Search PubMed⌕ Search

Biomedical subjects

D J Morris

Publications and source records attributed to D J Morris.

At least 91 records · Page 5Linked to original sources

Somatic cell hybrid mapping on mouse chromosome 11 (MMU11): assignment of markers relative to two breakpoints in band D.

Mouse x rat somatic cell hybrids were generated by fusing mouse cell lines that are heterozygous for reciprocal translocations involving the T42H and T9Ad breakpoints on mouse chromosome 11 (MMU11) to a thymidine kinase-negative (Tk-) rat cell line, RT2Tk-. Selection in HAT medium with geneticin disulfate (G418) resulted in some hybrid clones retaining only one derivative translocation chromosome with that part of MMU11 carrying the Tk-1 locus. Southern blot and PCR analyses of these hybrids were used to map the two breakpoints and 30 markers relative to them. The T42H breakpoint has been localized between Mpo and the Cola-1/Hox-2 cluster of loci and is proximal to the T9Ad breakpoint. The T9Ad breakpoint is proximal to the distal loci Tk-1, Gaa, D11Jkn1, and P4hb. The positions of 14 loci (Hox-2, Cola-1, Rara, Phb, Erba, Rnula-1, D11Pas1, Gfap, D11Mit13, D11Mit11, D11Mit12, Myla, Empb3 and Gh) have been further refined by their localization between the two breakpoints in band D. This study therefore improves the correlation of the genetic and physical maps of MMU11 and extends the known homology between MMU11 and human chromosome 17 (HSA17) by the assignment of three additional HSA17 markers, the profilin gene, Pfn, an anonymous marker, D17s28h, and the Crk oncogene, to above the T42H breakpoint; and the prohibitin gene, Phb, to between the T42H and T9Ad breakpoints in band D on MMU11.

Animals↗

11-Dehydrocorticosterone in the presence of carbenoxolone is a more potent sodium retainer than corticosterone.

In vivo, corticosterone and 11-dehydrocorticosterone are interconverted in the liver and possibly kidney by 11 beta-hydroxysteroid dehydrogenase. In an effort to evaluate the relevance of this reversible reaction in relation to urinary sodium and potassium excretion, we investigated the effects of 11-dehydrocorticosterone in the presence and absence of carbenoxolone, a potent inhibitor of the oxidative component of 11 beta-hydroxysteroid dehydrogenase, and compared them with the effects of similar doses of corticosterone in carbenoxolone-treated rats. All experiments were performed on adrenalectomized male rats. Here we describe that in carbenoxolone-treated rats 11-dehydrocorticosterone and corticosterone display antinatriuretic activity, although under the conditions of this study 11-dehydrocorticosterone is a more potent sodium retainer than its parent steroid corticosterone. In addition, the antinatriuretic effects of 11-dehydrocorticosterone (like the antinatriuretic effects of corticosterone in carbenoxolone-treated rats) were blocked by the specific antimineralocorticoid RU28318.

Adrenalectomy↗

18-Substituted steroids. Part 18. Chemical synthesis and mineralocorticoid activity of 2 alpha- and 2 beta-hydroxyaldosterone.

The 2 alpha-hydroxy and 2 beta-hydroxy derivatives of aldosterone have been synthesized chemically from aldosterone, after the earlier identification of 2 alpha-hydroxylated metabolites formed in liver. Both 2 alpha- and 2 beta-hydroxyaldosterone are potent mineralocorticoids, with activities on the order of 1/10 that of aldosterone on the basis of a rat bioassay.

Aldosterone↗

Fatal disseminated adenovirus type 2 infection following bone marrow transplantation for Hurler's syndrome: a primary infection.

A 5-month-old girl given an allogeneic bone marrow transplant for Hurler's syndrome succumbed to fatal pneumonia 5 weeks after the transplant. Adenovirus type 2 was isolated from her urine before she died. Immunoperoxidase and electron microscopical studies of liver and lungs post mortem confirmed a disseminated adenovirus infection. The serological findings and the patient's young age suggested that the infection was a primary one. The importance of considering exogenous sources of adenovirus infection in bone marrow transplant recipients is discussed.

Adenovirus Infections, Human↗

The polymerase chain reaction for detecting adenovirus DNA in formalin-fixed, paraffin-embedded tissue obtained post mortem.

