defined as detection of any antigen) was 3.81%-46.02%, with significant geographic variation noted. In Nigeria, the prevalence was 46.02%; in Colombia, 13.32%; in Costa Rica, 9.81%; in Argentina, 6.40%; in Ho Chi Minh City, Vietnam, 15.50%; in Hanoi, Vietnam, 11.26%; in Songkla, Thailand, 10%; in Lampang, Thailand, 8.63%; in Korea, 4.93%; and in Spain, 3.65%. The prevalence of KSHV slightly increased with increasing age among subjects in geographic areas where the prevalence of KSHV was high, such as Nigeria and Colombia, and it significantly decreased with increases in the educational level attained by subjects in those areas. KSHV was not statistically associated with age at first sexual intercourse, number of sex partners, number of children, patterns of oral contraceptive use, presence of cervical human papillomavirus DNA, or smoking status. The study provides comparable estimates of KSHV prevalence in diverse cultural settings across 4 continents and provides evidence that sexual transmission of KSHV is not a major source of infection in the general population.

Vulnerability to the infection by HIV in female prisoners of the P.F.B. assessed by serological and T.A.T. techniques

OpenAIRE

Leila Strazza de Azevedo

2003-01-01

O objetivo foi avaliar a vulnerabilidade do HIV de detentas da P.F.B.. Utilizou-se técnicas sorológicas e TAT. 290 detentas entrevistadas com questionário sobre comportamentos e hábitos destas mulheres e parceiros sobre: promiscuidade sexual; UDI; DST. Avaliou-se com detentas: mitos, crenças, idade, escolaridade e conhecimento HIV. A soroprevalência para HIV foi obtida e relacionada com os comportamentos de risco por análise univariada, com a utilização de tabelas de contingência entre variáv...

Evaluation of non-invasive multispectral imaging as a tool for measuring the effect of systemic therapy in Kaposi sarcoma.

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Jana M Kainerstorfer

Full Text Available Diffuse multi-spectral imaging has been evaluated as a potential non-invasive marker of tumor response. Multi-spectral images of Kaposi sarcoma skin lesions were taken over the course of treatment, and blood volume and oxygenation concentration maps were obtained through principal component analysis (PCA of the data. These images were compared with clinical and pathological responses determined by conventional means. We demonstrate that cutaneous lesions have increased blood volume concentration and that changes in this parameter are a reliable indicator of treatment efficacy, differentiating responders and non-responders. Blood volume decreased by at least 20% in all lesions that responded by clinical criteria and increased in the two lesions that did not respond clinically. Responses as assessed by multi-spectral imaging also generally correlated with overall patient clinical response assessment, were often detectable earlier in the course of therapy, and are less subject to observer variability than conventional clinical assessment. Tissue oxygenation was more variable, with lesions often showing decreased oxygenation in the center surrounded by a zone of increased oxygenation. This technique could potentially be a clinically useful supplement to existing response assessment in KS, providing an early, quantitative, and non-invasive marker of treatment effect.

Plasma accelerators

International Nuclear Information System (INIS)

Bingham, R.; Angelis, U. de; Johnston, T.W.

1991-01-01

Recently attention has focused on charged particle acceleration in a plasma by a fast, large amplitude, longitudinal electron plasma wave. The plasma beat wave and plasma wakefield accelerators are two efficient ways of producing ultra-high accelerating gradients. Starting with the plasma beat wave accelerator (PBWA) and laser wakefield accelerator (LWFA) schemes and the plasma wakefield accelerator (PWFA) steady progress has been made in theory, simulations and experiments. Computations are presented for the study of LWFA. (author)

Evaluation of c-kit expression in classic Kaposi's sarcoma in a cohort of Egyptian patients

International Nuclear Information System (INIS)

Hussein, T.M.; El-Sabaa, B.M.; Hanafy, N.F.

2012-01-01

Kaposis sarcoma (KS) is in angio proliferative disorder associated with human herpes virus 8 infection. Classic Ks is the most prevalent type of KS in countries of the Mediterranean basin including Egypt. Several in vitro studies have detected C-kit expression in AIDS related-KS however, only a few studies addressed this Issue In the classic type with no data on the ethnicity of studied cases. The prospect of installing targeted anti-c-kit treatment to KS patients presents a promising avenue in KS therapeutics. Aim: To elucidate the expression of c-kit in classic KS cases and study possible relations with expression of HHV8 latency-associated nuclear antigen-1 (LANA-1) and other clinico pathological parameters. Methods: Twenty four cases of classic KS of the plaque and nodular stages in the lower limb were studied. Immunohistochemical detection of HHV8-LANA-1 and c-kit was carried out on archival paraffin embedded tissue, possession of the pathology and dermatology Departments, Alexandria School Of Medicine, Egypt. Statistical analysis of possible reltions between both antigen and clinico pathological parameters (patient age and gender and histological stage) was performed. Results: HHV8 expression was detected in 100% of cases while c-kit immunoreactivity was found in 54.2% of cases. There was no correlation between c-kit and HHV8 immunoreactivity or any of the studied clinico pathological parameters. Conclusions: This is the first report of c-kit expression in classic KS in an ethnically homogeneous cohort of arabs of the Mediterranean region. We detected c-kit expression in about half the cases with no relationship to HHV8 LANA expression or clinico pathological parameters

A Review of Approaches for the Design of Li-Ion BMS Estimation Functions Revue de différentes approches pour l’estimation de l’état de charge de batteries Li-ion

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Di Domenico D.

2013-02-01

Full Text Available This paper aims at comparing different approaches for the estimation of the state of charge of lithium-ion batteries. The main advantages as well as the critical points of the considered techniques are analyzed, highlighting the impact of the cell model precision and complexity on the estimator performance. Among others, the electrical equivalent circuit based technique is selected for further development. The results of a complete procedure from the cell characterization to the online estimation are illustrated. The experimental tests based on the data collected on batteries testing facilities of IFP Energies nouvelles show that the proposed strategy allows a satisfying state of charge real time estimation. Cet article vise à comparer différentes approches pour l’estimation de l’état de charge pour les batteries Li-ion. Les principaux avantages ainsi que les points critiques des différentes techniques sont analysés, en soulignant l’impact de la complexité et de la précision du modèle sur les performances de l’estimateur. La procédure complète, allant de la caractérisation de la cellule jusqu’à l’estimation en ligne de l’état de charge, est présentée pour la modélisation par circuit électrique équivalent. Les tests expérimentaux sur la base des données acquises au laboratoire batteries d’IFP Energies nouvelles montrent que cette stratégie permet d’obtenir un estimateur en temps réel de l’état de charge présentant de bonnes performances.

Cellule État de l’Environnement Wallon (2003 Tableau de bord de l’environnement wallon 2003, Ed MRW –DGRNE, 144 p.

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Emilie Thuillier

2004-06-01

Full Text Available Le Tableau de bord de l'environnement wallon 2003 fait suite au Rapport sur l’état de l'environnement wallon 2000 et constitue la première édition qui sera éditée annuellement. Cette initiative est le fruit d’une collaboration entre, d’une part, la Direction Générale des Ressources Naturelles et de l’Environnement du Ministère de la Région wallone et, d’autre part, une coordination inter-universitaire fondée sur une équipe scientifique pluridisciplinaire permanente coordonnée par Edwin ZACCAÏ...

Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma

Science.gov (United States)

Little, Richard F.; Aleman, Karen; Kumar, Pallavi; Wyvill, Kathleen M.; Pluda, James M.; Read-Connole, Elizabeth; Wang, Victoria; Pittaluga, Stefania; Catanzaro, Andrew T.; Steinberg, Seth M.

2007-01-01

Thirty-six patients with AIDS-associated Kaposi sarcoma (KS) requiring chemotherapy were treated for six 3-week cycles of pegylated liposomal doxorubicin (20 mg/m2) plus interleukin-12 (IL-12; 300 ng/kg subcutaneously twice weekly), followed by 500 ng/kg subcutaneous IL-12 twice weekly for up to 3 years. All received highly active antiretroviral therapy (HAART). Twenty-two had poor-prognosis KS (T1S1). Thirty patients had a major response, including 9 with complete response, yielding an 83.3% major response rate (95% confidence interval: 67.2%-93.6%). Median time to first response was 2 cycles. Median progression was not reached at median potential follow-up of 46.9 months. Of 27 patients with residual disease when starting maintenance IL-12, 15 had a new major response compared with this new baseline. The regimen was overall well tolerated; principal toxicities were neutropenia, anemia, transaminitis, and neuropsychiatric toxicity. Patients had increases in serum IL-12, interferon gamma, and inducible protein-10 (IP-10), and these remained increased at weeks 18 and 34. The regimen of IL-12 plus liposomal doxorubicin yielded rapid tumor responses and a high response rate in patients with AIDS-KS receiving HAART, and responses were sustained on IL-12 maintenance therapy. A randomized trial of IL-12 in this setting may be warranted. This study is registered at http://www.clinicaltrials.gov as no. NCT00020449. PMID:17846226

Multifunctional non-viral gene vectors with enhanced stability, improved cellular and nuclear uptake capability, and increased transfection efficiency

Science.gov (United States)

Yang, Zhe; Jiang, Zhaozhong; Cao, Zhong; Zhang, Chao; Gao, Di; Luo, Xingen; Zhang, Xiaofang; Luo, Huiyan; Jiang, Qing; Liu, Jie

2014-08-01

We have developed a new multifunctional, non-viral gene delivery platform consisting of cationic poly(amine-co-ester) (PPMS) for DNA condensation, PEG shell for nanoparticle stabilization, poly(γ-glutamic acid) (γ-PGA) and mTAT (a cell-penetrating peptide) for accelerated cellular uptake, and a nuclear localization signal peptide (NLS) for enhanced intracellular transport of DNA to the nucleus. In vitro study showed that coating of the binary PPMS/DNA polyplex with γ-PGA promotes cellular uptake of the polyplex particles, particularly by γ-glutamyl transpeptidase (GGT)-positive cells through the GGT-mediated endocytosis pathway. Conjugating PEG to the γ-PGA led to the formation of a ternary PPMS/DNA/PGA-g-PEG polyplex with decreased positive charges on the surface of the polyplex particles and substantially higher stability in serum-containing aqueous medium. The cellular uptake rate was further improved by incorporating mTAT into the ternary polyplex system. Addition of the NLS peptide was designed to facilitate intracellular delivery of the plasmid to the nucleus--a rate-limiting step in the gene transfection process. As a result, compared with the binary PPMS/LucDNA polyplex, the new mTAT-quaternary PPMS/LucDNA/NLS/PGA-g-PEG-mTAT system exhibited reduced cytotoxicity, remarkably faster cellular uptake rate, and enhanced transport of DNA to the nucleus. All these advantageous functionalities contribute to the remarkable gene transfection efficiency of the mTAT-quaternary polyplex both in vitro and in vivo, which exceeds that of the binary polyplex and commercial Lipofectamine™ 2000/DNA lipoplex. The multifunctional mTAT-quaternary polyplex system with improved efficiency and reduced cytotoxicity represents a new type of promising non-viral vectors for the delivery of therapeutic genes to treat tumors.We have developed a new multifunctional, non-viral gene delivery platform consisting of cationic poly(amine-co-ester) (PPMS) for DNA condensation, PEG shell

Les inscriptions funéraires au cimetière d’Aïn El-Beida (Oran) : état des lieux

OpenAIRE

Hirreche Baghdad, Mohamed

2016-01-01

Ce papier résulte d’un projet établissement inscrit au CRASC (2009-2013) intitulé : « les inscriptions sur les stèles funéraires dans l’ouest algérien : permanence et évolution ». La problématique de ce projet est la suivante : qu’écrivent les algériens sur les tombes de leurs proches et comment expliquer la divergence ou la ressemblance des contenus épigraphiques des stèles funéraires ? La première partie de la question s’intéresse à l’état des lieux de l’épigraphie au cimetière d’Aïn El-Bei...

