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Biomedical subjects

H Hughes

Publications and source records attributed to H Hughes.

At least 55 records · Page 3Linked to original sources
PubMed1992

Effects of S14001 on adrenergic neuroeffector interaction in isolated canine saphenous veins.

1. The effects of (S) fluoro-6 (morpholinyl-2 methoxy)-8-tetrahydro-1,2,3,4 quinoleine (S14001) on adrenergic neurotransmission in isolated canine saphenous veins were investigated in experiments which measured the accumulation, overflow and metabolism of 3H-norepinephrine. 2. S14001 inhibited the accumulation of total tritium (3H-norepinephrine and 3H-metabolites of norepinephrine) in a concentration-dependent manner. 3. Under basal conditions, S14001 increased tension and basal effiux of total tritium; the latter consisted predominantly of 3H-DOPEG. The increases in these parameters were not inhibited by desmethylimipramine (DMI). 4. During electrical stimulation, S14001 increased the contraction and overflow of total tritium; the latter consisted predominantly of 3H-DOPEG. The increases in these parameters were inhibited by DMI. 5. These experiments suggest that S14001 has dual effects on adrenergic neurotransmission in the canine saphenous vein: (a) an inhibitory action on the neuronal accumulation; and (b) a pharmacological displacement of the transmitter from adrenergic nerve terminals.

Animals↗
PubMed1992

Role of leukotriene B4 in the pathogenesis of hepatic ischemia-reperfusion injury in the rat.

A common feature to most models of ischemia-reperfusion injury is the accumulation of polymorphonuclear leukocytes (PMNs) into the post-ischemic tissue during the reperfusion period. Interventions that lead to decreased PMN infiltration protect against tissue injury and therefore a knowledge of the chemotactic mediators leading to PMN accumulation is essential to understanding the pathogenesis of the injury and to the development of successful therapeutic strategies. Leukotriene B4 (LTB4), a metabolite formed via the 5-lipoxygenase pathway from arachidonic acid, is one of the most potent chemotactic mediators known. We have investigated the formation of LTB4 in a well characterized model of hepatic ischemia-reperfusion injury in the rat and made use of a specific leukotriene biosynthesis inhibitor, L663,536, to determine the importance of LTB4 in the pathogenesis of the injury. LTB4 concentrations were measured with a specific and sensitive gas chromatographic-mass spectrometric method previously developed in our laboratory. In liver tissue LTB4 levels were below the detection limit of 20 pg/g before 45 min ischemia and did not increase during the first 6 h of reperfusion. However, at 15 h and 24 h reperfusion LTB4 concentrations had increased to levels 50-fold those in control liver (867 +/- 267 pg/g). The increase of plasma alanine aminotransferase (ALT) activities indicated two phases of injury, an initial phase during the first few hours of reperfusion, and a second more severe injury phase between 6 h and 24 h reperfusion. PMNs accumulated in tissue throughout the reflow period reaching 700 +/- 49 per 50 high power fields (HPF) at 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1992

Inter-relation between measurement of serum prostatic specific antigen and transrectal ultrasound in the diagnosis of benign prostatic hyperplasia and prostatic cancer.

Serum prostatic specific antigen (PSA) and ultrasound-determined prostatic volume (UPV) were measured in 50 patients with histologically proven benign prostatic hyperplasia (BPH) and in 40 patients with histologically proven prostatic cancer of whom 17 had evidence of distant metastases (M1) and 23 did not (M0). A good correlation between log PSA and UPV was demonstrated in the BPH group and rearrangement of the linear regression equation allowed calculation of a single variable--the log PSA corrected to a standard prostate volume for any given individual. A volume-corrected PSA correctly identified all patients with M1 disease and greatly improved but did not eliminate overlap of M0 disease with BPH. Reduction of serum PSA to a single volume-corrected variable will allow the introduction of practical and optimum protocols for the management of patients with prostatic enlargement.

Aged↗
PubMed1992

Response of 6-pyruvoyl-tetrahydropterin synthase deficiency to tetrahydrobiopterin.

