Search PubMed⌕ Search

Biomedical subjects

D F Smith

Publications and source records attributed to D F Smith.

At least 181 records · Page 10Linked to original sources

Replacement of chloride deficit by use of 1.8% NaCl to correct experimentally induced hypochloremic metabolic alkalosis in sheep.

Five adult 40- to 50-kg female sheep were surgically fitted with a reentrant cannulae placed in the proximal part of the duodenum just distal to the pylorus. By diversion of abomasal outflow, this model has been shown to produce hypochloremic metabolic alkalosis accompanied by dehydration, hypokalemia, and hyponatremia. Each sheep was subjected to 3 separate, 12-hour IV treatment trials, in each case preceded by a control period of 48 hours, and a diversion period of 36 to 96 hours, during which a hypochloremic (Cl- less than or equal to 60 +/- 2 mEq/L) metabolic alkalosis with hypokalemia and hyponatremia was produced. Treatment 1, consisting of 6 L of isotonic Na gluconate, was designed to replace volume without replenishing the Cl-1 deficit. Although hydration improved, plasma Cl- decreased further, and the sheep became increasingly weak and depressed. Treatment 2, consisting of 2 L of 1.8% NaCl, was designed to replace the Cl- deficit without replacing total volume. Plasma Na+ and Cl- concentrations returned to normal during the 12 hours of treatment; acid-base balance and plasma K+ concentrations returned to normal within 36 hours of treatment. During treatment 3 (control, no treatment), measured metabolic values changed minimally. We concluded that the IV replacement of Cl- without K+ is effective in the correction of experimentally induced hypochloremic metabolic alkalosis in sheep.

Alkalosis↗

LAMP-1 in CHO cells is a primary carrier of poly-N-acetyllactosamine chains and is bound preferentially by a mammalian S-type lectin.

Recent studies indicate that some mammalian S-type lectins bind preferentially to oligosaccharides containing the repeating disaccharide [3Gal beta 1,4GlcNAc beta 1]n or poly-N-acetyllactosamine (PL) sequence. We report here our investigation on the distribution of these sequences in glycoproteins in Chinese hamster ovary (CHO) cells and the interaction of glycoproteins containing PL chains with an immobilized S-type lectin (L14) from calf heart tissue. Our results demonstrate that PL chains are carried by a few high molecular weight glycoproteins which are bound by tomato-lectin Sepharose and one of these was precipitated by antibody to LAMP-1 (a lysosomal-associated membrane glycoprotein). More importantly, these high molecular weight glycoproteins, including LAMP-1, were bound with high affinity by L14. These results indicate that mammalian S-type lectins are highly specific in their interactions with glycoproteins and that LAMPs carry important recognition sequences for these lectins.

Animals↗

Accuracy of radiography of the reticulum for predicting surgical findings in adult dairy cattle with traumatic reticuloperitonitis: 123 cases (1981-1987).

Radiographic and surgical findings were compared in 123 cattle suspected of having traumatic reticuloperitonitis. Radiography of the reticulum proved to be a sensitive test for detection of a foreign body (FB). An abnormal FB position on a radiograph was a good predictor of FB perforation. If an FB was fully attached to a magnet, it was unlikely to be perforating the reticular wall. When abnormal reticulum size, abnormal reticulum location, and gas shadows adjacent to the reticulum were found simultaneously on a radiograph, hepatic or perireticular abscess was likely. Reticular radiography proved to be a useful diagnostic aid in cattle suspected of having traumatic reticuloperitonitis.

Animals↗

Job satisfaction amongst resident medical officers.

This paper reports the results of an attitudinal survey of resident medical officers (RMOs) to assess their level of job satisfaction. The survey questionnaire consisted of 31 statements or questions concerning RMOs' attitudes towards various aspects of their work. One-third of RMOs employed in New Zealand hospitals were questioned, totalling 524 doctors, and yielding a 74.4% response. Levels of job satisfaction were higher than expected given recent publicity which has stressed dissatisfaction and low morale. The study found that about 66% were satisfied, 20% were neutral and 14% were dissatisfied. Registrars were significantly more satisfied than house surgeons. There were some relatively minor differences by region and specialty. There were no differences by gender, medical school, or whether partnered or nonpartnered. Hours of work, pay, holidays, rostering and other general working conditions were considered by most RMOs to be adequate to positive. The nature of the work was felt to be interesting, stimulating and providing an adequate level of responsibility. However, low morale seems endemic amongst RMOs in hospitals. There was a generally unfavourable view of hospital administration by all RMOs. Of those who claimed to be satisfied with their jobs, 28% stated that they would not re-enroll at medical school again if they had prior knowledge of their working conditions.