Dominique Thomas, Générations djihadistes. Al-Qaïda – État islamique, histoire d’une lutte fratricide

OpenAIRE

Blanc, Théo

2017-01-01

La multiplication des attentats en Europe est souvent décrite comme la conséquence de l’hégémonie du groupe État islamique (EI) sur la mouvance djihadiste. Pourtant, le massacre de Charlie Hebdo le 7 janvier 2015 par des militants d’Al-Qaïda (AQ) vient rappeler avec force que l’organisation initiatrice du djihad global est loin d’avoir été éclipsée. En réalité, AQ et EI se livrent une bataille idéologique et stratégique pour le « monopole du djihadisme » (p. 153). Leur divergence sur les fina...

First muon acceleration using a radio-frequency accelerator

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S. Bae

2018-05-01

Full Text Available Muons have been accelerated by using a radio-frequency accelerator for the first time. Negative muonium atoms (Mu^{-}, which are bound states of positive muons (μ^{+} and two electrons, are generated from μ^{+}’s through the electron capture process in an aluminum degrader. The generated Mu^{-}’s are initially electrostatically accelerated and injected into a radio-frequency quadrupole linac (RFQ. In the RFQ, the Mu^{-}’s are accelerated to 89 keV. The accelerated Mu^{-}’s are identified by momentum measurement and time of flight. This compact muon linac opens the door to various muon accelerator applications including particle physics measurements and the construction of a transmission muon microscope.

Acceleration Modes and Transitions in Pulsed Plasma Accelerators

Science.gov (United States)

Polzin, Kurt A.; Greve, Christine M.

2018-01-01

Pulsed plasma accelerators typically operate by storing energy in a capacitor bank and then discharging this energy through a gas, ionizing and accelerating it through the Lorentz body force. Two plasma accelerator types employing this general scheme have typically been studied: the gas-fed pulsed plasma thruster and the quasi-steady magnetoplasmadynamic (MPD) accelerator. The gas-fed pulsed plasma accelerator is generally represented as a completely transient device discharging in approximately 1-10 microseconds. When the capacitor bank is discharged through the gas, a current sheet forms at the breech of the thruster and propagates forward under a j (current density) by B (magnetic field) body force, entraining propellant it encounters. This process is sometimes referred to as detonation-mode acceleration because the current sheet representation approximates that of a strong shock propagating through the gas. Acceleration of the initial current sheet ceases when either the current sheet reaches the end of the device and is ejected or when the current in the circuit reverses, striking a new current sheet at the breech and depriving the initial sheet of additional acceleration. In the quasi-steady MPD accelerator, the pulse is lengthened to approximately 1 millisecond or longer and maintained at an approximately constant level during discharge. The time over which the transient phenomena experienced during startup typically occur is short relative to the overall discharge time, which is now long enough for the plasma to assume a relatively steady-state configuration. The ionized gas flows through a stationary current channel in a manner that is sometimes referred to as the deflagration-mode of operation. The plasma experiences electromagnetic acceleration as it flows through the current channel towards the exit of the device. A device that had a short pulse length but appeared to operate in a plasma acceleration regime different from the gas-fed pulsed plasma

Accelerator development

International Nuclear Information System (INIS)

Anon.

1975-01-01

Because the use of accelerated heavy ions would provide many opportunities for new and important studies in nuclear physics and nuclear chemistry, as well as other disciplines, both the Chemistry and Physics Divisions are supporting the development of a heavy-ion accelerator. The design of greatest current interest includes a tandem accelerator with a terminal voltage of approximately 25 MV injecting into a linear accelerator with rf superconducting resonators. This combined accelerator facility would be capable of accelerating ions of masses ranging over the entire periodic table to an energy corresponding to approximately 10 MeV/nucleon. This approach, as compared to other concepts, has the advantages of lower construction costs, lower operating power, 100 percent duty factor, and high beam quality (good energy resolution, good timing resolution, small beam size, and small beam divergence). The included sections describe the concept of the proposed heavy-ion accelerator, and the development program aiming at: (1) investigation of the individual questions concerning the superconducting accelerating resonators; (2) construction and testing of prototype accelerator systems; and (3) search for economical solutions to engineering problems. (U.S.)

Accelerator Technology: Geodesy and Alignment for Particle Accelerators

CERN Document Server

Missiaen, D

2013-01-01

This document is part of Subvolume C 'Accelerators and Colliders' of Volume 21 'Elementary Particles' of Landolt-Börnstein - Group I 'Elementary Particles, Nuclei and Atoms'. It contains the the Section '8.9 Geodesy and Alignment for Particle Accelerators' of the Chapter '8 Accelerator Technology' with the content: 8.9 Geodesy and Alignment for Particle Accelerators 8.9.1 Introduction 8.9.2 Reference and Co-ordinate Systems 8.9.3 Definition of the Beam Line on the Accelerator Site 8.9.4 Geodetic Network 8.9.5 Tunnel Preliminary Works 8.9.6 The Alignment References 8.9.7 Alignment of Accelerator Components 8.9.8 Permanent Monitoring and Remote Alignment of Low Beta Quadrupoles 8.9.9 Alignment of Detector Components

Influence of maternal depression on children's brooding rumination: Moderation by CRHR1 TAT haplotype.

Science.gov (United States)

Woody, Mary L; Kudinova, Anastacia Y; McGeary, John E; Knopik, Valerie S; Palmer, Rohan H C; Gibb, Brandon E

2016-01-01

There is growing evidence that brooding rumination plays a key role in the intergenerational transmission of major depressive disorder (MDD) and may be an endophenotype for depression risk. However, less is known about the mechanisms underlying this role. Therefore, the goal of the current study was to examine levels of brooding in children of mothers with a history of MDD (n = 129) compared to children of never depressed mothers (n = 126) and to determine whether the variation in a gene known to influence hypothalamic-pituitary-adrenal axis functioning--corticotropin-releasing hormone receptor 1 (CRHR1)--would moderate the link between maternal MDD and children's levels of brooding. We predicted children of mothers with a history of MDD would exhibit higher levels of brooding than children of mothers with no lifetime depression history but that this link would be stronger among children carrying no copies of the protective CRHR1 TAT haplotype. Our results supported these hypotheses and suggest that the development of brooding among children of depressed mothers, particularly children without the protective CRHR1 haplotype, may serve as an important mechanism of risk for the intergenerational transmission of depression.

2014 CERN Accelerator Schools: Plasma Wake Acceleration

CERN Multimedia

2014-01-01

A specialised school on Plasma Wake Acceleration will be held at CERN, Switzerland from 23-29 November, 2014.   This course will be of interest to staff and students in accelerator laboratories, university departments and companies working in or having an interest in the field of new acceleration techniques. Following introductory lectures on plasma and laser physics, the course will cover the different components of a plasma wake accelerator and plasma beam systems. An overview of the experimental studies, diagnostic tools and state of the art wake acceleration facilities, both present and planned, will complement the theoretical part. Topical seminars and a visit of CERN will complete the programme. Further information can be found at: http://cas.web.cern.ch/cas/PlasmaWake2014/CERN-advert.html http://indico.cern.ch/event/285444/

Virtual Accelerator for Accelerator Optics Improvement

CERN Document Server

Yan Yi Ton; Decker, Franz Josef; Ecklund, Stanley; Irwin, John; Seeman, John; Sullivan, Michael K; Turner, J L; Wienands, Ulrich

2005-01-01

Through determination of all quadrupole strengths and sextupole feed-downs by fitting quantities derivable from precision orbit measurement, one can establish a virtual accelerator that matches the real accelerator optics. These quantities (the phase advances, the Green's functions, and the coupling eigen-plane ellipses tilt angles and axis ratios) are obtained by analyzing turn-by-turn Beam Position Monitor (BPM) data with a model-independent analysis (MIA). Instead of trying to identify magnet errors, a limited number of quadrupoles are chosen for optimized strength adjustment to improve the virtual accelerator optics and then applied to the real accelerator accordingly. These processes have been successfully applied to PEP-II rings for beta beating fixes, phase and working tune adjustments, and linear coupling reduction to improve PEP-II luminosity.

Calcium ions effectively enhance the effect of antisense peptide nucleic acids conjugated to cationic tat and oligoarginine peptides

DEFF Research Database (Denmark)

Shiraishi, Takehiko; Pankratova, Stanislava; Nielsen, Peter E

2005-01-01

Cell-penetrating peptides have been widely used to improve cellular delivery of a variety of proteins and antisense agents. However, recent studies indicate that such cationic peptides are predominantly entering cells via an endosomal pathway. We now show that the nuclear antisense effect in He......La cells of a variety of peptide nucleic acid (PNA) peptide conjugates is significantly enhanced by addition of 6 mM Ca(2+) (as well as by the lysosomotrophic agent chloroquine). In particular, the antisense activities of Tat(48-60) and heptaarginine-conjugated PNAs were increased 44-fold and 8.5-fold......, respectively. Evidence is presented that the mechanism involves endosomal release. The present results show that Ca(2+) can be used as an effective enhancer for in vitro cellular delivery of cationic peptide-conjugated PNA oligomers, and also emphasize the significance of the endosomal escape route...

Analyzing radial acceleration with a smartphone acceleration sensor

Science.gov (United States)

Vogt, Patrik; Kuhn, Jochen

2013-03-01

This paper continues the sequence of experiments using the acceleration sensor of smartphones (for description of the function and the use of the acceleration sensor, see Ref. 1) within this column, in this case for analyzing the radial acceleration.