The polymerase chain reaction (PCR) was used to detect adenovirus DNA in formalin-fixed, paraffin-embedded tissue obtained post mortem. Adenovirus DNA was successfully amplified from specimens of lung and liver from two patients with disseminated adenovirus infection confirmed by virus isolation, electron microscopy and/or immunohistochemistry. Negative results were obtained for specimens of lung from two patients with cytomegalovirus pneumonia. The specificity of the adenovirus PCR was confirmed by means of a digoxigenin-labelled probe generated in a separate PCR. Detection of viral nucleic acid by PCR in tissues obtained post mortem has considerable diagnostic potential.

Adenovirus Infections, Human↗

Interactions between glucocorticoids and mineralocorticoids in the regulation of renal electrolyte transport.

The enzyme 11 beta-hydroxy steroid dehydrogenase (11 beta-OHSD) was described and its location in various organs noted more than 30 years ago (Mahesh and Ulrich, 1960; Jenkins, 1966). 11 beta-OHSD inactivates circulating glucocorticoids by transforming the hydroxyl group at the 11-carbon to a keto group. This chemical reaction has taken on a greater degree of physiologic and clinical significance in recent years. It has been suggested that 11 beta-OHSD, present in mineralocorticoid target tissues, can act as a 'guardian' over the mineralocorticoid receptor by transforming circulating endogenous glucocorticoids to their respective 'biologically inert' 11-dehydro derivatives (Edwards et al., 1988; Funder et al., 1988). These derivatives do not bind to mineralocorticoid receptors (MR) while both their parent compounds and mineralocorticoids bind to cloned MR with equal affinity (Arriza et al., 1987). 11 beta-OHSD has generated a growing sense of scientific excitement since this enzyme may represent one of a family of metabolic pathways or mechanisms which can regulate steroid induced renal reabsorption of sodium. Such 'protective' enzymatic pathways, present in the kidney and elsewhere, may not only control the access of glucocorticoids to MR, but control the access of glucocorticoids to glucocorticoid receptors (GR) (Teelucksingh et al., 1990; Monder, 1990) as well as access of mineralocorticoids to their own receptors. This review will focus on this concept of a family of protective enzymatic pathways and the possible physiological implications.

11-beta-Hydroxysteroid Dehydrogenases↗

Reduced aldosterone metabolites in hypertension.

Significant quantities of 5 alpha and 5 beta-Ring A-reduced metabolites and several polar cytochrome P-450 dependent hydroxylated neutral metabolites of aldosterone (Aldo) (NMA) are soon present in the kidney during the latent period, prior to the expression of Aldo's effects on Na+ and K+. Their levels in the kidney (a) correlate, in a dose-dependent manner, with the magnitude of physiological responses to Aldo in male rats, (b) are lower in the kidneys of females, which show smaller responses to Aldo than males, (c) are lower in the kidneys of males treated with the anti-mineralocorticoid spironolactone, and (d) their synthesis can be regulated by dietary Na+ and K+. Anti-mineralocorticoids completely inhibit synthesis of 5 alpha-reduced metabolites of Aldo in both kidney and toad bladder and of several of the polar hydroxylated NMA in both liver and kidney. 5 alpha-Reduced metabolites and their 2-hydroxylated derivatives possess significant mineralocorticoid activity and their synthesis is increased in rats fed a low Na+ diet and decreased with a high Na+ diet. We have suggested that their synthesis may play a major role in the expression and/or regulation of the individual renal anti-natriuretic and kaliuretic actions of Aldo.

Aldosterone↗

Double fillet of foot free flaps for emergency leg and hand coverage with ultimate great toe to thumb transfer.

A 42-year-old woman presented with avulsion amputation of her right leg 14 cm below the knee joint and a hemihand amputation of the opposite hand. Two free flaps, taken from the amputated foot, were used to cover the injured extremities. The sole fillet flap was used to preserve length and cover the injured leg, while the dorsal fillet flap covered the injured hand and provided ectopic storage for the great toe. The great toe was later transferred on a pedicle for thumb reconstruction. Spare parts surgery is now a well-accepted technique. This case demonstrates maximum utilization of amputated parts for functional and aesthetic reconstruction.

