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Biomedical subjects

R Cohn

Publications and source records attributed to R Cohn.

At least 19 recordsLinked to original sources
PubMed1992

CD10 antigen density in childhood common acute lymphoblastic leukaemia: comparisons of race and sex.

During the 25 month period from July 1989 until August 1991, 58 children with FAB defined acute lymphoblastic leukaemia (ALL) were referred for immunophenotypic analysis. Of these, 42 children with a common/pre-B phenotype (CD19/CD10-positive) were studied specifically to assess CD10 antigen density. A pattern of segregation was found between males and females and between black and white children. Black males, who are the worst prognostic group, had the lowest CD10 density, while white females, known to constitute the best prognostic group, had significantly higher CD10 antigen density than the other groups. Black females and white males occupied intermediate positions with respect to CD10 antigen density. A two way analysis of variance showed that although sex had contributed significantly to this variation (p = 0.0038), the contribution of race was marginal (p = 0.0530). It is hypothesized that low CD10 antigen density patterns in males and in Blacks could be causally related to poor prognosis.

Black People↗
PubMed1992

Reduced latency of the visual evoked cortical response following cryogenic injury to the cerebral cortex--a neuroexcitatory phenomenon.

Changes in the latency of visual cortical evoked responses (VER) were studied in rats subjected to cryogenic injury of the cerebral cortex. Four hours after cold injury the animals revealed a significant reduction of VER latency, which lasted approximately one week, with maximal reduction in latency occurring after 3 days. A potential role of excitotoxic amino acids in this phenomenon was tested by direct application of glutamate to the exposed cerebral cortex of the control rat and by administration of MK-801, antagonist of the NMDA receptor, in rats subjected previously to cryogenic injury and displaying a significant reduction in the VER latency. The direct application of glutamate to the cortex resulted in a decrease of the VER latency similar in magnitude to that observed after cold injury and this effect could repeatedly be demonstrated after washing out the initial application of the glutamate. The administration of MK-801 in animals subjected previously to cryogenic injury produced, within 5 minutes, reversion of reduced VER latencies. The maximal prolongation of latency occurred 30 min after MK-801 administration and reached in some cases latency values greater than in controls. Reduced latencies, corresponding to those observed originally, reappeared within 2 to 4 hours. Our studies suggest that the described reductions in the VER latencies are related to cortical areas of hyperexcitation due to excessive release of neuroexcitatory transmitters.

Animals↗
PubMed1992

Decreased visual evoked cortical response latency associated with cerebral ischaemia in the gerbil.

The observation of Xu et al. concerning reduction in latency of the visual evoked responses (VER) following cortical cryogenic injury, prompted us to ascertain whether similar VER changes could be demonstrable after ischaemic brain injury, especially, since both conditions have in common involvement of neuroexcitatory mechanisms. In our study, the Mongolian gerbils, which were subjected to 10 min bilateral carotid occlusion ischaemia, revealed decreased latency of the VER, with the peak of latency reduction between 4 and 7 h. An almost immediate decrease in VER latency was observed when glutamate was directly applied to the pial surface of the brain. These observations indicate that the reduction of VER latency may be related to neuroexcitation induced by release of excitatory amino acids, the latter constituting a widespread phenomenon, concomitant with brain injuries of various aetiologies.

Animals↗
PubMed1991

Neuropsychological deficit in haemophiliacs with human immunodeficiency virus.

Neuropsychological impairment is widely accepted as being common in acquired immunodeficiency syndrome (AIDS) but infrequent in asymptomatic human immunodeficiency virus (HIV)-infected individuals. The neuropsychological function of a homogenous sample of HIV-infected haemophiliacs was investigated. Neuropsychological impairment, the nature of which is compatible with that described in the existing literature, was found in one of four AIDS cases. Eleven AIDS related complex (ARC) and 12 asymptomatic HIV-infected individuals were free of neuropsychological deficit.

AIDS Dementia Complex↗
PubMed1990

Characterization of beta-amyloid precursor proteins with or without the protease-inhibitor domain using anti-peptide antibodies.

