Previous studies using in vitro cell culture systems have shown the role of the dynamin-related GTPase Opa1 in apoptosis prevention and mitochondrial DNA (mtDNA) maintenance. However, it remains to...Full Text Available
The purpose was to study the toxicity of drugs known to generate free radicals on isolated pancreatic islets. The accumulattion of "8"6Rb"+ by mouse pancreatic islets was measured in vitro. Exposing the islets to 6-hydroxydopamine, minhydrin, or phenazine methosulphate + NADH inhibited the Rb"+ uptake, whereas paraquat or acetylphenylhydrazine had no effect. This effect of 6-hydroxydopamine was prevented by either of the hydroxyl radical scavengers, sodium benzoate and mannitol, but not by the non-scavenger,urea; ninhydrin was partially protected against by mannitol but not by benzoate. Protection against 6-hydroxydopamine was also afforded by D-glucose but not by L-glucose or 3-O-methyl-D-glucose; none of the sugars protected against ninhydrin. In damaging islet beta-cells and in being protected against by D-glucose, 6-hydroxydopamine closely resembles the diabetogenic drug, alloxan. It is suggested that protection against ...
Pancreatic amyloid deposits of amylin are a hallmark of Type II diabetes and considerable evidence indicates that amylin oligomers are cytotoxic to beta-cells. Many efforts are presently spent to find out naturally occurring molecules, or to design synthetic ones, able to hinder amylin aggregation or to protect cells against aggregate cytotoxicity. In this context, a protective effect of some polyphenols against amyloid cytotoxicity was reported. Actually dietary polyphenols are endowed with multiple health benefits, and extra virgin olive oil is attracting increasing interest as a source of these substances. Here, we investigated the effects on amylin aggregation and cytotoxicity of the secoiridoid oleuropein aglycon, the main phenolic component of extra virgin olive oil. We found that oleuropein, when present during the aggregation of amylin, consistently prevented its cytotoxicity to RIN-5F pancreatic ...
Glucagon plays critical roles in regulating glucose homeostasis, mainly by counteracting the effects of insulin. Consequently, the dysregulated glucagon secretion that is evident in type 2 diabetes has significant implications in the pathophysiology of the disease. Glucagon secretion from pancreatic -cells has been suggested to be modulated by blood glucose, signals from the nervous system and endocrine components. In addition to these regulators, intraislet factors acting in a paracrine manner from neighbouring -cells are emerging as central modulator(s) of -cell biology. One of the most important of these paracrine factors, insulin, modulates glucagon secretion. Indeed, the -cell-specific insulin receptor knockout (IRKO) mouse manifests hypersecretion of glucagon in the postprandial stag...
Active oxygens produced by low-dose irradiation can induce the synthesis of proteins involved in the active oxygen reduction path and can activate the chemical self-defense mechanisms in vivo, which can alleviate the injuries caused by active oxygens themselves. The following findings suggests that it is not only by low-dose irradiation that can induce the responses described above but also by any physical and/or chemical stresses which can produce small amount of active oxygens in vivo. 1. X-irradiation with 0.5 Gy and/or water immersion and restraint induced heat shock protein (HSP)70 in rat stomach cells. HSP70 was also induced in adrenal cells by paraquat administration. 2. The SOD activity in pancreas of rat significantly increased by #gamma#-irradiation with 0.5 Gy. 0.5 Gy irradiation preceeding the alloxan administration significantly suppressed the increase in pancreatic lipid peroxides and in blood glucose levels, degranulation in ...
Walled-off pancreatic necrosis (WOPN), formerly known as pancreatic abscess is a late complication of acute pancreatitis. It can be lethal, even though it is rare. This critical review provides an overview...Full Text Available
Autoimmune pancreatitis (AIP) is a rare cause of recurrent acute pancreatitis or chronic pancreatitis in middle-aged patients, and is characterised by a marked infiltration of lymphocytes and plasma...Full Text Available
Standard pancreatic resections, such as pancreaticoduodenectomy, distal pancreatectomy, or total pancreatectomy, result in an important loss of normal pancreatic parenchyma and may cause impairment...Full Text Available
The most common causes of omental sac collections (OSC) are necrotic pancreatitis (90%) and pancreatic trauma (10%). Acute OSC is a form of local peritonitis in acute pancreatitis, subacute OSC are caused by internal pancreatic fistulas. The clinical and radiological signs, enzymatic activity of the exudate, morphological features of peritonitis were investigated. Treatment of acute OSC included conservative measures, of subacute OSC-surgical procedures. PMID:9163152
Eosinophils are associated with helminth immunity and allergy, often in conjunction with alternatively activated macrophages (AAMs). Adipose tissue AAMs are necessary to maintain glucose homeostasis...Full Text Available
The central nervous system (CNS), generally accepted to regulate energy homeostasis, has been implicated in the metabolic perturbations that either cause or are associated with obesity. Normally, the CNS receives hormonal, metabolic, and neuronal input to assure adequate energy levels and maintain stable energy homeostasis. Recent evidence also supports that the CNS uses these same inputs to regulate glucose homeostasis and this aspect of CNS regulation also becomes impaired in the face of dietary-induced obesity. This review focuses on the literature surrounding hypothalamic regulation of energy and glucose homeostasis and discusses how dysregulation of this system may contribute to obesity and T2DM.
We have identified the nonreceptor tyrosine kinase syk as a marker of differentiation/tumor suppressor in pancreatic ductal adenocarcinoma (PDAC). Syk expression is lost in poorly differentiated PDAC...Full Text Available
Pain caused by chronic pancreatitis is medically intractable and resistant to conventional interventional or surgical treatment. We report a case of spinal cord stimulation (SCS) for intractable pain...Full Text Available
Objectives:Cachexia is common in pancreatic cancer and may have an influence on longterm survival but few studies have investigated this in patients with operable tumours. Therefore,...Full Text Available
BackgroundGastrointestinal stromal tumours (GIST) frequently occur in patients with neurofibromatosis type 1 (NF-1). It has been reported that GIST may co-exist with pancreatic endocrine...Full Text Available
Patients with pancreatic cancer normally present with advanced disease that is lethal and notoriously difficult to treat. Survival has not improved dramatically, despite routine use of chemotherapy...Full Text Available
The virtual lack of well-characterized metastatic pancreatic cancer tissues for study has limited systematic studies of the metastatic process of this deadly disease. To address this important...Full Text Available
BackgroundASCL1 role in pancreatic endocrine tumourigenesis has not been established. Recently it was suggested that ASCL1 negatively controls expression of the...Full Text Available
Of 868 patients admitted with pancreatitis between 1971 and 1976, coexisting hyperbilirubinemia was noted in 125 (14%). The patient population was primarily composed of alcoholics (84%) with chronic...Full Text Available
We examined the association between N-acetyltransferase 1 and 2 (NAT1 and NAT2) haplotype and risk of pancreatic cancer by genotyping eight...Full Text Available
Recently, there has been significant progress in the development of genetically-engineered mouse (GEM) models. By introducing genetic alterations and/or signaling alterations of human pancreatic cancer...Full Text Available
AIM: To distinguish anastomotic from parenchymal leakage at duct-to-mucosa reconstruction of the pancreatic remnant.METHODS: We reviewed the charts of 68 pancreaticod-uodenectomies performed...Full Text Available
Pancreatic cysts are challenging lesions to diagnose and to treat. Determining which of the five most common diagnoses—pancreatic pseudocyst, serous cystic neoplasm (SCN), solid pseudopapillary...Full Text Available
BackgroundThe elevated serum and peritoneal cytokine concentrations responsible for the systemic response syndrome (SIRS) and multiorgan failure in patients with severe acute pancreatitis...Full Text Available
The purpose of this study was to determine the clinical significance of nodal micrometastasis detected by immunohistochemistry in patients that had undergone curative surgery for pancreatic cancer....Full Text Available
Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancy with dismal prognosis and few effective therapeutic options. Novel agents that are safe and effective are urgently...Full Text Available
A hitherto unrecognized variant of solid-pseudopapillary tumor (SPT) of the pancreas is reported. The tumor presented in the pancreatic tail of a 44-year-old female patient. It was a well-defined, solid...Full Text Available
Autoimmune pancreatitis is frequently associated with elevated serum and tissue IgG4 levels in the adult population, but there are few reports of pediatric autoimmune pancreatitis, and even fewer reports...Full Text Available
In spite of the improved imaging techniques currently available, mortality for pancreatic cancer is still high, and pancreatics is often diagnosed only in its advanced stages. The authors investigated the value of different imaging techniques - i.e., US, CT, and ERCP - for an early diagnosis, when a more effective (curative?) treatment can be suggested. Fifty-six cases of pancreatic cancer and 36 cases of chronic pancreatitis were evaluated. The results indicate that ERCP, with the help of statistical methods, is superior to US and CT not only in evaluating early neoplastic or inflammatory lesions, but also for their differential diagnosis. In the letter case, ERCP can sometimes be used as a valid alternative to fine-needle aspiration biopsy.
