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Biomedical subjects

G Cohen

Publications and source records attributed to G Cohen.

At least 181 records · Page 10Linked to original sources
PubMed1994

The reproducibility of the response of the human newborn to CO2 measured by rebreathing and steady-state methods.

The ventilatory response (VR) of the full-term newborn to CO2 was studied during quiet sleep using rebreathing and steady-state methods. Rebreathing responses were obtained under normoxic (fractional inspired oxygen concentration, Fi,O2 = 0.21) and hyperoxic (Fi,O2 = 0.4) conditions. Ten infants were tested three to five times using each of the two rebreathing protocols and the results averaged. Overall, there was no significant difference between either the mean variability (coefficient of variation) or slope of the VR measured under normoxic and hyperoxic conditions. Four infants were studied using a steady-state technique. There was marked test-to-test variability in VRs measured by this method. The results appear to indicate that the variability of the VR of the newborn to CO2 is not a result of chemoreflex changes in ventilation elicited in response to fluctuations in arterial PO2.

Behavior↗
PubMed1994

Biotin synthase: purification, characterization as a [2Fe-2S]cluster protein, and in vitro activity of the Escherichia coli bioB gene product.

We report here the first purification of the protein encoded by the Escherichia coli bioB gene. One species of this protein runs on native gels with an electrophoretic mobility typical of a protein with m = 82 kDa, suggesting the protein is a dimer (gene sequence predicts m = 38.7 kDa). There are two iron- and two acid-labile sulfur atoms per protein monomer. Solutions containing the protein are red and have an absorbance spectrum characteristic of proteins with [2Fe-2S] clusters. In its oxidized native state, the protein is EPR-silent. Upon addition of dithionite, the protein's UV-visible absorbance spectrum is very slowly bleached, and an EPR active species is produced that displays a signal at gavg = 1.95. All these results are consistent with this protein containing one [2Fe-2S] cluster per monomer. The EPR spin quantitation is only 5-10% of expected. Since this protein loses iron upon reduction with dithionite, the low-spin quantitation is probably due to cluster instability in the reduced state. Another species of the bioB gene products has also been purified which runs on native gels with an electrophoretic mobility typical of a protein with m = 104 kDa. This species appears to be a dimer with one [2Fe-2S] cluster per dimer. The 104-kDa protein can be converted to the 82-kDa protein upon incubation with Fe3+ and S2-. The bioB gene product we have isolated is active in the conversion of dethiobiotin to biotin in vitro in the presence of NADPH, AdoMet, Fe3+ or Fe2+, and additional unidentified factors from the crude extracts of E. coli. The Km for dethiobiotin in this reaction has been found to be 2 microM.

Amino Acid Sequence↗
PubMed1994

Evaluating and validating two methods for estimating brain structure volumes: tessellation and simple pixel counting.

Developments in imaging technology have made three-dimensional visualization of internal brain structures possible with excellent resolution. Since improved visualization implies improved measurement, these advances hold promise to more accurately measure the volumes of internal structures. As new technologies and techniques emerge, evaluating the relative benefits of measurement methods becomes necessary. We compared and evaluated two methods of estimating volumes from images of brain structures. One method counted pixels within a region of interest, while the other method tessellated the surface between tracings on adjacent slices. Our study assessed both measurement error for true phantom volumes and method disparity for in vivo structures in a randomly selected sample of subjects (n = 100). For our comparisons, we focused on the temporal lobe, ventricular system, and hippocampus. Bias, independence of measurement errors and maximal discrimination of individual differences are properties that are relevant to validating and evaluating measurements of cerebral structure. Pixel counting proved to be the more robust of the two methods, being less sensitive to nuisance-interactions between size of object, shape, and slice thickness. Clinical and research applications of imaging techniques may have distinctive but overlapping needs when evaluating and validating new developments in imaging.

Adult↗
PubMed1994

Impaired oxidative decarboxylation of pyruvate in fibroblasts from patients with Parkinson's disease.

Whether or not a reported deficiency in brain mitochondrial complex I activity in Parkinson's disease represents a defect encompassing other organs or tissues has been a source of some controversy. We have examined mitochondrial respiration in fibroblasts from patients with Parkinson's disease by measuring the oxidative decarboxylation of [2-14C]pyruvate and [1,4-14C]succinate. We report that oxidation of pyruvate but not succinate was significantly reduced in fibroblasts from Parkinson patients when compared to healthy controls. These observations support the view that a widespread deficit in mitochondrial respiration exists in Parkinson's disease. Fibroblast cultures, moreover, are a source of affected proliferating cells, which can be used for in vitro studies of the nature of the respiratory defect and for testing of pharmacological interventions to correct the deficiency.

Adult↗
PubMed1994

A strategy of aggressive regional therapy for acute iliofemoral venous thrombosis with contemporary venous thrombectomy or catheter-directed thrombolysis.

