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Biomedical subjects

V Thakur

Publications and source records attributed to V Thakur.

At least 19 recordsLinked to original sources
PubMed2004

Absence of hemochromatosis associated Cys282Tyr HFE gene mutation and low frequency of hemochromatosis phenotype in nonalcoholic chronic liver disease patients in India.

BACKGROUND AND AIM: Hereditary hemochromatosis (HHC) is an autosomal recessive disorder causing primary iron overload syndrome and chronic liver disease (CLD). This genetic disease is commonly associated with C282Y mutation of the HFE gene, commonly seen in the Northern European population. Minor reports on HHC are available from Asia, however, so far no genetic study is available from India. We prospectively studied the prevalence of C282Y mutation in CLD patients and healthy subjects in a tertiary care referral center in India. METHODS: A total of 249 consecutive biopsy proven CLD (HBV = 112, HCV = 72, cryptogenic = 65) patients and 134 age matched healthy controls were included. Cases of secondary iron overload, pregnancy, chronic alcoholism, age < 30 years and hepatocellular carcinoma (HCC) were excluded. A transferrin saturation index (TSI) of >60% was suggestive of a phenotypic presentation of HHC. C282Y mutation was studied by restriction fragment length polymorphism (RFLP) using genomic DNA. The 387 bp fragment obtained after polymerase chain reaction was digested with 10 units of endonuclease Rsa1. The mutation was detected by creation of an additional restriction site, giving rise to fragments of 247 111 and 29 bp. RESULTS: While the mean TSI was comparable, serum ferritin was significantly higher in CLD patients compared to controls (38 +/- 16%vs 28 +/- 13%; p = not significant (NS), and 125 +/- 18 vs 42 +/- 25 ng/mL; p < 0.001). A TSI of >60% was detected in 24 (9.64%) patients. Only one restriction site was found for endonuclease Rsa1, giving rise to two fragments of 247 and 140 bp, suggesting absence of C282Y mutation in the HFE gene in all patients. CONCLUSIONS: Almost 10% of nonalcoholic CLD patients in India have iron overload, but this is independent of C282Y mutation of the HFE gene. Large population based studies are recommended to investigate the prevalence of this rare disorder in India.

Adult↗
PubMed2002

Renal and cardiovascular considerations for the nonpharmacological and pharmacological therapies of obesity-hypertension.

Obesity-associated hypertension is a common disease that involves a complex pathogenesis. Failure to control hypertension (HTN) in obese subjects provides a great threat to their renal and cardiovascular functions. The treatment of obesity-associated HTN is often difficult, and requires nonpharmacological and/or pharmacological approaches. Weight reduction is the cornerstone of the therapies of obesity-HTN, as it reverses the multiple components of its pathogenesis. When weight loss cannot be sustained or fails, pharmacological means should then be used. Angiotensin-converting enzyme inhibitors (ACEI) are the drug of choice: they can reduce blood pressure, protect the kidney and heart, and improve the metabolic abnormalities in obese subjects. Angiotensin-2 type-1 receptor blockers have a renoprotective benefit similar to ACEI, and they provide an important alternative to the use of ACEI. Diuretics are very effective in African-American obese hypertensives, but small doses should be used to avoid adverse effects on metabolic profiles. Long-acting calcium channel blockers are also effective and have the advantage of no adverse metabolic effects. Nondihydropyridine calcium channel blockers may provide additional renal and cardiovascular protective effects. The beta-adrenergic receptor blockers can cause further weight gain and metabolic abnormalities in obese subjects; therefore, careful monitoring is needed. There are few clinical data that support the efficacy and benefit of centrally acting alpha-2 agonists and alpha-adrenergic receptor antagonists in the treatment of obesity-HTN.

Cardiovascular Physiological Phenomena↗
PubMed2002

Correlation between serum magnesium and blood cyclosporine A concentrations in renal transplant recipients.

BACKGROUND: Low total serum magnesium concentration has been reported in renal transplant recipients on cyclosporine therapy, and this is a risk factor for hypertension and cardiac death. No study is yet available from the Indian subcontinent on the relationship between total serum magnesium and cyclosporine A concentration. METHODS: Blood cyclosporine A and total serum magnesium concentrations were estimated in 31 post renal transplant patients. Sixteen chronic renal failure patients who had not yet received a transplant served as controls. RESULTS: The mean total serum magnesium in post-transplant patients was 0.64+/-0.11 mmol/L (n = 31), which was significantly lower (P <0.001) than in the controls (1.0+/-0.16 mmol/L). An inverse correlation was found between total serum magnesium and blood cyclosporine A concentration (r = -0.532). Systolic and diastolic blood pressures were also higher in the cyclosporine-treated patients. CONCLUSIONS: We conclude that serum magnesium should be monitored regularly in patients receiving cyclosporine A.

