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Biomedical subjects

D R Smith

Publications and source records attributed to D R Smith.

At least 19 recordsLinked to original sources
PubMed1992

Vagal responses to adjustable sutures in strabismus correction.

The oculocardiac reflex is a recognized complication of ocular stimulation, precipitated most commonly by traction on the extraocular muscles. To determine the true incidence of occurrence of the oculocardiac reflex during suture adjustments, 20 patients undergoing suture adjustment were monitored for blood pressure, heart rate, and rhythm abnormalities during the suture adjustment. A control group of ten patients with strabismus were studied postoperatively for comparison. Thirteen study patients and two control patients were noted to have a vagal response (P less than .001). The most common response noted was a decrease in heart rate in 15 patients. Only two patients were symptomatic during vagal response (one patient became light-headed and another had an episode of nausea and vomiting). Suture adjustment was found to be the most common triggering event in precipitating vagal responses. Surgeons performing suture adjustment in strabismus correction should be cognizant of vagal responses so that they may properly inform patients of this possibility and take steps to minimize its occurrence.

Adolescent↗
PubMed1992

High resolution studies of the Xenopus laevis ribosomal gene promoter in vivo and in vitro.

The first high resolution maps of the Xenopus laevis ribosomal promoter and its flanking regions (-179 to +14) have been created by assaying point mutants both in oocyte and in vitro. Within the promoter boundaries (-141(-145) to +3(+4)), domains analogous to the Core Promoter and "Upstream Control Element" (UCE) were clearly detected. The base pairs at -133, within the UCE, and -20, -10, -7, and +3, within the Core, were all shown to be especially important for promotion. Between the Core and UCE, two central promoter elements (CPEs) were also resolved. Surprisingly, these CPEs did not correspond to the highly conserved enhancer homology (approximately -70 to -110), but to CCCGGCC motifs immediately flanking it. Although xUBF was shown to be a limiting component for in vitro transcription, none of the point mutations was found to affect the interaction of this factor with the promoter.

Animals↗
PubMed1992

Characterization and partial purification of an insulinase from Neurospora crassa.

An insulin-binding metal- and thiol-dependent proteinase has been purified 1491-fold from high speed cytosolic fractions of the fungus Neurospora crassa. This enzyme resembles insulin-degrading enzymes (insulinases) present in mammalian cells and in Drosophila melanogaster in the following ways: (i) it degrades radiolabeled insulin with a specificity similar to that of rat muscle insulinase, as demonstrated by HPLC analysis of the degradation products; (ii) it is inhibited by bacitracin, EDTA, 1,10-phenanthroline, and the sulfhydryl-reactive compounds N-ethylmaleimide and p-chloromercuribenzoate, but not by inhibitors of serine proteases or by lysosomal protease inhibitors. Cross-linking with 125I-insulin labels a band of ca. 120 kDa, and several smaller bands which may represent degradation products. The N. crassa insulinase is stimulated by Mn2+ and strongly inhibited by Zn2+; Mn2+ can also reactivate the enzyme after inhibition by EDTA, but Zn2+ is ineffective. The N. crassa protein differs in this regard from mammalian and insect insulinases which are generally activated by both Mn2+ and Zn2+. This finding extends the apparent evolutionary conservation of these metal- and thiol-dependent proteases into the microbial realm.

Cations, Divalent↗
PubMed1992

Stable isotopic tracers of lead mobilized by DMSA chelation in low lead-exposed rats.

The ability of DMSA to mobilize skeletal lead or effect a redistribution of endogenous lead to other target organs in low lead-exposed organisms is unclear. Discrepant results of past studies of DMSA and other lead chelators (e.g., CaNa2EDTA) may be due, in part, to experimental differences and difficulties in distinguishing mobilized skeletal lead from other endogenous or exogenous lead sources. Therefore, the influence of DMSA on the mobilization and redistribution of lead in skeletal and soft tissue compartments of low lead-exposed female Wistar (115-125 g) rats was investigated using ultraclean stable lead isotope tracer techniques. Rats that had been reared on a low lead-level diet (lead intake approximately 80 ng Pb/g body/day) were fed 206Pb-enriched drinking water (210 ng Pb/ml) for 1.5 days and then were chelated with a single ip injection of a 0.11 mmol/kg dose of DMSA. Blood, kidney, brain, tibia, urine and feces were collected 24 hr after chelation and analyzed for lead concentrations by graphite furnace atomic absorption spectrometry and for lead isotopic compositions by thermal ionization mass spectrometry. These analyses demonstrated that DMSA chelation significantly increased (15-fold) the diuresis of labile soft tissue lead, but not skeletal lead. DMSA also appeared to effect a redistribution and input of a comparable amount of lead to the skeleton and smaller relative amounts of lead to the soft tissues (blood, kidney) of the chelated animals. The clinical significance of these latter observations beyond the context of this preliminary study is not clear.

