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Biomedical subjects

K Hirst

Publications and source records attributed to K Hirst.

31 records · Page 2Linked to original sources
PubMed1991

Plasma and erythrocyte amino acids in mother and fetus.

Plasma (P) and whole blood (WB) amino acid concentrations were measured in arterial and venous blood of 9 mothers and their fetuses at elective cesarean section and compared to values obtained in 5 normal nonpregnant women. Erythrocyte (E) amino acid concentrations were calculated from P and WB concentrations. E/P ratios were significantly greater than 1.0 in all groups studied. Alanine, glycine, and serine presented E/P ratios significantly higher in pregnant women than in control nonpregnant women. Fetuses presented significantly lower E/P ratios for lysine than pregnant and nonpregnant women. Uterine arteriovenous amino acid differences were not significantly different from zero in both plasma and erythrocytes. Umbilical venous-arterial differences were significantly positive for most essential amino acids in plasma, whereas they were not significantly different from zero in erythrocytes. This finding suggests that erythrocytes do not play a major role in the transfer of amino acids from the placenta to the fetus.

Amino Acids↗
PubMed1990

The modulation of gap junctional communication by gossypol in various mammalian cell lines in vitro.

The effects of gossypol were examined in several cell lines including hamster V79 lung fibroblasts, WB-344 rat liver oval cells, human osteosarcoma cells and LC540 rat Leydig cells. Gossypol had little cytotoxic effects in these cell lines except at high concentrations. Plasma membrane integrity was maintained in LC540 except at high concentrations of gossypol. Gossypol did not increase mutational frequency as examined by the hypoxanthine guanine phosphoribosyl transferase and Na+,K(+)-ATPase loci in V79 cells. Gossypol inhibited gap junctional intercellular communication in some but not all of the cell lines. This selectivity might be the basis for the sensitivity of certain tissues or organs to gossypol. For example, the Leydig cell, which is the component of a target organ system for toxicity, was sensitive to gossypol. Modulation of gap junctional functions might play a significant role in both pharmacological and toxicological effects of gossypol.

Animals↗
PubMed1990

Fetal hind limb oxygen consumption and blood flow during acute graded hypoxia.

Hind limb blood flow and O2 uptake, mean blood pressure, and heart rate were measured in six fetal sheep at 127-141 d gestation in the control state and at different levels of hypoxia that were induced by partial occlusion of the maternal terminal aorta. Blood flow was measured by an ultrasonic flow transducer. Control fetal arterial O2 content ([O2]a) in the descending aorta was 3.25 + 0.17 mM. In response to graded acute hypoxia, blood flow first increased (22.2 versus 19.9 mL.min-1.100 g-1, p = 0.003) and then decreased abruptly at approximately 1.5 mM [O2]a.O2 uptake decreased about 12% (14.74 versus 16.71, p = 0.03) as [O2]a decreased to 1.5 mM, and then fell markedly, tending toward zero for [O2]a = 0.9 mM. In the 2.7- to 1.5-mM [O2]a range, heart rate increased above control (194 versus 169 min-1, p = 0.0024), whereas mean blood pressure did not change significantly. For [O2]a less than 1.5 mM, heart rate decreased to 148 min-1 (p = 0.0005) and mean blood pressure increased above baseline (55 versus 47 torr, p = 0.0001). In conjunction with previous evidence, these results define a state of acute moderate hypoxia in which the whole fetus can sustain a relatively high rate of oxidative metabolism, and a state of acute severe hypoxia ([O2]a between 1.5 and 1.0 mM) in which O2 uptake by some fetal organs is selectively and markedly decreased.

Animals↗
PubMed1989

Effects of glucose and insulin on fetal glucose oxidation and oxygen consumption.