Vitamin D is now known to be of physiological importance outside of bone health and calcium homeostasis, and there is mounting evidence that it plays a beneficial role in the prevention and/or treatment...Full Text Available
The biophysical properties of membrane phospholipids are controlled by the composition of their constituent fatty acids and are tightly regulated in Escherichia...Full Text Available
SummaryMammalian iron homeostasis is regulated by the interaction of the liver-produced peptide hepcidin and its receptor, the iron transporter ferroportin. Hepcidin binds to...Full Text Available
Temperature is an important modulator of longevity and aging in both poikilotherms and homeotherm animals. In homeotherms, temperature homeostasis is regulated primarily in the preoptic area...Full Text Available
According to classical concepts of physiologic control, healthy systems are self-regulated to reduce variability and maintain physiologic constancy. Contrary to the predictions of homeostasis, however,...Full Text Available
Physiological bone remodeling is a highly coordinated process responsible for bone resorption and formation and is necessary to repair damaged bone and to maintain mineral homeostasis. In addition to...Full Text Available
The role of apoptosis or programmed cell death in the regulation of development and maintenance of homeostasis in multicellular organisms is well established. During the last decade, naturally...Full Text Available
Background:Solid pseudopapillary tumor is a rare pancreatic neoplasm with uncertain to low malignant potential. This is an uncommon neoplasm with many pseudonyms, occurring...Full Text Available
Background This study aimed to evaluate the feasibility, safety, and follow-up results of endoscopic papilletomy (ESP) with pancreatic and biliary duct stent placement for ampullary tumors. The therapeutic approach to benign ampullary tumors remains unsettled. The ESP procedure is a curative treatment option for benign papillary tumors, but ESP raises concerns about a relatively high risk for procedure-related complications such as pancreatitis. A pancreatic stent may protect against complications. Methods Between September 2000 and June 2008, 36 patients with ampullary tumors confined to the mucosa and no intraductal tumor growth underwent ESP. The preprocedural diagnostic tools included endoscopic ultrasound, transpapillary intraductal ultrasound, and endoscopic retrograde cholangiopancr...
The typical MRI features of the most common pancreatic diseases, such as pancreatitis and adenocarcinoma of the pancreas, have been established. However, even in these common pancreatic disorders, MRI correlation with the underlying pathology is limited for clinical reasons. We emphasize MR-pathological correlation of inflammatory and neoplastic pancreatic changes, including pancreatitis, adenocarcinoma, acinar cell carcinoma, rare cystic and solid pancreatic neoplasms, and islet cell tumors. By highlighting the correlation of key pathological features with MR findings, a better understanding of the MR appearance of pancreatic pathology can be provided. In addition, MRI may prove a powerful tool in detection and characterization of pancreatic tumors. (orig.) [Deutsch] Das MR-tomographische Erscheinungsbild von ...
Pancreatitis-associated protein (PAP) is a secretory pancreatic protein present in small amounts in normal pancreas and overexpressed during the acute phase of pancreatitis. In this paper, the authors describe the cloning, characterization, and chromosomal mapping of the human PAP gene. The gene spans 2748 bp and contains six exons interrupted by five introns. The gene has a typical promoter containing the sequences TATAAA and CCAAT 28 and 52 bp upstream of the cap site, respectively. They found striking similarities in genomic organization as well as in the promoter sequences between the human and rat PAP genes. The human PAP gene was mapped to chromosome 2p12 using rodent-human hybrid cells and in situ chromosomal hybridization. This localization coincides with that of the reg/lithostathine gene, which encodes a pancreatic secretory protein structurally related to PAP, suggesting that both genes ...
The current investigation attempted to confirm the beneficial actions of a chemically characterized Radix Astragali decoction (AM-W) against type 2 diabetic (T2D) Sprague-Dawley (SD) rats. Using a case/control...Full Text Available
The state of prooxidant-antioxidant homeostasis in Guinea pigs exposed to whole-body fractionated X-irradiation (5 fractions of 0.2 Gy at a 24 hr interval, up to total dose of 1.0 Gy, at a dose rate of 0.425 R/min) and a possibility of its disturbance correction with the complex of vitamins C, E and P was studied. Accumulation of primary and secondary lipid peroxidation products, decrease of the ascorbic acid content, increase of the content of its oxidized forms (dehydroascorbic acid and diketogulonic acid) in radiosensitive and radioresistant organs were found. Antioxidant complex administration reduced the disturbances of prooxidant-antioxidant homeostasis, but did not provide complete normalization.
Nonfunctioning pancreatic endocrine tumors (PETs) are rare and generally asymptomatic. A 68-year-old woman who had refused treatment for a pancreatic mass, revealed by ultrasonography to be 55 mm in diameter, was referred to us again 29 months later with jaundice. Investigations showed an 82-mm tumor in the head of pancreas, exposed from the papilla of Vater to the duodenal lumen. After biliary decompression and drainage, we performed pancreatoduodenectomy with resection of the portal vein and superior mesenteric vein, followed by reconstruction using a cylindrically customized autologous graft harvested from the right ovarian vein. The tumor was resected curatively. Microscopically, it consisted of trabecular and ribbon-like arrangement of neoplastic cells. Immunohistochemical staining wa...
Wiskott-Aldrich syndrome protein (WASp) is essential for optimal T cell activation. Patients with WAS exhibit both immunodeficiency and a marked susceptibility to systemic autoimmunity. We investigated...Full Text Available
Iron overload is common in patients undergoing allogeneic hematopoietic cell transplantation (HCT), but the mechanisms leading to overload are unknown. Here, we determined iron levels and the expression...Full Text Available
Studies in rodents have shown that male sexual function can be disrupted by fetal or neonatal administration of compounds that alter endocrine homeostasis, such as the synthetic nonsteroidal estrogen...Full Text Available
Altered structure, and hence function, of cellular macromolecules caused by oxidation can contribute to loss of physiological function with age. Here, we tested whether the lifespan of bats, which generally...Full Text Available
BackgroundThe presence of regulatory T (Treg) cells in human endometrium is crucial for maintaining immunological homeostasis within the uterus. For this study we decided to evaluate...Full Text Available
BackgroundNFκB signaling is of paramount importance in the regulation of apoptosis, proliferation, and inflammatory responses during human development and homeostasis, as...Full Text Available
RasGRF1 is a Ras-guanine nucleotide exchange factor implicated in a variety of physiological processes including learning and memory and glucose homeostasis. To determine the role of RASGRF1 in aging,...Full Text Available
Several different neuronal populations are involved in regulating energy homeostasis. Among these, agouti-related protein (AgRP) neurons are thought to promote feeding and weight gain; however, the...Full Text Available
Genes of the S100 fused-type protein (SFTP) family are clustered within the epidermal differentiation complex and encode essential components that maintain epithelial homeostasis and barrier functions....Full Text Available
BackgroundCalcium signaling plays an important role in B lymphocyte survival and activation, and is critically dependent on the inositol-1,4,5-tris-phosphate-induced...Full Text Available
BackgroundNeuropeptide Y is a key neurotransmitter of the central nervous system which plays a vital role in the feed energy homeostasis in mammals. Mutations in the regulatory and...Full Text Available
Endogenous circadian clocks are robust regulators of physiology and behavior. Synchronization or entrainment of biological clocks to environmental time is adaptive and important for physiological homeostasis...Full Text Available
Background:The cardiac sodium–calcium exchanger (NCX1) is a key sarcolemmal protein for the maintenance of calcium homeostasis in the heart. Since heart failure...Full Text Available
In order to maintain stable functionality in the face of continually changing input, neurones in the CNS must dynamically modulate their electrical characteristics. It has been hypothesized that in...Full Text Available
BackgroundCalcium homeostasis is a known target of several environmental toxicants including lead and mercury.ObjectiveOur goal was to determine...Full Text Available
The objective of this experiment was to determine the effect of dietary grain on calcium homeostasis. Six rumen-fistulated dairy cows with 3 or more previous lactations and no history of parturient...Full Text Available
The liver plays a vital role in glucose homeostasis, the synthesis of bile acids and the detoxification of foreign substances. Liver culture systems are widely used to test adverse effects of drugs...Full Text Available
Polypeptides exiting the ribosome must fold and assemble in the crowded environment of the cell. Chaperones and other protein homeostasis factors interact with newly translated polypeptides to facilitate...Full Text Available
ATP-binding cassette A3 (ABCA3) is a lipid transport protein required for synthesis and storage of pulmonary surfactant in type II cells in the alveoli. Abca3 was conditionally deleted...Full Text Available
BackgroundIn mammals, vasopressin (AVP) is released from magnocellular neurons of the hypothalamus when osmotic pressure exceeds a fixed set-point. AVP participates to the hydromineral...Full Text Available
Cellular cholesterol homeostasis is controlled by sterol-regulated proteolysis of membrane-bound transcription factors called sterol-regulatory element binding proteins (SREBPs). CPP32, a cysteine protease,...Full Text Available
Calcium ions represent universal second messengers within neuronal cells integrating multiple cellular functions, such as release of neurotransmitters, gene expression, proliferation, excitability,...Full Text Available
AimsThe experiments explored for atrial arrhythmogenesis and its possible physiological background in recently developed hetero-(RyR2+/S) and homozygotic...Full Text Available
SUMMARYATG12, an ubiquitin-like modifier required for macroautophagy, has a single known conjugation target, another autophagy regulator called ATG5. Here, we identify ATG3 as...Full Text Available
... be able to watch the many intricate steps Dr. Richard Alexander must accomplish to remove the cancer. ... door to informed medical care. Now let's join Dr. Richard Alexander at the University of Maryland Medical ...