Animals↗
PubMed1992

Phase I/II study of intraperitoneal iproplatin in patients with minimal residual disease following platinum-based systemic therapy for epithelial ovarian carcinoma.

13 patients with minimal residual disease following platinum-based systemic therapy for epithelial ovarian cancer were treated with intraperitoneal iproplatin. A total of three cycles were given at monthly intervals. All patients had minimal residual disease (defined as less than 2 cm in diameter) or positive cytology documented at second look laparotomy following systemic chemotherapy. Iproplatin was administered via a temporary dialysis catheter (n = 11) or a semi permanent Tenckhoff peritoneal dialysis catheter (n = 2). The dose of iproplatin ranged from 150 to 450 mg/m2. No responses to therapy were documented. In this trial the major toxic side effects of iproplatin were thrombocytopenia, diarrhoea, nausea and vomiting. The maximum tolerated dose was 300 mg/m2.

Adult↗
PubMed1992

Lead sources to California sea otters: industrial inputs circumvent natural lead biodepletion mechanisms.

Lead levels (as Pb/Ca atom ratios) and stable isotopic compositions were measured in teeth of preindustrial and contemporary California sea otters (Enhydra lutris) to determine if postindustrial changes had occurred in the magnitude and source of accumulated lead. Lead/calcium atom ratios (means +/- SD) in teeth of some contemporary animals (110 +/- 37 x 10(-8), n = 3) were significantly elevated compared to levels in other contemporary (13 +/- 6.0 x 10(-8), n = 4) and preindustrial (7.3 +/- 3.9 x 10(-8), n = 6) otters. The isotopic ratios (means +/- 2 sigma means) revealed a change in the sources of accumulated leads, from natural continental-derived leads in the preindustrial animals (207Pb/206Pb = 0.820 +/- 0.002) to industrial sources dominated by aerosol leads in the contemporary otters (207Pb/206Pb = 0.836 +/- 0.003). The one exception was a contemporary Monterey Bay animal (207Pb/206Pb = 0.853), who contained lead derived from an industrial waste lead deposit in Monterery Harbor. These data establish distinguishable sources of lead assimilated by sea otters, and indicate that elevated exposures to some animals circumvented the natural biodepletion of lead through marine trophic pathways.

Age Factors↗
PubMed1992

Stable isotope labeling of lead compartments in rats with ultralow lead concentrations.

The role of the mammalian skeleton as an endogenous lead source is unclear. This is due in part to difficulties in distinguishing mobilized skeletal lead from other endogenous and exogenous lead sources. Therefore, we have applied ultraclean stable lead isotope techniques to label skeletal and soft tissue lead compartments within the rat with distinguishable lead isotopic signatures. Female Wistar (defined flora) rats were fed 206Pb-enriched drinking water ([Pb] = 110 ng/ml) and sacrificed after durations of 2, 4, 7, and 14 days. Blood, kidney, vertebra, and tibia tissues were analyzed for lead concentrations and stable isotopic compositions. The resulting isotopic ratios in soft (blood and kidney) and skeletal (vertebrae and tibia) tissues differed by approximately 40% after 2 days exposure to the 206Pb tracer. More than 90% of the tracer isotopic signature was contained in the soft tissues after 10 days exposure, while skeletal tissues acquired only approximately 50% of the tracer by the end of the study. Because these animals were maintained under trace metal-clean conditions, they contained lead concentrations in whole blood (0.3-3 ng/g), kidney (11-27 ng/g dry wt), and bone (35-70 ng/g dry wt) tissues that are the lowest known reported for contemporary terrestrial mammals, and they (in bone) are comparable to levels in preindustrial mammals. The elevated concentrations of lead in kidney (fresh weight) relative to levels in blood are consistent with the presence of specific lead-binding sites in the kidney at very low levels of exposure.

Animals↗
PubMed1992

Current needs for increased accuracy and precision in measurements of low levels of lead in blood.

Needs for accurate and precise measurements of low levels of lead in blood are discussed. Current methodologies are sufficient for measuring blood lead (PbB) levels greater than 0.5 microM, but the accuracy and precision of those methodologies are inadequate for measuring lower (less than 0.5 microM) PbB concentrations. These analytical limitations are primarily due to contamination bias incurred during sample collection, processing, and analyses. Consequently, trace metal-clean procedures should be adopted to elucidate the contribution of environmental lead to the PbB levels of the U.S. population and to estimate the threshold(s) of subclinical lead toxicity.

False Negative Reactions↗
PubMed1992

Ligation-mediated PCR of restriction fragments from large DNA molecules.

