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Biomedical subjects

A D Wright

Publications and source records attributed to A D Wright.

At least 73 records · Page 4Linked to original sources
PubMed1993

Exogenous tat protein activates human endothelial cells.

tat protein, a human immunodeficiency virus (HIV) gene product that functions as a transactivator for HIV replication, is known to be secreted extracellularly by infected cells. To determine the potential role of tat in the dissemination of HIV into extravascular tissue, this protein was examined for its ability to activate human endothelial cells. The results show that tat does indeed stimulate endothelial cells. This is evidenced by their expression of the endothelial-leukocyte adhesion molecules, E-selectin, critical for the initial binding of leukocytes to the blood vessel wall, and their increased synthesis of interleukin-6 (IL-6), a cytokine known to enhance endothelial cell permeability. Furthermore, tat acts synergistically with low concentrations of tumor necrosis factor-alpha to enhance IL-6 secretion. These data suggest that extracellular tat protein secreted or released into the microenvironment may contribute significantly to the determination of specific sites of leukocyte binding to blood vessels, to transmigration into tissue, and to eventual dissemination of HIV-infected cells or free virions into tissue.

Cell Adhesion Molecules↗
PubMed1993

Euglycaemic diabetic ketoacidosis: does it exist?

The original criteria described for euglycaemic ketoacidosis (initial blood glucose less than 16.7 mmol/l and plasma bicarbonate equal to or less than 10 mmol/l) were identified in 23 of 722 consecutive episodes (3.2%) of diabetic ketoacidosis. True euglycaemic ketoacidosis (initial blood glucose 10 mmol/l or less) was rare, occurring in 0.8-1.1% of all episodes depending on the defining plasma bicarbonate concentration. Management of euglycaemic ketoacidosis with low-dose continuous intravenous infusion of insulin together with adequate fluid replacement was effective. The clinical and biochemical data did not support the concept of euglycaemic ketoacidosis as a separate entity. The importance of ketone testing rather than glucose testing in the diagnosis of ketoacidosis is, however, emphasized. The importance of adequate insulin and fluid therapy in those few episodes where blood glucose is normal or near normal at presentation is also highlighted.

Bicarbonates↗
PubMed1993

Karsoside and scropolioside D, two new iridoid glycosides from Scrophularia ilwensis.

Two new iridoid glycosides, karsoside [1] and scropolioside D [2], were isolated from the aerial parts of Scrophularia ilwensis. Their structures were elucidated on the basis of chemical and spectral data as 6'-O-(beta-D-xylopyranosyl)-methylcatalpol and 6-O-[(2",4"-di-O-acetyl-3"-O-trans-cinnamoyl)-alpha-L-rhamnopyranosyl]- catalpol, respectively. Additionally, four known iridoids (aucubin, harpagide, 8-O-acetylharpagide, and ajugol), a phenylpropanoid glycoside (angoroside C), and two flavonoids (quercetin-3-O-rutinoside and kaempferol-3-O-rutinoside) were isolated and identified.

Acetylation↗
PubMed1993

Five new prenylated p-hydroxybenzoic acid derivatives with antimicrobial and molluscicidal activity from Piper aduncum leaves.

Five new prenylated benzoic acid derivatives, methyl 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxybenzoate (1), 1-(1-methylethyl)-4-methyl-3-cyclohexenyl 3,5-bis(3-methyl-2-butenyl)-4-hydroxybenzoate (2), 1-(1-methylethyl)-4-methyl-3-cyclohexenyl 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoate (3), methyl 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoate (4), and 4-hydroxy-3-(3-methyl-2-butenyl)-5-(3-methyl-2-butenyl)-benzoic acid (5) were isolated from the dried leaves of Piper aduncum L. (Piperaceae). Together with the new metabolites, four known prenylated benzoic acid derivatives, 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoic acid (6), 4-hydroxy-3,5-bis(3-methyl-2-butenyl)-benzoic acid (nervogenic acid, 7), methyl 4-hydroxy-3,5-bis(3-methyl-2-butenyl)-benzoate (8), and methyl 4-hydroxy-3-(3-methyl-2-butenyl)-benzoate (9) as well as, dillapiol (10), myristicin, and the three sesquiterpenes humulene, caryophyllene epoxide, and humulene epoxide were isolated. Compounds 7, 8, and 9 are reported as natural products for the first time. The structures of the isolates were elucidated by spectroscopic methods, mainly 1D-and 2D-NMR spectroscopy. Isolates 4-7, 9, and 10 were molluscicidal while 2, 5-7, and 9 displayed significant antibacterial activities.