Glucose and insulin clamp experiments were performed in late-gestation fetal lambs to quantify the separate and combined effects of physiological concentrations of fetal glucose (G; 7.3-62.6 mg/dl) and insulin (I; 2-119 uU/ml) on fetal glucose metabolism and O2 consumption. Fetal glucose utilization rate (GUR) varied from 2.82 to 15.12 mg.min-1.kg-1. Fetal CO2 production from fetal glucose carbon oxidation (CO2Pr) varied from 32 to 234 mumol.min-1.kg-1 and was directly related to G and I [CO2Pr = -0.00868 + 0.00578 (G) + 0.000901 (I) - 0.0000619 (G)2, r = 0.88] and to GUR (CO2Pr = 0.0159 GUR - 0.0130, r = 0.89). CO2Pr accounted for 54.7% of the mean GUR and for 35.9% of the mean umbilical O2 uptake (UO2U), ranging from 26.0% in the control studies to 36.5% in hyperinsulinemic-euglycemic studies and to 45.1% in hyperinsulinemic-hyperglycemic studies. UO2U varied from 0.200 to I [UO2U = 0.303 + [0.000813 (G)] + [0.0000461 (I)], r = 0.89] and to GUR (UO2U = 0.0098 GUR + 0.275, r = 0.91). These results define independent (additive) effects of G and I on glucose oxidation in the late gestation fetal lamb and demonstrate the necessity for considering the levels of both G and I when studying these aspects of fetal metabolism.

Animals↗
PubMed1988

A heat shock element in the phosphoglycerate kinase gene promoter of yeast.

The phosphoglycerate kinase (PGK) promoter is often employed in yeast expression vectors due to its very high efficiency. Its activity in unstressed cells has been shown to be due to an upstream activator site (UASPGK) at -402 to -479. Since levels of PGK mRNA can sometimes be elevated by heat shock of yeast cultures this investigation determined how specific deletions of PGK promoter sequences effect levels of PGK mRNA both before and after heat shock. A series of PGK promoter deletions was inserted on a high copy plasmid into cells having a TRP1 gene disruption of the solitary chromosomal PGK locus. This enabled PGK transcripts of plasmid and chromosomal origin to be distinguished by virtue of their different sizes. Certain deletions lacking UASPGK displayed activities that were very low in unstressed cells, but which increased fifty to one-hundred fold after heat shock. With UASPGK present heat shock had only a relatively small or negligible effect on PGK mRNA levels. Heat shock activation was abolished when the -256 to -377 region with homology to the heat shock element consensus of eukaryotes was deleted in addition to UASPGK, but was unaffected by the deletion of regions further downstream containing TATA- and CAAT- sequence motifs. This is the first demonstration of a heat shock element, an activator site normally found upstream of eukaryotic heat shock protein genes, as a natural constituent of a high efficiency glycolytic promoter. It is proposed that PGK may be one member of a small subset of yeast genes that are highly expressed in unstressed cells yet possess a heat shock element to ensure their continued transcription after heat shock.

Base Sequence↗
PubMed1988

Catabolite control of the elevation of PGK mRNA levels by heat shock in Saccharomyces cerevisiae.

Heat shock enhances the very high level of transcription of the phosphoglycerate kinase (PGK) gene in fermentative cultures of Saccharomyces cerevisiae. This response of PGK mRNA levels was not found on gluconeogenic carbon sources, and could be switched on or off subject to availability of fermentable carbon source. The addition of glucose to yeast growing on glycerol resulted in acquisition, within 30-60 min, of the ability to elevate PGK mRNA levels after heat shock. In addition, in aerobic cultures growing on glucose the exhaustion of the medium glucose coincided with a loss of the heat-shock effect on PGK mRNA and a switch-over to slower growth by aerobic respiration. Levels of hsp26 mRNA were analysed during these experiments. Contrasting with this requirement for fermentable catabolite for manifestation of a heat-shock response of PGK mRNA levels, the PGK enzyme was not synthesized at a greater level in heat-shocked fermentative than in gluconeogenic cultures. PGK is one of only a few proteins made efficiently after mild heat shock of yeast. Thus, heat-stress-induced elevation of PGK mRNA levels does not appreciably increase PGK synthesis during exposure to high temperatures and so its role may be to assist cells repressed in mitochondrial function during recovery following a heat shock.

