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Biomedical subjects

S Long

Publications and source records attributed to S Long.

At least 73 records · Page 4Linked to original sources

The interaction of proinsulin with the insulin-like growth factor-I receptor in human liver, muscle, and adipose tissue.

Because of the sequence homology and tertiary structure similarities between proinsulin (PI) and insulin-like growth factor-I (IGF-I), it is possible that PI interacts with the IGF-I receptor with higher affinity than insulin. To test this hypothesis in man, we have partially purified IGF-I receptors from liver, muscle, and adipose tissue and studied their interaction with PI, insulin, IGF-I, and IGF-II. With some tissue to tissue variation, [125I]insulin binding was 4- to 8-fold greater than IGF-I binding. Unlabeled IGF-I at about 1 x 10(-9 M, IGF-II at about 1 x 10(-8) M, and insulin at about 1 x 10(-6) M displace 50% the binding of [125I]IGF-I to its receptor, whereas PI at 1 x 10(-6) M displaces less than 20% of the binding of [125I]IGF-I to its receptor. We conclude that in human liver, muscle, and adipose tissue, PI does not interact with the IGF-I receptor at a higher affinity than insulin, and the affinity of IGF-I receptors is several-fold lower than that of insulin receptors. It is, therefore, unlikely that if PI were to be administered to man any of its biological effects would be by interacting with the IGF-I receptor.

Adipose Tissue↗

A cAMP-activated chloride channel in the plasma membrane of cultured human gastric cells (HGT-1).

Hydrochloric acid (HCl) secretion by gastric parietal cells involves an apical Cl- conductance, the properties of which have not been defined. In the present study, forskolin and histamine [agonists that increase intracellular cyclic adenosine monophosphate (cAMP)], and dibutyryl cAMP, activated channels in previously quiescent cell-attached membrane patches on cultured human gastric cells (HGT-1). In the cell-attached configuration (Cl- 149 mmol/l in bath and pipette), channels exhibited outward rectification, voltage dependence, inward current (-0.7 pA) at zero holding potential and a reversal potential of +24 mV, consistent with the presence of a Cl- conductive pathway. In excised inside-out patches, channels (i) exhibited degrees of outward rectification and voltage dependence that were comparable to those seen in cell-attached patches, (ii) demonstrated a -21 mV shift of their reversal potential when bath Cl- was decreased from 149 mmol/l to 53 mmol/l (calculated Cl-:cation permeability ratio 17:1), and (iii) were highly sensitive to the Cl- channel blocker diphenylamine-2-carboxylic acid (DPC, 10(-3) mol/l). This cAMP-activated Cl- channel bears many similarities to other Cl- channels within intestinal epithelia, and may represent the apical Cl- channel operating in HCl-secreting gastric parietal cells.

Adenocarcinoma↗

Acute phase proteins in neonatal rabbits: diminished C-reactive protein response.

Acute phase protein response accompanies tissue injury, inflammation, or infection. During the acute phase, serum levels of C-reactive protein (CRP) can increase as much as 1,000-fold. We found that in response to an intramuscular injection of turpentine, neonatal rabbit CRP-specific RNA and serum CRP rose minimally. In contrast, adult serum levels of CRP increased 20-fold and mRNA for CRP in adults increased commensurately. However, during neonatal acute phase reactions, changes in the synthesis of the third component of complement (C3) and albumin were induced, implying a dysynchronous development of the response of various acute phase proteins.

Acute-Phase Reaction↗

Liver pathology in morbidly obese patients with and without diabetes.

