Memory for proper names: a review.
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Aging↗
Biomedical subjects
G Cohen
Publications and source records attributed to G Cohen.
Use of digitized fluorescein angiogram system to evaluate laser treatment for subretinal neovascularization: technique.
In patients with subretinal neovascular membranes (SRNVM), persistence of the SRNVM after laser treatment is a major cause of decreased visual acuity. Persistence is associated with inadequate initial laser treatment. A technique using a digitized fluorescein angiogram (DFA) system is presented that allows immediate evaluation of the adequacy of laser treatment for SRNVM. This involves overlaying a red-free photograph taken after treatment on a fluorescein angiogram taken before treatment using a digital angiogram system that evaluates the adequacy of treatment. A protocol for augmentation of laser treatment has been developed that will aid in the reduction of persistence after laser treatment of SRNVM.
Aged↗
Evaluation of persistence of subretinal neovascular membranes using digitized angiographic analysis.
A study was conducted using the digitized fluorescein angiogram (DFA) system to evaluate adequacy of coverage of laser treatment for subretinal neovascular membranes (SRNVM) and to confirm that complete coverage lowers the incidence of persistent SRNVMs. Ten consecutive cases were evaluated with the DFA system after undergoing a single laser treatment. Three cases were judged to be adequately treated, and the remaining seven cases were judged to be inadequately treated. The DFA system was then used during photocoagulation in 16 consecutive cases to verify complete coverage of the SRNVM or to indicate the need for photocoagulation augmentation. Despite augmentation, 2 of the 16 cases remained inadequately treated. Overall, the cases that were adequately treated had a 12% (2/17) persistence rate, whereas those that were inadequately treated had a persistence rate of 67% (6/9). The data indicate that adequate coverage of SRNVMs is essential to prevent persistence.
Adult↗
Incidence of lead poisoning in young children from inner-city, suburban, and rural communities.
The Centers for Disease Control (CDC) have recently lowered the acceptable blood lead concentration in young children from < or = 25 to < or = 10 micrograms/dl (< or = 1.21 to < or = 0.48 mumol/L). The incidence of lead toxicity with respect to geographical areas and socioeconomic status has not yet been defined. We evaluated the incidence of increased lead concentration in inner-city, suburban, and rural children aged 9 months to 3 years. Seven hundred eighty of the 4,196 studied inner-city samples (18.6%) had lead concentrations > or = 10 micrograms/dl (0.48 mumol/L), of which only 71 (1.6%) had lead values > or = 25 micrograms/dl (1.21 mumol/L). Only 5 of the 212 studied children (2.4%) from suburbia and 7 of the 120 children (5.8%) from rural communities had blood lead concentrations > or = 10 micrograms/dl (0.48 mumol/L). None of these children, however, had a lead concentration > or = 15 micrograms/dl (0.73 mumol/L). In contrast, 276 inner-city subjects (6.6%) had lead values > or = 15 micrograms/dl (0.73 mumol/L). Our data indicate that a correlation exists between geographical location and blood lead concentration in young children. Government health agencies at all levels should prioritize their limited resources for those areas that are most at risk for lead poisoning.
Centers for Disease Control and Prevention, U.S.↗
Dynamic autoresonance and global chaos in a slowly evolving system of two coupled oscillators.
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Journal Article↗
Toxic and protective effects of L-dopa on mesencephalic cell cultures.
The autoxidation of L-DOPA or dopamine (DA) and the metabolism of DA by monoamine oxidase generate a spectrum of toxic species, namely, hydrogen peroxide, oxy radicals, semiquinones, and quinones. When primary dissociated cultures of rat mesencephalon were incubated with L-DOPA (200 microM) for 48 h, the number of tyrosine hydroxylase-positive neurons (DA neurons) was reduced to 69.7% of control values, accompanied by a decrease in [3H]DA uptake to 42.3% of control values; the remaining DA neurons exhibited reduced neurite length and overall deterioration. Lack of simultaneous change in the number of neurons stained with neuron-specific enolase indicated that toxicity was relatively specific for DA neurons. At the same time, the level of GSH, a major cellular antioxidant, rose to 125.2% of control values. Thus, exposure of mesencephalic cultures to L-DOPA results in both damaging and antioxidant actions. Ascorbate (200 microM), an antioxidant, prevented the rise in GSH. The effect of ascorbate on GSH points to an oxidative signal to initiate the rise in GSH content. On the other hand, neither inhibition of monoamine oxidase with pargyline nor addition of superoxide dismutase or catalase to the culture medium prevented the rise in GSH level or the loss in [3H]DA uptake. The latter results tend to exclude the products of monoamine oxidase activity or the presence of hydrogen peroxide or superoxide in the medium as responsible agents for the rise in GSH or neuronal toxicity. In cultures treated with L-buthionine sulfoximine (L-BSO), an inhibitor of GSH synthesis, L-DOPA prevented cell death by L-BSO.