Adult↗
PubMed2002

Clinical implications of viral activity in dual infection with hepatitis B and C in chronic liver disease.

BACKGROUND: There is limited information on the clinical and biochemical profile of chronic liver disease due to dual infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. There are variable reports on the severity of liver disease in dual infections. This is important, from clinical and therapeutic point of view. The present study analyzes liver disease in dual infections as compared to HBV and HCV infection present alone. MATERIAL AND METHODS: Out of 186 histologically proven non-alcoholic chronic liver disease patients, 30 (16.1%) were serologically diagnosed to be HBV and HCV dual infection (Group A, n=30). The clinical profile of these patients was compared with consecutively seen HBV related (Group B, n=30) and HCV related chronic liver disease (Group C, n=30) patients. Patients with dual infection were further grouped based on predominant HBV or HCV viral activity. RESULTS: Patients with dual infection were younger than those with chronic HCV infection (38.4 +/- 14.4 vs. 45.9 +/- 14.7 years, p < 0.05); with male predominance (p=0.06). Patients with chronic HCV infection more often presented with low-grade fever than dual infection group (60% vs. 30%, p < 0.05). Ascites and variceal bleeding were common presentations of HBV related cirrhosis. Patients with dual infection had significantly more deranged liver functions. The duration of illness was shorter in these patients compared with chronic HCV (2.9 +/- 1.6 vs. 7.3 +/- 1.4 year, p < 0.05). When patients with dual infection were subgrouped on HBV DNA and HCV RNA positivity, there was a tendency for increased biochemical derangement with active HBV infectionity. CONCLUSIONS: Our results highlight the fact that patients with HBV and HCV dual infection related chronic liver disease have a more aggressive course. There is a tendency for a more severe liver disease when HBV is active in the dual infection group.

Adult↗
PubMed2002

High seroprevalence and clinical significance of hepatitis B and C infection in hospitalized patients with alcoholic cirrhosis.

OBJECTIVES: Patients with alcoholic cirrhosis (AC) are frequently infected with hepatotropic viruses which could alter the clinical spectrum of the disease. We studied the seroprevalence of hepatitis B (HBV) and hepatitis C virus (HCV) and their impact on the clinical profile of patients with AC. METHODS: Two hundred and ten hospitalized patients of AC were studied and screened for markers of HBV and HCV infection. Clinical, biochemical and virological correlation was done. RESULTS: One hundred and forty (66.6%) patients had no viral infection Group I, 50 (23.8%) were positive for HBsAg Group II and 20 (9.5%) for anti-HCV Group III. All patients were males with comparable ages (43.9 years, 44 years and 45.9 years respectively). The amount of alcohol consumed by patients in Group III (130 +/- 115 g/d) was significantly less than Group II (204 +/- 130 g/d, P < 0.05) and Group I (281 +/- 188 g/d, p < 0.001). The duration of alcohol abuse was shorter in Group II and III, although not statistically significant. Presentation as jaundice was common in Group II and III (p < 0.05). The AST and ALT values (IU/L) were significantly higher in Group II (239 +/- 351, 197 +/- 266) and III (157 +/- 170, 86 +/- 52) than Group I (89 +/- 78, 66 +/- 54) (P < 0.05). The serum alkaline phosphatase (IU/L) was higher in Group III (349 +/- 223) as compared to Group II (263 +/- 186) and Group I (162 +/- 62) (P < 0.05). There was however, no difference in Child's grade or the discriminant function between the three groups of patients. CONCLUSIONS: (i) One-third of the hospitalized patients with AC are infected with HBV or HCV infection, (ii) these infections hasten clinical presentation of patients with alcoholic liver disease, with lesser amount of alcohol consumption and (iii) jaundice, raised ALT/AST and alkaline phosphatase are more common with superadded viral infection.

Adult↗
PubMed2001

Seizure activity results in increased tyrosine phosphorylation of the N-methyl-D-aspartate receptor in the hippocampus.

