Biomedical subjects

J K Lin

Publications and source records attributed to J K Lin.

At least 73 records · Page 4Linked to original sources

PubMed1999

Suppression of extracellular signals and cell proliferation by the black tea polyphenol, theaflavin-3,3'-digallate.

Previous studies in our laboratory have shown that the major green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), suppressed autophosphorylation of epidermal growth factor (EGF) receptor induced by EGF in human A431 epidermoid carcinoma cells. In this study, we examined the inhibitory effects of black tea polyphenols, including theaflavin (TF-1), a mixture (TF-2) of theaflavin-3-gallate (TF-2a) and theaflavin-3'-gallate (TF-2b), theaflavin-3,3'-digallate (TF-3) and the thearubigin fraction on the autophosphorylation of the EGF and PDGF receptors in A431 cells and mouse NIH3T3 fibroblast cells, respectively. First, we examined the effects of these polyphenols on the proliferation of A431 and NIH3T3 cells. Both EGCG and TF-3 strongly inhibited the proliferation of A431 and NIH3T3 cells more than the other theaflavins did. In cultured cells with pre-treatment of tea polyphenol, TF-3 was stronger than EGCG on the reduction of EGF receptor and PDGF receptor autophosphorylation induced by EGF and PDGF, respectively. Other theaflavins slightly reduced the autophosphorylation of the EGF and PDGF receptors; furthermore, TF-3 could reduce autophosphorylation of the EGF receptor (or PDGF receptor) even with co-treatment with EGF (or PDGF) and TF-3, but EGCG was inactive under these conditions. In addition, TF-3 was stronger than EGCG in blocking EGF binding to its receptor. These results suggest that not only the green tea polyphenol, EGCG, but also the black tea polyphenol, TF-3, have an antiproliferative activity on tumor cells, and the molecular mechanisms of antiproliferation may block the growth factor binding to its receptor and thus suppress mitogenic signal transduction.

3T3 Cells↗

PubMed1999

Biotransformation of curcumin through reduction and glucuronidation in mice.

Curcumin, the yellow pigment in turmeric and curry, has antioxidative and anticarcinogenic activities. In this study, we investigated the pharmacokinetic properties of curcumin in mice. After i.p. administration of curcumin (0.1 g/kg) to mice, about 2.25 microg/ml of curcumin appeared in the plasma in the first 15 min. One hour after administration, the levels of curcumin in the intestines, spleen, liver, and kidneys were 177.04, 26.06, 26.90, and 7.51 microg/g, respectively. Only traces (0.41 microg/g) were observed in the brain at 1 h. To clarify the nature of the metabolites of curcumin, the plasma was analyzed by reversed-phase HPLC, and two putative conjugates were observed. Treatment of the plasma with beta-glucuronidase resulted in a decrease in the concentrations of these two putative conjugates and the concomitant appearance of tetrahydrocurcumin (THC) and curcumin, respectively. To investigate the nature of these glucuronide conjugates in vivo, the plasma was analyzed by electrospray. The chemical structures of these metabolites, determined by mass spectrometry/mass spectrometry analysis, suggested that curcumin was first biotransformed to dihydrocurcumin and THC and that these compounds subsequently were converted to monoglucuronide conjugates. Because THC is one of the major metabolites of curcumin, we studied its stability at different pH values. THC was very stable in 0.1 M phosphate buffers of various pH values. Moreover, THC was more stable than curcumin in 0.1 M phosphate buffer, pH 7.2 (37 degrees C). These results, together with previous findings, suggest that curcumin-glucuronoside, dihydrocurcumin-glucuronoside, THC-glucuronoside, and THC are major metabolites of curcumin in vivo.

Administration, Oral↗

PubMed1999

Diagnosis and treatment of cystic lymphangioma of the ascending colon by laparoscopic-assisted surgery: a case report.

Lymphangioma of the colon is a rare disease. Its clinical silence and absence of specific symptoms and signs make it difficult to diagnose preoperatively. We present a case of cystic lymphangioma of the ascending colon associated with constipation in a 72-year-old man and review the pertinent literature. The patient underwent laparoscopic-assisted segmental resection of the colon. The characteristic histologic appearance of cystic lymphangioma provided the definitive diagnosis. The recovery course was uneventful. Two years postoperatively, the patient was symptom-free and without evidence of tumor recurrence.

