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Biomedical subjects

M Smith

Publications and source records attributed to M Smith.

At least 865 records · Page 48Linked to original sources
PubMed1990

Kinetics of intestinal calcium absorption in humans measured using stable isotopes and high-precision thermal ionization mass spectrometry.

Oral (44Ca: 0.13-0.20 mmol) and intravenous (42Ca: 0.02-0.037 mmol) isotopically enriched stable calcium (Ca) tracers were given together with an oral dose of 2.5 mmol of natural Ca to normal subjects. Blood and urine samples were collected up to 24 h after the tracer doses and atom fractions (AFs) of these tracers (relative to natural Ca) were measured by high-precision thermal ionization mass spectrometry (TIMS). The time-dependent fractional rate of oral dose absorbed and true fractional intestinal Ca absorption (alpha) were derived from the Afs by mathematical deconvolution. After 6 h, the ratio AF oral tracer/AF intravenous tracer in blood equalled that in urine and did not change thereafter. Reproducibility of the combination of chemical precipitation of Ca (from a urine standard) and subsequent TIMS measurements, in nine runs over 13 months, was 1.2% (coefficient of variation). This was in accord with the within-run reproducibility. An estimate of alpha derived from a single blood or urine measurement was 6-10% higher than the reference value obtained by deconvolution. This discrepancy could be explained by a correction factor depending, in part, on the elapsed time for peak Ca intestinal absorption rate. Instrumentally induced mass fractionation, as well as contributions from radiogenic Ca, had a significant effect on the accuracy and reproducibility of the ratio of AFs of tracers in blood and urine.

Administration, Oral↗
PubMed1990

Human lactation: forearm trabecular bone loss, increased bone turnover, and renal conservation of calcium and inorganic phosphate with recovery of bone mass following weaning.

The calcium (Ca) metabolism of established human lactation was studied in 40 adult women (mean age 32.4 years) who had been breast-feeding for 6 months (Lac) and in 40 age-matched controls (Con) using fasting urine and blood biochemistry and forearm single-photon bone mineral densitometry (BMD). Serial studies were performed up to 6 months after weaning in Lac women and repeated once in Con women. During lactation the significant findings were (1) a selective reduction (7.1%, P less than 0.03) in BMD at the ultradistal site containing 60% trabecular bone, but not at two more proximal, chiefly cortical bone sites; (2) increased bone turnover affecting bone resorption [fasting hydroxyproline excretion, Lac 2.22 +/- 0.12 mumol/liter GF (mean +/- SEM), Con 1.19 +/- 0.04, P less than 0.001] and affecting bone formation (plasma alkaline phosphatase, Lac 81.9 +/- 2.5 IU/liter, Con 53.5 +/- 2.7, P less than 0.001, and serum osteocalcin, Lac 14.0 +/- 0.7 microgram/liter, Con 7.3 +/- 0.4, P less than 0.001); and (3) renal conservation in the fasting state of both Ca and inorganic phosphate (Pi) with a resultant moderate increase in plasma Pi but not in plasma Ca (total or ionized). There were no differences between the groups in serum parathyroid hormone (PTH, intact and midmolecule assays), 25-hydroxy- and 1,25-dihydroxyvitamin D, nephrogenous cyclic AMP production, or plasma creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Spatial and biological characterisation of the complete quinic acid utilisation gene cluster in Aspergillus nidulans.

Heterologous probing of restriction digests of chromosomal DNA from Aspergillus nidulans with radioactively labelled probes encoding dehydroshikimate dehydratase (QA-4) and a repressor gene (QA1-S) from Neurospora crassa revealed a pattern of hybridisation inconsistent with an equivalent single copy of each gene in A. nidulans. Screening of size-selected and total genome A. nidulans DNA libraries allowed the isolation of four unique classes of sequence, two of which hybridised to the QA-4 probe, and two of which hybridised to the QA1-S probe. In each case, one of each pair of unique sequences was able to complement the equivalent mutations qutC (= QA-4) and qutR (= QA1-S) in A. nidulans, whereas the second of each pair was unable to complement the same mutation. The complementing sequences were physically mapped relative to the previously cloned A. nidulans QUT gene cluster, demonstrating that QUTR is distal and divergently transcribed from QUTA with approximately 3.6 kb between the ATG translational start codons, and that QUTC is transcribed in the same direction as QUTD on the other side of the cluster, approximately 1.65 kb downstream of the QUTD TAA translational stop signal. The physical and genetic maps of the QUT gene cluster correlate precisely. The non-complementing A. nidulans DNA sequences that hybridise to the N. crassa QA-4 (= QUTC) and QA1-S (= QUTR) fulfill many of the criteria characteristic of pseudogenes.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1990

Pharmacokinetics and pharmacodynamics of ritodrine after intramuscular administration to pregnant women.