1. Proteolytic enzyme activities were examined in the pancreas of zinc-deficient and control rats. 2. No change was detected in trypsin-plus-chymotrypsin activity. 3. Carboxypeptidase activity was...Full Text Available
BACKGROUNDSolid-pseudopapillary neoplasms (SPNs) are rare pancreatic tumors with malignant potential. Clinicopathologic characteristics and outcomes of patients with...Full Text Available
We report here a case of a pathologically proven solitary fibrous tumor of the pancreas. A 54-year-old man was referred to our hospital for further evaluation of a pancreatic mass that was found incidentally....Full Text Available
AIM: To investigate differential points of solid-pseudopapillary neoplasm (SPN) of the pancreas and pancreatic endocrine tumor (PET).METHODS: Ten cases of SPN and fourteen cases of PET were studied...Full Text Available
Menin, which is encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, is a tumor suppressor and transcriptional regulator. Menin controls proliferation and apoptosis of cells, especially pancreatic...Full Text Available
This case report describes the second known instance of a multifocal capillary pancreatic neoplasm. Both cases occurred in young African American females. A less-than-total pancreatectomy was performed...Full Text Available
Middle segment pancreatectomy (MSP) is a new operation where the advantages of parenchymal preservation are counterbalanced by a high postoperative complication rate and unease among surgeons with adopting...Full Text Available
Type 2 diabetes mellitus (T2DM) results from insulin resistance and β-cell dysfunction, in the setting of hyperglucagonemia. Glucagon is a 29 amino acid peptide hormone, which is secreted from...Full Text Available
Pancreatic islet transplantation into the liver provides a possibility to treat selected patients with brittle type 1 diabetes mellitus. However, massive early β-cell death increases the number...Full Text Available
Endoscopic Retrograde Cholangiopancreatography (ERCP) is a widely used diagnostic and therapeutic modality in the management of biliary and pancreatic disease. Some of the complications of the procedure,...Full Text Available
In spite of their rarity, cystic neoplasms of the pancreas are characterized by existing or potential malignancy that cannot be ignored during decisive process with regard to the choice of treatment....Full Text Available
ObjectiveThe goal of the study was to investigate the genetic and molecular basis of a novel syndrome of marked hyperglucagonemia and pancreatic α cell hyperplasia...Full Text Available
Nerve growth factor (NGF), a survival factor for neurons enforces pain by sensitizing nociceptors. Also in the pancreas, NGF was associated with pain and it can stimulate the proliferation of pancreatic cancer cells. Hepatic stellate cells (HSC) respond to NGF with apoptosis. Transforming growth factor (TGF)-b, one of the strongest pro-fibrogenic activators of pancreatic stellate cells (PSC) induced NGF and its two receptors in an immortalized human cell line (ihPSC) and primary rat PSC (prPSC) as determined by RT-PCR, western blot, and immunofluorescence. In contrast to HSC, PSC expressed both NGF receptors, although p75NTR expression was weak in prPSC. In contrast to ihPSC TGF-b activated both Smad signaling cascades in prPSC. NGF secretion was diminished by the activin-like kinase (ALK)...
The solid-pseudopapillary tumor (SPT) of the pancreas is a rare type of exocrine pancreatic neoplasm. SPT predominantly affects young women and female children, and is usually discovered incidentally. This tumor is generally benign with a low incidence of malignancy. A 13-year-old girl was admitted to the hospital with a few weeks' history of mild abdominal pain and jaundice. On physical examination, there was no palpable mass. The laboratory tests showed increased SR, CRP, high bilirubin, amylase and lipase serum levels. Ultrasound imaging revealed a solid lesion in the region of the pancreatic head. On MRI, precise tumor localization in the head of the pancreas with pancreatic duct dilatation and compression of the common bile duct were visualized. Pancreaticoduodenectomy and cholecystectomy was performed with good clinical outcome. Microscopic and immunohistochemical studies indicated that tumor cells were typical of SPT ...
The mortality in undrained abdominal abscesses is high with a mortality rate ranging between 45 and 100%. The outcome in abdominal abscesses, however, has improved due to advances in image guided percutaneous interventional techniques. The main indications for the catheter drainage include treatment or palliation of sepsis associated with an infected fluid collection, and alleviation of the symptoms that may be caused by fluid collections by virtue of their size, like pancreatic pseudocele or lymphocele. The single liver abscesses may be drained with ultrasound guidance only, whereas the multiple abscesses usually require computed tomography (CT) guidance and placement of multiple catheters. The pancreatic abscesses are generally drained routinely and urgently. Non-infected pancreatic pseudocysts may be simply observed unless they are symptomatic or cause problems such as pain or obstruction of the biliary or the ...
The Wnt signaling pathway is a robust regulator of skeletal homeostasis. Gain-of-function mutations promote high bone mass, whereas loss of Lrp5 or Lrp6 co-receptors decrease bone mass. Similarly, mutations...Full Text Available
Peroxisome proliferator activated receptor-{gamma} (PPAR{gamma}) regulates metabolic homeostasis and adipocyte differentiation, and it is activated by oxidized and nitrated fatty acids. Here we report the crystal structure of the PPAR{gamma} ligand binding domain bound to nitrated linoleic acid, a potent endogenous ligand of PPAR{gamma}. Structural and functional studies of receptor-ligand interactions reveal the molecular basis of PPAR{gamma} discrimination of various naturally occurring fatty acid derivatives.
It has been postulated that fetal vascular abnormalities in aryl hydrocarbon receptor null (ahr−/−) mice may alter cardiovascular homeostasis in adulthood....Full Text Available
In both type 1 and type 2 diabetes, pancreatic islet dysfunction results in part from cytokine-mediated inflammation. The ubiquitous eukaryotic translation initiation factor 5A (eIF5A), which is the...Full Text Available
The nucleotide sequence of the 5'-terminal oligonucleotides produced by pancreatic RNase digestion of bacteriophage T3 RNA polymerase (EC 2.7.7.6) transcripts of T3 DNA has been determined. The sequence...Full Text Available
Background/AimsAlthough endoscopic ultrasound guided fine needle aspiration (EUS-FNA) has been introduced and its use has been increasing in Korea, there have not been many reports...Full Text Available
Extracellular ATP has been proposed as a paracrine signal in rodent islets, but it is unclear what role ATP plays in human islets. We now show the presence of an ATP signaling pathway that enhances...Full Text Available
Macroautophagy is a multistep, vacuolar, degradation pathway terminating in the lysosomal compartment, and it is of fundamental importance in tissue homeostasis. In this review, we consider macroautophagy in the light of recent advances in our understanding of the formation of autophagosomes, which are double-membrane-bound vacuoles that sequester cytoplasmic cargos and deliver them to lysosomes. In most cases, this final step is preceded by a maturation step during which autophagosomes interact with the endocytic pathway. The discovery of AuTophaGy-related genes has greatly increased our knowledge about the mechanism responsible for autophagosome formation, and there has also been progress in the understanding of molecular aspects of autophagosome maturation. Finally, the regulation of au...
Central nervous system (CNS) development, homeostasis, stress responses, and plasticity are all mediated by epigenetic mechanisms that modulate gene expression and promote selective deployment of functional gene networks in response to complex profiles of interoceptive and environmental signals. Thus, not surprisingly, disruptions of these epigenetic processes are implicated in the pathogenesis of a spectrum of neurological and psychiatric diseases. Epigenetic mechanisms involve chromatin remodeling by relatively generic complexes that catalyze DNA methylation and various types of histone modifications. There is increasing evidence that these complexes are directed to their sites of action by long non-protein-coding RNAs (lncRNAs), of which there are tens if not hundreds of thousands speci...