Aged↗

PubMed1999

Involvement of heat-shock protein 70 and P53 proteins in attenuation of UVC-induced apoptosis by thermal stress in hepatocellular carcinoma cells.

Induction of apoptosis is a function of external stimuli and cellular gene expression. Many cells respond to DNA damage by the induction of apoptosis, which depends on a functional p53 protein and is signaled by elevation of p53 levels. In this study, we found that a prior exposure to mild stress (42 degrees C) can protect HepG2 (p53+/+) cells from a subsequent UVC-induced apoptosis determined by DNA fragmentation and ratio of sub-G1 peak, but no heat-enhanced protection was found in Hep3B (p53-/-) cells. Although a similar inductive pattern of HSP70 protein and mRNA was detected in the two cell lines under thermal stress, the effect of thermal stress on UVC-induced apoptosis in HepG2 and Hep3B cells was obviously different. Overexpression of HSP70 by transient transfection of HSP70 expression vector in HepG2 cells significantly inhibited UVC-induced cell death; however, this inhibitory effect did not occur in transfected-Hep3B cells. Treatment of HepG2 cells with p53-specific antisense oligonucleotide could effectively block the antiapoptotic effect of thermal stress on UVC-induced apoptosis and increase of intracellular wild-type p53 protein by transfecting wtp53 expression plasmid into Hep3B cells yielded more resistance to UVC irradiation after prior thermal stress exposure. The results reveal an involvement of p53 in the antiapoptotic effect of thermal stress on UVC irradiation. Finally, a p53 protein increase was detected in UVC-treated HepG2 cells and could be coimmunoprecipitated with HSP70 after a thermal stress treatment. Prolonged p53 binding activity and enhanced expression of p53-controlled genes such as G1 arrest and DNA damage 45 and wild-type p53 activation factor 1/Cdk-interacting protein 1 by thermal stress are also observed in UVC-irradiated HepG2 cells. Based on these results, we propose that the antiapoptotic effect of thermal stress is mediated by increasing HSP70 and modulating intracellular p53 function.

Apoptosis↗

PubMed1999

Chemoprevention of cancer and cardiovascular disease by resveratrol.

Resveratrol (trans-3,4',5-trihydroxystibene) is a phytopolyphenol isolated from the seeds and skins of grapes. Recent studies indicate that resveratrol can block the process of multistep carcinogenesis, namely, tumor initiation, promotion and progression. Resveratrol can also reduce the risk of cardiovascular disease in man. The molecular mechanisms of resveratrol in chemoprevention of cancer and cardiovascular disease are interesting and under intensive investigation. Resveratrol was found to strongly inhibit nitric oxide (NO) generation in activated macrophages, as measured by the amount of nitrite released into the culture medium, and resveratrol strongly reduced the amount of cytosolic inducible nitric oxide synthase (iNOS) protein. The activation of nuclear factor kappa B (NF kappa B) induced by lipopolysaccharide (LPS) was inhibited by resveratrol. The phosphorylation and degradation of nuclear factor inhibitor kappa B alpha (I kappa B alpha) were inhibited by resveratrol simultaneously. Reactive oxygen species (ROS) are regarded as having carcinogenic potential and have been associated with tumor promotion. Resveratrol may act as a reactive oxygen species scavenger to suppress tumor development. In addition, resveratrol may block multistep carcinogenesis through mitotic signal transduction blockade. Reactive oxygen species are pivotal factors in the genesis of heart disease. Meanwhile, efficient endogenous antioxidants, including superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and catalase, are present in tissues. A fine balance between reactive oxygen species and endogenous antioxidants is believed to exist. Any disturbance of this balance in favor of reactive oxygen species causes an increase in oxidative stress and initiates subcellular changes, leading to cardiomyopathy and heart failure. The experimental results indicate that exogenous antioxidant resveratrol is of value in chemopreventing the development of heart disease. It is urgent that more efforts be made to investigate newer therapies employing antioxidants for the chemoprevention of cardiovascular disease and cancer.