Alternative splicing of the transcript encoding the beta-amyloid precursor protein (BAPP) of Alzheimer's disease produces multiple mRNA species. Translation of these mRNAs predicts protein products of 770, 751, and 695 amino acids. The difference arises from the inclusion in BAPP-770/751 of a 56-residue insert region which is homologous to Kunitz-type protease inhibitors. We have prepared and affinity-purified anti-peptide antibodies that react specifically with either BAPP-770/751 (insert-specific) or BAPP-695 (junction-specific). A detectable level of the mRNA corresponding to the BAPP-770/751 protein was found in all cell lines tested. Immunoprecipitation of 35S-labeled proteins from these cell lines showed them to contain one or two Mr 105,000 bands reactive with the insert-specific serum, i-291. In contrast, only cos-7 cells and the human neuroblastoma cell line, IMR-32, contained mRNA species that encode the BAPP-695 protein, as shown by Northern analysis with a junction-spanning oligonucleotide probe. A band of Mr 95,000 was immunoprecipitated specifically from these two cell lines using the junction-specific serum, J-284. Indirect immunofluorescence labeling of cells corroborated these findings. All cells reacted with the insert-specific antibodies, i-291 and i-324. Only cos-7 and IMR-32 cells reacted with the junction-specific antibody, J-284. These results demonstrate the usefulness of anti-peptide antibodies for the differential detection of the BAPP-695 and BAPP-770/751 proteins.

Alzheimer Disease↗
PubMed1989

Biochemical characterisation of the haemophilias on the Witwatersrand.

Blood samples obtained from patients on the Witwatersrand with haemophilia A, haemophilia B and von Willebrand disease were analysed. Factor activities were assayed by conventional methods. Immunoradiometric assay using labelled monoclonal anti-VIIIC:Ag was developed to assay factor VIIIC:Ag in haemophilia A. Factor IX:Ag levels were determined by a commercial ELISA kit. Multimer pattern analysis of von Willebrand factor was performed by agarose gel electrophoresis and Western blotting. In 43 patients haemophilia A was severe, in 8 it was moderate and in 2 it was mild. Factor VIIIC:Ag was undetected in 36 haemophiliacs (CRM-) while VIIIC:Ag was detected in levels exceeding or correlating with those of VIII:C in 17 cases (CRM+). Four severe, CRM- haemophiliacs were found to have inhibitors. An assay of IX:Ag in 6 severely and 2 moderately affected patients with haemophilia B revealed 6 to be CRM- while 2 were CRM+. Multimer pattern analysis was performed on 11 von Willebrand disease patients, of which 5 were type I, 5 were type II and 1 was type III. More informative techniques for the diagnosis and classification of haemophilia are now available. In addition, these results will assist in further molecular studies of these disorders.

Electrophoresis, Agar Gel↗
PubMed1989

Compliance with chemotherapy in childhood leukaemia in Africa.

Compliance with chemotherapy in childhood leukaemia is usually good because of parental fear of the disease. However, poor compliance and refusal of treatment have been reported from both the USA and the UK. Little is known about African concepts of leukaemia, attitudes to treatment or compliance. A study was undertaken to investigate factors which might affect compliance in 15 black and 30 white families of leukaemic children in Johannesburg. The socio-economic and educational status of the black families was lower than that of the white. Only 53% of black children attended hospital on the appointed day compared with 90% of white children. Less than 50% of black parents understood the nature of their child's illness. Both black and white families had unused medication at home. White parents more frequently reported toxic effects related to chemotherapy and more white children than black children exhibited lymphopenia during maintenance therapy. Assessment of drug compliance should be included as an independent variable when evaluating factors affecting response to chemotherapy in communities of diverse ethnic, socio-economic and cultural backgrounds.

Black or African American↗
PubMed1989

Comparisons of cause of death verification methods and costs in the lipid research clinics program mortality follow-up study.