Phase II Study of Bevacizumab in Patients With HIV-Associated Kaposi's Sarcoma Receiving Antiretroviral Therapy

Science.gov (United States)

Uldrick, Thomas S.; Wyvill, Kathleen M.; Kumar, Pallavi; O'Mahony, Deirdre; Bernstein, Wendy; Aleman, Karen; Polizzotto, Mark N.; Steinberg, Seth M.; Pittaluga, Stefania; Marshall, Vickie; Whitby, Denise; Little, Richard F.; Yarchoan, Robert

2012-01-01

Purpose Alternatives to cytotoxic agents are desirable for patients with HIV-associated Kaposi's sarcoma (KS). Vascular endothelial growth factor-A (VEGF-A) contributes to KS pathogenesis. We evaluated the humanized anti–VEGF-A monoclonal antibody, bevacizumab, in patients with HIV-KS. Patients and Methods Patients with HIV-KS who either experienced progression while receiving highly active antiretroviral therapy (HAART) for at least 1 month or did not regress despite HAART for at least 4 months were administered bevacizumab 15 mg/kg intravenously on days 1 and 8 and then every 3 weeks. The primary objective was assessment of antitumor activity using modified AIDS Clinical Trial Group (ACTG) criteria for HIV-KS. HIV-uninfected patients were also eligible and observed separately. Results Seventeen HIV-infected patients were enrolled. Fourteen patients had been receiving effective HAART for at least 6 months (median, 1 year). Thirteen patients had advanced disease (ACTG T1), 13 patients had received prior chemotherapy for KS, and seven patients had CD4 count less than 200 cells/μL. Median number of cycles was 10 (range, 1 to 37 cycles); median follow-up was 8.3 months (range, 3 to 36 months). Of 16 assessable patients, best tumor responses observed were complete response (CR) in three patients (19%), partial response (PR) in two patients (12%), stable disease in nine patients (56%), and progressive disease in two patients (12%). Overall response rate (CR + PR) was 31% (95% CI, 11% to 58.7%). Four of five responders had received prior chemotherapy for KS. Over 202 cycles, grade 3 to 4 adverse events at least possibly attributed to therapy included hypertension (n = 7), neutropenia (n = 5), cellulitis (n = 3), and headache (n = 2). Conclusion Bevacizumab is tolerated in patients with HIV-KS and has activity in a subset of patients. PMID:22430271

Community Petascale Project for Accelerator Science and Simulation: Advancing Computational Science for Future Accelerators and Accelerator Technologies

Energy Technology Data Exchange (ETDEWEB)

Spentzouris, P.; /Fermilab; Cary, J.; /Tech-X, Boulder; McInnes, L.C.; /Argonne; Mori, W.; /UCLA; Ng, C.; /SLAC; Ng, E.; Ryne, R.; /LBL, Berkeley

2011-11-14

The design and performance optimization of particle accelerators are essential for the success of the DOE scientific program in the next decade. Particle accelerators are very complex systems whose accurate description involves a large number of degrees of freedom and requires the inclusion of many physics processes. Building on the success of the SciDAC-1 Accelerator Science and Technology project, the SciDAC-2 Community Petascale Project for Accelerator Science and Simulation (ComPASS) is developing a comprehensive set of interoperable components for beam dynamics, electromagnetics, electron cooling, and laser/plasma acceleration modelling. ComPASS is providing accelerator scientists the tools required to enable the necessary accelerator simulation paradigm shift from high-fidelity single physics process modeling (covered under SciDAC1) to high-fidelity multiphysics modeling. Our computational frameworks have been used to model the behavior of a large number of accelerators and accelerator R&D experiments, assisting both their design and performance optimization. As parallel computational applications, the ComPASS codes have been shown to make effective use of thousands of processors. ComPASS is in the first year of executing its plan to develop the next-generation HPC accelerator modeling tools. ComPASS aims to develop an integrated simulation environment that will utilize existing and new accelerator physics modules with petascale capabilities, by employing modern computing and solver technologies. The ComPASS vision is to deliver to accelerator scientists a virtual accelerator and virtual prototyping modeling environment, with the necessary multiphysics, multiscale capabilities. The plan for this development includes delivering accelerator modeling applications appropriate for each stage of the ComPASS software evolution. Such applications are already being used to address challenging problems in accelerator design and optimization. The ComPASS organization

Accelerator Service

International Nuclear Information System (INIS)

Champelovier, Y.; Ferrari, M.; Gardon, A.; Hadinger, G.; Martin, J.; Plantier, A.

1998-01-01

Since the cessation of the operation of hydrogen cluster accelerator in July 1996, four electrostatic accelerators were in operation and used by the peri-nuclear teams working in multidisciplinary collaborations. These are the 4 MV Van de Graaff accelerator, 2,5 MV Van de Graaff accelerator, 400 kV ion implanter as well as the 120 kV isotope separator

Oncogenic Herpesvirus Utilizes Stress-Induced Cell Cycle Checkpoints for Efficient Lytic Replication

OpenAIRE

Balistreri, Giuseppe; Viiliainen, Johanna; Turunen, Mikko; Diaz, Raquel; Lyly, Lauri; Pekkonen, Pirita; Rantala, Juha; Ojala, Krista; Sarek, Grzegorz; Teesalu, Mari; Denisova, Oxana; Peltonen, Karita; Julkunen, Ilkka; Varjosalo, Markku; Kainov, Denis

2016-01-01

Kaposi?s sarcoma herpesvirus (KSHV) causes Kaposi?s sarcoma and certain lymphoproliferative malignancies. Latent infection is established in the majority of tumor cells, whereas lytic replication is reactivated in a small fraction of cells, which is important for both virus spread and disease progression. A siRNA screen for novel regulators of KSHV reactivation identified the E3 ubiquitin ligase MDM2 as a negative regulator of viral reactivation. Depletion of MDM2, a repressor of p53, favored...

Was Kaposi's sarcoma-associated herpesvirus introduced into China via the ancient Silk Road? An evolutionary perspective.

Science.gov (United States)

Liu, Zhenqiu; Fang, Qiwen; Zuo, Jialu; Minhas, Veenu; Wood, Charles; He, Na; Zhang, Tiejun

2017-10-01

Kaposi's sarcoma-associated herpesvirus (KSHV) has become widely dispersed worldwide since it was first reported in 1994, but the seroprevalence of KSHV varies geographically. KSHV is relatively ubiquitous in Mediterranean areas and the Xinjiang Uygur Autonomous Region, China. The origin of KSHV has long been puzzling. In the present study, we collected and analysed 154 KSHV ORF-K1 sequences obtained from samples originating from Xinjiang, Italy, Greece, Iran and southern Siberia using Bayesian evolutionary analysis in BEAST to test the hypothesis that KSHV was introduced into Xinjiang via the ancient Silk Road. According to the phylogenetic analysis, 72 sequences were subtype A and 82 subtype C, with C2 (n = 56) being the predominant subtype. The times to the most recent common ancestors (tMRCAs) of KSHV were 29,872 years (95% highest probability density [HPD], 26,851-32,760 years) for all analysed sequences and 2037 years (95% HPD, 1843-2229 years) for Xinjiang sequences in particular. The tMRCA of Xinjiang KSHV was exactly matched with the time period of the ancient Silk Road approximately two thousand years ago. This route began in Chang'an, the capital of the Han dynasty of China, and crossed Central Asia, ending in the Roman Empire. The evolution rate of KSHV was slow, with 3.44 × 10 -6 substitutions per site per year (95% HPD, 2.26 × 10 -6 to 4.71 × 10 -6 ), although 11 codons were discovered to be under positive selection pressure. The geographic distances from Italy to Iran and Xinjiang are more than 4000 and 7000 kilometres, respectively, but no explicit relationship between genetic distance and geographic distance was detected.

Community petascale project for accelerator science and simulation: Advancing computational science for future accelerators and accelerator technologies

International Nuclear Information System (INIS)

Spentzouris, P.; Cary, J.; McInnes, L.C.; Mori, W.; Ng, C.; Ng, E.; Ryne, R.

2008-01-01

The design and performance optimization of particle accelerators are essential for the success of the DOE scientific program in the next decade. Particle accelerators are very complex systems whose accurate description involves a large number of degrees of freedom and requires the inclusion of many physics processes. Building on the success of the SciDAC-1 Accelerator Science and Technology project, the SciDAC-2 Community Petascale Project for Accelerator Science and Simulation (ComPASS) is developing a comprehensive set of interoperable components for beam dynamics, electromagnetics, electron cooling, and laser/plasma acceleration modelling. ComPASS is providing accelerator scientists the tools required to enable the necessary accelerator simulation paradigm shift from high-fidelity single physics process modeling (covered under SciDAC1) to high-fidelity multiphysics modeling. Our computational frameworks have been used to model the behavior of a large number of accelerators and accelerator R and D experiments, assisting both their design and performance optimization. As parallel computational applications, the ComPASS codes have been shown to make effective use of thousands of processors.

Advanced concepts for acceleration

International Nuclear Information System (INIS)

Keefe, D.

1986-07-01

Selected examples of advanced accelerator concepts are reviewed. Such plasma accelerators as plasma beat wave accelerator, plasma wake field accelerator, and plasma grating accelerator are discussed particularly as examples of concepts for accelerating relativistic electrons or positrons. Also covered are the pulsed electron-beam, pulsed laser accelerator, inverse Cherenkov accelerator, inverse free-electron laser, switched radial-line accelerators, and two-beam accelerator. Advanced concepts for ion acceleration discussed include the electron ring accelerator, excitation of waves on intense electron beams, and two-wave combinations

Accelerating tube for the ''EG-1'' electrostatic accelerator

International Nuclear Information System (INIS)

Romanov, V.A.; Ivanov, V.V.; Krupnov, E.P.; Debin, V.K.; Dudkin, N.I.; Volodin, V.I.

1980-01-01

A design of an accelerating tube (AT) for an electrostatic accelerator of the EG-1 type is described. Primary consideration in the development of the AT has been given to increasing the electric strength of accelerating gaps, the vacuum conductivity and better insulator screening from charged particles. After AT vacuum and high-voltage ageing in the accelerator, a hydrogen ions beam of up to 80 μA has been produced. The beam was adequately shaped in the energy range from 1.8 to 5.0 MeV [ru

CAS CERN Accelerator School superconductivity in particle accelerators

International Nuclear Information System (INIS)

Turner, S.

1989-01-01

One of the objectives of the CERN Accelerator School is to run courses on specialised topics in the particle accelerator field. The present volume contains the proceedings of one such course, this time organized in conjunction with the Deutsches Elektronen Synchrotron (DESY) on the subject of superconductivity in particle accelerators. This course reflects the very considerable progress made over the last few years in the use of the technology for the magnet and radio-frequency systems of many large and small accelerators already in use or nearing completion, while also taking account of the development work now going on for future machines. The lectures cover the theory of superconductivity, cryogenics and accelerator magnets and cavities, while the seminars include superfluidity, superconductors, special magnets and the prospects for high-temperature superconductors. (orig.)

