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Biomedical subjects

M Holland

Publications and source records attributed to M Holland.

At least 37 records · Page 2Linked to original sources
PubMed1999

The fermionic hanbury brown and twiss experiment

A Hanbury Brown and Twiss experiment for a beam of electrons has been realized in a two-dimensional electron gas in the quantum Hall regime. A metallic split gate serves as a tunable beam splitter to partition the incident beam into transmitted and reflected partial beams. In the nonequilibrium case the fluctuations in the partial beams are shown to be fully anticorrelated, demonstrating that fermions exclude each other. In equilibrium, the cross-correlation of current fluctuations at two different contacts is also found to be negative and nonzero, provided that a direct transmission exists between the contacts.

Journal Article↗
PubMed1999

Cannabinoid CB1 receptors fail to cause relaxation, but couple via Gi/Go to the inhibition of adenylyl cyclase in carotid artery smooth muscle.

1. The aim of the current study was to characterize which cannabinoid receptors, if any, are present on rat carotid artery smooth muscle. Additionally, the effects of cannabinoids on carotid artery tone, on cyclic AMP accumulation and on forskolin-induced relaxation were examined in the same tissue. 2. Stimulation of carotid arteries with forskolin (10 microM) significantly increased cyclic AMP accumulation, an effect that was inhibited in a concentration-dependent manner by the cannabinoid receptor agonist, methanandamide. 3. Similar inhibition was seen with the CB1 agonist HU-210 but this inhibition was not mimicked by the CB2 agonist, WIN 55,2212-2. 4. The inhibitory effect of methanandamide on cyclic AMP accumulation was prevented by incubation of the arteries with pertussis toxin and was significantly reduced by LY320135, a selective CB1 antagonist, but not by SR 144528, a CB2-selective antagonist. 5. Methanandamide failed to relax carotid arteries pre-contracted with phenylephrine, but inhibited forskolin-induced relaxation of these arteries. This functional inhibition of relaxation by methanandamide was inhibited by CB1-selective (LY320135 and SR 141716A), but not a CB2-selective antagonist (SR 144528). 6. These data demonstrate the presence of functional G protein-linked cannabinoid receptors of the CB1 subtype in the rat carotid artery, but show that these receptors inhibit cyclic AMP accumulation rather than cause relaxation.

Adenylyl Cyclase Inhibitors↗
PubMed1999

Coordinate augmentation in expression of genes encoding transcription factors and liver secretory proteins in hypo-oncotic states.

BACKGROUND: In the nephrotic syndrome (NS) proteins of intermediate size (40 to 200 kD) are lost into the urine resulting in a decrease in plasma albumin concentration and as a consequence a reduction in plasma colloid osmotic pressure (pi). Plasma pi has also been reported to be reduced in the condition of hereditary analbuminemia. The liver, in an apparent compensatory response, increases synthesis of a group of secreted proteins defending plasma pi. Regulation of several of these proteins, including both positive and negative acute phase proteins, is at the transcriptional level. This is the only known condition in which transcription of both positive and negative acute phase proteins (APPs) are increased simultaneously. The specific transcription factor(s) that might regulate this cascade is not defined. METHODS: RNA was extracted from livers of 5 rats with hereditary analbuminemia (the Nagase analbuminemic rat, NAR), 5 rats with NS induced by adriamycin (Adria), 5 rats with NS caused by passive Heymann nephritis (NS) and 5 control animals. The concentrations of mRNAs encoding four secreted proteins (albumin, transferrin, fibrinogen, and apo A-1), five transcription factors, early growth response factor 1 (EGRF-1), HNF-4, NGFI-C, EGR-3, and Krox20 relative to two housekeeping genes, beta actin and GAPDH were determined simultaneously using kinetic reverse transcriptase polymerase chain methodology (kRT-PCR). RESULTS: The levels of all mRNAs encoding secreted proteins except for albumin (which was reduced in NAR) were increased in NS and NAR and correlated significantly with one another. mRNA encoding EGRF 1 was increased fivefold in NS and NAR, and correlated significantly with mRNAs encoding Apo A-1, transferrin and albumin in the two NS groups. HNF-4 mRNA was increased approximately twofold in both NS groups and correlated with albumin (R = 0.881, P < 0.001), transferrin (R = 0.563, P = 0.012) and apo A-1 (R = 0.644, P = 0. 003). While fibrinogen mRNA correlated with that of each of the other secreted proteins, it did not correlate with either HNF-4 or EGRF-1 mRNA. Krox20, EGR3 and NGF1C were expressed at nearly undetectable levels. CONCLUSIONS: The hepatic response in conditions characterized by reduced plasma pi include increased levels of mRNAs encoding a group of secreted proteins, including the negative APPs albumin, transferrin and apo A-1, and the positive APP fibrinogen. Levels of mRNAs encoding negative APPs and fibrinogen correlate with one another, suggesting that they are coordinately controlled. Both EGRF-1 and HNF-4 may regulate the expression of the negative APPs, which have increased transcription in hypo-oncotic states.

