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Biomedical subjects

M T Baker

Publications and source records attributed to M T Baker.

At least 37 records · Page 2Linked to original sources
PubMed1991

Evidence for the stability and cytochrome P450 specificity of the phenobarbital-induced reductive halothane-cytochrome P450 complex formed in rat hepatic microsomes.

The hypothesis that the reduced spectral halothane-cytochrome P450 complex formed in rat hepatic microsomes is a stable cytochrome P450 specific species was examined. Comparisons of the cytochrome P450 inducers, phenobarbital (PB), pregnenolone-16 alpha-carbonitrile (PCN) and beta-naphthoflavone (beta-NF) showed that PB was the most effective inducer of the halothane-cytochrome P450 complex and the cytochrome P450 which liberates the halothane metabolites, 2-chloro-1,1-difluoroethene (CDE) and 2-chloro-1,1,1-trifluoroethane (CTE). However, the ratio of CDE produced to quantity of complex was found to be reduced 70-77% in these microsomes. A large portion of total microsomal cytochrome P450 was destroyed upon halothane reduction (up to 39%), yet the complexed cytochrome P450, particularly in microsomes from PB-treated animals, was resistant to the irreversible inactivation mechanisms of halothane reduction. The effects of reductive halothane metabolism on subsequent warfarin metabolism showed that 7-hydroxywarfarin formation from either (R)- or (S)-warfarin in microsomes from PCN-treated, PB-treated or untreated rats was highly susceptible to irreversible inhibition. In microsomes from PB-treated, but not PCN or untreated rats, the formation of one warfarin metabolite, 4'-hydroxywarfarin from (R)-warfarin, could be shown to be increased when complex was eliminated by photodissociation. These results suggest that PB-B is preferentially bound as complex and resistant to inactivation because of complex stability, and that halothane reduction readily destroys the cytochrome P450 form, PB-C.

Animals↗
PubMed1991

Reliability and validity of the appraisal of diabetes scale.

The present research evaluated the psychometric properties of a brief self-report instrument designed to assess appraisal of diabetes. Two hundred male subjects completed the Appraisal of Diabetes Scale (ADS) and provided blood samples that were subsequently assayed to provide an index of glycemic control (i.e., glycosylated hemoglobin). Subjects also completed either (a) additional measures of diabetes-related health beliefs, diabetic daily hassles, perceived stress, diabetic adherence, and psychiatric symptoms or (b) the ADS on two additional occasions. Results indicated that the ADS is an internally consistent and stable measure of diabetes-related appraisal. The validity of the measure was supported by correlational analyses which documented the relationship between the ADS and several related self-report measures.

Adaptation, Psychological↗
PubMed1991

The influence of inhalational anesthetics on in vivo and in vitro benzodiazepine receptor binding in the rat cerebral cortex.

The effect of volatile anesthetics on benzodiazepine receptor binding was examined autoradiographically in the rat brain both in vivo and in vitro with the use of [3H]-Ro-15-1788, a benzodiazepine antagonist. For in vitro studies, slide-mounted brain sections were incubated at 37 degrees C in Tris buffer (50 mM, pH 7.4) with [3H]-Ro-15-1788 (flumazenil, 0.5-12.0 nM) in the presence of air (control) or 1 MAC concentrations of halothane or isoflurane. Brain sections were exposed to x-ray film and their images digitized, and specific cortical [3H]-Ro-15-1788 binding was determined. A Scatchard plot of specific cortical binding was constructed, and the dissociation constant (KD) and maximum bound ligand per milligram tissue (Bmax) were determined for each experimental group. In the in vivo trials, rats were anesthetized with 1 MAC halothane or isoflurane; 0.5 microCi/g [3H]-Ro-15-1788 was given intravenously, and the animals were killed 15 min later. Seven standardized sagittal brain sections were examined from autoradiographs. Mean specific cortical binding was determined for each group and was compared with binding in unanesthetized control rats. A third experimental trial analyzed the timed arterial blood history of [3H]-Ro-15-1788 in animals prepared exactly as in the in vivo study. The [3H]-Ro-15-1788 blood clearance over 20 min and plasma [3H]-Ro-15-1788 levels at 15 min after injection of isotope were evaluated. In vitro Scatchard analysis showed no difference in experimental groups in KD or Bmax at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗
PubMed1990

The development of the lamprey pattern generator for locomotion.