Anticarcinogenic Agents↗

PubMed1999

Induction of apoptosis by S-nitrosoglutathione and Cu2+ or Ni2+ ion through modulation of bax, bad, and bcl-2 proteins in human colon adenocarcinoma cells.

In this study, the amount of S-nitrosoglutathione (GSNO) was measured spectrophotometrically at 334 nm. A spontaneous decrease in absorbency at 334 nm was detected when GSNO was exposed to 37 degrees C and a high pH (pH 8.0). We investigated the catalytic roles of various metal ions on the decomposition of GSNO. The degradation of GSNO (0.5 mM) was enhanced by the presence of Cu(2+) and Ni(2+) ions. The amount of nitric oxide (NO) released from GSNO degradation was estimated by the Griess reaction based on nitrite accumulation. The results indicated that nitrite production was elevated at least twofold in the presence of Cu(2+). Our study further indicated that Cu(2+) enhanced GSNO-induced apoptosis in human colon adenocarcinoma HT 29 cells. We also found that copper ions modulated the expression of bad, bax, and bcl-2 in GSNO-treated HT 29 cells. The levels of bax and bad proteins in treated cells were significantly elevated about fourfold to sixfold when compared with mock-treated cells 24 h after combined treatment with GSNO plus Cu(2+) or Ni(2+). On the other hand, significant inhibition of bcl-2 occurred in HT 29 cells with simultaneous treatment of GSNO with Cu(2+) (or Ni(2+)). It seemed that Cu(2+) and Ni(2+) can enhance the decomposition of GSNO, which liberates NO to activate the pathways. Our results demonstrated that the apoptotic effects induced by GSNO were promoted by Ni(2+) and Cu(2+) through two different mechanisms: depletion of intracellular glutathione and triggering of NO release from GSNO, which then promotes NO-induced apoptosis in human cells.

Adenocarcinoma↗

PubMed1999

Autofluorescence spectroscopic differentiation between normal and cancerous colorectal tissues by means of a two-peak ratio algorithm.

We conducted an ex vivo study with light-induced autofluorescence spectroscopy to distinguish between normal and cancerous colorectal tissues. A total of 20 normal and 20 cancerous tissue samples were obtained from 20 patients undergoing oncologic surgery of the colon and rectum. The tissue diagnosis was confirmed histologically. After excitation, the autofluorescence spectra of each sample were measured and recorded. To determine the most appropriate excitation wavelength, we analyzed the autofluorescence spectra at excitation wavelengths of 280 to 400 nm, in 10-nm increments. To distinguish between normal and cancerous tissues, we first calculated the "two-peak ratio" (the ratio of the integrated intensity of the first peak +/- 6 nm to the integrated intensity of the second peak +/- 6 nm) of the autofluorescence spectra. By applying receiver operating characteristic (ROC) curves and calculating the areas under the ROC curves (AUC), we found 330 and 340 nm to be the most appropriate excitation wavelengths to distinguish between cancerous and normal colorectal tissue. When approximate thresholds were selected, autofluorescence spectroscopy with 330 nm excitation yielded a sensitivity of 85%, a specificity of 90%, and a positive predictive value of 89% for detection of cancerous tissue. The ex vivo autofluorescence study and two-peak ratio algorithm developed herein may be very useful for developing an algorithm for in vivo diagnosis of colorectal cancer.

Colorectal Neoplasms↗

PubMed1999

Induction of apoptosis by apigenin and related flavonoids through cytochrome c release and activation of caspase-9 and caspase-3 in leukaemia HL-60 cells.