Human Herpesvirus-8 Infection Associated with Kaposi Sarcoma, Multicentric Castleman's Disease, and Plasmablastic Microlymphoma in a Man with AIDS: A Case Report with Review of Pathophysiologic Processes

Directory of Open Access Journals (Sweden)

Christian Eaton

2011-01-01

Full Text Available Kaposi sarcoma (KS, multicentric Castleman's disease (MCD, and plasmablastic microlymphoma, are all linked to human herpesvirus-8 (HHV-8 infection and HIV-induced immunodeficiency. Herein, we describe the case of a Kenyan man diagnosed with HIV in 2000. He deferred highly active antiretroviral therapy (HAART and remained in good health until his CD4+ count declined in 2006. He was hospitalized with bacterial pneumonia in 2008, after which he agreed to take HAART but did so sporadically. In 2010, he was hospitalized with fever, lymphadenopathy, pancytopenia, and an elevated HHV-8 viral load. A lymph node biopsy showed findings consistent with KS, MCD, and plasmablastic microlymphoma. Eight months after starting liposomal doxorubicin, Rituximab, and a new HAART regimen, he has improved clinically, and his HIV and HHV-8 viral loads are suppressed. These three conditions, found in the same lymph node, underscore the inflammatory and malignant potential of HHV-8, particularly in the milieu of HIV-induced immunodeficiency.

Study on the limiting acceleration rate in the VLEPP linear accelerator

International Nuclear Information System (INIS)

Balakin, V.E.; Brezhnev, O.N.; Zakhvatkin, M.N.

1987-01-01

To realize the design of colliding linear electron-positron beams it is necessary to solve the radical problem of production of accelerating structure with acceleration rate of approximately 100 MeV/m which can accelerate 10 12 particles in a bunch. Results of experimental studies of the limiting acceleration rate in the VLEPP accelerating structure are presented. Accelerating sections of different length were tested. When testing sections 29 cm long the acceleration rate of 55 MeV/m was attained, and for 1 m section the value reached 40 MeV/m. The maximum rate of acceleration (90 MeV/m) was attained when electric field intensity on the structure surface constituted more than 150 MV/m

Particle-accelerator decommissioning

International Nuclear Information System (INIS)

Opelka, J.H.; Mundis, R.L.; Marmer, G.J.; Peterson, J.M.; Siskind, B.; Kikta, M.J.

1979-12-01

Generic considerations involved in decommissioning particle accelerators are examined. There are presently several hundred accelerators operating in the United States that can produce material containing nonnegligible residual radioactivity. Residual radioactivity after final shutdown is generally short-lived induced activity and is localized in hot spots around the beam line. The decommissioning options addressed are mothballing, entombment, dismantlement with interim storage, and dismantlement with disposal. The recycle of components or entire accelerators following dismantlement is a definite possibility and has occurred in the past. Accelerator components can be recycled either immediately at accelerator shutdown or following a period of storage, depending on the nature of induced activation. Considerations of cost, radioactive waste, and radiological health are presented for four prototypic accelerators. Prototypes considered range from small accelerators having minimal amounts of radioactive mmaterial to a very large accelerator having massive components containing nonnegligible amounts of induced activation. Archival information on past decommissionings is presented, and recommendations concerning regulations and accelerator design that will aid in the decommissioning of an accelerator are given

State Constrained Optimal Control Applied to Supervisory Control in HEVs Commande optimale avec restrictions d’états appliquée à la supervision de l’énergie de véhicules hybrides

Directory of Open Access Journals (Sweden)

Pérez L.V.

2010-02-01

Full Text Available The optimization of the supervisory control of hybrid electric vehicles over predetermined driving cycles has been used as a previous study for determining on-line strategies and also for design and sizing purposes. This problem may be posed as an optimal control problem, in which the energy in the bank of batteries is often the state variable, and the power from any of the system sources is, the control action. As both of these quantities are bounded, the optimal control problem has control constraints or state constraints or both. Usually, the charge-sustaining mode of operation is ensured just by imposing a transversality condition, i.e. a fixed final energy, or including an additional term in the cost functional that penalizes the moving away of the state variable from the nominal value. We considered the problem where the state is allowed to move freely within a band. This led to an optimal control problem with control and state constraints. In this work we describe the difficulties that arise while solving the equations given by the Pontryagin’s Maximum Principle and how these difficulties can be overcome by using the so-called Direct Transcription approach that consists of a programming tool to solve the resultant large-scale finite dimensional optimization problem. L’optimisation de la commande au niveau superviseur de véhicules hybrides sur cycles d’usage prédéterminés a été utilisée comme une première étude pour déterminer des stratégies en ligne mais aussi avec des objectifs de conception et dimensionnement. Ce problème peut être posé comme un problème de commande optimale, où l’énergie dans les batteries est généralement la variable d’état et où la puissance de n’importe quelle source du système est l’action de commande. Comme ces deux quantités sont bornées, le problème de commande optimale a des restrictions sur la fonction de commande et sur l’état. Généralement, le fonctionnement �

Role of defective Oct-2 and OCA-B expression in immunoglobulin production and Kaposi's sarcoma-associated herpesvirus lytic reactivation in primary effusion lymphoma.

Science.gov (United States)

Di Bartolo, Daniel L; Hyjek, Elizabeth; Keller, Shannon; Guasparri, Ilaria; Deng, Hongyu; Sun, Ren; Chadburn, Amy; Knowles, Daniel M; Cesarman, Ethel

2009-05-01

Primary effusion lymphoma (PEL) is a distinct type of B-cell non-Hodgkin lymphoma characterized by the presence of Kaposi's sarcoma-associated herpesvirus (KSHV/human herpesvirus 8). Despite having a genotype and gene expression signature of highly differentiated B cells, PEL does not usually express surface or cytoplasmic immunoglobulin (Ig). We show the lack of Oct-2 and OCA-B transcription factors to be responsible, at least in part, for this defect in Ig production. Like Ig genes, ORF50, the key regulator of the switch from latency to lytic reactivation, contains an octamer motif within its promoter. We therefore examined the impact of Oct-2 and OCA-B on ORF50 activation. The binding of Oct-1 to the ORF50 promoter has been shown to significantly enhance ORF50 transactivation. We found that Oct-2, on the other hand, inhibited ORF50 expression and consequently lytic reactivation by competing with Oct-1 for the octamer motif in the ORF50 promoter. Our data suggest that Oct-2 downregulation in infected cells would be favorable to KSHV in allowing for efficient viral reactivation.

The C Terminus of the Nucleoprotein of Influenza A Virus Delivers Antigens Transduced by Tat to the trans-Golgi Network and Promotes an Efficient Presentation through HLA Class I

OpenAIRE

Bettosini, Francesca; Fiorillo, Maria Teresa; Magnacca, Adriana; Leone, Laura; Torrisi, Maria Rosaria; Sorrentino, Rosa

2005-01-01

Cytotoxic T lymphocytes (CTLs) are the most powerful weapon of the immune system to eliminate cells infected by intracellular parasites or tumors. However, very often, escape mechanisms overcome CTL immune surveillance by impairing the classical HLA class I antigen-processing pathway. Here, we describe a strategy for CTL activation based on the ability of Tat to mediate transcellular delivery of viral proteins encompassing HLA class I-restricted epitopes. In this system, the recombinant prote...

Source-to-accelerator quadrupole matching section for a compact linear accelerator

Science.gov (United States)

Seidl, P. A.; Persaud, A.; Ghiorso, W.; Ji, Q.; Waldron, W. L.; Lal, A.; Vinayakumar, K. B.; Schenkel, T.

2018-05-01

Recently, we presented a new approach for a compact radio-frequency (RF) accelerator structure and demonstrated the functionality of the individual components: acceleration units and focusing elements. In this paper, we combine these units to form a working accelerator structure: a matching section between the ion source extraction grids and the RF-acceleration unit and electrostatic focusing quadrupoles between successive acceleration units. The matching section consists of six electrostatic quadrupoles (ESQs) fabricated using 3D-printing techniques. The matching section enables us to capture more beam current and to match the beam envelope to conditions for stable transport in an acceleration lattice. We present data from an integrated accelerator consisting of the source, matching section, and an ESQ doublet sandwiched between two RF-acceleration units.

Electrostatic accelerators

CERN Document Server

Hinterberger, F

2006-01-01

The principle of electrostatic accelerators is presented. We consider Cockcroft– Walton, Van de Graaff and Tandem Van de Graaff accelerators. We resume high voltage generators such as cascade generators, Van de Graaff band generators, Pelletron generators, Laddertron generators and Dynamitron generators. The speci c features of accelerating tubes, ion optics and methods of voltage stabilization are described. We discuss the characteristic beam properties and the variety of possible beams. We sketch possible applications and the progress in the development of electrostatic accelerators.

Poussée de maladie de Kaposi et élévation du CA 19-9: penser à la tuberculose!

Science.gov (United States)

Ajili, Faida; Hariz, Héla; Souissi, Asmahen; Abid, Rim; Boussetta, Najeh; Laabidi, Besma; Battikh, Riadh; Louzir, Bassem; Othmani, Salah

2013-01-01

La maladie de Kaposi (MK) est une entité pathologique qui peut survenir chez les patients VIH positifs et dans le cadre d'une immunodépression, d'origine tuberculeuse très rarement. On décrit le cas d'une MK chez un patient VIH négatif au décours d'une tuberculose. Nous rapportons le cas d'un patient âgé de 81 ans, VIH négatif, ayant présenté deux nodules angiomateux de l'avant bras gauche dont la biopsie cutanée était en faveur d'une MK. L’évolution était marquée 2 mois plus tard, par l'apparition de placards angiomateux extensifs des deux membres supérieurs et d'adénopathies cervicales jugulo-carotidiennes bilatérales. La biopsie ganglionnaire était en faveur d'une tuberculose ganglionnaire. Par ailleurs, il avait un taux sérique élevé des CA 19-9. La régression de l’étendue des lésions au niveau des membres supérieurs et la normalisation du taux sérique des CA 19-9 ont été obtenues sous traitement anti-tuberculeux. Chez les patients atteints d'une MK avec une élévation des CA 19-9, il faut penser à la tuberculose. PMID:24711871

Acceleration of 14C beams in electrostatic accelerators

International Nuclear Information System (INIS)

Rowton, L.J.; Tesmer, J.R.

1981-01-01

Operational problems in the production and acceleration of 14 C beams for nuclear structure research in Los Alamos National Laboratory's Van de Graaff accelerators are discussed. Methods for the control of contamination in ion sources, accelerators and personnel are described. Sputter source target fabrication techniques and the relative beam production efficiencies of various types of bound particulate carbon sputter source targets are presented

Multiperiodic accelerator structures for linear particle accelerators

International Nuclear Information System (INIS)

Tran, D.T.

1975-01-01

High efficiency linear accelerator structures, comprised of a succession of cylindrical resonant cavities for acceleration, are described. Coupling annular cavities are located at the periphery, each being coupled to two adjacent cylindrical cavities. (auth)

Beam transport through electrostatic accelerators and matching into post accelerators

International Nuclear Information System (INIS)

Larson, J.D.

