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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 1,189 records · Page 66Linked to original sources
PubMed1986

Characterization and chromosome assignment of the human homolog of int-2, a potential proto-oncogene.

int-2 is one of two cellular genes (int-1 and int-2) currently implicated in the genesis of mammary carcinomas by mouse mammary tumor virus and may constitute a novel cellular proto-oncogene. Using low-stringency hybridization with mouse int-2 probes, we established that homologous genes exist in a variety of mammalian species, including humans, but failed to detect related sequences in other classes and phyla. Recombinant bacteriophage clones and a single cosmid encompassing the human int-2 gene were isolated and characterized by restriction enzyme mapping. A survey of nine primary human breast tumors, three breast tumor cell lines, and three normal individuals revealed no evidence for gross amplification or rearrangement of the int-2 locus. Three distinct restriction fragment length polymorphisms were observed which could prove useful in future linkage studies. By a combination of in situ hybridization of metaphase chromosomes and somatic cell genetics, the human int-2 gene was mapped to chromosome 11, band q13.

Animals↗
PubMed1986

Gallbladder perforation: diagnostic utility of cholescintigraphy in suggested subacute or chronic cases.

The preoperative cholescintigrams of 16 patients with subacute or chronic gallbladder (GB) perforation demonstrated at surgery were reviewed, and the scintigraphic findings were characterized. Persistent GB nonvisualization was found in each study. Additional findings included a band of increased pericholecystic hepatic activity (PCHA) (n = 7) and/or a photopenic region in the GB fossa (n = 7). PCHA and photopenic region findings, when visualized, were most commonly associated with a subacute localized perforation with pericholecystic abscess formation. However, the sensitivity of each of these findings was only 44%. Cholescintigrams did not directly demonstrate the perforation site in any patient. Although the presence of the PCHA sign and/or GB fossa photopenic region appears to identify a subgroup of patients at increased risk for perforation, cholescintigraphy is relatively insensitive for detection of subacute or chronic GB perforation.

Adult↗
PubMed1986

Role of chest radiography in predicting the extent of airway disease in patients with suspected pulmonary embolism.

An independent evaluation of the chest radiographs and ventilation-perfusion (VP) scintigrams of 119 patients (121 studies) was performed to assess the ability of radiographic findings to indicate the extent of ventilation abnormalities in patients suspected of having pulmonary embolism (PE). VP scans were obtained with krypton-81m in 72 cases and with xenon-133 in 49. All scintigrams showing ventilation abnormalities in greater than 50% of the lung were considered indeterminate for PE, owing to an increased likelihood of false-negative interpretations, as reported in previous studies. Indeterminate VP studies were found in all 21 patients who had radiographic findings of widespread obstructive pulmonary disease (OPD), in 35% with radiographic findings of focal OPD (P less than .001), and in only 18% with no OPD seen radiographically (P less than .001). VP scintigraphy is likely to be indeterminate for PE when widespread OPD is seen by chest radiography and ventilation imaging may not be warranted in these patients.

Adult↗
PubMed1986

Amyotrophic lateral sclerosis and occupational heavy metal exposure: a case-control study.

A retrospective case-control study of occupational heavy metal exposure was conducted using 66 amyotrophic lateral sclerosis (ALS) patients and 66 age- and sex-matched controls. Cases were ascertained primarily through a neurology support and research clinic. The self-administered questionnaire probed potential exposure to nine heavy metals: aluminum, lead, lead alkyl, magnesium, manganese, mercury, mercury alkyl, nickel and selenium. Using McNemar's test and a Mantel Haenszel extended analysis, no association was found between heavy metal exposure and the pathogenesis of ALS in this patient population. Demographic factors, fracture history, immunizations, travel and other variables were similar in ALS patients and controls.

Adult↗
PubMed1986

Acute hemorrhagic stress in conscious sheep elevates immunoreactive beta-endorphin in plasma but not in cerebrospinal fluid.

