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Biomedical subjects

T J Harrison

Publications and source records attributed to T J Harrison.

At least 19 recordsLinked to original sources

Dideoxyinosine for chronic hepatitis B infection.

Six patients positive for both human immunodeficiency virus (HIV) and hepatitis B were studied to assess the effect of dideoxyinosine (DDI) on hepatitis B virus (HBV) replication. Two patients died during the follow-up period and four had at least 8 weeks of therapy. One patient demonstrated HBV DNA suppression and became transiently negative. In the remaining five patients, there was no appreciable change in HBV DNA levels during DDI therapy. DDI was well tolerated in all patients, the only significant side effect being diarrhoea. It is concluded that DDI has no notable antiviral effect in patients with chronic HBV infection when coinfected with HIV.

Adult

Independent emergence of a vaccine-induced escape mutant of hepatitis B virus.

We investigated the case of a child who was vaccinated at birth against hepatitis B and was also given hepatitis B immune globulin, but who nevertheless later became infected with the virus. Hepatitis B virus-specific deoxyribonucleic acid covering the region of the genome encoding the predominant a epitope of hepatitis B surface antigen was amplified using the polymerase chain reaction and the nucleotide sequence determined. We present evidence for the independent emergence of an escape mutant, similar to that previously identified in Italy, where a substitution of arginine for glycine has occurred in the second loop of the a epitope.

Amino Acid Sequence

Detection of viruses using hybridization techniques.

Nucleic acid hybridization provides a direct means of detection of viruses, their genomes or the transcripts found in infected cells. A brief introduction to the biochemistry involved is given in this article. Examples of the methods available are illustrated by the detection of hepatitis B viruses both in serum samples and at the site of replication, the liver.

Blotting, Southern

Antimicrobial effect of fermented Ghanaian maize dough.

Unhygienic conditions of a typical rural community in a developing country were simulated in the laboratory by inoculating fermented maize dough porridge with Shigella flexneri and enterotoxigenic Escherichia coli (ETEC). The antimicrobial effects of the different processes involved in the preparation of fermented maize dough porridge were assessed. The soaking process reduced the pH but no antimicrobial effect against shigella and ETEC was noted. Unfermented maize dough did not inhibit any of the test strains. When the fermentation process had become established, half of the strains tested were inhibited by the fermented maize dough when examined 8 h after inoculation. Cooking the fermented maize dough into porridge reduced the antimicrobial effect but there was still significant inhibition of pathogens. This suggests that the antimicrobial effect of fermented maize dough is not due to pH per se. Fermentation of maize dough appears to be a useful strategy for reducing contamination of weaning foods by Sh. flexneri and ETEC. The possible nature of the antimicrobial agent(s) produced during the fermentation of maize dough is discussed.

Escherichia coli

Fermentation of cereals for reduction of bacterial contamination of weaning foods in Ghana.

Unfermented and fermented maize dough weaning foods prepared by mothers in a Ghanaian village were examined for gram-negative bacilli (GNB) immediately after preparation and during storage to assess the antimicrobial effect of fermentation. GNB were cultured from all samples of unfermented dough (51) and from 16 of 51 samples of fermented dough. The extent of contamination was significantly higher in the unfermented dough than in fermented dough (5.9 [SEM 0.1] vs 4.0 [0.4] log10 colony forming units/g). After 6 h and 12 h storage, a higher proportion of samples of porridge made from unfermented dough contained GNB than did those made with fermented dough (45/51 vs 22/55; 49/51 vs 20/51, respectively) and levels of GNB were significantly higher in the porridge made from unfermented dough after 6 h (4.2 [0.2] vs 3.8 [0.2]). Fermentation of maize dough is an effective method to reduce contamination of maize dough weaning foods with GNB.

Diarrhea, Infantile

Hepatitis B virus DNA in peripheral blood leukocytes: a brief review.