PURPOSE: Occlusive iliofemoral venous thrombosis is associated with morbid short- and long-term consequences. Having been disappointed with standard anticoagulant therapy and systemic fibrinolysis, we embarked on an aggressive multidisciplinary regional approach to treat these patients, with the goals of therapy being (1) to eliminate iliofemoral venous thrombus, (2) to provide unobstructed venous drainage from the affected limb, and (3) to prevent recurrent thrombosis. METHODS: Twelve consecutive patients were treated for extensive iliofemoral venous thrombosis. Each had thrombus from their infrapopliteal veins through their iliofemoral system, and four had vena caval involvement. The conditions of 11 patients failed to improve when the patients were given anticoagulants, and prior systemic fibrinolysis failed in five patients. The treatment strategy includes catheter-directed thrombolysis with intrathrombus infusion of the plasminogen activator or operative thrombectomy or venous bypass with a permanent 4 mm arteriovenous fistula (AVF). RESULTS: Nine of 12 patients had a good or excellent clinical outcome (mean follow-up 25 months), which correlated with restored unobstructed venous drainage from the affected limb. Seven patients had catheter-directed lytic therapy attempted. In five patients the catheters were appropriately positioned, and lysis was successful. Five of the eight patients who underwent operations had successful procedures. Two of the three patients with poor operative outcomes had residual thrombus in their iliac veins or vena cava after thrombectomy (without bypass). The third patient, in whom anticoagulation was contraindicated, had an initially successful thrombectomy and AVF; however, vena caval thrombosis developed 2 months after operation. No patient had symptomatic pulmonary emboli, and routine posttreatment ventilation/perfusion lung scanning was not performed. CONCLUSIONS: An aggressive multidisciplinary regional approach to patients with obliterative iliofemoral venous thrombosis, designed to remove thrombus and provide unobstructed venous drainage, offers substantially better clinical outcome compared with systemic fibrinolysis and standard anticoagulation. Catheter-directed thrombolysis is successful if the catheter is appropriately positioned within the thrombus. Contemporary venous thrombectomy, which includes thrombus removal, completion phlebography, AVF, and cross-pubic bypass when necessary, is associated with high success rates. Failures can be anticipated and avoided in most patients.

Acute Disease↗
PubMed1994

Flashbulb memories in older adults.

In this study of age differences in flashbulb memory, groups of young and older adults gave detailed accounts of how they heard the news of the resignation of the British Prime Minister Margaret Thatcher. They were tested within 14 days after the event and again 11 months later. They also gave ratings for the encoding variables (surprise, emotion, importance, knowledge, and interest) and for frequency of rehearsal. Memories that met a strict criterion of consistency between the original and delayed responses were classified as flashbulb memories. Although 90% of young Ss had flashbulb memories, only 42% of the elderly met the criterion. The age groups also differed in the type of details remembered and in the relationship between the encoding and rehearsal variables and the occurrence of flashbulb memory. The age-related deficit in flashbulb memory is related to source amnesia and to a deficit in memory for context.

Adolescent↗
PubMed1994

Carbon dioxide concentrations in the environment of sleeping infants.

In 22 infants continuous measurements were made of the concentration of carbon dioxide (CO2) in inspired air during sleep. Evidence was found of CO2 enrichment of inspired air in certain environmental conditions. The levels achieved were not sufficiently high to acutely endanger an infant. Carbon dioxide concentrations as high as 2-3% were observed in the prone position when the infant's head was under a blanket and when the lower face was obscured by bedding. Sleeping prone on a sheepskin also resulted in an increased concentration of CO2 but to a lesser extent than being under a blanket. In awake infants the presence of a pacifier also promoted an excess of CO2 in the inspired air, both in the prone and supine positions. The physiological and clinical implications of these findings, in relation to the Sudden Infant Death Syndrome (SIDS), are unknown and warrant investigation.

Air↗
PubMed1994

The thioredoxin system of Penicillium chrysogenum and its possible role in penicillin biosynthesis.

Penicillium chrysogenum is an important producer of penicillin antibiotics. A key step in their biosynthesis is the oxidative cyclization of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) to isopenicillin N by the enzyme isopenicillin N synthase (IPNS). bis-ACV, the oxidized disulfide form of ACV is, however, not a substrate for IPNS. We report here the characterization of a broad-range disulfide reductase from P. chrysogenum that efficiently reduces bis-ACV to the thiol monomer. When coupled in vitro with IPNS, it converts bis-ACV to isopenicillin N and may therefore play a role in penicillin biosynthesis. The disulfide reductase consists of two protein components, a 72-kDa NADPH-dependent reductase, containing two identical subunits, and a 12-kDa general disulfide reductant. The latter reduces disulfide bonds in low-molecular-weight compounds and in proteins. The genes coding for the reductase system were cloned and sequenced. Both possess introns. A comparative analysis of their predicted amino acid sequences showed that the 12-kDa protein shares 26 to 60% sequence identity with thioredoxins and that the 36-kDa protein subunit shares 44 to 49% sequence identity with the two known bacterial thioredoxin reductases. In addition, the P. chrysogenum NADPH-dependent reductase is able to accept thioredoxin as a substrate. These results establish that the P. chrysogenum broad-range disulfide reductase is a member of the thioredoxin family of oxidoreductases. This is the first example of the cloning of a eucaryotic thioredoxin reductase gene.