Classification of causes of death by a nosologist is standardized and relatively inexpensive, although the quality of the data recorded on death certificates has been subjected to criticism and the level of detail may not allow examination of specific circumstances of the death. A costly alternative is classification by a panel of physicians reviewing additional clinical information. The costs associated with both methods of classification as utilized by the Lipid Research Clinics Program Mortality Follow-up Study are presented along with their advantages and disadvantages. For deaths among the elderly (65 years or older), determination of the underlying cause of death may be difficult, especially as regards cardiovascular disease causes of death using only the death certificate, and impossible for classifying sudden death. Both classification methods are compared for 268 deaths among the elderly and 155 deaths among the nonelderly males and females participating in the study. The kappa statistics for observer agreement indicate moderate agreement (k = 0.58) and were not significantly different between the two age-groups (p greater than 0.10). Thus, the agreement between the methods was not affected significantly by the age of the deaths being classified. However, examination of the agreement chart showed a preference by the nosological classification for cardiovascular classification in the elderly population. The effect of the different classifications upon the analysis of the predictive value of high-density lipoprotein cholesterol on coronary heart disease mortality showed little difference between both methods of classification.

Adult↗
PubMed1987

Long duration Jakob-Creutzfeldt disease.

The first patient was a woman hospitalized at the age of 43 years; she received the diagnosis of presenile dementia because of a progressive deterioration of her intellectual functions over an interval of 3 years. On admission there were no localizing neurological findings. During the ensuing years she became unable to speak and was no longer able to respond to commands. Death occurred at the age of 46 years from bronchopneumonia. The brain showed marked atrophy of the frontal lobes, moderate in the temporal lobes. The anterior horns of the lateral ventricles were greatly dilated. Microscopically cortical atrophy was severe, with marked depletion of neurons in involved regions. Lamination and polarity were not preserved. There was considerable increase of astrocytes and microglia, and focal sponginess was prominent. The hippocampus showed atrophy of Sommer's sector and subiculum. There were no neurofibrillary tangles and no argyrophilic plaques. The occipital sections showed little neuronal loss and no increased astrocytes or sponginess. The insulae showed neuronal loss and gliosis. There was bilateral atrophy of the caudate nuclei and globus pallidus adjacent to the dystrophic anterior limbs of the internal capsule. In the brain stem the frontopontine tracts were partially demyelinated and showed reactive gliosis. Ventral horns were atrophic with moderate glial reaction. In the second patient the microscopic changes were quite similar to those in Case 1, but there was more severe degeneration of the corticospinal tracts and the ventral horns of the spinal cord which showed considerable loss of neurons and degenerative changes in the remaining nerve cells and nerve fibers. There were many instances of axonal degeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Lipoproteins as mediators for the effects of alcohol consumption and cigarette smoking on cardiovascular mortality: results form the Lipid Research Clinics Follow-up Study.

Because alcohol consumption is associated with increased high density lipoprotein (HDL) cholesterol and decreased low density lipoprotein (LDL) cholesterol, and cigarette smoking is associated with lower HDL cholesterol and higher LDL cholesterol, there has been speculation that the protective effect of moderate alcohol consumption and/or the noxious effect of cigarette smoking for cardiovascular disease might be mediated in large part by a lipoprotein mechanism. The authors examined this question in a prospective study of 7,461 men and women in 10 North American populations initially seen in 1972-1976 and followed for an average of 8.5 years. Moderate alcohol consumption was weakly protective for cardiovascular disease, while cigarette smoking was strongly and significantly associated with cardiovascular disease mortality. As expected, LDL cholesterol was positively related and HDL cholesterol was inversely related to cardiovascular disease mortality. However, multivariable analysis of cardiovascular disease mortality alternately excluding and including HDL cholesterol and LDL cholesterol as covariates indicated that the effect of alcohol consumption on cardiovascular disease mortality was independent of an LDL cholesterol pathway and only partially mediated by an HDL cholesterol pathway, while the effect of cigarette smoking was independent of both the HDL cholesterol and LDL cholesterol pathways, suggesting alternative biologic mechanisms of action for both alcohol consumption and cigarette smoking on cardiovascular disease.

Adult↗
PubMed1986

Acute childhood leukemia in Johannesburg. Ethnic differences in incidence, cell type, and survival.

