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Biomedical subjects

M C Kew

Publications and source records attributed to M C Kew.

At least 253 records · Page 14Linked to original sources
PubMedDate not supplied

Thyroxine binding globulin and thyroid function tests in patients with hepatocellular carcinoma.

To determine the prevalence of elevated serum concentrations of thyroxine binding globulin (TBG) in patients with hepatocellular carcinoma (HCC) and the influence of the associated cirrhosis, TBG was measured in 39 patients with HCC, 22 with and 17 without cirrhosis, in 20 patients with cryptogenic macronodular cirrhosis but without HCC, and in 40 matched controls. The mean serum TBG concentration in the patients was 34.5 +/- 17.7 microgram per ml, compared to 21.4 +/- 6.8 microgram pr ml in controls and 20.5 +/- 6.3 microgram per ml in cirrhosis without HCC (p less than 0.01). The presence or absence of cirrhosis in the HCC patients did not significantly influence the frequency with which elevated TBG levels were found; levels were normal in every subject with cirrhosis and no HCC. The mean thyroxine (T4): TBG ratio was 5.58 +/- 1.78 in controls and was reduced in HCC patients with both elevated (3.33 +/- 0.80, p less than 0.001) and normal TBG values (4.39 +/- 1.90, p less than 0.05), and in cirrhotics without HCC (4.29 +/- 1.01, p less than 0.01). T4 and TBG concentrations correlated significantly in controls, in HCC patients with elevated TBG, and in the cirrhotics without HCC. It is concluded that in patients with HCC (i) TBG levels may be elevated both in the presence or absence of cirrhosis; (ii) there is reduced binding of T4 TBG, and (iii) a low T4:TBG ratio excludes the diagnosis of hyperthyroidism in the presence of high T4 levels. TBG levels are normal in patients with cryptogenic macronodular cirrhosis without HCC.

Adult↗
PubMedDate not supplied

Hepatitis B virus status of southern African Blacks with hepatocellular carcinoma: comparison between rural and urban patients.

Hepatocellular carcinoma (HCC) is less common and occurs at a much older age in urban than in rural southern African Blacks. These differences may reflect differences in the etiology of the tumor in the two populations. The purpose of this study was to compare the hepatitis B virus (HBV) status of 150 HCC patients who were born and had lived all their lives in a rural environment with 158 patients who were born and brought up in a rural setting but then became urbanized. HBsAg and all markers of present or past HBV infection [HBsAg(+) or anti-HBc(+) or anti-HBs] were significantly less common in the urban patients when the two groups were considered as a whole (p less than 0.001 and p less than 0.05, respectively). However, because the rural patients were considerably younger (mean age 34.7 years; 66% less than 40 years of age) than in urban patients [mean age 50.9 years (p less than 0.0005), 19.0% less than 40 years of age (p less than 0.001)], an age-related analysis was performed. No significant difference in any HBV marker was found between rural and urban patients. The association between active HBV infection and HCC was similar in young patients, both rural and urban, and the prevalence of HBs antigenemia decreased in both groups with increasing age. We conclude that the differences in incidence and age of onset of HCC in rural and urban southern African Blacks cannot be attributable to differences in HBV status.

Adult↗
PubMedDate not supplied

Glutathione S-transferase in human hepatocellular carcinoma.

Qualitative and quantitative changes in glutathione S-transferase (GSH-T) were studied in human hepatocellular carcinoma. GSH-T specific activity (mumoles per min per mg protein) was variably reduced in hepatocellular carcinoma. Similar changes were seen in "cationic" GSH-T (ligandin) concentration determined by radioimmunoassay. Immunohistochemical studies with antihuman liver ligandin suggest that positive staining was more frequently found in well-differentiated tumors. The relative activities of "cationic," "neutral," and "anionic" transferases (pI greater than 7.5) activity ranged from virtually absent to near normal values. "Neutral" (pI 6 to 6.5) and "anionic" (pI less than 5.4) species were present more often in tumors than in normal liver. In two cases, normal liver tissue and tumor were obtained from the same patient. In one, only quantitative differences were present, while in the other "cationic" and "neutral" GSH-Ts were present in the normal liver tissue while both "cationic" and "anionic" species were found in the tumor. Our studies indicate that qualitative as well as quantitative changes of GSH-T occur in human hepatocellular carcinoma.

Biopsy↗
PubMedDate not supplied

Detection of hepatitis B virus DNA directly in human serum by a simplified molecular hybridization test: comparison to HBeAg/anti-HBe status in HBsAg carriers.