The Zollinger-Ellison syndrome (ZES) is taken as an example of the diagnostic and therapeutic strategy in gastro-entero-pancreatic endocrine tumours, given the standard characteristics of this procedure, whatever the nature of the primitive tumour. Management of ZES includes: anatomical localization of gastrinoma and of possible metastases, in 60 % of cases this step conditioning therapeutic indications and chances of cure; search of a type 1-multiple endocrine neoplasia (MEN A), in 25 % of cases; therapeutic indications: ablative surgery with curative intent in case of gastrinoma and of resectable liver metastases, palliative treatment otherwise: anti-secretory drugs, somatostatin analogues, chemotherapy and interferon {alpha}; long-term follow-up of patients with resected tumour. At each step, somatostatin receptor scintigraphy with indium 111-pentetreotide does play a pivotal role. (author). 110 refs.
Purpose of this item is to report the CT patterns of pancreatic mesenchymal lesions and to investigate the capabilities and limitations of this technique in terms of characterization. In selected cases, CT can provide virtually diagnostic information (lipoma and teratoma), or at least highly suggestive findings (NHL, plexiform neurofibroma, lymphangioma). Moreover, knowledge of the variable morphostructural patterns of mesenchymal hisototypes (SCH, Sarcoma etc.) permits to include them in the differential diagnosis of pancreatic masses. [Italian] Scopo di questo rapporto e' descrivere gli aspetti semeiologici dei tumori mesenchimali del pancreas con la TC verificandone le possibilita e i limiti per la caratterizzazione. Pur nella rarita' dei reperti considerati, la TC puo' consentire l'effettiva caratterizzazione in alcuni casi (lipoma, neurofibroma plessiforme, linfangioma) o includere anche istotipi meno ...
We have studied the impact of overexpression of an intracellular signaling protein, integrin-linked kinase (ILK), on the survival and function of encapsulated islet tissue used for the treatment of type 1 diabetes. The dimensions of the encapsulated tissue can impact the stresses placed on the tissue and ILK overexpression shows the ability to extend function of dissociated cells as well as intact islets. These results suggest that lost cell-extracellular matrix interactions in cell encapsulation systems can lead to decreased insulin secretion and ILK signaling is a target to overcome this phenomenon. (communication)
The authors made peritoneal dialisis with 5% of glucose (7 ml/kg of body weight) in 11 dogs under the conditions of an acute experiments. They examined cortiosl and ADH activity, hematocrite and plasma protein in the samples of blood, obtained on the 20th and 50th minute. ADH was titrated biologicaly by a new method, proposed by Nacev. The results were compared with the changes in the circulatory and renal indices, obtained at the same procedure in the preceding investigations. There was an increase in the cortisol and ADH activity, which could be explained by the total hypovolemia, induced by peritoneal dialisis. The increase of the cortisol level is described as a separate link in a more complex mechanism, assuring metabolic homeostasis. PMID:1222705
In patients subjected to bone marrow transplantation the aggressive measures necessarily preceding this treatment lead to drastic metabolic changes which, in turn, are a cause of marked disturbances of homeostasis. The general preparatory measures in the form of cytoreduction by cytostatic drugs are broadened for leukaemic patients to include wholebody irradiation. During the study described here investigations were carried out into the resulting strain on the metabolism. One of the most essential changes observed in those patients was a nitrogen loss of up to approx. 20 g/day that occurred during the immunosuppressive phase. This was accompanied by markedly pronounced variations in fluid elimination, which partly were of an iatrogenic nature. An immediate and sufficient substitution of amino acids in connection with complete parenteral nutrition rapidly acted to compensate for the nitrogen losses, even though these could not be totally reversed to achieve a ...
Aims: Rapamycin (sirolimus) is an antibiotic that inhibits protein synthesis through mammalian targeting of rapamycin (mTOR) signaling, and is used as an immunosuppressant in the treatment of organ rejection in transplant recipients. Rapamycin confers preconditioning-like protection against ischemic-reperfusion injury in isolated mouse heart cultures. Our aim was to further define the role of rapamycin in intracellular Ca^2^+ homeostasis and to investigate the mechanism by which rapamycin protects cardiomyocytes from hypoxic damage. Main methods: We demonstrate here that rapamycin protects rat heart cultures from hypoxic-reoxygenation (H/R) damage, as revealed by assays of lactate dehydrogenase (LDH) and creatine kinase (CK) leakage to the medium, by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-d...
Concerns for potential vulnerability to manganese (Mn) neurotoxicity during fetal and neonatal development have been raised due to increased needs for Mn for normal growth, different sources of exposure to Mn, and pharmacokinetic differences between the young and adults. A physiologically based pharmacokinetic (PBPK) model for Mn during human gestation and lactation was developed to predict Mn in fetal and neonatal brain using a parallelogram approach based upon extrapolation across life stages in rats and cross-species extrapolation to humans. Based on the rodent modeling, key physiological processes controlling Mn kinetics during gestation and lactation were incorporated, including alterations in Mn uptake, excretion, tissue-specific distributions, and placental and lactational transfer ...
Many existing agents for diabetes therapy are unable to restore or maintain normal glucose homeostasis or prevent the eventual emergence of hyperglycemia-related complication. Therefore, agents based on novel mechanisms are sought to complement and extend the current therapeutic approaches. Based on the initial paper research, we focused on active STAT3 as an attractive pharmacological target for type 2 diabetes. The subsequent text mining with a unique query to identify suppressors but not activators of STAT3 revealed the ERK2/STAT3 pathway as a novel diabetes target. The description of ERK2 inhibitors as diabetes target had not been found in our text mining research at present. The mechanism-based peptide inhibitor for ERK2 was identified using the knowledge of the KIM sequence, which ha...
Dysregulation of intracellular Ca2+ homeostasis is associated with various pathological conditions and arrhythmogenesis of the heart. The objective of this study was to investigate the effects of an acute increase in intracellular Ca2+ concentration ([Ca2+]i) on the electrophysiology of ventricular myocytes by mimicking intracellular Ca2+ overload. The [Ca2+]i was clamped to either a controlled (65?100 nmol L?1) or increased (1 ?mol L?1) level. The transmembrane action potentials and ionic currents were recorded using whole-cell patch clamp techniques. We found that the acute increase in [Ca2+]i shortened the action potential duration, reduced the action potential amplitude, maximum depolarization velocity and resting membrane potential, caused delayed after-depolarizations (DADs), and tri...
Adipose tissue plays an essential role in energy homeostasis as a metabolic and endocrine organ. Accordingly, adipocytes are emerging as a major drug target for obesity and obesity-mediated metabolic syndrome. Dysfunction of enlarged adipocytes in obesity is involved in obesity-mediated metabolic syndrome. Adipocytokines, such as adiponectin released from small adipocytes, are able to prevent these disorders. In this study, we found that honokiol, an ingredient of Magnolia officinalis used in traditional Chinese and Japanese medicines, enhanced adipocyte differentiation in 3T3-L1 preadipocytes. Oil Red O staining showed that treatment with honokiol in the presence of insulin dose-dependently increased lipid accumulation in 3T3-L1 preadipoyctes although its activity was weak compared with r...
Glucose homeostasis requires the tight regulation of glucose utilization by liver, muscle and white or brown fat, and glucose production and release in the blood by liver. The major goal of maintaining glycemia at -5 mM is to ensure a sufficient flux of glucose to the brain, which depends mostly on this nutrient as a source of metabolic energy. This homeostatic process is controlled by hormones, mainly glucagon and insulin, and by autonomic nervous activities that control the metabolic state of liver, muscle and fat tissue but also the secretory activity of the endocrine pancreas. Activation or inhibition of the sympathetic or parasympathetic branches of the autonomic nervous systems are controlled by glucose-excited or glucose-inhibited neurons located at different anatomical sites, mainl...
Apelin is a peptide known as the ligand of the G-protein-coupled receptor APJ. Several active apelin forms exist such as apelin-36, apelin-17, apelin-13, and the pyroglutamated form of apelin-13. Apelin and APJ are expressed in the central nervous system, particularly in the hypothalamus and in many peripheral tissues. Apelin has been shown to be involved in the regulation of cardiovascular and fluid homeostasis, food intake, cell proliferation, and angiogenesis. In addition to be an ubiquitous peptide, apelin is also produced and secreted by adipocytes and thus considered as an adipokine. This has opened a new field of investigation establishing a link between apelin and metabolic disorders (obesity, type 2 diabetes, etc.) which is the focus of the present review. Several studies, but not...