To define the pharmacokinetics and pharmacodynamics of ritodrine after intramuscular injection, we administered 5 or 10 mg ritodrine into the gluteus or deltoid muscles of 12 pregnant volunteers. Six women received 5 mg and six received 10 mg into each muscle group on different days. We withdrew blood samples before and 12 times in the 6 hours after ritodrine injection. Blood pressure and heart rate were recorded at each time. Ritodrine was measured by high-performance liquid chromatography. Peak ritodrine concentrations (mean +/- SD) after a single 5 mg injection in the deltoid or gluteus were 38 +/- 13 and 26 +/- 8 ng/ml, respectively. After a 10 mg dose in the deltoid or gluteus, peak concentrations were 59 +/- 30 and 47 +/- 22 ng/ml, respectively. Although higher, the peak plasma concentrations after injections into the deltoid were not significantly greater than those after injection into the gluteus. None of the pharmacokinetic parameters differed according to dose or injection site. The pharmacodynamic effects of ritodrine were unaffected by injection site, but ritodrine caused a dose-related increase in heart rate and systolic blood pressure and a dose-related decrease in diastolic blood pressure. After a 10 mg injection, the maximal changes in heart rate, systolic, and diastolic blood pressure were 22%, 10%, and 19%, respectively. However, mean blood pressure was not altered by either the 5 or 10 mg dose. These findings indicate that there are few differences in pharmacokinetic parameters between deltoid and gluteal injection of ritodrine. The single intramuscular injection of 5 or 10 mg ritodrine results in labor-inhibiting concentrations with clinically insignificant cardiovascular effects.

Arm↗
PubMed1990

C5a-mediated release of interleukin 6 by human monocytes.

Recombinant human C5a (rC5a) was assessed for its ability to induce interleukin 6 (IL-6) production in human peripheral blood-derived mononuclear cell (PBMC) cultures. rC5a was observed to induce IL-6 production as measured by hybridoma growth promotion (B9.9 assay) and human B cell differentiation (SKW6.4 assay). Optimal IL-6 production was obtained after 24 hr stimulation with 0.1-0.5 micrograms/ml rC5a. In addition, natural human C5ades Arg and natural porcine C5a were able to induce a similar level of IL-6. The observed IL-6 activity appeared not to be due to endotoxin contamination since heat treatment (100 degrees C/15 min) inhibited rC5a induction of IL-6. The rC5a stimulation also induced an increase in steady-state IL-6 mRNA as determined by Northern blot analysis. Pretreatment of PBMC with leucine-methyl ester to deplete monocytes reduced the rC5a-induced IL-6 production to background levels. In addition, stimulation of purified T cell preparations with rC5a produced little IL-6 activity, suggesting that monocytes are the major source of IL-6 in this system. These results suggest that the inflammatory and immunoregulatory activities of C5a may in part be due to the stimulation of IL-6 release, a cytokine which possesses potent pleiotropic functions.

Complement C5a↗
PubMed1990

Molecular analysis of a myxoid chondrosarcoma with rearrangements of chromosomes 10 and 22.

Myxoid chondrosarcoma is a rare tumor of adulthood. An associated nonrandom reciprocal translocation between chromosome 9 and 22 was previously reported in this tumor. We performed cytogenetic and molecular genetic analysis of a myxoid chondrosarcoma derived from the sphenoid bone. Using restriction fragment length polymorphism (RFLP) analysis, we demonstrated rearrangement and a possible allele loss close to the chromosome 22 breakpoint. In addition, structural rearrangement in the chromosome 10q21.1 region and an allele loss in the chromosome 10q21-q23 region were also detected. In tumor DNA an additional hybridization fragment was detected by pAS-1 probe, which recognizes multiple pseudogenes of argininosuccinate synthetase dispersed in various chromosomes. We were unable to detect chromosomal abnormalities with two additional chromosome 9q probes. This study suggests that multiple gene rearrangements occurred in the myxoid chondrosarcoma and the significance of this is discussed.

