Bioassay of pesticides and industrial chemicals for tumorigenicity in mice: a preliminary note.
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Animals↗
Biomedical subjects
J Peters
Publications and source records attributed to J Peters.
Onset of cerebral electrical activity associated with behavioral sleep and attention in the developing chick.
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Animals↗
[Metabolism of xanthates in man and in guinea pigs].
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Animals↗
Effects of arginine-vasopressin on regional blood volume distribution in supine humans.
In healthy humans, the increase in arterial blood pressure seen in patients with autonomic dysfunction in response to exogenous vasopressin (AVP) is abolished. We tested the hypothesis that redistribution of blood from the intra- to the extrathoracic vascular compartment might contribute to this buffer response. Regional distribution of 99mTc labeled autologous red cells was assessed in healthy supine volunteers (n = 7) during arginine-vasopressin administration (1 ng.kg-1 bolus i.v. followed by a 14-min infusion of 3 ng.kg-1 x min-1), along with arterial and central venous pressures, and heart rate. Exogenous vasopressin increased plasma vasopressin concentration from 4.0 +/- 1.4 SEM to 91 pg.ml-1 +/- 12. Thoracic counts increased slightly but significantly by 2.2% +/- 0.9, while global abdominal counts remained unchanged. Most surprisingly, counts in the liver markedly increased (+8.1% +/- 1.8, p = 0.02), but significantly decreased in the spleen (-3.1% +/- 1.4). Intestinal (-2.5% +/- 2.4) and limb counts did not change significantly. Consistent with the increase in thoracic counts central venous pressure increased from 3.6 mmHg +/- 1 to 4.7 +/- 1 (p = 0.02), while arterial pressure and heart rate did not change. All changes reversed towards baseline when vasopressin administration ceased. Thus, in humans with an intact autonomic system, vasopressin, at concentrations observed during hypotension, increases liver and, albeit to a small extent, also thoracic blood volume, but decreases splenic blood content. These results: 1) are incompatible with the hypothesis that AVP induces a shift of blood from intra- to extrathoracic capacitance vessels, and 2) show that AVP increases rather than decreases central blood volume.
Adult↗
Atrial natriuretic peptide decreases hepatic and cardiac blood content, but increases intestinal blood content in supine humans.
The authors evaluated in humans whether atrial natriuretic peptide (ANP) alters the regional distribution of blood in capacitance vessels. Eight healthy male volunteers (mean age: 30 years, range: 24-39) were studied twice. On different days and in a randomized, double blind fashion they received either alpha h-ANP (99-126), 25 micrograms intravenously followed by infusion of 0.1 microgram kg-1 min-1, or vehicle. Changes of regional blood content in heart, liver, and intestine were evaluated at 3-min intervals using autologous radioactively (99mTc) labeled red cells. Calf circumference (strain gauge), central venous pressure, and heart rate were recorded continuously while arterial pressure (oscillometry), hematocrit, ANP and cGMP plasma concentrations were determined intermittently. Exogenous ANP increased plasma concentrations of ANP (49 pg ml-1 +/- 8 SE to 614 +/- 190) and cGMP (1.7 pmol ml-1 +/- 0.2 to 30.8 +/- 4.4). This elicited significant and profound decreases in liver (-11%) and cardiac (-10%) radioactivity, contrasted by a smaller but significant increase (+4%) of intestinal radioactivity. These changes became gradually apparent about 15 min during ANP administration and reached their nadir at the end of the infusion period. Central venous pressure significantly decreased by 3.4 cm H2O and calf volume by 0.3 ml/100 ml while hematocrit increased by 2.6%. All changes were at least partly reversed when ANP administration ceased. Of note, two subjects developed a near syncope with abrupt bradycardia and arterial hypotension following an initial gradual decrease in cardiac counts and central venous pressure. We conclude that in humans ANP markedly alters the regional blood distribution in the capacitance vasculature as blood content decreased profoundly in both heart and liver, but increased in the intestine, albeit to a lesser extent. Accordingly, a redistribution of blood away from the heart represents another unique mechanism by which ANP can exert its cardiovascular actions.
Adult↗
Vaginal Ureaplasma urealyticum colonization: influence on pregnancy outcome and neonatal morbidity.