The contribution of obesity and/or diabetes to liver pathology in the morbidly obese patient is controversial. We studied the liver biopsies of 100 consecutive patients undergoing gastric bypass surgery for morbid obesity. Multiple morphologic parameters were analyzed and graded independently, without knowledge of the clinical history, liver function tests, and oral glucose tolerance results of the patients. Six percent of the entire group demonstrated no fat, 42% mild fat, 20% moderate fat, and 24% severe fatty metamorphosis of the liver. Twenty-three percent of the patients had central vein fibrosis, 23% sinusoidal fibrosis, 19% bridging fibrosis, and 4% cirrhosis. Thirty-six percent of the patients had some degree of steatohepatitis, 66% possessed so-called glycogen nuclei of hepatocytes, 6% had PAS-positive thickening of blood vessels in the portal tracts, and 1% had lipogranulomas. The degree of fatty metamorphosis and fibrosis was analyzed in three separate groups, categorized by the glycemic status of the patient: 46 patients with normal glucose tolerance (NGT), 23 patients with impaired glucose tolerance (IGT), and 31 patients with non-insulin-dependent diabetes mellitus (NIDDM). Increasing severity of fatty metamorphosis from the normoglycemic obese to the diabetic obese patients was found, which was statistically significant by chi 2 analysis. Four of the six patients showing no fatty metamorphosis were normoglycemic. Glycogen nuclei and PAS-positive blood vessels were significantly more prevalent in the diabetic obese than in the normal obese. In conclusion, the distribution of significant liver histopathology in the morbidly obese patient correlates in severity with the degree of impaired glycemic status.

Adult↗

Applicability of a threshold loading device for inspiratory muscle testing and training in patients with COPD.

We evaluated application of a Pth device for testing inspiratory muscle endurance among patients with severe but stable COPD. Endurance time in five patients was reproducible. Magnitude of variability was +/- 1.26 minutes with a range of +/- 0.19 to +/- 2.28 minutes. Eleven inpatients completed inspiratory muscle training twice daily for four weeks in addition to their usual program of respiratory rehabilitation. The mean age of our experimental cohort was 65 years; FEV1, 33 +/- 12 percent predicted; and Dsb, 42 +/- 7 percent predicted. Baseline measurements showed no significant differences in pulmonary function, exercise tolerance, inspiratory muscle strength or inspiratory muscle endurance between control and study groups. Following training, the study group significantly improved inspiratory muscle endurance as evidenced by an increase in endurance time while breathing against the same absolute external Pth load used during baseline assessments. There were no associated changes in lung mechanics, muscle strength or exercise tolerance.

Aged↗

Genetic analysis of a cluster of genes required for synthesis of the calcofluor-binding exopolysaccharide of Rhizobium meliloti.

Rhizobium meliloti produces an acidic, Calcofluor-binding exopolysaccharide which plays a role in nodulation of alfalfa plants by this bacterium. We constructed and mapped 102 transposon insertions in a 48-kilobase (kb) region previously shown to contain several exo genes. Mutations affecting production of the Calcofluor-binding exopolysaccharide were clustered in a 22-kb region and fell into 12 complementation groups. Strains carrying mutations in seven of the complementation groups (exoA, exoB, exoF, exoL, exoM, exoP, and exoQ) produced no Calcofluor-binding exopolysaccharide and induced non-nitrogen-fixing nodules on alfalfa. Mutants in an eighth complementation group, exoH (Leigh et al., Cell 51:579-587, 1987), produce an altered exopolysaccharide and also induce the formation of non-nitrogen-fixing nodules. Mutants in the remaining four complementation groups produced less Calcofluor-binding material than the wild type. Mutants carrying mutations in two of these complementation groups (exoK and exoN) formed apparently normal, nitrogen-fixing nodules, while mutants in the other two groups (exoG and exoJ) formed normal nodules less efficiently than the wild type.

Benzenesulfonates↗

Symbiotic loci of Rhizobium meliloti identified by random TnphoA mutagenesis.

We have developed a system for using TnphoA (TnphoA is Tn5 IS50L::phoA), which generates fusions to alkaline phosphatase (C. Manoil and J. Beckwith, Proc. Natl. Acad. Sci. USA 82:8129-8133, 1985), in Rhizobium meliloti. Active fusions expressing alkaline phosphatase can arise only when this transposon inserts in genes encoding secreted or membrane-spanning proteins. By confining our screening to 1,250 TnphoA-generated mutants of R. meliloti that expressed alkaline phosphatase, we efficiently identified 25 symbiotically defective mutants, all of which formed ineffective (Fix-) nodules on alfalfa. Thirteen of the mutants were unable to synthesize an acidic exopolysaccharide (exo::TnphoA) that is required for nodule invasion. Twelve of the mutations created blocked at later stages of nodule development (fix::TnphoA) and were assigned to nine symbiotic loci. One of these appeared to be a previously undescribed locus located on the pRmeSU47a megaplasmid and to encode a membrane protein. Two others were located on the pRmeSU47b megaplasmid: one was a new locus which was induced by luteolin and encoded a membrane protein, and the other was dctA, the structural gene for dicarboxylic acid transport. The remaining six loci were located on the R. meliloti chromosome. One of these was inducible by luteolin and encoded a membrane protein which determined lipopolysaccharide structure. Three additional chromosomal loci also appeared to encode membrane proteins necessary for symbiosis. The remaining two chromosomal loci encoded periplasmic proteins required for symbiosis.

