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Biomedical subjects

D J Morris

Publications and source records attributed to D J Morris.

At least 73 records · Page 4Linked to original sources
PubMed1994

Analysis of 133 meioses places the genes for nevoid basal cell carcinoma (Gorlin) syndrome and Fanconi anemia group C in a 2.6-cM interval and contributes to the fine map of 9q22.3.

Four disease genes (NBCCS, ESS1, XPAC, FACC) map to 9q22.3-q31. A fine map of this region was produced by linkage and haplotype analysis using 12 DNA markers. The gene for nevoid basal cell carcinoma syndrome (NBCCS, Gorlin) has an important role in congenital malformations and carcinogenesis. Phase-known recombinants in a study of 133 meioses place NBCCS between (D9S12/D9S151) and D9S176. Haplotype analysis in a two-generation family suggests that NBCCS lies in a smaller interval of 2.6 cM centromeric to D9S287. These flanking markers will be useful clinically for gene tracking. Recombinants also map FACC (Fanconi anemia, group C) to the same region, between (D9S196/D9S197) and D9S287. The recombination rate between (D9S12/D9S151) and D9S53 in males is 8.3% and 13.2% in females, giving a sex-specific male:female ratio of 1:1.6 and a sex-averaged map distance of 10.4 cM. No double recombinants were detected, in agreement with the apparently complete level of interference predicted from the male chiasmata map.

Basal Cell Nevus Syndrome↗
PubMed1994

A YAC contig spanning the nevoid basal cell carcinoma syndrome, Fanconi anaemia group C, and xeroderma pigmentosum group A loci on chromosome 9q.

Nevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome) is an autosomal dominant disorder, characterized primarily by multiple basal cell carcinomas, epithelium-lined jaw cysts, and palmar and plantar pits, as well as various other features. Loss of heterozygosity studies and linkage analysis have mapped the NBCCS gene to chromosome 9q and suggested that it is a tumor suppressor. The apparent sensitivity of NBCCS patients to UV and X-irradiation raises the possibility of hypersensitivity to DNA-damaging reagents or defective DNA repair being etiological in the disorder. The recent mapping of the Fanconi anaemia group C (FACC) and xeroderma pigmentosum complementing group A (XPAC) genes to the same region on 9q has led us to begin the molecular dissection of the 9q22-q31 region. PCR analysis of the presence or absence of 10 microsatellite markers and exons 3 and 4 of the XPAC and FACC genes, respectively, allowed us to order 12 YACs into an overlapping contig and to order the markers as follows: D9S151/D9S12P1-D9S12P2-D9S197-D9S196-D9 S280-FACC-D9S287/XPAC-D9S180-D9S6-D9 S176 . Sizing of the YACs has provided an initial estimate of the size of the NBCCS candidate region between D9S12 and D9S180 to be less than 1.65 Mb.

Basal Cell Nevus Syndrome↗
PubMed1994

Possible endogenous regulators of steroid inactivating enzymes and glucocorticoid-induced Na+ retention.

Various endogenous substances which bear similar structural resemblances to glycyrrhetininc acid were screened for inhibitory activity against 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) and 5 beta-reductase (5 beta-R). Among the compounds screened, 3 alpha, 5 beta-tetrahydroprogesterone (3 alpha,5 beta-THP) was a potent inhibitor of 11 beta-OHSD and a moderate inhibitor of 5 beta-R. Of the bile acids tested, chenodeoxycholic acid (CDCA) was the most potent inhibitor of both 11 beta-OHSD and 5 beta-R. Cholic acid (CA), a moderate inhibitor of 11 beta-OHSD was a weak inhibitor of 5 beta-R, whereas deoxycholic acid was a moderate inhibitor of 5 beta-R but a weak inhibitor of 11 beta-OHSD. 3 alpha, 5 beta-THP and bile acids were also tested to determine whether, like GA, they could confer mineralocorticoid actions upon corticosterone (B). In adrenalectomized rats pretreated with CDCA or 3 alpha,5 beta-THP, B caused a significant antinatriuresis; the effect of B plus CDCA was blocked by the antimineralocorticoid, RU 28318. Thus, we report on two structurally similar endogenous substances, 3 alpha, 5 beta-THP and CDCA, which inhibit both 11 beta-OHSD and 5 beta-R activity, and which can confer mineralocorticoid actions upon the glucocorticoid, B.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

Other physiological considerations of protective mechanisms of mineralocorticoid action.