The aim of this study was to investigate the mechanism of flavonoid-induced apoptosis in HL-60 leukaemic cells. Thus, the effect of structurally related flavonoids on cell viability, DNA fragmentation and caspase activity was assessed. Loss of membrane potential and reactive oxygen species generation were also monitored by flow cytometry. The structurally related flavonoids, such as apigenin, quercetin, myricetin, and kaempferol were able to induce apoptosis in human leukaemia HL-60 cells. Treatment with flavonoids (60 microM) caused a rapid induction of caspase-3 activity and stimulated proteolytic cleavage of poly-(ADP-ribose) polymerase (PARP). Furthermore, these flavonoids induced loss of mitochondrial transmembrane potential, elevation of reactive oxygen species (ROS) production, release of mitochondrial cytochrome c into the cytosol, and subsequent induction of procaspase-9 processing. The potency of these flavonoids on these features of apoptosis were in the order of: apigenin > quercetin > myricetin > kaempferol in HL-60 cells treated with 60 microM flavonoids. These results suggest that flavonoid-induced apoptosis is stimulated by the release of cytochrome c to the cytosol, by procaspase-9 processing, and through a caspase-3-dependent mechanism. The induction of apoptosis by flavonoids may be attributed to their cancer chemopreventive activity. Furthermore, the potency of flavonoids for inducing apoptosis may be dependent on the numbers of hydroxyl groups in the 2-phenyl group and on the absence of the 3-hydroxyl group. This provides new information on the structure-activity relationship of flavonoids.

Apigenin↗

PubMed1998

p53 point mutation enhanced by hepatic regeneration in aflatoxin B1-induced rat liver tumors and preneoplastic lesions.

Aflatoxin B1 (AFB1) is a well-known mutagen and carcinogen which induces human hepatocellular carcinoma (HCC). It has been found to be an important factor in inducing a high frequency of codon 249 mutation in the p53 gene. We characterized p53 mutations in specimens from preneoplastic lesions or tumors from the liver of rats induced by AFB1 with or without regeneration by partial hepatectomy treatment. PCR-SSCP and direct sequencing were used for screening and identification of p53 gene mutations in these samples. In rats treated with AFB1 with or without liver regeneration, 29% (5/17) of rats with hepatoma or neoplastic lesion had p53 mutation. No p53 mutations were found in the tumor samples from the rats without liver regeneration. However, in samples from the rats with liver regeneration, 38% (5/13) of the rats with hepatoma or neoplastic lesion were found to have p53 mutations. In one of these samples, we also observed a transversion mutation G --> T on codon 247, compared to codon 249 in humans. These findings suggest that the process of hepatocarcinogenesis induced by AFB1 does not necessarily involve p53 mutation, but mutation of the p53 gene can be enhanced by liver regeneration and that there is a possibility of a high mutability of the third base of codon 247, even though there is a small probability of detecting such a mutation in rats due to its silent mutation.

Aflatoxin B1↗

PubMed1998

Involvement of reactive oxygen species and caspase 3 activation in arsenite-induced apoptosis.

Recent studies indicate that arsenic may generate reactive oxygen species to exert its toxicity. However, the mechanism is still unclear. In this study, we demonstrate that arsenite is able to induce apoptosis in a concentration- and time-dependent manner; however, arsenate is unable to do so. An increase of intracellular peroxide levels was accompanied with arsenite-induced apoptosis, as demonstrated by flow cytometry using DCFH-DA. N-Acetyl-L-cysteine (a thiol-containing antioxidant), diphenylene iodonium (an inhibitor of NADPH oxidase), 4,5-dihydro-1,3-benzene disulfonic acid (a selective scavenger of O2-), and catalase significantly inhibit arsenite-induced apoptosis and intracellular fluorescence intensity. In contrast, allopurinol (an inhibitor of xanthine oxidase), indomethacin (an inhibitor of cyclooxygenase), superoxide dismutase, or PDTC had no effect on arsenite-induced cell death. Activation of CPP32 activity, PARP (a DNA repair enzyme) degradation, and release of cytochrome c from mitochondria to the cytosol are involved in arsenite-induced apoptosis, and Bcl-2 antagonize arsenite-induced apoptosis by a mechanism that interferes in the activity of CPP32. These results lead to a working hypothesis that arsenite-induced apoptosis is triggered by the generation of hydrogen peroxide through activation of flavoprotein-dependent superoxide-producing enzymes (such as NADPH oxidase), and hydrogen peroxide might play a role as a mediator to induce apoptosis through release of cytochrome c to cytosol, activation of CPP32 protease, and PARP degradation.

3T3 Cells↗

PubMed1998

Induction of apoptosis by thiuramdisulfides, the reactive metabolites of dithiocarbamates, through coordinative modulation of NFkappaB, c-fos/c-jun, and p53 proteins.

