The physical complications of alcoholism are numerous. It is still not clear why some alcoholic patients acquireDifferent mechanisms are probably involved in different alcocertain organ-specific complications of alcoholism hol-induced end organ diseases, such as those in the liver, whereas other alcoholic patients acquire different ones.pancreas, heart and neuromuscular system. It is still not As we know the liver alcohol dehydrogenase (ADH), clear why some alcoholic patients acquire certain organ-spealdehyde dehydrogenase (ALDH), and cytochrome cific complications of alcoholism, whereas other alcoholics ac-P4502E1 (P4502E1) are polymorphic at the ADH2, ADH3, quire different ones. and ALDH2 loci and the 5-flanking region of the Alcohol is metabolized in the hepatocyte via three path-P4502E1. The aim of this study was to investigate the ways: the alcohol dehydrogenase (ADH) pathway in the cytodifferences between Chinese alcoholic patients with cirsol, the microsomal ethanol oxidizing system in the endoplasrhosis and acute pancreatitis by studying the genetic mic reticulum, and catalase in the peroxisomes. ADH and polymorphisms of ADH2, ADH3, ALDH2, and P4502E1.the microsomal ethanol oxidizing system produce specific Genotyping of ADH2, ADH3, ALDH2, and P4502E1 was metabolic and toxic disturbances, and all three pathways reperformed using polymerase chain reaction-restriction sult in the production of acetaldehyde, which then is metabofragment length polymorphism (PCR-RFLP) methods on lized by aldehyde dehydrogenase (ALDH) into acetate.2-4 Acperipheral white blood cell DNA from 75 alcoholic cir-etaldehyde, a metabolite more toxic than alcohol itself, is one rhotic patients, 48 acute alcoholic pancreatitis patients, of several factors implicated in the onset or development of 19 heavy drinkers without liver disease or pancreatitis, cirrhosis.5 Genetic polymorphisms in ADH2, ADH3, and and 235 controls. The results showed that the frequen-ALDH2 and in the 5-flanking region of the human cytocies of the alleles ADH2*1 and ALDH2*1 in the alcoholic chrome P4502E1 gene (P4502E1) and its ethnic variations cirrhotic patients were significantly higher than those have been reported.2-14 A number of studies have looked for in the nonalcoholic controls. In acute alcoholic pancre-differences in alcohol metabolizing enzymes to explain susatitis patients, only the frequency of allele ALDH2*1, not ceptibility to alcoholism and to alcohol-induced liver dis-ADH2*1 was significantly higher than in the nonalco-ease. [3][4][5][9][10][11][12][15][16][17][18] We previously reported that the ADH2*1, holic controls. The allele frequency of ADH2*1 in acute ADH3*2, and ALDH2*1 genes can affect predisposition to pancreatitis patients was significantly lower (P õ .01) alcoholism in Chinese patients. 15 In that study, we investithan in alcoholic cirrhotic patients. The daily amount of gated only alcohol-induced cirrhotic patients but no other alcohol consumption was significantly lower in patients subpopulation of alcoholic patients with differ...
Abstract. Isoniazid (INH) and rifampicin (RIF) are the first-line drugs for antituberculosis (anti-TB) chemotherapy. The levels of serum transaminases [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] are abnormal in 27% of patients undergoing INH and RIF treatments and in 19% of patients undergoing treatment with INH alone. Cytochrome P450 2E1 (CYP2E1) metabolizes many toxic substrates, including ethanol, carbon tetrachloride, and INH, which ultimately results in liver injury. The objective of this study was to screen for CYP2E1 inhibitors in vitro and investigate whether the selected compound could prevent INH/RIF-induced hepatotoxicity in vivo. We screened 83 known compounds from food and herbal medicines as inhibitors of CYP2E1. The hepatotoxic dose of INH/RIF was 50/100 mg kg −1 day −1 . Hepatotoxicity was assessed using galactose single-point (GSP) method (a quantitative measurement of liver function), histopathological examination of the liver, malondialdehyde (MDA) assay, and measurement of AST and ALT activities. Kaempferol inhibited CYP2E1 activity in mice by 0.31-to 0.48-fold (p<0.005). Mice with INH/RIF-induced hepatotoxicity showed significantly abnormal serum levels of AST and ALT, and GSP value, and these values could be decreased by the administration of kaempferol (p<0.005). Kaempferol significantly reduced the depletion of hepatic glutathione and prevented the increase in MDA formation in mice. Furthermore, kaempferol did not affect the anti-TB effects of INH/RIF. To our knowledge, this is the first report of kaempferol's utility as an adjuvant for preventing CYP2E1-mediated hepatotoxicity induced by drugs such as INH and RIF.
