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Biomedical subjects

A Freeman

Publications and source records attributed to A Freeman.

At least 91 records · Page 5Linked to original sources
PubMed1988

Cosolvent effects on gel-entrapped oxidoreductase: the glucose oxidase model.

An intrinsic problem often involved in biotransformations carried out by immobilized cells is the poor solubility of substrate and product in water. Increase in hydrophobic substrate availability to such gel-entrapped cells may be attained by the replacement of a fraction of the aqueous medium by water-miscible solvents (cosolvents). The introduction of cosolvents results in increased solubility, but may simultaneously affect enzymic activity and stability. Recently, criteria and guidelines for cosolvent selection on the basis of its effect on intracellular enzyme stability were reported (Freeman, A., and Lilly, M.D. (1987) Appl. Microbiol. Biotechnol. 25, 495-501). In order to understand the impact of the preferable or unsuitable cosolvents on enzyme kinetics and stability, the effects of 1-5 M concentrations of a series of cosolvents (e.g., ethylene glycol, dimethylsulfoxide, N,N-dimethylformamide, ethanol) on a well-characterized, highly specific enzyme model (glucose oxidase) were investigated. The presence of 1-5 M of the cosolvents studied imposed 10-50% reduction in Vmax of the enzyme, but Km was only mildly affected (+/- 25%). This inhibition was attributed to cosolvent effect on small, reversible, conformational changes in the enzyme native structure. Determination of the rate constant of thermal inactivation (at 55 degrees C) of glucose oxidase, in the presence of cosolvents, was employed for the quantitative evaluation of cosolvent effect on enzyme stability. A clear pattern of cosolvent preference in respect to its denaturing effect was obtained, which was identical to the pattern previously observed in a study of oxidoreductases operating from within a whole cell. In both cases diols (e.g., ethylene glycol) were found to be the preferable group of cosolvents. Our results indicate that a soluble enzyme and an intracellular enzyme operating from a whole cell are affected by cosolvents via the same mechanism.

Aspergillus niger↗
PubMed1987

An autopsy study of 1206 acute and chronic leukemias (1958 to 1982).

Autopsy data on 1,206 children and adult patients with acute myelocytic leukemia (AML) (585), chronic granulocytic leukemia (CGL) (204), acute lymphocytic leukemia (ALL) (308), and chronic lymphocytic leukemia (CLL) (109) obtained from 1958 to 1982 were reviewed. This analysis has shown that, whereas the proportion of patients with residual AML at any anatomic site decreased significantly and uniformly over the entire study period, significant corresponding decreases in patients with CGL and ALL occurred only since 1976 and 1978, respectively. No significant corresponding decreases were noted in patients with CLL at any time. Significant decreases were also noted over time in the rates of extramedullary site involvement by AML, CGL, and ALL. Whereas the lymphoreticular organs, kidneys, adrenals, and pituitary were most often involved at autopsy by CLL, the testes, leptomeninges, dura mater, uterus, large bowel, and pancreas were most often involved by ALL. In general, patients with AML and CGL showed the lowest relative rates of involvement of the various organs by leukemia during the 24-year period. Whereas patients with AML and ALL showed significant decreases in the rates of involvement of nearly all anatomic sites during the most recent study periods, those with CGL and CLL showed corresponding decreases in only a few organ sites. The lower rates of organ involvement in patients with AML and ALL attest to the more aggressive eradication of leukemic cells by therapeutic regimens in these diseases over time. In particular, the significant decrease in the rate of meningeal involvement by ALL during the most recent period is probably attributable to central nervous system prophylaxis.

Adolescent↗
PubMed1987

Intrathecally administered natural human fibroblast interferon reduces exacerbations of multiple sclerosis. Results of a multicenter, double-blind study.

A randomized, double-blinded, placebo-controlled, two-year multicenter study demonstrated that natural human fibroblast interferon (interferon beta) administered intrathecally (IT) is effective in reducing the exacerbations of exacerbating-remitting multiple sclerosis (MS). The mean reduction in exacerbation rate of 34 patients with MS who received interferon beta administered IT was significantly greater during the study than that of 35 control patients who received placebo. The prestudy exacerbation rates were comparable for both patients who received interferon beta and control patients, but the exacerbation rate of patients receiving interferon beta at the end of the study was significantly lower than that of the control patients. Interferon beta was administered by nine or ten lumbar punctures for the first six months of the study, and observations were continued for two years. In 95% of the recipients, interferon beta therapy was well tolerated, and the side effects experienced were clearly acceptable for the benefits achieved. Low doses of indomethacin dramatically reduced the toxicity of interferon beta therapy and played an important role in successful double blinding. This study confirms a preliminary report on 20 patients that initially suggested that interferon beta administered IT was of benefit in patients with MS. The number of treatments was fewer and the dosage of interferon beta administered was less in the present study than in the preliminary one. It is possible that even fewer treatments with lower doses of interferon beta administered might provide a similar degree of prophylaxis against exacerbations.