Porcine pancreatic lipase immobilized on celite particles has been employed as a catalyst for the esterification of dodecanol and decanoic acid in a predominantly organic system. Solvent influence on the equilibrium position and on the catalyst activity has been studied using 20 solvents, including aliphatic and aromatic hydrocarbons, ethers, ketones, nitro- and halogenated hydrocarbons, and esters. The equilibrium constant for esterification correlates well with the solubility of water in the organic solvent, which in turn shows a good relationship with a function of Guttman's donor number and the electron pair acceptance index number of the solvent. This may be rationalized in terms of the requirements for solvation of water and of the reactants. The catalyst activity, measured as the initial rate of the esterification reaction, is best correlated as a function of both n-octanol-water partition coefficient (log P) and either the electron pair acceptance index or ...
The authors have cloned a full-length putative rat pancreatic lysophospholipase cDNA by an improved mRNA isolation method and cDNA cloning strategy using (/sup 32/P)-labelled nucleotides. These new methods allow the construction of a cDNA library from the adult rat pancreas in which the majority of recombinant clones contained complete sequences for the corresponding mRNAs. A previously recognized but unidentified long and relatively rare cDNA clone containing the entire sequence from the cap site at the 5' end to the poly(A) tail at the 3' end of the mRNA was isolated by single-step screening of the library. The size, amino acid composition, and the activity of the protein expressed in heterologous cells strongly suggest this mRNA codes for lysophospholipase.
PURPOSE: To determine the recommended dose of radiotherapy when combined with full-dose gemcitabine and erlotinib for unresected pancreas cancer. METHODS AND MATERIALS: Patients with unresected pancreatic cancer (Zubrod performance status 0-2) were eligible for the present study. Gemcitabine was given weekly for 7 weeks (1,000 mg/m(2)) with erlotinib daily for 8 weeks (100 mg). A final toxicity assessment was performed in Week 9. Radiotherapy (starting at 30 Gy in 2-Gy fractions, 5 d/wk) was given to the gross tumor plus a 1-cm margin starting with the first dose of gemcitabine. A standard 3 plus 3 dose escalation (an additional 4 Gy within 2 days for each dose level) was used, except for the starting dose level, which was scheduled to contain 6 patients. In general, Grade 3 or greater gastrointestinal toxicity was considered a dose-limiting toxicity, except for Grade 3 anorexia or Grade 3 fatigue alone. RESULTS: A total of 20 patients were treated (10 men and 10 ...
Insulitis is considered the histopathological hallmark of type I diabetes. In the non-obese diabetic (NOD) mouse, diabetes has never been observed in the absence of insulitis. The in vivo detection of insulitis could be of relevance for early prediction of diabetes. As approximately 15% of islet-infiltrating lymphocytes express interleukin 2 receptors, the authors have labelled recombinant inter-leukin 2 with "1"2"3I and used this radiopharmaceutical to detect insulitis by gamma camera imaging. The authors studied 71 prediabetic NOD and 27 normal Balb/c mice. Labelled #alpha#-lactalbumin was used as the control protein. In the first set of experiments the tissue distribution of radiolabelled interleukin 2 in isolated organs from animals sacrificed at different time points was studied. Higher radioactivity was detected in the pancreas of NOD mice injected with labelled interleukin 2, as compared to NOD mice receiving labelled #alpha#-lactalbumin. In another set of experiments, gamma ...
BackgroundDespite an ever-improving understanding of the molecular biology of cancer, the treatment of most cancers has not changed dramatically in the past three decades and drugs that do not discriminate between tumor cells and normal tissues remain the mainstays of anticancer therapy. Since Hsp90 is typically involved in cell proliferation and survival, this is thought to play a key role in cancer, and Hsp90 has attracted considerable interest in recent years as a potential therapeutic target.MethodsWe focused on the interaction of Hsp90 with its cofactor protein p60/Hop, and engineered a cell-permeable peptidomimetic, termed "hybrid Antp-TPR peptide", modeled on the binding interface between the molecular chaperone Hsp90 and the TPR2A domain of Hop.ResultsIt was demonstrated that this designed hybrid Antp-TPR peptide inhibited the interaction of Hsp90 with the TPR2A domain, inducing cell death of breast, pancreatic, renal, lung, prostate, and gastric cancer ...
The aim of this study was to compare multidetector-row computed tomography (MDCT) findings between cases of sclerosing cholangitis with autoimmune pancreatitis (SC-AIP) and infiltrative extrahepatic cholangiocarcinoma (IEC). We retrospectively assessed MDCT findings from 16 IEC cases and 13 SC-AIP cases. MDCT findings were analyzed with regard to location, length, wall thickness, contour, stricture wall enhancement pattern, proximal duct diameter, and the presence of diffuse concentric thickening in the proximal duct and gallbladder wall thickness. Stricture length, stricture wall thickness, and proximal duct diameter were significantly smaller for SC-AIP than for IEC: 19.3#+-#8.7 vs. 31.8#+-#12.0 mm (P=0.004), 2.1#+-#1.3 vs. 4.1#+-#1.3 mm (P<0.001), and 9.2#+-#3.9 vs. 13.3#+-#5.0 mm (P=0.012), respectively. SC-AIP was correlated with stricture location in both the intrapancreatic and hilar hepatic bile ducts, concentric stricture contour (P<0.001), and ...
Vildagliptin is a potent and selective dipeptidyl peptidase IV inhibitor in development for the treatment of type 2 diabetes that improves glycemic control by enhancing alpha- and beta-cell responsiveness to glucose. Two open-label, single-dose, randomized, crossover studies in healthy subjects (ages 18-45 years) investigated the dose proportionality of vildagliptin pharmacokinetics (n = 20) and the effect of food (n = 24) on vildagliptin pharmacokinetics. There was a linear relationship (r(2) = 0.999) between vildagliptin doses of 25, 50, 100, and 200 mg and area under the plasma concentration-time curve from time zero to infinity (AUC(0-infinity)) and maximum plasma concentration (C(max)). Dose proportionality was assessed using a statistical power model [X = alpha x (dose)(beta)]. The 90% confidence intervals of the proportionality coefficient, beta, for AUC(0-infinity) (1.15-1.19) and C(max) (1.04-1.14) indicated that deviations from dose proportionality were ...
Autoreactive cytotoxic CD8 T-cells (CTLs) play a key pathogenic role in the destruction of insulin-producing beta-cells resulting in type 1 diabetes. However, knowledge regarding their targets is limited, restricting the ability to monitor the course of the disease and immune interventions. In a multi-step discovery process to identify novel CTL epitopes in human preproinsulin (PPI), PPI was digested with purified human proteasomes, and resulting COOH-fragments aligned with algorithm-predicted HLA-binding peptides to yield nine potential HLA-A1, -A2, -A3 or -B7-restricted candidates. An UV-exchange method allowed the generation of a repertoire of multimers including low-affinity HLA-binding peptides. These were labeled with quantum dot-fluorochromes and encoded in a combinatorial fashion, allowing parallel and sensitive detection of specific, low-avidity T-cells. Significantly increased frequencies of T-cells against four novel PPI epitopes (PPI(4-13)/B7, ...
Abstract in english Cytokines are molecules that were initially discovered in the immune system as mediators of communication between various types of immune cells. However, it soon became evident that cytokines exert profound effects on key functions of the central nervous system, such as food intake, fever, neuroendocrine regulation, long-term potentiation, and behavior. In the 80's and 90's our group and others discovered that the genes encoding various cytokines and their receptors are e (more) xpressed in vascular, glial, and neuronal structures of the adult brain. Most cytokines act through cell surface receptors that have one transmembrane domain and which transduce a signal through the JAK/STAT pathway. Of particular physiological and pathophysiological relevance is the fact that cytokines are potent regulators of hypothalamic neuropeptidergic systems that maintain neuroendocrine homeostasis and which regulate the body's response to stress. The mechanisms ...
Stroke-prone spontaneously hypertensive rats (SHRSP) induce spontaneous osteoporosis. To elucidate the specific characteristics of bone metabolism, the SHRSP was compared with age matched Wistar-Kyoto (WKY) rats. We investigated the effects of prolonged swimming exercise training on bone mineral density (BMD) and metabolism in the SHRSP. Seven-week-old male SHRSP and WKY were divided into three groups; the sedentary control WKY group (n = 6, WKY), the sedentary control SHRSP group (n = 6, SP) and the swimming exercise training SHRSP group (n = 6, SWIM) (in pool with 60 min./day, 5 days/week for 12 weeks). The femoral BMD, bone mineral content (BMC), strength, Ca and P contents (%) of SHRSP were approximately 17, 27, 25, 20 and 9%, respectively, lower than that of WKY (p swimming exercise training in the SHRSP induces more cruelly hypophosphatemia, and leading to osteopenia eventually. We conclude that SHRSP induces osteopenia with disturbance of phosphate ...
