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Biomedical subjects

D Cohen

Publications and source records attributed to D Cohen.

At least 577 records · Page 32Linked to original sources

Two DR beta allelic series defined by exon II-specific synthetic oligonucleotide genomic hybridization: a method of HLA typing?

Comparisons of exon II HLA-DR beta sequences have shown that nucleotide variations are principally clustered within the following three regions: V1 (amino acid 8-15), V2 (25-32), and V3 (70-77). V1, V2, and V3-derived 24-mers have been synthesized, the DR beta sequences coming from DR1, DR3, Drw6, DR4, DR5, and DRw53 haplotypes. Each oligonucleotide was hybridized to Pvu II-digested DNA samples from 13 HLA genotyped families; therefore, 52 haplotypes have been investigated. Six polymorphic Pvu II fragments were detected, constituting two allelic series probably corresponding to the beta 1 and beta 2 locus of the DR region. The first series (beta 1) comprises a minimum of nine alleles while the second series (beta 2), which is less polymorphic, comprises at least four alleles. Certain patterns correlate perfectly with certain DR specificities, whereas other patterns define new subdivisions as in DR3 and DRw6 haplotypes. Although it appears that some mismatches do not always prevent hybridization in the conditions used in this work, this method will provide in many instances a convenient tool for HLA-DR typing.

Alleles↗

DNA polymorphism in the major histocompatibility complex of man and various farm animals.

In the past few years it has been possible by combining enzymatic cleavage of genomic DNA and the Southern blot hybridization technique to explore the endonuclease recognition site polymorphism of the MHC. HLA class I and DR and DQ alpha and beta class II specific probes as well as human C4 and Bf class III probes were used. All these probes were shown to cross-hybridize with DNA from pigs, cattle, sheep and horses. Hybridization of human genomic DNA with a class I probe showed 15-25 bands per genome depending on the enzyme used. Distinct endonucleases generated clusters of restriction fragments (RF) in HLA-informative families which correlated with HLA specificities. While numerous clusters were found associated with HLA-A alleles almost no cluster was related to HLA B or C specificities. Similarly, class II probes provided a large number of clusters. The existence of these clusters suggested that some polymorphic restriction sites are found in strong linkage disequilibrium and that the underlying mechanism might be gene conversion with heteroduplex correction. Since the degree of polymorphism detected by RF appears to be greater than the polymorphism defined by more traditional methods stronger associations between RF and pathological conditions are to be expected. Southern blot analysis was applied to unrelated pigs and sheep, as well as to families. Preliminary studies have also been performed on a few unrelated cattle and horses. Depending on the endonuclease used the HLA class I probe hybridized with around 15 bands in MHC heterozygous pigs and ruminants while up to 20 bands were found in horses. Therefore, a several-fold greater number of potential class I genes exist compared to those actually expressed. With the class II beta probe, cattle and sheep showed around 10 bands whereas 15 were observed in pigs and around 20 in horses. Based on limited results obtained with DQ alpha and beta probes and with the DR alpha probe there appeared to be fewer of these respective genes. Only one C4 gene has been detected in pig and this gene maps within the SLA region. Hybridization with the human C4 probe in cattle, sheep and horses revealed two to four bands which could possibly account for two C4 genes. To date their linkage to the MHC has not been established. The Southern blot hybridization technique represents a powerful tool for future immunogenetic studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

An experimental device for low-energy, precise ablation of AV conduction.

A combination suction catheter-bipolar lead system permits precise ablation of AV conduction with low energy. The electrode is positioned to maximize the bipolar His potential, then to maximize the HP between the tip and a surface electrode. With the tip held in place by 100-200 mmHg of suction, this site is paced. If the St-V interval is short and the ventricular morphology is similar to a sinus beat, a shock of 10 or 20 J is delivered. If complete heart block does not result, additional shocks are delivered. The device was used in eight dogs. When the St-V was close to the unpaced H-V interval, a shock of 20 J always produced permanent CHB. In contrast, an initial shock of 10 J always failed, and more shocks of up to 30 J were required to produce CHB which, even then, did not always persist. At 60 days the hearts were healed with a round, white, dense scar of about 2 mm in diameter just above the leaflet of the tricuspid valve. This device can produce permanent dissociation of the atria and ventricles with a shock of 20 J. It also enables precise positioning of the electrode.

Animals↗

Hemodynamic effects of nifedipine in hypertension in the presence of elevated angiotensin-II and beta-adrenergic blockade.