Adult↗
PubMed1990

Mapping of a gene determining tuberous sclerosis to human chromosome 11q14-11q23.

Tuberous sclerosis (TSC) is a dominantly inherited disorder characterized by hamartomas and hamartias in one or more organs, most often in skin, brain, and kidneys. Analysis of the basic genetic defect in tuberous sclerosis would be greatly expedited by definitive determination of the chromosomal location of the TSC gene or genes. We have carried out genetic linkage studies in 15 TSC families, using 34 polymorphic markers including protein markers and DNA markers. Pairwise lod scores were calculated using LIPED, and multipoint analyses were carried out using MENDEL. In the pairwise linkage analysis, using a penetrance value of 90%, a significant positive lod score was obtained with MCT128.1 (D11S144), 11q22-11q23, Zmax 3.26 at theta = 0.08. The tyrosinase probe TYR (11q14-11q22) gave a maximum lod score of 2.88 at theta = 0. In the multipoint analyses the most likely order is (TYR,TSC)-MCT128.1-HHH172. Homogeneity analysis was carried out using the USERM9 subprogram of MENDEL, which conducts the admixture test of C. Smith (1963, Ann. Hum. Genet. 27: 175-182). This test provided no evidence for genetic heterogeneity (that is, non-11-linked families) in this data set.

Alleles↗
PubMed1990

Effect of acute selenium restriction on whole body endogenous selenium and the selenite-exchangeable metabolic pool in the adult rat.

The time course of changes in whole body endogenous selenium (Se(end)) was investigated during a short-term (7-day) selenium restriction study in the adult rat. The method of continuous feeding with a stable isotope of selenium was used to permit normal intake of selenium while distinguishing between the dietary and endogenous components of body selenium. Additionally, the effect of short-term selenium restriction on the time course of the selenite-exchangeable metabolic pool (Se-EMP) was investigated. Two groups of adult male rats were intubated with the in vivo stable isotope (74)SeO(3)(2-), then fed a Torula yeast diet (selenium <0.02 microg/g) and either deionized water (-Se group) or deionized water containing selenium as (76)SeO(3)(2-) (0.1 microg selenium/ml) (+Se group). Three animals from each group were killed at 24-hour intervals. Whole body Se(end) and the estimated size of Se-EMP (W(Se-EMP)) were determined using hydride generation-inductively coupled plasma mass spectrometry for isotopic measurements. Whole body Se(end) decreased linearly in the +Se group (Se degrees (end): 54.4 microg; Se(end) at 3 days: 49.3 +/- 2.1; Se(end) at 7 days: 45.2 +/- 2.2). The decrease was exponential for the -Se group (Se degrees (end): 54.4 microg; Se(end) at 3 days: 42.9 +/- 0.3; Se(end) at 7 days: 42.2 +/- 0.7). The value of W(Se-EMP,pl) (microg) was 19.8 +/- 0.6 at 1 day and 19.7 +/- 1.0 at 7 days for the +Se group. The corresponding values for the -Se group were 15.7 +/- 1.5 and 18.8 +/- 0.4. All respective values of W(Se-EMP,pl) for the -Se group were significantly smaller than for the +Se group (P < 0.05), with the exception of values at days 6 and 7. The value of W(Se-EMP,urine) (microg) was 2.1 +/- 0.2 at 1 day, increasing rapidly to 23.5 +/- 1.5 at 7 days for the +Se group. The corresponding values for the -Se group were 3.0 and 23.1.

Journal Article↗
PubMed1990

Acute theophylline toxicity and the use of esmolol to reverse cardiovascular instability.

Theophylline overdoses are frequent conditions that may require emergency treatment. Clinical features common to severe theophylline toxicity include nausea and vomiting, tachydysrhythmias, metabolic disturbances, seizures, and cardiovascular collapse. Several reports have described these manifestations and their treatments. We report the case of a patient suffering from an acute, intentional theophylline overdose who exhibited the classic features of a toxic ingestion and describe the first reported use of IV esmolol in the treatment of accompanying cardiovascular manifestations.

Adrenergic beta-Antagonists↗
PubMed1990

Differential effects of cigarette smoke condensate and its fractions on cultured normal and malignant human bronchial epithelial cells.