Amino Acid Sequence↗
PubMed1993

Brain ischemia markedly elevates levels of the neurotoxic amino acid, cysteine.

The mechanisms underlying cell damage in stroke or during experimental brain ischemia are not fully understood. L-Cysteine, an excitotoxic amino acid that could contribute to tissue damage, is normally found in relatively low levels in brain (ca. 0.05 mumol/g), compared to the cysteine-containing tripeptide, glutathione (GSH, ca. 1.5 mumol/g). We have observed that during brain ischemia in gerbils, levels of cysteine rise 10-13-fold over an 8 h period to 0.66 and 0.62 mumol/g, respectively, in the ischemic hippocampus and striatum. At the same time, levels of GSH fall by 0.84 and 0.94 mumol/g, respectively. The elevated free cysteine may be derived largely from GSH. The levels of cysteine found in ischemic brain are similar to those reported after parenteral administration of neurotoxic doses of L-cysteine to perinatal rats. The remarkable increase in cysteine during brain ischemia, coupled to its neurotoxic properties, may play a role in aspects of brain damage during or following brain ischemia.

Animals↗
PubMed1993

Catecholamine uptake inhibitors elevate 6-hydroxydopamine in brain after administration of 6-hydroxydopa.

Desipramine and nomifensine, two norepinephrine uptake blockers, elevated by 63-248% the levels of 6-hydroxydopamine found in the frontal cortex at 1-4 h after administration of 6-OH-DOPA. Nomifensine also elevated 6-hydroxydopamine by 83% in the striatum at 4 h. These results nullify prior suggestions in the literature that 6-OH-DOPA is decarboxylated to 6-hydroxydopamine mainly outside of catecholamine nerve terminals and that 6-hydroxydopamine subsequently gains access to nerve terminals via the axonal membrane transport system for catecholamines.

Animals↗
PubMed1993

The neuropsychology of the prefrontal cortex.

Single photon emission computed tomography with the xenon inhalation technique is used to compare activation of regional cerebral blood flow in frontal brain regions during the performance of four widely used neuropsychological tests: the Continuous Performance Test, the Wisconsin Card Sorting Test, the Tower of London, and Porteus Mazes. Healthy normal volunteers performing these tasks show significant increases in frontal regions during the Continuous Performance Test, the Wisconsin Card Sorting Test, and the Tower of London, but not the Porteus Mazes. Activation produced by the Continuous Performance Test and the Tower of London are mesial and bilateral and may reflect stimulation of midline attentional circuits. The Wisconsin Card Sorting Test produces a left dorsolateral area of prefrontal activation. These findings indicate that regional activation of the frontal lobes occurs in response to cognitive challenges produced through performance of standard neuropsychological tests.

Adult↗
PubMed1993

Methylation of RNA purine bases by methyl radicals.

During the metabolism of 1,2-dimethylhydrazine (a colon carcinogen) in rats, methyl radicals (.CH3) are produced. To gain an insight into the nature of .CH3 interactions with biomolecules in vivo, we conducted in vitro studies using RNA as a model compound. RNA was incubated in a system where .CH3 was generated from the oxidation of dimethyl sulfoxide by hydroxyl radicals (.OH); .OH was produced from a Fenton-type reaction between Fe(2+)-EDTA and H2O2. Four new products were detected from acid hydrolysates of .CH3-treated RNA: 8-methylguanine, 2-methyladenine, 8-methyladenine, and a highly unstable compound of unknown structure. The production was significantly affected by pH. The concentrations of Fe2+ and H2O2 influenced the production of methylated purine residues in a dose-dependent manner. Catalase, ethanol, alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone, and O2 inhibited the production of methylated nucleobases.

1,2-Dimethylhydrazine↗
PubMed1993

Delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase, the multienzyme integrating the four primary reactions in beta-lactam biosynthesis, as a model peptide synthetase.

ACV synthetase forms the tripeptide precursor of penicillins and cephalosporins from alpha-aminoadipate, cysteine, and valine. Catalytic sites for substrate carboxyl activation as adenylates, peptide bond formations, epimerization and release of the tripeptide-thioester are integrated in multifunctional enzymes of 405 to 425 kD. These have been characterized from several pro- and eukaryotic beta-lactam producers. Implications of these results for the thio-template mechanism of peptide formation are discussed, as well as the use of this multienzyme as a model system for enzymatic peptide synthesis.

Amino Acid Sequence↗