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Biomedical subjects

M E Harper

Publications and source records attributed to M E Harper.

At least 91 records · Page 5Linked to original sources
PubMed1986

HTLV-III expression in infected lymph nodes and relevance to pathogenesis of lymphadenopathy.

In situ hybridization with a 35S-labeled probe of cryosections from 14 lymph nodes of HTLV-III/LAV-seropositive individuals with lymphadenopathy showed the presence of rare cells containing HTLV-III RNA at levels consistent with virus replication. Positive cells were observed at a frequency of only 1-10 per section. In all lymph nodes studied, including those showing follicular hyperplasia or involution, most of the cells expressing viral RNA were present in the follicular areas. Only a minority of such cells were found outside the follicles. The nature of the follicular, virus-replicating cells was not evident from the processed cryosections. After prolonged autoradiography, another pattern of hybridization was observed, suggesting low levels of viral RNA diffusely distributed throughout most, but not all, follicles. This may represent extracellular virus and/or virus-antibody complexes, but was not consistent with intracellular viral RNA or phagocytosed virus particles. Comparison of hybridization levels in relation to histology suggested a decrease in both the number of HTLV-III replicating cells as well as in the diffusely distributed viral RNA with progression of follicular involution. Our observations indicate that in HTLV-III-infected subjects, lymph node follicles are an important site of virus replication and trapping, suggesting a decisive role of the virus in the characteristic reactive and cytopathogenic changes of HTLV-III-associated lymphadenopathy.

AIDS-Related Complex↗
PubMed1985

HTLV-III infection in brains of children and adults with AIDS encephalopathy.

Unexplained debilitating dementia or encephalopathy occurs frequently in adults and children with the acquired immune deficiency syndrome (AIDS). Brains from 15 individuals with AIDS and encephalopathy were examined by Southern analysis and in situ hybridization for the presence of human T-cell leukemia (lymphotropic) virus type III (HTLV-III), the virus believed to be the causative agent of AIDS. HTLV-III DNA was detected in the brains of five patients, and viral-specific RNA was detected in four of these. In view of these findings and the recent demonstration of morphologic and genetic relatedness between HTLV-III and visna virus, a lentivirus that causes a chronic degenerative neurologic disease in sheep, HTLV-III should be evaluated further as a possible cause of AIDS encephalopathy.

Acquired Immunodeficiency Syndrome↗
PubMed1985

The effect of prolactin on human BPH epithelial cell proliferation.

Epithelial cell monolayers derived from specimens of human benign prostatic hyperplasia (BPH) tissue by an explant culture technique were cultured with prolactin in the presence and absence of androgens. Proliferation of the cells was measured by both autoradiographic assessment of [3H]-thymidine uptake and stathmokinetic procedures. Prolactin significantly stimulated the growth of these cells in the concentration range 0.5 mIU/ml to 10 mIU/ml but was inhibitory at a concentration of 100 mIU/ml. In the presence of testosterone (1 X 10(-7) M), prolactin at low concentrations (greater than 1 mIU/ml) but not at 10 mIU/ml, the concentration at which all other experiments were performed, produced a further stimulation in the proliferation. The increase in growth seen with cells cultured with 5 alpha-dihydrotestosterone (1 X 10(-7) M) was reduced with addition of prolactin at high concentrations (10-100 mIU). When the fetal calf serum used in the cultures was stripped of endogenous steroids, prolactin still increased cell proliferation, although to a reduced extent. This indicated that the effects of prolactin were not dependent on the presence of androgens.

Cells, Cultured↗
PubMed1985

A prognostic index for the clinical management of patients with advanced prostatic cancer: a British Prostate Study Group investigation.

Patients with histologically proven carcinoma of the prostate (n = 186) were initially assessed and followed up according to the standardized protocol of the British Prostate Study Group, urologists from which contributed patients to this investigation. These patients were given either endocrine therapy or orchidectomy as first line treatment; the ratio of the number of patients receiving these two treatments was similar in each group of subjects compared for survival. Prognostic indices were derived for all patients and for those classified according to the presence (M1) or absence (M0) of metastases. The prognostic indices were derived from clinical and hormone data obtained at initial presentation. Whereas the degree of tumor differentiation and plasma testosterone concentrations were significant prognostic factors in both M0 and M1 disease, growth hormone was only significant in M1 patients, where age was also of borderline significance; elevated growth hormone, higher Gleason grade, younger age, and lower testosterone indicated a poorer prognosis in M1 patients. These findings indicated the feasibility of selecting a poor prognostic group of patients that may derive benefit from a more aggressive therapy.

Age Factors↗
PubMed1985

Chromosomal localization, structure, and expression of the human alpha-fetoprotein gene.