Alkaline Phosphatase↗

Reversal of sleep-induced hypoventilation and chronic respiratory failure by nocturnal negative pressure ventilation in patients with restrictive ventilatory impairment.

The efficacy of negative pressure ventilation (NPV) in alleviating sleep-induced reductions in alveolar ventilation and in producing long-term clinical benefits was studied in 5 patients (54 +/- 8 yr of age; mean +/- SD) with chronic respiratory failure secondary to restrictive ventilatory impairment (VC, 40 +/- 14% predicted; TLC, 72 +/- 18% predicted; FEV1/FVC, 89 +/- 15%). In control sleep studies, arterial O2 saturation decreased from 81 +/- 6% during wakefulness to 79 +/- 1% during non-REM sleep and to 67 +/- 3% during REM sleep, and transcutaneous PCO2 increased from 80 +/- 16 mm Hg during wakefulness and non-REM sleep to 87 +/- 16 mm Hg during REM sleep. Nocturnal NPV in a cuirass ventilator improved baseline ventilation during wakefulness and prevented deterioration of alveolar ventilation during sleep. Upper airway obstruction during sleep induced by NPV was successfully managed with either a tricyclic medication or nasal CPAP. After 8 wk of nocturnal NPV, all patients felt considerably better. Daytime resting arterial PCO2 decreased from 56 +/- 2 to 46 +/- 3 mm Hg (p less than 0.05) and PO2 increased from 51 +/- 9 to 70 +/- 10 mm Hg (NS). Four patients have continued NPV at home on a regular basis and have returned to full-time employment. We conclude that nocturnal NPV is an effective method of preventing sleep-induced reductions in alveolar ventilation and a practical method of long-term management of patients with nonobstructive chronic respiratory failure.

Carbon Dioxide↗

Assisting ventilation in respiratory failure by negative pressure ventilation and by rocking bed.

The present study was undertaken to evaluate the effectiveness of acute ventilation by rocking bed (RB) and by negative-pressure ventilator (NPV) on arterial oxygenation and carbon dioxide tension in seven patients in whom respiratory failure (PaCO2 [+/- SD], 64 +/- 4 mm Hg; PaO2, 54 +/- 10 mm Hg) was consequent on nonobstructive ventilatory impairment. The increase in SaO2 (percent above baseline, 5 percent RB and 6 percent NPV) was similar for both methods, but a greater fall in PCO2 (percentage change in PCO2, 3 percent RB; 15 percent NPV; p less than 0.05) was observed during NPV. Diaphragmatic and accessory muscle electrical activity was markedly reduced during NPV but remained unchanged or increased on RB. Asynchronous breathing was frequently observed with RB but only rarely with NPV. These preliminary results suggest that effective mechanical ventilatory support could be achieved with either RB or NPV. However, their long-term effects as compared with those of positive-pressure ventilation remain to be explored.

Beds↗

2-Fluoro-oestradiol does not cause uterine refractoriness but inhibits oestradiol-induced implantation in rats.

An intravenous injection of 2-fluoro-oestradiol simultaneously with an implantation-inducing dose of oestradiol reduced the number of implantation sites in delayed implanting hypophysectomized rats maintained with progesterone. Administration of 2-fluoro-oestradiol 1 h before or after oestradiol had no effect. Furthermore, injection of as much as 500 ng 2-fluoro-oestradiol 48 h before administration of oestradiol failed to have any effect upon implantation, i.e. failure to block implantation was correlated with failure to induce the uterine refractory state. These results suggest that conversion of primary oestrogens to catechol oestrogens could be important for implantation as well as for the induction of the oestrogen refractory state in the uterus.

Animals↗

Teaching computation/shopping skills to mentally retarded adults.

