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Biomedical subjects

B J Morris

Publications and source records attributed to B J Morris.

At least 163 records · Page 9Linked to original sources
PubMed1988

Dopaminergic regulation of striatal proenkephalin mRNA and prodynorphin mRNA: contrasting effects of D1 and D2 antagonists.

In situ hybridization was used to measure the levels of proenkephalin mRNA and prodynorphin mRNA in regions of rat striatum and nucleus accumbens. Chronic administration of haloperidol (2.4 mg/kg/day for 7 days) increased the levels of proenkephalin mRNA in both striatum and nucleus accumbens. In contrast, the levels of prodynorphin mRNA were not significantly affected in any region. Chronic administration of the D1 antagonist SCH 23390 (2.4 mg/kg/day for 7 days) decreased the striatal content of proenkephalin mRNA. A similar effect was seen in the lateral nucleus accumbens. The levels of prodynorphin mRNA were unaffected by SCH 23390 treatment in all regions examined. These results suggest that there is no major tonic dopaminergic regulation of prodynorphin synthesis in the basal ganglia. However, it appears that there is a tonic suppression, via D2 receptors, and a tonic enhancement, via D1 receptors, of proenkephalin synthesis, in the striatum and nucleus accumbens.

Animals↗
PubMed1988

Distinct GABAA receptor alpha subunit mRNAs show differential patterns of expression in bovine brain.

Specific oligonucleotide probes have been used to visualize the regional and cellular distribution of the mRNAs encoding three structurally distinct GABAA receptor alpha subunits in bovine brain. In situ hybridization analysis showed that these transcripts differ in distribution and in relative abundance. In frontal cortex the alpha 1 and alpha 2 transcripts are most abundant in layers II-IV, whereas the alpha 3 mRNA is most abundant in layers V and VI. In the hippocampal complex, the alpha transcripts are differentially distributed in the entorhinal cortex and subiculum. The alpha 2 transcript is enriched in the dentate gyrus and CA4/CA3 regions of the hippocampus. In the cerebellum, essentially only the alpha 1 transcript is detectable in granule cells, Purkinje cells, and stellate/basket cells. These results suggest that the different alpha subunits represent components of distinct GABAA receptor subtypes.

Animals↗
PubMed1988

Human papillomavirus: the untreated male reservoir.

Human papillomavirus infection currently is accepted as a major factor in the etiology of carcinoma of the cervix, vagina and vulva. While the nature of genital human papillomavirus infection in women is well documented, detailed knowledge of the disease in the male partners is lacking. Therefore, a prospective study was done to define the disease in the genitals of heterosexual men and to formulate an appropriate plan of management. We studied 52 men during an 8-month period for evidence of genital human papillomavirus infection. The majority of the lesions occurred on the shaft of the penis and on the foreskin of uncircumcised men. Deoxyribonucleic acid dot hybridization of biopsies of macroscopic warts and suspected warty lesions with mixed human papillomavirus types 6 and/or 11 and 16 and/or 18 probes revealed that 87 and 55 per cent, respectively, were positive for 1 or more of these human papillomavirus types. Of the macroscopic warts and subclinical lesions 52 and 29 per cent, respectively, contained the more potentially oncogenic types 16 and/or 18, either alone or in combination with types 6 and/or 11. There was no evidence of human papillomavirus in any semen or urine sample but human papillomavirus deoxyribonucleic acid sequences were detected in 31 per cent of the biopsies from apparently normal penile skin and in 18 per cent of the urethral mucosal biopsies. We suggest that management of human papillomavirus infection be directed toward prevention and contact screening, together with ablation of localized lesions.

Acetates↗
PubMed1988

Electrical stimulation in vivo increases the expression of proenkephalin mRNA and decreases the expression of prodynorphin mRNA in rat hippocampal granule cells.

In situ hybridization histochemistry in combination with RNA blot techniques was used to study the regulation of opioid gene expression in rat hippocampus. By use of a prodynorphin cDNA probe, a strong hybridization signal was identified in the granule cell layer of the hippocampus. However, experiments using a proenkephalin cDNA probe revealed that the content of proenkephalin mRNA was considerably lower than that of prodynorphin mRNA. Following five brief trains of high-frequency electrical stimulation to the dentate gyrus, the proenkephalin mRNA content of the granule cells, measured 22 hr later, was substantially increased on the stimulated side. In contrast, levels of prodynorphin mRNA were markedly decreased ipsilateral to the stimulation site. These results were confirmed by RNA blot analysis of extracted mRNA. The decrease in prodynorphin mRNA content first became apparent between 4 and 7 hr after the end of stimulation. Distinct mechanisms, therefore, regulate the expression of proenkephalin mRNA and prodynorphin mRNA in rat hippocampus.