Adult↗
PubMed1987

Intensive remission consolidation therapy in the treatment of acute nonlymphocytic leukemia.

A pilot study was conducted to determine the possible efficacy and the toxicities associated with the administration of four courses of intensive consolidation chemotherapy to patients with acute nonlymphocytic leukemia in remission. All therapy was completed within 6 months. The median duration of remission was 22 months, with 45+% of patients in remission at 3 years and few relapses to date thereafter. Sixty percent of patients experienced significant side effects after each course of therapy. The therapy appeared to be particularly efficacious for patients less than 45 years of age, since 65% are alive at 3 years and there is no projection for a median duration of remission as yet. The cytogenetic characteristics of the leukemic cells, the percentage of S phase cells, and the height of the WBC count were the most important prognostic characteristics at diagnosis.

Acute Disease↗
PubMed1987

Genital findings in sexually abused, symptomatic and asymptomatic, girls.

Although evaluation of the vulva of sexually abused girls using magnification with a colposcope or pediatric otoscope has become increasingly popular, the incidence of various genital findings in sexually abused and asymptomatic children has not been reported. A prospective study was carried out in which 20 genital findings from three groups of girls (mean age 4.8 +/- 2.6 years) were analyzed. The three groups were (1) sexually abused girls (n = 119), (2) normal girls with no genital complaints (n = 127), and (3) girls with other genital complaints (n = 59). Group 1 was more likely than group 2 to have scars on the hymen or posterior forchette (9% v 1%, P = .002), increased friability of the posterior forchette (10% v 1%, P = .001), attenuated hymen (18% v 4%, P = .0003), and synechiae from the hymenal ring to the vagina (8% v 0%, P = .0009). Groups 1 and 3 were remarkably similar with the exception of erythema which was more common in group 3 (34% v 68%, P = .0001). Hymenal diameter was slightly greater in group 1 than 2 but not 3. Although genital findings distinguish some sexually abused girls from asymptomatic girls, many findings also occur in girls with other genital complaints, which suggests that many of these girls have also been molested or that vulvar inflammation may lead to some of these findings.

Adolescent↗
PubMed1985

Intrathecal interferon in the treatment of multiple sclerosis. Patient follow-up.

Follow-up observations on patients with multiple sclerosis who were treated with human fibroblast interferon (interferon beta) administered intrathecally for six months revealed a persisting beneficial effect in terms of a reduction in exacerbation rates. At the time of our last report in 1982, ten interferon beta recipients had shown a reduction in their mean exacerbation rate from 1.8/yr before the study to 0.2/yr during the study while ten control patients with multiple sclerosis showed no change in their rates during the study (0.69/yr) compared with before it (0.68/yr). That report was based on observations made for means of 1.9 years in the recipients and 1.6 years in the controls. The recipient patients have now been followed up for 4.4 years (mean) and their exacerbation rates have continued to decrease to a current mean level of 0.16/yr. The control patients were "crossed over" and began receiving interferon beta intrathecally after they had been in the study for two years without showing any change in their rate. During the 2.0 years since crossover they also have shown a reduction in exacerbation rate to a mean of 0.30/yr. The toxic side effects of interferon beta administered intrathecally were acceptable in view of the benefit achieved. Interferon was identified in the cerebrospinal fluid (but not the serum) of two patients prior to treatment, which is probably a manifestation of de novo production of interferon by the central nervous system in response to the multiple sclerosis disease process.

Adolescent↗
PubMed1985

Newly developed microcarrier culturing systems--an overview.

Microcarrier (MC) culturing systems are widely employed for the production of biological products required for human and veterinary uses and serve as a tool for basic research in cell biology. Three types of MCs were developed by our group: cellulose, polyacrylamide and polystyrene based MCs. These newly developed MCs were used for the propagation of primary cells, cells from a human diploid cell strain and cells from established cell lines, for the production of biological products (various viruses, mouse interferon and carcinoembryonic antigen) as well as for studying cell differentiation. Basic questions regarding the effect of the chemical nature of MCs on cell attachment, spreading and growth were investigated throughout the development of these MCs.

Acrylic Resins↗
PubMed1984

The relationship between fetal heart rate accelerations, fetal movements, and uterine contractions.