A hallmark of congestive heart failure (CHF) is the activation of the cardiac endocrine system, in particular atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). The natriuretic peptides are a group of structurally similar but genetically distinct peptides that have diverse actions in cardiovascular, renal, and endocrine homeostasis. ANP and BNP are of myocardial cell origin and C-type natriuretic peptide (CNP) is of endothelial origin. ANP and BNP bind to the natriuretic peptide-A receptor (NPR-A), which, via 3',5'-cyclic guanosine monophosphate (cGMP), mediates natriuresis, vasodilatation, renin inhibition, antimitogenesis, and lusitropic properties. CNP lacks natriuretic actions but possesses vasodilating and growth inhibiting actions via the guanylyl cyclase-linked natriuretic peptide-B receptor. All three peptides are cleared by the natriuretic peptide-C receptor and degraded by the ectoenzyme neutral endopeptidase 24.11, both of which are ...
Abstract in english Cell death is preceded by severe disruption of inorganic ion homeostasis. Seconds to minutes after an injury, calcium, protons, sodium, potassium and chloride are exchanged between the cell and its environment. Simultaneously, ions are shifted between membrane compartments inside the cell, whereby mitochondria and endoplasmic reticulum play a crucial role. Depending of the type and severity of injury, two mutually exclusive metastable states can be reached, which predict (more) the final outcome. Cells characterized by large increases in cytosolic [Ca2+], [Na+]; and [Mg2+] swell and die by necrosis; alternatively, cells characterized by high [H+]and low [K+], with normal [Na+] and normal to moderate [Ca2+] increases die by apoptosis. The levels of these ions represent central determinants in signaling events leading to cell death. Their movements are explained mechanistically by specific modulation of membrane transport proteins including ...
The effects of atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) on guanylate cyclase activity and cyclic GMP accumulation were examined, since these hormones appear to be intimately associated with blood pressure and intravascular volume homeostasis. ANP was found to increase cyclic GMP accumulation in ten cell culture systems, which were derived from blood vessels, adrenal cortex, kidney, lung, testes and mammary gland. ANP receptors were characterized in intact cultured cells using {sup 125}I-ANP{sub 8-33}. Specific {sup 125}I-ANP binding was saturable and of high affinity. Scratchard analysis of the binding data for all cell types exhibited a straight line, indicating that these cells possessed a single class of binding sites. Despite the presence of linear Scatchard plots, these studies demonstrated that cultured cells possess two functionally and physically distinct ANP-binding sites. Most of the ANP-binding sites in cultured cells have a ...
Systemic sclerosis is an autoimmune connective tissue disorder characterized by a widespread microangiopathy, autoimmunity and fibrosis of the skin and of various internal organs. Microangiopathy is characterized by a reduced capillary density and an irregular chaotic architecture that lead to chronic tissue hypoxia. Despite the hypoxic conditions, there is no evidence for a sufficient compensative angiogenesis in SSc. Furthermore, vasculogenesis is also impaired. An imbalance between angiogenic and angiostatic factors might explain the pathogenetic mechanisms of SSc vasculopathy. As far as angiogenic factors are concerned, within the most important are vascular endothelial growth factor (VEGF) and its receptors, platelet derived growth factor (PDGF), transforming growth factor beta (TGF-?), fibroblast growth factor -2 (FGF-2), angiopoietin 1 (Ang-1), stromal cell-derived factor 1 (SDF-1/CXCL12), endothelin-1 (ET-1), monocyte chemoattractant protein -1 (MCP-1), urokinase type ...
Radiation therapy has had a significant and an expanded role in the management of cancer of the pancreas during the last decade. In particular, for locally advanced disease, radiation therapy has improved the median survival of patients to 1 year. Intraoperative electron beam therapy has been applied to unresectable and resectable pancreatic cancer in an attempt to enhance local control of disease and to improve patient survival. This paper presents a survey of the role of radiation therapy in treatment of cancer of the pancreas, provides information on the radiobiological aspects of this treatment modality and details the physical and dosimetric characteristics of intraoperative radiation therapy with electrons. Presented are the design specifics of an applicator system, central axis beam data, applicator parameters, dose distribution data, shielding, treatment planning and means of verification. Emphasis is placed on the collaboration and cooperation necessary ...
Radiation therapy has had a significant and an expanded role in the management of cancer of the pancreas during the last decade. In particular, for locally advanced disease, radiation therapy has improved the median survival of patients to 1 year. Intraoperative electron beam therapy has been applied to unresectable and resectable pancreatic cancer in an attempt to enhance local control of disease and to improve patient survival. This paper presents a survey of the role of radiation therapy in treatment of cancer of the pancreas, provides information on the radiobiological aspects of this treatment modality and details the physical and dosimetric characteristics of intraoperative radiation therapy with electrons. Presented are the design specifics of an applicator system, central axis beam data, applicator parameters, dose distribution data, shielding, treatment planning and means of verification. Emphasis is placed on the collaboration and cooperation necessary ...
The authors studied the resolution of racemic glycidol through esterification with butyric acid catalyzed by porcine pancreatic lipase in organic media. A screening of seven solvents (log P values between 0.49 and 3.0, P being the n-octanol-water partition coefficient of the solvent) showed that neither log P nor the logarithm of the molar solubility of water in the solvent provides good correlations between enantioselectivity and the properties of the organic media. Chloroform was one of the best solvents as regards the enantiometic purity (e.p.) of the ester produced. In this solvent, the optimum temperature for the reaction was determined to be 35C. The enzyme exhibited maximum activity at a water content of 13 [plus minus] 2% (w/w). The enantiomeric purity obtained was 83 [plus minus] 2% of (S)-glycidol butyrate and did not depend on the alcohol concentration or the enzyme water content for values of these parameters up to 200 mM and 25% (w/w), respectively. ...
A radioimmunoassay is described for the molluscan neuropeptide, Phe-Met-Arg-Phe-NH"2(FMRFamide). The antibody used is C-terminal-specific and shows slight but significant (1-2%) cross-reactivity with chicken pancreatic polypeptide (APP). The assay has been used to identify in rat brain extracts a pair of molecules that may represent mammalian counterparts of FMRFamide. Their concentrations were highest in spinal cord and hypothalamus (>10 pmol.g"-_1) and lowest in cerebellum and striatum (<3.5 pmol.g"-_1). The two immunoreactive peptides were separated on CM ion-exchange chromatography where they appeared to be less basic than FMRFamide. On Sephadex G50 gel filtration one eluted in a similar position to FMRFamide and the other slightly earlier suggesting it may be of higher molecular weight. The rat immunoreactive components do not correspond to previously described neuropeptides or hormones, and may be members of a new group of mammalian neuropeptides with ...
Gallstone is a common disease with a 10% prevalence in the United States and Western Europe. However, it is only symptomatic in 20-30% of patients, with biliary pain "colic" being the most common symptom. Complications of asymptomatic gallstone disease are generally rare, with an incidence of <1 %/yr. The most common complications of gallstone disease are acute cholecystitis, acute pancreatitis, ascending cholangitis, and gangrenous gallbladder. Less frequent complications include Mirizzi syndrome, cholecystocholedochal fistula, and gallstone ileus. Mirizzi syndrome and cholecystocholedochal fistula are two manifestations of the same process that starts with impaction of a gallstone in the gallbladder neck that results in obstruction of the bile duct, causing jaundice. The gallstone may erode into the bile duct, causing cholecystocholedochal fistula. Gallstone ileus refers to small bowel obstruction resulting from the impaction of one or more gallstones after ...
Serum ferritin levels were measured in 72 normal subjects and in 214 cases with various diseases by an immunoradiometric assay. In normal subjects, the serum ferritin levels were 27-230 ng/ml. Elevated serum ferritins were observed in most cases with iron excess and acute hepatitis. Markedly elevated levels were found in the majority of cases with acute leukemia, malignant lymphoma, hepatoma, and pancreatic cancer. High ferritin levels were also found in other malignant diseases. However, the range overlapped broadly with that of nonmalignant diseases. The serum ferritin correlated significantly with serum iron in normals and in those with iron deficiency anemia. In most nonmalignant cases, the serum ferritin and iron levels distributed on a regression line obtained from levels in normals and those with iron deficiency anemia. However, 92% of the malignant cases showed a serum ferritin to iron ratio higher than that of normal subjects. The estimation of the serum ...