The hemodynamic effects of the slow release form of a calcium channel blocker, nifedipine retard, in essential hypertension patients after angiotensin II (AII) infusion were studied using nuclear ventriculography. Sublingual nifedipine lowered blood pressure that had been acutely raised by an infusion of AII to its baseline level. When used for 4 weeks, nifedipine retard maintained its blood-pressure-lowering effects without a change in heart rate, both when used alone and when used in addition to beta-adrenergic blockers. In the patients with untreated essential hypertension, nifedipine counteracted the lowering effect of AII on left ventricular ejection fraction (LVEF), which was 67.5 +/- 8.9% at recumbency, 61.2 +/- 6.6% (+/- SD) during AII infusion, and 72.1 +/- 7.5% 30 minutes after sublingual nifedipine. These acute effects seem to result from a marked reduction in total peripheral resistance (TPR) and are accompanied by a rise in cardiac index (CI). The TPR, in dynes/sec/cm-5, was 1376.9 +/- 275.8 at recumbency, 2000.7 +/- 358 during AII infusion, and 1228.6 +/- 289 30 minutes after sublingual nifedipine. The corresponding figures for CI in liters/M2 BSA, were 4.02 +/- 0.77, 3.03 +/- 0.64, and 4.32 +/- 0.79. In patients receiving beta-blocker therapy (propranolol or atenolol) with inadequate control of blood pressure, similar results were obtained in LVEF (69.7 +/- 8.87% at recumbency, 63.7 +/- 11.9% during AII infusion, and 72.2 +/- 6.05% 30 minutes after sublingual nifedipine). The initial TPR was much higher than that of untreated essential hypertensive patients. Nevertheless, the increase obtained during AII infusion was counteracted by sublingual nifedipine. CI was decreased by AII.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Potential for real-time processing of the continuously monitored electrocardiogram in the detection, quantitation, and intervention of silent myocardial ischemia.

Current technology for monitoring and analyzing the ST segment allows for accurate description of ST-segment deviation, which in most cases is a valid measure of myocardial ischemia. In this article, the authors describe a new method that utilizes microprocessor analysis of the electrocardiogram to detect ST-segment deviation in ambulatory subjects. This technique results in the ability to characterize the total ischemic burden over long periods of time and to intervene acutely in order to treat myocardial ischemia and possibly to prevent complications of coronary artery disease.

Algorithms↗

[Risk factors in insulin-dependent diabetes].

The relative risks (RR) of the immunogenetic markers of insulin-dependent diabetes mellitus (IDDM) have been calculated in a population of 235 IDDM patients compared with a control population. The highest relative risk was that of subjects heterozygous DR3/DR4 (RR = 47, P less than 0.001) which was still more increased in those who carry this combination associated with the RFLP cluster DQR4 (RR = 72). Further, a sample of 51 secondary affected siblings of IDD index cases has been compared with 265 non affected siblings (one child of each family, excluding index cases). The highest risks have been found in addition to DR3/DR4, for DR3 alone and particularly for the combination C4BQ0, DR3 (RR = 9, p less than 0.001) suggesting a role for this peculiar association in the familial penetrance. In the group of siblings HLA-identical with the index case, only two factors showed some capacity of discriminating between affected and non affected siblings: HLA-DR3 and age (less than or equal to 10 years old at onset of IDDM in the index case) (p less than 0.01). In the group of haploidentical siblings, the combination DR3/DR4 and the associations C4BQ0, DR3 and BfF1, DR3 significantly increased the susceptibility for higher familial occurrence of the disease. If confirmed by additional family series, this scale of risk factors could be helpful in predicting risk of IDDM to siblings of diabetic children.

Diabetes Mellitus, Type 1↗

Ongoing patient randomization: an innovation in medical care research.

Hospitals often have rotational assignment of patients to one of several similar provider care teams. The research potential of these arrangements has gone unnoticed. By changing to random assignment of patients and physicians to provider care teams (firms) this kind of organization can be used for sequential, randomized clinical trials which are ethical and efficient. The paper describes such arrangements at three different hospitals: Cleveland Metropolitan General Hospital, Brooke Army Medical Center, and University Hospitals of Cleveland. Associated methodologic issues are discussed. This is a new, more widely applicable method for medical care research.

Clinical Trials as Topic↗

Calcium entry-blockade with verapamil in cyclosporine A plus ischemia induced acute renal failure in rats.

