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Biomedical subjects

J M Wright

Publications and source records attributed to J M Wright.

At least 145 records · Page 8Linked to original sources

Multiple effects of tetraethylammonium on N-methyl-D-aspartate receptor-channels in mouse brain neurons in cell culture.

1. The mechanisms of tetraethylammonium (TEA) antagonism of N-methyl-D-aspartate (NMDA) responses were investigated in cultured mouse cortical neurons by analysing single-channel and whole-cell currents from patch clamp recordings. TEA (1-5 mM) decreased whole-cell NMDA responses. Kainate and quisqualate receptor-mediated responses were unaffected at these TEA concentrations. 2. In whole-cell recordings, increasing the NMDA concentration while keeping the TEA concentration constant resulted in greater inhibition by TEA. Thus, TEA-mediated inhibition of NMDA responses was not due to competitive antagonism, and the greater inhibition by a single dose of TEA as NMDA concentration was elevated indicated some form of non-competitive inhibition. In single-channel recordings, two inhibitory effects were seen in 1-5 mM-extracellular TEA: single-channel conductance (gamma) was decreased, and the frequency of channel events was decreased. These effects were not accompanied by any change in average channel open time. 3. Single-channel current-voltage (I-V) curves obtained in 2, 5, 10 and 30 mM-TEA indicated the decrease in NMDA channel conductance was voltage dependent with larger reduction occurring as patches were hyperpolarized. The data were well fitted by the Woodhull model with the dissociation constant (KD) showing an e-fold increase in inhibition for a 43-45 mV change in membrane potential. The 0 mV KD was 45 mM-TEA decreasing to about 11 mM at -60 mV. The TEA block site appeared to sense approximately 60% of the transmembrane potential field (delta = 0.6) for extracellular application of TEA. 4. The decrease in channel opening frequency seen in TEA was concentration dependent and generally more sensitive to extracellular TEA than the channel block effect. There was a 50% reduction in the number of NMDA channel openings observed in 5 mM-TEA. Increasing either NMDA or glycine concentrations in constant TEA concentration caused an additional decrease in the frequency of NMDA channel opening. In contrast to extracellular TEA, intracellular TEA had no noticeable effect on open-state probability. 5. NMDA single-channel currents were observed at positive potentials after completely replacing pipette Cs+ by 140 mM-TEA-Cl indicating TEA could serve as a current carrier through NMDA channels. Single channel I-V curves obtained with pipettes containing 70 or 140 nM-TEA in place of equivalent amounts of Cs+ were fitted by the Goldman-Hodgkin-Katz (GHK) equation over the range of -80 to +70 mV assuming a permeability of 0.45 compared with a Cs+ permeability of 1.0.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Continuing medical education in psychiatry.

The increasing importance of continuing medical education (CME) in psychiatry is discussed. The need to take account of the principles of adult education (AE) and also of the diversity of current psychiatric practice and individual differences when developing CME programmes is emphasised. The relevance of mandatory CME to the assessment of practitioner performance is also discussed.

Australia↗

Effectiveness and tolerability of once versus twice daily nitrendipine in the treatment of mild to moderate hypertension. The Canadian Nitrendipine Study Group.

Improved measurement of plasma concentrations of nitrendipine demonstrates a plasma half-life of 17 to 21 h allowing once daily dosing for antihypertensive treatment. To determine the effectiveness and tolerability of nitrendipine given once versus twice daily, 78 patients with mild to moderate essential hypertension were randomized in a double-blind fashion to 12 weeks of treatment with either nitrendipine 20 mg once daily (n = 39) or nitrendipine 10 mg bid (n = 39). Blood pressures measured at the end of the dosing interval were similar on 20 mg once daily and 10 mg bid. Adverse events considered to be drug related (flushing and headaches) occurred mostly at the beginning of active treatment and more frequently on the once daily dosing, resulting in a greater number of patients being withdrawn from the once daily treatment group. Thus, nitrendipine 20 mg once daily lowered blood pressure as effectively as 10 mg bid but was associated with a higher incidence of adverse events. These could be minimized by starting at nitrendipine 10 mg once daily and increasing to 20 mg once daily after two to four weeks.

Blood Pressure↗

A satellite DNA family from pollock (Pollachius virens).

We have cloned and sequenced a highly reiterated EcoRI fragment of DNA from pollock (Pollachus virens). The EcoRI repeat is 200 (+/- 5) bp long, A + T-rich (65%) and exhibits a high degree of sequence conservation among representative members. It comprises 13% of the pollock nuclear DNA with a copy number of 5 x 10(5) per haploid genome. Partial digestion of pollock DNA with EcoRI or Hinf1, which cleaves within the repeat, followed by blot hybridization to a cloned repeat sequence, produced a ladder of hybridising bands indicating a tandemly arrayed organisation for the EcoRI repeat. Longer range periodicities, revealed by restriction endonuclease digestion, are superimposed on the tandem array.

Animals↗

Pressor responses to tracheal intubation after sublingual captopril. A pilot study.