We examined the ability of purified protein derivative (PPD) of Mycobacterium tuberculosis to induce transforming growth factor 1 (TGF-1), a potent immunosuppressive and macrophage-deactivating molecule, in blood monocytes from healthy individuals. TBF-1 activity in PPD-induced monocyte supernatants was identified by Western immunoblot analysis and was not inhibited by polymyxin B, an inhibitor of bacterial lipopolysaccharide (LPS). Furthermore, PPD at equivalent amounts in weight to LPS was as potent in stimulation of monocyte production of TGF-1 at 24 h of culture, as quantified by enzyme-linked immunosorbent assay. The inducing effect of PPD, in contrast to that of LPS, was sustained at later time points of culture (72 h). PPD enhanced the constitutive expression of TGF-1 steady-state mRNA in monocytes at 24 and 48 h of culture. In contrast, neither mycobacterial heat shock protein (64-kDa protein of M. bovis) nor LPS induced TGF-1 mRNA. Decay studies suggested a transcriptional rather than a posttranscriptional effect of PPD on TGF-1 gene expression.
A splice variant of CD44 (exon V4-V7) confers metastatic behavior in a rat carcinoma model; aberrant expression of splice variants has been detected on a variety of human tumor cell lines as well as primary and metastatic human tumors, including lymphomas, carcinomas (colon, thyroid, mamma, bladder), and glioma. We used enzyme-linked immunosorbent assay to determine the concentration of soluble CD44 in the serum samples of 10 normal individuals and 41 patients with various stages of gastric cancer. Soluble CD44S and its isoforms, V5 and V6, were present in the serum of normal individuals (288.53 +/- 18.33, 25.49 +/- 1.70, and 148.32 +/- 3.15 ng/ml, respectively). The concentrations of soluble CD44 V5 and V6 were elevated in patients with advanced gastric carcinoma (69.39 +/- 6.06 and 216.62 +/- 32.98 ng/ml, respectively). Serum CD44 V5 concentrations correlated with the extent of tumor invasion (T), the status of lymph node involvement (N), and distant metastasis (M) (TNM staging) (p< 0.05), whereas CD44S did not. These results suggest that detection of abnormal regulation of CD44 splicing could be helpful in gastric cancer diagnosis and disease evaluation.