Despite being essentially hepatotropic, hepatitis B virus has frequently been detected in peripheral blood leukocytes. In most cases, viral DNA has been detected by hybridisation, though, occasionally, evidence of viral RNA and virus-specific proteins has been reported. Though definitive evidence is lacking, it appears likely that the virus is able to replicate in at least a subfraction of these cells. The possible consequences with respect to the transmission and reactivation of virus infections are discussed.

Animals

Hepatitis B virus-associated hepatocellular carcinoma in African patients.

We have examined several tumors from South African patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma for the presence of integrated viral DNA. In contrast with our findings in patients from Taiwan, few copies of the viral genome were integrated in each tumor. Furthermore, Southern hybridization showed similarities in integration patterns between different tumors. We are presently constructing genomic libraries from selected single-copy tumors in order to make a more detailed analysis of HBV DNA integration at the molecular level.

Africa

Pre-S proteins in hepatitis B.

Two reactive sequences of the pre-S regions of hepatitis B surface antigen were synthesized chemically and used in micro-ELISAs for the assay of pre-S1 and pre-S2 antigens in serum from patients with acute and chronic hepatitis B. Pre-S1 antigen correlated well with the presence of HBV-DNA and was no longer detectable on cessation of viral replication, after natural recovery and after successful treatment with alpha-interferon. Pre-S2 proteins were also lost after treatment with alpha-interferon. The results show that the assay of pre-S1 and pre-S2 proteins in serum provides additional useful markers for assessing patients with acute and chronic hepatitis B infection and for monitoring the response to treatment with interferon.

Amino Acid Sequence

Enterotoxigenic Escherichia coli in the domestic environment of a Malaysian village.

The membrane-filter assay, GM1-ELISA, and DNA-DNA hybridization assay, were used to detect enterotoxigenic Escherichia coli (ETEC) in samples of water, weaning food, food preparation surface swabs, fingerprints of mothers, and the fingerprints and stools of children under 5 years of age, in 20 households in a Malaysian village. Weaning food and environmental samples were frequently contaminated by faecal coliforms, including ETEC. The membrane-filter assay detected and enumerated faecal coliforms and LT-ETEC in all types of water and weaning food samples. Highest concentrations of faecal coliforms and LT-ETEC were found in weaning food, followed by well-water, stored water and stored drinking water. The GM1-ELISA detected LT-ETEC in weaning food, food preparation surfaces, fingerprints and stool samples. The DNA-DNA hybridization assay detected a larger proportion of STa2-ETEC than the other toxotypes, either singly or in combination. All the assays in combination detected the presence of ETEC in all types of samples on at least one occasion in each household. It was not possible to classify households as consistently more or less contaminated with ETEC. On individual occasions it was possible to show a significant association of the presence of LT-ETEC between the fingerprints of children and their stools, fingerprints of mothers and children, and weaning food and the stools of the child consuming the food.

Child, Preschool

Structure and per-rectal ultrasonography of prostatic disease using cadaver specimens.

One hundred cadaver prostates were examined by per-rectal ultrasound and the findings correlated with the microradiographic and histopathological features of whole sections taken at the levels of scanning. The normal gland consists of both periurethral muscle and glands. The periurethral muscle has little structure on microradiography and is therefore hypoechoic (low amplitude echoes) on ultrasound scanning. The gland itself, both central and peripheral zones, has a lattice appearance on microradiography (reticular structure) and therefore produces mid-range amplitude echoes on ultrasound. Benign hypertrophy develops at the edge of the periurethral muscle and is microadenomatous in structure. This produces mid-range amplitude echoes which are coarser than in the normal gland. Associated calcification has a characteristic distribution around the adenomas. Cancer produces an amorphous structure resulting in loss of ultrasonic echoes (hypoechoic). In a few cancers irregular calcification is present, resulting in high echoes in the ultrasound scan (hyperechoic) which are not in the typical benign distribution. The internal structure of the prostate was therefore demonstrated in its histopathological states by the technique of microradiography and seen to relate to its representation by ultrasound.