Mineralocorticoid receptors (MR) are protected from the effects of endogenous glucocorticoids (GC) in mineralocorticoid (MC) target tissues such as the kidney and the parotid gland. This protection is thought to be provided by 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD). 11 beta-OHSD metabolizes cortisol (in humans) and corticosterone (B) (in the rat) to cortisone and 11-dehydro-B, their respective inactive dehydro products. We have previously shown that the antinatriuretic actions of the MC deoxycorticosterone (DOC) are amplified in carbenoxolone (CBX) treated adrenalectomized (ADX) rats. CBX is believed to inhibit 11 beta-OHSD activity; DOC, however, is not a substrate for this enzyme. We now report on 11-desoxycortisol (11-desoxy-F) and 2 alpha-methylcortisone, substances which possess no intrinsic antinatriuretic activity, are not metabolized by 11 beta-OHSD and yet cause Na+ retention in CBX-treated ADX rats. Given that none of the above steroids are substrates for 11 beta-OHSD it is unlikely that the inhibition of this enzyme is involved in the unmasking of the Na+ retention observed when these substances are given to CBX-treated animals. These results provide further evidence for an additional protective mechanism, that protects MR from the inappropriate binding of excessive amounts of endogenous MCs.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

Same-day testing for human immunodeficiency virus antibodies.

We analysed the specificity of a screening enzyme-linked immunosorbent assay for human immunodeficiency virus antibodies, and found that 18 of 1878 serum specimens (1.0%) from an open access clinic gave false reactive results. Introduction of true same-day testing therefore required the use of more than one assay before a reactive result could be reported. A testing strategy was devised with a 4 h turn-around time which gave accurate results for 11 positive and 119 negative specimens.

AIDS Serodiagnosis↗
PubMed1994

Developmental changes in rat renal 11 beta-hydroxysteroid dehydrogenase.

11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) transforms endogenous glucocorticoids to their respective "biologically inert" 11-dehydro derivatives. A decrease in enzyme activity allows glucocorticoids to induce mineralocorticoid-like renal sodium retention. Since positive sodium balance is required for optimum growth in the newborn, we hypothesized that renal 11 beta-OHSD activity would be low in the postnatal period, a time of active growth. To test this, incubations with corticosterone were carried out using minces or homogenates prepared from kidneys of newborn, 8-day-old, and mature Sprague-Dawley rats. 11 beta-OHSD activity in renal minces, assessed by the percent of corticosterone (10(-8) M) transformed to 11-dehydrocorticosterone (compound A), was significantly lower in the newborn kidney (newborn 45.7 +/- 3.8%, 8 day 70.2 +/- 3.8%, and adult 73.4 +/- 3.1%, P < 0.001 1 vs. 8 day). Parallel studies were conducted using an antibody directed against liver 11 beta-OHSD counter stained with immunofluorescent labeled IgG. Kidneys from mature rats were brightly stained at S2 and S3 segments of proximal tubules. In contrast, staining was barely detectable in kidneys from the newborn and 8-day-old rats. When enzyme kinetics were examined in kidney homogenates (average protein concentration 2.5 mg/ml) in the presence of 200 microM NADP+, the apparent Km for corticosterone in the adult was 4.42 x 10(-6) M with a corresponding Vmax of 1.33 x 10(-9) mol/min/mg protein, while the apparent Km for corticosterone in the newborn was calculated to be 12.8 x 10(-8) M with a Vmax of 2.08 x 10(-11) mol/min/mg protein.(ABSTRACT TRUNCATED AT 250 WORDS)

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

Gastroenteritis due to adenovirus type 41 in an adult with chronic lymphocytic leukemia.

We describe a case of gastroenteritis due to adenovirus type 41 that lasted for 46 days (until the patient's death) in a 56-year-old woman with terminal B cell chronic lymphocytic leukemia. Adenovirus particles were detected by electron microscopy in five stool specimens collected between 5 and 39 days after the onset of the diarrheal illness. The virus was identified as adenovirus type 41 by viral neutralization tests and other assays. We discuss the potential pathogenicity of subgenus F adenoviruses in immunocompromised patients.