A simple, direct molecular hybridization test was employed to detect hepatitis B virus (HBV) DNA sequences in human serum. In 61 HBsAg carriers, many with HBV-related diseases (chronic persistent hepatitis, chronic active hepatitis, or posthepatitic cirrhosis), 28/28 (100%) who were HBeAg+ and 16/32 (50%) who were anti-HBe+ had HBV DNA sequences in their serum. Among 22 South African black patients with hepatocellular carcinoma, 7 (32%) had detectable HBV DNA in their serum but at reduced levels when compared to HBsAg carriers without hepatocellular carcinoma, suggesting that viral replication is suppressed or inactive in many hepatocellular carcinoma patients. Hybridization analysis also distinguished carriers with high, moderate, or low amounts of HBV DNA in serum. Ten to 20% of HBsAg+/HBeAg+ carriers showed high serum levels of HBV DNA but, surprisingly, a similar percentage of HBsAg+/anti-HBe+ carriers also showed relatively high serum levels of HBV DNA. Five patients who had undergone immunosuppression therapy and most of whom were on chronic hemodialysis had very high serum levels of HBV DNA, in the range observed during acute HBV infection. By epidemiologic analysis, two of these individuals were implicated in transmission of hepatitis to other hemodialysis patients, paramedical personnel, or intimate family contacts. Serum HBV DNA hybridization analysis identifies carriers with high serum levels of HBV irrespective of HBeAg/anti-HBe status and may define individuals with potentially high risk of transmitting infection to their immediate contacts.

Antibodies, Viral↗
PubMedDate not supplied

Natural history of hepatitis B virus infection in renal transplant recipients--a fifteen-year follow-up.

Hepatitis B virus (HBV) markers were measured in 83 immunosuppressed renal transplant patients who were followed for periods of 2 to 15 years. Sixty-nine patients were negative for HBsAg before transplantation, of whom 14 were positive for anti-HBs. The remaining 14 patients were HBsAg positive prior to transplantation. Eighteen patients were identified as being HBsAg positive during the follow-up period. Four patients acquired primary type B hepatitis; one died of submassive hepatic necrosis and the remaining three became chronic HBV carriers with positive HBeAg, DNA polymerase, and HBV DNA. Several patterns of HBV expression were observed in HBsAg-positive patients. Four patients were HBsAg, HBeAg, DNA polymerase, and HBV DNA positive prior to transplantation, and these markers persisted. Reactivation of HBV replication occurred in eight patients, seven of whom were HBsAg positive and HBeAg and anti-HBe negative originally; one patient was anti-HBc positive. A single patient was HBsAg and anti-HBe positive and remained so for 22 months. The remaining previously HBsAg-positive patient is currently HBsAg negative. These serological data suggest that reactivation of HBV replication or continued hepatitis B virion replication occurs as commonly or more commonly than de novo infection in renal transplant recipients. The presence of HBeAg in serum predisposes to long-term Dane particle expression in immunosuppressed patients, whereas anti-HBe-positive carriers may not always be susceptible to reactivation of HBV replication despite immunosuppression.

Adult↗
PubMedDate not supplied

Hepatitis B virus replication in southern Africa blacks with HBsAg-positive hepatocellular carcinoma.

Sera from 106 southern African blacks with hepatocellular carcinoma and hepatitis B surface antigenemia (HBsAg) were tested for hepatitis B viral DNA (HBV-DNA) activity, HBV-DNA polymerase concentrations, and HBV e antigen (HBeAg) and antibody (anti-HBe) to investigate the state of viral replication in these patients. HBeAg and anti-HBe were detected by radioimmunoassay, HBV-DNA by molecular hybridization using a 32p-labeled HBV-DNA probe, and HBV-DNA polymerase was measured by incorporation of 3H-labeled thymidine triphosphate into double-stranded HBV-DNA. HBeAg was present in 30.2% (32/106) of the patients, almost always in low titer; 63.8% of the patients were anti-HBe positive. Circulating HBV-DNA was detected in 18.8% (20/106) of patients, including 14 of 32 (43.7%) who were HBeAg positive and 6 of 74 (8.1%) who were anti-HBe positive. In most patients, only trace amounts of HBV-DNA were evident. Raised HBV-DNA polymerase activity was found in 5.6% (6/106) of the patients, all of whom were HBeAg positive and 4 of whom had detectable amounts of circulating HBV-DNA. The HBV-DNA polymerase activity was relatively low in these patients. HBV replication thus appears to be present in only a minority of southern African Blacks with HBV-related hepatocellular carcinoma, and when present is of low grade activity.

Adolescent↗
PubMedDate not supplied

Liver morphology in southern African blacks with hepatocellular carcinoma: a study within the urban environment.