Acute childhood leukemia was found to be less common in black children than in white children in the Johannesburg area of South Africa. Of 195 consecutive patients, 78 were black and 117 white. The annual incidence was 0.8/100,000 black children and 3.3/100,000 white. The low incidence in black children was due to the very low incidence of acute lymphoblastic leukemia (ALL), which was 0.41/100,000 black children compared with 2.73/100,000 white children. The incidence of acute nonlymphoblastic leukemia (ANLL) was approximately the same for both ethnic groups; 0.38/100,000 black children and 0.57/100,000 white children. Remission rates for black children with ALL were lower than for white children and the cumulative proportion of black patients surviving at 60 months was only 32% compared with 72% of white patients (p = 0.0001). The most significant poor prognostic factors in ALL were ethnic group and age (p = 0.0006), CNS disease at onset (p = 0.006), FAB L2 and L3 morphology (p = 0.05), and irregular clinic attendance during maintenance therapy (p = 0.05). In ANLL, remission and survival rates were less favorable than in ALL but there were no significant differences between black and white patients. Black patients exhibited certain clinical features rarely seen in white patients, including chloromata, oropharyngeal lesions, and CNS involvement at onset. Karyotypic abnormalities were common. The most significant poor prognostic factors in ANLL were CNS disease at onset (p = 0.03), generalized lymphadenopathy (p = 0.0001), and FAB morphology classification M3-M6 (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1985

Differential visual evoked cortical responses to direct and peripheral stimulation in man.

Clearly defined differential summated cortical evoked responses are demonstrated for central and peripherally applied visual stimuli. Central vision is associated with a low amplitude positive peak at 75 msec and a prominent high voltage positive peak at around 100 msec; later relatively low amplitude positive peaks are generally also observed. With peripheral stimulation at 15 degrees and greater the 75 msec positive peak is accentuated; the 100 msec positive peak becomes inconspicuous, and the later positive peaks at 165 msec and greater are strongly enhanced. These data support the hypothesis that the positive peaks are the cortical responses to the differential actions of the rod and cone cell components of the retina.

Evoked Potentials, Visual↗
PubMed1979

On the clinical significance of the plasma alpha-amino-n-butyric acid:leucine ratio.

The ratio of plasma alpha-aminobutyric acid to plasma leucine that has been proposed as a specific biochemical marker of alcoholic liver injury, was measured in normal children an children with a variety of metablic disorders. The ratio was found to be lower in children that in adults. It was elevated in children with Reye's syndrome, tyrosinemia, homocystinuria, nonketotic hyperglycinemia, and ornithine transcarbamylase deficiency. The results indicate that an elevated ratio is not specific for adults with alcoholic liver injury and that the ratio may be high even without the presence of clinically apparent hepatic disease. An altered ratio may reflect the presence of an inherent metabolic defect.

Adult↗
PubMed1979

Biotin-response organicaciduria. Multiple carboxylase defects and complementation studies with propionicacidemia in cultured fibroblasts.

Fibroblast cultures from two individuals with biotin-responsive organicacidemia were found to have a pleiotropic deficiency of propionyl-CoA carboxylase, beta-methylcrotonyl-CoA carboxylase, and pyruvate carboxylase activities after growth in biotin limited culture medium, conditions which do not affect the carboxylase activities of normal cells. All three enzyme activities were restored to normal levels after transferring the mutant strains to biotin-rich medium. Both patients excreted abnormal levels of an array of metabolic intermediates, including beta-methylcrotonate, beta-hydroxyisovalerate, beta-hydroxypropionate, and lactate, which reflect metabolic blocks at all three carboxylase sites.14 mutants deficient in only propionyl-CoA carboxylase activity from patients with propionicacidemia and the two biotin-responsive strains were examined for complementation with seven previously mapped pcc mutants. No new pcc complementation groups were identified. Nine of the mutants were mapped to group pccA. The remaining 12 mutants mapped to pccBC or its B or C subgroups, confirming the complex nature of this group. The biotin-responsive mutants failed to complement each other but did complement mutants from all the pcc groups. Thus biotin-responsive organicacidemia is defined by a new complementation group, bio. The results obtained in this study suggest that the bio mutants have a defect of either biotin transport or a common holocarboxylase synthetase required for the biotin activation of all three mitochondrial carboxylases.

Acidosis↗