Adenovirus Infections, Human↗
PubMed1994

Local fasciocutaneous flaps for olecranon coverage.

In 1989 we began to treat soft-tissue defects around the olecranon process with local fasciocutaneous flaps as our preferred method of treatment. These soft-tissue defects are complications of bursitis, degenerative joint disease, and burns. They may also result from pressure necrosis over the olecranon in patients with impaired sensation. Because of the difficulty in treating these wounds a variety of local muscle, musculocutaneous, fasciocutaneous, distant, and free flaps have been described. Fasciocutaneous flaps have the advantage of using regional tissue in a single stage. Fasciocutaneous flaps around the elbow can be categorized as proximally or distally based. Proximally based flaps include the radial and ulnar forearm flaps as well as the posterior interosseous flap. Distally based flaps are based on upper elbow collaterals including the radial collateral artery, the middle collateral artery, and the anterior and posterior ulnar recurrent arteries. Eleven fasciocutaneous flaps were used in 10 patients with a follow-up of 1 to 3 years. All flaps survived and provided primary wound closure. Complications included 1 patient with recurrent ulceration after being healed for 6 months and 1 patient with a transient neuropraxia of the posterior interosseous nerve that resolved after 2 weeks. These flaps provide long-term stable coverage of olecranon wounds by using regional tissue with an acceptable donor site morbidity.

Adult↗
PubMed1994

Three-dimensional folded free-flap reconstruction of complex facial defects using intraoperative modeling.

Free-tissue transfer has emerged as the ideal way of reconstructing complex facial defects. Multifaceted free flaps are often needed, and we have developed a simple technique to determine both the volume of tissue required and the localization of the various epithelial surfaces, thereby simplifying these complex reconstructions. We report our experience in reconstructing 19 complex facial defects in which we have used an intraoperative alginate moulage that has provided an accurate three-dimensional model of the defect, helping to determine the volume of the flap required. The reconstruction was further simplified by converting this three-dimensional model into a two-dimensional pattern by wrapping the model with a piece of Esmarch bandage, thereby determining the locations and sizes of the epithelial surfaces. The pattern was then transferred to the donor site and the flap de-epithelialized and thinned in situ with complete confidence that the tissue was "tailor-made" for the defect.

Adolescent↗
PubMed1994

Adverse effects and drug interactions of clinical importance with antiviral drugs.

Most antiviral drugs are nucleoside analogues with potential teratogenic, embryotoxic, carcinogenic and antiproliferative activities. They must be administered with caution during pregnancy, because some are known teratogens (e.g. amantadine) and a similar propensity cannot be entirely excluded for others (e.g. aciclovir). Their adverse effects mostly involve bone marrow depression (e.g. granulocytopenia with ganciclovir, anaemia with zidovudine) or neurotoxicity (e.g. seizures with interferon-alpha, peripheral neuropathy with zalcitabine), although gastrointestinal effects are also seen. Idiosyncratic reactions include didanosine-induced acute pancreatitis. Only inosine pranobex is largely free from toxicity. Idoxuridine must be administered topically, given the severity of its systemic adverse effects. Drug interactions involving antiviral agents mostly reflect shared toxicity with other agents (e.g. neutropenia with ganciclovir and zidovudine, pancreatitis with didanosine and alcohol), although renal excretion or hepatic metabolism may be implicated. Given the possibility of severe adverse reactions and drug interactions, antiviral chemotherapy should only be used for potentially serious virus infections. Topical administration avoids systemic adverse effects but not mutagenic risks, and may result in exposure of individuals other than the patient (e.g. aerosolised ribavirin).

AIDS-Related Opportunistic Infections↗
PubMed1993

Computer network for a diagnostic virology laboratory.