Summary The presence of tumour cells in the blood circulation may predict disease recurrence and metastasis. We have evaluated the specificity and sensitivity of detecting hepatoma cells in blood using nested polymerase chain reaction with primers specific for the alphafetoprotein (AFP) gene. The nested polymerase chain reaction amplified a 270-base pair AFP DNA fragment from cDNA of Hep 3B hepatoma cells. In a reconstitution experiment, AFP mRNA was detected from peripheral mononuclear cells isolated from 10 ml of blood containing as few as ten Hep 3B cells. Peripheral mononuclear cells from the blood of 20 hepatoma patients were analysed, and 19 patients showed positive AFP mRNA expression. Seven of 13 samples from hepatitis patients also showed positive AFP mRNA expression. All five paired samples of peripheral blood or umbilical cord blood from pregnant mothers and their babies, respectively, showed positive AFP expression. None of 22 control samples was positive. The presence of AFP mRNA in the blood of hepatitis or hepatoma patients suggests the presence of circulating hepatoma cells or hepatocytes in the circulation. The high incidence of AFP mRNA in the blood of hepatoma patients supports the notion of early haematogenous spreading of the disease.Keywords: alphafetoprotein; hepatocellular carcinoma; hepatitis; polymerase chain reaction Hepatocellular carcinoma (HCC) is one of the most common malignancies in Taiwan, mainland China and southern Africa. The disease is highly associated with hepatitis B and C virus infections as well as with the carcinogen aflatoxin (Chen, 1987). Despite improved survival of some cancer patients in recent years, the therapeutic efficacy for HCC remains very limited. Survival after the onset of symptoms is only a few months (Lai et al, 1987). It is therefore important to establish techniques for the early diagnosis of HCC.Alphafetoprotein (AFP) is a glycoprotein that is normally expressed during embryogenesis. The concentration of AFP in serum decreases as the liver develops and matures. However, AFP levels can become elevated in some disease states, particularly in HCC (Bellet et al, 1985;Chen, 1987;Di Bisceglie and Hoofnagle, 1989). Elevated serum AFP is employed as a highly specific and sensitive marker for the diagnosis of HCC, as about 82% of HCC patients have elevated serum AFP levels (Bellet et al, 1985). However, AFP can also be elevated in non-malignant forms of liver disease, such as acute and chronic hepatitis and cirrhosis (Chen, 1987;Di Bisceglie and Hoofnagle, 1989). In addition, increasing AFP levels have also have been associated with liver regeneration (Silver et al, 1974).A major characteristic of cancer is the ability of tumour cells to metastasize to other sites. The process of tumour metastasis involves multiple host-tumour interactions, and it is thought that (Chen, 1987). To understand stage tumour progression better, several laboratories have reported using the polymerase chain reaction (PCR) to detect metastatic cells in peripheral blood or lymph nod...
The human cytochrome P4502E1 gene (P4502E1), coding for an ethanol-inducible nitrosamine-metabolizing P-450, is involved in the metabolism of ethanol and many known carcinogens. Recently, restriction fragment length polymorphisms (RFLPs) within the P4502E1 have been suggested as genetic markers of susceptibility to alcohol-induced liver disease but the previous studies disagree whether alcoholics with c1 or c2 allele are more susceptible to alcohol-induced liver diseases. Using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, we determined the RsaI and PstI polymorphism of P4502E1 in 77 Chinese alcoholic patients (54 with alcohol-induced cirrhosis and 23 with acute alcohol-induced pancreatitis) and 164 non-alcoholics and compared them with previously published data. The PCR-RFLPs showed three P4502E1 genotypes: type A, homozygote c1/c1; type B, heterozygote c1/c2; and type C, homozygote c2/c2. The RsaI and PstI polymorphism of P4502E1 were completely linked in both Chinese alcoholics and nonalcoholic controls. The rare allele (c2) occurs at similar frequency of 0.232 and 0.234 (P > .05) in nonalcoholic controls and alcoholics, respectively. The genotype distributions of P4502E1 between Chinese alcoholics and nonalcoholics are not significantly different. The genotype and allele frequencies of P4502E1 for Chinese are significantly different from those of Swedes, European-Americans, and African-Americans, respectively (P < .00001), but very similar to Japanese (P > .05). In conclusion, ethnic variations exist between Asians and Caucasians and between Asians and African-Americans. No allelic variants at loci associated with RsaI/PstI RFLPs result in phenotypes displaying greater susceptibility to alcohol-induced cirrhosis or alcoholism in Chinese populations, which contradicts previous reports from Japanese groups.
A 64-year-old married female was admitted with a presentation of anorexia, easy fatiguability, skin discoloration, tea-colored urine and weight loss of 1 month's duration. After a series of clinical and laboratory examinations including radiological image studies, a diagnosis of gall bladder tumor was presumed. A final diagnosis of tuberculosis of the liver and gall bladder was established by histopathological examination of tissue specimens obtained during exploratory laparotomy. Hepatobiliary tuberculosis presenting as a gall bladder tumor is rare and no pathognomonic diagnostic characteristics can be relied upon. It is necessary to confirm the diagnosis by histopathology, polymerase chain reaction (PCR), or microbiological studies on biopsy specimens in order to make possible appropriate, early therapy.
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