Anti-Infective Agents↗
PubMed1993

Ketoacidosis in diabetic pregnancy.

A study was carried out to determine the incidence of maternal ketoacidosis in 635 insulin-treated diabetic pregnancies managed in a combined antenatal/diabetic clinic between 1971 and 1990. A total of 11 episodes occurred, representing 1.73% of diabetic pregnancies of which 9 were in the antenatal period. Overall fetal loss including spontaneous abortion was 22%, but there was only one fetal death in the seven episodes of ketoacidosis in the second and third trimesters. Ketoacidosis is an infrequent occurrence in diabetic pregnancy managed in a combined clinic and is not associated with a high fetal loss after the first trimester.

Abortion, Spontaneous↗
PubMed1993

Persisting mortality in diabetic ketoacidosis.

An overall hospital mortality rate of 3.9% was found in 929 episodes of diabetic ketoacidosis treated in single centre over a 21-year period. The mortality rate in the first half of the survey (4.4%) was not significantly different from that in the second half of the survey (3.4%). Six deaths in patients under 50 years of age occurred in the first half, but only one death under 50 years occurred in the second half of the survey. The number of deaths from a metabolic cause where no other illness was identified also fell from nine (43% of deaths) in the first half to five (33% of deaths) in the second half of the study (not significant). The remaining deaths were due to concurrent illness, mainly myocardial infarction and serious infections. Many of the residual deaths occurred in elderly patients with such medical illness in addition to the ketoacidosis. It may, therefore, prove difficult to reduce mortality further in diabetic ketoacidosis.

Age Factors↗
PubMed1993

Successful treatment of severe refractory sulfonylurea-induced hypoglycemia with octreotide.

OBJECTIVE: To test the clinical use of octreotide in the treatment of sulfonylurea-induced hypoglycemia. RESEARCH DESIGN AND METHODS: A case is reported of sulfonylurea-induced hypoglycemic coma in a nondiabetic subject, which was complicated by relapse of hypoglycemia after resuscitation with intravenous dextrose. Subcutaneous octreotide, 50 micrograms 12 hourly, suppressed stimulated endogenous insulin secretion, thereby preventing a further recurrence of hypoglycemia. RESULTS: No adverse effects of treatment were observed. CONCLUSIONS: These results suggest a significant role for octreotide as an adjunct to intravenous dextrose in the management of severe and refractory cases of sulfonylurea-induced hypoglycemia.

Adult↗
PubMed1992

Balanitoside, a furostanol glycoside, and 6-methyldiosgenin from Balanites aegyptiaca.

In addition to a known spirostanol glycoside, balanitin-3, and a new sapogenol, 6-methyldiosgenin, a new furostanol saponin, balanitoside has been isolated from the fruits (mesocarp) of Balanites aegyptiaca. The structure of the glycoside has been determined as 26-O-beta-D-glucopyranosyl-3 beta, 22,26-trihydroxy-furost-5-ene 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D- glucopyranosyl-(1-->4)-beta-D-glucopyranoside, on the basis of spectroscopic and chemical evidence.

Carbohydrate Sequence↗
PubMed1992

Four new antibacterial sesterterpenes from a marine sponge of the genus Luffariella.

The structures of four new sesterterpenoid compounds 1-4 isolated from a marine sponge of the genus Luffariella, collected from The Great Barrier Reef, Australia, have been determined by analysis of their 1H-nmr, 13C-nmr, ir, uv, and eims spectral data. The new metabolites 1-4 were found to co-occur with the compounds manoalide, secomanoalide, Z-neomanolaide [5], and E-neomanoalide.

