Biomedical subjects
Publications and source records attributed to M Gilbert.
A selected review of the literature about short-term therapy and social skills as they may apply to depressed adolescents is presented. Two forms of group therapy are described. These are social skills and a traditional discussion group format. Some of the difficulties in establishing and evaluating a group therapy program are outlined.
This study examined global hemodynamic responses to increasing concentrations of halothane and isoflurane in pigs with an acute critical coronary stenosis (CCS) on the left anterior descending coronary artery (LAD). The CCS was caused by graded inflation of an hydraulic occluder to the point where no hyperemic response was observed following a 10 sec. total LAD-occlusion. A minute, piezoelectric epicardial Doppler probe applied without dissection was used to monitor the stenosis. Previously reported minimum alveolar concentrations (MAC) were used as endtidal concentrations ([ Et]). The [Et] was increased stepwise until each animal died. Recordings obtained in this study were compared to recordings obtained during similar stepwise increments of these anesthetics in pig preparations without CCS. Isoflurane had a significantly less depressant effect on global hemodynamics compared to halothane and caused death at higher MAC than halothane in either case. A critical LAD-stenosis caused no major changes in the general dose-response pattern of isoflurane but further aggravated the depression of cardiac output and stroke volume induced by increasing concentrations of halothane.
Percutaneous absorption has received comparatively little attention in occupational health, although this route of entry has repeatedly caused occupation-related intoxications. In practice, the evaluation of skin penetration rates is far from simple. Much evidence has been obtained from studies of chemicals used for cosmetics and topical therapeutics, but the information available on compounds encountered in occupational health is limited. The data obtained from experimental studies have confirmed that the concentration, type of vehicle, skin area, skin condition, and extent of occlusion are important factors in determining the degree of percutaneous absorption, but no general model has been developed. Also, too little is known about the basic chemical properties governing the rate of penetration. Thus, prediction is difficult and bound to be rather inaccurate. Current preventive practice follows the procedure used by ACGIH and is mainly based on a "skin" denotation in official listings of chemicals to which exposure limits have been allocated. The number of substances and groups of chemicals which have received skin denotation in 17 selected countries varies between 24 and 179 and a total of 275 are listed as a skin hazard in one or more countries; ACGIH lists 143. Thus, the denotation practice varies. As an unfortunate result of these discrepancies and the dichotomy of skin denotation, the absence of skin denotation may erroneously indicate that efforts to protect the skin are unnecessary. Thus, an evaluation of skin penetration potentials should be incorporated in occupational health practice as a supplement to the official denotations.
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The effects of fasting on maternal glucose metabolism were investigated in nonpregnant and 29-day pregnant conscious rabbits. Pregnancy decreased the glucose metabolic index by 60% in maternal red postural muscles. Fasting induced similar modifications in nonpregnant rabbits and exaggerated the changes observed in fed pregnant animals. These data suggest that the decreased glucose utilization by maternal red muscles observed during pregnancy and fasting is related to the increase in circulating fat-derived substrates, because the fall in plasma insulin concentration is a specific adaptation to fasting.
In utero, glucose utilization by fetal muscles (heart and hindlimb) displays important interspecies differences. In the fed state, it is 5-fold higher in rat than in rabbit fetal muscles. Maternal fasting induces a decrease in glucose utilization in fetal muscles of the rat but not of the rabbit.
To assess the dose-response effects of isoflurane and halothane anesthesia on hemodynamics and coronary artery reactivity, the authors studied myocardial hyperemic responses following brief single artery flow arrests in 21 open chest, isocapnic swine in which arterial blood pressures and cardiac outputs were recorded. A specially designed Doppler probe was used to measure the peak and time course of coronary blood flow velocity in the left anterior descending coronary artery (LAD) after 15-s LAD occlusions. The ratio of peak velocity of blood flow to resting velocity (coronary reserve), relative repayment of flow debt, and duration of hyperemic responses were studied. Surgery was performed at MAC end-tidal concentrations ([Et]isoflurane = 1.45%. [Et]halothane = 1.25%) of isoflurane (n = 7) or halothane (n = 7), and recordings were made after 15-min steady state [Et]agent at 0.5, 1, 1.25, 1.5, 1.75, 2 MAC, and further 0.5 MAC increments until the demise of each animal. To compare coronary reactivity at similar coronary pressures, an aortic snare was used to elevate arterial pressures in a third group of halothane anesthesized pigs (n = 7) to those in the previously studied isoflurane group at each MAC level. There were three major differences between halothane and isoflurane. First, cardiac depression (reduction in arterial pressure, cardiac output, and stroke volume) was less with isoflurane compared with halothane anesthesia. Second, with halothane anesthesia, there was a marked decrease in coronary reactivity independent of coronary perfusion pressures with marked, dose-dependent reductions in both coronary reserve and relative flow repayment. During isoflurane anesthesia, coronary reactivity and coronary reserve was well preserved within physiologic limits up to 1.75 MAC [Et]. Third, halothane anesthesized pigs died in cardiac collapse at much lower agent concentrations than with isoflurane (no animals survived 1.75 MAC halothane, whereas all animals survived 2.5 MAC isoflurane). Therefore, pigs anesthesized with isoflurane had greater coronary reserve, better preserved cardiac function, and greater tolerance to increasing agent concentration than pigs anesthesized with halothane.