By in situ hybridization of cloned human alpha-fetoprotein cDNA to human mitotic chromosome preparations, the alpha-fetoprotein gene was localized within the q11-22 region on the long arm of human chromosome 4. In addition, the human alpha-fetoprotein gene was isolated from a genomic phage library. The gene is split into 15 exons and 14 introns, and the entire structure is contained within two large (9.5 and 9.0) and two small (0.3 and 0.25 kb) EcoRI fragments of contiguous chromosomal DNA. The structure of alpha-fetoprotein and its gene is very similar to the corresponding structures of serum albumin, indicating a common evolutionary origin of these two serum proteins. However, the two genes are differentially expressed during normal development and under certain pathological conditions such as hepatomas, germ-cell tumors, or ataxia-telangiectasia. The molecular basis of this differential gene expression remains to be understood.

Chromosome Mapping↗
PubMed1985

Pharmacological inhibition of infectivity of HTLV-III in vitro.

Acquired immunodeficiency syndrome (AIDS) is a pandemic immunosuppressive disease that predisposes to life-threatening opportunistic infections and unusual forms of neoplasms. A recently discovered member of the human T-lymphotrophic virus (HTLV) family, designated HTLV-III, has been shown to be the etiological agent of AIDS. We have shown previously that a trypanosomicidal drug, suramin, can block the in vitro infectivity and cytopathic effect of HTLV-III at doses that are attainable in human beings. In the present work we report our findings that suramin can block the cytopathic effect of HTLV-III even after a defined exposure of the target helper/inducer T-cells to the virus and that the T-cells protected by suramin remain immunologically functional.

B-Lymphocytes↗
PubMed1984

Gene for T-cell growth factor: location on human chromosome 4q and feline chromosome B1.

T-cell growth factor (TCGF) or interleukin-2 (IL-2), an immunoregulatory lymphokine, is produced by lectin- or antigen-activated mature T lymphocytes and in a constitutive manner by certain T-cell lymphoma cell lines. By means of a molecular clone of human TCGF and DNA extracted from a panel of somatic cell hybrids (rodent cells X normal human lymphocytes), the TCGF structural gene was identified on human chromosome 4. In situ hybridization of the TCGF clone to human chromosomes resulted in significant labeling of the midportion of the long arm of chromosome 4, indicating that the TCGF gene was located at band q26-28. Genomic DNA from a panel of hybrids prepared with HUT-102 B2 cells was examined with the same molecular clone. In this clone of cells, which produces human T-cell leukemia virus, the TCGF gene was also located on chromosome 4 and was apparently not rearranged. The homologous TCGF locus in the domestic cat was assigned to chromosome B1 by using a somatic cell hybrid panel that segregates cat chromosomes. Linkage studies as well as high-resolution G-trypsin banding indicate that this feline chromosome is partially homologous to human chromosome 4.

Animals↗
PubMed1984

Carcinoma of the prostate: relationship of pretreatment hormone levels to survival.

Pretreatment hormone levels were determined in 222 patients with prostatic cancer and their prognostic value assessed. The patients were grouped into yearly survival categories and only those whose cause of death was due to the disease were included in the study. Low concentrations of testosterone in plasma at the time of diagnosis related to a poor prognosis. Patients who died within 1 yr of diagnosis had the lowest mean plasma levels of this steroid. The pretreatment mean plasma testosterone concentrations were found to be higher as the survival period of the various groups lengthened. This relationship was observed both when the total data were analysed and also when the patients were subgrouped depending on clinical evidence of spread of the tumour beyond the prostatic capsule (T3) or on the presence of metastases (M1). High pretreatment plasma concentrations of luteinizing hormone were also associated with poor survival. Follicle-stimulating hormone, prolactin and growth hormone concentrations did not correlate with survival time. The indications from this study are that poor testicular function is associated with early death from prostatic carcinoma and that the measurement of blood levels of testosterone at diagnosis could provide a prognosis of subsequent life-span.

Aged↗
PubMed1984

Chromosomal mapping of murine c-fes and c-src genes.

The murine homologs of two viral oncogenes associated with tyrosine-specific kinase activity have been assigned to different loci in the mouse genome. The segregation of restriction site polymorphisms, as detected by probes that are specific for endogenous c-fes and c-src sequences, was followed in the DNA of recombinant inbred strains. The c-fes gene was mapped to the proximal portion of chromosome 7, very close to the Gpi-1 locus, whereas c-src was linked to the Psp locus on the distal half of chromosome 2.

Alleles↗
PubMed1984

Localization of the human glucagon gene (GCG) to chromosome segment 2q36----37.

Hybridization of a 3H-labeled bovine glucagon cDNA plasmid to human metaphase chromosomes revealed significant labeling of the distal portion of the long arm of chromosome 2. A large portion (37%) of the cells analyzed exhibited labeling of the 2. A significant percentage (40%) of the labeled sites on the 2 were in segment 2q36----37. Therefore, the human glucagon gene (GCG), was assigned to this segment. Localization of the glucagon gene, whose chromosomal assignment was previously not known, demonstrates the general applicability of in situ hybridization as a powerful gene mapping technique.

Chromosome Mapping↗
PubMed1984

Growth hormone and prostatic tumours: localization using a monoclonal human growth hormone antibody.