Animals↗
PubMed1988

Three Alu repeated sequences associated with a human glandular kallikrein gene.

1. Recently the complete primary structure of a human glandular kallikrein gene, hGK-1, was reported. The present paper presents further structural information. 2. Associated with the gene were three Alu repeated sequences; one in the second intron and two approximately 0.4 kb and 1.2 kb upstream. 3. The 5' non-coding and 5' flanking DNA was highly homologous to that in the mouse genes. 4. Different polyadenylation signals are used in different human kallikrein genes.

Animals↗
PubMed1988

Triton WR-1339 injected into rats enters renal renin granules.

To test directly the possibility that substances in extracellular fluid can gain access to renin storage granules in renal juxtaglomerular cells, rats were injected with Triton WR-1339, which binds to plasma proteins. A heavy granule fraction was prepared, and isopycnic sucrose density gradient centrifugation was performed. The renin granule peak was found to be altered from a mean equilibrium density of 1.202 g/ml in control rats to 1.196 g/ml for rats injected with Triton WR-1339 (P less than 0.005). The distribution of angiotensinogen, which is bound in kidney granules having a different buoyant density, was also examined and found to be unaltered. After injection, Triton WR-1339 binds to circulating plasma proteins. The results for renin support the possibility of pinocytotic uptake of protein-Triton WR-1339 complexes by the juxtaglomerular cells with subsequent fusion of the endocytotic lysosomal vacuoles with renin granules accounting for the translocation of ingested substances into the granule matrix. If so, the potential would therefore exist for interaction(s) of ingested extracellular substances with renin or other components in the granules. The present study has therefore demonstrated directly that endogenous extracellular substances may enter renin granules.

Angiotensinogen↗
PubMed1988

Antagonist-induced opioid receptor up-regulation. I. Characterization of supersensitivity to selective mu and kappa agonists.

In this study, chronic opioid antagonist-induced alterations in sensitivity to selective mu- and kappa-opioid agonists were examined. Administration of naloxone (0.5 mg/kg/hr) via osmotic minipumps eliminated the antinociception elicited by the mu-agonist, morphine, but did not affect that induced by the kappa-agonist, U50, 488H. After 1 week of treatment and after pump removal, dose-response curves for the induction of antinociception by morphine against noxious heat, pressure and electrical stimulation were shifted to the left across the entire time course of action: this supersensitivity subsided over a period of 1 week postremoval. No facilitation of the actions of U50,488H was seen. Three days of infusion also induced a significant supersensitivity to morphine but a single, acute high dose of naloxone (3.0 mg/kg) was ineffective. The effect of naloxone was dose-dependent (0.05-0.50 mg/kg/hr). Chronic treatment at 3.0 mg/kg/hr blocked the antinociception induced by both U50,488H and morphine. After 1 week and after pump removal, the antinociceptive action of U50,488H against pressure, but not heat, was enhanced; the antinociceptive action of morphine against both heat and pressure was facilitated. These data, in conjunction with our autoradiographical findings suggest: 1) it is possible to selectively block and up-regulate mu as compared to kappa receptors; 2) chronic treatment with naloxone can induce a supersensitivity to kappa-agonists; and 3) the pool of kappa-receptors acting antinociceptively against pressure may differ from that acting against heat.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1988

Antagonist-induced opioid receptor up-regulation. II. Regionally specific modulation of mu, delta and kappa binding sites in rat brain revealed by quantitative autoradiography.

The neurochemical basis for the supersensitivity to mu or kappa opiate agonists observed after chronic naloxone infusion (reported in the preceding paper) has been investigated using the technique of quantitative in vitro autoradiography. The binding of [3H]-D-Ala2MePhe4Glyol enkephalin (3H-DAGO) to mu opioid sites was increased in many brain regions after chronic administration (7 days) of a low dose of naloxone (0.5 mg/kg/hr). The greatest increases were seen in the hippocampal strata moleculare and lucidum. The binding of [3H]-D-Ala2-D-Leu5 enkephalin (3H-DADL) to delta sites and of [3H]-bremazocine to kappa sites were not significantly affected in any region. In contrast, after administration of a higher dose of naloxone (3.0 mg/kg/hr), the binding to mu, delta and kappa sites was increased in many brain areas, suggesting that up-regulation is observed only when a sufficient proportion of the receptors in vivo are occupied by the antagonist. However, a different regional pattern of up-regulation was seen for each class of opiate binding site. The greatest increases in kappa binding in the brain were seen in the periaqueductal gray and the hippocampal molecular and pyramidal cell layers. The substantia nigra showed up-regulation of kappa but not of mu sites. Differences in the pattern of mu and kappa binding site up-regulation were also noted in the spinal cord. This regionally specific modulation of opiate binding sites suggests that, for each receptor type, the level of tonic activation varies between individual brain areas. In addition, the data demonstrate that all three types of opiate receptor can undergo up-regulation "in vivo."