The life cycle of the lamprey includes a larval stage that can last for several years. The motor behavior of the larval lamprey, the ammocoete, has been only minimally studied and little is known of the neural correlates of that behavior. Comparison of known larval behavior to that of adults leaves unclear whether there are large or small changes in the spinal nervous system during transformation. The motor output of isolated larval and transforming spinal cords when stimulated to "swim" with D-glutamate has some differences from that of comparable adult preparations, but shares many important features with adults. Primarily, the fictive swimming is less well regulated and less stable than adults of the same species. We propose that a major difference in the structure and organization of the central pattern generator for locomotion between adults and ammocoetes is a relative lack or immaturity of some cell types that participate in the coordination of the segments and the generation of the rhythm of the periodic bursting.

Animals↗
PubMed1988

One-year psychosocial follow-up of patients with chest pain and angiographically normal coronary arteries.

As many as 30% of patients with chest pain symptoms who are referred for arteriography are found to have normal coronary arteries. Research has shown that patients with anginal symptoms and normal coronary arteries score higher on neuroticism measurements (anxiety, depression and somatic concerns) at the time of catheterization than patients with anginal symptoms who have coronary artery disease. Research examining the cardiac course of chest pain patients with normal coronary arteries indicates that this is a nonprogressive disorder. Although follow-up studies of these patients report continued chest pain and diminished physical activity, these studies have ignored the psychologic status of the patients. Thus, it is not known whether their higher neuroticism scores at the time of catheterization persist following angiography or whether such elevated indexes of neuroticism are transient phenomena associated with precatheterization anticipatory stress. The present study examined 48 Veterans Administration Medical Center patients: 24 with anginal symptoms and normal coronary arteries and 24 with documented coronary artery disease. The patients completed a structured clinical interview and a set of psychologic inventories on the day before catheterization and 1 year later. The findings established continued high neuroticism scores among patients with anginal symptoms only and supported the findings of other investigators regarding continuing chest pain and restricted physical activity. The knowledge alone of benign coronary artery status resulted in virtually no change in the psychosocial status of these patients. Alternative treatment methods are discussed.

Angiography↗
PubMed1988

Reductive metabolism of halothane by purified cytochrome P-450.

The reductive metabolism of halothane was determined using purified RLM2, PBRLM4 and PBRLM5 forms of rat liver microsomal cytochrome P-450. The metabolites, 2-chloro-1,1,1-trifluoroethane (CTE) and 2-chloro-1,1-difluoroethylene (CDE), were determined. All three forms of cytochrome P-450 produced CTE with relatively small differences in its production among the various forms. There were major differences, however, in the production of CDE, with PBRLM5 being the most active. PBRLM5 was also the only form to show the development of a complex between halothane and cytochrome P-450. This complex absorbed light maximally at 470 nm. The complex formation and the production of CDE by PBRLM5 were stimulated by the addition of cytochrome b5. Cytochrome b5 had no effect on CDE production by PBRLM4 and inhibited the production of both CTE and CDE by RLM2. These results show that the two-electron reduction of halothane by cytochrome P-450 was catalyzed by the PBRLM5 form and that cytochrome b5 stimulated the transfer of the second electron to halothane through PBRLM5, but not RLM2 or PBRLM4.

Animals↗
PubMed1987

Stabilization of the reduced halocarbon-cytochrome P-450 complex of halothane by N-alkanes.

Under anaerobic conditions, various halogenated compounds, when metabolized by cytochrome P-450, form complexes which are spectrally detectable. Previous studies have shown that halothane forms such a complex with cytochrome P-450, and the result is a strong absorption at 470 nm. Stabilization of this proposed intermediate carbanion complex has never been demonstrated in a biological system. Data are presented which show that several organic solvents (C5-C7N-alkanes) will stabilize the complex formed between halothane and cytochrome P-450. Stabilization allowed the decay of the complex to be studied, and it is demonstrated that the product of decay was chlorodifluoroethylene, which substantiates the hypothesis that the complex is a two electron-reduced carbanion. Carbon tetrachloride and benzyl bromide, which also produce spectrally visible intermediate complexes, were not stabilized by this treatment. Stabilization of the halothane complex in a biological system may facilitate studies to identify precisely the halothane-cytochrome P-450 complex and to clarify the mechanisms of halothane reduction by cytochrome P-450.

