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Biomedical subjects

N Segal

Publications and source records attributed to N Segal.

At least 37 records · Page 2Linked to original sources

Apparent culture-negative endocarditis of the prosthetic valve caused by Cardiobacterium hominis.

To date, there have been fewer than 50 reported cases of endocarditis caused by C hominis. Only six of these involved prosthetic heart valves. To our knowledge, in no previous case has the organism been cultured directly from the valve, an aspect we believe gives our case special relevance. Our case also illustrates the fact that whenever a fastidious organism is thought to be responsible for infective endocarditis, not only blood cultures but also cardiac tissue cultures should be held beyond the customary period of time.

Aged↗

Heritability of substance abuse and antisocial behavior: a study of monozygotic twins reared apart.

Thirty-two sets of monozygotic twins reared apart since shortly after birth (31 pairs and one set of triplets; median age at separation was 0.2 years) were interviewed separately and blindly using the Diagnostic Interview Schedule for presence of DSM-III Axis I psychiatric disorders and antisocial personality. Because the sample was recruited from a nonclinical population, predictably few subjects met criteria for such disorders. However, items counting toward diagnoses were cumulated into four scores: alcohol-related problems, drug-related problems, childhood antisocial behavior, and adult antisocial behavior. The scores showed within-scale cohesion as measured by Cronbach's coefficient alpha. The drug scale and both antisocial scales showed significant heritability (p less than 0.1), but the alcohol scale had an estimated heritability of zero (albeit with a broad confidence interval). There appeared to be substantial commonalities in the genetic factors responsible for these traits.

Adolescent↗

Genetic factors in the electrocardiogram and heart rate of twins reared apart and together.

Important physiologic mechanisms have been thought not to exhibit large amounts of variability, due in part to the assumption that critical biologic functions will have evolved to an evolutionary optimum. The attainment of this optimum would necessarily eliminate individual differences in these variables. Using a sample of monozygotic and dizygotic twins reared apart since birth or early infancy, 12-lead electrocardiographic recordings and vectorcardiograms were obtained. Values of these variables for monozygotic and dizygotic twins reared together were obtained from other studies. Maximum likelihood tests of genetic and environmental components of variation for PR interval, QRS duration, QT interval and ventricular rate indicated a significant contribution of genetic effects (most heritabilities ranged from 30 to 60%), with a negligible contribution from common familial environmental effects.

Electrocardiography↗

Beta-cell memory to insulin secretagogues: characterization of the time-dependent inhibitory control system in the isolated rat pancreas.

Most secretagogues, in addition to their acute stimulatory effect on insulin release, modify the responsiveness of the islet to subsequent stimulations. According to the nature and duration of the stimulus, the generated islet memory may either amplify [time-dependent potentiation, (TDP)] or diminish [time-dependent inhibition (TDI)] the responsiveness of the beta-cell. This work characterizes the kinetic parameters of TDI in the isolated rat pancreas. When subjected to a low dose (8.3 mmol/liter) glucose stimulus, maximal TDI was observed after 5 min of priming, while at a higher dose (16.7 mmol/liter) shorter exposures were sufficient. Longer periods of stimulation (10-40 min) resulted in the predominance of TDP, thus amplifying the release rate. TDI was not affected by previous generation of TDP; 40-min priming with 16.7 mmol/liter glucose markedly augmented the subsequent insulin responses to a pair of 6.9 mmol/liter stimuli, but the response to the second stimulus was inhibited, as in unprimed pancreas. Stimulation with arginine (5.0 mmol/liter) in the presence of basal (3.3 mmol/liter) glucose activated TDI only, and hence revealed monophasic insulin release. Tolbutamide (100 micrograms/ml), glucagon (5 micrograms/ml), and isobutylmethylxanthine (0.1 mmol/liter) also demonstrated TDI when given as a pair of 10-min stimuli; they all elicited monophasic insulin responses during prolonged stimulation. Arginine was chosen for detailed characterization of TDI because of its potency. Using identical concentrations of arginine for the generation and expression of TDI, a similar degree of inhibition (60-80%) was observed at all doses tested (0.5-5.0 mmol/liter). However, there existed competition between TDI and the acute secretory signal. Thus, TDI generated by 1.0 mmol/liter arginine had a minimal effect on insulin release induced by 2.0-5.0 mmol/liter amino acid, while it was fully inhibitory of the response to 1.0 mmol/liter arginine. Similarly, inhibition of the insulin response to 5.0 mmol/liter arginine was dependent on the dose (0.5-5.0 mmol/liter) of the priming pulse of arginine. The generation of TDI was unaffected by the insulin release rate during priming, since synergistic augmentation (combined arginine-glucose or arginine-isobutylmethylxanthine stimulation) or partial inhibition (arginine plus epinephrine) of the response had no effect on the subsequent expression of TDI. It is concluded that TDI and TDP are two distinct regulatory systems that independently control the rate of insulin release, most probably operating through different mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)

1-Methyl-3-isobutylxanthine↗

Retinyl ester hydrolase of bovine retina and pigment epithelium: comparisons to the rat liver enzyme.