Prolinedithiocarbamate (PDTC) and diethyldithiocarbamate (DDTC) are cancer chemopreventive agents and can be biotransformed to prolinethiuramdisulfide (PTDS) and tetraethylthiuramdisulfide (disulfiram; DTDS), respectively. We found that the reactive metabolites PTDS and DTDS induced apoptosis after G1/S arrest. Phosphorylation of cyclin E, inhibition of cyclin-dependent kinase 2 activity, and degradation of cyclin E were found in human hepatoma Hep G2 cells during apoptosis. Moreover, PTDS and DTDS decreased the level of bcl-2 but increased the level of p53. In contrast, PDTC, DDTC, and ammonium dithiocarbamate (ADTC) did not induce apoptosis; rather they led to the induction of p53 and p21 followed by G1/S arrest. PDTC, DDTC, and ADTC also arrested cells in G1 phase. We then examined the effects of PTDS and DTDS on the signal transduction mechanisms leading to apoptosis. Although the transcription factors NFkappaB and AP-1 cooperatively decreased their DNA-binding activities to kappaB and 12-O-tetradecanoylphorbol-13-acetate-responsive elements, respectively, and p53 increased DNA-binding activity in the early stage but decreased it in the latter stage after treatment with PTDS, when the human Hep G2 cells were undergoing apoptosis. In summary, our results indicated that (i) PTDS and DTDS induced apoptosis and G1/S arrest mediated by p53, whereas PDTC, DDTC, and ADTC induced p53-dependent p21 expression leading to G1/S arrest; (ii) PDTC, DDTC, and ADTC induced p21/KIP1/CIP1 expression in a p53-dependent pathway leading to G1/S arrest; and (iii) NFkappaB, AP-1, and bcl-2 were downregulated during PTDS- and DTDS-induced apoptosis. These results suggested that PTDS and DTDS induced p53-dependent apoptosis, whereas PDTC, DDTC, and ADTC induced G1/S arrest. Apoptosis is regulated by the modulation of intracellular effectors such as NFkappaB, AP-1, and bcl-2 and activation of p53 in early stages.

Alcohol Deterrents↗

PubMed1998

Ketoconazole-induced apoptosis through P53-dependent pathway in human colorectal and hepatocellular carcinoma cell lines.

In this study, we first demonstrated that the widely used oral antifungal drug, ketoconazole (KT), can induce apoptosis in various type of human cancer cells and in a primary culture of rat liver cells. We further investigated the molecular mechanisms of KT-induced apoptosis. It was found that KT induced nuclear accumulation of p53 protein in a dose- and time-dependent manner. The level of p53 protein was elevated approximately three times as much in treated cells 24 h after KT (5 microM) exposure as in cells receiving mock treatment. We found that cells containing wild-type p53 (COLO 205 and Hep G2) were more sensitive to KT exposure. The bax protein was induced and the bcl-2 protein was inhibited by KT in cells containing wild-type p53 (Hep G2, COLO 205) but not in cells without p53 (Hep 3B). The caspase-3 was activated 24 h after KT treatment. The Poly-(ADP ribose) polymerase (PARP) and the lamin A degradation was induced by KT, which promoted nuclear membrane disassembly and eventually caused apoptosis. Our results also indicated that none of the PKC gene family was involved in KT-induced apoptosis.

Adenocarcinoma↗

PubMed1998

Oltipraz, a novel inhibitor of hepatitis B virus transcription through elevation of p53 protein.