Alkanes↗
PubMed1987

Comprehension of informed consent information by young-old through old-old volunteers.

Comprehension of typewritten informed consent information was evaluated for young-old (60-69 years) through old-old (80-89 years) volunteers as a function of years of education (less than 12, 12, and greater than 12), readability of information (low [college level] vs high [7th grade]), and typeface used in the preparation of the materials (Prestige Elite 72, Letter Gothic, and Orator). All volunteers (N = 235) read a typewritten information sheet and retained it for review while answering eight multiple choice questions. Immediate feedback was provided, and a second test was administered if any answers were incorrect. The findings indicated that comprehension varied directly with education and inversely with age. Typeface and age interacted due to age-related differences with the two smaller (Prestige Elite and Letter Gothic), but not with the largest of the typefaces (Orator). These findings suggest that the observed age-related differences may have been due to visual and not cognitive deficits. Readability did not affect performance either by itself or in combination with any other variable.

Age Factors↗
PubMed1987

Stimulatory effects of halothane and isoflurane on fluoride release and cytochrome P-450 loss caused by metabolism of 2-chloro-1,1-difluoroethene, a halothane metabolite.

The structural similarity of the halothane metabolite, 2-chloro-1,1-difluoroethene (CDE), to haloethenes that are metabolized by and inactivate cytochrome P-450, suggests that CDE may undergo secondary metabolism and degrade these isozymes. This possibility was examined in hepatic microsomes by determining fluoride release and cytochrome P-450 loss due to CDE metabolism in the presence of several anesthetics. CDE alone decreased cytochrome P-450 from phenobarbital-treated rats by as much as 37%, but the addition of isoflurane or halothane to incubations containing CDE increased the loss of cytochrome P-450 nearly twofold. Fluoride release was enhanced approximately 2.5 to 3 times by halothane or isoflurane; however, fluroxene inhibited fluoride release and did not enhance the loss of cytochrome P-450. Extrapolation of these results to the clinical situation suggests that the metabolism of CDE produced during halothane anesthesia and the accompanying cytochrome P-450 loss may contribute to the inhibition of drug metabolism produced by halothane.

Animals↗
PubMed1986

Informed consent for research. Effects of readability, patient age, and education.

Comprehension of informed consent materials from a study of psychological variables associated with chest pain was evaluated as a function of age (27 to 69 years), education (5 to 20 years), and readability of information [low (college level) versus high (7th grade)]. The potentially confounding effect of memory was eliminated by allowing patients to use the written information sheets to find answers to the multiple choice test. Feedback and a repeat test were provided if any answers were incorrect. The findings indicated that comprehension varied inversely with age and directly with education. It is suggested that while ensuring informed consent may be difficult for all volunteers, it may be a critical problem for elderly patients with low education. The effects of readability were not consistent, suggesting that simplifying informed consent materials by shortening words and sentences may not, by itself, be sufficient to improve comprehension.

Adult↗
PubMed1985

The formation of chlorobenzene and benzene by the reductive metabolism of lindane in rat liver microsomes.

The major metabolite produced by incubating [14C]lindane with rat liver microsomes under anaerobic conditions was determined to be chlorobenzene, with lesser amounts of benzene also being formed. Using relatively high lindane concentrations (250 microM), four nonvolatile metabolites of lindane were also produced anaerobically, the predominant one being identified by mass spectrometry as tetrachlorocyclohexene (TCCH). TCCH, likewise, was reduced to chlorobenzene and benzene in microsomes under anaerobic conditions. Binding of [14C]lindane to microsomal protein occurred under aerobic as well as anaerobic incubation conditions; however, lindane protein binding was greatest in anaerobic incubations compared to those containing an atmosphere of air or 100% oxygen. Hemin reduced by dithionite also readily produced chlorobenzene and benzene from lindane. These results indicate that lindane interacts readily with heme and heme proteins, including cytochrome P-450, in the absence of oxygen to undergo multiple chloride eliminations forming chlorobenzene and benzene as end products.

Animals↗
PubMed1984

Metabolism-dependent binding of the chlorinated insecticide DDT and its metabolite, DDD, to microsomal protein and lipids.