The immunocytochemical detection of endogenous human GH and the binding of exogenously applied human GH in tumour tissue from patients with benign prostatic hyperplasia or prostatic carcinoma is reported. Monoclonal human GH antibody binding was exclusively to the connective tissue in both benign and carcinomatous specimens. Specificity control experiments indicated that the antibody could be absorbed with human GH but not with human prolactin. Preincubating the sections with human GH considerably altered the immunocytochemical staining, reducing the reaction product within the connective tissue in a concentration-dependent manner and revealing a binding site for GH within the cytoplasm of epithelial cells.

Antibodies, Monoclonal↗
PubMed1983

Chromosomal mapping of Xenopus 5S genes: somatic-type versus oocyte-type.

Xenopus 5S RNA genes exhibit a pattern of differential expression during development in which some members (oocyte-type) are transcribed only in oocytes, while others (somatic-type) are expressed in both oocytes and somatic cells. Using cloned DNA probes specific for each gene type, we determined the positions of these genes on Xenopus metaphase chromosomes by in situ hybridization. Somatic-type 5S genes in both X. laevis and X. borealis are located at the distal end of the long arm of only one chromosome (number 9). The oocyte-type 5S RNA genes are found at the distal ends of the long arms of most Xenopus chromosomes, including chromosome 9. Thus, large scale differences in chromosomal location cannot explain the selective expression of these genes, as suggested previously.

Animals↗
PubMed1983

The distribution of zinc in the prostate of rhesus and cynomolgus monkeys determined by electron microscopy and x-ray microanalysis.

The distribution of zinc in the prostate of the mature rhesus monkey is described. High levels of zinc were located in the nuclei of epithelial and basal cells in both lobes of the gland, while elevated concentrations of the metal were also found in secretory granules and along lateral cell membranes. A similar zinc distribution pattern was observed in the 2 lobes of the gland, but in general organelles in the cranial region had a higher content of the metal. In whole tissue, however, a 15 times greater zinc content was measured in the caudal lobe. This difference could be explained in terms of the high levels of the metal present in secretory granules and luminal secretion in the caudal lobe. A similar ultrastructural appearance and distribution of zinc was observed in the prostate of the cynomolgus monkey (Macaca fascicularis).

Animals↗
PubMed1983

Chromosomal mapping of the mink cell focus-inducing and xenotropic env gene family in the mouse.

Chromosomal locations of members of the xenotropic-related env gene family in the mouse genome have been determined. Endonuclease restriction site polymorphisms detected by molecular hybridization were used to study the inheritance of mink cell-focus inducing and xenotropic env gene-related sequences in recombinant inbred strains of mice. Some of the endogenous env sequences appear to be closely linked to genes determining leukemia virus induction and to genes involved in the immune response, such as the heavy and light chains of the immunoglobulin molecules or allotypic determinants on B and T lymphocytes. The use of probes that detect restriction fragment length polymorphisms in a small family of dispersed sequences promises to yield a large number of markers that can be used together with recombinant inbred strains for efficient mapping of the mouse genome.

Animals↗
PubMed1983

Linkage of the evolutionarily-related serum albumin and alpha-fetoprotein genes within q11-22 of human chromosome 4.

Albumin and alpha-fetoprotein are structurally related serum proteins, having a similar gene structure and, conceivably, a common evolutionary origin. To test their relative arrangement in the human genome, the serum albumin and alpha-fetoprotein genes were mapped by in situ hybridization of cloned human albumin or alpha-fetoprotein cDNA to human mitotic chromosome preparations. Analysis of cells hybridized with the serum albumin probe showed that 39% of cells exhibited grains on the proximal portion of the long arm of chromosome 4 (bands q11-22), with these grains comprising 30% of all labeled sites throughout these mitoses. Similarly, in cells hybridized with the alpha-fetoprotein probe, 39% of cells were observed to contain silver grains on 4q11-22, these grains constituting 20% of all labeled sites in these cells. These results demonstrate chromosomal localization and linkage of the serum albumin and alpha-fetoprotein genes within bands q11-22 of the long arm of human chromosome 4.

Biological Evolution↗
PubMed1982

Proliferation of human prostatic epithelial cells in culture: aspects of identification.

A reproducible explant culture technique has been developed to study in monolayer, the growth of human prostatic epithelium from specimens of tissue removed from patients with benign prostatic hyperplasia. The procedure was used to study hormone responsiveness of prostatic tissue. The cells appear to originate from the progenitors of glandular epithelium and possess epithelial characteristics, as assessed by histologic, electron microscopic and immunocytochemical procedures. Close cell-to-cell contacts, desmosomes and microvilli were visualized in electron micrographs. In addition, we observed immunocytochemical localization of epithelial antigens in the cells which constituted the monolayer by using antisera raised against purified prostatic epithelium. Prostatic acid phosphatase was not detected histochemically in the monolayers and may reflect the non-secretory state of the cells. Growth parameters under various hormonal conditions were assessed by counting metaphase arrested cells, total cell number and measurement of the area covered by the monolayers. Proliferation was significantly increased by the addition of physiological concentrations of either testosterone or 5 alpha-dihydrotestosterone.

Cell Count↗