Attitude of Health Personnel↗

Micronucleated erythrocytes as an index of cytogenetic damage in humans: demographic and dietary factors associated with micronucleated erythrocytes in splenectomized subjects.

Erythrocytes containing micronuclei serve as an indicator of genotoxic exposure in splenectomized individuals. Micronucleated erythrocytes, derived from cytogenetically damaged RBC precursors, are not selectively removed from peripheral blood in individuals who lack splenic function. The relationship between micronucleated cell frequencies and demographic, environmental, and dietary factors was examined in 44 subjects with previous splenectomy due to trauma. Their micronucleated cell counts fit a log-normal distribution, with geometric means of 3.3 micronucleus-containing cells/1000 reticulocytes and 2.7/1000 normochromatic erythrocytes. A multiple regression analysis showed that drinking five cups of coffee or tea/day (relative to none) was associated with an approximately 2-fold higher frequency of micronucleated cells. Weaker statistical associations were also noted with micronucleus frequency and the consumption of calcium supplements (associated with a higher frequency) and vitamins A, C, or E (lower frequency). An apparent trend of higher micronucleus counts with age was attenuated when other factors were considered in the regression. Cigarette smoking and decaffeinated coffee consumption were among the factors not associated with elevated micronucleated cell frequencies. Because the occurrence of micronuclei in reticulocytes reflects cytotoxic exposures within the past 3-8 days, it may be possible to test directly the relationship of these factors to micronucleus formation through intervention studies.

Chromosome Aberrations↗

Transfer and expression of a murine UDP-Gal:beta-D-Gal-alpha 1,3-galactosyltransferase gene in transfected Chinese hamster ovary cells. Competition reactions between the alpha 1,3-galactosyltransferase and the endogenous alpha 2,3-sialyltransferase.

The cDNA encoding a murine UDP-Gal:beta-D-Gal-alpha 1,3-galactosyltransferase has recently been cloned and sequenced using a transient expression method (Larsen, R.D., Rajan, V.P., Ruff, M.M., Kukowska-Latallo, J., Cummings, R.D., and Lowe, J.B. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 8227-8231). This report describes the construction and analysis of a Chinese hamster ovary (CHO) cell line in which in vitro expression alpha 1,3-galactosyltransferase activity has been achieved via transfer and expression of the murine alpha 1,3-galactosyltransferase gene. A primary aim of this research was to explore the role of the alpha 1,3-galactosyltransferase in regulating glycoprotein and glycolipid biosynthesis. CHO cells were cotransfected with murine genomic DNA fragments from F9 cells and plasmid DNA containing a resistance gene to the antibiotic G418. Cells resistant to G418 were then selected for expression of surface glycoconjugates containing terminal alpha 1,3-galactosyl residues by isolating cells bound to immobilized Griffonia simplicifolia-I-B4, a lectin which binds to alpha 1,3-galactosyl residues. A positive, stable transfectant clone, designated Clone 3, was obtained and analyzed for expression of the murine of alpha 1,3-galactosyltransferase. Fluorescence-activated cell sorting demonstrated that Clone 3, but not parental, CHO cells bound significant amounts of fluorescein isothiocyanate-labeled G. simplicifolia-I-B4. Southern and Northern blot analyses using the murine alpha 1,3-galactosyltransferase cDNA demonstrated that clone 3, but not parental, CHO cells contain murine alpha 1,3-galactosyltransferase genomic DNA sequences, and express a homologous transcript that comigrates with the authentic 3.6 kilobase alpha 1,3-galactosyltransferase murine mRNA. Enzyme assays confirmed that clone 3, but not parental CHO cells, contained the alpha 1,3-galactosyltransferase activity and that the level of activity is comparable to that found in F9 cells. [3H]Galactose-labeled glycopeptides and glycolipids were obtained from metabolically radiolabeled parental and Clone 3 cells and were analyzed for the presence of terminal alpha 1,3-galactosyl residues. Complex-type, Asn-linked oligosaccharides from both parental and Clone 3 cells contain the repeating disaccharide [3Gal beta 1, 4GlcNAc beta 1]n or poly-N-acetyllactosamine sequences, but only the poly-N-acetyllactosamine chains from clone 3 cells contained the terminal sequence Gal alpha 1,3Gal beta 1,4GlcNAc beta 1-R.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Purification of unactivated progesterone receptor and identification of novel receptor-associated proteins.

