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Biomedical subjects

M C Kew

Publications and source records attributed to M C Kew.

At least 127 records · Page 7Linked to original sources
PubMed1985

Clinical and serological events accompanying changes in hepatitis B viral replication: case reports.

We measured serum markers of hepatitis B virus replication in two HBsAg-, HBeAg-positive hepatitis B carriers with chronic active hepatitis and cirrhosis. The first of these patients was HBsAg-, HBeAg-, HBV DNA- and HBV DNA polymerase-positive initially and spontaneously lost HBV DNA polymerase and HBV DNA. During the HBeAg-positive, DNA polymerase-negative "window phase", an increase in viral replication, characterized by the reappearance of HBV DNA and HBV DNA polymerase occurred, together with an aggravation of the underlying chronic hepatitis. In the second HBsAg-, HBeAg-positive carrier, spontaneous fluctuations in HBV replication were associated with clinical deterioration. Delta agent and hepatitis A virus superinfection were excluded. These observations suggest that spontaneous low-grade fluctuations of HBV replication accompanied by an increase in the biochemical activity of the underlying chronic hepatitis can be observed in certain HBV carriers.

Alanine Transaminase↗
PubMed1985

The role of interleukin 1 (IL 1) in tumor-NK cell interactions: correction of defective NK cell activity in cancer patients by treating target cells with IL 1.

This study examined the importance of interleukin 1 (IL 1) in the large granular lymphocyte (LGL)-target cell interaction. K562 target cells when treated with highly purified human IL 1 for 1 hr bound greater numbers of LGL than untreated cells. LGL from patients with hepatocellular carcinoma (HCC) that bound few untreated K562 cells, attached to considerably increased numbers of IL 1-treated target cells. Cytotoxicity of LGL against target cells could similarly be increased by pulsing the latter cells with IL 1, and defective cytotoxicity of LGL from HCC patients could be corrected by treating the target K562 cells with IL 1. Lysis of PLC/PRF/5 cells, Yac-1 cells, and normal skin fibroblasts could also be increased by treatment with IL 1 for 1 hr. The enhanced binding and cytotoxicity of IL 1-treated target cells was only observed when the latter cells were preincubated with IL 1 at 37 degrees C, and was not evident at 4 degrees C. Furthermore, the IL 1-mediated effect could be abolished by treating the target cells with cycloheximide before the IL 1 pulse, or by adding rabbit anti-human IL 1 together with the IL 1. These results indicate that IL 1 affects a variety of target cells and increases their ability to bind and be lysed by enriched LGL. They demonstrate, furthermore, that defective natural cytotoxicity by the LGL of patients with advanced malignant disease can be corrected in vitro by treating the target cells with IL 1.

Adult↗
PubMed1984

Hepatocellular carcinoma in white South Africans--aetiological considerations.

The aetiological associations of hepatocellular carcinoma in 25 White South African patients were assessed. The most frequent association was cirrhosis, which was present in 13 out of 23 patients (56,5%)--7 had alcoholic cirrhosis, 5 (including 1 of those with alcoholic cirrhosis) markers of current or past hepatitis B virus infection, 1 idiopathic haemochromatosis, and 1 no obvious cause. Two further patients in whom the presence or absence of cirrhosis could not be ascertained with certainty also drank to excess. Markers of current hepatitis B virus infection were detected in 24,5% of the patients and evidence of current or past infection in 45,5%. These prevalences are lower than those in matched South African Blacks with hepatocellular carcinoma, but are significantly higher than those in White blood donors. Two young female patients had taken oral contraceptives and another had taken conjugated equine oestrogens.

Adult↗
PubMed1984

Autonomous cholesterol biosynthesis in murine hepatoma. A receptor defect with normal coated pits.

These studies indicate that autonomous cholesterol biosynthesis by hepatocellular carcinoma may result from absent or defective receptors for chylomicron remnants on the surface of the malignant hepatocytes. In vivo, DAB2 hepatoma or liver were perfused with chylomicron remnants labeled with tritiated palmitic acid. Normal liver had chylomicron remnant uptake/gm tissue that was ten times that of hepatoma. In vitro studies using isolated hepatocytes and cultured DAB2 hepatoma cells showed similar results. Uptake of chylomicron remnants labeled with 3H-palmitic acid by normal hepatocytes during a 4-hour period was ten times that of hepatoma cells. Both in vivo and in vitro differences were statistically highly significant (P less than 0.005). Since many surface receptors are related to the coated pits, the cellular membranes of both neoplastic and normal liver cells were examined by electron microscopy. Coated pits were present in both the hepatoma and normal liver cells and occupied 2.61% and 2.65% of the cell surface, respectively. The defective uptake of chylomicron remnants by DAB2 hepatoma appears to be related to the chylomicron remnant receptor and not to the coated pit-internalization mechanism.

Animals↗
PubMed1984

Hepatitis B virus carrier state in black children in Ovamboland: role of perinatal and horizontal infection.