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Glucose utilization by the placenta and individual fetal tissues was studied in vivo in conscious pregnant rabbits at 29 days of gestation. In the fed state, the rate of glucose utilization was similar in the placenta and the gravid uterus, suggesting that the rate of fetal glucose utilization was approximately 40 nmol/min/g. A 96-h maternal fast induced a significant decrease in glucose utilization by the myoendometrium and in the glucose utilization index by fetal liver and brown adipose tissue. No modification was observed in other fetal tissues. These results indicate that glucose utilization by the placenta and the whole fetus from 96-h fasted rabbits does not decrease despite profound changes in endocrine and metabolic maternal parameters.
The production rate, the disappearance rate and the half life of calcitriol in gravid rabbit does at 24 days of gestation were compared, under unstressed steady state conditions, to those of nonpregnant animals. The contribution of the fetoplacental unit to the circulating levels of fetal calcitriol was also assessed. The calcitriol levels (139.6 +/- 19.9 vs 55.3 +/- 8.8 pmol/l and production rates (113.9 +/- 8.8 vs 59.2 +/- 9.2 pmol/min/Kg) were higher in pregnant than in nonpregnant animals (P less than 0.01). However, clearance rates (1.07 +/- 0.18 vs 1.12 +/- 0.20 ml/min/Kg and circulating half life (442 +/- 49 vs 368 +/- 35 min; NS) were similar in both groups of animals. Fetal levels (62.3 +/- 1.6 pmol/l) and specific activity (11166 +/- 864 dpm/pmol) of calcitriol were lower than those of the respective mothers (P less than 0.005). Taken together these data suggest that, calcitriol is transported through the placenta; and that the fetoplacental unit contributes to the fetal and perhaps to the maternal calcitriol levels.
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To better define the function of Saccharomyces cerevisiae SSB1, an abundant single-stranded nucleic acid-binding protein, we determined the nucleotide sequence of the SSB1 gene and compared it with those of other proteins of known function. The amino acid sequence contains 293 amino acid residues and has an Mr of 32,853. There are several stretches of sequence characteristic of other eucaryotic single-stranded nucleic acid-binding proteins. At the amino terminus, residues 39 to 54 are highly homologous to a peptide in calf thymus UP1 and UP2 and a human heterogeneous nuclear ribonucleoprotein. Residues 125 to 162 constitute a fivefold tandem repeat of the sequence RGGFRG, the composition of which suggests a nucleic acid-binding site. Near the C terminus, residues 233 to 245 are homologous to several RNA-binding proteins. Of 18 C-terminal residues, 10 are acidic, a characteristic of the procaryotic single-stranded DNA-binding proteins and eucaryotic DNA- and RNA-binding proteins. In addition, examination of the subcellular distribution of SSB1 by immunofluorescence microscopy indicated that SSB1 is a nuclear protein, predominantly located in the nucleolus. Sequence homologies and the nucleolar localization make it likely that SSB1 functions in RNA metabolism in vivo, although an additional role in DNA metabolism cannot be excluded.
Insulin sensitivity of maternal nonuterine tissues (liver and skeletal muscles) has been investigated in the conscious rabbit during late gestation (24 and 30 days). The specific effect of insulin on glucose production and utilization was evaluated with the hyperinsulinemic euglycemic clamp technique. The net balance of glucose across the hindlimb muscles was studied by means of the Fick principle in basal and insulin stimulated conditions (clamp study). Our results show that an insulin-resistant state develops between days 24 and 30 of gestation in the rabbit and involves both glucose producing (liver) and utilizing (muscles) tissues. On day 30 of gestation, muscle glucose uptake was not significantly stimulated at a plasma insulin concentration of 700 microU/ml, whereas it was stimulated by 30-40% in nonpregnant and 24 day pregnant rabbits. At similar plasma insulin concentration, endogenous glucose production was suppressed by 85% in both nonpregnant and 24 day pregnant rabbits, whereas it was decreased by only 30% in 30 day pregnant rabbits. The present data suggest that hindlimb muscles of late pregnant rabbits are able to reduce their insulin-induced glucose utilization. This could contribute to meet the glucose requirements of pregnant uterus in late gestation.