Dichlorodi[U-14C]phenyltrichloroethane ( [14C]DDT), incubated with rat hepatic microsomes and NADPH, produced reactive intermediates which covalently bound to microsomal protein and lipids. In atmospheric oxygen, DDT bound to microsomal protein; however, binding was increased up to approximately 70% by oxygen depletion. Low levels of [14C]DDT binding to microsomal lipids occurred under atmospheric oxygen but, in contrast to protein binding, DDT-phospholipid binding was increased up to 20-fold by oxygen depletion. Dichlorodiphenyldichloroethane (DDD) was rapidly formed from DDT under anaerobic conditions, although when DDD was utilized as substrate, binding to microsomal protein occurred only in the presence of oxygen. Sodium dithionite, added to microsomes, produced [14C]DDT phospholipid and protein binding, and DDD formation, but failed to support DDD metabolism or binding. The data are consistent with the reductive formation of a DDT free-radical intermediate that led to the formation of DDD and that was bound preferentially to microsomal lipids.

Animals↗
PubMed1984

Reductive halothane metabolite formation and halothane binding in rat hepatic microsomes.

The production of the reductive [14C]halothane metabolites, 2-chloro-1, 1,1-trifluoroethane ( CTE ) and 2-chloro-1,1- difluoroethylene (CDE), was determined in anaerobic microsomal incubations by high pressure liquid chromatography (HPLC). The HPLC technique used allowed accurate measurements of low levels of [14C]halothane metabolites. Comparisons of metabolic profiles and halothane binding in microsomes reduced with NADPH and sodium dithionite show that dithionite stimulates CDE production and total halothane degradation, but inhibits CTE formation and [14C]halothane binding. Similarly, the addition of isoflurane, but not enflurane, to microsomes increases CDE production and decreases CTE formation and [14C]halothane-lipid binding. Measurement of fluoride in similar incubations show that fluoride release from halothane correlates with the formation of CDE and not CTE . The results demonstrate that the relative production of CTE and CDE may not remain constant in microsomal preparations, and that halothane binding correlates with CTE formation and not CDE and fluoride production.

Animals↗
PubMed1984

Effect of thiamin deprivation on the in vitro metabolic activation of benzo(a)pyrene.

Feeding a thiamin-deficient diet to male and female rats for 3 weeks alters the mixed function oxidases responsible for metabolizing benzo(a)pyrene and enhances the response of these enzymes to induction by phenobarbital or 3-methylcholanthrene. The caloric restriction observed in thiamin deprivation may be partially responsible for the enhanced metabolism in this condition but, as established in pair-feeding studies, was not responsible for the enhanced response to enzyme inducers seen in these animals. The degree of altered response was also seen to depend on the sex of the rat and on the substrate concentration of the incubation mixture.

Animals↗
PubMed1983

Readability of informed consent forms for research in a Veterans Administration medical center.

This study examined the effects of federal regulations on the readability and length of consent forms used in medical research from 1975 through 1982. Materials evaluated were 49 information sheets from four sample time periods and the 1975 and 1979 revisions of the Veterans Administration consent document. Flesch readability scores were at college level for both the consent documents and information sheets from all sample time periods. Thus, consent forms always may have been too difficult for typical volunteers to comprehend. Changes in length and content of the consent documents suggest that difficulty levels actually may have increased since 1975. Efforts to protect the rights of research subjects through federal regulations have resulted in presentation of appropriate information, but little progress has been made in ensuring that the information is comprehensible, understood, and used.

Behavioral Research↗
PubMed1983

The effect of repeated testing upon comprehension of informed consent materials by elderly volunteers.

One hundred elderly adults (mean = 71.3 years of age, range = 59-88 years) in four WAIS vocabulary subgroups (less than 40, 40-49, 50-59, greater than or equal to 60) served in an evaluation of the effects of using multiple comprehension test trials to improve informed consent procedures. Participants in Group I were given a single comprehension test and feedback before signing consent documents, while those in Group II were provided with as many as three comprehension trials, if necessary. All participants were tested for memory of the information 2-3 weeks later. Results indicated that both comprehension and memory performance varied directly with vocabulary level. The multi-trial approach improved comprehension scores at all vocabulary levels, but had no effect upon memory.

Aged↗