The effects of Ureaplasma urealyticum colonization on pregnancy and neonatal outcome was prospectively studied in women with impending term or preterm delivery. One hundred and seventy women colonized with U. urealyticum as the only pathogenic microorganism and 83 women with negative cultures were enrolled for study. Compared to the controls, U. urealyticum colonization was associated with a significantly increased rate of amnionitis (2% vs 35%; p < 0.001), chorioamnionitis (0% vs 10%; p < 0.05), premature rupture of membranes (12% vs 35%; p < 0.001) and preterm delivery (10% vs 41%; p < 0.001). The rate of vertical transmission ranged from 38% in term infants to 95% in very low birth weight infants. U. urealyticum colonization at birth was associated with an increased risk for the development of respiratory distress syndrome (9% vs 51%), intraventricular hemorrhage (1% vs 7%) and bronchopulmonary dysplasia (4% vs 17%) in very low birth weight infants (< 1500 g). It is concluded that maternal U. urealyticum colonization is associated with amnionitis, chorioamnionitis and preterm delivery, and that tracheal colonization with U. urealyticum increases the risk for respiratory and neurological complications in very low birth weight infants.
Adult↗
The Strecker stent: indications and results in iliac and femoropopliteal arteries.
We have implanted more than 100 Strecker stents in the iliac and femoral arteries. In iliac arteries, follow-up is available from 8 to 48 months (mean 20 months) and in peripheral arteries, from 8 to 32 months (mean 19 months). In iliac and proximal femoral arteries there was a patency rate of 98% (mean 20 months after stent implantation) whereas in peripheral arteries the patency rate was 70.8% (mean 19 months after stent implantation). Besides careful selection of patients, anticoagulation is very important for successful stenting. Because of the excellent results of stents in iliac vessels there is a wide range of good indications, including primary stenting after recanalization of occlusions. In contrast, stent implantation in peripheral vessels should be restricted to special cases such as acute dissection or reocclusion after successful recanalization.
Anticoagulants↗
Pharmacokinetic and pharmacodynamic aspects of concomitant mibefradil-digoxin therapy at therapeutic doses.
This study investigated the effect of mibefradil on digoxin pharmacokinetics an pharmacodynamics. Following a loading dose of digoxin (0.375 mg, three times, day 1), 0.375 mg was administered once daily to 40 healthy subjects (days 2-15). Mibefradil was administered daily at 50 mg, 100 mg, or 150 mg (days 9-15). With co-administration of 50 mg or 100 mg mibefradil (the recommended doses), mean digoxin Cmax values increased 1.19- and 1.32-fold, respectively; Cmin values were 0.95- and 1.04-fold, respectively; mean AUC0-24 h increased 1.05- and 1.11-fold, respectively; and the total amount of digoxin excreted in urine remained unchanged. Digoxin monotherapy produced modest but transient prolongations of PQ interval, small decreases in heart rate, and no changes in blood pressure. With the addition of mibefradil, no effects on trough blood pressure or cardiac index were observed, but there was a further increase in PQ interval and decrease in heart rate. In a previous study, mibefradil had no significant effect on trough plasma digoxin concentration in patients with congestive heart failure and ischemia. Therefore, while the vast majority of patients should not need their digoxin dosages adjusted when given mibefradil, an occasional patient may require dose reductions based on clinical response and plasma digoxin.
Adult↗
Sleep disturbance and computerized axial tomographic scan findings in former prisoners of war.
Ten drug-free former American prisoners of war (POWs), captured on Bataan and Corregidor by the Japanese in World War II, participated in a study of the relationship between structural brain abnormalities on computerized axial tomographic (CT) scans and sleep electroencephalographic (EEG) findings. All subjects had complaints of sleep disturbances and other posttraumatic stress disorder (PTSD)-related symptoms. Six of 10 subjects had no stage 4 sleep, and had significantly higher mean ventricular brain ratios (VBRs). Structural brain measures such as VBRs and global sulcal widening (GSW) correlated significantly with the number of awakenings; GSW also correlated significantly with time spent asleep. However, because data from normal age-matched controls are not available, it remains to be seen whether our findings are PTSD specific.
Aged↗
Neuropeptide Y-like immunoreactivity in schizophrenia. Relationships with clinical measures.
Neuropeptide Y-like immunoreactivity (NPY-li) was measured in CSF of 35 drug-free chronic schizophrenic patients. Compared to a group of drug-free controls, CSF NPY-li was significantly higher in these patients. CSF NPY-li decreased with age and longer duration of illness. Measures of structural brain abnormalities on CT scans were significantly associated with lower CSF NPY-li. Relationships between NPY-li and schizophrenic behavior, i.e. positive symptoms, were observed only in the clinically stable (nonrelapsed) drug-free patients. In 31 of the patients CSF was obtained before and after withdrawal from haloperidol maintenance treatment. This withdrawal from haloperidol treatment was associated with a significant increase in CSF NPY-li. There was no significant difference in CSF NPY-li between patients who did and those who did not relapse within 6 weeks following haloperidol withdrawal. The present findings suggest a relationship of CSF NPY-li with various aspects of schizophrenia.