Adolescent

Comparative histopathology, microradiography and per-rectal ultrasonography of the prostate using cadaver specimens.

A technique for examining cadaver prostates by per-rectal ultrasonography has been developed. The ultrasonic plane was defined and corresponding sections taken for microradiographic and histopathological examination. The technique has enabled a comparison to be made of the structural changes that occur in the prostate in disease states and the corresponding ultrasonic features.

Adolescent

Investigation of the vasoconstrictor action of subarachnoid haemoglobin in the pig cerebral circulation in vivo.

1. Angiographic techniques have been used to study the influence of intracisternally injected haemoglobin on the diameters of the main intrathecal and representative extrathecal (ascending pharyngeal and facial) cranial arteries of the anaesthetized pig. 2. Intracisternal injection of haemoglobin caused concentration-dependent decreases in the diameters of intra- but not extrathecal arteries suggesting that haemoglobin possesses local vasoconstrictor activity. 3. When infused into one ascending pharyngeal artery, acetylcholine (ACh) caused slight dilatation of the intrathecal arteries but no change in the diameters of the ascending pharyngeal and facial arteries. The dilator response induced by ACh in the intrathecal arteries was converted into frank constriction after intracisternal injection of haemoglobin (cerebrospinal fluid concentration approximately 2 x 10(-5) M). 4. These findings are consistent with the hypothesis that subarachnoid haemoglobin can induce cerebral artery constriction by acting as an extraluminal 'sink' for intimally released endothelium-derived relaxing factor (EDRF) and may be relevant to the pathogenesis of vasospasm after subarachnoid haemorrhage in man.

Acetylcholine

The correlation of histopathological, microradiographic and ultrasonographic features in disease of the prostate gland.

The histopathological, microradiographic and ultrasonographic features of corresponding areas of 100 cadaveric prostates were examined and correlated statistically to investigate their relationship. Benign glands are seen to be related to reticular structure and mid-range echoes. Benign prostatic hyperplasia is related to microadenomatous structure and mid-range echoes, whilst cancer is related to amorphous structure and low echoes. A small number of cancers have irregular calcification present and these tumours are related to high echoes. The structure of the prostate gland is therefore related to its pathology and explains its ultrasound echogenicity.

Humans

Incidence and significance of hepatitis B core antibody in a healthy blood donor population.

To determine the current incidence of hepatitis B core antibody (anti-HBc) in a healthy blood donor population, 1,893 donors were screened for anti-HBc. Forty-one (2.16%) were found to be initially positive and 35 (1.85%) repeatably positive. Sera from the repeatably positive donors were further screened for hepatitis B surface antibody (anti-HBs), and hepatitis B virus DNA (HBV DNA) by dot hybridisation. The repeatably positive donors were subsequently recalled for further investigation, and their peripheral blood lymphocytes were also screened for HBV DNA by dot hybridisation. Eighteen (51.4%) of the anti-HBc-positive donors were also anti-HBs-positive. HBV DNA was not detected in the serum or the lymphocytes of any of the anti-HBc-positive donors.

Blood Donors

Effect of fermentation of Ghanaian maize dough on the survival and proliferation of 4 strains of Shigella flexneri.

Fermented and non-fermented Ghanaian maize dough was seeded with approximately 10(7) colony forming units of 4 strains of Shigella flexneri which had been isolated from patients with dysentery. In the non-fermented maize dough (pH 6.2) the shigellae were detectable in large numbers for up to 24 h after exposure. In the maize dough that had been fermented for 3 d (pH 3.2) 3 strains were detectable in small numbers for up to 6 h after inoculation. Thereafter none was isolated. The fourth strain, though detectable for up to 24 h after inoculation, had its numbers reduced considerably. This suggests that traditional methods of food preparation using fermentation have important anti-diarrhoeal functions and the current decline in popularity of such food technologies in certain developing countries may increase the risk of childhood diarrhoea.

Colony Count, Microbial

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