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Biomedical subjects

A Harris

Publications and source records attributed to A Harris.

At least 397 records · Page 22Linked to original sources
PubMed1991

Rapid orocecal transit in chronically active persons with high energy intake.

Although chronic physical activity by humans can raise energy requirements and energy intake severalfold above sedentary levels, whether these increases alter digestive strategy remains unknown. To investigate this possibility, food passage rate (mouth-to-large intestinal lactulose transit) and absorption (xylose) were compared in a cross section of young men chosen to represent a wide range of daily physical activity and food intake. In 20 men (energy intake 1,272-5,342 kcal/day), resting mouth-to-cecum transit was faster in high caloric consumers (r = -0.69, P less than 0.01). In contrast, xylose absorption (n = 26; measured either as urinary xylose excretion or integrated breath H2 production from the sugar) was unrelated to food intake. Dietary fiber intake was uncorrelated with energy intake. This apparent human digestive strategy of rapid transit across the gut absorptive surface, without a sacrifice in absorption, parallels the adaptations made by several animal species similarly faced with increased energy demand at constant fiber intake. We therefore conclude that the hyperphagia of chronic exercise in humans may be linked with significant gastrointestinal adaptations.

Adaptation, Physiological↗
PubMed1991

Expression of the cystic fibrosis gene in human development.

The specialised epithelia lining the respiratory tract, pancreatic ducts, male genital ducts and sweat gland ducts are defective in the severe inherited disease, cystic fibrosis (CF). We have looked at the expression of the CF gene in human fetal tissues to throw light on the development of function in specialised ductal epithelia and to determine the age of onset of the CF disease process. The CF gene is already seen to be transcribed in mid-trimester fetal lung, pancreas and male genital ducts. Hence, by this developmental stage, and before they are fully differentiated, these epithelia have the capability to perform important transport functions. Epithelial cell cultures derived from fetal pancreas and male genital ducts maintain expression of the CF gene in vitro and so form good models for analysing CF gene function and differentiation of these specialised epithelia.

Blotting, Northern↗
PubMed1991

Immortalization of male genital duct epithelium: an assay system for the cystic fibrosis gene.

The epithelia lining the vas deferens and epididymis are directly involved in the pathology of the autosomal recessive disease cystic fibrosis (CF). We have established culture systems for these epithelial cells. Long-term cell lines have now been generated from these primary epithelial cells by transformation with a plasmid containing an origin-defective simian virus 40 (SV40). Lines have been established from vas deferens and epididymis and both maintain expression of the CF gene.

Base Sequence↗
PubMed1990

[Long-term treatment of acromegaly with the somatostatin analog octreotide (Sandostatin). On the predictive significance of acute tests].

Twelve acromegalic patients were treated (mean +/- SD) 26 +/- 15 months with daily doses of 440 +/- 330 micrograms of the somatostatin analogue octreotide acetate (SMS 201-995, Sandostatin). The levels of somatomedin-C (Sm-C) decreased by 63% from 8.1 +/- 7.7 U/ml to 3.0 +/- 1.3 U/ml. Before starting therapy a long oral glucose tolerance test (oGTT) and a TRH test were performed both without and after s.c. injection of 100 micrograms octreotide. Under long-term treatment with octreotide four of twelve patients reached normal Sm-C-values. The GH levels of all of these patients were continuously suppressed to less than 2 ng/dl in an oGTT after a test dose of 100 micrograms octreotide s.c. till the end of the test (5 1/2 hours after octreotide injection). The other eight patients had a relief of acromegalic symptoms and five had a decrease of their Sm-C-levels, but none of them reached normal Sm-C-values. None of these patients had a continuous suppression of GH after a test dose of octreotide in an oGTT. Hyperprolactinemia (n = 4) was observed only in those patients with an insufficient response to octreotide. The GH-response to TRH showed neither without nor after injection of octreotide a correlation with the results of long-term treatment. Thus it is concluded that GH-suppression in a long oGTT after administration of a test dose of 100 micrograms octreotide acetate s.c. allows to identify those acromegalic patients who will benefit from long-term treatment with the somatostatin analogue octreotide acetate.