Adult↗
Topology of the anion-selective porin Omp32 from Comamonas acidovorans.
Limited proteolysis experiments were performed with outer membranes from Comamonas acidovorans to probe the topology of its major protein component, the anion-selective porin Omp32. Proteinase K treatment above a critical temperature of 42 degrees C cleaved the surface-exposed regions of the porin, yielding membrane-embedded fragments which were separated by SDS polyacrylamide gel electrophoresis or reversed phase chromatography. The identification of the proteinase K-sensitive sites was performed by microsequencing. This allowed us to determine six surface-exposed sites of the porin, all located in nonconserved primary structure regions. These results along with the previously determined amino acid sequence and in conjunction with some structural constraints applicable to porins allowed us to propose a chain-folding model of the Omp32 porin. The features of our model are compared with the structure of the Rhodobacter capsulatus porin, recently established by X-ray crystallography (Weiss et al., 1991) and they are used to elucidate the structural basis of the anion selectivity.
Amino Acid Sequence↗
The association between body mass and health care expenditures.
With several studies estimating the health care costs attributable to obesity-related medical conditions, the economic consequences of being overweight are beginning to come into focus. The present study complements this growing body of literature by directly estimating health care costs across a broad range of body mass index values. Data were obtained from the 1987 National Medical Expenditure Survey (NMES) public use data tapes and retrospective analyses conducted on NMES Household Survey data only. The analyses included a total of 16,217 individuals between the ages of 18 and 65. Four classes of health care utilization and expenditures were derived using the NMES data: (1) use of any health care service and total health care expenditures, (2) use of inpatient services and inpatient expenditures, (3) use of outpatient services and outpatient expenditures, and (4) use of prescription medication and medication expenditures. Estimates based on our findings suggested strong relationships between body mass and the likelihood of using health care services and between body mass and average annual health care expenditures for both men and women. Increased body mass was associated with increased expenditures. However, this association was greater among males than among females and did not hold for individuals in the lowest body mass category. Ideal body mass was associated with 6.3% to 36.1% lower annual health care expenditures among females and 3.6% to 18.2% lower health care expenditures among males. The results of this set of analyses suggest that health care expenditures increase as weight deviates from the ideal-that is, health care expenditures among both underweight and overweight individuals in the United States were increased in relation to ideal weight. Separate analyses including weight-related diseases such as diabetes and hypertension indicated that body mass increased health care expenditures largely by increasing the risk for these costly chronic medical conditions.
Adult↗
Molecular-organization and biosynthesis of pigment-protein complexes of Rhodopseudomonas capsulata.
The photosynthetic apparatus of the facultative phototrophic bacterium Rhodopseudomonas capsulata contains three bacteriochlorophyll-carotenoid-protein complexes: the reaction center and the light-harvesting (LH) antenna complexes LHI (B870) and LHII (B800--850). In contrast to green anoxygenic phototrophic bacteria and the oxygenic cyanobacteria, the light-harvesting complexes of Rhodospirillaceae and Chromatiaceae are integral membrane particles. Variations in light fluxes induce membrane differentiation mainly expressed as variations in the size of the photosynthetic unit and in the area of intracytoplasmic membrane per cell. The B800--850 complex is the variable part of the photosynthetic apparatus. Synthesis of bacteriochlorophyll and of the polypeptides of the pigment complexes was found to be strongly coordinated. The synthesis of these polypeptides was followed immediately by the assembly of the complexes in the membrane. Bacteriochlorophyll or a signal substance triggered by bacteriochlorophyll synthesis regulated the synthesis of these polypeptides at the level of translation. The pigment-binding subunits of the B800--850 complex form oligomeric structures which interact with subunit H of the reaction center. A model of the topographical relationships of the pigment complexes is discussed.
Bacterial Proteins↗
Two-dimensional echocardiographic features of double outlet left ventricle.
In a cyanotic newborn infant, the diagnosis of double outlet left ventricle was made from the two-dimensional echocardiographic examination. The diagnosis was later confirmed at cardiac catheterization and surgery. The parasternal and subcostal views were especially useful for identification of the origin of both great arteries from the morphologic left ventricle. A review of the medical literature since 1967 revealed 77 cases of double outlet left ventricle, most of which were diagnosed only at surgery or postmortem examination. The anatomic features demonstrated with two-dimensional echocardiography in this case are representative of the findings cited most often in the cases reported in the medical literature.
Double Outlet Right Ventricle↗
Comparative pharmacokinetics of oral versus sublingual clonidine.
