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Biomedical subjects

G Cohen

Publications and source records attributed to G Cohen.

At least 217 records · Page 12Linked to original sources
PubMed1992

Segmentation techniques for the classification of brain tissue using magnetic resonance imaging.

A technique is described for classifying brain tissue into three components: gray matter, white matter, and cerebrospinal fluid. This technique uses simultaneously registered proton density and T2-weighted images. Samples of each of the three types of tissue are identified on both image sets and used as "training classes"; these tissue samples are then used to generate a linear discriminant function, which is used to classify the remaining pixels in the image data set. Effects of varying the location and number of training classes have been explored; six pairs of training classes have been found to yield a suitable classification. Interrater and test-retest reliability have been examined and found to be good. Intrascanner and interscanner reproducibility has also been evaluated; classification rates are reproducible within the same individual when the same scanner is used, but in this study poor reproducibility occurs when the same individual is scanned on two different scanners. The validity of the technique has been tested by examining correlations between traced and segmented regions of interest, evaluating correlations with age, and conducting phantom studies, in addition to using visual inspection of the classified images as an indication of face validity. From all four perspectives, the method has been found to have good validity. Additional applications, strengths, and limitations are discussed.

Age Factors↗
PubMed1992

Penicillin and cephalosporin biosynthetic genes: structure, organization, regulation, and evolution.

Penicillins and cephalosporins are produced by a wide variety of microorganisms, including some filamentous fungi, many gram-positive streptomycetes, and a few gram-negative unicellular bacteria. All produce these beta-lactam antibiotics by essentially the same biosynthetic pathway. Recently, most of the penicillin and cephalosporin biosynthetic genes have been cloned, sequenced, and expressed. The biosynthetic genes code for enzymes that possess multifunctional peptide synthetase, cyclase, epimerase, expandase, hydroxylase, lysine aminotransferase, and acetyltransferase activities and are organized in chromosomal gene clusters and coordinately expressed. DNA hybridization screens of streptomycetes demonstrate that beta-lactam biosynthetic genes may be more widespread in nature than is indicated by conventional antibiotic screens. They offer the possibility of expanding the search for organisms with potential to make new beta-lactam antibiotics. Attempts to improve current yields of beta-lactams in production strains by introducing into them additional copies of biosynthetic genes have been partially successful. Comparative sequence analysis of bacterial and fungal beta-lactam biosynthetic genes show they share very high sequence identity. A model that explains the similarity of biosynthetic genes from an evolutionary standpoint assumes horizontal gene-transfer between the two groups of organisms. Indirect evidence suggests the transfer occurred from the bacteria to the fungi.

Amino Acid Sequence↗
PubMed1992

Image processing for the study of brain structure and function: problems and programs.

Fundamental problems in the analysis of functional and structural imaging data include data transport, boundary identification (including manual tracing, edge detection, and tissue segmentation), volume estimation, three-dimensional reconstruction and display, surface and volume rendering, shape analysis, and image overlay. These problems require that research investigators have access to suitable methods of image analysis, implemented on a set of software programs, in order to conduct neuroimaging research. The authors describe a group of software programs designed to provide a comprehensive solution for these problems.

Brain↗
PubMed1992

Long-term study of brain lesions following soman, in comparison to DFP and metrazol poisoning.

The long-term histopathological effects of acute lethal (95 micrograms kg-1) and sublethal (56 micrograms kg-1) doses of soman were studied in rats and were compared to lesions caused by equipotent doses of either another cholinesterase (ChE) inhibitor, DFP (1.8 mg kg-1), or a non-organophosphorus convulsant, metrazol (100 mg kg-1). Severe toxic signs were noted following one LD50 dose administration of all the compounds, yet only soman induced brain lesions. Moreover, even when administered at a sublethal dose (0.5 LD50), soman induced some histological changes without any clinical signs of intoxication. Soman-induced brain lesions were assessed quantitatively using a computerized image analyser. The analysis was carried out for up to 3 months following administration, and a dynamic pattern of pathology was shown. The cortical thickness and area of CA1 and CA3 cells declined significantly as early as 1 week post-exposure. No pathological findings were detected following DFP and metrazol administration. It is therefore suggested that brain lesions are not common for all ChE inhibitors and that convulsions per se are not the only factor leading to brain damage following the administration of soman. The degenerative process (found also with the sublethal dose of soman) might be due to a secondary effect, unrelated to soman's clinical toxicity, but leading to long-term brain injuries.

Animals↗
PubMed1992

[The estrogen-androgen profile is unchanged in men with cholelithiasis].

It is well established that cholelithiasis is more frequent in women than in men. This difference is usually explained by the effects of estrogens and progesterone on the metabolism of bile acids, biliary cholesterol secretion and saturation, and gallbladder motility. Another explanation could be a protective effect of androgens against cholelithiasis in men. To test this hypothesis, we determined the hormonal, androgenic and estrogenic, status of 15 male patients with asymptomatic gallstone disease and in 15 control patients with normal gallbladder matched for age and body weight. No significant difference in the plasma concentrations and the urinary excretion rate of sex hormones (testosterone, dihydrotestosterone, androstenedione, testosterone and androstanediol glucuronides, estradiol, estrone, total estrogens), as well as in the plasma sex hormone binding globulin, was found between the 2 groups of patients. The development of cholelithiasis in men, therefore, does not appear to be related to modification of sex steroids.

