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Biomedical subjects

J Kountouras

Publications and source records attributed to J Kountouras.

At least 37 records · Page 2Linked to original sources
PubMed1995

Recombinant a2 interferon (a-IFN) with chemo-hormonal therapy in patients with hepatocellular carcinoma (HCC).

Recent studies on HCC treatment reveal a tendency to use combined immuno-chemo-therapy. Additionally, new agents have been suggested in this field. We therefore studied 7 patients with proven inoperable HCC who were treated in accordance with the following protocol, and 5 untreated patients used as controls. Therapeutic trial: 1) 1FNa (Roferon): 6 MU x 7 days consecutively every 3 weeks, 2) Adriamycin (doxorubicin): 60 mg/m2 i. v. once every 3 weeks (500 mg total dose), 3) Tamoxifen: 10 mg p.o. twice daily continuously 4) Desferrioxamine (DFO): 500 mg i.m. daily x 7 days consecutively every 3 weeks, 5) ascorbic acid: 300 mg p.o. daily 1 hour after DFO administration x 7 days consecutively every 3 weeks. Follow-up studies were performed monthly and comprised clinical, biochemical, radiological and immunological (T-cell subsets, NK cells, monocyte-macrophage function, IL-2r expression, HLA-DR expression) parameters. Compared with the control group, the treated group had a longer survival rate (p < 0.001), increased tumor regression and less progressive disease. Immunologically, the treated patients with the maintenance of a sufficient immune status were associated with a prolonged survival rate. No serious side effects of the regimen were observed. In conclusion, IFNa combined with chemohormonal therapy appears to be beneficial in HCC patients. In addition, a prolonged survival rate might correlate with the maintenance of an adequate immune status in the patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

In vivo effect of omeprazole on HLA-DR expression and the monocyte-macrophage function in patients with duodenal ulcer disease.

It is not known if omeprazole possesses any action on immune system. Therefore, we examined the effect of omeprazole on parameters of cellular immunity [T-cell subsets-CD3+, CD4+, CD(8+)- and HLA-DR expression on peripheral blood lymphocytes (PBLs)] and on function of peripheral blood monocyte-macrophages (PBMMs) [random migration (RM), directed migration (DM), phagocytosis index (P-I) and HLA-DR expression] in 13 duodenal ulcer patients before and during 3-mo omeprazole treatment. The number of T-cell subsets varied at pretreatment values (p > 0.05), whereas the percentage of HLA-DR positive PBLs increased significantly after 3-mo therapy (p < 0.001). On the other hand, all studied parameters concerning PBMMs (RM, DM, P-I and HLA-DR expression) increased significantly after 3-mo therapy (p < 0.001, p < 0.001, p < 0.003, p < 0.001, respectively vs. baseline values). In conclusion, omeprazole exerts an immunopotentiating effect on functions of PBMMs and may also influence T-cell function. These effects can be considered as an advantage of omeprazole in long-term treated patients with peptic ulcer disease.

Adult↗
PubMed1991

Cholangiocarcinoma and severe renal hypouricemia: a study of the renal mechanisms.

Hypouricemia in malignant neoplasms is rarely reported. We present a previously unreported case of cholangiocarcinoma associated with severe persistent hypouricemia (serum uric acid levels ranged from 0.07 to 0.08 mmol/L [1.16 to 1.40 mg/100 mL], and increased urate clearance (50.90 to 57.33 mL/min v a mean value in 20 normal subjects of 9.75 +/- 1.65 mL/min). High fractional urate clearance (Cus/Ccr = 0.50 to 0.58 v 0.09 +/- 0.01 in normals) was suppressed only slightly following pyrazinamide (PZA), to 0.29 versus 0.007, and was surprisingly enhanced by probenecid (PB) to 1.78 versus 0.63 in normals. No other renal tubular or metabolic abnormalities were detected. This previously unreported association of a high PZA-nonsuppressible urate excretion with a postprobenecid urate clearance exceeding glomerular filtration rate suggests that a combined renal tubular defect is responsible for hypouricemia. The patient described here provides evidence to support the presence of a presecretory reabsorptive defect in association with a "relatively high" urate secretion by the renal tubule. This report adds to the list of hypouricemic conditions and presents an important clue to elucidate urate handling mechanisms in man.