Acetylglucosaminidase↗
PubMed1998

The design, synthesis and properties of highly potent and selective inhibitors of herpes simplex virus types 1 and 2 thymidine kinase.

The rational design and synthesis of nucleotide analogues as inhibitors of herpes simplex virus (HSV) thymidine kinase is described. Starting from thymidine, product analogues which included phosphates, phosphonates, sulphonates, sulphonamides and carboxamides were prepared. The carboxamide series showed good structure-activity relationships and afforded a lead structure which inhibited the HSV-2 enzyme in the low micromolar range. Replacing the 5-methyl group in thymidine by ethyl enhanced the potency of the lead structure 10-fold. Further optimization of the carboxamide moiety afforded inhibitors active in the sub-nanomolar range and finally the introduction of a 2'-beta-fluoro substituent improved the potency a further twofold. The low water solubility of the most potent inhibitor was overcome by conversion to the 3'-valyl ester, which had good oral bioavailability and showed activity by the oral route in murine models of infection.

Animals↗
PubMed1997

Use of electromyography in seven injured wild birds.

Seven wild birds with traumatic injuries affecting the peripheral nervous system were evaluated with the aid of electromyography. Initially, electromyography was performed on these birds because of loss of motor control and muscle atrophy that could not be explained by clinical signs alone. It can be difficult to assess postural reactions and reflexes in these birds. Use of electromyography to provide prognostic information for rehabilitation potential had not been reported. Reviews in the literature indicate that electromyography in human beings helps when assessing prognosis in sports-related injuries. Because wild birds require nearly total function for complete rehabilitation, electromyographic findings of functional motor units or evidence of axonal degeneration can assist in determining their potential for release.

Animals↗
PubMed1997

Evidence that anandamide and EDHF act via different mechanisms in rat isolated mesenteric arteries.

The endogenous cannabinoid, anandamide, has been suggested as an endothelium-derived hyperpolarizing factor (EDHF). We found that anandamide-evoked relaxation in isolated segments of rat mesenteric artery was associated with smooth muscle hyperpolarization. However, although anandamide-evoked relaxation was inhibited by either charybdotoxin (ChTX) or iberiotoxin, inhibition of the relaxation to EDHF required a combination of ChTX and apamin. The relaxations induced by either anandamide or EDHF were not inhibited by the cannabinoid receptor (CB1) antagonist SRI41716A, or mimicked by selective CB1 agonists. Thus, anandamide appears to cause smooth muscle relaxation via a CB1 receptor-independent mechanism and cannabinoid receptor activation apparently does not contribute to EDHF-mediated relaxation in this resistance artery.

Animals↗
PubMed1997

Plinth padding and measures of posteroanterior lumbar stiffness.

OBJECTIVE: To investigate whether measurement of posteroanterior (PA) lumbar stiffness is affected by the presence of padding on the testing plinth. DESIGN: Within a repeated-measures design, measurements were made of lumbar PA stiffness in subjects without low back pain on both a rigid and a padded plinth surface. SUBJECTS: Nineteen subjects with no history of any low back pain requiring treatment over the preceding 12 months participated in this study. METHODS: PA stiffness was measured at L3 on two occasions under two different conditions. The first condition involved measurement of lumbar stiffness on a rigid plinth surface; the second involved measurement on a padded plinth surface. A reliable mechanical device was used to obtain the PA stiffness measures. RESULTS: Mean lumbar PA stiffness values obtained when testing on a padded plinth were 2.86 N/mm less than those values obtained when testing the same lumbar spines on a rigid plinth. A paired t test showed a significant difference between the PA stiffness measures at L3 obtained on the padded plinth and those obtained on the rigid plinth (t = 6.66, df = 18, p < or = .0001). CONCLUSIONS: These findings suggest that to improve the reliability of lumbar PA stiffness assessment, testing should be performed under the same plinth surface conditions.

Adult↗
PubMed1996

Pancytopenia associated with administration of captopril to a dog.

An 11-year-old castrated male Dachshund was determined to have pancytopenia on the basis of results of CBC and bone marrow cytologic examination. Pancytopenia was believed to have resulted from administration of captopril, which had been administered for treatment of chronic mitral insufficiency, because other causes of pancytopenia were not found. Treatment consisted of discontinuing captopril and stimulating the bone marrow with recombinant human erythropoietin and granulocyte colony-stimulating factor. Although neutralizing antibodies will develop against the heterologous human protein, recombinant human granulocyte colony-stimulating factor should be considered for short-term treatment of neutropenias associated with adverse drug reactions, canine parvovirus infections, and bone marrow suppression from primary bone marrow disease, cancer chemotherapy, or total body irradiation before bone marrow transplantation.

Angiotensin-Converting Enzyme Inhibitors↗