Animals↗
PubMed1992

Antimalarial activity of sesquiterpenes from the marine sponge Acanthella klethra.

Five sesquiterpenoids containing isonitrile or isothiocyanate groups were isolated from the sponge Acanthella klethra. Compounds 1 and 2 were identified as axisonitrile 3 and the corresponding isothiocyanate derivative, respectively. Compounds 3-5 were found to be eudesmane sesquiterpenes. None of these compounds was cytotoxic toward cultured KB-3 cells, but varying degrees of activity were observed with cultured Plasmodium falciparum. Compound 1 demonstrated greatest promise as an antimalarial agent.

Animals↗
PubMed1992

Acetazolamide and high altitude diseases.

Acetazolamide is a useful prophylactic for acute mountain sickness causing marked reduction in headache, nausea, vomiting, weakness, etc. Improvements correlate with increased arterial oxygen concentrations, reduction in proteinuria and peripheral oedema and other objective measures of acute mountain sickness. Evidence that Acetazolamide is beneficial for pulmonary oedema or cerebral oedema is scanty because of the lower frequency of these severe forms of mountain sickness. Dexamethasone, used prophylactically, also reduces the symptoms of acute mountain sickness partly due to its euphoric effect. Use of Acetazolamide as a treatment for established acute mountain sickness has been investigated. Large doses of Acetazolamide increase arterial oxygen levels over a few hours and this leads to a reduction of symptoms but data is limited and faster acting carbonic anhydrides inhibitors such as Methazolamide may be preferable in an emergency situation. There is no comparison of the effectiveness of Acetazolamide with other drugs used for treating acute mountain sickness such as steroids and calcium channel blocking drugs. Also, there is no data on drug combinations which could have additive effects and thereby be more beneficial than individual drugs.

Acetazolamide↗
PubMed1992

The maize auxotrophic mutant orange pericarp is defective in duplicate genes for tryptophan synthase beta.

orange pericarp (orp) is a seedling lethal mutant of maize caused by mutations in the duplicate unlinked recessive loci orp1 and orp2. Mutant seedlings accumulate two tryptophan precursors, anthranilate and indole, suggesting a block in tryptophan biosynthesis. Results from feeding studies and enzyme assays indicate that the orp mutant is defective in tryptophan synthase beta activity. Thus, orp is one of only a few amino acid auxotrophic mutants to be characterized in plants. Two genes encoding tryptophan synthase beta were isolated from maize and sequenced. Both genes encode polypeptides with high homology to tryptophan synthase beta enzymes from other organisms. The cloned genes were mapped by restriction fragment length polymorphism analysis to approximately the same chromosomal locations as the genetically mapped factors orp1 and orp2. RNA analysis indicates that both genes are expressed in all tissues examined from normal plants. Together, the biochemical, genetic, and molecular data verify the identity of orp1 and orp2 as duplicate structural genes for the beta subunit of tryptophan synthase.

Amino Acid Sequence↗
PubMed1992

Growth hormone secreting pituitary carcinoma: a case report and literature review.

Only five cases of growth hormone secreting pituitary carcinoma have been documented. We present a 49-year-old West Indian male with grossly elevated plasma growth hormone (760-10,400 mU/l), and a large aggressive pituitary tumour that continued to grow despite repeated pituitary surgery, radiotherapy and medical therapy (bromocriptine and somatostatin analogue). Thirteen years after diagnosis the patient died secondary to left ventricular failure. A post-mortem revealed a large locally invasive pituitary tumour, but in addition numerous tumour seedlings within the cerebrospinal fluid space, and a solitary intraparenchymal tumour deposit within the right temporal lobe, clearly separate from the primary tumour. Pituitary carcinoma should be considered in any acromegalic with grossly elevated plasma growth hormone levels who fails to respond to conventional therapy.

Acromegaly↗
PubMed1992

Control of diabetes mellitus in shift workers.

