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Biomedical subjects

A Cohen

Publications and source records attributed to A Cohen.

At least 631 records · Page 35Linked to original sources
PubMed1988

Globotriosyl ceramide is specifically recognized by the Escherichia coli verocytotoxin 2.

Two Escherichia coli cytotoxins (verotoxins 1 and 2) have been previously implicated in the cytopathology of the Hemolytic Uremic Syndrome. We have examined the glycolipid binding specificity of verotoxin (VT)2. This toxin specifically binds to globotriosyl ceramide (galactose alpha 1-4 galactose beta 1-4 glucosyl ceramide). Removal, or substitution of the terminal a galactose residue with N-acetyl galactosamine in beta 1-3 linkage, deletes binding activity. The toxin does not recognize similar terminal a galactose residues on a glycoglycerolipid. Thus the binding specificity of VT2 is the same as previously reported for VT1. Liposomes containing globotriosyl ceramide are able to specifically remove VT1 and VT2 cytotoxicity and cell lines selected in vitro for resistance to VT1 are cross resistant to VT2.

Bacterial Toxins↗
PubMed1988

Phorbol esters and calcium ionophores differentially regulate the transcription of gamma-T-cell antigen receptor gene in human thymocytes.

The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and the calcium ionophore ionomycin differentially regulated the expression of the gamma-T-cell antigen receptor (gamma-TCR) gene in human thymocytes. Ionomycin induced an increase in gamma-TCR mRNA while TPA prevented this effect. The effects of ionomycin and TPA are completely reversed upon their removal. Protein kinase C-depleted cells are unable to respond to TPA but the induction of gamma-TCR by ionomycin was unimpaired. The regulation of gamma-TCR gene expression by TPA and ionomycin occurred at the level of gene transcription, whereas the rate of gamma-TCR mRNA degradation was unaffected by TPA or ionomycin.

Child↗
PubMed1988

Antagonistic effects of calcium ionophores and phorbol esters on T cell receptor mRNA levels in human thymocytes.

Levels of mRNA of the T cell antigen receptors (TcR) in human thymocytes are differentially regulated in response to distinct intracellular signals. Activation of protein kinase C by the phorbol ester, tetradecanoyl phorbol acetate or other phorbol esters increases the levels of the alpha and beta T cell receptor (TcR-alpha, TcR-beta) mRNA, whereas an increase in cytosolic free Ca2+, induced by ionomycin or other Ca2+ ionophores, results in a decrease of alpha and beta TcR mRNA levels. In contrast, ionomycin increases the expression TcR-gamma mRNA whereas tetradecanoyl phorbol acetate prevents this induction. Our results suggest the existence of two opposing intracellular pathways that control expression of TcR-alpha and TcR-beta mRNA levels, on the one hand and TcR-gamma mRNA, on the other. These results provide the first evidence for antagonistic actions of protein kinase C and cytosolic-free Ca2+ on gene expression.

Calcium↗
PubMed1988

Postrhinoplasty epistaxis. Role of vitamin E?

Postrhinoplasty epistaxis occurred in two patients, both of whom were found to be ingesting megadoses of vitamin E. The rate of vitamin E consumption in a population of 100 uncomplicated nasal operations during this same period was 16%. A review of the medical literature on vitamin E found recent evidence demonstrating a marked decrease in platelet adhesiveness with megadose ingestion of vitamin E. It is concluded that this should be avoided in the perioperative period.

Adult↗
PubMed1988

Bioavailability of potassium from three dosage forms: suspension, capsule, and solution.