The effects of acute hemorrhagic stress on the concentrations of immunoreactive beta-endorphin (IR beta EP) in cerebrospinal fluid (CSF) and blood plasma were investigated in conscious sheep in which the cisterna magna, a carotid artery, and a jugular vein were chronically cannulated. Serial samples of CSF and jugular venous blood were collected before and after acute arterial hemorrhage and in control experiments. Basal concentrations of IR beta EP were higher in plasma than in CSF. Plasma concentrations of cortisol and IR beta EP increased within 45 min of the commencement of hemorrhage and returned to near baseline levels within 2.25 h. The concentrations of cortisol and IR beta EP in plasma observed after hemorrhage were significantly different from those observed in controls (analysis of variance). Neither the molar nor the relative changes from initial concentrations of IR beta EP in CSF were significantly different between hemorrhage-stressed and controls by analysis of variance. These results show that hemorrhagic stress in conscious sheep elevates concentrations of IR beta EP in plasma but not in CSF, indicating that pituitary beta EP secreted into blood does not enter CSF in significant amounts.

Animals↗
PubMed1986

Role of cell adhesion in contact-dependent transfer of a lysosomal enzyme from lymphocytes to fibroblasts.

Normal lymphocytes were found to adhere strongly to monolayer cultures of fibroblasts deficient in the lysosomal enzyme, beta-glucuronidase. During this co-culture, the fibroblasts acquired from the lymphocytes substantial amounts of this enzyme, which often accumulated at sites of contact between the two types of cell. Enzyme transfer was prevented by addition to the co-cultures either of purified lymphocyte plasma membranes or of antibody raised against such plasma membranes, but it was not inhibited by the addition of antibody raised against lymphocyte-derived beta-glucuronidase. An active role for the lymphocyte in this contact-dependent process was suggested by interference contrast, immunofluorescence and scanning electron-microscopic studies. These revealed extensive arrays of projections of the lymphocyte that ramified over the fibroblast cell surface. By transmission electron microscopy, conspicuous clusters of micropinocytotic vesicles were evident in the cytoplasm of the 'recipient' fibroblasts, subjacent to the surface in regions closely apposed to adherent lymphocytes. Such high frequencies of these vesicles were restricted to sites of lymphocyte-fibroblast contact, suggesting that they may play an important part in the transfer of enzyme between these two types of cell.

Animals↗
PubMed1986

Calculation of 2,3,7,8-TCDD equivalent concentrations of complex environmental contaminant mixtures.

Sufficient toxicological data are now available to permit use of conventional risk assessment techniques to estimate the hazards associated with human exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). However, many real-world exposures involve complex mixtures of dibenzodioxins, dibenzofurans, and related compounds. Historical approaches to risk assessment on such mixtures have ranged from ignoring all compounds except 2,3,7,8-TCDD itself to assuming that all compounds have potencies equal to 2,3,7,8-TCDD. An alternative approach which uses existing literature data and analytical results to calculate the "2,3,7,8-TCDD equivalent" concentration of a mixture in order to "predict" its biological potency relative to 2,3,7,8-TCDD itself is advanced here. Previously reported in vivo acute and subchronic studies and some recently obtained analytical chemistry data are integrated here to clarify the utility of this important approach and to assess the uncertainties associated with its use. This predictive approach, and various conceptually similar ones, have now found wide applicability to the risk assessment process associated with exposure to complex mixtures of dioxins, dibenzofurans, and related compounds.

Alanine Transaminase↗
PubMed1986

Ornithine decarboxylase activity in the neonatal rat heart following prenatal exposure to ethylene glycol monomethyl ether.