Hepatitis B surface antigen (HBsAg) was detected in 17% of adult males and 11% of mothers in Ovamboland , South West Africa/Namibia. Hepatitis B e antigen (HBeAg) was present in 15% of HBsAg-positive mothers. Only 1% of children less than 6 months of age were HBsAg-positive, compared with 13% of children over the age of 1 year. 27% of mothers who were HBsAg-positive had HBsAg-positive children, whereas the corresponding figure for mothers who were HBsAg-negative was 6%. 63% of mothers who were positive for both HBsAg and HBeAg had HBsAg-positive children. 37% of HBsAg-positive children had HBsAg-positive mothers, compared with 8% of HBsAg-negative children. Later "horizontal" rather than neonatal maternal-infant transmission of the hepatitis B virus (HBV) seems to be the more important mode of spread of this infection in Ovambo children. The difference in the pattern of transmission of this virus between the Far East and Africa seems to centre mainly on the differences in the HBeAg status of the mothers in these two regions.

Adolescent↗
PubMed1984

Primary squamous cell carcinoma of the liver occurring in association with hepatolithiasis.

Primary squamous cell carcinoma of the liver has previously been reported to arise only from the lining of a developmental hepatic cyst or in a hepatic teratoma. The authors describe the occurrence of such a tumor in association with multiple intrahepatic cholesterol gallstones. It is suggested that the gallstones may have caused squamous metaplasia of the lining of the bile ducts and that this in turn was responsible for squamous carcinoma formation.

Adult↗
PubMed1984

Defective interleukin-1 production by monocytes from patients with malignant disease. Interferon increases IL-1 production.

Interleukin-1 (IL-1) production by monocytes of patients with various forms of malignant disease was measured after activating the cells with either lipopolysaccharide or malignant K562 cells. Monocytes from all the patients with large tumour masses, including 10 patients with hepatocellular carcinoma, produced considerably less IL-1 than controls or patients with small tumour burdens. After treating control or patient monocytes with human leucocyte interferon for 1 h prior to activation, IL-1 production was markedly improved. Depressed IL-1 production is, therefore, a further aberration in mononuclear function observed in patients with cancer.

Adult↗
PubMed1984

Tumour-associated isoenzymes of gamma-glutamyl transferase in the serum of patients with hepatocellular carcinoma.

Sera from 391 southern African Blacks with hepatocellular carcinoma, matched controls, patients with other malignant tumours, and with various forms of hepatobiliary disease were fractionated by polyacrylamide gradient gel electrophoresis to determine the prevalence of tumour-associated gamma-glutamyl transferase isoenzymes in Black patients with hepatocellular carcinoma. One or more tumour-associated isoenzymes (I', I'' or II') were present in 58.6% of the patients with hepatocellular carcinoma: I' in 54.5%, I'' in 27.1%, and II' in 34%. These isoenzymes were detected in one patient with prostatic cancer, occasionally in patients with acute viral hepatitis, but in no normal individuals. The presence of tumour-associated isoenzymes was not related to patient age, sex or hepatitis-B virus status or to the tumour burden. Isoenzymes were present in 42 percent of hepatocellular carcinoma patients with a normal serum alpha-foetoprotein concentration and in 50% of those with a non-diagnostic value. gamma-glutamyl transferase isoenzymes may be supplementary to alpha-foetoprotein in the diagnosis of hepatocellular carcinoma.

Adolescent↗
PubMed1984

Relationship between hepatocellular carcinoma and cirrhosis.

The precise nature of the relationship between cirrhosis and HCC remains to be elucidated. However, it seems likely that no single explanation will cover the various forms the association takes in different parts of the world. In the high HCC incidence regions of sub- Saharan Africa and the Far East, an etiology common to the two disorders, HBV and possibly other hepatitis viruses, seems to account for the majority of cases. The role of aflatoxin in these areas is uncertain because it appears not to cause cirrhosis in man. In populations in which HCC is uncommon, alcoholic cirrhosis is the most frequent association of HCC. There is no convincing evidence to support a shared etiology in this situation because alcohol has not thus far been proved to be directly oncogenic for the liver. Possibly, cirrhosis renders the hepatocytes more susceptible to environmental carcinogenic factors. The same explanation may apply to hemochromatosis. There is at present little evidence for the postulate that HCC is an inevitable consequence of the hyperplasia of cirrhosis.

Aflatoxins↗
PubMed1984

Radiocolloid liver imaging in tuberculous hepatitis.

Twenty of 22 patients with tuberculous hepatitis had abnormal Tc-99m tin colloid liver scans. However, in the majority of the patients the changes were mild and nonspecific. The most frequent scintigraphic picture was a decreased uptake of the radiocolloid by the liver, with shunting to the spleen and bone marrow. The decreased hepatic uptake was usually mildly heterogeneous, but it was sometimes homogeneous, and in five patients obvious defects were present. The liver was enlarged in six patients and the spleen in six patients. Increased extrahepatic uptake of the radiocolloid was the only abnormality in five patients. The severity of the scintigraphic changes did not correlate with the following histologic findings: number of granulomas, degree of associated fibrosis, degree of hepatocyte swelling, or extent of fatty change.

Colloids↗
PubMed1984

Isolation of ferritin from human hepatocellular carcinoma.