Progesterone receptor complexes were purified from crude cytosol in a rapid, gentle, one-step procedure using anti-receptor monoclonal antibodies covalently attached to an agarose resin. Five nonreceptor proteins specifically co-purified with unactivated avian progesterone receptor; these proteins had molecular masses of approximately 90, 70, 54, 50, and 23 kDa. The 90- and 70-kDa proteins have been previously identified as the 90-kDa heat shock protein and a member of the 70-kDa heat shock protein family, respectively. The 54-, 50-, and 23-kDa proteins have not been previously described as associated with avian progesterone receptor. Two-dimensional gel electrophoresis revealed charge heterogeneities for all five proteins. Except for p70, each could be dissociated from receptor by salt, a process inhibited by sodium molybdate. However, molybdate was not required for protein association with receptor in low ionic strength. Following progesterone treatment in vivo p70 still co-purified with cytosolic receptor although the other affiliated proteins were reduced, suggesting hormone-dependent dissociation in conjunction with receptor activation. One of the proteins, p54, displayed in vitro hormone-dependent dissociation which was not prevented by molybdate.

Animals↗

Comparison of mutagenic activities of several peroxyacyl nitrates.

Salmonella typhimurium, strain TA100 was exposed to a series of peroxyacyl nitrates including peroxyacetyl nitrate (PAN), peroxypropionyl nitrate (PPN), peroxybutyryl nitrate (PBN), peroxybenzoyl nitrate (PBzN), and chloroperoxyacetyl nitrate (CPAN). Gas-phase concentrations for the individual exposures were in the high part per billion by volume ppbv range. The dose was determined from the deposition rate and measured from the net decrease of the test compound in the exposure chamber and the exposure time. The mutagenic activity for each compound determined from the dose-response relationship gave values ranging from 250 (PBN) to 6,500 (PBzN) revertants/mumols. The mutagenic activity for CPAN could not be determined, due to an interference from chloroacetaldehyde. The difficulties of quantifying the actual gas-phase chemical dose the bacteria are exposed to in this variant of the Ames test are delineated.

Gases↗

Antinociceptive effects of the stereoisomers of nicotine given intrathecally in spinal rats.

Spinalized rats received an intrathecal injection of either (-)-nicotine or (+)-nicotine in order to study the stereoselectivity of antinociception. Pain threshold was measured using the tail-flick test. Both stereoisomers had anti-nociceptive effects, but (-)-nicotine was up to 970 times more potent, depending on test conditions. The antinociceptive action of (-)-nicotine was antagonized by mecamylamine and yohimbine but not by naloxone and atropine. The findings show that spinal mechanisms are highly stereoselective toward nicotine, and suggest that primarily nicotinergic and alpha-adrenergic receptors are involved in its central antinociceptive effects.

Analgesia↗

Isolation of genes showing increased or unique expression in the infective promastigotes of Leishmania major.

The trypanosomatid parasite Leishmania major is one of the principal causal agents of human cutaneous leishmaniasis. Promastigotes grown in vitro undergo growth cycle-dependent differentiation, associated with morphological and biochemical changes, to produce forms which are infective to the mammalian host. By differentially screening a cDNA library constructed from stage-specific mRNA, we have isolated 4 clones encoding mRNAs which show unique or elevated expression in the infective promastigotes of Leishmania major. One of these clones is homologous to a heat-shock protein 70-related gene, that is non-heat-inducible but shows up-regulation during promastigote differentiation. Each of the other cDNAs isolated also recognises multiple transcripts, which show differential regulation between parasite stages and are encoded by repeated, linked nuclear genes. In trypanosomatids, this genomic organisation is indicative of polycistronic transcription.

Animals↗

Surgery of the bovine small intestine.

Cattle require surgery for small-intestinal problems less frequently than they do for abomasal, forestomach, or large-intestinal problems. Close attention to local vascular anatomy is critical to success when intestinal resection is required. Cows with signs of severe abdominal pain may make rapid recoveries following prompt surgical treatment. This article discusses relevant anatomy of the small intestine and the diagnosis and treatment of intussusception, volvulus, obstruction by incarceration or entrapment, and duodenal obstruction.

Animals↗

An assessment of error in parental occupation from the birth certificate.