Adenoma, Bile Duct↗
PubMed1987

The effect of secretin on bile flow and bile acid and bilirubin excretion following relief of prolonged bile duct obstruction in the rat.

Bile flow was re-established in rats whose bile ducts had been obstructed for 5, 10, 15 and 28 days (Groups I, II, III and IV, n = 5). The effect of i.v. secretin on bile flow in control rats, whose bile ducts had been cannulated, was minimal, but in cholestatic rats there was an immediate response which was related to the duration of the obstruction and the degree of bile duct proliferation. In 40 min the mean excess bile flow production amounted to 76, 258, 320 and 432 microliters/100 g body wt. in Groups I, II, III and IV, respectively. Choleresis was prolonged in the Group IV rats that had developed cirrhosis. Synthetic secretin had a minimal effect on bile acid and bilirubin excretion. It is postulated that the proliferating bile ductules are the site of secretin choleresis, although the possibility that reduced inactivation of the hormone plays a role cannot be excluded.

Animals↗
PubMed1985

Effect of prolonged bile duct obstruction in the rat on hepatic transport of bilirubin.

In order to investigate the effect of extra-hepatic biliary obstruction on bilirubin transport, bile flow was re-established after 5, 10, 15 and 28 days when the mean (+/- SEM) plasma bilirubin concentrations of the four groups of five rats were 226 +/- 17.9, 201 +/- 22.4, 178 +/- 8.1 and 145 +/- 3.8 mumol/l, respectively. After 12 h of bile drainage in the conscious animal, the mean plasma bilirubin concentrations of the four groups had decreased by 88, 86, 73 and 46%, respectively. The bile flow rate increased with the duration of the obstruction and was maximal in the 28 day obstructed rats, although the bilirubin output in these animals was significantly less than in the other groups. Histological evidence of biliary obstruction was apparent in the livers of the 5 and 10 day obstructed animals. After 15 days of obstruction cirrhosis developed. In conclusion, the disposal of endogenous bilirubin in the bile duct obstructed rat appears to be influenced by the development of cirrhosis.

Animals↗
PubMed1984

Prolonged bile duct obstruction: a new experimental model for cirrhosis in the rat.

Hepatic morphological abnormalities were examined in rats whose bile ducts had been either cannulated and then obstructed or irreversibly ligated for 5, 10, 15 and 28 days or longer. Throughout the experiment most of the morphological changes observed in the cannulated group were comparable to those in the ligated group. Portal inflammation and marginal bile duct proliferation were noted with the same frequency in both groups. Biliary obstruction for 15 days or more led to cirrhosis. After 28 days obstruction, five out of six cannulated rats and four out of six ligated animals respectively developed cirrhosis. The development of cirrhosis was progressive and associated with ascites. It is concluded that in the rat the morphological sequelae of long term cholestasis induced by either cannulation and obstruction or ligation of bile ducts are similar and are accompanied by cirrhosis. The advantages of this experimental model for the study of human cirrhosis are discussed.

Animals↗
PubMed1982

A study of cell-mediated immunity to gastric antigens in patients with atrophic type A and B gastritis.

The leucocyte migration in the presence of gastric antigens was studied in 10 patients with type A gastritis, 38 patients with type B gastritis (28 with atrophic and 10 with superficial gastritis) and 10 healthy controls. A positive leucocyte migration was found in a significant proportion of patients with both types of gastritis, whereas no difference between the two types was observed. These results indicate that cellular immunity is implicated in the aetiology of both types of gastritis, is of greater importance than auto-antibody production and is associated with the severity of the atrophic lesion.

Animals↗
PubMed1980

Levamisole in the treatment of chronic brucellosis.