Ferritin was extracted from human hepatocellular carcinoma tissue and purified using column chromatography, gradient gel electrophoresis and cadmium sulphate crystallization. DEAE cellulose chromatography showed a difference between hepatoma and normal liver ferritin, indicative of a more acidic isoferritin profile in the tumour. Column-purified and crystalline ferritin and that remaining in the mother-liquor after crystallization was subjected to isoelectric focusing. Hepatoma ferritin showed higher concentrations of acidic isoferritins than liver ferritin. This was most obvious with mother-liquor ferritin, as crystallization tended to select out more basic isoferritins. Subunit analysis of hepatoma and liver ferritin showed a higher proportion of heavy subunits in the tumour ferritin, in keeping with the presence of acidic isoferritins. An antibody against hepatoma mother-liquor ferritin was raised in rabbits. However, hepatoma ferritin proved to be antigenically identical with normal liver ferritin, and we were thus unable to develop a specific radioimmunoassay for hepatoma ferritin.

Carcinoma, Hepatocellular↗
PubMed1983

Alpha-1-antitrypsin deficiency and hepatocellular carcinoma. Determination of Pi phenotypes using iso-electric focusing.

Alpha-1-antitrypsin (AAT) deficiency resulting from the homozygous protease inhibitor (Pi) ZZ and the heterozygous Pi Z states has been reported to be aetiologically associated with hepatocellular carcinoma (HCC). We studied the phenotype distribution of AAT variants (Pi) by iso-electric focusing on polyacrylamide gel and measured serum AAT concentrations by rocket immuno-electrophoresis in 80 unselected southern African Black patients with HCC and 103 age-, sex- and tribally matched control subjects. Aberrant (non-MM) phenotypes were present in 7 HCC patients (8,7%) and 13 controls (12,6%), an insignificant difference. None of the patients or controls had the Pi ZZ phenotype, while 4 HCC patients (5,0%) and 2 controls (1,9%) (P greater than 0,05) were found to be heterozygous carriers of the Z gene. No HCC patient had a subnormal serum AAT value, and the values in the patients were not lower than those in the controls. We conclude that AAT deficiency does not play an aetiological role in HCC in southern African Blacks. The 4 patients with the heterozygous Z phenotype did not have fibrolamellar carcinomas.

Adult↗
PubMed1983

Baseline epidemiological studies for a hepatitis B vaccine trial in Kangwane.

Hepatitis B markers were determined by radioimmunoassay of serum samples from 1 495 Black subjects representative of the resident population of Kangwane, a rural area with a high incidence of chronic liver disease and hepatocellular carcinoma. Pregnant women formed an important part of the study group, since it was intended to assess the frequency of perinatal transmission and the passive immunity of their infants, two factors which would markedly influence an infant immunization programme. A high overall marker positivity rate was found, indicating that hepatitis B is endemic. The hepatitis B surface antigen (HBsAg) carrier rate was 14,6% in adult males and 4,6% in adult females, while 82.6% of adult males and 69,4% of adult females were positive for at least one marker, indicating that infection had been present at some stage. Of infants under 1 year of age 34,5% were positive for antibodies to HBsAg (anti-HBs), compared with 9,3% at 13-24 months, which indicates that transplacental transfer of anti-HBs is frequent. Other markers were acquired even in the 1st year of life, with the sharpest increase at 3-11 years. Perinatal transmission was not common, however, and horizontal transmission during early childhood seemed to play an important role. It was concluded that the risk and frequency of infection justified a vaccine trial in this population and that the target group for vaccination should be infants under 1 year of age.

Adolescent↗
PubMed1983

Sinus bradycardia in obstructive jaundice--correlation with total serum bile acid concentrations.

Obstructive jaundice is often listed among the causes of sinus bradycardia. The latter is usually attributed to the effect of bile salts on the sino-atrial node. The purpose of this study was to determine the frequency of sinus bradycardia (heart rate less than 50/min) in 50 patients with severe or moderate cholestasis, and to relate sinus rate and intracardiac conduction to total serum conjugated bile acid concentrations. The latter were measured using a solid-phase 125I radio-immunoassay. The mean sinus rate (+/- SD) in the patients was 74.1 +/- 11.6/min (range 47-100/min). One patient had a sinus rate of less than 50/min and 2 had rates of 50-60/min. The mean total serum conjugated bile acid concentration was 251.1 +/- 198.8 mumol/l (range 13-1000 mumol/l). There was no correlation in individual patients between total serum bile acid concentration and sinus rate (r = +0.097), P-R interval (r = +0.210) or corrected Q-T interval (r = -0.085). We conclude that sinus bradycardia is not a feature of obstructive jaundice and that high serum bile acid concentrations do not exert a slowing effect on the sino-atrial node.

Adult↗
PubMed1983

Immune response to hepatitis B vaccine in newborns.

Three injections of 10 microgram/ml hepatitis B vaccine (Merck) given in the first week after birth, a month later and again at the age of six months to 63 neonates in a rural African population, elicited an antibody response in 93 per cent. The initial hepatitis B marker status of the babies and mothers did not influence the results at nine months. Side-effects were minor and we conclude that the vaccine can effectively and safely be used from birth in endemic situations.

Female↗