Adult↗

Stimulus features affecting psychophysical detection thresholds for electrical stimulation of the cochlea. II: Frequency and interpulse interval.

Psychophysical detection thresholds for electrical stimulation of the cochlea were measured in nonhuman primates (macaques) as part of a series of experiments exploring the stimulus features affecting detection. The monkeys were trained psychophysically using operant conditioning. One ear was treated with neomycin to destroy hair cells, and implanted with electrodes in the scala tympani and/or the cochlear wall. In experiment 1, detection thresholds were measured for trains of fixed-duration pulses and for sinusoids. For long-duration pulses (1 to 2 ms/phase), thresholds decreased as a function of frequency (pulse rate), reaching a minimum at a frequency between 125 and 210 pps, then increased as frequency was further increased. For shorter duration pulses, thresholds usually decreased monotonically as a function of frequency but sometimes showed a slight increase as a function of frequency near the highest frequencies tested. Typically slopes of the threshold versus frequency functions for fixed-duration pulses were equal to or less than slopes of threshold versus frequency functions for sinusoidal signals, where frequency and phase duration covaried. Additional observations on two of the cases were made in experiments 2 and 3. In experiment 2, thresholds for pairs of pulses were measured as a function of interpulse interval. Thresholds decreased as a function of interpulse interval up to intervals of 2 to 4 ms and then increased slightly. In experiment 3, thresholds were measured as a function of stimulus duration at two frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Measles encephalitis during immunosuppressive treatment for acute lymphoblastic leukaemia.

Between 1971 and 1989 measles encephalitis was identified in five children receiving chemotherapy for acute lymphoblastic leukaemia. Review of these and previously reported cases of measles encephalitis in immunosuppressed patients failed to identify any pathognomonic features in the history, the clinical presentation, or the results of electroencephalography or computed tomography. Detection of measles virus antigen in nasopharyngeal secretions or intrathecal synthesis of specific antibody was not possible in all instances. Early diagnosis by direct detection of viral antigen in the brain was confounded by difficulties in identifying areas of the brain suitable for biopsy. Increasing herd immunity to measles in the general population by vaccination is the only effective intervention against measles encephalitis in immunosuppressed children. Measles encephalitis must be remembered as a possible explanation of encephalopathy in the immunocompromised child: the benefits of early use of antiviral agents need to be evaluated.

Brain↗

Activity of 11 beta-hydroxysteroid dehydrogenase in toad bladder: effects of 11-dehydrocorticosterone.

11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) transforms circulating glucocorticoids to their "biologically inert" 11-dehydro derivatives. Isoforms of 11 beta-OHSD with different cofactor requirements and biochemical properties [Michaelis constant (Km) and maximal velocity (Vmax)] exist in the kidney. Since epithelial cells derived from the toad bladder also contain this enzyme, we wished to further characterize its properties in prepared cell homogenates. 11 beta-OHSD from toad bladder demonstrated a clear preference for NAD+ over NADP+ as a cofactor similar to that observed in renal cortical collecting duct (CCD) cells. Furthermore, 11 beta-OHSD had a rapid onset of action. The apparent Km for corticosterone was 16.3 x 10(-8) M, a value comparable to that observed for enzyme from CCD, and a Vmax of 4.8 x 10(-12) mol.mg protein-1.min-1. The end product, 11-dehydrocorticosterone (compound A), influenced enzyme activity; it increased 11 beta-OHSD activity at corticosterone concentrations below the apparent Km for the enzyme and inhibited 11 beta-OHSD activity at corticosterone concentrations above the Km for the enzyme. The inhibitory effects of compound A appeared noncompetitive with an apparent equilibrium constant (Ki) of 2.8 x 10(-7) M. Consistent with its inhibitory action on 11 beta-OHSD, compound A (10(-6) M) enhanced the short-circuit current response to corticosterone (10(-7) M) in the intact toad bladder (experimental 2.03 +/- 0.33 vs. control 1.40 +/- 0.17 times above baseline; n = 7, P < 0.01). Thus 11 beta-OHSD in toad bladder resembles the isoform found in CCD, and compound A may be biologically important as a regulator of 11 beta-OHSD.

11-beta-Hydroxysteroid Dehydrogenases↗

Cowpox virus.

Explore the source record for details and available documents.

Adolescent↗