Adult↗
PubMed1992

Evidence for the interaction between antacid and gastric mucosa using an "artificial stomach" model including gastric mucosa.

In light of evidence that certain aluminum-based antacids adhere to the gastric mucosa, we modified our previously described "artificial stomach" (AS) model by including a piece of hog stomach and compared the antacid activity of six aluminum-containing antacid products in the model with and without gastric mucosa. The activity of three of these, Maalox, Riopan and Supralox, was not significantly different in the two systems. In contrast, the activity of the other three, Aludrox, Phosphalugel and Simeco, was significantly greater with mucosa. Antacid activity of one product from each set (Supralox, Phosphalugel) was evaluated in two in vivo methods in human volunteers. For both antacids, results in vivo were similar to those obtained with the AS-containing mucosa. Without mucosa, in vivo and in vitro results were dissimilar for Phosphalugel, thus validating the modified AS. The difference between the two sets of antacids can be explained by 1) the fact that the Al:Mg ratio in the set affected by mucosa is greater than that of unaffected antacids, and 2) a weaker antacid load than in unaffected Supralox. We suggest that in an acid milieu, aluminum ions in antacids like Aludrox, Phosphalugel and Simeco are bound to sialic acid residues in mucus glycoproteins, thus retarding the transit of these antacids through both the AS and the real stomach and prolonging their activity in both situations. When the Al:Mg ratio is low or when the amount of antacid salts is large, aluminum ions tend to be buried in complexes, giving them less chance to interact with gastric mucus, so they transit the stomach more quickly.

Adult↗
PubMed1991

High level expression in Escherichia coli of isopenicillin N synthase genes from Flavobacterium and Streptomyces, and recovery of active enzyme from inclusion bodies.

A T7 promoter-based vector was used to express the isopenicillin N synthase (IPNS) genes of Flavobacterium sp. 12,154 and Streptomyces jumonjinensis in Escherichia coli. Most of the IPNS synthesized at 37 degrees C, and representing some 22% and 51% of the total cell protein respectively, occurred in an insoluble, enzymatically inactive form. Active IPNS was recovered in a rapid and simple two-step procedure in which the insoluble material was first denatured in 5 M urea and then refolded by passing the solubilized IPNS through a G-25 Sephadex sizing column. Further chromatography on DEAE-Sepharose resulted in highly active IPNS preparations. This procedure was found to be well suited for scaling up to produce large amounts of IPNS.

Cloning, Molecular↗
PubMed1991

Role of transesophageal echocardiography in the diagnosis and management of prosthetic valve thrombosis.

Thrombosis is a serious complication of heart valve replacement. Diagnosis is often difficult with previously reported techniques, including precordial two-dimensional echocardiography, suffering from low sensitivity and specificity. Management is similarly difficult, with a 40% to 50% reported mortality rate in early surgical series. Three cases are presented in which thrombosis of a left-sided prosthetic valve (one aortic, three mitral) was diagnosed by means of transesophageal echocardiography. All three patients were treated with streptokinase and had clinical and echocardiographic resolution. In one patient, who had recurrent thrombosis and received a second course of streptokinase, the course was complicated by a massive embolic stroke and death. Another patient with a recurrence underwent successful valve replacement. Transesophageal echocardiography is ideal for the diagnosis and follow-up of patients with prosthetic valve thrombosis. Although effective, thrombolysis in this setting is associated with a high risk of thromboembolic phenomena and significant risk of death. Thrombolytic therapy may be considered in highly selected patients who have an unacceptable risk for reoperation.

Adult↗
PubMed1991

T1 and T2 relaxation times in schizophrenia as measured with magnetic resonance imaging.

T1 and T2 relaxation times were measured in ten brain regions on the right and left side in a sample of 27 schizophrenic patients and 37 normal controls. The schizophrenic patients showed a prolongation of T2 relaxation time, and to a lesser extent of T1 relaxation time, which was more predominantly localized in the right hemisphere and in gray matter structures. These results may indicate that metabolic, physiological, or neurochemical brain function in schizophrenia is related in some way to a change in tissue fluid in neuronal cell bodies or interstitial gray matter.

Adult↗
PubMed1991

Problems with ratio and proportion measures of imaged cerebral structures.

Ratio measures, such as the ventricle-brain ratio (VBR) based on computed tomography or magnetic resonance imaging, are widely used in psychiatric research in studies of brain function and morphology. While imaging techniques have advanced considerably, the form of the index of a structure's size has remained the same--a proportion based on an estimate of the structure's size divided by a like estimate of the whole brain size. We demonstrate that ratio and similar indices can suffer greatly in reliability when compared with simple volume measures. This loss of reliability is related to the relation of a structure's size and whole brain size. We review various methods for measuring the size of structures and discuss their strengths and limitations in terms of reliability and validity. In many instances, other methods of "correcting" for brain size (e.g., regression or covariance) may yield measurements that are more appropriate than ratios.