1986-01-01

Ion beam transport through electrostatic acceleration is briefly reviewed. Topics discussed include injection, matching into the low-energy acceleration stage, matching from the terminal stripper into the high-energy stage, transport to a post accelerator, space charge, bunching isochronism, dispersion and charge selection. Beam transport plans for the proposed Vivitron accelerator are described. (orig.)

Can Accelerators Accelerate Learning?

International Nuclear Information System (INIS)

Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

2009-01-01

The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ)[1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

Can Accelerators Accelerate Learning?

Science.gov (United States)

Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

2009-03-01

The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ) [1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

Accelerations in Flight

Science.gov (United States)

Doolittle, J H

1925-01-01

This work on accelerometry was done at McCook Field for the purpose of continuing the work done by other investigators and obtaining the accelerations which occur when a high-speed pursuit airplane is subjected to the more common maneuvers. The accelerations obtained in suddenly pulling out of a dive with well-balanced elevators are shown to be within 3 or 4 per cent of the theoretically possible accelerations. The maximum acceleration which a pilot can withstand depends upon the length of time the acceleration is continued. It is shown that he experiences no difficulty under the instantaneous accelerations as high as 7.8 G., but when under accelerations in excess of 4.5 G., continued for several seconds, he quickly loses his faculties.

Theoretical Investigations of Plasma-Based Accelerators and Other Advanced Accelerator Concepts

International Nuclear Information System (INIS)

Shuets, G.

2004-01-01

Theoretical investigations of plasma-based accelerators and other advanced accelerator concepts. The focus of the work was on the development of plasma based and structure based accelerating concepts, including laser-plasma, plasma channel, and microwave driven plasma accelerators

Large tandem accelerators

International Nuclear Information System (INIS)

Jones, C.M.

1976-01-01

The increasing importance of energetic heavy ion beams in the study of atomic physics, nuclear physics, and materials science has partially or wholly motivated the construction of a new generation of tandem accelerators designed to operate at maximum terminal potentials in the range 14 to 30 MV. In addition, a number of older tandem accelerators are now being significantly upgraded to improve their heavy ion performance. Both of these developments have reemphasized the importance of negative heavy ion sources. The new large tandem accelerators are described, and the requirements placed on negative heavy ion source technology by these and other tandem accelerators used for the acceleration of heavy ions are discussed. First, a brief description is given of the large tandem accelerators which have been completed recently, are under construction, or are funded for construction, second, the motivation for construction of these accelerators is discussed, and last, criteria for negative ion sources for use with these accelerators are presented

A novel branched TAT(47-57) peptide for selective Ni(2+) introduction into the human fibrosarcoma cell nucleus.

Science.gov (United States)

Szyrwiel, Łukasz; Shimura, Mari; Shirataki, Junko; Matsuyama, Satoshi; Matsunaga, Akihiro; Setner, Bartosz; Szczukowski, Łukasz; Szewczuk, Zbigniew; Yamauchi, Kazuto; Malinka, Wiesław; Chavatte, Laurent; Łobinski, Ryszard

2015-07-01

A TAT47-57 peptide was modified on the N-terminus by elongation with a 2,3-diaminopropionic acid residue and then by coupling of two histidine residues on its N-atoms. This branched peptide could bind to Ni under physiological conditions as a 1 : 1 complex. We demonstrated that the complex was quantitatively taken up by human fibrosarcoma cells, in contrast to Ni(2+) ions. Ni localization (especially at the nuclei) was confirmed by imaging using both scanning X-ray fluorescence microscopy and Newport Green fluorescence. A competitive assay with Newport Green showed that the latter displaced the peptide ligand from the Ni-complex. Ni(2+) delivered as a complex with the designed peptide induced substantially more DNA damage than when introduced as a free ion. The availability of such a construct opens up the way to investigate the importance of the nucleus as a target for the cytotoxicity, genotoxicity or carcinogenicity of Ni(2+).

Kaposi sarcoma-associated herpes virus targets the lymphotactin receptor with both a broad spectrum antagonist vCCL2 and a highly selective and potent agonist vCCL3

DEFF Research Database (Denmark)

Lüttichau, Hans R; Johnsen, Anders H; Jurlander, Jesper

2007-01-01

virus (KSHV) encodes three chemokine-like proteins named vCCL1, vCCL2, and vCCL3. In this study vCCL3 was probed in parallel with vCCL1 and vCCL2 against a panel of the 18 classified human chemokine receptors. In calcium mobilization assays vCCL1 acted as a selective CCR8 agonist, whereas vCCL2......Large DNA viruses such as herpesvirus and poxvirus encode proteins that target and exploit the chemokine system of their host. These proteins have the potential to block or change the orchestrated recruitment of leukocytes to sites of viral infection. The genome of Kaposi sarcoma-associated herpes...... was found to act as a broad spectrum chemokine antagonist of human chemokine receptors, including the lymphotactin receptor. In contrast vCCL3 was found to be a highly selective agonist for the human lymphotactin receptor XCR1. The potency of vCCL3 was found to be 10-fold higher than the endogenous human...

Plasma particle accelerators

International Nuclear Information System (INIS)

Dawson, J.M.

1988-01-01

The Superconducting Supercollider (SSC) will require an 87-kilometer accelerator ring to boost particles to 40 TeV. The SSC's size is due in part to the fact that its operating principle is the same one that has dominated accelerator design for 50 years: it guides particles by means of magnetic fields and propels them by strong electric fields. If one were to build an equally powerful but smaller accelerator, one would need to increase the strength of the guiding and propelling fields. Actually, however, conventional technology may not be able to provide significant increases in field strength. There are two reasons. First, the forces from magnetic fields are becoming greater than the structural forces that hold a magnetic material together; the magnets that produce these fields would themselves be torn apart. Second, the energy from electric fields is reaching the energies that bind electrons to atoms; it would tear electrons from nuclei in the accelerator's support structures. It is the electric field problem that plasma accelerators can overcome. Plasma particle accelerators are based on the principle that particles can be accelerated by the electric fields generated within a plasma. Because the plasma has already been ionized, plasma particle accelerators are not susceptible to electron dissociation. They can in theory sustain accelerating fields thousands of times stronger that conventional technologies. So far two methods for creating plasma waves for accelerators have been proposed and tested: the wakefield and the beat wave. Although promising electric fields have been produced, more research is necessary to determine whether plasma particle accelerators can compete with the existing accelerators. 7 figs

Molecular ion acceleration using tandem accelerator

Energy Technology Data Exchange (ETDEWEB)

Saito, Yuichi; Mizuhashi, Kiyoshi; Tajima, Satoshi [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

1996-12-01

In TIARA compound beam radiation system, cluster beams have been produced using 3 MV tandem accelerator (9SDH-2) to supply them to various radiation on injection experiments. Till now, productions of C{sub 2-8}, Si{sub 2-4} and O{sub 2} and their accelerations up to 6 MeV have been succeeded. This study aimed at production and acceleration of B{sub 2-4} and LiF. Anion clusters were produced using the conventional ion source of cesium sputter type. The proportions of atoms, molecules and clusters elicited from the ion source were varied depending on the material`s properties and the operating conditions of ion source such as sample temperature, sputter voltage and the shape of sample. The anion clusters were accelerated toward the high voltage terminal in the center of tandem accelerator, leading to cations through losing their electrons by the collision to N{sub 2} gas in a charge conversion cell at the terminal. Positively charged cluster ions could be obtained by modulating the pressure of N{sub 2} gas. Thus, B{sub 2} (64 nA), B{sub 3} (4.4 nA) and B{sub 4} (2.7 nA) have been produced and their maximum survival probabilities were higher than those of carbon or silicon clusters. In addition, the relationship between beam current and gas pressure was investigated for Bn (n = 2-4) and LiF. (M.N.)

TeV/m Nano-Accelerator: Current Status of CNT-Channeling Acceleration Experiment

Energy Technology Data Exchange (ETDEWEB)

Shin, Young Min [Northern Illinois U.; Lumpkin, Alex H. [Fermilab; Thangaraj, Jayakar Charles [Fermilab; Thurman-Keup, Randy Michael [Fermilab; Shiltsev, Vladimir D. [Fermilab

2014-09-17

Crystal channeling technology has offered various opportunities in the accelerator community with a viability of ultrahigh gradient (TV/m) acceleration for future HEP collider. The major challenge of channeling acceleration is that ultimate acceleration gradients might require a high power driver in the hard x-ray regime (~ 40 keV). This x-ray energy exceeds those for x-rays as of today, although x-ray lasers can efficiently excite solid plasma and accelerate particles inside a crystal channel. Moreover, only disposable crystal accelerators are possible at such high externally excited fields which would exceed the ionization thresholds destroying the atomic structure, so acceleration will take place only in a short time before full dissociation of the lattice. Carbon-based nanostructures have great potential with a wide range of flexibility and superior physical strength, which can be applied to channeling acceleration. This paper presents a beam- driven channeling acceleration concept with CNTs and discusses feasible experiments with the Advanced Superconducting Test Accelerator (ASTA) in Fermilab.

Accelerator mass spectrometry at the Rossendorf 5 MV tandem accelerator

International Nuclear Information System (INIS)

Friedrich, M.; Buerger, W.; Curian, H.; Hartmann, B.; Hentschel, E.; Matthes, H.; Probst, W.; Seidel, M.; Turuc, S.; Hebert, D.; Rothe, T.; Stolz, W.

1992-01-01

The Rossendorf electrostatic accelerators (5 MV tandem accelerator and single ended 2 MV van de Graaff accelerator) are already used for ion beam analysis. The existing methods (RBS, PIXE, ERDA, NRA, nuclear microprobe and external beam) will be completed by introduction of Accelerator Mass Spectrometry (AMS). A short description of the Rossendorf AMS system is given and first experimental results are presented. (R.P.) 4 refs.; 6 figs

Truck acceleration behavior study and acceleration lane length recommendations for metered on-ramps

Directory of Open Access Journals (Sweden)

Guangchuan Yang

2016-10-01

Full Text Available This paper investigated the actual truck acceleration capability at metered on-ramps. Truck acceleration performance data were collected through a video-based data collection method. A piecewise constant acceleration model was employed to capture truck acceleration characteristics. It was found that the existing acceleration length will affect truck drivers’ acceleration behavior. At the taper type ramp that has limited acceleration distance, acceleration profile indicated a decreasing trend with distance. While for the ramp with an auxiliary lane that has sufficient acceleration distance, it was found that the acceleration behavior is to have a high acceleration rate in the beginning, then acceleration rate decrease with speed increase, and high acceleration rate again as drivers approach the merging area. Field data show that the truck acceleration performance data documented in the ITE’s (Institute of Transportation Engineers “Traffic Engineering Handbook” are much lower than the field collected data. Also, based on the regression analysis of speed versus distance profiles, it was found that the AASHTO’s (American Association of State Highway and Transportation Officials Green Book acceleration length design guidance is insufficient to accommodate trucks at metered on-ramps. The required acceleration lengths for medium and heavy trucks are approximately 1.3 and 1.6 times of the Green Book design guideline, respectively.