Aerobiosis↗
PubMed1988

Effects of insulin and glucose concentrations on glucose utilization in fetal sheep.

Glucose and insulin clamp experiments were performed in vivo in chronically catheterized, late-gestation fetal lambs to quantify the effects of glucose and insulin on fetal glucose metabolism. Fetal glucose uptake from the placenta via the umbilical circulation (umbilical glucose uptake) was measured by application of the Fick principle, and fetal glucose utilization rate (GUR) was measured using [U-14C]glucose tracer. Fetal plasma insulin concentrations ranged from 2 to 119 microU.ml-1 and fetal blood glucose concentrations ranged from 7.3 to 62.6 mg.dl-1. GUR varied from 2.82 to 15.12 mg/min/kg and the exogenous glucose entry rate (umbilical glucose uptake + glucose infusion) varied from 2.46 to 13.95 mg/min/kg. The mean GUR [6.53 +/- 0.28 (SEM) mg/kg/min] was not different from the mean exogenous glucose entry rate [6.29 +/- 0.30 (SEM) mg/kg/min]. Multiple linear regression analysis on a glucose-by-insulin surface demonstrated a best-fit model of fetal glucose utilization following the quadratic equation: GUR = -0.322 + [0.289 (glucose)] + [0.108 (insulin)] - [0.00319 (glucose)2] - [0.000673 (insulin)2], r = 0.883 (all terms significant at p less than 0.02). This model predicted a GURmax of 10.56 mg/min/kg at blood glucose concentration = 45.3 mg/dl and plasma insulin concentration = 80 microU/ml and Km values for blood glucose concentration and plasma insulin concentration of 20.6 mg/dl and 10 microU/ml, respectively. According to this model, the glucose and insulin effects were additive. Furthermore, change in GUR was not proportionate to change in glucose concentration, accounting for a decreasing metabolic clearance rate at higher glucose concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Saccharomyces cerevisiae mRNA populations of different intrinsic stability in unstressed and heat shocked cells display almost constant m7GpppA:m7GpppG 5'-cap structure ratios.

The half-lives of mRNAs in yeast vary from about 1 to over 100 min. While mRNA stabilities must strongly influence overall gene expression in this organism, very little is known about how they are determined. Labellings of yeast cells were conducted to investigate whether the 5'-cap structures of yeast mRNAs might influence their stability. Variation of the pulse-labelling period from 7.5 min to 120 min did not have any major influence on the relative labelling of m7GpppA (A cap) and m7GpppG (G cap) in total polyadenylated RNA. Whether an mRNA has the A cap or the G cap does not therefore have a marked effect on its stability. During the heat shock response the relative labelling of A caps to G caps in total polyadenylated RNA also does not fluctuate appreciably. This indicates that cap structure alone does not determine the destabilisation of non-heat shock mRNAs and stabilisation of heat shock mRNAs during this stress response.

Heat-Shock Proteins↗
PubMed1984

Inhibition of cis-diamminedichloroplatinum secretion by the human kidney with probenecid.

The renal handling of cis-diamminedichloroplatinum (CP) was investigated by measuring the renal clearance of creatinine, inulin, and free platinum in ten cancer patients. Free platinum clearances exceeded the glomerular filtration rate in all time periods. For example, at 1 to 2 hr, the mean clearance of free platinum was 224 +/- 32 (S.E.) ml/min compared to a mean creatinine clearance of 94 +/- 15 ml/min or a mean inulin clearance of 94 +/- 17 ml/min (p less than 0.01), indicating secretion of CP or a metabolite. Seven additional cancer patients were treated with probenecid prior to CP. Fractional platinum clearances, calculated as a ratio of free platinum clearance to creatinine clearance, were reduced significantly in the probenecid-treated group (158 +/- 17%) compared to controls (270 +/- 57%) (p less than 0.03). Fractional platinum clearances, calculated as a ratio of free platinum clearance to inulin clearance, were also significantly reduced in the treated group (154 +/- 14%) compared to controls (271 +/- 47%) (p = 0.04). These results suggest that cisplatin is secreted by the human kidney, and this can be inhibited by probenecid. Such maneuvers may be helpful in improving the therapeutic index of this important chemotherapeutic agent.

