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Biomedical subjects

T J Harrison

Publications and source records attributed to T J Harrison.

At least 181 records · Page 10Linked to original sources

The complete nucleotide sequence of the genome of a hepatitis B virus isolated from a naturally infected chimpanzee.

The complete nucleotide sequence of a strain of hepatitis B virus, originally isolated from a naturally infected chimpanzee, has been determined. Interesting features of the sequence include the presence of an in-phase stop codon in the 'pre-core' region of the core antigen open reading frame. The sequence shows approximately 10% nucleotide divergence from all of the other hepatitis B virus sequences previously published and the possibility that this divergence is the result of passage through chimpanzees is discussed.

Amino Acid Sequence↗

X-ray microscopy of the prostate gland.

A technique is described for investigating the internal structure of the prostate gland (including calcification) by projection X-ray microscopy (microradiography). The results show that the technique can be used in conjunction with the corresponding histological preparations to complement the examination of the prostate gland by demonstrating tissue density and the structure and location of microcalcification less than 5 microns in diameter.

Humans↗

Endothelium-derived relaxing factor (EDRF) and resistance vessels in an intact vascular bed: a microangiographic study of the rabbit isolated ear.

1. Microradiographic techniques have been used to show that endothelium-derived relaxing factor (EDRF), which is believed to be nitric oxide, influences vasomotor responses in small arteries and arterioles down to 25 micron in diameter in an isolated, intact, buffer-perfused ear preparation of the rabbit. Arteries down to 75 micron in diameter, i.e. the central ear artery (G0) and its first three generations of branch vessels (G1, G2 and G3) were studied quantitatively. 2. Relative constrictor responses to 1 micron 5-hydroxytryptamine (5-HT) and the combination of 1 microM 5-HT and 1 microM histamine diminished progressively from G0 to G3. Constrictor responses to 5-HT were doubled in all generations by 1 microM haemoglobin which abolishes EDRF activity. 3. Relative dilator responses to acetylcholine or to substance P in preconstricted arteries were, in contrast, equal in the different generations. Mean -log (IC50) values calculated from diameter measurements were 7.63 +/- 0.10 M and 9.80 +/- 0.11 M, respectively. These dilator responses were abolished by 1 microM haemoglobin, implying that they were EDRF-mediated. Spatial homogeneity of relative dilator responses was found also with glyceryl trinitrate (10 or 50 microM) whose activity is thought to depend on biotransformation to nitric oxide, in both the presence and the absence of haemoglobin. 4. This finding of spatial homogeneity of the diameter response to changes in EDRF activity (or to glyceryl trinitrate) implies that EDRF influences hydrodynamic resistance more in vessels where constrictor tone is high.

Acetylcholine↗

Intraocular Echinococcus multilocularis.

Alveolar hydatid disease, caused by the organism Echinococcus multilocularis, is a potentially lethal helminthic infection. After initial hepatic infestation, the organism may spread locally and hematogenously to distant sites. Death occurs secondary to hepatic failure, local extension into vital structures, or metastasis to the brain or lungs. A 67-year-old male Alaskan Eskimo developed decreased visual acuity secondary to a choroidal mass in the right eye eight years after an initial diagnosis of alveolar hydatid disease and four years before the development of symptomatic cerebral metastasis. A pathologic examination disclosed characteristic parasitic membranes involving the posterior pole of the right eye. To our knowledge, this is the first report of ocular involvement in alveolar hydatid disease.

Aged↗

Comparison of five assays for the heat-labile enterotoxin of Escherichia coli.

Enzyme-linked immunosorbent assay (ELISA), DNA-DNA hybridisation, Vero cell assay, the Biken test and a new membrane-filter method were compared in the detection of heat-labile enterotoxin (LT) of Escherichia coli. Six subcultures of each of 50 strains of E. coli from the Biken collection were evaluated "blind" in the laboratory. The combined results of the most reproducible tests (ELISA and DNA-DNA hybridisation) were used to calculate the sensitivity and specificity of the other assays. The Vero-cell assay had a high sensitivity (98%) but a lower specificity (91%). The Biken and membrane-filter assays had sensitivities of 58-71% and 77-84% respectively, depending on the type of antiserum used. Only one false positive result was obtained with the Biken test; specificity of the membrane-filter assay was 94-95%. The membrane-filter assay, with anti-cholera toxin, is specific and reasonably sensitive. It has particular advantages over DNA-DNA hybridisation and the Biken test, and it may prove suitable for screening large numbers of E. coli isolates in epidemiological studies in developing countries.