STUDY OBJECTIVE: To compare the pharmacokinetic and pharmacodynamic profile of orally versus sublingually administered clonidine. DESIGN: Randomized, crossover, nonblinded, open-label study. SETTING: University tertiary-care center. PATIENTS: 10 healthy male and female volunteers aged 20 to 42 years. INTERVENTIONS: A heparinized catheter was placed intravenously for blood-sampling purposes. An automatic sphygmomanometer was placed on the volunteers' left upper arm to obtain systolic and diastolic blood pressure, and a pulse oximeter was placed on the right index finger to measure heart rate (HR). MEASUREMENTS AND MAIN RESULTS: Serial blood samples were collected throughout the 24-hour study period to determine clonidine concentrations. The effect of clonidine on blood pressure (BP) and HR also was measured. The half-life, area under the curve, maximum concentration, and time to reach maximum concentration were similar for both the sublingual and oral routes. BP and HR changes were similar for both sublingual and oral clonidine. CONCLUSION: Both routes of administration resulted in similar pharmacokinetic and pharmacodynamic profiles. Attempts to shorten clonidine's latency with sublingual administration were unsuccessful. Our study shows that a single dose of clonidine 0.3 mg has the same pharmacokinetic and dynamic profile when administered orally or sublingually. Therefore, the sublingual route can be predictably used in fasting patients, those having difficulty swallowing, or those who are unable to absorb drugs through the gastrointestinal tract; the sublingual dose is the same as the oral dose.
Administration, Oral↗
Death of mouse embryos that lack a functional gene for glucose phosphate isomerase.
A null allele of the Gpi-1s structural gene, that encodes glucose phosphate isomerase (GPI-1; E.C. 5.3.1.9), arose in a mutation experiment and was designated Gpi-1sa-m1H. The viability of homozygotes has been investigated. No offspring homozygous for the null allele were produced by intercrossing two heterozygotes, so the homozygous condition was presumed to be embryonic lethal. Embryos were produced by crossing Gpi-1sa/null heterozygous females and Gpi-1sb/null heterozygous males. Homozygous null embryos were identified at different stages of development by electrophoresis and staining either for GPI-1 alone or GPI-1 plus phosphoglycerate kinase (PGK) activity. At 6 1/2 and 7 1/2 days post coitum homozygous null embryos were present at approximately the expected 25% frequency (37/165; 22.4% overall) although at 7 1/2 days the homozygous null embryos tended to be small. By 8 1/2 days most homozygous null embryos were developmentally retarded and had not developed significantly further than at 7 1/2 days; some were dead or dying. By 9 1/2 days the homozygous null conceptus was characterised by a small implantation site that contained trophoblast and often a small amount of extraembryonic membrane. Surviving trophoblast tissue was also detectable at 10 1/2 days. Previous studies have shown that oocyte-coded GPI-1 persists only until 5 1/2 or 6 1/2 days. Survival of homozygous null embryos to 7 1/2 or 8 1/2 days and survival of certain extraembryonic tissue to 10 1/2 days suggests that the homozygous null condition may not be cell-lethal although it is certainly embryo-lethal. Mutant cells that are deficient in glycolysis may use the pentose phosphate shunt to bypass the block in glycolysis created by the deficiency of glucose phosphate isomerase, and/or might be rescued by the transport, from the maternal blood, of energy sources other than glucose (such as glutamine). Either strategy may only permit slow cell growth that would not be adequate to support normal embryogenesis. Transport of maternal nutrients would be more efficient to the trophoblast and extraembryonic membranes and this may help to explain why these tissues survive for longer than the embryo itself. The morphological similarity between homozygous nulls and androgenetic conceptuses, where the trophoblast also survives better than the embryo, is discussed.
Animals↗
Parental influences on expression of glucose-6-phosphate dehydrogenase, G6pd, in the mouse; a case of imprinting.
Glucose-6-phosphate dehydrogenase (G6PD) activity was measured in blood from heterozygotes for the normal allele G6pda and the low activity allele G6pda-mlNeu. In adult mice lower activity was found in G6pda/G6pda-mlNeu than in the reciprocal heterozygote G6pda-mlNeu/G6pda (the maternal allele being listed first). Thus, either the paternally derived allele was over-expressed or the maternally derived allele was under-expressed. By contrast, in younger mice the difference in G6PD activity in reciprocal crosses was less marked. The findings are interpreted in terms of differential imprinting of maternally and paternally inherited information. The explanation offered for age related differences is that, as a consequence of imprinting, either the paternal X-chromosome is preferentially reactivated, or cells in which the paternally derived allele is active are at a selective advantage, and proliferate better than those in which the maternally inherited allele is active.
Alleles↗