Animals↗
Thioredoxin-thioredoxin reductase system of Streptomyces clavuligerus: sequences, expression, and organization of the genes.
The genes that encode thioredoxin and thioredoxin reductase of Streptomyces clavuligerus were cloned, and their DNA sequences were determined. Previously, we showed that S. clavuligerus possesses a disulfide reductase with broad substrate specificity that biochemically resembles the thioredoxin oxidoreductase system and may play a role in the biosynthesis of beta-lactam antibiotics. It consists consists of two components, a 70-kDa NADPH-dependent flavoprotein disulfide reductase with two identical subunits and a 12-kDa heat-stable protein general disulfide reductant. In this study, we found, by comparative analysis of their predicted amino acid sequences, that the 35-kDa protein is in fact thioredoxin reductase; it shares 48.7% amino acid sequence identity with Escherichia coli thioredoxin reductase, the 12-kDa protein is thioredoxin, and it shares 28 to 56% amino acid sequence identity with other thioredoxins. The streptomycete thioredoxin reductase has the identical cysteine redox-active region--Cys-Ala-Thr-Cys--and essentially the same flavin adenine dinucleotide- and NADPH dinucleotide-binding sites as E. coli thioredoxin reductase and is partially able to accept E. coli thioredoxin as a substrate. The streptomycete thioredoxin has the same cysteine redox-active segment--Trp-Cys-Gly-Pro-Cys--that is present in virtually all eucaryotic and procaryotic thioredoxins. However, in vivo it is unable to donate electrons to E. coli methionine sulfoxide reductase and does not serve as a substrate in vitro for E. coli thioredoxin reductase. The S. clavuligerus thioredoxin (trxA) and thioredoxin reductase (trxB) genes are organized in a cluster. They are transcribed in the same direction and separated by 33 nucleotides. In contrast, the trxA and trxB genes of E. coli, the only other organism in which both genes have been characterized, are physically widely separated.
Amino Acid Sequence↗
Characterization of a broad-range disulfide reductase from Streptomyces clavuligerus and its possible role in beta-lactam antibiotic biosynthesis.
Streptomyces clavuligerus is a potent producer of penicillin and cephalosporin antibiotics. A key step in the biosynthesis of these beta-lactam compounds is the cyclization of the thiol tripeptide delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) to isopenicillin N by the enzyme isopenicillin N synthase (IPNS). However, bis-ACV, the oxidized disulfide form of the tripeptide, is not a substrate for IPNS. We show here that S. clavuligerus possesses an NADPH-dependent disulfide reductase of broad substrate specificity that efficiently catalyzes the reduction of disulfide bonds in bis-ACV and in other low-molecular-weight disulfide containing compounds and proteins. The disulfide reductase comprises two protein components, a 70-kDa reductase consisting of two identical subunits, and a 12-kDa heat-stable protein reductant. The structural and functional properties of the disulfide reductase resemble those of the thioredoxin class of oxidoreductases. When the disulfide reductase system is coupled with IPNS, it quantitatively converts bis-ACV to isopenicillin N. These findings suggest that the disulfide reductase may play a role in the biosynthesis of penicillins and cephalosporins in streptomycetes. We also show here that S. clavuligerus lacks glutathione reductase and have previously reported that Streptomyces species do not contain glutathione. This disulfide reductase may therefore be important in determining the thiol-disulfide redox balance in streptomycetes.
Anti-Bacterial Agents↗
Low-molecular-weight thiols in streptomycetes and their potential role as antioxidants.