We have given tetrahydrobiopterin (BH4) in doses ranging from 2.5 to 20 mg/kg/day, each for a duration of 5 days to three patients with 6-pyruvoyltetrahydropterin synthase deficiency. As small a dose as 2.5 mg/kg/day BH4 reduced the blood phenylalanine to normal levels. However, the required dose of BH4 to reduce neopterin and to increase urine biopterin was 5 to 10 mg/kg/day, while 20 mg/kg/day was required for biopterin to appear in cerebrospinal fluid. The results suggest that BH4 effectively reduces endogenous neopterin synthesis. The dose of BH4 needed to normalize liver phenylalanine hydroxylase is one eighth to one fourth that required for normal neurotransmitter metabolism in the central nervous system.

Alcohol Oxidoreductases↗
PubMed1991

Gas chromatographic-mass spectrometric analysis of lipoxygenase products in post-ischemic rabbit myocardium.

Leukotriene B4 (LTB4) is a potent chemotactic compound for neutrophils and is thought to be an important mediator of myocardial ischemia-reflow injury. We have measured LTB4 in rabbit cardiac tissue following ischemia-reflow using a sensitive and specific gas chromatographic-mass spectrometric (GC-MS) assay. The concentration of LTB4 in rabbit myocardium following 45 min ischemia and 3 h reflow was 48.7 +/- 12.5 pg/g, significantly higher than in non-ischemic tissue from the same animal (17.5 +/- 3.9 pg/g). These concentrations were at least an order of magnitude lower than previously reported values assessed by radioimmunoassay (RIA). Compared with the GC-MS method, RIA greatly overestimated LTB4 concentrations in cardiac tissue. The capacity of post-ischemic myocardium to produce lipoxygenase products, LTB4, 5-, 12- and 15-HETEs was also assessed following incubation of myocardium ex vivo with calcium ionophore. In all animals ischemic cardiac tissue produced greater amounts of LTB4, 5-, and 12-HETEs than non-ischemic myocardium and 12-HETE was the major product. Neutrophils that have accumulated in the injured tissue may be a major source of these products. However, in contrast to cardiac tissue, isolated rabbit neutrophils stimulated with A23187 produced 5-HETE as the major product with very little 12-HETE formed. These latter findings suggest that cells other than neutrophils may contribute to the production of lipoxygenase products during myocardial ischemia-reflow injury.

Animals↗
PubMed1991

The effect of weight correction on risk calculations for Down's syndrome screening.

Recent advances in prenatal screening have led to the possibility that the risk of Down's syndrome associated pregnancy may be assessed by blood tests for maternal serum alphafetoprotein, human chorionic gonadotrophin (and possibly unconjugated oestriol) taken at 15-18 weeks of gestation. In neural tube defect screening correction of maternal serum alphafetoprotein for maternal weight has been recommended, although the precise method for weight correction is still under debate. We report an assessment of weight correction for maternal serum alphafetoprotein and human chorionic gonadotrophin based on 1408 singleton pregnancies and for unconjugated oestriol based on 197 singleton pregnancies. We demonstrate that weight correction of maternal serum alphafetoprotein and human chorionic gonadotrophin is statistically valid but that correction of unconjugated oestriol is not.

Body Weight↗
PubMed1991

Biopterin-dependent hyperphenylalaninemia due to deficiency of 6-pyruvoyl tetrahydropterin synthase.

We describe the clinical, neurologic, and biochemical findings in 10 patients with 6-pyruvoyl tetrahydropterin synthase (6-PTS) deficiency from seven families, all of whom originate from one large tribe in Saudi Arabia. This deficiency presents with severe, early onset of failure to thrive, neurologic deterioration, and morbidity and mortality secondary to repeated episodes of bronchopneumonia or cardiorespiratory abnormalities. The urinary pterin excretion pattern indicates deficient activity of 6-PTS, which has been confirmed by direct enzyme assay in red blood cells of three patients. We treated our patients with combined use of tetrahydrobiopterin 20 mg/kg/d, L-dihydroxyphenylalanine 15 mg/kg/d, carbidopa 3.75 mg/kg/d, and L-5-hydroxytryptophan 5 mg/kg/d. Neurologic findings improved significantly in all after 5 to 24 months. Although head circumference and weight returned to the lower limit of normal in four, height normalized only in one of seven patients. Despite an unrestricted diet during combined therapy, blood phenylalanine and urinary excretion of neopterin and biopterin returned to normal.