Ten patients with chronic brucellosis were treated with levamisole, 150mg daily for 3 consecutive days every week for 6 months. Patients were followed up for another 6 months after the end of treatment. By the end of the treatment period, patients improved clinically, their E rosettes showed a significant increase and specific leukocyte inhibition migration factor (LIF) was produced. By the end of the follow up period, all patients except one became symptom free, antiglobulin titers were very low or negative, E rosettes showed a further increase ranging to normal levels and specific LIF activity was not detected to most of the patients. Our results suggest that levamisole might prove to be beneficial in the treatment of chronic brucellosis.

Adult↗
PubMedDate not supplied

A concept on the role of Helicobacter pylori infection in autoimmune pancreatitis.

Autoimmune pancreatitis, an inflammatory process of the pancreas due to an autoimmune mechanism establishing etiology of chronic pancreatitis, is characterized by the presence of autoantibodies, hypergammaglobulinemia, pancreatic enlargement, pancreatic duct strictures, and pathologic features of fibrotic changes with intense, mainly lymphocytic infiltrations, which may contribute to tissue destruction probably by apoptosis. In almost 60% of the cases, this type of pancreatitis coexists with other autoimmune diseases such as Sjogren's syndrome, sclerosing extrahepatic cholangitis, primary biliary cirrhosis, autoimmune hepatitis, or other extrapancreatic disorders, and recently with gastric peptic ulceration. The diversity of extrapancreatic lesions with similar histopathologic findings suggests general involvement of the digestive system in this disease, although the presence of such involvement has not been fully elucidated. Similarly, Helicobacter pylori (H. pylori) infection, a well known cause of gastric ulcer, has been associated, via molecular mimicry of host structures by its constituents with the same autoimmune conditions, also characterized by fibrotic changes and/or lymphoplasmacytic inflammations, accompanied by aberrations of T cell apoptosis that contribute to hepatobiliary- or extrahepatic-tissue destruction. Considering that H. pylori is involved in the pathogenesis and pathophysiology of these autoimmune disorders, we propose that this organism might trigger autoimmune pancreatitis through induction of autoimmunity and apoptosis.

Apoptosis↗
PubMedDate not supplied

Transplenic and transtumoral in vivo immunostimulation: effect on cellular immunity parameters.

BACKGROUND/AIMS: It has been shown that IL-2 and gamma-IFN own an additive immunostimulatory effect against tumors. Moreover, it has been suggested that the locoregional route of administration of immunopotentiating agents has substantial advantages compared to the systemic route. The aim of the present study was to evaluate the immune response of patients with advanced unresectable liver and pancreatic malignant disease who were submitted for transplenic and transtumoral IL-2 and gamma-IFN combination immunotherapy. METHODOLOGY: In 32 patients, the following therapeutic regimen was applied for 10 consecutive days: a) 5 days transplenic administration of 5 mg IL-2 plus 50 micrograms gamma-IFN in a Lipiodol-Urografin emulsion, and b) 5 days transtumoral administration of the same drug cocktail. In the beginning (T1) and on day 15 (T2) after treatment, the following parameters were performed: CD3+, CD4+, CD8+, IL-2r+, HLA-DR+ lymphocytes in peripheral blood spontaneously, and after 48-hour T-lymphocyte cultures in the presence of PHA. RESULTS: CD3+, CD4+ and CD8+ T-lymphocytes were significantly increased in peripheral blood after treatment (p < 0.05, p < 0.05, and p < 0.003, respectively), whereas IL-2r expression and HLA-DR expression on CD4+ T-cells were not influenced significantly (p > 0.05). After PHA 48-hour T-cell cultures, T-cell subpopulations showed the following alterations: CD3+, CD4+ and CD8+ T-cells were significantly increased (p < 0.001, p < 0.006 and p < 0.01, respectively). Moreover, IL-2r expression as well as HLA-DR expression on CD4+ T-cells were also significantly increased (p < 0.001). CONCLUSIONS: Locoregional treatment exerted a beneficial immunopotentiating effect on T-cell populations, IL-2r expression and HLA-DR expression. This is a promising mode of action in the management of malignant metastatic disease.