Systemic administration of kainic acid (KA) induces status epilepticus (SE) that causes neurodegeneration and may subsequently lead to spontaneous recurrent seizures. We investigated the effects of KA-induced SE on tyrosine phosphorylation and solubility properties of the NMDA receptor. Following 1 h of SE, total protein tyrosine phosphorylation was elevated in both the hippocampus and frontal cortex relative to controls. Tyrosine phosphorylation of the NMDA receptor subunits NR2A and NR2B was also enhanced following SE. Animals that received KA but did not develop SE, did not exhibit increased tyrosine phosphorylation. SE resulted in a decrease in the solubility of NMDA receptor subunits and of PSD-95 in 1% deoxycholate. In contrast, the detergent solubility of AMPA and kainate receptors was not affected. These findings demonstrate that SE alters tyrosine phosphorylation of the NMDA receptor, and indicate that the interaction of the NMDA receptor with other components of the NMDA receptor complex are altered as a consequence of seizure activity.

Animals↗
PubMed2001

Subtotal hysterectomy for uterine rupture.

OBJECTIVE: The aim of this paper was to stratify patients with uterine rupture in extremis (with hypotension, change in vital organ function, and altered mental status) and evaluate outcome for patients undergoing subtotal hysterectomy (STH) vs. uterine repair (UR). METHODS: Of 39667 hospital deliveries between 1993 and 1998 at a university hospital, 367 presented with uterine rupture. Of these, 96 presented in extremis and had an irregularly torn uterus found at operation. Charts were retrospectively reviewed to stratify patient population with uterine rupture and their outcome. Results were analyzed using Fisher's exact test. RESULTS: Patients with uterine rupture were 31-35 years old, para> or =3, had received no antenatal care, and presented with rupture in the lower uterine segment. Sixty-one patients underwent STH while 35 underwent UR. The groups were similar with respect to patient age, parity, cause of rupture, and clinical condition at the time of evaluation (P=0.2). The operative time for STH was significantly less than UR, 35 min vs. 75 min (P<0.01). Maternal mortality was significantly higher in patients undergoing UR vs. STH, 46% vs. 20% (P=0.01). Maternal morbidity occurred in 30% of patients undergoing STH vs. 50% in patients undergoing UR (P=0.01). The time to discharge was significantly less in patients undergoing STH compared to UR, 14.5 days vs. 27 days (P<0.01). CONCLUSIONS: Patients with uterine rupture in extremis tend to be young, multiparous, receive no antenatal care, and have uterine rupture of the lower segment. STH significantly lowered operative time, morbidity, time to discharge, and mortality than UR in patients in extremis with uterine rupture.

Adult↗
PubMed2001

Base-pair alterations in the epsilon-lower stem due to a novel double substitution in the precore gene of HBV-e negative variant were recovered by secondary mutations.

The HBe negative phenotype, a natural precore mutant (G1896A/G1897A) of HBV with aborted HBeAg expression is known to cause chronic hepatitis. The destabilized C : G base-pairing in the lower stem of epsilon-hairpin due to G1896A substitution is reportedly compensated by a second C1858T mutation and suggested to play an important role in enhanced selection of the HBe negative variant. We undertook to investigate presence of such compensatory mutations at other positions by analyzing epsilon-sequences (nts. 1847-1907) as well as to look for their effect(s), if any, on the consensus sequence of the overlapping core-initiator of HBe negative HBV variants in CLD patients. Three of the 5 HBe negative patients had classical G1896A mutation having a second compensatory mutation at nt. 1858. One patient showed an additional G1897A substitution, presenting as a novel precore stop codon mutation (UGG-->UAA), followed by a compensatory mutation at position 1857. In the third patient, a G1899A substitution was seen which compensated the impaired U at position 1855. Other substitution and deletion mutations were also observed in the remaining epsilon-hairpin, which however, did not produce any compensatory mutation. Further, all the precore variants showed a conserved G at position 1904, important for the optimal context of their core-initiator which however, remained impaired with A (nt. 1850). Our results suggest that the nts. 1851-1859 and nts. 1895-1904 in the lower stem, and restoration of authentic base-pairings therein, maintain the structural integrity and stability of the epsilon-hairpin. This may have a role in the enhanced selection of the HBe negative variants and persistence of HBV infection in chronic liver disease patients.

Base Pairing↗
PubMed2001

Profile of hepatocellular carcinoma in India: an insight into the possible etiologic associations.