Animals↗
PubMed1988

Kallikrein genes: cloning in man and expression in rat renal hypertension.

Genes for the small human glandular kallikrein gene family were isolated. Members of this family include renal/pancreatic kallikrein, prostate-specific antigen and a kallikrein encoded by the first gene that was isolated and completely sequenced, hGK-1. All share strong nucleotide sequence homology, although hGK-1 and the prostate-specific antigen gene are more closely related (86% identity in coding nucleotides). Renal/pancreatic kallikrein has 77% nucleotide homology to prostate-specific antigen, but only 60% amino acid homology. There is strong homology in the 5'-flanking DNA with mouse kallikrein genes, suggesting common regulatory mechanisms. In the rat one-kidney, one clip model of hypertension, renal kallikrein messenger (m)RNA increased during the initial transient rise in plasma renin, and then decreased.

Amino Acid Sequence↗
PubMed1987

Levels of prodynorphin mRNA in rat dentate gyrus are decreased during hippocampal kindling.

The effect of hippocampal kindling on the levels of prodynorphin mRNA in rat hippocampus was examined by in situ hybridization using a synthetic oligonucleotide probe. Cryostat tissue sections were hybridised with a 32P-labelled 100 mer DNA probe complementary to the coding region of rat prodynorphin mRNA, and exposed to X-ray film. In rats exhibiting stage 4 seizures, the levels of prodynorphin mRNA in the dentate gyrus were dramatically reduced compared to control animals. This suggests that the development of kindling is accompanied by a reduction in the rate of synthesis of peptides derived from prodynorphin.

Animals↗
PubMed1987

A model of chronic pain in the rat: high-resolution neuroanatomical approach identifies alterations in multiple opioid systems in the periaqueductal grey.

Inoculation of the tail base of rats with Mycobacterium butyricum led to an arthritic swelling and inflammation of the limbs which displayed a hyperalgesia to noxious pressure: these effects peaked at 3 weeks postinoculation. In vitro autoradiography of coronal sections of rat brain was used for a parallel determination of binding to mu-, delta- and kappa-opioid binding sites. In only two regions, the dorsomedial and dorsolateral parts of the periaqueductal grey (PAG), was a significant change seen: this comprised an increase in binding to kappa-sites, whereas mu- and delta-sites therein were unaffected. This region was analysed for opioid peptides derived from each of the three opioid peptide families known. While no change was seen in levels of immunoreactive (ir)-dynorphin1-17 A (DYN) and ir-Met-enkephalin, a decrease was detected in those of ir-beta-endorphin (beta-EP): this change was restricted to the PAG. These data demonstrate a highly localized and selective influence of chronic arthritic pain upon multiple opioid systems in the PAG of the rat, a structure playing a key role in the control of pain and in the expression of the antinociceptive actions of opioids. The data suggest a possible significance of PAG pools of beta-EP and kappa-receptors in the response to and modulation of chronic pain.

Animals↗
PubMed1987

Detection of specific types of human papillomavirus in cervical scrapes, anal scrapes, and anogenital biopsies by DNA hybridization.

Specific varieties of human papillomavirus (HPV) infecting the anogenital region were detected in clinical samples by use of a filter hybridization technique suitable for rapid screening of cervical and anal scrapes. In this way possibly benign types (HPV6 and HPV11) could be differentiated from types thought to be capable of malignant transformation (HPV 16 and HPV 18). Cervical or anal canal cells were applied directly to nylon filters and fixed by u.v. irradiation before hybridization with mixed viral DNA probes under both low- and high-stringency conditions. In addition, probe for the human Alu-repeated DNA sequence was used to assess the relative amount of total nucleic acids in each sample applied to the filter. HPV DNA was detected in 3 of 19 cervical scrapes from patients with no past or present history of wart virus infection or cervical dysplasia. Within a positive study group totalling 71 patients, HPV (6/11 or 16/18) was detected in cervical scrapes from 24% of 41 patients who did not have visible genital dysplasia, 30% of 27 patients with visible genital dysplasia or cervical intraepithelial neoplasia (CIN) I, and in 1 of 3 patients with past CIN II/III. In addition, HPV6/11 or 16/18 DNA was detected in anal scrapes from 3 of 6 male patients and in 85% of genital biopsies. A notably high proportion (4/6) of vaginal condylomata were positive with both the HPV6/11 and the HPV16/18 mixed viral DNA probes. Of the biopsies prepared for histopathology and positive for HPV DNA, the HPV group-specific antigen could be detected in only 60%.