Adjuvants, Immunologic↗
PubMedDate not supplied

New epidemiological data on liver oncogenesis.

The purpose of this review is to address and discuss the following: a) the malignant transformation of hepatocytes may occur, irrespective of the etiologic agent, in the context of increased cellular turnover induced by chronic hepatic damage and regeneration, with genetic mutations being a frequent event prior to the development of this tumor; b) although it is clear that hepatitis B virus-induced chronic liver injury, regeneration and cirrhosis is a major risk factor for hepatocellular carcinoma development, there are also several reports of the direct carcinogenic effects of hepatitis B virus. For instance, integration of hepatitis B virus DNA can directly induce chromosomal rearrangements and viral gene product transactivating properties may influence cellular genes important in the control of the growth process; c) hepatitis C virus and other risk agents, including alcohol, environmental factors and metabolic diseases may operate, mainly through chronic liver damage that progress to liver cirrhosis, a major predisposing factor for the development of hepatocellular carcinoma, regardless of etiology; d) at the molecular level, the interaction between oncogenes, tumor suppressor genes (with or without aflatoxins and hepatitis B virus) and several growth factors may play an additional role in hepatocellular carcinoma development.

Animals↗
PubMedDate not supplied

New concepts of molecular biology for colon carcinogenesis.

The progressive accumulation of genetic changes in both oncogenes and tumor-suppressor genes parallels the clinical and histopathologic progression from normal colonic epithelium through benign adenomas to frank colon cancer. A similar progression is postulated in the transition of normal squamous epithelium to metaplastic mucosa (Barrett's esophagus) and subsequently through dysplasia to adenocarcinoma of the esophagus. A common link between colorectal cancer and Barrett's esophagus or esophageal carcinoma might be explained by either genetic predisposition or common environmental risk factors. The multistep nature of oncogenesis is most directly illustrated by molecular experimental genetic studies which demonstrate that the progression from adenoma to colon carcinoma results from the accumulation of molecular genetic alterations involving mainly 3 factors: activation of oncogenes; inactivation of tumor-suppressor genes; and abnormalities in genes involved in DNA mismatch repair. Changes in oncogenes encoding four distinct groups of proteins (peptide growth factors, protein kinases, signal transducing proteins, and nuclear transcriptional regulatory proteins) can contribute to colon carcinogenesis. In addition, various carcinogens may act at different stages of this model, affecting somatic mutations and resulting in additional genetic alterations. Other promoters, including hormones, may enhance the likelihood of these events through the stimulation of the rate of cell turnover. Diseased detoxification processes may also play a role in carcinogenesis.

Cell Adhesion Molecules↗
PubMedDate not supplied

Omeprazole and regulation of cytokine profile in Helicobacter pylori-infected patients with duodenal ulcer disease.

BACKGROUND/AIMS: To estimate the cytokine profile in Helicobacter pylori-positive patients with duodenal ulcers treated with omeprazole. METHODOLOGY: The subjects were 22 patients with endoscopically defined active duodenal ulcers and H. pylori infection treated with omeprazole for 3 months after initial 1-week triple therapy. Peripheral blood CD3+ CD4+ and CD8+ T lymphocytes, percentage of HLA-DR+ peripheral blood lymphocytes, and cytokine levels (GM-CSF, IL-6 and IL-2) were measured in the supernatants from PHA-cultured peripheral blood lymphocytes at baseline conditions and after 3-months' omeprazole treatment. RESULTS: The H. pylori eradication triple regimen cured H. pylori infection in 86.4% of our patients. Peripheral blood CD3+ CD4+ and CD8+ T lymphocytes were not affected by omeprazole treatment (P > 0.05), whereas the percentage of HLA-DR+ peripheral blood lymphocytes increased significantly post-treatment (P < 0.05). All cytokine levels measured in the supernatants showed a significant decrease after treatment (P < 0.001). CONCLUSIONS: The significant decrease in the two pro-inflammatory cytokines (GM-CSF, IL-6) and the major inflammatory cytokine IL-2, implies that the potential cytokine synthesis of the Th1 pattern from peripheral blood lymphocytes is highly suppressed after treatment. This effect on cytokine regulation seems to be a result of the positive H. pylori infection outcome at the immunological level, which leads to "normalization" of cytokine production.