BACKGROUND: Several etiologic factors including hepatitis viruses, alcohol and aflatoxin have been implicated in the pathogenesis of hepatocellular carcinoma (HCC). There is, however, limited information from the Indian subcontinent. METHODS: Seventy-four consecutive cases of HCC were studied. A detailed history, tests for hepatitis B virus (HBV; HBsAg, HBeAg, anti-HBe, IgG anti-HBc, anti-HBs and HBV-DNA), hepatitis C virus (HCV; anti-HCV and HCV-RNA) infection, liver histopathology and HBV-DNA integration by using Southern blot hybridization were studied. A p53 gene mutation was also studied by using PCR and single-strand conformation polymorphism. RESULTS: Hepatocellular carcinoma patients were predominantly males (mean age 49.5 +/- 14.0 years). Portal hypertension and cirrhosis were seen in 56 (76%) patients, more often (P < 0.05) in viral marker positive cases. Forty-five percent of patients had features of hepatic decompensation at presentation. Evidence of HBV infection was present in 53 (71%) patients. Twenty-six (49%) of these patients had either HBeAg + ve, HBV-DNA + ve (n = 12), or HBsAg - ve, HBV-DNA + ve (n = 14) forms of HBV infection. Hepatitis B virus DNA integration in the liver tissue was seen in 10 of 17 (59%) patients. Infection with HCV alone was detected in three (4%) and dual HBV and HCV infection in six (8%) patients. A majority (78.5%) of the chronic alcoholics had associated viral infection. The etiology of HCC remained undetermined in 15 (20%) patients. The p53 gene mutations were detected only in three of 21 (14%) liver tissues. Aflatoxin toxicity, oral contraceptive use or metabolic disorder were not seen. CONCLUSIONS: In India: (i) HBV infection is the predominant factor for the development of HCC, often related to mutant forms of HBV; (ii) a majority of the HCC patients have overt cirrhosis of the liver; and (iii) HCV and alcohol per se are uncommonly associated.

Aflatoxin B1↗
PubMed2001

Gene transfer to the embryo: strategies for the delivery and expression of proteins at 48 to 56 hours postfertilization.

BACKGROUND/PURPOSE: Although gene and protein transfer may potentiate the cure of genetic disease, current strategies involving fetal gene therapy remain nonfocal and confounded by the lack of imaging techniques and in vivo markers for precise gene transfer. METHODS: Fourteen white Leghorn chick eggs were incubated for 48 to 56 hours postfertilization until they reached stages 11 to 16, about 3 mm in size. In 7 chick embryos, a glass needle was placed at the midbrain/hindbrain level and 1 x 10(7) pfu of an adenovirus containing the green fluorescent protein (GFP) reporter gene was injected into the lateral head. In another 7 chicken embryos, colored agarose beads coated with Sonic hedgehog (Shh) protein were implanted at the level of the hindbrain under direct microscopy. The eggs were then sealed, incubated at 37 degrees C for 24 hours, and reimaged using fluorescent microscopy and confocal laser microscopy. RESULTS: At 24 hours postinjection, all embryos were alive and were imaged in vivo. Fluorescent microscopic imaging showed green fluorescence in the region of the injection site in all the embryos. In embryos that underwent bead placement, the beads were visualized under microscopy in the lateral hindbrain of all embryos, and the presence of the Shh protein was confirmed using fluorescein isothiocyanate (FITC)-conjugated secondary antibody. CONCLUSIONS: This study shows that embryonic 3-mm chick embryos survive adenoviral transduction or agarose bead implantation in a focal manner in vivo and that this delivery results in production of imageable levels of protein. This may be used in mammalian systems, including humans, to introduce genes and proteins.

Animals↗
PubMed2001

Enhanced immunogenicity of recombinant hepatitis B vaccine in exposed family contacts of chronic liver disease patients.

Close family contacts of hepatitis B virus (HBV)-related chronic liver disease patients have a high risk of exposure to HBV. Variable responses to vaccination have been reported in family contacts, especially in previously exposed contacts (IgG antiHBc-positive). Seventy-nine healthy family contacts, who were HBsAg-negative with normal alanine amino-transferase level and no evidence of liver disease, were vaccinated using a recombinant HBV vaccine, irrespective of past exposure status. A significantly higher number of previously exposed subjects (n = 25; Group I) developed early seroprotective anti-HBs titers with 2 initial doses of vaccine compared to the unexposed contacts (Group II; n = 54) (64% vs. 33%, respectively; P < 0.05). However, the responses were comparable on completion of the schedule (96% vs. 94%, respectively). HBV DNA was detected in 11 of 25 (44%) exposed and none of the unexposed contacts at baseline. Post-vaccination, 3 of 11 (27%) subjects became HBV DNA-negative and remained negative for the next 12 months. These results suggest that exposed family contacts achieve efficient seroprotection after HBV vaccination, irrespective of the IgG anti-HBc status. The response to vaccination resembles an anamnestic reaction and possibly demonstrates a therapeutic effect.