The possible alleviating effect of verapamil, a calcium entry blocker, on the resulting renal damage from the combination of a short episode of ischemia and CyA was studied in rats. Immediately after right nephrectomy the rats were divided into five experimental groups. Group 1: left renal pedicle clamping for 20 minutes. Group 2: as group 1 plus CyA 60 mg/kg bw i.p. Group 3: CyA as in group 2 but sham operated. Group 4: as group 2 plus verapamil 10 mg% in the drinking water. Group 5: as group 3 plus verapamil given as in group 4. The experiments lasted 4 days. By analysis of variance: CyA + ischemia (group 2) showed lower creatinine clearance (p less than 0.001), higher blood urea (p less than 0.01), fractional excretion of sodium (p less than 0.05) and fractional excretion of potassium (p less than 0.01) and fractional excretion of negative free water clearance (p less than 0.001) compared to ischemia alone (group 1). The CyA + ischemia rats treated with verapamil had higher creatinine clearance (p less than 0.05), lower blood urea (p less than 0.01), fractional excretion of sodium (p less than 0.001), fractional excretion of potassium (p less than 0.001) and fractional excretion of negative free water clearance (p less than 0.05) compared with the untreated verapamil CyA + ischemia group. The CyA + sham operated verapamil treated group had similar creatinine clearance with the corresponding verapamil untreated group. The CyA + ischemia group had the higher mean daily body weight reduction compared with all other groups. Histology showed more vacuolization of tubular epithelial cells in the CyA + ischemia than in ischemia alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Arhinia.

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Humans↗

Light damage in the developing retina of the albino rat: an electroretinographic study.

The albino rat retina is severely damaged by exposure to bright light. The degree of damage depends upon the intensity of the exposure and its duration. In the present study, electroretinographic (ERG) responses were measured in rats exposed at different ages during the period of retinal development to 24 hr of bright light and then transferred to darkness for about 2 months. The ERG data indicated that if the bright-light exposure was done prior to 20 days of age, the retina was resistant to the light damage, and the dark-adapted ERG responses measured later were normal. In rats older than 20 days, light damage increased with age until, in rats exposed to light at age 30 days, the ERG was unrecordable. Further experiments showed that light exposure did damage the 15-day-old rat retina; however, complete recovery was attained within 15 days postexposure.

Aging↗

Inhibition of arachidonic acid metabolism by antipyrine and 4-aminoantipyrine.

Antipyrine and 4-aminoantipyrine are used to determine uterine and umbilical blood flows. When administered in vivo, these compounds produce a decrease in uterine contracture activity and maternal uterine vein 13,14-dihydro-15-keto-prostaglandin F2 alpha concentrations. In this paper we report that they also inhibit in vitro activity of prostaglandin synthase in bovine seminal microsomes.

Ampyrone↗

Genotyping with DNA probes in combined immunodeficiency syndrome with defective expression of HLA.

We performed HLA genotyping by using restriction-enzyme fragments hybridized with specific HLA probes instead of traditional immunologic methods in two patients whose lymphocytes expressed so few HLA antigens on the cell surface that serologic methods failed. Segregation of restriction-fragment-length polymorphism permitted identification of the genotypes. In addition, known correlations between serologically determined antigens and restriction-fragment-length polymorphism were confirmed. We applied this approach in making therapeutic decisions regarding bone marrow transplantation.

Bone Marrow Transplantation↗

Electrical sources in human somatosensory cortex: identification by combined magnetic and potential recordings.

Magnetic fields and electrical potentials produced by neuronal activity have different properties that can be used for the identification of electrical sources in the human brain. Fields and potentials occurring 20 to 30 milliseconds after median nerve stimulation in human subjects were compared in order to investigate the sources of evoked potential components that have been attributed by different investigators to the thalamus or thalamocortical afferents, to separate radial sources in somatosensory cortex and motor cortex, or to a tangential source in somatosensory cortex. The magnetic and potential wave forms were highly similar in morphology, and their spatial distributions were centered over sensorimotor cortex, were dipolar in shape, and differed in orientation by approximately 90 degrees; distances between the minimum and maximum of the magnetic distributions were about 60 percent of those of the potential distributions. These results cannot be accounted for by thalamic sources or radial cortical sources alone, but are consistent with a tangential source in somatosensory cortex, with an additional smaller contribution from radial sources.

Electrophysiology↗