Hepatocellular carcinoma has a lower prevalence and presents at a later age in urban Blacks than in rural Blacks. These differences have previously been shown not to be attributable to differences in serum hepatitis B virus markers. In the present study, the average age of patients with hepatocellular carcinoma in a developing urban Black population is shown to have risen from 38.9 to 56.5 years (p less than 0.0001) over a 20-year interval, while the prevalence of co-existing cirrhosis has declined from 66 to 44% (p less than 0.05) and tissue HBsAg positivity has fallen from 44 to 17.7% (p = 0.002). The lower prevalence of tissue HBsAg in the recent patients may be explained by their older age. Macronodular cirrhosis was present in 56% of cases in the earlier period but declined to 18.9% in the later period, with micronodular cirrhosis becoming the dominant nontumor pathology (p = 0.002). Liver damage attributable to the abuse of alcohol is now found in more than half of the cases (48/90) of hepatocellular carcinoma occurring in this population. The remainder show no changes (12 cases) or show macronodular or incomplete septal cirrhosis (30 cases), presumed to be of viral origin. The latter cases are more likely to have serum markers of current hepatitis B virus infection than those with evidence of alcohol abuse. We conclude that alcohol is increasing in importance as an etiologic association of hepatocellular carcinoma in urban South African Blacks. At the same time, the prevalence of macronodular cirrhosis (and of cirrhosis as a whole) in urban patients with this tumor has declined. The reason for this decline is not known.

Adult↗
PubMedDate not supplied

Comparison between polyclonal and first and second generation monoclonal radioimmunoassays in the detection of hepatitis B surface antigen in patients with hepatocellular carcinoma.

Serum from 221 black patients with hepatocellular carcinoma was tested for HBsAg using a polyclonal radioimmunoassay, and first and second generation monoclonal radioimmunoassays designated M1-RIA and M2-RIA. These monoclonal radioimmunoassays have a lower limit of detection of about 55 and 15 pg of HBsAg-associated epitopes per ml of serum. Correlations were made with other hepatitis B virus serologic markers such as anti-HBc and anti-HBs, using polyclonal radioimmunoassays. We found 47.5% (105/221) of the patients were HBsAg positive by conventional polyclonal radioimmunoassay; all of these patients were also reactive by monoclonal radioimmunoassay. Of the 116 polyclonal radioimmunoassay-negative patients, 4 (3.4%) were reactive by M1-RIA. These four patients were all positive for anti-HBc and/or anti-HBs antibodies. There were 106 of 112 patients negative for HBsAg by polyclonal radioimmunoassay and M1-RIA available for testing by the M2-RIA; 11 (10.4%) were found to be positive only by this test. Thus, with the use of M1- and M2-RIAs, the number of hepatocellular carcinoma patients negative for HBsAg by polyclonal radioimmunoassay was reduced by 14% in this population. More importantly, of the 11 M2-RIA-positive patients, six demonstrated anti-HBc and/or anti-HBs antibodies whereas the remaining five had no serologic evidence of recent or past hepatitis B virus exposure. Finally, of the 21 patients in this series with no markers of hepatitis B virus infection using polyclonal radioimmunoassay and M1-RIA, five (24%) were reactive for HBsAg-associated epitopes by M2-RIA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Do mutant woodchuck hepatitis viruses play a role in hepatocellular carcinogenesis?

Although hepadnaviruses are implicated in the aetiology of hepatocellular carcinoma, the pathogenic mechanisms involved remain uncertain. Clonally propagated integrations of hepadnaviral DNA into cellular DNA can be demonstrated in most virally induced hepatocellular carcinomas. Integration occurs at random sites in cellular DNA, but the highly preferred sites in viral DNA are adjacent to the directly repeated sequence, DR1, less often DR2, or in the cohesive overlap region. Integrants invariably contain simple deletions or complex rearrangements that have been thought to occur after integration. We report here the detection, in the serum of woodchucks with hepatocellular carcinoma, of mutant woodchuck hepatitis viruses that are strikingly similar to the rearranged genomes found previously as integrated sequences in cellular DNA. Of the four mutants studied, two had large inverted duplications, one a 219 nucleotide direct duplication, and one a 219 nucleotide deletion. Virus-virus DNA junctions occurred either adjacent to DR1 or DR2 or in the cohesive overlap region at topoisomerase I cleavage sites. Thus, it is possible that rearrangement of the hepadnavirus genome precedes integration of viral DNA into cellular DNA and that mutant genomes that are preferentially integrated into cellular DNA have an aetiological role in hepatocarcinogenesis.

Animals↗
PubMedDate not supplied

Renal blood flow in obstructive jaundice: an experimental study in baboons.

