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Biomedical subjects

A Charles

Publications and source records attributed to A Charles.

At least 55 records · Page 3Linked to original sources

Neutrophil chemoattractant production by cultured serotonin-stimulated bovine and human endothelial cells.

Recent studies have demonstrated that serotonin (5-HT) is avidly taken up and metabolized by vascular endothelial cells (EC) and have suggested that 5-HT may contribute to inflammatory responses. Because EC can produce neutrophil cytokines among their biologically active molecules, we hypothesized that the interaction of 5-HT and EC might cause production of such a cytokine. Using a modified Boyden chamber assay, we found that cultured bovine aortic (BA), bovine pulmonary arterial (BPA), and human umbilical vein (HUV) EC incubated with 5-HT produced a neutrophil chemoattractant (NCA). The NCA was predominantly chemotactic, was not stored in an active form, appeared within 5 min of incubation with 5-HT, and required de novo protein synthesis for its appearance. The mechanism of NCA production was different in the three types of EC examined. Elaboration of NCA and BAEC and HUVEC was apparently mediated by 5-HT1 receptors and did not require uptake of 5-HT, whereas its elaboration from BPAEC required 5-HT uptake and was apparently mediated by 5-HT2 receptors. Incubation with three different lipoxygenase inhibitors blocked production of NCA, whereas incubation with a cyclooxygenase inhibitor did not. Further characterization of the NCA demonstrated that it was a mixture of several different chemotactic lipids and was distinct from other lipid or phospholipid neutrophil chemoattractants. These studies suggest that the interaction of the platelet-release product, 5-HT, with the adjacent endothelium results in the production of a chemoattractant that could affect neutrophil accumulation at sites of inflammation.

Animals↗

Severe hemolysis and red cell fragmentation caused by the combination of a spectrin mutation with a thrombotic microangiopathy.

Two patients are described who presented with severe hemolysis and erythrocyte fragmentation. One patient had renal allograft rejection and disseminated intravascular coagulation, and the other had thrombotic thrombocytopenia purpura. The severity of hemolysis and the red cell abnormalities were considerably more profound than usually seen in patients with thrombotic microangiopathies. After evaluation of blood smears prepared before the onset of the disease and biochemical characterization of proteins of the red blood cell skeleton, a mutation of the skeletal protein spectrin, designated Sp alpha l/65, was identified. In the heterozygous form, this mutation manifests as mild, often asymptomatic, hereditary elliptocytosis. We conclude that in these two patients with thrombotic microangiopathy, the intrinsic red cell membrane instability resulting from the underlying skeletal defect aggravated the mechanical red cell fragmentation, producing morphological features similar to the severe hemolytic form of hereditary elliptocytosis or hereditary pyropoikilocytosis.

Adolescent↗

Harlequin fetus and micromelia.

A fetus was born prematurely after a 34-week pregnancy whose evolution was marked by the ultrasonic finding at 23 weeks of a considerable shortening of the long bones. At birth, the newborn infant bore the appearance of a harlequin fetus. There was no dwarfism, but the micromelia discovered in utero was confirmed both clinically and radiologically. Such global micromelia associated with this kind of pathology has never been described, not to mention witnessed, in utero and may be part of the fetal akinesia sequence phenotype.

Abnormalities, Multiple↗

Effect of human insulin administration on urinary acidification in patients with insulin-dependent diabetes.

A previous study has shown that oral glucose administration results in a transient fall in urinary acid excretion in humans. The present study was undertaken to determine the effect of physiologic doses of insulin on urinary acidification while maintaining serum glucose concentration constant. This was accomplished by using a euglycemic insulin clamp method. Eight patients with insulin-dependent diabetes and no clinical or laboratory evidence of detectable renal disease were studied. Data obtained during two 2-hour periods of steady state insulin infusion rates of 0.2 and 0.5 mU/kg/min were compared. This resulted in steady state serum free insulin levels of 15 +/- 0.1 and 39 +/- 0.6 uU/ml respectively. Urinary pH and bicarbonate excretion rate rose while the excretion rates of titratable acid, ammonium and net acid fell significantly with increased insulin administration. These changes occurred in the absence of any significant changes in serum glucose, potassium, Ca2+ or phosphorus concentrations or urinary excretion rates of Na+, K+, phosphorus or Ca2+. These data suggest that increased insulin levels within the physiological range can result in a transient fall in the rate of urinary acid excretion. These findings confirm previous observations in animals and suggest that insulin may be the cause of post prandial urinary "alkaline tide".

Adult↗

Outpatient use of intermediate- and short-acting semisynthetic human insulins.

To determine if semisynthetic human insulins are useful in the outpatient management of insulin-dependent diabetes, the conditions of eight patients were evaluated for three months using short- and intermediate-acting insulins. No complications of either insulin preparation were observed. Hemoglobin A1c levels were decreased from 8.4% to 6.9% during human insulin use, and, in addition, normal hemoglobin A1c levels were maintained in patients using portable insulin infusion pumps. These results were achieved because of the health care provision team and were not directly the result of human insulin. Semisynthetic human insulins were also associated with lower levels of circulating insulin antibody. These data indicate that both short- and intermediate-acting semisynthetic human insulins are effective in stringent diabetes metabolic control, provided adequate health care provision is available.

Adult↗

Lack of effects of beta sympathetic blockade on the metabolic and respiratory responses to carbohydrate feeding.

Increases in metabolic rate, heart rate and ventilation occur following carbohydrate feeding or during beta sympathetic stimulation. Furthermore, insulin secretion and hypokalemia are features common to both which raises the question as to whether these effects of carbohydrate depend upon an intact sympathetic nervous system. Accordingly, in the present study, we measured the effects of carbohydrate feeding (250 gram meal) before and after chronic beta sympathetic blockade in sex normal men. Before blockade metabolic rate (O2 consumption) rose (P less than 0.05) from a fasting mean of 248 +/- 19.7 (SEM) ML O2/min to 292 +/- 15.2 at 1 hr. 269 +/- 13.7 at 2, and 262 +/- 18.0 at 3 hr following the meal. During blockade (oral propranolol 80 mg p.o. Q 6 h for 3 days) the post-prandial increase in O2 consumption was also significant (P less than 0.05) and almost identical to that found before blockade. A similar pattern was found for ventilation, heart rate, insulin secretion and hypokalemia, where the significant postprandial changes were not altered by blockade. A transient increase in serum triiodothyronine from a mean of 92 +/- 8.4 microgram/ML to 109 +/- 9.4 occurred at 1 hr (P less than 0.05) only during blockade. No other changes in thyroid hormonal concentrations occurred as a result of the meal. We conclude that although similarities exist between beta sympathetic stimulation and carbohydrate feeding, the post-prandial effects studied do not depend on intact beta sympathetic receptors.

Dietary Carbohydrates↗