Anti-Ulcer Agents↗
PubMedDate not supplied

Liver regeneration after hepatectomy.

Following hepatectomy, liver "knows" when to start and when to stop growing, and thereby accurately regulates its mass. Partial hepatectomy triggers hepatocyte proliferation whereas excessive liver mass (transplant) is regulated by apoptosis. Liver regeneration mainly involves the activation of adult hepatocytes and possibly of liver precursor ("stem") cells. The multistep process of liver regeneration comprises at least 2 critical phases: the transition of the quiescent hepatocyte into the cell cycle (priming) and the progression beyond the restriction point in the G1 phase of the cycle. The priming phase is characterized by the expression of immediate early genes. Activation of protooncogenes in the immediate early gene response involves both transcriptional and post-transcriptional mechanisms. Activation of four transcription factors, NF kappa B, STAT3, AP-1, and C/EBP beta, causes secondary activation of multiple genes and plays an important role in the initiation of hepatic regeneration. The passage of primed hepatocytes through the cell cycle is characterized by the expression of cell cycle genes and requires growth factors. An equilibrium between stimulator and inhibitor genes of the cell cycle expressed after hepatectomy, may explain why the liver regeneration is a tightly regulated growth process. Based on the knowledge of the regulation of liver regeneration, several practical considerations and potential therapeutic strategies can be applied in humans with hepatic dysfunction due to liver resection.

Animals↗
PubMedDate not supplied

Reactive oxygen metabolites and upper gastrointestinal diseases.

Reactive oxygen metabolites play an important role in the pathogenesis of gastroduodenal mucosal inflammation (mucosal ischemic injury and other models of mucosal damage induced by nonsteroidal anti-inflammatory drugs, ethanol, or H. pylori), peptic ulcer disease, and gastric cancer. H. pylori achieves its pathogenetic role by triggering an intense leukocyte infiltration of the gastric mucosa, and neutrophil activation provides a major source of reactive oxygen metabolites which can cause tissue damage mainly in the absence of antioxidants. H. pylori virulence factors promote release of a variety of chemoattractants/inflammatory mediators. Circulating leukocytes are recruited to sites of inflammation by a well-regulated and coordinated process that largely occurs in postcapillary venules. Adhesion molecules are expressed on the surface of endothelial cells and leukocytes serve to ensure an orderly sequence of cell-to-cell interactions that sustain leukocyte adherence to vascular endothelium and the subsequent transendothelial migration into inflamed tissue. Transcriptional factors are involved in the expression of endothelial adhesion molecules, and regulation of activity of these factors (i.e., NF-kappa B) is a very attractive target for therapeutic interventions. Longstanding H. pylori-associated gastritis predisposes to gastric cancer development and reactive oxygen metabolites play a part in H. pylori-related gastric carcinogenesis. Various regimens of reactive oxygen metabolite scavengers appear to be new treatment strategies for upper gastrointestinal diseases.

Animals↗
PubMedDate not supplied

Tumor immunity and immunotherapy.

Recent advances in understanding fundamental mechanisms of regulation of the immune response are throwing light into mechanisms of tumor growth. The understanding of the immunological aspects of tumor expansion is leading to the development of new strategies to stimulate the immune system to mount more effective responses to tumors. This progress as well as some promising results in clinical trials is generating considerable optimism. The goal of this review is to present recent advances concerning tumor immunology, identify some of the pitfalls and problems that still exist and present new areas of immunotherapy that look promising.

Antigen Presentation↗