The differential effects of cigarette smoke condensate (CSC) and its fractions (neutral, basic, and acidic fractions) on proliferation and squamous differentiation of normal human bronchial epithelial (NHBE) cells versus human lung carcinoma cells were investigated. CSC, and the neutral and acidic fractions inhibited cellular proliferation more than the basic fraction. When compared to the acidic and basic fractions, CSC and the neural fraction were more effective in causing squamous differentiation of NHBE cells and inhibiting specific binding of phorbol dibutyrate (PDBU). There were no significant changes in ionized cytosolic calcium concentration when NHBE cells were treated with CSC. In contrast to the normal epithelial cells, neither HUT-292 nor the 3 other carcinoma cell lines examined showed marked squamous morphological changes when exposed to either CSC or its fractions and the carcinoma cells were more resistant to their inhibiting effects on cellular proliferation. These results are consistent with the hypothesis that differential effects of tobacco smoke components on cellular proliferation may allow clonal expansion of preneoplastic and neoplastic human bronchial epithelial cells during lung carcinogenesis.

Bronchi↗
PubMed1990

Characteristics of unmarried adolescent mothers: determinants of child rearing versus adoption.

The sociodemographic and biographical characteristics of a group of unmarried adolescent mothers who opted to rear their children were compared with those of a matched group who placed their children for adoption. Those choosing adoption were more likely to be of higher socioeconomic status, to have higher educational aspirations, and to be from suburban residences. Suggestions for intervention and appropriate services are offered.

Adolescent↗
PubMed1990

Characterization of cerebral energetics and brain pH by 31P spectroscopy after graded canine cardiac arrest and bypass reperfusion.

Recovery of cerebral energy metabolism is used to indicate CNS viability after ischemia. This study utilized 31P nuclear magnetic resonance (NMR) spectroscopy to measure cerebral energy state and intracellular pH in dogs subjected to 8, 12, or 16 min of cardiac arrest and reperfusion using cardiopulmonary bypass. Spectra were obtained throughout ischemia and initial reperfusion and repeated at 30 and 144 h post ischemia. Neurologic deficit scoring was performed at 12 and 24 h post insult and then daily. High-energy phosphates were depleted by the end of all ischemic intervals. Recovery occurred within 60 min of reperfusion and persisted with no differences in the rate of return between groups (p greater than 0.05). Brain pH (pHb) decreased by the end of ischemia in all groups (p less than 0.0001). Neither the pHb nadir nor its recovery differed between groups (p greater than 0.05). Although longterm neurologic outcome differed between groups, the spectra were similar. Assessment of cerebral energy state using 31P NMR spectroscopy does not appear to be a sensitive indicator of neurologic outcome after global ischemia in dogs. Return of high-energy phosphates may be a necessary but not sufficient condition for cerebral recovery after ischemia. The return of high-energy phosphates after a 16-min cardiac arrest, however, indicates a potential for neurological recovery.

Acid-Base Equilibrium↗
PubMed1990

Double-blind comparison of topical lignocaine-prilocaine cream (EMLA) and lignocaine infiltration for arterial cannulation in adults.

In a double-blind, double-dummy study, the efficacy of topical 5% EMLA cream was compared with that of lignocaine infiltration in alleviating the pain of arterial cannulation. Forty unpremedicated adults were allocated randomly to four groups to receive EMLA cream alone, EMLA and 0.9% saline infiltration, EMLA and 1% lignocaine infiltration or placebo cream and 1% lignocaine infiltration. Following arterial cannulation, pain was assessed by the patient using a visual analogue score and by an independent observer using a four-category verbal rating score. Significantly lower pain scores were observed in all patients receiving EMLA compared with those receiving placebo cream and lignocaine infiltration by both patient (P less than 0.01) and observer (P less than 0.001) assessments. There were no significant differences between the three EMLA groups.

Administration, Topical↗
PubMed1990

Endotracheal tube safety with the erbium:yttrium aluminum garnet laser.

The erbium:yttrium aluminum garnet (Er:YAG) laser operates in the infrared spectrum at a wavelength of 2.94 microns. The absorption coefficient for water at this wavelength is approximately 10 times that of the carbon dioxide laser. It is anticipated that this laser will produce more precise surgical ablation with decreased surrounding tissue destruction. The results of impacting endotracheal tubes with the Er:YAG laser are presented. The CO2 laser was used as a reference. Metallic tape that was not perforated by the CO2 laser after 240 seconds of continuous exposure at 20 W was perforated by the Er:YAG laser with use of 15 pulses of 1 J per pulse. Silver foil tape with a Meroplicable to otolaryngology, modification of current safety standards will be necessary.

Aluminum↗