Animals↗

Randomised controlled trial of lymphoblastoid interferon for chronic active hepatitis B.

Thirty male patients (27 homosexual) with biopsy proven chronic active hepatitis B were randomised to receive lymphoblastoid interferon (Wellferon) or no treatment. All patients were HBeAg positive and had continuing viral replication. Patients receiving treatment were given a single daily intramuscular injection of interferon for 28 days at a starting dose of 2.5 MU/m2 increasing to a maximum of 7.5 MU/m2/day. Transient side effects of malaise and influenza like symptoms occurred in all patients and resolved rapidly after treatment. Hepatitis B viral replication was suppressed during interferon treatment in all patients but the effect was limited to the period of therapy. After one year there was no appreciable difference in viral markers between the two groups of patients and this treatment schedule appears less effective than the thrice weekly, three month regimes recently reported from other centres.

Adult↗

Hepatitis B virus chronic liver disease and hepatocellular carcinoma.

Numerous studies have shown the presence of a highly significant excess of HBsAg, core and surface antibody in patients with hepatocellular carcinoma (HCC). An important factor in the aetiological association between hepatitis B and HCC may lie in the early age of infection. Although hepatitis B virus (HBV) DNA has been found in HCC tissue, there is no simple correlation between serum markers of hepatitis B infection and viral DNA in the tumour. Nevertheless, it is clear that in the case of HBV-associated HCC, integrated HBV sequences may be present in more than 80% of the tumours. The possible molecular basis for the resulting neoplastic transformation is discussed. Whatever the molecular basis of HBV involvement in the causation of HCC, immunization against HBV is likely to prevent primary liver cancer.

Carcinoma, Hepatocellular↗

Membrane filter assay for detection of enterotoxigenic Escherichia coli in epidemiological studies.

A membrane filter assay is described for detection of heat-labile toxin (LT) production by Escherichia coli. Bacterial colonies were isolated on a membrane filter which was then incubated on an agar medium containing anti-cholera toxin. LT produced by bacterial colonies diffused through the membrane filter, complexed with the antiserum, and formed a zone of precipitation in the agar. Requirements for reagents and materials were simple. The membrane filter assay showed good agreement with both the ganglioside-enzyme-linked immunosorbent assay and the DNA-DNA hybridisation assay and may prove to be an important technique for the study of the epidemiology of enterotoxigenic E coli in developing countries.

Cellulose↗

Hepatitis B virus DNA in the hepatocyte. A series of 160 biopsies.

DNA-DNA hybridisation was used to examine 160 liver biopsies for the presence of the hepatitis B virus genome. HBeAg-positive HBsAg carriers were found to have replicating viral DNA in the hepatocytes and, very occasionally, HBV DNA was also integrated into the chromosomes. A high proportion of the anti-HBe-positive HBsAg carriers also have replicating HBV DNA and in the remainder integrated sequences are often, but not always, seen. No evidence was found, however, to implicate HBV in HBsAg-negative patients with alcoholic liver disease, nor in patients with a variety of other liver diseases including non-A, non-B hepatitis.

Base Sequence↗

Randomised controlled trial of lymphoblastoid interferon for chronic active hepatitis B.

Thirty male patients (28 homosexual or bisexual) with biopsy proven chronic active hepatitis B were randomised to receive lymphoblastoid interferon (Wellferon) or no treatment. All patients were HBeAg-positive and had continuing viral replication. Interferon was given as a single daily i.m. injection for 28 days at a starting dose of 2.5 megaunits/m2 increasing to a maximum of 7.5 megaunits/m2/day. Transient side-effects occurred in all patients. Hepatitis B viral replication was suppressed during interferon treatment in all patients but the effect was limited to the period of therapy. After 1 year there was no appreciable difference in viral markers between the two groups of patients and this treatment schedule appears less effective than the thrice weekly, 3-month regimes reported from other centres.