OBJECTIVE: To determine whether the control of diabetes is different in insulin treated diabetic subjects who work shifts compared with those who do not work shifts and whether control is related to the type of shift worked. DESIGN: Prospective controlled study of 32 diabetic subjects working either regular days or shifts in a large car assembly factory. Insulin treated subjects who underwent a change in their pattern of shift work had diabetic control assessed before and six months after a change in shifts. MAIN OUTCOME MEASURES: Random plasma glucose, serum fructosamine, and haemoglobin A1 while at work. RESULTS: Diabetic control of insulin treated subjects who worked shifts was not significantly different from insulin treated subjects who worked days only. Diabetic control was poor in both groups and similar to that of diabetic subjects treated with oral hypoglycaemic agents. In those subjects that moved to a more rapidly rotating shift pattern there was a significant deterioration in control (serum fructosamine concentration before, 405 (SD 68); after, 481 (SD 90) mumol/l, p less than 0.01). CONCLUSIONS: The control of diabetes in insulin treated diabetic subjects who worked shifts was no worse than those who worked days only. Slowly rotating shifts were associated with better diabetic control than more rapidly rotating shifts.

Blood Glucose↗
PubMed1991

New indole alkaloid glycosides from Nauclea orientalis.

Two new indole alkaloid glycosides, 10-hydroxystrictosamide and 6'-O-acetylstrictosamide, as well as the known alkaloids strictosamide and vincosamide were isolated from the leaves of Nauclea orientalis L. The structures of the isolated compounds were determined using spectroscopic methods, mainly 1D- and 2D-NMR spectroscopy.

Animals↗
PubMed1991

Metabolic effects of pharmacological adrenergic blockade in phaeochromocytoma.

Twelve-hour hormonal and metabolic profiles were performed in a 68-year-old woman with a benign adrenal phaeochromocytoma (a) prior to adrenergic blockade, (b) after the establishment of pharmacological alpha-blockade with phenoxybenzamine, (c) after combined alpha and beta-blockade with phenoxybenzamine and propranolol, and (d) after successful surgery and withdrawal of medication. Pretreatment, (a) vs (d), significant elevations (12-h mean +/- SD) were observed in the concentrations of noradrenaline (44.9 +/- 14.4 vs 2.3 +/- 0.7 nmol/l, P less than 0.01), glucose (6.9 +/- 1.9 vs 5.0 +/- 1.0 mmol/l, P less than 0.05), glycerol (0.22 +/- 0.02 vs 0.07 +/- 0.01 mmol/l, P less than 0.01), non-esterified fatty acids (0.71 +/- 0.28 vs 0.34 +/- 0.08 mmol/l, P less than 0.01), and total ketone bodies (0.08 +/- 0.03 vs 0.03 +/- 0.02 mmol/l, P less than 0.01). Alpha-blockade, (b) vs (a), was associated with an increase in noradrenaline levels (P less than 0.01) but not with any significant alterations in intermediary metabolite concentrations. Following the establishment of combined alpha and beta-blockade, (c) vs (b), plasma noradrenaline returned to its pretreatment level while the concentrations of glycerol, fatty acids and ketone bodies were normalized. A completely physiological 12-h blood glucose profile, however, was observed only post-operatively. No significant differences were observed in mean plasma insulin levels between the four studies. These results indicate impaired regulation of multiple aspects of carbohydrate, lipid and ketone body metabolism in our patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1991

A comparison of the metabolic effects of flosequinan and propranolol in patients with non-insulin-dependent diabetes mellitus.

The effects of steady-state flosequinan, a new peripheral vasodilator, and propranolol on glucose tolerance and plasma lipids in 22 non-insulin-dependent diabetics were investigated in a randomized double-blind placebo-controlled, three-way crossover trial. Flosequinan produced no impairment of glucose tolerance compared with placebo. Propranolol produced significant increases in fasting plasma glucose (P less than 0.01) and increases in the area under the glucose tolerance curve (P less than 0.05) compared to placebo. No significant effects on cholesterol levels were seen on either treatment but triglyceride levels were significantly elevated on propranolol compared with placebo (P less than 0.01). These data suggest that flosequinan, used in therapeutic dosage, has no adverse metabolic effects on the non-insulin-dependent diabetic and this may be an advantage for a drug used in the treatment of hypertension or congestive heart failure.

Adult↗