Three moderately/mildly retarded adults, ranging in age from 32 to 53 years, were trained in adaptive community skills. Behaviors identified for intervention (computational and shopping skills) were the same for all three clients. Assessment followed a multiple-baseline design across skills for each subject. The subjects were assessed in a classroom and in grocery stores in the community. Following baseline, treatment was provided that involved instructions, performance feedback, social reinforcement, in-vivo modeling, self-evaluation, and social and tangible reinforcement. Gains on both computational and shopping skills were stable or decreased during baseline, but rapid and dramatic improvements occurred soon after treatment began. Skills generalized to other stores, and these gains were maintained at a 2-month follow-up. Implications of the findings were discussed.

Activities of Daily Living↗

Blebs and hematomas in the lips of CL/Fr and A/J mice.

Newborn-CL/Fr mice have +/- 20% frequency of cleft lip with or without cleft palate (CLP) depending on environment. However, examination of early fetal development from days 12 to 15 disclosed an increased number of hematomas or fluid-filled blebs in the regions of maxillary process fusion. The earliest stages do not appear to involve the blood supply directly but separate the epithelium from underlying mesenchyme by clear blebs. Similar defects were found in untreated A/J mice. These findings suggest that osmotic and hemodynamic abnormalities may be part of the mechanism of cleft lip formation in these related strains and that these defects may result from a biochemical defect of the connective tissue matrix in regions of process fusion.

Animals↗

Compliance with disulfiram treatment of alcoholism.

One hundred twenty-four men were randomly assigned to receive disulfiram with a riboflavin marker or riboflavin alone. During a one year follow-up urine specimens were collected at each visit and analyzed for riboflavin. There was a strong relationship between excellent attendance and infrequent drinking. For subjects taking disulfiram there was a high correlation between a subject submitting 15 or more positive urines during follow-up and infrequent drinking. For the disulfiram patients there was also a strong relationship between continuous usage of disulfiram and infrequent drinking. However, the correlation between percentage of urine specimens positive for the riboflavin marker and infrequent drinking was slight. This occurred because a person who was drinking tended to return for follow-up only when he was not drinking and thus submitted only a few specimens of which the majority were positive. We conclude that (1) excellent attendance, (2) submission of a large number of positive urines and (3) a period of continuous compliance to the disulfiram regimen were highly associated with infrequent drinking.

Adult↗

The role of urinary precipitates in the excretion of electrolytes and urate in the domestic fowl.

1. In order to quantify losses of Na and K associated with precipitate fractions in semi-solid avian urines, Na, K, uric acid and urates (UA + U) and inulin were measured in plasma, in whole ureteral urine, and in urinary precipitates of hens. Ten animals were used, five fed a control commercial poultry meal (Diet A) and five maintained on a high protein, low-Na feed (Diet B). 2. In ureteral urines from hens on Diet A, dried precipitate accounted for 5.6% of the total whole urine weight, on the average. UA + U constituted about two-thirds of the precipitates' weight and 80% of the total excreted UA + U load of 97.4 mM. The average molar fractions, [Na]/[UA + U] and [K]/[UA + U], in precipitates were in the range 0.1-0.2; and the Na and K lost in these fractions were 12.8 mequiv and 9.6 mequiv, respectively, per 1 whole urine. These losses represent 9% and 23% of total Na and K excretion. 3. Diet B was used to accentuate potential cation loss in precipitates if obligatory binding of K and especially Na were to occur in precipitates. Urinary [UA + U] in whole urine rose to 146 mM of which 95% was found in precipitates. The average molar fraction [Na]/[UA + U], however, fell to 0.06 and that of [K]/[UA + U] to 0.08. Renal loss of Na was 8.5 mequiv and of K was 11.5 mequiv per 1 whole urine. 4. These experiments reveal that significant but minor fractions of excreted Na and K are associated with precipitates of avian urine, although the loss is insignificant compared to that reported in starlings (Braun, 1978). They further indicate that the Na/inulin clearance ratio, based on measurements in whole urine and plasma, adequately reflects fractional excretion which, on Diet A, was 1.8% of the filtered load and, on the Na-poor Diet B, less than 0.1%. These values place the Na-reabsorbing abilities of these birds easily within the range reported for ureotelic vertebrates and suggest that uricotelism does not impose a major renal salt loss in birds.

Animals↗