A data base for a large diagnostic virology laboratory is described. The system uses a network of personal computers. It allows the entry, long-term storage, and subsequent retrieval of specimen and patient records (comprising personal identifiers and specimen and result information), and hard-copy results reporting. Sited entirely within the laboratory, the network is not connected to a modem. Within the laboratory there is restricted access to human immunodeficiency virus test results to guarantee patient confidentiality. Retention of a hard-copy of specimen request cards ensures the availability of the original clinical information. The data base is copied on a second file server to facilitate searches, and daily streaming onto magnetic tape provides system protection in the event of hard disc failure. Matching of old and new patient records is done by surname, date of birth, and sex, and therefore duplicate records accumulate when patient names are misspelt on specimen request forms. The system requires further development to speed searches of the data base and to achieve automatic generation of laboratory worksheets. Future goals are the replacement of hard-copy records of clinical information and hard-copy reporting with on-line access to hospital data bases and on-line requesting by and reporting to the clinician.

Clinical Laboratory Information Systems↗
PubMed1993

Comparative epidemiology of rotavirus, subgenus F (types 40 and 41) adenovirus and astrovirus gastroenteritis in children.

We report a 5 year prospective study of episodes of rotavirus, subgenus F adenovirus, and astrovirus gastroenteritis diagnosed by electron or immune electron microscopy in a single regional virology laboratory. Of 1426 total infections, the numbers in each category were 1117 (78.3%), 254 (17.8%), and 20 (7.9%), respectively. Using restriction endonuclease analysis or immune electron microscopy, all but 20 of the subgenus F adenovirus strains were classified as type 40 (n = 50) or type 41 (n = 184). Rotavirus and astrovirus infections were more prevalent in winter than summer, whereas subgenus F (either type 40 and 41) adenoviruses showed no seasonal variation in prevalence. The ratio of type 40 to all typable subgenus F adenoviruses declined between 1984 and 1986 and then increased again. Adenoviruses were relatively more important as causes of viral gastroenteritis in infants aged less than 6 months than in toddlers aged 12 months or more, but even in young infants more rotavirus than adenovirus infections were diagnosed. Our data confirmed the epidemiological differences between rotavirus, subgenus F adenovirus and rotavirus gastroenteritis and documented the shared epidemiological characteristics of type 40 or 41 adenovirus infections.

Adenovirus Infections, Human↗
PubMed1993

Immunohistological detection of human herpes virus 6 in formalin-fixed, paraffin-embedded lung tissues.

Human herpes virus type 6 (HHV-6) infection is widespread in healthy individuals. The only definite disease association is with exanthem subitum in infants though the virus has been linked with a variety of other diseases including interstitial pneumonitis in bone marrow allograft recipients. In order to investigate the role of HHV-6 in the latter disease we have developed an optimised staining method for the demonstration of specific antigen in routinely processed post-mortem tissues. Formalin-fixed, paraffin-embedded lung tissue from 8 immunocompromised patients who died from interstitial pneumonitis was subjected to immunoperoxidase staining with monoclonal antibodies against HHV-6, cytomegalovirus (CMV), and adenovirus, using a modified avidin-biotin complex (ABC) method. Staining for HHV-6 was obtained in 6 of the 8 patients studied and was present in pneumocytes and macrophages. CMV and adenovirus antigens were identified in 4 and 6 patients, respectively. Whilst the lung tissue of 6 patients contained more than one virus, there was no evidence of cross-reactivity between the monoclonal antibodies. We demonstrated that accurate localisation of HHV-6 using monoclonal antibodies is possible in post-mortem lung tissue and conclude that either HHV-6 alone or in combination with other viruses may play a role in the development of interstitial pneumonitis following bone marrow transplantation or chemotherapy.

Adenoviridae Infections↗
PubMed1993

HLA mismatching and cytomegalovirus infection as risk factors for transplant failure in cyclosporin-treated renal allograft recipients.

In a study of the effects on renal allograft survival of HLA mismatching, mismatching for cytomegalovirus (CMV) antibody status, and post-transplant CMV infection, 148 cyclosporin-treated renal transplant recipients were given kidneys optimally matched for HLA-A, -B, and -DR antigens but not matched for CMV antibody status. Mismatching for HLA-B and -DR antigens was associated with a greater number of rejection episodes and a lower graft survival, but mismatching for CMV antibody status and posttransplant primary or recurrent CMV infection exerted no effect on graft survival. The role of matching of renal transplant recipients and donors for CMV antibody status in preference to HLA matching (proposed as a means of reducing the mortality associated with primary CMV infection) is discussed.

Antibodies, Viral↗