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Biomedical subjects

A Freeman

Publications and source records attributed to A Freeman.

At least 19 recordsLinked to original sources
PubMed1992

Stabilization of NAD(+)-dependent dehydrogenases and diaphorase by bilayer encagement.

A feasibility study aimed at stabilization of L-lactate-dehydrogenase, L-malate-dehydrogenase, alcohol-dehydrogenase and diaphorase by the recently described method of enzyme 'encagement' was conducted. This method involves derivatizing the enzymes with polyglutaraldehyde, followed by secondary crosslinking with amino derivatives of polyacrylamide. Encagement conditions were optimized for each of the four enzymes, so as to achieve the highest thermal stability combined with highest catalytic activity. Depending on the encagement conditions, residual activities were in the range of 18% to 96% with higher values in the presence of cofactors. Increases in thermal stabilization of up to 26-fold were obtained. For high retention of enzymic activity and stability, the most significant factor was the concentration of polyglutaraldehyde; the crosslinking polymers had only a negligible effect. Furthermore, the significant enhancement in thermal stability could be attained without perturbing the kinetic parameters: Km values for NADH and pH optima remained unaltered for the stabilized enzymes.

Acrylic Resins↗
PubMed1991

Continuous delta 1-hydrocortisone dehydrogenation with in situ product recovery.

A continuous aerated process for delta 1-hydrocortisone dehydrogenation by polyacrylamide-hydrazide (PAAH) bead-entrapped A. simplex cells was developed. The process allows for stable conversion of 1.6 g l-1 hydrocortisone (x 5 the solubility in water), made possible by the incorporation of selected cosolvent [5% (v/v) triethyleneglycol]. A large difference in substrate and product solubilities in the cosolvent-buffer medium allowed for in situ product recovery in an aerated, fluidized-bed, immobilized-cell reactor by the controlled addition of fine product-adsorbing powder (microcrystalline cellulose). The product was recovered at the reactor outlet as a fine complex with the adsorbent. Stable continuous operation of at least 4 weeks was recorded for a prototype reactor configuration, followed by the exhibition of similar operational stability in a modified version of a commercially available 2.5-l airlift reactor. Our results demonstrate that in addition to an obvious desirable cosolvent effect on substrate solubility enhancement, it may also enable easy in situ product recovery by creating a large gap in the solubilities of the substrate and the product in the cosolvent-containing reaction medium.

Arthrobacter↗
PubMed1991

Electrophysiologic analysis of early Parkinson's disease.

We have been interested in the application of quantitative measures of motor performance as a possible means of early detection of Parkinson's disease. To assess motor function, we have measured movement time (the physiologic correlate of bradykinesia) and reaction time (simple and directional choice) with an upper limb motor task, and tremor with accelerometry and electromyographic recordings. In this report we describe preliminary data from a Parkinson's disease patient group with symptoms of fewer than 2 years' average duration (compared with an age- and gender-matched normal control group) which indicate that precise, quantitative tests of motor function can detect the slight deviations from normal that are present in early Parkinson's disease. It appears that tests of bradykinesia are most sensitive, and detection of rest tremor is most specific. These tests may be applicable in screening individuals who are suspected of having or are "at risk for" Parkinson's disease and other related disorders.

Adult↗
PubMed1991

Electrophysiologic analysis of early Parkinson's disease.

We have been interested in the application of quantitative measures of motor performance as a possible means of early detection of Parkinson's disease. To assess motor function, we have measured movement time (the physiologic correlate of bradykinesia) and reaction time (simple and directional choice) with an upper limb motor task, and tremor with accelerometry and electromyographic recordings. In this report we describe preliminary data from a Parkinson's disease patient group with symptoms of fewer than 2 years' average duration (compared with an age- and gender-matched normal control group) which indicate that precise, quantitative tests of motor function can detect the slight deviations from normal that are present in early Parkinson's disease. It appears that tests of bradykinesia are most sensitive, and detection of rest tremor is most specific. These tests may be applicable in screening individuals who are suspected of having or are "at risk for" Parkinson's disease and other related disorders.

Adult↗
PubMed1990

Personality disorders among depressed outpatients as identified by the MCMI.

Personality disorders frequently are seen among depressed psychiatric inpatients. In a group of 73 depressed psychiatric outpatients, this study identified 85% whose response to the Millon Clinical Multiaxial Inventory (MCMI) suggested a personality disorder. On retest 12 weeks later, only 64% manifested a response style consistent with the DSM-III personality disorders. These findings are discussed in relation to methodology, characteristics of the MCMI, and the response style of the depressed patient, which may lead to an overidentification of personality disorders on a self-report measure. Related aspects of the diagnostic criteria for personality disorders also are discussed.