Adolescent↗
PubMed2001

Obesity, hypertension, and the heart.

Hypertension occurs more commonly in obese than in lean persons at virtually every age. A variety of endocrine, genetic, and metabolic mechanisms have been linked to the development of obesity hypertension. These include insulin resistance and hyperinsulinemia, increased serum aldosterone levels, salt sensitivity and expanded plasma volume in the presence of increased peripheral vascular resistance, a genetic predisposition, and possibly increased leptin levels. Pressure and volume overload are present in obese hypertensives. This leads to a mixed eccentric-concentric form of left ventricular hypertrophy and increases the predisposition to congestive heart failure. Weight loss, even in modest decrements, is effective in reducing obesity-hypertension, possibly by ameliorating several of the proposed pathophysiologic mechanisms. There are currently no specific recommendations concerning pharmacotherapy of obesity-hypertension because each drug group has pros and cons.

Antihypertensive Agents↗
PubMed2001

Elevated serum cancer antigen 125 levels in advanced abdominal tuberculosis.

A 48-yr-old female presented with a 1-yr history of pain in the hypochondrium and epigastrium. All routine investigations and computed tomography (CT) of the abdomen were done. CT findings revealed a well-defined cystic mass in the right ovary, and ascitis with features suggestive of secondaries over the omentum and peritoneal surface. The serum CA125 was 1255 U/mL (normal range 0-35 U/mL), which was indicative of ovarian malignancy. An exploratory laparotomy was performed. Histopathological examination of organs revealed the presence of granuloma. The patient was advised to undergo antitubercular treatment (ATT) and follow-up every month. After 1 mo of ATT, the CA125 level came down to 42 U/mL, which was near normal. As tuberculosis requires only a conservative management, we suggest that in cases of abdominopelvic mass with or without ascitis, high serum CA125 should always raise a suspicion of tuberculosis and a laparoscopy combined with peritoneal biopsy should be performed to confirm the diagnosis. This will prevent unnecessary laparotomies. Moreover, serum CA125 can be used to monitor the response of disease to antitubercular treatment.

Adnexal Diseases↗
PubMed2000

Ontogeny of insulin-like growth factor 1 in a rabbit model of growth retardation.

Many cases of intrauterine growth retardation (IUGR) result from placental insufficiency, but the molecular signals accompanying this event are unknown. Insulin-like growth factor 1 (IGF-1) is a potent mitogen for fetal tissues and is lowered in the serum of human infants with IUGR. The rabbit provides an optimal model for the study of IUGR based on fetal position. To determine if IGF-1 expression is altered in the growth-retarded fetus, this naturally occurring rabbit model of IUGR was used. Four fetal rabbit pairs were harvested on Days 21, 23, 25, 27, 29, and 31 of their normal 31-day gestation; they were identified based on uterine position as normal or growth retarded. Fetal weight was recorded and the serum, amniotic fluid, liver, kidney, and small intestine (SI) were collected. The SI was divided into three equal segments: proximal, middle, and distal. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure IGF-1/beta-actin mRNA densitometric band ratios in all tissues. Radioimmunoassay (RIA) was used to measure IGF-1 protein levels in the serum and amniotic fluid. Statistical analysis was performed using ANOVA and the paired Student's t test. Weights were decreased in fetuses with IUGR at all time points (P < 0.05), further validating this rabbit model in the study of IUGR. Liver, proximal, and distal SI IGF-1 mRNA decreased during late gestation (P < 0.01). Kidney IGF-1 mRNA increased throughout late gestation (P < 0.01). Compared with their normal counterparts, fetuses with IUGR had a trend toward decreased IGF-1 mRNA in the kidney, liver, and SI at all time points, reaching significance in the liver on Day 27 (P = 0.002). Serum IGF-1 decreased throughout gestation in all fetuses (P < 0.05). Compared with normal fetuses, fetuses with IUGR had lower serum IGF-1 at all time points, reaching significance at Day 27 (P = 0.02). Amniotic fluid IGF-1 was lower in fetuses with IUGR than in normal fetuses, though not quite reaching significance. Compared with normal fetuses, growth-retarded fetal rabbits trend toward depressed liver, kidney, and intestinal expression of IGF-1 mRNA and lower serum and amniotic fluid IGF-1 protein. Serum IGF-1 levels correlate with fetal weight change. Further studies and potential manipulation of fetal IGF-1 are warranted to investigate potential prenatal intervention in the treatment of IUGR.