The hydrolysis of 3H-retinyl ester was examined in the retinal pigment epithelium (RPE) and neural retina of cattle eyes and compared to that in homogenates of rat liver. The optimum pH for hydrolysis was 4.0-4.5 for RPE and 7.5-8.0 for liver. The RPE activity, which shows no variability between individual animals, is localized mainly in the lysosomal fraction of the cell. It is strongly inhibited by bile salts at concentrations as low as 0.2-0.5% and conversely, is strongly activated by Triton X-100, with maximum stimulation found at a concentration of approximately 1%. The apparent Vmax for hydrolysis of labeled retinyl ester in the RPE is 2.7 nmoles/hr/mg protein, a value approximately 1/150 to 1/200 of the rate of retinol esterification in these cells. Little or no hydrolytic activity could be detected in neural retina or in rod outer segments. Studies on the specificity of the RPE retinyl ester hydrolase activity revealed unexpectedly high hydrolytic activity toward both cholesteryl oleate and triolein, approximately 20 and 5 times greater, respectively, than in rat liver. The hydrolytic activity for cholesteryl oleate in the RPE was mainly at pH 3.5, while that for triolein showed three pH maxima, one at pH 4.5-5.0, a second near neutral pH and the third at pH 8. These findings reflect an active and complex pattern of fatty acyl ester lipid-metabolizing enzymes in cattle RPE whose interrelationships to one another require further clarification.

Animals↗

Enzymatic esterification of vitamin A in the pigment epithelium of bovine retina.

The kinetic properties and subcellular distribution of an esterifying enzyme in the pigment epithelium of bovine retina have been studied using both [1-3H]retinol and [3H]retinol bound to cellular retinol-binding protein as substrates. The most active esterifying fraction in pigment epithelial cell preparations was the microsomes, but the lysosome plus mitochondria fraction also showed some activity, probably due to endoplasmic reticulum present as an impurity. The microsomal enzyme showed optimum activity at pH 7.5, and the reaction was linear up to 30 microgram protein and for the first 10-15 min. The apparent Km values were 16.6 . 10(-6) and 5.5 . 10(-6) M for [3H]retinol and bound [3H]retinol, respectively. This is the first time that retinol bound to cellular retinol-binding protein has been shown to undergo metabolic transformation. The microsomal esterifying activity was destroyed by boiling for 1 min, or after freezing for 2 months. No clear requirement for ATP, CoA or fatty acid could be demonstrated. Of all the other tissues examined under the same experimental conditions as those used for the pigment epithelium, only intestine showed measurable activity. With larger amounts of tissue protein and longer incubation periods, activity was also detectable in microsomes of liver, testis and retina.

Animals↗

Subcellular distribution of free and esterified forms of vitamin A in the pigment epithelium of the retina and in liver.

1. The distribution of vitamin A was examined in various subcellular fractions of rat liver and bovine retinal pigment epithelium. In rat liver, the major portion of the vitamin is in the cytosol, whereas in pigment epithelium, it is concentrated mainly in the microsomes. The microsomal vitamin A of pigment epithelium is tightly bound to membranes, as shown by the inability to release it except by organic solvent extraction or incubation with Triton X-100. 2. In both tissues, two different forms of cytosol vitamin A could be distinguished by ultracentrifugation. The major portion in liver is in the floating lipid phase and consists mainly of retinyl ester. The remainder (less than 10% of the total) is in the underlying infranatant; about 90% of the vitamin A in this fraction is esterified. By contrast, two-thirds of the vitamin A of pigment epithelial cell cytosol is in the infranatant; it consists of both esterified and unesterified retinol. The floating layer in the pigment epithelial cytosol consists entirely of retinyl ester. 3. These two forms of cytosol vitamin A in the pigment epithelium could also be separated by gel filtration on Sephadex G-100 which yielded two distinct fluorescent peaks. The first, which appeared in the void volume and corresponded in all probability to the floating layer obtained by ultracentrifugation, consisted only of retinyl ester. The second peak, which was eluted in approximately the same position as myoglobin, contained only unesterified retinol. It was abolished completely by preincubation with pronase. These findings support the view that the second peak represents the endogenous retinol-retinol binding protein complex of pigment epithelial cytosol. The fluorescent enhancement of the retinol bound to protein in this peak was about 4--5-fold compared to retinol in organic solvents.

Animals↗

Eyelash length in children and adolescents with allergic diseases.

Long eyelashes may be congenital, acquired in association with certain systemic diseases, or drug induced. In the past, long eyelashes were considered an external sign found in children with allergic diseases. However, this claim has never been examined in a controlled study. We compared the eyelash lengths of allergic children and adolescents with perennial allergic rhinitis, with or without bronchial asthma and atopic dermatitis (n = 60) to those of age- and sex-matched nonallergic controls (n = 80). The eyelashes of the allergic patients were found to be significantly longer than those of the controls: 9.43 +/- 1.39 mm versus 8.45 +/- 1.30 mm (p < 0.001). Eyelash length did not differ between patients with allergic rhinitis only (n = 31; 9.65 +/- 1.43 mm) and patients with allergic rhinitis and other allergic diseases (n = 29; 9.19 +/- 1.31 mm) (p = 0.196). These results indicate that children and adolescents with allergic diseases have longer eyelashes compared to nonatopic controls and that long eyelashes may be a part of the phenotype of the allergic patient.

Adolescent↗

Neutropenia complicating Rh-hydrops fetalis: the effect of treatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF).

Neutropenia is a less commonly encountered feature of Rh hemolytic disease of the newborn, and its management may be problematic. Two newborn infants with neutropenia complicating Rh incompatibility-induced hydrops fetalis were treated with intravenous recombinant human granulocyte colony-stimulating factor (rhG-CSF), 5 micrograms/kg/day for 5 days. Both patients responded to therapy with a rapid and persistent increase of their neutrophil counts to normal values. The treatment was well tolerated and no adverse clinical events were observed. rhG-CSF induces a significant increase in peripheral absolute neutrophil counts of neutropenic neonates with Rh hydrops fetalis and was well tolerated. The contribution of rhG-CSF to clinical recovery warrants further investigation.

Adult↗