In mammals, ornithine decarboxylase (ODC) activity is highest during periods of rapid cellular growth and development, and the normal pattern of ODC activity during this period is sensitive to chemical and drug exposure. The industrial solvent ethylene glycol monomethyl ether (EGME) is teratogenic to rats and mice, with the heart being particularly sensitive. Basal ODC activity and ODC activity following an isoproterenol challenge were used to assess heart function in 3-, 9-, 16- and 22-day-old offspring from dams treated with 25 mg/kg EGME by gavage on days 7-13 or 13-19 of gestation. Reproductive outcome was not affected by EGME and none of the offspring had gross physical abnormalities. Gestation length was prolonged by both EGME treatments, but the increase was statistically significant only in the group treated on days 7-13 gestation. ODC activity per mg protein was greatest in 3-day-old rats and dropped off sharply during the following 3 weeks. In 3-day-old rats exposed on days 7-13 of gestation, ODC activity was 54% of that found in controls. ODC activity was comparable to that in controls in 3-day-old rats exposed on days 13-19 of gestation. Isoproterenol increased ODC activity in all groups, but additional functional abnormalities were not revealed by the isoproterenol challenge.

Aging↗
PubMed1986

Osteogenesis imperfecta.

It is now virtually certain that the brittle bone syndrome results from a variety of mutations in the alpha chains of type I collagen. Whilst the increasing biochemical knowledge makes prenatal diagnosis sometimes possible, the care of those with severe physical disability still provides a clinical challenge which is not always met. Future research in this disease therefore needs to be clinical as well as biochemical.

Collagen↗
PubMed1986

Effects of mitogenic stimulation on lymphocyte alpha-D-mannosidases.

Three types of alpha-D-mannosidase are present in human and murine lymphocytes. Their levels increased substantially when the cells were activated by T-cell mitogens, concanavalin A (Con A) and phytohaemagglutinin (PHA), and in the murine cells also by lipopolysaccharide (LPS), a B-cell mitogen. The intracellular localization of the alpha-D-mannosidases in the non-stimulated and activated murine cells was investigated by fractionation of lymphocyte lysates on colloidal silica (Percoll) and discontinuous sucrose gradients. In both types of cell, an enzyme having optimal activity at neutral pH was obtained in the cytosolic fraction and another alpha-D-mannosidase most active at an intermediate pH was obtained partly in membrane-bound form. In contrast, an acidic alpha-D-mannosidase, which was particularly elevated in the activated murine spleen cells, had a distribution in these lymphoblasts which was markedly different from that in non-stimulated lymphocytes. In the latter, the major proportion of the activity was obtained in a cytosolic fraction and the remainder in a particulate fraction of light density, whereas the enzyme in activated lymphocytes was distributed between vesicles of light and heavy density comparable with lysosomal organelles. Moreover, the acidic alpha-D-mannosidase still remained membrane bound even when cell lysates were prepared under hypotonic conditions which disrupt lysosome integrity. These results suggest that lymphocyte activation involves either stabilization of fragile lysosomes present in resting cells or de novo synthesis of lysosome-like structures. The acidic alpha-D-mannosidase present within isolated, intact lysosomes was found to be in a form, A, whereas a different form, B, was most prominent in whole-cell extracts of both types of lymphocyte.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Compartmentation↗
PubMed1985

Secretion of N-terminal pro-opiomelanocortin-derived peptides in response to acute haemorrhagic stress in conscious sheep.

To determine whether peptides derived from the N-terminus of the corticotropin/melanotropin/endorphin precursor, pro-opiomelanocortin, are released into blood in response to acute haemorrhagic stress, we examined the effect of haemorrhage on plasma concentrations of immunoreactive gamma 3-melanotropin, beta-endorphin and cortisol. Plasma concentrations of immunoreactive gamma 3-melanotropin (mean +/- SEM) increased within 30 min of haemorrhage from 71.1 +/- 10.4 to 106.8 +/- 6.3 fmol/mL (p less than 0.01) and plasma cortisol increased from 16.2 +/- 3.8 to 85.9 +/- 22.4 pmol/mL (p less than 0.025). The changes in plasma immunoreactive gamma 3-melanotropin and beta-endorphin were positively correlated (p less than 0.025). This study shows that peptides derived from the N-terminus of pro-opiomelanocortin are co-secreted with the C-terminal peptide beta-endorphin during acute haemorrhagic stress in sheep.

Animals↗