A general method is described for PCR amplification of single restriction fragments from large DNA molecules. The method involves sequence-specific ligation of synthetic oligonucleotides to ambiguous 4-base 5' overhangs produced by type IIS restriction endonucleases. Such "adapter-tags" provide one target for primer annealing in subsequent PCR reactions. The second target for primer annealing is provided by a universal "bubble-tag" ligated to blunt ends produced with another endonuclease. The key advantage of this approach is that specific fragments can be isolated without any prior knowledge of the nucleotide sequence of the target. Using bacteriophage lambda DNA as a test system, unique PCR products could be generated consistently. Conditions of temperature, ionic strength, and substrate concentration in the adapter-tag ligations--which affect sequence specificity--were found to have a major influence on the purity of PCR-generated fragments. In principle, the method permits the amplification of virtually any sequence from purified cosmid or YAC DNA using a library of only 240 adapter-tags.

Base Sequence↗
PubMed1992

Pituitary-specific transcriptional initiation sites of the rat carboxypeptidase-H gene and the influence of thyroid hormone status.

Carboxypeptidase-H (CPH) is a metallocarboxypeptidase implicated in the processing of peptide hormones. Consistent with such a role, the gene for CPH is expressed in cells that secrete regulatory peptides, such as those of the brain and endocrine tissues. In the rat brain, CPH is transcribed from a single transcriptional start site associated with the initiator-type element first described in the gene encoding lymphocyte-specific terminal deoxynucleotidyltransferase. We have used a combination of Northern blot analysis and S1 nuclease protection mapping to describe the expression and transcription initiation pattern of the gene for CPH in the peripheral tissues and brain regions of the normal rat. The single transcriptional start site is used in all tissues examined, except the pituitary, where two additional specific initiation sites are found. The expression of the CPH gene is up-regulated in the anterior pituitary gland as a consequence of systemic thyroid hormone depletion, and this increase is associated with a preferential utilization of the novel upstream transcriptional initiation sites. Thus, the use of different major transcriptional initiation sites of the CPH gene in the pituitary gland is subject to differential direct or indirect thyroid hormone regulation.

Amino Acid Sequence↗
PubMed1992

Ruminal biohydrogenation of fatty acids from high-oleate sunflower seeds.

The objective of these experiments was to examine methods of modifying the fatty acid composition of bovine tissues. In the first experiment, four steers were fitted with duodenal fistulas and were assigned to four diets in a Latin square design. The steers were fed a control diet or the same diet containing 10% high-oleate partially crushed sunflower seeds, serum-coated sunflower seeds, and heat-treated, serum-coated sunflower seeds for 5 d. Samples of digesta and feces were collected on d 5. The inclusion of sunflower seeds (plain or serum-coated) in the diet increased (P less than .05) the digesta concentration of stearate. The percentage of stearate in the digesta and feces was increased (P less than .05) from 51 to 67% and from 64 to 74%, respectively, when steers were fed the untreated sunflower seed. The fecal concentration of oleate was increased (P less than .05) by dietary sunflower seeds in steers that were fed the serum-coated, unheated sunflower seeds. In a second experiment, heifers (four per group) were fed a corn-based control diet or diets containing 10% of high-oleate sunflower oil encapsulated with calcium alginate, either plain, coated with blood meal, or with blood meal integrated into the pellet. After 50 d on treatment, samples of perianal adipose tissue were obtained by biopsy. The fatty acid composition of the adipose tissue was not modified by the inclusion of the encapsulated oleate in the diet. In summary, limited ruminal bypass of sunflower seed oleate was accomplished with sunflower seed but not with encapsulated oleate.

Adipose Tissue↗
PubMed1992

Spontaneous hemothorax. Report of 6 cases and review of the literature.

We present 6 cases of spontaneous hemothorax and comprehensively review the medical literature on this subject. We categorize the reported causes and offer a rational diagnostic approach to patients with nontraumatic hemothorax. We recommend specific treatments for specific etiologies, and emphasize the importance of well-established surgical principles for the treatment of hemothorax. Our suggestions should enable physicians to accurately diagnose and expeditiously treat patients with spontaneous hemothorax.

Adult↗
PubMed1991

Medical apartheid. An American perspective.

The suppressive policies and practices of apartheid in South Africa have directly contributed to preventable morbidity and mortality in black Africans. Due to socioeconomic segregation ("functional apartheid"), America's citizens of color also suffer excess death and disability. Health status measurements in the United States confirm the failure of the current fragmented health care system to recognize or respond to the unmet need or the barriers that exist. Predictably, the changes needed to improve the health status of black South Africans are similar to those that are necessary to remedy the situation in the United States. Community-Oriented Primary Care is a health service provision model that holds promise as a comprehensive community-based strategy that can begin to address some of the shortcomings of the current medical care systems of both nations.

Black or African American↗