A crossover study was performed in 28, healthy, male volunteers to determine the bioavailability of potassium from a suspension containing microencapsulated potassium chloride compared with that from a marketed microencapsulated potassium chloride capsule and a marketed potassium chloride solution. The 20-day study consisted of four, five-day periods. In three of the periods, a single, 40-mEq dose of one of the potassium formulations was administered; no drug treatment was given in the remaining period so that the amount of potassium contributed by dietary sources could be determined. Meals were served that provided controlled amounts of potassium and sodium. Bioavailability was represented by cumulative amount of K+ excreted in urine 24 and 48 hours after drug administration. The rate of absorption was calculated from excretion rates during each of the intervals of urine collection on Days 4. The pattern of excretion exhibited by the solution indicated rapid absorption and elimination. The potassium from the suspension and the capsules was excreted more slowly and over a longer period, indicating that the potassium content from these formulations was not being dumped. No statistically significant differences between the suspension and the capsules were found. The extent of absorption of K+ was similar from all three products, and the potassium from the suspension was found to be fully bioavailable when compared with the liquid and the capsule.

Adult↗
PubMed1988

Steady state pharmacokinetics of naproxen in young and elderly healthy volunteers.

The pharmacokinetic properties of naproxen (375 mg twice daily and 750 mg twice daily) were evaluated in 23 young (age range, 19 to 32 years) and 25 elderly (age range, 65 to 74 years) healthy male volunteers. After an initial screening examination, each subject received 15 doses of naproxen in this double-blind parallel study. Comparison of trough plasma naproxen concentrations (12 hours after each of the last two morning doses) verified steady state and provided no evidence of drug accumulation in either age or dosage group beyond that achieved after seven days of naproxen administration. Plasma naproxen concentrations determined at 0, 0.5, 1, 2, 4, 8, 12, and 24 hours after the final dose revealed no statistically significant differences between age groups, at either dosage, with respect to total area under the 12-hour time-concentration curve or peak plasma naproxen concentrations. Terminal plasma half-life was longer in the elderly group at each dosage, but these differences are probably not clinically important since the steady state area under the curve was similar in the two age groups. There were no statistically significant changes in serum creatinine levels (monitored as an indicator of kidney function) in either group at either dosage. These results suggest that advanced age per se does not alter naproxen pharmacokinetics in any clinically significant way.

Adult↗
PubMed1988

Tests of a temporal theory of attentional binding.

Different features of stimuli present in the field of view appear to be registered in different cortical maps. How, then, are the features that come from the same object bound together rather than mistakenly assembled with features coming from other simultaneously present objects? One theory supposes that an attentional mechanism intercepts input coming from particular retinal locations at a way station prior to parsing of the features from the same object. Any enhancement (or facilitation) at that stage will cause all the features from that object to be modified simultaneously in the downstream registers. The imposed temporal synchronicity serves as the essential binding cue. Five experiments provided no support for the theory. There is no tendency for synchronicity of features to cause binding unless the features come from the same location. Location, rather than temporal synchronicity, appears to be the essential cue for binding.

Attention↗
PubMed1988

Coordinate regulation of mRNAs encoding adenosine deaminase, purine nucleoside phosphorylase, and terminal deoxynucleotidyltransferase by phorbol esters in human thymocytes.

Incubation of human thymocytes in the presence of phorbol esters caused a reversible decrease in the mRNAs encoding terminal deoxynucleotidyltransferase (TdT; EC 2.7.7.31) and adenosine deaminase (ADA; EC 3.5.4.4) and an increase in the mRNA encoding purine nucleoside phosphorylase (PNP; EC 2.4.2.1). The effect of phorbol esters on TdT and ADA mRNA levels can be attributed to an apparent decrease in the stability of the mRNAs. The changes in ADA, TdT, and PNP mRNAs closely simulate changes in the activities of these enzymes that occur during T-cell differentiation in vivo, suggesting a role for protein kinase C activation in the regulation of the expression of these genes during intrathymic T-cell differentiation. A role for these purine degradation enzymes in the regulation of intracellular pools of the deoxynucleotide substrates of TdT is discussed.

Adenosine Deaminase↗
PubMed1988

Dynamics of the pulmonary circulation in systemic hypertension.