The association between fetal heart rate (FHR) accelerations and fetal movements during uterine contractions was studied in 52 pregnant women near term or at the beginning of labor. FHR and uterine contractions were recorded by tococardiograph. At the same time, fetal movements, whether associated or not with contractions, were viewed by real-time ultrasound. During uterine contractions, 95.5% of the FHR accelerations were associated with fetal movements. Also, 90.9% of the accelerations which appeared when the uterus was not contracting were associated with fetal movements. Fetal movements were not seen in 91% of uterine contractions which were not associated with FHR accelerations. The suggestion is made that uterine contractions stimulate both fetal movements and FHR accelerations.

Female↗
PubMed1984

Monooxygenase activity of rat liver microsomes immobilized by entrapment in a crosslinked prepolymerized polyacrylamide hydrazide.

Rat liver microsomes were immobilized by entrapment in a chemically crosslinked synthetic gel obtained by crosslinking prepolymerized polyacrylamide-hydrazide with glyoxal. Approximately 88% of the microsomal fraction was entrapped in the gel. The specific rate of O-demethylation of p-nitroanisole was used to assay the microsomal cytochrome P-450 activity of the immobilized microsomal preparations. The gel entrapped microsomes showed monooxygenase activity at 37 degrees C of Vmax = 2.3 nmol p-nitrophenol/min per nmol cytochrome P-450, similar to that of microsomes in suspension. The Km value for the p-nitroanisole-immobilized microsomal cytochrome P-450 system (1.2 X 10(-5) M) was rather close to that of microsomes in suspension (0.8 X 10(-5) M). Under the experimental conditions used the pH activity curve of the immobilized preparation was shifted towards more alkaline values by approx. 0.5 pH unit in comparison with microsomes in suspension. The rate of cytochrome c reduction by the immobilized microsomal system (11.7 nmol/min per mg protein) at 25 degrees C was considerably lower than that of the control (microsomes in suspension, 78 nmol/min per mg protein). Enzyme activity in both preparations showed the same temperature dependence at the temperature range of 10 to 37 degrees C. The immobilized microsomal monooxygenase system could be operated continuously for several hours at 37 degrees C provided that adequate amounts of an NADPH-generating system were added periodically. Under similar conditions a control microsomal suspension lost its enzymic activity within 90 min.

Acrylic Resins↗
PubMed1984

Demographic and clinical data associated with acute necrotizing ulcerative gingivitis in a dental school population (ANUG-demographic and clinical data).

This study was undertaken to determine the prevalence of demographic and clinical factors of patients diagnosed as having ANUG as determined by the presence of painful, bleeding, necrotic and ulcerated interproximal gingival papillae. Results showed that ANUG patients were evenly divided between males and females relative to the general clinic population. 58% of the patients with ANUG were under 25 years of age as compared to 31% under 25 in the general clinic population. Overall, the ANUG group accounted for 1.4% of the under 34 age group in the general clinic population. 76% of the ANUG group had a high school education or less with 67% having less than $5,000 annual income. Only 20% presented with elevated temperature. Only 6% of the patients with ANUG were non-smokers as compared to 63% in a matched control group. Of great significance was the fact that only 1 patient with ANUG was black as compared to a 41% black population in the clinic population.

Adolescent↗
PubMed1984

CT abnormalities and altered methotrexate clearance in children with CNS leukemia.

Seventeen children with CNS leukemia treated with chemotherapy and 5 children treated with both cranial radiation (CRT) and chemotherapy were evaluated. Eighty-eight percent of patients treated with chemotherapy alone had CT abnormalities, and all treated with CRT and chemotherapy had abnormal CT. The severity of CT abnormality paralleled intraventricular methotrexate levels and clinical signs of leukoencephalopathy. Children who receive chemotherapy for CNS leukemia, even without cranial irradiation, are more likely to have leukoencephalopathy than children without CNS leukemia. Moreover, patients with CNS leukemia may have abnormalities of CSF clearance of intraventricularly administered drugs.

Central Nervous System Diseases↗
PubMed1983

Teaching psychiatry to non-psychiatrists: I. The application of educational methodology.

It is becoming increasingly clear that psychiatric and psychosocial needs of medical patients are not being adequately met. This need has led to an increasing emphasis on the psychiatric education of nonpsychiatrists, at varying levels of experience. Given the many problems involved in these educational efforts as well as the paucity of evaluation studies and the uncertainty of results, the authors argue that the systematic application of empirically validated educational principles may lead to greatly improved effectiveness. In this first section of a two-part series, the authors review educational methodology as it relates to the development of training objectives, the selection of teaching procedures, and the use of evaluation techniques. Part two presents a detailed "model" curriculum for primary care residents, developed according to the principles of educational methodology.

Attitude of Health Personnel↗