Molecular epidemiological studies of populations at high risk for liver cancer have shown that hepatitis B virus (HBV) and aflatoxin B1 exposures are two major risk factors for this disease. Oltipraz is currently being considered for clinical trial to protect against aflatoxin B1-induced hepatocarcinogenesis based on its proven protective effect in many different animal models. In addition, oltipraz inhibits human immunodeficiency virus (HIV) replication. The inactivation of reverse transcriptase of HIV appears to be the antiviral mechanism. It has been demonstrated that a number of compounds that inhibit HIV replication also inhibit HBV replication in vitro. Therefore, we tested the possibility of oltipraz blocking HBV replication in 2.2.15 cells (clonal cells derived from HepG2 cells that were transfected with a plasmid containing HBV DNA) in vitro. Results of the experiments indicate that oltipraz has a dose-dependent inhibitory effect on HBV replication and specifically blocks HBV transcription in 2.2.15 cells. In addition, oltipraz induces endogenous wild-type p53 protein in a dose- and time-course-dependent manner. Taken together, we speculate that the effects of oltipraz against replication of HBV and specific blocking of HBV transcription may be through the induction of p53-mediated pathway in 2.2.15 cells. In addition to its known chemopreventive action on aflatoxin B1 hepatocarcinogenesis, oltipraz was shown here to inhibit HBV replication. These dual effects put oltipraz as the excellent candidate for the chemopreventive agent of human hepatocellular carcinoma.

Alleles↗

PubMed1998

Weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin in patients with advanced colorectal cancer: Taiwan experience.

Between January 1994 and November 1995, 41 patients with metastatic colorectal carcinoma were enrolled in this study. All these patients had recurrent disease after a prior 5-fluorouracil based adjuvant chemotherapy or failed to achieve response by prior chemotherapy that included 5-fluorouracil. 5-Fluorouracil, 2600 mg/m2, was administered concurrently with 100 mg/m2 leucovorin over 24 hours of continuous intravenous infusion. The treatment was repeated every week until progressive disease was documented. Forty-one patients received a total of 810 courses of treatment. The overall response rate was 17.1% (95% confidence interval 5.6-28.6%). In two patients who achieved complete response, the liver was the metastatic site. The median survival was 18.4 months for responders and 12.6 months for non-responders. Gastrointestinal toxicities including diarrhea, stomatitis, nausea and vomiting were the major side-effects. Sixteen incidences (39.0%) of grade 2-3 gastrointestinal toxicities were observed. One patient (2.4%) developed a grade 3 cardiac toxicity, and another one (2.4%) had a grade 2 neurotoxicity. Hematological toxicities were minimal with no evidence of severe (grade 2 or more) leukopenia or thrombocytopenia. We conclude that in patients with pretreated metastatic colorectal cancer, weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin is associated with higher efficacy and tolerable toxicity. This regimen is a good option as a second-line treatment for those whose diseases are recurrent from or refractory to prior 5-fluorouracil, and deserves a longer period of follow-up.

Adult↗

PubMed1998

Comparative investigation on the mutagenicities of organophosphate, phthalimide, pyrethroid and carbamate insecticides by the Ames and lactam tests.

The Salmonella lactam test is a newly developed method for detecting genotoxins. This technique is based on the ability of DNA damaging agents to reverse expression of the beta-lactamase gene, an important gene that enables microbes to resist beta-lactam antibiotics. A construct p-SELECT Control DNA plasmid containing a beta-lactamase gene site was constructed in many mutant forms, including point and frameshift mutants. These mutant constructs were introduced into Salmonella tester strains whose mutagenicity is based on their ability to reverse expression of the beta-lactamase gene. Fourteen pesticides were evaluated for genotoxicity using our newly developed Salmonella typhimurium strains JK947 and JK3, which are useful for detecting base substitution mutations. Six pesticides, namely allethrin, captan, folpet, monocrotophos, acephate and carbofuran, proved highly mutagenic in strain JK947, while the first four pesticides were more weakly mutagenic in strain JK3. In comparison, results from the Ames test show strain JK947 to be more sensitive to these pesticides than strains TA100 and TA1535. Strains TA98 and JK1 proved insensitive to allethrin, captan, folpet, acephate, carbofuran and monocrotophos. Among the many advantages of the lactam test are: large numbers of cells can treated and the test is operationally simple and inexpensive; revertant colonies form faster in the lactam test (16 h) than in the Ames test (48 h); the lactam test can detect mutagens present in biological specimens contaminated by histidine and biotin, samples that may give false positive results in the Ames test.

Ampicillin Resistance↗

PubMed1998

The changing pattern of intestinal tuberculosis: 30 years' experience.