The functional interaction between the peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) and its coactivator PGC-1{alpha} is crucial for the normal physiology of PPAR{gamma} and its pharmacological response to antidiabetic treatment with rosiglitazone. Here we report the crystal structure of the PPAR{gamma} ligand-binding domain bound to rosiglitazone and to a large PGC-1{alpha} fragment that contains two LXXLL-related motifs. The structure reveals critical contacts mediated through the first LXXLL motif of PGC-1{alpha} and the PPAR{gamma} coactivator binding site. Through a combination of biochemical and structural studies, we demonstrate that the first LXXLL motif is the most potent among all nuclear receptor coactivator motifs tested, and only this motif of the two LXXLL-related motifs in PGC-1{alpha} is capable of binding to PPAR{gamma}. Our studies reveal that the strong interaction of PGC-1{alpha} and PPAR{gamma} is mediated through both hydrophobic and specific ...
Four major natriuretic peptides have been isolated: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and Dendroaspis-type natriuretic peptide (DNP). Natriuretic peptides play an important role in the regulation of cardiovascular homeostasis maintaining blood pressure and extracellular fluid volume. The classical endocrine effects of natriuretic peptides to modulate fluid and electrolyte balance and vascular smooth muscle tone are complemented by autocrine and paracrine actions that include regulation of coronary blood flow and, therefore, myocardial perfusion; modulation of proliferative responses during myocardial and vascular remodeling; and cytoprotective anti-ischemic effects. The actions of natriuretic peptides are mediated by the specific binding of these peptides to three cell surface receptors: type A natriuretic peptide receptor (NPR-A), type B natriuretic peptide receptor (NPR-B), and type C natriuretic ...
By catalyzing the rate-limiting step in adipose tissue lipolysis, hormone-sensitive lipase (HSL) is an important regulator of energy homeostasis. The role and importance of HSL in tissues other than adipose are poorly understood. We report here the cloning and expression of a testicular isoform, designated HSL{sub tes}. Due to an addition of amino acids at the NH{sub 2}-termini, rat and human HSL{sub tes} consist of 1068 and 1076 amino acids, respectively, compared to the 768 and 775 amino acids, respectively, of the adipocyte isoform (HSL{sub adi}). A novel exon of 1.2 kb, encoding the human testis-specific amino acids, was isolated and mapped to the HSL gene, 16 kb upstream of the exons encoding HSL{sub adi}. The transcribed mRNA of 3.9 kb was specifically expressed in testis. No significant similarity with other known proteins was found for the testis-specific sequence. The amino acid composition differs from the HSL{sub adi} sequence, with a notable hydrophilic ...
Consensus principles from radiation biology were used to describe a generic set of nonlinear, first-order differential equations for modeling of toxicity-induced compensatory cell kinetics in terms of sublethal injury, repair, direct killing, killing of cells with unrepaired sublethal injury, and repopulation. This cellular model was linked to a probit model of hematopoietic mortality that describes death from infection and/or hemorrhage between {approximately} 5 and 30 days. Mortality data from 27 experiments with 851 doseresponse groups, in which doses were protracted by rate and/or fractionation, were used to simultaneously estimate all rate constants by maximum-likelihood methods. Data used represented 18,940 test animals distributed according to: (mice, 12,827); (rats, 2,925); (sheep, 1,676); (swine, 829); (dogs, 479); and (burros, 204). Although a long-term, repopulating hematopoietic stem cell is ancestral to all lineages needed to restore normal ...
ZnMT has been postulated to function in essential metal homeostasis and metal detoxication. This study was undertaken to evaluate the potential of liver ZnMT to mediate the interaction of Zn and Pb with the Zn metalloenzyme, ALAD. Pretreatment of rats with Zn activated liver ALAD and attenuated the inhibition of ALAD by Pb in vitro and in vivo. Liver cytosol from Zn-pretreated rats injected with /sup 203/Pb was fractionated via gel filtration and anion-exchange chromatography and disclosed that both Zn and /sup 203/Pb co-eluted in the MT fractions. Both purified ZnMT-I and ZnMT-II bound /sup 203/Pb in vitro as shown by gel filtration chromatography. Addition of purified liver ZnMT to purified bovine liver ALAD reaction mixtures increased enzyme activity by 2-fold and prevented inhibition of ALAD by Pb. Addition of apothionein alone decreased the activity of Zn-activated ALAD and also attenuated Pb inhibition of the enzyme. Gel filtration studies of incubates ...
Intercrosses of heterozygous pro-opiomelanocortin (POMC) mice result in homozygous null progeny at lower frequencies than expected. Genotyping offspring at pre-, peri-, and postnatal stages revealed that over half of homozygous null mutants die in the early postnatal stages. To investigate the reasons for this early postnatal lethality, we analyzed in detail different parameters in the initial hours after birth. POMC null mutants born to heterozygous dams presented at birth with corticosterone levels no different from wildtype littermates, were euglycemic, and had normal liver glycogen stores. However, already 30 min after birth corticosterone levels dropped by 80% and were undetectable thereafter, while corticosterone levels in wildtype animals increased during postnatal hours. Circulating adrenaline was almost below detection 1h after birth. Blood glucose levels fell sharply in all genotypes within 30 min after birth; however, wildtype and heterozygous pups overcame hypoglycemia ...
Human senescence marker protein 30 (SMP30), which functions enzymatically as a lactonase, hydrolyzes various carbohydrate lactones. The penultimate step in vitamin-C biosynthesis is catalyzed by this enzyme in nonprimate mammals. It has also been implicated as an organophosphate hydrolase, with the ability to hydrolyze diisopropyl phosphofluoridate and other nerve agents. SMP30 was originally identified as an aging marker protein, whose expression decreased androgen independently in aging cells. SMP30 is also referred to as regucalcin and has been suggested to have functions in calcium homeostasis. The crystal structure of the human enzyme has been solved from X-ray diffraction data collected to a resolution of 1.4 {angstrom}. The protein has a 6-bladed {beta}-propeller fold, and it contains a single metal ion. Crystal structures have been solved with the metal site bound with either a Ca{sup 2+} or a Zn{sup 2+} atom. The catalytic role of the metal ion has been ...
No prospective studies have evaluated the effects of correction of iron deficiency anemia on insulin resistance in non-diabetic premenopausal women with iron deficiency anemia. All patients were treated with oral iron preparations. Insulin resistance was calculated with the Homeostasis Model Assessment formula. All patients were dichotomized by the median for age and BMI to assess how the relationship between iron deficiency anemia and insulin resistance was affected by the age and BMI. Although the fasting glucose levels did not change meaningfully, statistically significant decreases were found in fasting insulin levels following anemia treatment both in the younger age (<40 years) (P=0.40) women and in the low BMI (27 kg/m) (P=0.22) subgroups but not in the older age (>= 40 years) and the high BMI (>-27Kg/m) subgroups. Post-treatment fasting insulin levels were positively correlated both with BMI (r=0.386, P=0.004) and post-treatment hemoglobin levels. ...
To investigate the problems of the Hanaro stent (Solco Intermed, Seoul, Korea) when used in the palliative treatment of patients with inoperable malignant biliary obstruction. Between January 2000 and May 2001, the treatment of 46 patients with malignant biliary obstruction involved percutaneous placement of the Hanaro stent. Five patients encountered problems during removal of the stent's introduction system. The causes of obstruction were pancreatic carcinoma (n=2), cholangiocarcinoma (n=2), and gastric carcinoma with biliary invasion (n=1). In one patient, percutaneous transhepatic cholangiography and stent insertion were performed as a one-step procedure, while the others underwent conventional percutaneous transhepatic biliary drainage for at least two days prior to stent insertion. A self-expandable Hanaro stent, 8-10 mm in deameter and 50-100 mm in lengh, and made from a strand of nitinol wire, was used in all cases. Among the five patients who ...
We wanted to determine the technical and clinical efficacy of placing a self-expandable PTFE-covered nitinol stent for the management of inoperable malignant biliary obstruction. Thirty six patients with inoperable malignant biliary obstructions were treated by placement of self-expandable PTFE-covered nitinol stents (S and G Biotech Corporation, Seongnam, Korea). Clinical evaluation was done with assessment of the serum bilirubin and alkaline phosphatase levels, which were measured before and after stent placement within 1 week, at 1 month and at 3 months. The patient survival rate and stent patency rate were calculated with performing Kaplan-Meier survival analysis. Successful stent placement was achieved in all the patients without procedure-related complication. Pancreatitis as an early complication occurred in two cases. The serum bilirubin and alkaline phosphatase levels were significantly decreased after the procedure. During the follow-up, recurrent ...