Adult↗
PubMed1991

Peroxisomes in Saccharomyces cerevisiae: immunofluorescence analysis and import of catalase A into isolated peroxisomes.

To isolate peroxisomes from Saccharomyces cerevisiae of a quality sufficient for in vitro import studies, we optimized the conditions for cell growth and for cell fractionation. Stability of the isolated peroxisomes was monitored by catalase latency and sedimentability of marker enzymes. It was improved by (i) using cells that were shifted to oleic acid medium after growth to stationary phase in glucose precultures, (ii) shifting the pH from 7.2 to 6.0 during cell fractionation, and (iii) carrying out equilibrium density centrifugation with Nycodenz containing 0.25 M sucrose throughout the gradient. A concentrated peroxisomal fraction was used for in vitro import of catalase A. After 2 h of incubation, 62% of the catalase was associated with, and 16% was imported into, the organelle in a protease-resistant fashion. We introduced immunofluorescence microscopy for S. cerevisiae peroxisomes, using antibodies against thiolase, which allowed us to identify even the extremely small organelles in glucose-grown cells. Peroxisomes from media containing oleic acid were larger in size, were greater in number, and had a more intense fluorescence signal. The peroxisomes were located, sometimes in clusters, in the cell periphery, often immediately adjacent to the plasma membrane. Systematic immunofluorescence observations of glucose-grown S. cerevisiae demonstrated that all such cells contained at least one and usually several very small peroxisomes despite the glucose repression. This finding fits a central prediction of our model of peroxisome biogenesis: peroxisomes form by division of preexisting peroxisomes; therefore, every cell must have at least one peroxisome if additional organelles are to be induced in that cell.

Acyl-CoA Oxidase↗
PubMed1991

Ventilatory response of the sleeping newborn to CO2 during normoxic rebreathing.

The ventilatory response of the newborn to CO2 was studied using a rebreathing method that minimized changes in arterial PO2 during the test. The aim was to study the variability of the ventilatory response to CO2 and take this into account to assess the relative magnitude of the response to CO2 during rapid-eye-movement (REM) sleep and quiet sleep (QS). Five full-term babies aged 4-6 days were given 5% CO2 in air to rebreathe for 1.5-3 min. O2 was added to the rebreathing circuit to maintain arterial O2 saturation and transcutaneous PO2 (Ptco2) at prerebreathing levels. Tests were repeated four to five times in REM sleep and QS. Mean Ptco2 levels varied between individuals but were similar during REM sleep and QS tests for each subject. The mean coefficient of variability of the ventilatory response was 35% (range 15-77%) during QS and 120% (range 32-220%) during REM sleep. PtcO2 fluctuations during tests [6.0 +/- 3.0 (SD) Torr, range 1-13 Torr] were not correlated with ventilatory response. Overall the ventilatory response was significantly lower in REM sleep than in QS (12.2 +/- 3.0 vs. 38.7 +/- 3.0 ml.min-1.Torr-1.kg-1, P less than 0.001; 2-way analysis of variance) due to a small (nonsignificant) fall in the tidal volume response and a significant fall in breathing rate. In 12 REM sleep tests there was no significant ventilatory response; mean inspiratory flow increased significantly during 8 of these 12 tests. We conclude that there is a significant decrease in the ventilatory response of the newborn to CO2 rebreathing during REM sleep compared with QS.

Carbon Dioxide↗
PubMed1990

Magnetic resonance imaging of the brain in schizophrenia. The pathophysiologic significance of structural abnormalities.

In a second large series of schizophrenic patients studied with magnetic resonance imaging at the University of Iowa, Iowa City, earlier findings of decreased frontal, cerebral, and cranial size were not replicated. In this second series, control subjects were selected to be educationally equivalent to the schizophrenic patients, a modification in design that may partially account for the failure to replicate. By means of coronal images, ventricular volume was compared in patients and controls and found to differ to a highly significant degree, with the frontal horns being possibly slightly more enlarged than the rest of the ventricular system. A prominent sex effect was also observed, with most of the increased ventricular size occurring in the male patients. Within the male patients, the thalamus was also observed to be significantly smaller, a finding that could be consistent with periventricular injury. Patients with prominent negative symptoms had significantly larger ventricular size than did those with the mixed or positive subtypes. Because of its superior resolution, magnetic resonance imaging appears to offer a more sensitive index of ventricular enlargement than that provided by computed tomography.

Adult↗
PubMed1990

Monoamine oxidase and oxidative stress at dopaminergic synapses.

Increased oxidation of dopamine by monoamine oxidase (MAO) in the striatum is associated with an oxidant stress, expressed as a rise in the level of oxidized glutathione. Oxidation of glutathione is suppressed by MAO inhibitors, such as deprenyl and clorgyline. These observations related to Parkinson's disease and to the clinical trial of deprenyl as an agent that may retard progression of the disease.

Animals↗