Acromegaly↗
PubMed1990

Protection against allergen-induced asthma by salmeterol.

The effects of the long-acting beta 2-agonist salmeterol on early and late phase airways events provoked by inhaled allergen were assessed in a group of atopic asthmatic patients. In a placebo-controlled study, salmeterol 50 micrograms inhaled before allergen challenge ablated both the early and late phase of allergen-induced bronchoconstriction over a 34 h time period. Salmeterol also completely inhibited the allergen-induced rise in non-specific bronchial responsiveness over the same time period. These effects were shown to be unrelated to prolonged bronchodilatation or functional antagonism. These data suggest novel actions for topically active long-acting beta 2-agonists in asthma that extend beyond their protective action on airways smooth muscle.

Administration, Inhalation↗
PubMed1990

A crying baby.

Explore the source record for details and available documents.

Adult↗
PubMed1990

Identical orocecal transit time and serum motilin in hyperthermia and normothermia.

Fever, exercise, and exposure to a hot environment can all cause symptoms of gastrointestinal dysfunction as they elevate body temperature. Nonetheless, the link between hyperthermia per se and these symptoms is unknown. To test the functional significance of increased body temperature, we investigated the influence of substantial passive hyperthermia on orocecal transit in 12 young, healthy men. Transit time was determined by a consistent rise in H2 concentration in a rebreathing apparatus after oral ingestion of 0.7 g lactulose/kg body weight. Lactulose was given in combination with a 350-ml liquid meal (360 kcal). After raising core temperature in warm water to 38.3 degrees C, orocecal transit time was identical to control (90 +/- 13 min at 38.3 degrees C, 92 +/- 13 min at 37.1 degrees C). While hyperthermia did elevate heart rate and minute ventilation, serum motilin, gastrin, and cortisol were similar in the two conditions. The failure of a passive core temperature rise to alter mouth-to-cecum transit suggests that this aspect of alimentary function is independent of body temperature.

Adult↗
PubMed1990

The actions of GR32191B, a thromboxane receptor antagonist, on the effects of inhaled PAF on human airways.

We investigated acute bronchoconstriction and changes in airway responsiveness to methacholine following the inhalation of platelet activating factor (PAF) in an open study of 12 non-asthmatic subjects. Ventilatory function was monitored using a flow rate at 30% of vital capacity (V30) and airway responsiveness was measured as PD40V30, i.e. the dose of metacholine causing a 40% fall in V30. PAF (3-422 micrograms) resulted in dose-related acute bronchoconstriction in 10 of the 12 subjects. There was no association between the airway responsiveness to PAF and to methacholine. Ten subjects showed some increase in airway responsiveness to methacholine 1 or 3 days following PAF. Overall, these changes were statistically significant (P less than 0.05) but were of small magnitude (geometric mean PD40V30pre-PAF = 457 micrograms; 24 hr after PAF = 259 micrograms; 72 hr after PAF = 258 micrograms) and variable: only seven subjects showing increased airway responsiveness on both day 1 and day 3 after PAF. Six subjects who appeared to show increases in airway responsiveness following PAF were re-studied with the inhaled PAF pre-medicated by either placebo or a specific thromboxane receptor antagonist (GR32191B) in a double-blind fashion. GR32191B did not reduce the acute bronchoconstriction due to PAF. In this part of the study, these six subjects did not show significant increases in airway responsiveness following the placebo pre-medicated PAF challenge and so no effect of the drug on airway responsiveness could be shown.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1990

Long-term treatment of metastatic medullary thyroid carcinoma with the somatostatin analogue octreotide.