The effect of sublingual captopril on the pressor response to intubation was studied in 40 patients. Captopril was used in one of two doses (12.5 mg and 25 mg) 25 minutes before tracheal intubation. Both doses were associated with a significant reduction in the pressor response to intubation (p less than 0.05) compared to placebo, but no significant difference existed between the two doses. Neither dose controlled changes in heart rate at intubation. Untoward hypotension occurred in the treatment groups. Caution is advised in the peri-operative use of angiotensin-converting enzyme inhibitors.

Administration, Sublingual↗

Dominantly inherited apathy, central hypoventilation, and Parkinson's syndrome: clinical, biochemical, and neuropathologic studies of 2 new cases.

We describe 2 new patients from a family in which 10 persons in 3 successive generations had a dominant neuropsychiatric disorder characterized by apathy, central hypoventilation, and parkinsonism. Neuropathologically, both patients showed severe neuronal loss and reactive gliosis in the substantia nigra. Neurochemical studies showed a marked depletion of dopamine in substantia nigra, putamen, and caudate nucleus, as well as reduction in serotonin content in the substantia nigra. Glutamate contents were low in frontal cortex and thalamus, and gamma-aminobutyric acid (GABA) contents were low in thalamus and substantia nigra of both patients. In addition, phosphoethanolamine contents were reduced in all brain regions of both patients, especially in the substantia nigra. One patient with severe symptoms had low levels of homovanillic acid, 5-hydroxyindoleacetic acid, and GABA in his CSF repeatedly for 3 years before death (aged 58), while the 2nd patient died (aged 51) of an unrelated cause before developing any symptoms of the familial disorder. Because brain deficiencies of multiple neurotransmitters appear to be involved, this disorder is unlikely to respond to treatment; however, neurochemical studies of CSF may make presymptomatic diagnosis feasible.

Adult↗

The role of liaison psychiatry in an AIDS unit.

The experience of a liaison psychiatry team working in the setting of an AIDS unit is described. Several clinical themes are identified which highlight crucial issues with regard to both diagnosis and management. These issues are illustrated by case histories. Discussion draws attention to the value of using a biopsychosocial model in order to understand aetiology and to formulate appropriate management. Issues related to staff involvement provide a further theme for discussion.

AIDS Dementia Complex↗

Direct determination of urinary oxalate by a continuous flow method.

A continuous flow method is described for estimation of urinary oxalate, using oxalate oxidase (EC 1.2.3.4) and ascorbate oxidase (EC 1.10.3.3) immobilised on the inner surface of O-alkylated nylon tubes. Linearity, precision, oxalate recovery, freedom from interference by other urinary substances, accuracy, specificity, absence of interaction between samples and correlation with an established enzymic method were all excellent. The method has advantages over other methods in terms of speed, ease of use and cost. As the immobilised enzyme system has been stable for 15 months the method is suitable for both research and routine use.

Ascorbate Oxidase↗

Nucleotide sequence, genomic organization and evolution of a major repetitive DNA family in tilapia (Oreochromis mossambicus/hornorum).

A highly repetitive DNA sequence from tilapia (Oreochromis mossambicus/hornorum) has been cloned and sequenced. It is a tandemly arrayed sequence of 237 bp and constitutes 7% of the fish genome. The copy number of the repeat is approximately 3 x 10(5) per haploid genome. DNA sequence analysis of 7 cloned repeats revealed a high degree of conservation of the monomeric unit. Within the monomeric unit, a 9 bp AT rich motif is regularly spaced approximately 30 bp apart and may represent the progenitor of the amplified sequence. One cloned repeat, Ti-14, contained a 30 bp deletion at a position flanked by a 7 bp direct repeat. The Ti-14 sequence appears to have been amplified independently of the major 237 bp tandem array. A higher-order repeat unit, defined by longer-range periodicities revealed by restriction endonuclease digestion, is further imposed on the tandem array.

Animals↗

Zidovudine-related mania.

Two patients with the acquired immunodeficiency syndrome (AIDS), who had no past psychiatric history, developed a mania-like illness soon after commencing treatment with zidovudine. The neurotoxic effects of zidovudine have been described previously, but to our knowledge no reports of a psychiatric disorder that is related to the drug have appeared. Our report emphasizes the need to monitor patients with AIDS for neuropsychiatric problems.

Adult↗

Regional odontodysplasia presenting as a soft tissue swelling.

An unusual case of regional odontodysplasia in a 13-year-old black girl is presented. Although the affected teeth displayed features characteristic of odontodysplasia, the patient appeared with significant soft tissue swelling of the buccal and palatal maxilla. Treatment consisted of extraction of affected teeth, removal of involved tissue, and histologic examination.

Adolescent↗

Cow-calf association delays postpartum ovulation in mastectomized cows.