Alcohol Oxidoreductases↗
PubMed1991

The uptake of oestrone from the lumen of the isolated perfused rat gut.

1. In the isolated perfused rat gut oestrone was not taken up from the perfusate but was rapidly taken up from the gut lumen when administered in dimethyl sulphoxide or in 10% acetone in water. 2. Uptake from corn oil was much slower and the rate was concentration-dependent. 3. When given in dimethyl sulphoxide or in aqueous acetone, the residual oestrone in the gut lumen was largely unchanged, with only about 10% being present as the glucuronide. Of the oestrone in the gut perfusate, some 40% was glucuronidated. 4. No evidence was obtained for any reduction or hydroxylation, or for any sulphation, during uptake of oestrone by the gut. 5. No secretion of oestrone or its metabolites into lymph could be detected.

Animals↗
PubMed1991

Pathological changes in bovine mammary glands following intramammary infusion of recombinant interleukin-2.

Eighteen lactating dairy cows were used to evaluate the physiological response of mammary glands to increasing doses of recombinant bovine interleukin-2. Right front and rear quarters were intramammarily infused with five different doses (.1 to 100 micrograms per quarter) of interleukin-2 as either a single or multiple treatment. Left front and rear quarters were intramammarily infused with a saline placebo and served as within-animal controls. Milk secretion samples for compositional analysis were collected from each quarter prior to infusion and at 12, 24, 36, and 48 h following infusion. Animals were slaughtered by exsanguination immediately following the 48-h sampling period, and mammary gland tissue was obtained for morphometric analysis. No changes in milk composition were observed between control quarters and those infused with up to 10 micrograms of interleukin-2 per quarter, administered as either a single or multiple treatment. Quarters infused with a single 100-micrograms dose of interleukin-2 or three consecutive doses of 25 and 100 micrograms of interleukin-2 had significantly lower lactose concentrations; there was a concomitant increase in bovine serum albumin, pH, and SCC compared with preinfusion concentrations or with control quarters. Morphometric analysis of tissue demonstrated an increase in stroma, a decrease in lumenal area, and a marked increase in the number of infiltrating leukocytes in those quarters infused with the higher doses of interleukin-2. Results suggest that interleukin-2 can be intrammammarily infused at doses as high as 10 micrograms per quarter without adversely affecting milk quality or normal mammary gland function.

Animals↗
PubMed1991

Recovery of S. epidermidis and E. coli from effluent peritoneal dialysate.

The effect of incubation temperature and duration was studied on the growth of organisms in peritoneal dialysate effluent. Penicillin-sensitive, and gentamicin-sensitive clinical isolates of S. epidermidis (SE) and E. Coli (EC), respectively, were inoculated into freshly drained dialysate of 19 CAPD patients who did not have peritonitis. Each dialysate was 1.5% dextrose in strength and had a minimum dwell of 6 hours. Control and test aliquots were incubated at 4 degrees C, 20 degrees C and 37 degrees C for periods of up to 12 hours, and samples collected and plated to determine colony counts. Initial counts at time zero were 9.4 x 10(4) (SE) and 6.6 x 10(3) (EC) CFU/ml. SE showed no change in count at 4 or 20 degrees C up to 12 hours. There was a significant increase (p less than 0.005) at 37 degrees C, at 12 hours to 1.72 x 10(6) CFU/ml. EC showed no change at 4 or 20 degrees C. There was a significant decrease in count for EC at 37 degrees C, 6 hours (5.5 x 10(2) CFU/ml, p less than 0.01) and 37 degrees, 12 hours (2.9 x 10(2) CFU/ml, p less than 0.0001). It is recommended that infected dialysate should be stored in cool conditions until it can be transported for culture to ensure adequate recovery of gram negative organisms.