Three patients with symptomatic metastatic medullary thyroid carcinoma (MTC), one with sporadic form and two with MEN IIa, were treated with the long-acting somatostatin analogue octreotide (SMS 201-995, Sandoz) for 3 to 17 months. Octreotide was administered subcutaneously in a starting dose of 0.6 to 1.0 mg/day by automatic pump (Travax ASH6, Travenol). Symptoms of diarrhoea, weight loss and malaise improved in all patients. Maximal percentage decrease in mean serum calcitonin was 47, 52 and 81% of the basal values, and was observed 1-3 months from the beginning of treatment. Likewise, carcinoembryonic antigen (CEA) levels initially dropped to 45, 60 and 63% of the levels before therapy. A continuing effect was seen in the two patients with MEN IIa after 15 and 17 months of treatment. However, after the initial decrease, calcitonin (CT) levels went up again to 67 and 68% of the basal values and the dose of octreotide had to be increased to 1.5 mg and 2.0 mg/day. CEA also returned to 84 and 105% of the pretreatment titres. Response to 1.5 mg/day octreotide was lost in the patient with the sporadic form of disease after 3 months. Side-effects were minimal. Effects on tumour size could not be evaluated. These suggest that octreotide might be a valuable adjuvant in the long-term management of metastatic MTC. Tachyphylaxis may occur.

Adult↗
PubMed1990

DNA markers near the cystic fibrosis locus: further analysis of the British population.

Genetic analysis of the CF locus in the British Caucasian population has been extended using six DNA probes detecting nine polymorphic loci. Data are presented on (1) diagnostic usefulness of probes, and (2) allele frequencies for each probe in this population. For the probes pXV2C and KM19 (those closest to the CF locus) allele frequencies are further subdivided into male and female derived chromosomes 7. The allele frequencies for both probes on non-CF bearing chromosomes 7, but not on CF carrying chromosomes 7, are substantially different in males and females. Combined haplotypes for pXV2C and KM19 show that, as has been observed in other northern European populations, almost 90% of CF chromosomes in this population carry the pXV2C/KM19, 1/2 (2.1 kb/6.6 kb) haplo-type.

Alleles↗
PubMed1990

Anion selectivity and block of the small-conductance chloride channel on pancreatic duct cells.

Rat and human pancreatic duct cells have small-conductance Cl- channels in their apical plasma membranes. These channels are regulated by secretin and adenosine 3',5'-cyclic monophosphate and may function in parallel with Cl(-)-HCO3- exchangers to allow HCO3- secretion from the duct cell. Using the patch-clamp technique, we have now determined the anion permeability sequence of the channel as NO3- greater than Br- approximately I- approximately Cl- much greater than HCO3- much greater than gluconate. From this we conclude 1) that anion permeation involves a weak interaction with charged sites inside the channel pore, 2) that because of the low HCO3-/Cl- permeability ratio it is unlikely that significant amounts of HCO3- could be secreted directly via the channel, and 3) that channel permeability may determine the anion selectivity of secretion. We also show that 5-nitro-2-(3-phenylpropylamino)benzoic acid blocks the small-conductance Cl- channel, whereas 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid has no effect.

Animals↗
PubMed1990

Orocecal transit during mild exercise in women.

Little is known of the influence of exercise on movement of ingested food through the alimentary tract or of the association of several gastrointestinal hormones with transit rate in exercise. In this study, orocecal transit during mild exercise was measured in 21 women by detecting a rise in expired H2 after ingestion of 20 g lactulose in a 350-ml (360 kcal) liquid meal. Motilin, gastrin, and cortisol were measured in peripheral venous blood when, as evidenced by a breath H2 rise, the first portion of the meal arrived at the cecum. Comparison was made between seated rest and a treadmill walk at 5.6 km/h up a 2% grade. The walk predictably elevated heart rate, O2 uptake, and rectal temperature and also reduced transit time from 98 min at rest to 75 min during exercise (P less than 0.001). Faster transit in exercise was associated with a significant rise in cortisol, while gastrin and motilin levels were both unchanged. In conclusion, in women mild concurrent exercise accelerates orocecal transit rate of at least the first portion of nonabsorbable carbohydrate in a liquid meal. Although the mechanism for the effect remains unknown, it may be secondary to some aspect of the stress response to physical activity.

Adult↗
PubMed1990

Mechanisms of hypochlorite injury of target cells.