Eleven 3-yr-old crossbred Angus cows that had raised one calf each were mastectomized at 6 to 7 mo of their second gestation. All calves were removed from cows within 12 h after birth. Cows were kept in a drylot with a fertile bull for 60 d after parturition. Cows were observed for estrus every 6 h, and blood serum was collected daily and assayed for progesterone. The average first ovulation and first estrus occurred at 13.9 and 20.1 d after parturition, respectively. Nine of 11 cows conceived, and the average time of conception was 34.3 d after parturition. The next year, eight of the same mastectomized cows were allocated to two equal groups. In one group, calves were removed from cows within 12 h after birth, whereas in the other group, calves remained with cows for 46 to 53 d. Calves that remained with their dams were hand fed from a bottle or bucket every 12 h. The two groups of cows were kept in separate drylots about 50 m apart, and a fertile bull was kept with each group. Blood samples were obtained from all cows, and they were observed for estrus as before. Cows withcut calves ovulated before 22 d (average 16.0), exhibited estrus by 33 d (average 24.0), and conceived by 40 d (average 30.5) after calving. None of the cows with calves ovulated or exhibited estrus earlier than 49 d after calving. However, all cows ovulated by 4 d (average 3), exhibited estrus by 10 d (average 5.5), and conceived by 11 d (average 9.3) after calf removal. We conclude that cow-calf interaction can suppress ovulation and estrus even when suckling and lactation do not take place.

Journal Article↗

The mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity: role of intracellular calcium.

The mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity to isolated hepatocytes was studied. MPTP was more toxic to hepatocytes than its major metabolite, 1-methyl-4-phenylpyridine (MPP+); this may, in part, be explained by the lesser permeability of the hepatocyte plasma membrane to the cation compared to its parent compound, MPTP. Loss of cell viability was preceded by plasma membrane bleb formation and disturbance of intracellular Ca2+ homeostasis. MPTP caused a rapid depletion of the mitochondrial Ca2+ pool which was followed by a marked and sustained elevation of cytosolic free Ca2+ concentration. This increase of cytosolic Ca2+ level appeared to be associated with the impairment of the cell's Ca2+ extrusion system since the plasma membrane Ca2+-ATPase was markedly inhibited in MPTP-treated hepatocytes. Preincubation of hepatocytes with inhibitors of monoamine oxidase type B, but not A, protected the cells from MPTP-induced cytotoxicity. Moreover, the monoamine oxidase B inhibitor, pargyline, prevented the rise in cytosolic free Ca2+ concentration and partially protected the plasma membrane Ca2+-ATPase from inhibition by MPTP. As observed with MPTP, MPP+ caused an extensive loss of mitochondrial Ca2+ and significantly decreased the rate of Ca2+ efflux from hepatocytes. However, MPP+ was without effect on the plasma membrane Ca2+-ATPase. In conclusion, our studies demonstrate that MPTP caused a substantial elevation of cytosolic Ca2+ which preceded loss of cell viability and we propose that calcium ions are of major importance in the mechanism of MPTP- and MPP+-induced toxicity in hepatocytes.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Induction by torsional stress of an altered DNA conformation 5' upstream of the gene for a high mobility group protein from trout and specific binding to flanking sequences by the gene product HMG-T.

We have used enzymic and chemical probes to search for altered DNA conformations in the 5' flanking region of the gene for a high mobility group protein (HMG-T) from trout. This search was conducted in order to identify potential genetic elements that might be involved in the transcriptional control of the HMG-T gene. We identified, in supercoiled plasmid DNA molecules containing a 900 base pair insert of the 5' region of the gene, an S1-sensitive site situated within an (AT)12 sequence approximately 120 base pairs upstream from the start of the HMG-T gene. Chemical modification of supercoiled DNA with the single-strand-selective reagent bromoacetaldehyde was limited to a region coincident with the S1 nuclease site. T7 endonuclease I, a probe highly specific for four-way helical junctions, cleaved predominantly at the boundaries of the (AT)12 stretch. These data are most consistent with the interpretation that the (AT)12 sequence adopts a cruciform structure when torsionally stressed by negative supercoiling. DNase I footprinting analyses demonstrated that HMG-T protects two regions almost equidistant from the center of the (AT)12 sequence, indicating that HMG-T is a sequence-specific DNA binding protein.

Animals↗

Inhibition of hamster buccal pouch carcinogenesis by green coffee beans.

Forty female Syrian Golden hamsters were divided into two equal groups and placed on one of two diets. The hamsters in Group I received a normal chow, and the animals in Group II were given the same chow supplemented with powdered green coffee beans (20%). After the hamsters adjusted to the diets, 16 animals from each group were selected. The right buccal pouch of each of these hamsters was painted three times weekly with a 0.5% solution of 7, 12-dimethylbenz(a)anthracene (DMBA) in heavy mineral oil. The eight remaining animals, four in each group, served as controls and were treated three times weekly with heavy mineral oil. After a total of 50 treatments (16 1/2 weeks), the hamsters were killed. The animals receiving green coffee beans exhibited a significant delay in the development of DMBA-induced carcinogenesis of the buccal pouch mucosa, as determined by both visual and histologic examination.

9,10-Dimethyl-1,2-benzanthracene↗