The present study was designed to develop the techniques for chronic catheterization of the hepatic and portal venous circulation in conscious rabbits and to apply these techniques to a study of hepatic metabolism in this species. Experiments were made after an 18-h fast and for 4 h after the initial feeding. Measurements of arteriovenous differences of substrates were combined with measurements of hepatic and gastrointestinal blood flow. Hepatic glucose production was suppressed by 60% at 1 h and had returned to control levels by 4 h. The hepatic uptake of lactate declined slightly at 1 h and had returned to control level 2 h after the meal. There was a marked and rapid fall in hepatic ketone body output after refeeding. Although amino acid concentrations displayed a transient increase 1 h after the meal, only the arterial concentration of branched-chain amino acids remained significantly elevated for 4 h. The total hepatic uptake of the gluconeogenic amino acids (alanine, serine, threonine) remained constant. Refeeding resulted in a doubling of arterial insulin concentrations at 1 h followed by a progressive decline over the next 3 h. It is concluded that in rabbits fed a mixed meal partial suppression of hepatic glucose output is mainly due to a decline in glycogenolysis rather than a decrease in gluconeogenesis, shortly after refeeding the liver is able to virtually shut off its ketone body production, the major gluconeogenic precursors (lactate, alanine, glycine, serine, and threonine) may contribute to approximately 40% of the glucose release.(ABSTRACT TRUNCATED AT 250 WORDS)
The activities of three key enzymes of glycerol metabolism were measured in liver samples from 37 human fetuses ranging in gestational age from 18 weeks to term, from neonates (1-3 days) and from infants to 2 years. Glycerol kinase specific activity was constant throughout the period of fetal development examined, and was comparable to that measured in neonates and infants. However, the subcellular distribution of the activity changed markedly, being predominantly particulate in fetal samples and cytoplasmic in postnatal samples. The particulate activity had an elevated Km for glycerol. Cytoplasmic glycerol-3-phosphate dehydrogenase activity was very low in the fetal period, and then rose to adult levels during infancy. There were no kinetic differences between the fetal and postnatal activities. Mitochondrial glycerol-3-phosphate dehydrogenase activity rose somewhat after birth to near adult levels. The data indicate that glycerol can be metabolized by human fetal, neonatal and infant liver.
The present study provides some metabolic features of the gravid uterus in the nonanesthetized gilt during the last fourth portion of pregnancy. Substrate and oxygen arteriovenous differences across the uterus were determined in eight gilts with chronically implanted arterial and uterine venous catheters. Glucose represents the main substrate taken up by the conceptus and glucose extraction amounts to 8.3 +/- 0.5%. By contrast, there is a constant release of lactate from the pregnant uterus. The coefficient of extraction of oxygen is 20.2 +/- 1.9%. Glucose plus lactate/oxygen quotient is high (1.3 +/- 0.2), suggesting that glucose alone is sufficient to account for the oxidative metabolism of the pig uterus. Nonesterified fatty acid and ketone body are not significantly extracted by the pig uterus whereas a significant amino acid extraction occurs in late pregnancy. Uterine uptake of amino acids depends on maternal arterial concentrations and a great part (78%) of this uterine uptake is represented by neutral amino acids and especially glutamine.
The fatal/anesthetic ratio (FAR) in 44 swine weighing 32.6 +/- 0.7 kg (SEM) was determined. Fatal anesthetic concentration (the numerator for FAR) was defined as the end-tidal concentration at which the pig lived at least 10 min, during experiments that involved step increments in anesthetic concentrations. Previously reported MAC was used as the "anesthetic" concentration (denominator) to determine FAR. Halothane was compared to isoflurane and the question of whether major surgery might reduce FAR was investigated. The major surgery groups included one open chest group with each volatile anesthetic studied during coronary reserve measurements, and two groups that had LAD critical coronary stenoses. Thus volatile agents were compared with vs without major surgery, and with vs without a critical coronary stenosis. The FAR for isoflurane was approximately double that of halothane. Further, addition of major surgery did not produce significant deterioration in FAR with isoflurane. In contrast, with halothane there was a significant (approximately 20%) decrease in FAR, despite values already only half that seen with isoflurane, when major surgery was added. Presence of a critical coronary stenosis was not associated with a worsened FAR for isoflurane or halothane. It was concluded that the fatal/anesthetic ratio for isoflurane in pigs is 1.9 times greater than that for halothane. Addition of major surgery did not affect FAR when isoflurane was the anesthetic but did when halothane was used. Critical coronary stenosis did not worsen FAR. Because these results are nearly identical with those reported previously in small mammals, the doubled safety margin seen with isoflurane may have clinical relevance.
We have explored various strategies for exploiting the yeast genetic and biochemical system for understanding DNA replication. Because of the long time that has intervened between the isolation of random replication mutants of yeast and the identification of the gene products affected, an alternative approach to elucidating the molecular basis of replication has been needed. One such alternative involves purifying replication proteins, isolating the genes encoding them, and constructing the appropriate mutant from the cloned gene. We have applied this "reverse genetics" strategy to three different replication activities: DNA polymerases, single-stranded DNA binding proteins, and proteins that bind to autonomously replicating sequence (ARS) elements.