Probing electron acceleration and x-ray emission in laser-plasma accelerators

International Nuclear Information System (INIS)

Thaury, C.; Ta Phuoc, K.; Corde, S.; Brijesh, P.; Lambert, G.; Malka, V.; Mangles, S. P. D.; Bloom, M. S.; Kneip, S.

2013-01-01

While laser-plasma accelerators have demonstrated a strong potential in the acceleration of electrons up to giga-electronvolt energies, few experimental tools for studying the acceleration physics have been developed. In this paper, we demonstrate a method for probing the acceleration process. A second laser beam, propagating perpendicular to the main beam, is focused on the gas jet few nanosecond before the main beam creates the accelerating plasma wave. This second beam is intense enough to ionize the gas and form a density depletion, which will locally inhibit the acceleration. The position of the density depletion is scanned along the interaction length to probe the electron injection and acceleration, and the betatron X-ray emission. To illustrate the potential of the method, the variation of the injection position with the plasma density is studied

Microelectromechanical acceleration-sensing apparatus

Science.gov (United States)

Lee, Robb M [Albuquerque, NM; Shul, Randy J [Albuquerque, NM; Polosky, Marc A [Albuquerque, NM; Hoke, Darren A [Albuquerque, NM; Vernon, George E [Rio Rancho, NM

2006-12-12

An acceleration-sensing apparatus is disclosed which includes a moveable shuttle (i.e. a suspended mass) and a latch for capturing and holding the shuttle when an acceleration event is sensed above a predetermined threshold level. The acceleration-sensing apparatus provides a switch closure upon sensing the acceleration event and remains latched in place thereafter. Examples of the acceleration-sensing apparatus are provided which are responsive to an acceleration component in a single direction (i.e. a single-sided device) or to two oppositely-directed acceleration components (i.e. a dual-sided device). A two-stage acceleration-sensing apparatus is also disclosed which can sense two acceleration events separated in time. The acceleration-sensing apparatus of the present invention has applications, for example, in an automotive airbag deployment system.

Channel-accelerating gap interaction and beam acceleration and transport experiments with the recirculating linear accelerator (RLA)

International Nuclear Information System (INIS)

Mazarakis, M.G.; Smith, D.L.; Poukey, J.W.; Wagner, J.S.; Bennett, L.F.; Olson, W.R.; Turman, B.N.; Prestwich, K.R.; Wells, J.; Struve, K.

1992-01-01

The lifetime of the Ion Focusing Regime (IFR) channel following the pulsing of the post-accelerating gaps is critical for open-ended low energy devices. It dictates the number of allowable beam recirculations through the gaps. In the case of a closed racetrack configuration, it is significant but not as critical, since the presence of the electron beam focuses the ions and lengthens the lifetime of the ion channel. The authors have experimentally established that pulsing an accelerating gap perturbs the IFR channel. However for the parameters studied, the lifetime is long enough to allow at least four beam recirculations in a spiral device. In addition transparent grids of cusp fields positioned upstream and downstream from the gaps prevent them from perturbing the IFR channel. Experiments were performed with and without injected electron beams. For the experiments investigating the IFR channel interaction with the accelerating gap, the injector was removed and the beam line was extended downstream and upstream from the accelerating cavity. Only the first straight section of the RLA with one accelerating cavity (ET-2) was utilized. The acceleration and transport experiments were performed utilizing two injectors: first the low energy 1.3-MV Isolated Blumlein (IB) injector and most recently the new 4-MV 20-kA injector. Beams of 6--20 kA current were produced and successfully transported and accelerated through the ET-2 post-accelerating gap. For both injectors an apertured non-immersed ion-focused foilless diode was selected among various options. It is the simplest and easiest to operate and can be adjusted to provide variable beam impedance loads to the injector. The transport efficiencies were 90% for the low energy injector and 100% for the new 4-MV injector. The beam Gaussian profile and radius (5 mm) remain the same through acceleration. Experimental results will be presented and compared with numerical simulations

Kaposi sarcoma herpes virus latency associated nuclear antigen protein release the G2/M cell cycle blocks by modulating ATM/ATR mediated checkpoint pathway.

Directory of Open Access Journals (Sweden)

Amit Kumar

Full Text Available The Kaposi's sarcoma-associated herpesvirus infects the human population and maintains latency stage of viral life cycle in a variety of cell types including cells of epithelial, mesenchymal and endothelial origin. The establishment of latent infection by KSHV requires the expression of an unique repertoire of genes among which latency associated nuclear antigen (LANA plays a critical role in the replication of the viral genome. LANA regulates the transcription of a number of viral and cellular genes essential for the survival of the virus in the host cell. The present study demonstrates the disruption of the host G2/M cell cycle checkpoint regulation as an associated function of LANA. DNA profile of LANA expressing human B-cells demonstrated the ability of this nuclear antigen in relieving the drug (Nocodazole induced G2/M checkpoint arrest. Caffeine suppressed nocodazole induced G2/M arrest indicating involvement of the ATM/ATR. Notably, we have also shown the direct interaction of LANA with Chk2, the ATM/ATR signalling effector and is responsible for the release of the G2/M cell cycle block.

Accelerator reliability workshop

International Nuclear Information System (INIS)

Hardy, L.; Duru, Ph.; Koch, J.M.; Revol, J.L.; Van Vaerenbergh, P.; Volpe, A.M.; Clugnet, K.; Dely, A.; Goodhew, D.

2002-01-01

About 80 experts attended this workshop, which brought together all accelerator communities: accelerator driven systems, X-ray sources, medical and industrial accelerators, spallation sources projects (American and European), nuclear physics, etc. With newly proposed accelerator applications such as nuclear waste transmutation, replacement of nuclear power plants and others. Reliability has now become a number one priority for accelerator designers. Every part of an accelerator facility from cryogenic systems to data storage via RF systems are concerned by reliability. This aspect is now taken into account in the design/budget phase, especially for projects whose goal is to reach no more than 10 interruptions per year. This document gathers the slides but not the proceedings of the workshop

Accelerator reliability workshop

Energy Technology Data Exchange (ETDEWEB)

Hardy, L; Duru, Ph; Koch, J M; Revol, J L; Van Vaerenbergh, P; Volpe, A M; Clugnet, K; Dely, A; Goodhew, D

2002-07-01

About 80 experts attended this workshop, which brought together all accelerator communities: accelerator driven systems, X-ray sources, medical and industrial accelerators, spallation sources projects (American and European), nuclear physics, etc. With newly proposed accelerator applications such as nuclear waste transmutation, replacement of nuclear power plants and others. Reliability has now become a number one priority for accelerator designers. Every part of an accelerator facility from cryogenic systems to data storage via RF systems are concerned by reliability. This aspect is now taken into account in the design/budget phase, especially for projects whose goal is to reach no more than 10 interruptions per year. This document gathers the slides but not the proceedings of the workshop.

Future accelerator technology

International Nuclear Information System (INIS)

Sessler, A.M.

1986-05-01

A general discussion is presented of the acceleration of particles. Upon this foundation is built a categorization scheme into which all accelerators can be placed. Special attention is devoted to accelerators which employ a wake-field mechanism and a restricting theorem is examined. It is shown how the theorem may be circumvented. Comments are made on various acceleration schemes

Accelerating Inspire

CERN Document Server

AUTHOR|(CDS)2266999

2017-01-01

CERN has been involved in the dissemination of scientific results since its early days and has continuously updated the distribution channels. Currently, Inspire hosts catalogues of articles, authors, institutions, conferences, jobs, experiments, journals and more. Successful orientation among this amount of data requires comprehensive linking between the content. Inspire has lacked a system for linking experiments and articles together based on which accelerator they were conducted at. The purpose of this project has been to create such a system. Records for 156 accelerators were created and all 2913 experiments on Inspire were given corresponding MARC tags. Records of 18404 accelerator physics related bibliographic entries were also tagged with corresponding accelerator tags. Finally, as a part of the endeavour to broaden CERN's presence on Wikipedia, existing Wikipedia articles of accelerators were updated with short descriptions and links to Inspire. In total, 86 Wikipedia articles were updated. This repo...

Requirements of a proton beam accelerator for an accelerator-driven reactor

International Nuclear Information System (INIS)

Takahashi, H.; Zhao, Y.; Tsoupas, N.; An, Y.; Yamazaki, Y.

1997-01-01

When the authors first proposed an accelerator-driven reactor, the concept was opposed by physicists who had earlier used the accelerator for their physics experiments. This opposition arose because they had nuisance experiences in that the accelerator was not reliable, and very often disrupted their work as the accelerator shut down due to electric tripping. This paper discusses the requirements for the proton beam accelerator. It addresses how to solve the tripping problem and how to shape the proton beam

Substantial regional differences in human herpesvirus 8 seroprevalence in sub-Saharan Africa: insights on the origin of the "Kaposi's sarcoma belt".

Science.gov (United States)

Dollard, Sheila C; Butler, Lisa M; Jones, Alison M Graves; Mermin, Jonathan H; Chidzonga, Midion; Chipato, Tsungai; Shiboski, Caroline H; Brander, Christian; Mosam, Anisa; Kiepiela, Photini; Hladik, Wolfgang; Martin, Jeffrey N

2010-11-15

Equatorial Africa has among the highest incidences of Kaposi's sarcoma (KS) in the world, thus earning the name "KS Belt." This was the case even before the HIV epidemic. To date, there is no clear evidence that HHV-8 seroprevalence is higher in this region but interpretation of the available literature is tempered by differences in serologic assays used across studies. We examined representatively sampled ambulatory adults in Uganda, which is in the "KS Belt," and in Zimbabwe and South Africa which are outside the Belt, for HHV-8 antibodies. All serologic assays were uniformly performed in the same reference laboratory by the same personnel. In the base-case serologic algorithm, seropositivity was defined by reactivity in an immunofluorescence assay or in 2 enzyme immunoassays. A total of 2,375 participants were examined. In Uganda, HHV-8 seroprevalence was high early in adulthood (35.5% by age 21) without significant change thereafter. In contrast, HHV-8 seroprevalence early in adulthood was lower in Zimbabwe and South Africa (13.7 and 10.8%, respectively) but increased with age. After age adjustment, Ugandans had 3.24-fold greater odds of being HHV-8 infected than South Africans (p Africa. These findings help to explain the high KS incidence in the "KS Belt" and underscore the importance of a uniform approach to HHV-8 antibody testing.