Anal Canal↗
PubMed1987

Distinct distribution of opioid receptor types in rat lumbar spinal cord.

The distribution of opiate binding sites was studied in sections of rat lumbar spinal cord under conditions selective for mu, delta and kappa receptors. While the levels of mu binding sites were highest in the substantia gelatinosa, elevated levels were also observed in laminae III, IV, V and VIII. In contrast, delta binding was notable only in lamina I. The levels of typical kappa sites were low, and were concentrated in the substantia gelatinosa. An additional, atypical site was detected using 3H-diprenorphine in the presence of mu, delta and kappa receptor blocking agents, and this site was also concentrated in the substantia gelatinosa.

Animals↗
PubMed1987

Primary structure of a human glandular kallikrein gene.

To isolate a human glandular kallikrein gene, a human genomic library was screened with a probe made from a mouse kallikrein cDNA (pMK-1). Overlapping clones were obtained and nucleotide sequence determination showed that they together contained a human glandular preprokallikrein gene, hGK-1, of 5.2 kb. The gene encoded a unique preproprotein of 261 amino acids. The sequence of the mature 237-amino-acid protein had 66% homology with the sequence predicted for human kallikrein synthesized in the pancreas, kidney, and salivary gland. Moreover, it had even stronger homology (78%) with human prostate-specific antigen. The latter lacks an aspartic acid residue essential for kallikrein-specific cleavage, whereas the sequence of this new protein had all of the attributes needed to confer kallikrein-like specificity. Southern blotting indicated that the number of glandular kallikrein genes in man could be limited to three, a situation very different from mouse and rat, which each have a large multigene family. Furthermore, unlike kallikrein genes in the mouse, hGK-1 was not closely linked to other human kallikrein genes. In other respects the structure of the human kallikrein gene resembled that in mouse: coding sequences in the five exons were organized similarly, homology was higher with other members of the kallikrein gene family in the same species, and the three key amino acid residues required by serine proteases for their catalytic activity, together with the residue that confers kallikrein-specific cleavage, were conserved and located on different exons. Thus, if hGK-1 is expressed, its product represents a new, and possibly the only other enzyme with true kallikrein-like specificity in man.

Amino Acid Sequence↗
PubMed1987

Cell biology of cultured anogenital warts.

A simple, reliable culture system for keratinocytes from anogenital warts is described. Using this technique we found that it was possible to produce multiple confluent keratinocyte cultures from two-thirds of the surgically-excised anogenital wart specimens received in our laboratory. Some morphological and cultural differences between these cells and normal keratinocytes derived from neonatal foreskins were observed, although there was no evidence that wart-derived keratinocytes were 'transformed'. The cultures were tested for evidence of HPV-DNA replication using 32P-labelled HPV-DNA probes, for the production of viral capsid proteins using peroxidase-antiperoxidase staining and for whole virus particles using electron microscopy. Fifty-seven per cent (8 of 14) of the wart cultures tested showed persistence of HPV-DNA (5-100 copies HPV-DNA/cell genome equivalent). However, no viral proteins or particles were detected in any culture. This system may prove to be a useful in vitro model for the study of virus-cell interaction and the role of HPV in the malignant conversion of epithelial cells.

Anus Diseases↗
PubMed1987

Renin secretion from malignant pulmonary metastatic tumour cells of vascular origin.

1. A pulmonary chemodectoma/glomangiosarcoma that had metastasized from the thigh was studied after removal from a 22 year old Algerian patient with hypertension, high plasma prorenin and signs of secondary aldosteronism. 2. Renin and renin mRNA were localized in sections of the tumour tissue using monoclonal anti-human renin antibody and human renin cDNA probe, respectively. 3. The cells grew prolifically in culture, but, even though their renin content was similar to that of transfected human juxtaglomerular cell tumour cells (approximately 1 pg/microgram DNA), their rate of secretion of renin was much lower (0.05-0.15 cf. 0.5-1.5 pg/h per microgram DNA). 4. Forskolin (10 mumol/l for 24 h) increased secretion of renin from 1.9 +/- 0.36 to 4.1 +/- 0.64 pg/ml per h of culture (P less than 0.001, n = 11), consistent with cAMP being a second messenger in the secretory mechanism. 5. The cells should provide valuable information about intracellular mechanisms for the regulation of renin synthesis and secretion.

Adolescent↗