HOCl, which is produced by the action of myeloperoxidase during the respiratory burst of stimulated neutrophils, was used as a cytotoxic reagent in P388D1 cells. Low concentrations of HOCl (10-20 microM) caused oxidation of plasma membrane sulfhydryls determined as decreased binding of iodoacetylated phycoerythrin. These same low concentrations of HOCl caused disturbance of various plasma membrane functions: they inactivated glucose and aminoisobutyric acid uptake, caused loss of cellular K+, and an increase in cell volume. It is likely that these changes were the consequence of plasma membrane SH-oxidation, since similar effects were observed with para-chloromercuriphenylsulfonate (pCMBS), a sulfhydryl reagent acting at the cell surface. Given in combination pCMBS and HOCl showed an additive effect. Higher doses of HOCl (greater than 50 microM) led to general oxidation of -SH, methionine and tryptophan residues, and formation of protein carbonyls. HOCl-induced loss of ATP and undegraded NAD was closely followed by cell lysis. In contrast, NAD degradation and ATP depletion caused by H2O2 preceded cell death by several hours. Formation of DNA strand breaks, a major factor of H2O2-induced injury, was not observed with HOCl. Thus targets of HOCl were distinct from those of H2O2 with the exception of glyceraldehyde-3-phosphate dehydrogenase, which was inactivated by both oxidants.

Animals↗
PubMed1990

Short term treatment of acromegaly with the somatostatin analog octreotide: the first double-blind randomized placebo-controlled study on its effects.

Several studies suggest that the somatostatin analog octreotide, or SMS 201-995, may effectively reduce GH hypersecretion. However, no double blind, placebo-controlled study has substantiated these findings. We present the results of a randomized double blind 14-day clinical trial with octreotide in 20 patients with acromegaly. The drug was given sc every 8 h and to the initial dose (50 micrograms) was added another 50 micrograms every other day up to 200 micrograms. GH levels, calculated as the mean values of 12 observations at hourly intervals during 0700-1800 h, and insulin-like growth factor-I (IGF-I) levels were significantly reduced during octreotide treatment. Responses varied from a reduction of 97% of the basal mean GH level to no significant reduction in 2 of 10 patients. There was a good correlation between the reduction of GH and IGF-I levels. The main side-effects were gastrointestinal and well tolerated. We found a spontaneous variation of daily mean GH and IGF-I levels (at 0700 h) in the placebo group, ranging from approximately 150% to 50% of the GH and 120% to 80% of the IGF-I levels noted on day 0. In patients treated with octreotide, the occurrence of GH rises between administration times suggests that it may be desirable to give octreotide every 6 h in some patients.

Acromegaly↗
PubMed1990

Oxygen delivery and cardiac output during exercise following oral phosphate-glucose.

Phosphate has been proposed as an ergogenic aid since it may enhance O2 delivery and cardiac work efficiency by increasing plasma phosphate (P Pi), red blood cell phosphate (RBC Pi), 2,3-diphosphoglycerate (DPG), RBC adenosine triphosphate (ATP), and P50. In 10 normal, fasting males we measured cardiac output (Q) by CO2 rebreathing, heart rate (HR), O2 deficit (O2DEF), and O2 consumption (VO2) during cycle ergometer exercise (60% of peak VO2). Stroke volume (SV) and arteriovenous O2 difference (A-VO2) were calculated. Following a baseline blood sample (BASE) for P Pi, RBC Pi, DPG, RBC ATP, and P50 (3 h before exercise), a single oral dose of dicalcium phosphate (129 mmol) and glucose (500 ml/10% sol, PHOS), or placebo (PLA), was administered in a random, crossover, double-blind fashion. Blood sampling was repeated immediately before and after exercise (PRE-EX and POST-EX). PHOS induced increases in P Pi (3.87 to 4.35 mg.dl-1, P less than 0.05), RBC Pi (3.86 to 4.63 mg.dl-1, P = 0.08), DPG (11.8 to 13.1 mumol.g-1 Hb, P less than 0.05), RBC ATP (4.2 to 4.4 mumol.g-1 Hb, P less than 0.05), and P50 (26.8 to 27.9 mm Hg, P less than 0.05) from BASE to PRE-EX. All variables remained elevated through the exercise period, as evidenced by higher levels than BASE at POST-EX (P less than 0.05). However, P50 was not different across conditions at PRE-EX (PHOS P50 = 27.9, PLA P50 = 28.3 mm Hg) or POST-EX (PHOS P50 = 28.0, PLA P50 = 28.1 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