Pulmonary and systemic hemodynamics in 28 mild to moderate hypertensive patients (group II) with left ventricular (LV) hypertrophy (ECG and echo criteria) and 22 severe hypertensive patients with LV hypertrophy (group III) were compared with 20 patients with mild-to-moderate hypertension in WHO stage I (group I). Mean right atrial pressure was equivalent in groups II and III and significantly higher in the last group than in group I. An increased pulmonary arterial resistance (PAR) in group II and, to a large extent, in group III accounted for the elevation of diastolic and mean pulmonary arterial pressure in both groups in comparison with group I. Cardiac index (CI) was lower and systemic vascular resistance (SVR) higher in group III than in group I. Pulmonary capillary wedge pressure (PCWP) values were within the normal range and equivalent between groups II and III, and both significantly higher than in group I. PAR showed a positive relation with SVR (r = 0.30, P less than 0.01) and an inverse relation with CI (r = -0.561, P less than 0.001). Findings indicate that in systemic hypertension with LV hypertrophy there is an elevation of the right ventricular filling pressure and the pulmonary arterial pressure whose degree is even higher in severe hypertension. This increase is not necessarily a consequence of impairment of LV function as suggested by the normal range of PCWP values.

Blood Pressure↗
PubMed1988

Chemical quality of maternal drinking water and congenital heart disease.

We undertook a case-control study to investigate the association between chemicals in maternal drinking water consumed during pregnancy and congenital heart disease in the offspring. Two hundred and seventy affected children and 665 healthy children were enrolled in the study. Information on contaminant levels in maternal drinking water was available from records of routine water analysis of samples taken from public taps in the communities where the mothers resided during pregnancy. Mothers provided information during a telephone interview on their health, pregnancy management, and demographic characteristics. Nine inorganic metals were analysed for detection of an association with congenital heart disease. The chemical exposures of particular interest were arsenic, lead, mercury and selenium. None of the chemicals was associated materially with an increase in the frequency of congenital heart disease overall. Arsenic exposure at any detectable level was associated with a threefold increase in occurrence of coarctation of the aorta (prevalence odds ratio = 3.4, 95% confidence interval = 1.3-8.9). Detectable traces of selenium in drinking water were associated with a lower frequency of any congenital heart disease than was observed among children exposed to drinking water not containing detectable levels of selenium (prevalence odds ratio = 0.62, 95% confidence limits = 0.40-0.97). A dose-response effect was observed over four levels of selenium exposure. Non-differential errors in the measurement and classification of exposure to contaminants routinely monitored in drinking water could account for lack of positive findings. In addition, most of the contaminant levels were below the maximum levels set by the Environmental Protection Agency, so that lack of evidence of effect may have been due to the low exposure levels in this population.

Arsenic↗
PubMed1988

Incidence and treatment of fractures in thalassemia.

Thalassemia major, a disorder of hemoglobin synthesis, contributes to skeletal deformities, marked osteopenia, and frequent fractures. Hypertransfusion therapy in the last 20 years has prolonged the life expectancy of thalassemics and decreased the orthopaedic manifestations of the disease. This study examines the incidence and treatment of fractures in hypertransfused thalassemics in whom the hemoglobin is kept above 8 g/dl. Over a 5-year period, there were eight fractures in 38 patients, which yields an incidence that is approximately 70% above the fracture rate in the general population. With the exception of one patient, all of the fractures healed in the expected time utilizing nonoperative treatment. The results of this study indicate that, although thalassemics are at moderately high risk for sustaining fractures, they respond well to standard casting methods. However, the iron overload found in thalassemia can deplete the body of vitamin C, which can subsequently retard fracture healing. Attention must, therefore, be paid to replenishing vitamin C very cautiously in order to avoid this complication.

Adolescent↗
PubMed1988

Synergistic antiproliferative effects on HL-60 cells: deferoxamine enhances cytosine arabinoside, methotrexate, and daunorubicin cytotoxicity.