This study used data obtained through interview with the mother to determine whether parental occupations from the California birth certificate were representative of maternal occupations during the first trimester of pregnancy or paternal occupations 3 months before conception. For 71% of mothers and 80% of fathers, the occupation on the birth certificate was the same as the occupation elicited from the interview. The sensitivity of the birth certificate for determining whether a mother or father was employed or employed in a particular standard occupational category ranged from 50 to 100%. The bias to the odds ratio associated with a sensitivity of 75% and a specificity of 80% is presented. The results suggest that the use of birth certificate information on parental occupation to screen for associations with congenital malformations will miss all but very strong associations.

Adult↗

The pharmacokinetics of midazolam in patients with congestive heart failure.

The disposition of midazolam was investigated in six patients with congestive heart failure (CHF) and six age- and weight-matched healthy subjects by administering two single doses of the drug (3.75 mg i.v. and 7.5 mg p.o.) separated by 1 week. Serial blood samples were collected for 24 h after each dose and plasma was assayed for midazolam by GC-MS. In the CHF patients, the elimination half-life was prolonged (4 to 4.5 vs less than 3 h), the systemic clearance was lowered (376 vs 551 ml min-1) and the peak plasma drug concentration after the p.o. dose was higher (76 vs 42 ng ml-1). The systemic availability (45 vs 41%), the steady state volume of distribution (111 vs 108 l) and the time of peak plasma drug concentration after the p.o. dose (0.9 vs 0.9 h) were unchanged. The predominant effect of CHF was on the clearance of midazolam which was decreased by 30%. The drug was well tolerated and did not cause any adverse effects.

Adult↗

Amplification and analysis of human DNA present in mosquito bloodmeals.

DNA fingerprinting should permit the identification of individual human hosts of haematophagous arthropods, providing epidemiologically useful information, for example, the biting rates on different people and the impact of insecticide-impregnated bednets. Investigations reported here demonstrate that it is possible to extract, amplify and fingerprint human DNA from the bloodmeals of individual female Anopheles gambiae mosquitoes kept at 24 degrees C for up to 10-15 h post-ingestion.

Animals↗

Normal values for Type A behaviour patterns in Danish men and women and in potential high-risk groups.

The Jenkins Activity Survey (JAS) was administered to a normal population of randomly selected Danish adults, to patients consulting a cardiologist, and to physicians in order to compare those groups in terms of their coronary-prone (Type A) behaviour patterns. The standard procedure of rating the JAS was used in order to obtain scores for each of the four subscales: Type A (time urgency and ambitiousness), Factor S (speed and impatience) Factor H (hard-driving and competitive) and Factor J (job involvement). Gender differences were observed in the normal population for each of the four subscale scores, and age-related differences were obtained for Factor J. Elevated scores for Factor S were obtained by physicians and by people in the population who had a cardiovascular disorder. Physicians had also elevated scores for Factor J, whereas their Factor H scores tended to be reduced. No reliable differences in JAS subscale scores were observed between four groups of heart patients (i.e. angina pectoris, arterial hypertension, atrial fibrillation and atherosclerosis), although there was a tendency for Factor J to be elevated in atherosclerosis. The findings provide normal values for JAS scores in Danish men and women, and suggest that some facets of coronary-prone behaviour may be enhanced in Danish high-risk groups.

Adult↗

Effects of lithium and rolipram enantiomers on locomotor activity in inbred mice.

Rolipram is a racemic drug that increases brain cAMP availability by inhibiting phosphodiesterase. Lithium, on the other hand, reduces cAMP levels in brain by inhibiting adenylate cyclase and by increasing phosphodiesterase activity. Inbred strains of mice were used in the present study to determine whether the opposite effects of lithium and rolipram on cAMP levels were evident from behavioural effects of the drugs. In the first experiment, locomotor activity was measured in strains of male and female mice given an injection of either vehicle, (+)- or (-)-rolipram in order to find appropriate test conditions for studying interactions with lithium. (-)-Rolipram was more potent than its antipode in inducing hypokinesia, and the effects of (+)- and (-)-rolipram depended on mouse strain. In the second experiment, mice received lithium in their food for 3-4 weeks prior to testing, and they were then given an injection of vehicle, (+)- or (-)-rolipram before behaviour tests. Lithium reduced locomotor activity in mice given the vehicle, whereas it counteracted activity-suppressant effects of rolipram. The behavioural findings are consistent with the opposite pharmacological effects of lithium and rolipram on cAMP, and support the notion that cAMP availability in brain may play a role in behavioural effects of lithium and rolipram.

Animals↗