Clinical Trials as Topic↗

Detection of hepatitis B virus DNA in hepatocellular carcinoma.

DNA-DNA hybridization was used to examine tissue from 31 patients with hepatocellular carcinoma (HCC) in Taiwan for the presence of the hepatitis B virus genome. Twenty-four of the DNA samples had discrete high molecular weight bands when cut with HindIII and hybridized with a radiolabelled HBV DNA probe, and similar results were obtained with 25 of the samples when cut with EcoRI. Thus integrated HBV DNA was present in almost 80% of the specimens. None of the samples had a similar pattern and most contained HBV DNA integrated at multiple sites. Seventeen out of 19 HBsAg carriers and one out of two patients with anti-HBs were found to have integrated HBV DNA in the tumour tissue, providing further evidence of the strong association between HBV infection and development of hepatocellular carcinoma.

Autoradiography↗

Hepatitis B virus DNA and e antigen in serum from blood donors in the United Kingdom positive for hepatitis B surface antigen.

Serum samples from 214 blood donors in the United Kingdom who were carriers of hepatitis B surface antigen (HBsAg) were examined for hepatitis B virus deoxyribonucleic acid (DNA) by DNA:DNA hybridisation and for hepatitis B e antigen (HBeAg) and its antibody. One fifth of the donors carried infectious virus in their circulation. The presence of hepatitis B virus DNA correlated well with that of HBeAg, although hepatitis B virus DNA was found in five serum samples that were negative for HBeAg. It is concluded that analysis of serum samples for hepatitis B virus DNA by hybridisation should be the method of choice for determining whether carriers of HBsAg are infectious.

Antibodies, Viral↗

Production of hybrids of mouse myeloma cells and protozoa which express parasite antigens.

Mouse myeloma cells were fused with blood stage forms of the rodent malaria parasite Plasmodium chabaudi and with promastigotes of Leishmania donovani, the causative agent of kala-azar in man. The fusion was carried out by polyethylene glycol treatment. The parasites provided the enzyme which enabled the hybrids to grow in selective medium containing aminopterin. Clones of parasite-myeloma hybrids grown in continuous culture for up to 5 months expressed parasite antigen and induced anti-parasite antibodies in mice.

Animals↗

Free osteocutaneous groin flap in the reconstruction of large mandibular defects. A case study.

Multiple tissue transfers are being used more and more in head and neck reconstruction. With the development of microvascular surgery, free flaps have been used as one such method of reconstruction. We have found that the use of the osteocutaneous groin flap, a free flap, is an excellent choice for filling all the requirements of reconstruction of massive oral defects in which large segments of the mandible are resected. This flap is not to be used routinely as a first-choice flap, and it should only be used in patients who are healthy enough to tolerate the prolonged anesthesia necessary to complete such a procedure and in the patient who has a good prognosis from his disease.

Carcinoma, Squamous Cell↗

Assay of HBV DNA in the plasma of HBV-carrier chimpanzees superinfected with non-A, non-B hepatitis.

A dot hybridisation technique was used to monitor the levels of hepatitis B virus (HBV) DNA in the plasma of two HBV-carrier chimpanzees which had been inocula ed with documented infectious non-A, non-B hepatitis agents. A marked decrease in the quantity of HBV DNA in the plasma during the acute phase of the non-A, non-B hepatitis was observed in both carriers. The possible role of interferon or a similar antiviral agent in modulation of the HBV-carrier state is discussed. Hybridisation may become, in due course, the method of choice for examining blood samples for infectious hepatitis B virus.

Animals↗

A host range mutant of human adenovirus type 5 defective for growth in hamster cells.

A host-range mutant of adenovirus type 5, which grows in human cells but not in hamster cells, has been isolated. This mutant is complemented in mixed infection in hamster cells at 38.5 degrees C by temperature-sensitive mutants of type 5 belonging to seventeen complementation groups, and may constitute a new group. In mixed infection of human cells at 32 degrees C with the host-range and temperature-sensitive mutants, recombination takes place and by a series of two factor crosses the host-range mutation has been approximately located on the adenovirus genetic map.

Adenoviruses, Human↗