The intracellular low-molecular-weight thiols present in five gram-positive Streptomyces species and one Flavobacterium species were analyzed by high-performance liquid chromatography after fluorescence labeling with monobromobimane. Bacteria were chosen to include penicillin and cephalosporin beta-lactam producers and nonproducers. No significant amount of glutathione was found in any of the streptomycetes. Major intracellular thiols in all strains examined were cysteine, coenzyme A, sulfide, thiosulfate, and an unknown thiol designated U17. Those streptomycetes that make beta-lactam antibiotics also produce significant amounts of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV), a key intermediate in their biosynthesis. In Streptomyces clavuligerus, a potent producer of beta-lactams, the level of ACV was low during the early phase of growth and increased rapidly toward the end of exponential growth, paralleling that of antibiotic production. These and other observations indicate that ACV does not function as a protective thiol in streptomycetes. U17 may have this role since it was the major thiol in all streptomycetes and appeared to occur at levels about 10-fold higher than those of the other thiols measured, including ACV. Purification and amino acid analysis of U17 indicated that it contains cysteine and an unusual amine that is not one of the common amino acids. This thiol is identical to an unknown thiol found previously in Micrococcus roseus and Streptomyces griseus. A high level of ergothioneine was found in Streptomyces lactamdurans, and several unidentified thiols were detected in this and other streptomycetes.
Amino Acids↗
Intelligence and brain structure in normal individuals.
OBJECTIVE: This study was designed to evaluate the relation between intelligence and a variety of measures of brain structure. METHOD: Magnetic resonance imaging scans were used to measure the volume of the intracranial cavity, cerebral hemispheres, lateral ventricles, temporal lobes, hippocampus, caudate, and cerebellum, as well as the overall volume of gray matter, white matter, and CSF, in 67 healthy, normal volunteers. Intelligence was measured with the Wechsler Adult Intelligence Scale--Revised. RESULTS: Full-scale IQ was found to be significantly correlated with intracranial, cerebral, temporal lobe, hippocampal, and cerebellar volume but not with caudate and lateral ventricle volume. There were also significant correlations of full-scale, verbal, and performance IQ with overall gray matter volume but not with white matter or CSF volume. Gender differences were noted in the pattern and number of correlations between the volume of the brain and its subregions and full-scale, verbal, and performance IQ. CONCLUSIONS: The results suggest that the size of some cerebral structures may account for a significant, but modest, proportion of the variance in human intelligence.
Brain↗
Voxel processing techniques for the antemortem study of neuroanatomy and neuropathology using magnetic resonance imaging.
BRAINBLAST, a program that uses voxel processing, was developed in order to produce high-fidelity three-dimensional reconstructions of the brain. Four steps were used to produce images: washing away cerebrospinal fluid (via histogramming), dissecting away the blood vessels (via a connectivity heuristic), highlighting the sulci and gyri (via a lighting model), and resampling the interior contents of the brain. After reconstruction, the images can be resampled, rotated, written on, measured, or redissected. The technique has a variety of applications: study of individual variation in sulcal and gyral patterns, evaluation of structure/function relationships, measurement of volumes or subregions using anatomically defined landmarks, and teaching of neuroanatomy.
Brain↗
Streptomyces contain a 7.0 kDa cold shock like protein.
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Amino Acid Sequence↗
Time-of-flight spectroscopy of electron transport in superlattices: From band transport to Stark localization.
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Journal Article↗
[Pneumopathies caused by Chlamydia pneumoniae].
Among the atypical pneumonias observed between March 1990 and March 1991, 6 were diagnosed as being caused by Chlamydia pneumoniae of the TWAR strain. The serological diagnosis was obtained by a microimmunofluorescence test. All 6 patients had anti-TWAR antibody levels higher than 512; they were treated with a macrolide administered by the oral route and were cured without sequelae or recurrences. Four cases received a ten day course of roxithromycin 300 mg/day and one case received erythromycin 2 g/day also for 10 days. The sixth case received a short course of azithromycin 500 mg once daily for three days. In 2 other patients presenting with clinical and radiological signs of pneumonia the diagnosis of C. pneumoniae infection could not be made despite an antibody level equal or higher than 512, since the serological results showed cross-reactions between C. pneumoniae, C. trachomatis and C. psittaci antibody responses.
Aged↗
Lead poisoning in young children in Washington, DC: a crisis that remains to be addressed.
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Child↗
Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia. Assessment with xenon 133 single-photon emission computed tomography and the Tower of London.