Colony Count, Microbial↗
PubMed1990

Haiti. Educating factory workers.

There are approximately 50,000 workers employed in the light assembly industry in Haiti. About 70% are women, the majority of whom are aged between 25 and 34 years, and are either single or in a nonpermanent relationship with the father of their children. Many live and work in appalling conditions, surviving on very low wages to support several children and an extended family. The acquired immunodeficiency syndrome (AIDS) is now a visible problem in many factories. In October 1988, the Center for the Promotion of Women Workers (Centre de Promotion des Femmes Ouvriers/CPFO) launched a pilot AIDS education program for factory women. The Center, based in a large industrial zone near the airport, runs a health clinic and courses in literacy, communications skills, health promotion and family planning. The new AIDS program allowed CPFO staff to gain entry into factories for the 1st time. Other courses were held outside working hours and outside factory premises. Staff contacted manages by telephone to arrange a meeting to discuss AIDS and to ask permission to hold educational "round tables" with workers. Of 18 managers in the factories approached over a 12-month period, only 2 refused entry to CPFO staff. Almost all managers reported they had registered between 2 and 5 deaths from AIDS among their employees over the past couple of years. A total of 85 educational sessions, each lasting about 2 hours, were held within 28 different factories, community or labor organizations reaching 3063 workers (male and female). In each session, the presentation was carried out by 2 CPFO trained monitors and included a slide show, flip charts, and the video "Met ko," originally produced for Haitian immigrants in New York. The most important aspect of the program was the training of 38 volunteer factory-based health promoters. These promoters attended the round table sessions, where they facilitated discussion and distributed condoms and were subsequently available for counseling co-workers. Initially, the Center intended to recruit only literate women as promoters, but several nonliterate women were selected for training by labor organizations 18 hours of tuition and discussion of AIDS/human immunodeficiency virus were held over 2 1/2 weeks, including sessions on group dynamics and organizational skills. To improve communications skills, sessions included role play exercises which were videotaped and played back to trainees. Training in communication skills also helps promoters participate in activities aimed at supporting a broader range of workers' rights.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Comparison of antioxidant and nonantioxidant lipoxygenase inhibitors on neutrophil function. Implications for pathogenesis of myocardial reperfusion injury.

The activation and accumulation of leukocytes during inflammatory processes such as that initiated by myocardial ischemia and reflow appear to be major determinants of irreversible tissue injury. Myocardial salvage by dual cyclooxygenase/lipoxygenase inhibitors and selective 5-lipoxygenase inhibitors has suggested a role for lipoxygenase (LOX) products, such as the potent chemotactic factor leukotriene B4, in ischemia-reflow injury. However, many LOX inhibitors are antioxidants and several have been shown to directly inhibit neutrophil function in vitro, thereby questioning the role of LOX products in reperfusion injury. To clarify further the protective mechanism of lipoxygenase inhibitors, we have examined the effects of two nonantioxidant inhibitors, SK&F 86002 and REV-5901, on human neutrophil activation and function in vitro. The antioxidant LOX inhibitor nordihydroguiaretic acid, which served as a positive control, exhibited a concentration-dependent inhibition of N-formyl-methionyl-leucyl-phenylalanine (fMLP) and recombinant C5a-induced neutrophil bipolarization, fMLP-induced upregulation of the adherence glycoprotein Mac-1 (CD11b/CD18), fMLP-induced aggregation and neutrophil adherence to and migration through interleukin-1-stimulated human endothelial monolayers. In contrast, neither SK&F 86002 nor REV-5901 (in concentrations up to 50 microM) had any effect on these functions, nor did they inhibit neutrophil oxidative metabolism (phorbol myristate acetate-induced chemiluminescence). Inasmuch as both of these agents have been observed to reduce myocardial ischemia-reflow injury in vivo, their failure to directly inhibit neutrophil function further supports an important role for chemotactic LOX products in the pathogenesis of reperfusion injury.

Antigens, Differentiation↗