Amniotic Fluid↗
PubMed2000

The outcome of research training during surgical residency.

BACKGROUND/PURPOSE: Graduates of a university surgical residency program were surveyed to identify the timing of specialty selection and the impact that studying in a research laboratory had on subsequent acceptance into a fellowship program. METHODS: Between 1975 and 1990, 86 residents completed general surgery training at UCLA Medical Center. A survey was sent to all graduates to determine the focus of their previous laboratory research and when they selected their eventual surgical specialty. Responses were received from 67 of the 86 graduates (78%). RESULTS: Forty-eight of the sixty-seven respondents (72%) took one or more years of surgical research during residency. Postresidency fellowship training was selected by 55 of 67 (82%); 50 applied to fewer than five programs; 49 of 55 (89%) received one of their top three choices. Twenty-seven of the sixty-seven residents pursued an academic career (40%). Residents who performed at least 2 years of research were more likely to become academicians (53%) than residents who did 1 year or less of research (22%). Only 39 of 67 residents (58%) had selected a specialty after 2 years of clinical training; 28 more made the selection after the third clinical year. All residents interested in cardiac surgery (n = 18) or plastic surgery (n = 4) prior to research were accepted into fellowships in those specialities, whereas only 37% of those who had an interest in other fields pursued the same specialty (P < 0.0001). Residents performing research in general surgery (n = 9), surgical oncology (n = 18), cardiac surgery (n = 14), and plastic surgery (n = 3) were more likely to practice in that specialty than those doing research in other specialty laboratories. CONCLUSIONS: General surgery residents performing research in a specialty laboratory are likely to pursue fellowship training relating to that field. Those who select a career in cardiac or plastic surgery prior to research are most likely to enter into these fields as their eventual specialty. Residents who perform 2 or more years of laboratory research publish more papers and often pursue an academic career.

General Surgery↗
PubMed2000

P53 tumor suppressor gene mutations in hepatocellular carcinoma patients in India.

BACKGROUND: Specific mutations of the p53 tumor suppressor gene in hepatocellular carcinoma (HCC) have been reported from several parts of the world, but to the authors' knowledge to date the status of this gene has not been studied in HCC patients in India, where HCC is one of the major cancers and the frequency of chronic hepatitis B virus (HBV) as well as hepatitis C virus (HCV) infection and exposure to dietary aflatoxin B(1) is very high. The most frequent mutation of the p53 gene in HCC is an AGG(Arg) to AGT(Ser) missense mutation at codon 249 of exon 7. METHODS: Liver biopsy specimens from 21 HCC patients and 10 healthy controls were obtained through surgery or by needle biopsy technique. Phenol-chloroform-extracted DNA specimens were employed for the detection of HBV infection and p53 gene mutations. Nucleotide mutations of exons 4-9 of the p53 gene were analyzed by polymerase chain reaction (PCR), single strand confirmation polymorphism, and direct sequencing. Third-generation sandwich enzyme-linked immunosorbent assay (ELISA) was used for the serologic detection of HBV and HCV infection. RESULTS: Analysis of exons 4-9 of the p53 gene revealed only 3 mutations (3 of 21 specimens, 14.28%; 95% confidence interval, -0.7-29.3), 2 mutations at codon 249 showing G-->T transversions, and 1 mutation (4.7%) at codon 250 with a C-->T transition. The base substitutions at the third base of codon 249 resulted in a missense mutation leading to a change in amino acid from arginine to serine whereas at codon 250 it caused a change from proline to serine. Dot blot hybridization and PCR for HBV DNA from HCCs revealed 58.8% (10 of 17 specimens) and 90. 47% (19 of 21 specimens), positivity, respectively. ELISA for hepatitis B virus surface antigen in serum showed a positivity of 71. 42% (15 of 21 specimens), but there was only 40% positivity (8 of 20 specimens) for hepatitis B virus envelope antigen whereas 6 of 17 patients (35.29%) showed the presence of antibodies against hepatitis B virus envelope protein. No patient was found to be positive for the HCV antibody. CONCLUSIONS: The very low frequency of p53 mutations and the extremely high frequency of HBV infection (> 90%) in HCC indicate that the mutations in the p53 gene frequently found in HCC reported from different endemic areas of the world may not play a direct role in the development of HCC in India. HBV infection and, possibly, exposure to the dietary aflatoxin B(1) appear to play major roles in the molecular pathogenesis of HCC in India.

Adolescent↗