Adult↗
PubMed1990

Stability of the MCMI among depressed psychiatric outpatients.

The Millon Clinical Multiaxial Inventory (MCMI) is a promising, yet somewhat unproven psychometric inventory developed to identify clinical syndromes and personality traits consonant with the Diagnostic and Statistical Manual of Mental Disorders (3rd ed. [DSM-III]; American Psychiatric Association, 1980). The stability of its measures for both the theoretically more stable personality characteristics and the clinical syndromes was investigated in a group of depressed psychiatric outpatients. In this test-retest design with a 3-month interval between tests, clinical syndrome scales of relevance changed significantly as expected. However, many of the personality scales also changed significantly. Only four of the personality scales met a two-fold test of stability. Findings are discussed in terms of characteristics of self-report inventories such as the MCMI, the uniqueness of the depressed population, and characteristics of personality disorders.

Adult↗
PubMed1990

Preliminary report on adrenal-brain transplantation for parkinsonism in man.

The attempt to restore lost neurological function through grafting of catecholaminergic tissue into the striatum is a dramatic new experimental treatment approach for parkinsonism. We have grafted autologous adrenal medullary tissue into the right caudate nucleus in 12 patients with advanced Parkinson's disease (10 males, 2 females, mean age 53 years, mean Hoehn and Yahr stage 'off' medications 4.2) applying a transcortical technique similar to that of Madrazo as modified by Allen using right adrenalectomy performed via a flank approach. There have been no deaths, surgical complications, or serious postoperative morbidity. Modified Columbia Parkinson's disease ratings of patients off all dopaminergic agents for 72 h revealed 22% improvement (p less than 0.01) 3-6 months postoperatively (n = 10) and 22% improvement (p less than 0.01) 7-12 months later (n = 9). Postoperative dyskinesias necessitated reduction of L-dopa by 11% and of carbidopa by 29%. Analysis of lumbar cerebrospinal fluid biogenic amine metabolites following a 4-day 'drug holiday' revealed that homovanillic acid increased to 159% of preoperative levels (p less than 0.01) 3-6 months (n = 9) and to 197% of preoperative levels (p less than 0.02) 7-12 months postoperatively (n = 5). We have observed a mild to moderate improvement persisting up to 1 year with this therapeutic approach, but further study is needed.

Adrenal Medulla↗
PubMed1990

Spontaneously occurring antibodies to parathyroid hormone.

A 76-yr-old female with acute pancreatitis and a normal/borderline elevated serum calcium level was found to have an elevated immunoreactive circulating PTH concentration using a C-terminal assay. This high PTH concentration misled the attending physicians and resulted, in retrospect, in an unnecessary neck exploration. When the patient's serum was examined it was found to contain a binding component that bound both C-terminal and PTH-(1-84). This binding component was not retained on a Sep-Pak column and was precipitated by antiserum directed against human immunoglobulin M. The presence of circulating anti-PTH immunoglobulin M explains the apparently high PTH concentrations measured by RIA. The antibodies occurred spontaneously. To the best of our knowledge, this phenomenon has not previously been described.

Acute Disease↗
PubMed1989

Lipid peroxides and atherosclerosis.

Plasma lipid peroxide concentrations were measured in 100 patients with occlusive arterial disease proved angiographically (50 patients with ischaemic heart disease, 50 with peripheral arterial disease) and compared with values in 75 control patients with no clinical evidence of atherosclerosis. Lipid peroxide concentrations were significantly higher in patients both with ischaemic heart disease (median 4.37 mumol/l (interquartile range 3.85-5.75 mumol/l); p less than 0.001) and with peripheral arterial disease (median 4.37 mumol/l (3.88-5.21 mumol/l); p less than 0.001) than in controls (median 3.65 mumol/l (interquartile range 3.29-3.89 mumol/l). Overall there was a significant but weak correlation between plasma lipid peroxide and plasma triglyceride concentrations (rs = 0.25; p less than 0.001) but not between plasma lipid peroxide and plasma total cholesterol concentrations. Furthermore, hypertension, obesity, diabetes, smoking, positive family history, and intake of beta blockers and thiazide diuretics were not associated with significant differences in lipid peroxide values. This study provides clinical support to experimental data indicating that peroxidised lipids may be important in atherogenesis and its complications and also suggests that peroxidised lipids may provide an index of the severity of atherosclerosis.

Adult↗
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↗