Cisplatin↗
PubMed1979

Ambient carbon monoxide levels and acute cardiorespiratory complaints: an exploratory study.

Over a 92-day seasonally excessive period of ambient carbon monoxide (CO), chief cardiorespiratory complaints (CRC) of a nontraumatic origin were identified from each of 8,556 patient encounters at the Emergency Room of Colorado General Hospital. Excessive numbers of CRC were seen above a CO level of 5 ppm for the 24-hour mean and 11 ppm for the one hour mean maximum ambient CO (p less than 0.05 for both). Increasing relative risk was shown by comparing daily numbers of CRC with its mean in two-day trend analyses with both ambient CO measures above and below these thresholds. Other ambient pollutants were generally low during the winter period studies. These findings suggest an association between health effects and lower levels of CO than has been previously reported.

Air Pollutants↗
PubMedDate not supplied

Worksite cancer screening and nutrition intervention for high-risk auto workers: design and baseline findings of the Next Step Trial.

BACKGROUND: This article describes the design and baseline findings of The Next Step Trial, a health promotion intervention targeting automobile industry employees at increased colorectal cancer risk. The intervention encouraged colorectal cancer screening participation and adoption of low-fat, high-fiber diets. METHODS: Twenty-eight worksites (n = 5,042) were randomized to control (a company-sponsored screening program) or intervention (an enhanced screening program including a personalized educational booklet and motivational telephone call and diet-change program including nutrition classes, self-help materials, and computer-generated personalized feedback). Outcomes included screening compliance and fat and fiber intake. RESULTS: Pretrial data indicated targeted employees were predominantly older, well educated, married, Caucasian men. Sixty-one percent (SE = 2) participated in the screening program in the preceding 2 years, and 24% (SE = 1) reported a history of colorectal polyps or cancer. Fifty-eight percent of the cohort responded to the baseline questionnaire; respondents were older and more educated; more were married, retired, and Caucasian than nonrespondents. Mean dietary intakes were 36.9% energy from fat (SE = 0.21), 8.8 g fiber/1000 kcal (SE = 0.07), and 3.4 servings of fruits and vegetables per day (SE = 0.04). CONCLUSIONS: Baseline data show moderate screening participation and dietary intakes that did not meet guidelines; hence intervention efforts were warranted. Data from this trial will support a rigorous test of whether this high-risk employee population is responsive to targeted health promotion, early cancer detection, and prevention interventions.

Automobiles↗
PubMedDate not supplied

Temporal profile of connexin 43 mRNA expression in a tetanus toxin-induced seizure disorder.

The messenger ribonucleic acid (mRNA) of gap junction protein connexin 43 was quantified in the tetanus toxin rat model of focal epilepsy following injection of toxin into the left amygdala. Animals were monitored electrographically at weekly intervals with bilateral amygdala electrodes. Cohorts of 3 rats were sacrificed at weeks 1, 2, 3, 4, 6, 8, and 10, and bilateral regions containing the amygdala and posterior cerebral cortex were sampled, frozen, and later pooled for northern blot analysis. Spike generation was manifest in all animals during the first 4 wk followed by variable attenuation and cessation by 10 wk. Electrode implantation alone was shown by regression analysis to cause significant (p < 0.05) elevation of connexin mRNA in weeks 1-4. Injection of toxin diminished connexin mRNA expression in the amygdala when compared to electrode implantation alone. No trend in connexin mRNA expression was established over time in either amygdala or cerebral cortex in the acute epileptic or chronic postepileptic phase. No association between connexin 43 mRNA expression and the development of epileptogenicity was found in the context of a self-limiting animal model of focal epilepsy.

Amygdala↗