Kaposi's-sarcoma-associated-herpesvirus-activated dendritic cells promote HIV-1 trans-infection and suppress CD4+ T cell proliferation

International Nuclear Information System (INIS)

Liu, Wan; Qin, Yan; Bai, Lei; Lan, Ke; Wang, Jian-Hua

2013-01-01

Infection of Kaposi's sarcoma-associated herpesvirus (KSHV) is commonly occurred in AIDS patients. KSHV and HIV-1 act cooperatively in regulating infection with each other and in human carcinogenesis. Dendritic cells (DCs), as the pivotal cells in host immunity, may be modulated by both viruses, for immunoevasion and dissemination, therefore, the interaction between DCs and each virus has been a prior focus for pathogenesis elucidation. Here, we assessed the potential effect of KSHV on DC–HIV-1 interaction. We found that KSHV stimulation could promote maturation of monocyte-derived DCs (MDDCs) and impaired the ability of MDDCs to drive proliferation of resting CD4 + T cells, demonstrating the immunosuppression induced by KSHV. More importantly, KSHV-stimulated MDDCs could capture more HIV-1 and efficiently transferred these infectious viruses to Hut/CCR5 T cell line. Our results reveal the novel modulation of DC-mediated HIV-1 dissemination by KSHV, and highlight the importance of studying DC–HIV-1 interaction to elucidate HIV/AIDS pathogenesis. - Highlights: ► KSHV impaired the ability of MDDCs to drive proliferation of resting CD4 + T cells. ► KSHV stimulation matured MDDCs and enhanced HIV-1 endocytosis. ► KSHV stimulated MDDCs increased ICAM-1 expression and tighten contact with T cells. ► KSHV-stimulated MDDCs promoted HIV-1 trans-infection of CD4 + T cells

SALOME: An Accelerator for the Practical Course in Accelerator Physics

OpenAIRE

Miltchev, Velizar; Riebesehl, Daniel; Roßbach, Jörg; Trunk, Maximilian; Stein, Oliver

2014-01-01

SALOME (Simple Accelerator for Learning Optics and the Manipulation of Electrons) is a short low energy linear electron accelerator built by the University of Hamburg. The goal of this project is to give the students the possibility to obtain hands-on experience with the basics of accelerator physics. In this contribution the layout of the device will be presented. The most important components of the accelerator will be discussed and an overview of the planned demonstration experiments will ...

Social-emotional characteristics of gifted accelerated and non-accelerated students in the Netherlands.

Science.gov (United States)

Hoogeveen, Lianne; van Hell, Janet G; Verhoeven, Ludo

2012-12-01

In the studies of acceleration conducted so far a multidimensional perspective has largely been neglected. No attempt has been made to relate social-emotional characteristics of accelerated versus non-accelerated students in perspective of environmental factors. In this study, social-emotional characteristics of accelerated gifted students in the Netherlands were examined in relation to personal and environmental factors. Self-concept and social contacts of accelerated (n = 148) and non-accelerated (n = 55) gifted students, aged 4 to 27 (M = 11.22, SD = 4.27) were measured. Self-concept and social contacts of accelerated and non-accelerated gifted students were measured using a questionnaire and a diary, and parents of these students evaluated their behavioural characteristics. Gender and birth order were studied as personal factors and grade, classroom, teachers' gender, teaching experience, and the quality of parent-school contact as environmental factors. The results showed minimal differences in the social-emotional characteristics of accelerated and non-accelerated gifted students. The few differences we found favoured the accelerated students. We also found that multiple grade skipping does not have negative effects on social-emotional characteristics, and that long-term effects of acceleration tend to be positive. As regards the possible modulation of personal and environmental factors, we merely found an impact of such factors in the non-accelerated group. The results of this study strongly suggest that social-emotional characteristics of accelerated gifted students and non-accelerated gifted students are largely similar. These results thus do not support worries expressed by teachers about the acceleration of gifted students. Our findings parallel the outcomes of earlier studies in the United States and Germany in that we observed that acceleration does not harm gifted students, not even in the case of multiple grade skipping. On the contrary, there is a

The miniature accelerator

CERN Multimedia

Antonella Del Rosso

2015-01-01

The image that most people have of CERN is of its enormous accelerators and their capacity to accelerate particles to extremely high energies. But thanks to some cutting-edge studies on beam dynamics and radiofrequency technology, along with innovative construction techniques, teams at CERN have now created the first module of a brand-new accelerator, which will be just 2 metres long. The potential uses of this miniature accelerator will include deployment in hospitals for the production of medical isotopes and the treatment of cancer. It’s a real David-and-Goliath story.   Serge Mathot, in charge of the construction of the "mini-RFQ", pictured with the first of the four modules that will make up the miniature accelerator. The miniature accelerator consists of a radiofrequency quadrupole (RFQ), a component found at the start of all proton accelerator chains around the world, from the smallest to the largest. The LHC is designed to produce very high-intensity beams ...

Accelerators for energy

International Nuclear Information System (INIS)

Inoue, Makoto

2000-01-01

A particle accelerator is a device to consume energy but not to produce it. Then, the titled accelerator seems to mean an accelerator for using devices related to nuclear energy. For an accelerator combined to nuclear fissionable fuel, neutron sources are D-T type, (gamma, n) reaction using electron beam type spallation type, and so forth. At viewpoints of powers of incident beam and formed neutron, a spallation type source using high energy proton is told to be effective but others have some advantages by investigation on easy operability, easy construction, combustion with target, energy and directivity of neutron, and so forth. Here were discussed on an accelerator for research on accelerator driven energy system by dividing its researching steps, and on kind, energy, beam intensity, and so forth of an accelerator suitable for it. And, space electric charge effect at beam propagation direction controlled by beam intensity of cyclotron was also commented. (G.K.)

Electrostatic accelerators

OpenAIRE

Hinterberger, F

2006-01-01

The principle of electrostatic accelerators is presented. We consider Cockcroft– Walton, Van de Graaff and Tandem Van de Graaff accelerators. We resume high voltage generators such as cascade generators, Van de Graaff band generators, Pelletron generators, Laddertron generators and Dynamitron generators. The speci c features of accelerating tubes, ion optics and methods of voltage stabilization are described. We discuss the characteristic beam properties and the variety of possible beams. We ...

Superconducting accelerator technology

International Nuclear Information System (INIS)

Grunder, H.A.; Hartline, B.K.

1986-01-01

Modern and future accelerators for high energy and nuclear physics rely increasingly on superconducting components to achieve the required magnetic fields and accelerating fields. This paper presents a practical overview of the phenomenon of superconductivity, and describes the design issues and solutions associated with superconducting magnets and superconducting rf acceleration structures. Further development and application of superconducting components promises increased accelerator performance at reduced electric power cost

Sector ring accelerator ''RESATRON''

International Nuclear Information System (INIS)

Schwabe, E.

1980-01-01

Project of sector ring accelerator RESATRON is described. The curiosity of this accelerator is the second cycle of acceleration of the beam after stripping it on the foil. In such an accelerator heavy ions with a different ratio Z to A can be accelerated. (S.B.)

2014 Joint International Accelerator School: Beam Loss and Accelerator Protection

CERN Document Server

JAS - Joint US-CERN-Japan-Russia Accelerator School

2016-01-01

Many particle accelerators operate with very high beam power and very high energy stored in particle beams as well as in magnet systems. In the future, the beam power in high intensity accelerators will further increase. The protection of the accelerator equipment from the consequences of uncontrolled release of the energy is essential. This was the motivation for organizing a first school on beam losses and accelerator protection (in general referred to as machine protection). During the school the methods and technologies to identify, mitigate, monitor and manage the technical risks associated with the operation of accelerators with high-power beams or subsystems with large stored energy were presented. At the completion of the school the participants should have been able to understand the physical phenomena that can damage machine subsystems or interrupt operations and to analyze an accelerator facility to produce a register of technical risks and the corresponding risk mitigation and management strategie...

Influence des conditions d'engorgement du sol sur l'évolution de l'état hydrique de jeunes plants d'Epicéa (Picea abies L.)

OpenAIRE

Granier, André; Levy, G.

1981-01-01

De jeunes plants d’Epicéa ont été soumis à différents types d’engorgement : nappe en surface ou à différentes profondeurs, > (barbotage d’air ou renouvellement quotidien de l’eau) ou non. L’état hydrique des plants a été évalué au moyen de la pression de sève, soit en conditions de transpiration nulle (pression de base), soit lorsqu’il y a transpiration. Les principaux résultats sont les suivants : - la pression de base des plants (mesures nocturnes) diminue au cours des premiers jours ...

Linear Accelerators

International Nuclear Information System (INIS)

Vretenar, M

2014-01-01

The main features of radio-frequency linear accelerators are introduced, reviewing the different types of accelerating structures and presenting the main characteristics aspects of linac beam dynamics

Accelerator structure for a charged particle linear accelerator working in standing wave mode

International Nuclear Information System (INIS)

Tran, D.T.; Tronc, Dominique.

1977-01-01

Charged particle accelerators generally include a pre-grouping or pre-accelerating structure associated with the accelerator structure itself. But pre-grouping or pre-accelerating structures of known type (Patent application No. 70 39261 for example) present electric and dimensional characteristics that rule them out for accelerators working at high frequencies (C or X bands for example), since the distance separating the interaction spaces becomes very small in this case. The accelerator structure mentioned in this invention can be used to advantage for such accelerators [fr

Development of bipolar pulse accelerator for intense pulsed ion beam acceleration

International Nuclear Information System (INIS)

Fujioka, Y.; Mitsui, C.; Kitamura, I.; Takahashi, T.; Masugata, K.; Tanoue, H.; Arai, K.

2003-01-01

To improve the purity of an intense pulsed ion beams a new type of pulsed ion beam accelerator named 'bipolar pulse accelerator (BPA)' was proposed. In the accelerator purity of the beam is expected. To confirm the principle of the accelerator experimental system was developed. The system utilizes B y type magnetically insulated acceleration gap and operated with single polar negative pulse. A coaxial gas puff plasma gun placed in the grounded anode was used as an ion source, and source plasma (nitrogen) of current density approx. = 25 A/cm 2 , duration approx. = 1.5 μs was injected into the acceleration gap. The ions are successfully accelerated from the grounded anode to the drift tube by applying negative pulse of voltage 180 kV, duration 60 ns to the drift tube. Pulsed ion beam of current density approx. = 40 A/cm 2 , duration approx. 60 ns was obtained at 42 mm downstream from the anode surface. (author)

KEK digital accelerator

Directory of Open Access Journals (Sweden)

T. Iwashita

2011-07-01

Full Text Available The High Energy Accelerator Research Organization KEK digital accelerator (KEK-DA is a renovation of the KEK 500 MeV booster proton synchrotron, which was shut down in 2006. The existing 40 MeV drift tube linac and rf cavities have been replaced by an electron cyclotron resonance (ECR ion source embedded in a 200 kV high-voltage terminal and induction acceleration cells, respectively. A DA is, in principle, capable of accelerating any species of ion in all possible charge states. The KEK-DA is characterized by specific accelerator components such as a permanent magnet X-band ECR ion source, a low-energy transport line, an electrostatic injection kicker, an extraction septum magnet operated in air, combined-function main magnets, and an induction acceleration system. The induction acceleration method, integrating modern pulse power technology and state-of-art digital control, is crucial for the rapid-cycle KEK-DA. The key issues of beam dynamics associated with low-energy injection of heavy ions are beam loss caused by electron capture and stripping as results of the interaction with residual gas molecules and the closed orbit distortion resulting from relatively high remanent fields in the bending magnets. Attractive applications of this accelerator in materials and biological sciences are discussed.