The "hypofrontality hypothesis" has been supported by many neuroimaging studies, but not all, perhaps because of heterogeneity of samples. The present study examined three different samples that permitted assessment of a variety of confounders, such as effects of long-term treatment, chronicity of illness, and presenting phenomenology: (1) 13 neuroleptic-naive schizophrenic patients, (2) 23 nonnaive schizophrenic patients who had been relatively chronically ill but were medication free for at least 3 weeks, and (3) 15 healthy normal volunteers. Regional cerebral blood flow was measured using single-photon emission computed tomography with xenon 133 as the tracer. The control condition consisted of looking at undulating colored shapes on a video monitor, while the experimental task was the Tower of London. We observed the Tower of London to be a relatively specific stimulant of the left mesial frontal cortex (probably including parts of the cingulate gyrus) in healthy normal volunteers. Both the neuroleptic-naive and the nonnaive patients lacked this area of activation, as well as a related one in the right parietal cortex (representing the circuitry specifically activated by the Tower of London). Decreased activation occurred only in the patients with high scores for negative symptoms. These results suggest that hypofrontality is related to negative symptoms and is not a long-term effect of neuroleptic treatment or of chronicity of illness.
Adult↗
The oxidant stress hypothesis in Parkinson's disease: evidence supporting it.
Oxidant stress, due to the formation of hydrogen peroxide and oxygen-derived free radicals, can cause cell damage due to chain reactions of membrane lipid peroxidation. Because the substantia nigra is rich in dopamine, which can undergo both enzymatic oxidation via monoamine oxidase and nonenzymatic autoxidation, hydrogen peroxide and oxyradicals (superoxide anion radical and hydroxyl radical) are generated in this midbrain nucleus. Although proof that oxidant stress actually causes the loss of monoaminergic neurons in patients with Parkinson's disease is lacking, there is a considerable body of evidence from studies in both animals and humans that support the concept. (1) Neurotoxins that selectively destroy the dopaminergic neurons in the nigra, such as 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), appear to act via oxidant stress. (2) The substantia nigra of patients with Parkinson's disease reveals evidence of oxidant stress by the findings of increased lipid peroxidation and decreased reduced glutathione. (3) Total iron is increased and ferritin is reduced in the substantia nigra pars compacta in patients with Parkinson's disease. This combination suggests that this transition metal is in a low molecular weight form, capable of catalyzing nonenzymatic oxidative reactions, especially the conversion of hydrogen peroxide to hydroxyl radical, which is the most reactive of the oxygen radicals. (4) Neuromelanin, a product of dopamine autoxidation, can serve as a reservoir for iron, promoting the generation of oxyradicals. (5) Antioxidant defense mechanisms appear to be reduced in the parkinsonian substantia nigra with the findings of decreased activities of glutathione peroxidase and catalase.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Enhancement of osteoinduction by vitamin D metabolites in rachitic host rats.
Diaphyseal bone from normal Sprague-Dawley rats was delipidated in chloroform-methanol and demineralized in 0.6 N HCl at 4 degrees C. The bones were then implanted for 7-28 days into rats made rachitic by a low-phosphate, vitamin D-deficient diet (VDP-) for 3 weeks. Bones from VDP- and normal rats were also implanted into normal hosts. When normal rats were used as the host environment, a consistent sequence of cartilage induction and bone formation was observed. Demineralized rachitic bone (RB) implanted into normal host rats resulted in cartilage and bone induction similar to that seen for normal bone (NB) implants. Transmission electron microscopy of RB in normal hosts revealed morphologically normal chondrocytes and cartilage matrix with normal mineralization. In contrast, implantation of NB in VDP- hosts resulted in delayed chondrogenesis and lack of calcification. Furthermore, similar results were observed when RB was implanted into VDP- hosts. Treatment of VDP- hosts with either 1 alpha-hydroxyvitamin D3 or 24,25-dihydroxyvitamin D3 did not accelerate the sequential appearance of precartilage or cartilage. However, 24,25-(OH)2D3 administered alone or in combination with 1 alpha-OHD3 significantly increased the amount of calcified cartilage observed at 2 weeks postimplantation compared to implants from either untreated VDP-hosts or those treated only with 1 alpha-OHD3. New bone formation was observed at 4 weeks postimplantation in all vitamin D-treated groups as determined by von Kossa staining or direct electron microscope examination. There was no apparent difference in the quantitative or qualitative bone formed within the various vitamin D-treated groups. Serum calcium and phosphorus levels were lower and alkaline phosphatase levels were higher in VDP- hosts compared with normal animals or those treated with vitamin D metabolites. The results of this study show a reduction in the capacity of progenitor cells in VDP- rat hosts to respond to osteoinductive factor(s). This impaired response appears to be corrected by vitamin D metabolites.
24,25-Dihydroxyvitamin D 3↗