SETTING: Although the incidence of tuberculosis had been decreasing for many years, it has recently risen. OBJECTIVES: To investigate the changes in the pattern and distribution of intestinal tuberculosis and to alert surgeons to the importance of maintaining a high index of suspicion for this disease entity. DESIGN: Retrospective analysis of 134 patients with intestinal tuberculosis discharged from the Veterans General Hospital in Taipei from 1965 to 1995. All records, bacteriological examinations and pathological specimens were reviewed and extracted onto a standard questionnaire. RESULTS: A decline in the case numbers of intestinal tuberculosis was noted after 1975. However, there seems to be a slight rise in case numbers since 1990. The average age of those patients after 1990 (64.8 years) is higher than those before 1990 (44.4 years). None of our patients had clinical signs of human immunodeficiency virus (HIV) infection. Most patients (81.3%, 109/134) had not received a definite diagnosis until surgery. Active pulmonary tuberculosis was found in 37 patients (29.1%). CONCLUSION: The possible reasons for the rise in cases of intestinal tuberculosis in our patients may be linked to an increased life expectancy, the reappearance of some formerly 'silent' tuberculosis cases, and relapse in patients having received incomplete antituberculosis chemotherapy. Its insidious and non-specific clinical presentation makes the diagnosis of intestinal tuberculosis difficult. An increased index of suspicion and greater familiarity with the disease may shorten the time of diagnosis and may also prevent some unnecessary operations.

Adolescent↗

PubMed1998

Serum endothelin and atrial natriuretic peptide in cirrhotic patients with ascites and hepatorenal syndrome.

BACKGROUND: The pathogenesis of cirrhotic ascites and hepatorenal syndrome remains unresolved. The involvement of both endothelin-1 and atrial natriuretic peptide have recently been suggested. This study investigated the concentrations of serum endothelin and atrial natriuretic peptide in cirrhotic patients. METHODS: Seven healthy subjects and 31 cirrhotic patients were studied. Cirrhotic patients were divided into three groups: Group I, 16 cirrhotic patients without ascites; Group II, 10 cirrhotic patients with ascites, but without hepatorenal syndrome; and Group III, five cirrhotic patients with hepatorenal syndrome and ascites. Their sera were analyzed for endothelin-1 and atrial natriuretic peptide concentrations. RESULTS: Cirrhotic patients with ascites, Group II and Group III, had higher plasma endothelin-1 concentrations (15.9 +/- 2.3 pg/ml and 24 +/- 2.1 pg/ml, respectively) than normal subjects and compensated cirrhotics (3.8 +/- 0.7 pg/ml and 6.4 +/- 1.1 pg/ml, respectively); p < 0.001). Atrial natriuretic peptide concentrations were also significantly higher in cirrhotic patients than in normal subjects (p < 0.025). Plasma endothelin-1 concentration had a negative correlation with creatinine clearance (r = -0.65, p < 0.001), as did atrial natriuretic peptide concentrations (r = -0.44, p = 0.012). Plasma endothelin-1 correlated significantly with atrial natriuretic peptide concentrations (r = 0.38, p = 0.035). CONCLUSIONS: Both endothelin-1 and atrial natriuretic peptide concentrations were elevated in cirrhotic patients with ascites and hepatorenal syndrome. Endothelin-1 may have a negative impact on renal function. Our data also suggested that impaired responsiveness rather than impaired secretion of atrial natriuretic peptide is responsible for sodium retention in cirrhotic patients with ascites.

Adult↗

PubMed1998

Irregular synchronous activity in stochastically-coupled networks of integrate-and-fire neurons.

We investigate the spatial and temporal aspects of firing patterns in a network of integrate-and-fire neurons arranged in a one-dimensional ring topology. The coupling is stochastic and shaped like a Mexican hat with local excitation and lateral inhibition. With perfect precision in the couplings, the attractors of activity in the network occur at every position in the ring. Inhomogeneities in the coupling break the translational invariance of localized attractors and lead to synchronization within highly active as well as weakly active clusters. The interspike interval variability is high, consistent with recent observations of spike time distributions in visual cortex. The robustness of our results is demonstrated with more realistic simulations on a network of McGregor neurons which model conductance changes and after-hyperpolarization potassium currents.

Nerve Net↗