Deferoxamine (DFO), a widely used therapeutic iron chelator, was found to inhibit proliferation of the promyelocytic leukemia cell line HL-60 in a dose-dependent fashion when tested in a clonogenic assay at concentrations ranging from 1.0 to 10.0 microM. Cytosine arabinoside, methotrexate, and daunorubicin also produced dose-dependent inhibition of HL-60 colony growth when tested singly in vitro. When DFO, 1.0 microM, was included with each agent in dose-response studies, a synergistic enhancement of the antiproliferative effects was observed. This synergism probably results from a DFO-induced decrease in intracellular levels of deoxyribonucleoside triphosphates and an inhibition of the cells at the early S-phase of cell cycle. Our data suggest that DFO has potential as an adjunctive antileukemic agent.

Antimetabolites, Antineoplastic↗
PubMed1988

Joint mobility and motor development.

The association of joint hypermobility and motor development was sequentially investigated in 715 infants from the ages of 8 to 14 months. Seven joints were evaluated for mobility, and each infant underwent a physical and neurological examination. Parents were given a Denver Developmental Parents' Questionnaire. All subjects with a general developmental delay, systemic illness or syndrome were excluded. The infants were classified as having normal or delayed motor development with normal or delayed joint mobility. They were re-examined six months later. Multivariate statistical techniques was used for categorical analysis, and three joints were found to be significantly associated with motor delay at the first examination--hip abduction, elbow hyperextension, and foot dorsiflexion. Of the 715 infants, 126 had joint hypermobility and of these 38 (30.2%) had motor delay. Sixty four of 589 (10.9%) with normal joints had delayed motor development. Six months later 23 out of 35 of the group with joint hypermobility and 42 out of 53 of the group with normal joints had normal motor function. Joint hypermobility is associated with an increased incidence of motor delay in infancy. Over the ensuing six months most of the subjects will catch up. These findings, indicating a favourable prognosis, have implications regarding clinical assessment and parental counselling.

Child Development↗
PubMed1988

Estimation of quantitative proteinuria by using the protein-creatinine ratio in random urine samples.

The protein-creatinine ratio was measured in urine samples obtained at three different times of the day and compared to the 24-hour protein excretion in 51 patients with a wide spectrum of renal function and proteinuria. A linear correlation, which was highly significant, was found between the two variables. The higher correlation was found in urine samples obtained at 08.00 and at 12.00 h and the lowest in samples obtained at 16.00 h. This correlation did not depend on the degree of proteinuria or on the sex of the patients, but was slightly dependent on the glomerular filtration rate. The protein-creatinine ratio was essentially identical with the 24-hour protein excretion. Thus, the normal range of proteinuria was represented by a ratio of less than 0.2, while nephrotic patients had a ratio above 3.5. We suggest that the protein-creatinine ratio in random urine samples could replace the timed collection methods at least for follow-up and screening.

Adolescent↗
PubMed1988

Reflex decrease of histamine-induced bronchoconstriction after laryngeal stimulation in asthmatic patients.

The aim of this work was to determine if the nonadrenergic noncholinergic nervous system can be reflexly activated in asthmatic patients by stimulating the vocal cords. The stimulation was produced by a cytology brush passed through a bronchoscope previously introduced transnasally and positioned just above the epiglottis. The subjects were premedicated with cholinergic blockers, and bronchoconstriction was induced by inhalation of histamine. In 11 experiments performed on six patients, vocal cords stimulation resulted in a decreased RL from 8.4 +/- 1.0 to 6.3 +/- 0.8 cm H2O.L-1.s (mean +/- SE) (p less than 0.01). To assess the possible contribution of circulating catecholamines to this decrease, plasma epinephrine and norepinephrine levels were measured in six experiments, before and 30 s, 1, 3, and 5 min after the stimulation. Pulmonary resistance fell from 10.0 +/- 1.3 to 7.6 +/- 0.9 cm H2O.L-1.s (mean +/- SE) (p less than 0.05) 30 s and to 7.9 +/- 0.9 cm H2O.L-1.s (p less than 0.05) 60 s after stimulation. Epinephrine and norepinephrine levels increased slightly but not significantly throughout the experiment. We conclude that in asthmatic patients, as in normal subjects, stimulation of the vocal cords produces a reflex decrease in histamine-induced bronchoconstriction which is modulated by the nonadrenergic noncholinergic nervous system.

Administration, Inhalation↗