To evaluate repeated hepatic intraarterial chemotherapy (HIC) as a palliative treatment option for unresectable cholangiocarcinoma and liver metastases of various origins that were progressive under systemic chemotherapy. Between 2002 and 2006, 55 patients were treated in 4-week intervals (mean five sessions). Combined gemcitabine/mitomycin was administered intraarterially within 1 h. Tumor response was evaluated after the third session according to RECIST. Treated tumor entities were colorectal carcinoma (CRC) (n = 12), breast cancer (BC) (n = 12), cholangiocarcinoma (CCC) (n = 10), pancreatic (n = 4), ovarian (n = 3), gastric, cervical, papillary (each n = 2), prostate, esophageal carcinoma, leiomyosarcoma (each n = 1), cancer of unknown primacy (CUP) (n = 5). All patients tolerated the treatment well without any major side effects or complications. In total, there were 1 complete response (CR), 19 partial responses (PR), 19 stable (SD) and 16 progressive ...
To evaluate the feasibility and clinical effectiveness of using a polyurethane-covered expandable nitinol stent in the palliative treatment of malignant duodenal obstruction. Under fluoroscopic guidance, a polyurethane-covered expandable nitinol stent was placed in 12 consecutive patients with malignant duodenal obstructions. All presented with severe nausea and recurrent vomiting. The underlying causes of obstruction were duodenal carcinoma (n=4), pancreatic carcinoma (n=4), gall bladder carcinoma (n=2), distal CBD carcinoma (n=1), and uterine cervical carcinoma (n=1). The sites of obstruction were part I (n=1), part II (n=8), and III (n=3). Due to pre-existing jaundice, eight patients with part II obstructions underwent biliary decompression prior to stent placement. An introducer sheath with a 6-mm outer diameter and stents 16 mm in diameter were employed, and to place the stent, and after-loading technique was used. Stent placement was technically successful in ...
Objective: Solid pseudopapillary tumor of the pancreas (SPTP tumor) is a rare pancreatic neoplasm with low malignant potential, which usually affects female patients in the second or third decades of life. It is a non-functional, slow-growing neoplasm that very often reaches considerable size before the first symptoms appear. Symptomatology is frequently related to tumor size. Surgical excision is usually curative in most cases. Infrequently the tumor can appear in male patients or in aged women, which can make the diagnosis more difficult. Some patients develop liver metastases in the follow-up that can be resected. Our purpose is to review the radiological and pathological findings of SPTP with emphasis on these infrequent cases. Subjects and methods: The medical records and radiological findings of patients who underwent surgery for SPTP between 2000 and 2005 were retrospectively reviewed. Study eligibility required that patients had undergone surgical resection ...
Objective: Solid pseudopapillary tumor of the pancreas (SPTP tumor) is a rare pancreatic neoplasm with low malignant potential, which usually affects female patients in the second or third decades of life. It is a non-functional, slow-growing neoplasm that very often reaches considerable size before the first symptoms appear. Symptomatology is frequently related to tumor size. Surgical excision is usually curative in most cases. Infrequently the tumor can appear in male patients or in aged women, which can make the diagnosis more difficult. Some patients develop liver metastases in the follow-up that can be resected. Our purpose is to review the radiological and pathological findings of SPTP with emphasis on these infrequent cases. Subjects and methods: The medical records and radiological findings of patients who underwent surgery for SPTP between 2000 and 2005 were retrospectively reviewed. Study eligibility required that patients had undergone surgical resection ...
The eastern oyster (Crassostrea virginica) developed neoplastic disorders when experimentally exposed both in the laboratory and field to chemically contaminated sediment from Black Rock Harbor (BRH), Bridgeport, Connecticut. Neoplasia was observed in oysters after 30 or 60 days of continuous exposure in a laboratory flow-through system to a 20 mg/L suspension of BRH sediment plus postexposure periods of 3, 30, or 60 days. Composite tumor incidence was 13.6% for both exposures. Tumor occurrence was highest in the renal excretory epithelium, followed in order by gill, gonad, gastrointestinal, heart, and embryonic neural tissue. Regression of experimental neoplasia was not observed when the stimulus was discontinued. In field experiments, gill neoplasms developed in oysters, deployed in cages for 30 days at BRH and 36 days at a BRH dredge material disposal area in Central Long Island Sound, and kidney and gastrointestinal neoplasms developed in caged oysters deployed 40 days in Quincy ...
CT of the gastrointestinal tract is commonly performed after administration of a high-density diluted iodinated oral contrast material. However, because if inadequate mixing of the contrast material with the gastrointestinal contents, pseudotumor and poor mucosal visualization are frequently shown on abdominal CT. To overcome these problem, 10% corn oil emulsion (COE) is tested as an alternative oral contrast agent in 40 patients. We analyse patients tolerance, gastric mucosal visualization and discrimination of pancreas from the duodenal C-loop to 10% COE in 40 patients compared with those obtained from 35 patients, who was received high-density diluted iodinated oral contrast agent (gastrografin). The results are as follows : 1. Patients' tolerance to 10% COE is similar to that to conventional oral contrast agent. 2. Image of the gastric mucosa from patients receiving 10% COE is superior to that receiving oral contrast agent. 3. The discrimination between ...
CT of the gastrointestinal tract is commonly performed after administration of a high-density diluted iodinated oral contrast material. However, because if inadequate mixing of the contrast material with the gastrointestinal contents, pseudotumor and poor mucosal visualization are frequently shown on abdominal CT. To overcome these problem, 10% corn oil emulsion (COE) is tested as an alternative oral contrast agent in 40 patients. We analyse patients tolerance, gastric mucosal visualization and discrimination of pancreas from the duodenal C-loop to 10% COE in 40 patients compared with those obtained from 35 patients, who was received high-density diluted iodinated oral contrast agent (gastrografin). The results are as follows : 1. Patients' tolerance to 10% COE is similar to that to conventional oral contrast agent. 2. Image of the gastric mucosa from patients receiving 10% COE is superior to that receiving oral contrast agent. 3. The discrimination between ...
ABSTRACT: BACKGROUND: The capacity to maintain internal ion homeostasis amidst changing conditions is particularly important for teleost fishes whose reproductive cycle is dependent upon movement from freshwater to seawater. Although the physiology of seawater osmoregulation in mitochondria-rich cells of fish gill epithelium is well understood, less is known about the underlying causes of inter- and intraspecific variation in salinity tolerance. We used a genome-scan approach in Arctic charr (Salvelinus alpinus) to map quantitative trait loci (QTL) correlated with variation in four salinity tolerance performance traits and six body size traits. Comparative genomics approaches allowed us to infer whether allelic variation at candidate gene loci (e.g., ATP1alpha1b, NKCC1, CFTR, and cldn10e) could have underlain observed variation. RESULTS: Combined parental analyses yielded genome-wide significant QTL on linkage groups 8, 14 and 20 for salinity tolerance performance ...
It has been previously stated that the minimum physiological recommendations for the indispensable amino acids in health adults, as proposed by FAO/WHO/UNU in 1985, are far too low, except for the methionine. An amino acid stable isotopic kinetic study was conducted to seek further experimental support to this hypothesis. Twenty healthy young men received an l-amino acid based diet, supplying 140 mg N.kg"-"1.d"-"1, patterned on egg protein for 1 week, then for 3 weeks either i) a pattern based on current international recommendations (FAO diet, n=7), ii) a the tentative Laboratory of Human Nutrition of the Massachusetts Institute of Technology, new amino acid recommendation pattern (MIT diet, n=7) or iii) again the egg hen pattern (EGG diet, n=6). All subjects were again studied for one final, consecutive week of the egg diet. At the end of the initial week, at the first and third week with the three experimental diets,and after three days following the return of the egg diet, an 8 h ...
Authors retrospectively analyzed the CT findings of mediastinal lesions in surgically or clinically confirmed 37 cases at Kosin Medical College during recent 4 years from September 1979 to August 1983. 1. Among 37 caes, malignant lymphoma were 7 cases, thymoma and vascular lesion or anomaly were 5 cases respectively, benign teratoma and tuberculous mediastinal lymphadenitis and neurogenic tumor were 4 cases respectively, pericardial cyst were 2 cases, bronchogenic cyst, non-specific cyst, pancreatic pseudocyst, mesothelioma, Bochdalek hernia was 1 case respectively. 2. The sex ratio between male and female was about 1 : 1 and the majority of the patients with malignant lymphoma and teratoma was under 20 years old. 3. CT findings of the each mediastinal lesion. 1) Primary mediastinal malignant lymphoma. (1) A large, matted, continuous and midline-crossing mass was observed in the superior and the anterior mediastinums in all cases. (2) In 3 cases, irregular lower ...