Semiconductor acceleration sensor

Science.gov (United States)

Ueyanagi, Katsumichi; Kobayashi, Mitsuo; Goto, Tomoaki

1996-09-01

This paper reports a practical semiconductor acceleration sensor especially suited for automotive air bag systems. The acceleration sensor includes four beams arranged in a swastika structure. Two piezoresistors are formed on each beam. These eight piezoresistors constitute a Wheatstone bridge. The swastika structure of the sensing elements, an upper glass plate and a lower glass plate exhibit the squeeze film effect which enhances air dumping, by which the constituent silicon is prevented from breakdown. The present acceleration sensor has the following features. The acceleration force component perpendicular to the sensing direction can be cancelled. The cross-axis sensitivity is less than 3 percent. And, the erroneous offset caused by the differences between the thermal expansion coefficients of the constituent materials can be canceled. The high aspect ratio configuration realized by plasma etching facilitates reducing the dimensions and improving the sensitivity of the acceleration sensor. The present acceleration sensor is 3.9 mm by 3.9 mm in area and 1.2 mm in thickness. The present acceleration sensor can measure from -50 to +50 G with sensitivity of 0.275 mV/G and with non-linearity of less than 1 percent. The acceleration sensor withstands shock of 3000 G.

Large electrostatic accelerators

Energy Technology Data Exchange (ETDEWEB)

Jones, C.M.

1984-01-01

The increasing importance of energetic heavy ion beams in the study of atomic physics, nuclear physics, and materials science has partially or wholly motivated the construction of a new generation of large electrostatic accelerators designed to operate at terminal potentials of 20 MV or above. In this paper, the author briefly discusses the status of these new accelerators and also discusses several recent technological advances which may be expected to further improve their performance. The paper is divided into four parts: (1) a discussion of the motivation for the construction of large electrostatic accelerators, (2) a description and discussion of several large electrostatic accelerators which have been recently completed or are under construction, (3) a description of several recent innovations which may be expected to improve the performance of large electrostatic accelerators in the future, and (4) a description of an innovative new large electrostatic accelerator whose construction is scheduled to begin next year. Due to time and space constraints, discussion is restricted to consideration of only tandem accelerators.

Large electrostatic accelerators

International Nuclear Information System (INIS)

Jones, C.M.

1984-01-01

The increasing importance of energetic heavy ion beams in the study of atomic physics, nuclear physics, and materials science has partially or wholly motivated the construction of a new generation of large electrostatic accelerators designed to operate at terminal potentials of 20 MV or above. In this paper, the author briefly discusses the status of these new accelerators and also discusses several recent technological advances which may be expected to further improve their performance. The paper is divided into four parts: (1) a discussion of the motivation for the construction of large electrostatic accelerators, (2) a description and discussion of several large electrostatic accelerators which have been recently completed or are under construction, (3) a description of several recent innovations which may be expected to improve the performance of large electrostatic accelerators in the future, and (4) a description of an innovative new large electrostatic accelerator whose construction is scheduled to begin next year. Due to time and space constraints, discussion is restricted to consideration of only tandem accelerators

CERN Accelerator School: Registration open for Advanced Accelerator Physics course

CERN Multimedia

2015-01-01

Registration is now open for the CERN Accelerator School’s Advanced Accelerator Physics course to be held in Warsaw, Poland from 27 September to 9 October 2015.   The course will be of interest to physicists and engineers who wish to extend their knowledge of accelerator physics. The programme offers core lectures on accelerator physics in the mornings and a practical course with hands-on tuition in the afternoons.  Further information can be found at: http://cas.web.cern.ch/cas/Poland2015/Warsaw-advert.html http://indico.cern.ch/event/361988/

CERN Accelerator School: Registration open for Advanced Accelerator Physics course

CERN Multimedia

2015-01-01

Registration is now open for the CERN Accelerator School’s Advanced Accelerator Physics course to be held in Warsaw, Poland from 27 September to 9 October 2015.   The course will be of interest to physicists and engineers who wish to extend their knowledge of Accelerator Physics. The programme offers core lectures on accelerator physics in the mornings and a practical course with hands-on tuition in the afternoons.  Further information can be found at: http://cas.web.cern.ch/cas/Poland2015/Warsaw-advert.html http://indico.cern.ch/event/361988/

Heavy ion accelerators

International Nuclear Information System (INIS)

Schmelzer, C.

1974-01-01

This review of the present state of work on heavy-ion accelerators pays particular attention to the requirements for nuclear research. It is divided into the following sections: single-particle versus collective acceleration, heavy-ion accelerators, beam quality, and a status report on the UNILAC facility. Among the topics considered are the recycling cyclotron, linacs with superconducting resonators, and acceleration to the GeV/nucleon range. (8 figures, 2 tables) (U.S.)

Accelerators at school

Energy Technology Data Exchange (ETDEWEB)

Anon.

1986-06-15

Latest subject covered by the CERN Accelerator School was 'Applied Geodesy of Particle Accelerators', which attracted an impressive number of outside participants to CERN for a week in April. Since the forerunners of today's particle accelerators were demonstrated over 50 years ago, the positioning of accelerator components has progressed from the laboratory bench-top to tunnels tens of kilometres long. Despite this phenomenal growth in size, sub-millimetre accuracy is still required.

Prevalência de sarcoma de Kaposi em pacientes com aids e fatores associados, São Paulo-SP, 2003-2010

Directory of Open Access Journals (Sweden)

Mariza Vono Tancredi

Full Text Available Resumo OBJETIVO: estimar a prevalência de sarcoma de Kaposi (SK em pacientes com aids e identificar os fatores associados à ocorrência da neoplasia. MÉTODOS: estudo transversal com dados de notificação em dois centros de referência em aids de São Paulo-SP, Brasil, de janeiro/2003 a março/2010; empregaram-se métodos de linkage probabilístico e regressão logística múltipla. RESULTADOS: entre 3.557 casos de aids, 213 (6% apresentavam SK, 95,3% deles do sexo masculino; associaram-se à ocorrência de SK sexo masculino (OR=3,1; IC95%=1,4;6,6, idade no momento do diagnóstico de aids >28 anos (OR=1,6; IC95%=1,0; 2,6, homens que fazem sexo com homens (OR=3,2; IC95%=2,0;4,9, uso prévio de terapia antirretroviral de alta atividade (HAART (OR=0,4; IC95%=0,3;0,5, período de diagnóstico de aids de 2007-2010 (OR=0,3; IC95%=0,2;0,4 e contagem de linfócitos T CD4+ <200cel/mm³ (OR=16,0; IC95%=6,0;42,7 e 200-500cel/mm³ (OR=2,5; IC95%=1,1;6,4. CONCLUSÃO: o SK tem alta prevalência em São Paulo-SP; estratégias para o diagnóstico precoce do HIV podem resultar em diminuição desta prevalência.

Geographical patterns of Kaposi's sarcoma, nonHodgkin lymphomas, and cervical cancer associated with HIV infection in five African populations.

Science.gov (United States)

Chaabna, Karima; Boniol, Mathieu; de Vuyst, Hugo; Vanhems, Philippe; Antônio de Ávila Vitoria, Marco; Curado, Maria-Paula

2012-01-01

The objective of this study is to describe the most recent geographical patterns of incidence of AIDS-related cancers, Kaposi's sarcoma (KS), nonHodgkin lymphoma (NHL), and cervical cancer in North African and subSaharan African populations. Data were extracted for the period 1998-2002 from five African population-based cancer registries: Kyadondo, Harare, Setif, Sousse, and Gharbiah. Age-standardized rates were calculated using the African standard population; a comparison was made between these populations by computing the standardized incidence ratio and 95% confidence intervals. The KS rate was found to be significantly higher in men than in women, and higher in Harare (women: 26.3/100,000; men: 50.4/100,000) and Kyadondo (women: 23.6/100,000; men: 30.2/100,000) than in the North African sites for both sexes (HIV/AIDS (15-49 years), and these rates were 4.5-fold higher in subSaharan populations than those in the North African sites. Thus, it was observed that the pattern of HIV prevalence is variable with the lowest prevalence in North African countries, intermediate prevalence in Uganda, and the highest prevalence in Zimbabwe. Our findings show that the incidence of NHL and cervical cancer, considered to be HIV/AIDS-related cancers, does not follow the pattern of HIV prevalence in the five studied African populations. Thus, the highest NHL incidence rate in both sexes in Gambia may be explained, at least in great part, by the highest hepatitis C virus prevalence observed there. Indeed, factors other than HIV infection likely contribute to their geographical patterns.

Role of radiotherapy in local control of non-AIDS associated Kaposi's sarcoma patients in Korea: a single institution experience

International Nuclear Information System (INIS)

Chang, Ji Hyun; Kim, Il Han

2012-01-01

There has been no definite consensus on standard treatment, either local or systemic, for the Kaposi's sarcoma (KS). Radiotherapy (RT) can be a good local therapeutic choice especially in non-AIDS associated KS (NAKS) for its indolent behavior. Medical records of 17 KS patients treated with RT at the Seoul National University Hospital from February 1998 to January 2012 were retrospectively reviewed. One human immunodeficiency virus (HIV)+ patient with 3 lesions was excluded. The total number of the lesion was 23 among the 16 patients. The median follow-up period was 27.9 months. Correlation between response and variables was analyzed using the logistic regression model. Median age of the patients was 75 years. All the 23 lesions were located at the extremities. Fourteen (61%) of those had pain or local swelling as the initial presentation. Ten patients had possible causes of immunodeficiency and were regarded as iatrogenic, and other 6 were classic KS. Median dose of RT was 36 Gy. No KS-related death was observed. Excluding 2 with short-term follow-up only, complete response and partial response were obtained in 2 (9%) and 19 (73%) lesions, respectively. Of those, 3 lesions underwent local progression. Six had out-of-field recurrence after RT. Symptom improvement was achieved in 13 (93%) of 14 patients. Grade 2 skin toxicities were found in 9 lesions but all got improvement after treatment. When divided into responsive and progressive group, free from progression was not related to any of the possible variables. RT is effective in local control of NAKS resulting great response rate.

Acceleration theorems

International Nuclear Information System (INIS)

Palmer, R.

1994-06-01

Electromagnetic fields can be separated into near and far components. Near fields are extensions of static fields. They do not radiate, and they fall off more rapidly from a source than far fields. Near fields can accelerate particles, but the ratio of acceleration to source fields at a distance R, is always less than R/λ or 1, whichever is smaller. Far fields can be represented as sums of plane parallel, transversely polarized waves that travel at the velocity of light. A single such wave in a vacuum cannot give continuous acceleration, and it is shown that no sums of such waves can give net first order acceleration. This theorem is proven in three different ways; each method showing a different aspect of the situation