1. The distribution of intrarenal blood flow has been measured using the 133Xe-washout technique in thirteen baboons 2 weeks after ligation of the common bile duct. 2. In comparison with eight sham-operated baboons, there was a signifigant decrease in the percentage distribution of blood to the cortex, although the rate of flow was unchanged. These changes were accompanied by a significantly increased flow rate and percentage distribution of flow through the juxtameduallary circulation. 3. In a further five baboons treated in the same way, various doses of noradrenaline were infused into the renal artery. In these animals there was an enhanced pressor response to noradrenaline, and this effect was completely abolished by an alpha-adrenoreceptor blocking agent (phenoxybenzamine). The beta-adrenoceptor blocking drug (propranolol) had no such effect. 4. This enhanced response was not seen when noradrenaline was infused into three sham-operated baboons. 5. These observations suggest that the alterations in renal perfusion in obstructive jaundice may be due to an increase renovascular sensitivity to circulating catecholamines and an enhanced alpha-adrenoceptor activity.

Animals↗
PubMedDate not supplied

Renovascular hypersensitivity to noradrenaline in dietary-induced hypercholesterolaemia in baboons.

1. Using the xenon-133 washout technique, the renovascular response to intrarenal infusions of 3 and 30 mumol/min noradrenaline in four baboons with dietary-induced hypercholesterolaemia was measured. 2. The degree of reduction in cortical blood flow rate during an intrarenal infusion of 3 mumol/min noradrenaline in the four hypercholesterolaemic baboons was not significantly different from that in normocholesterolaemic baboons. However, a significant difference in the degree of reduction in cortical blood flow rate was found with the 30 mumol/min noradrenaline infusion (P less than 0.05). 3. The mean arterial blood pressure of the four animals was significantly higher (P less than 0.001) than the mean blood pressure in baboons used in this laboratory for other experiments. 4. These results have shown that baboons with dietary-induced hypercholesterolaemia have an enhanced renovascular sensitivity to exogenous noradrenaline. However, the possibility that this enhanced sensitivity was due to the associated hypertension cannot be excluded.

Animals↗
PubMedDate not supplied

A comparison between des-gamma-carboxy prothrombin and alpha-fetoprotein as markers of hepatocellular carcinoma in southern African blacks.

Des-gamma-carboxy prothrombin (DCP), a precursor of prothrombin, has been reported recently to be as good a marker, or even better, of hepatocellular carcinoma than alpha-fetoprotein (alpha-FP). The sensitivity, specificity and predictive values of the two markers have been compared in 98 southern African Blacks with hepatocellular carcinoma and in 120 Black controls with various diseases which might be mistaken clinically for this tumour: 32 with hepatic metastases, 33 with amoebic hepatic abscesses, and 55 with chronic hepatic parenchymal disease. DCP levels were measured using a chromogenic assay with Dispholidus typus venom and staphylocoagulase. The agreement between the two methods was excellent (r = 0.995). alpha-FP concentrations were measured by radioimmunoassay. DCP levels were raised in 66 of 98 patients (67.3%) and alpha-FP levels in 82 of 98 patients (83.7%) with hepatocellular carcinoma (P = 0.006). The specificity of DCP was also less than that of alpha-FP, although the difference just failed to reach statistical significance (P = 0.085). The predictive values of both a positive and a negative test for DCP were significantly less than those for alpha-FP (P = 0.047 and 0.048, respectively). When, in an attempt to eliminate false positive results, the diagnostic cut-off level for DCP was increased from 1.5 to 5.0 mu/ml and that of alpha-FP from 20 to 400 ng/ml, the differences between the two markers remained the same. If the two tests were used together, the number of false negative alpha-FP results was reduced from 16.3% to 7.1% and the number of equivocal alpha-FP results was reduced from 11.2% to 5.1%.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗
PubMedDate not supplied

Differential lectin reactivities of alpha-fetoprotein in hepatocellular carcinoma: diagnostic value when serum alpha-fetoprotein levels are slightly raised.

The specificity and sensitivity of alpha-fetoprotein (AFP) binding to Concanavalin-A (Con-A) and Lens culinaris agglutinin (LCA) in 26 South African blacks with advanced symptomatic hepatocellular carcinoma (HCC) but only slightly raised serum AFP concentrations (20-500 ng/mL) was compared with that in patients with similar serum AFP levels from diseases that might be mistaken clinically for HCC (seven 'benign' liver disease [BLD] patients and six with metastatic liver disease [MLD] from gastrointestinal tumours). Con-A-Sepharose-4B affinity chromatography did not differentiate between the different groups: fucosylation rations for the HCC patients were 0.81 +/- 0.60, compared with 0.63 +/- 0.27 and 0.54 +/- 0.32 in patients with BLD and MLD, respectively. Electrophoresis of AFP serum and fraction in the presence or absence of Con-A and LCA showed an increase in the AFP C2 band. Rank correlation analysis of the AFP L2 and L3 bands combined could distinguish between patients with HCC and other hepatic diseases (P less than 0.05).

Biomarkers, Tumor↗