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Biomedical subjects

K R Smith

Publications and source records attributed to K R Smith.

At least 91 records · Page 5Linked to original sources

Manganese stimulates the oxidative burst of differentiated HL-60 cells.

Incubation with manganese results in a twofold increase in the oxidative burst of differentiated HL-60 cells. This stimulation was characterized by examining the dose response, length of incubation time, and specificity of manganese. Manganese only stimulated the burst in cells induced to differentiated with retinoic acid and not in undifferentiated HL-60 cells. Incubation with manganese did not result in a greater number of differentiated cells. The maximum stimulation occurred at 0.2 mumol/L manganese. Stimulation of the oxidative burst required 96 h of incubation with manganese, since cells incubated with the same levels of manganese for the last 24 h of culture did not result in any stimulation. Magnesium, present in the incubation medium at physiological serum levels (820 mumol/L) also stimulated the oxidative burst, whereas iron (0.3 mumol/L), zinc (18 mumol/L), and copper (12 mumol/L) had no effect. To determine whether manganese and magnesium stimulated the burst differently, the initial rates of superoxide anion production was determined. The initial rate of the reaction proceeded rapidly in cells incubated with manganese, whereas there appeared to be a lag before magnesium-treated cells produced superoxide anion. Thus, manganese seems to stimulate the oxidative burst differently than magnesium.

Analysis of Variance↗

Myocardial glucose transporters and glycolytic metabolism during ischemia in hyperglycemic diabetic swine.

We assessed the effects of 4 weeks of streptozocin-induced diabetes on regional myocardial glycolytic metabolism during ischemia in anesthetized open-chest domestic swine. Diabetic animals were hyperglycemic (12.0 +/- 2.1 v 6.6 +/- .5 mmol/L), and had lower fasting insulin levels (27 +/- 8 v 79 +/- 19 pmol/L). Myocardial glycolytic metabolism was studied with coronary flow controlled by an extracorporeal perfusion circuit. Left anterior descending coronary artery (LAD) flow was decreased by 50% for 45 minutes and left circumflex (CFX) flow was constant. Myocardial glucose uptake and extraction were measured with D-[6-3H]-2-deoxyglucose (DG) and myocardial blood flow was measured with microspheres. The rate of glucose conversion to lactate and lactate uptake and output were assessed with a continuous infusion of [6-14C]glucose and [U-13C]lactate into the coronary perfusion circuit. Both diabetic and nondiabetic animals had sharp decreases in subendocardial blood flow during ischemia (from 1.21 +/- .10 to 0.43 +/- .08 mL.g-1.min-1 in the nondiabetic group, and from 1.30 +/- .15 to 0.55 +/- .11 in the diabetic group). Diabetes had no significant effect on myocardial glucose uptake or glucose conversion to lactate under either well-perfused or ischemic conditions. Forty-five minutes of ischemia resulted in significant glycogen depletion in the subendocardium in both nondiabetic and diabetic animals, with no differences between the two groups. Glycolytic metabolism is not impaired in hyperglycemic diabetic swine after 1 month of the disease when compared with that in normoglycemic nondiabetic animals. The myocardial content of the insulin-regulatable glucose transporter (GLUT 4) was measured in left ventricular biopsies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effects of occupational class transitions on hypertension: racial disparities among working-age men.

OBJECTIVES: This study was undertaken to examine how the interaction between occupational class transitions and race affects the incidence of hypertension. METHODS: A cohort of 1982 men (183 Black), ages 25 to 55, received a baseline medical exam between 1971 and 1975 and a follow-up between 1982 and 1984. Logistic regressions were estimated for hypertension at follow-up controlling for hypertension at baseline, other risk factors associated with blood pressure, and interaction terms identifying specific occupational class transitions among Blacks and Whites. The occupational class matrix was based largely on scores of US Census Bureau occupations from the Dictionary of Occupational Titles. RESULTS: Relative to Whites who remained in professional and technical jobs between baseline and follow-up, Blacks and Whites who remained in lower occupational classes or made specific transitions--notably into the lowest class--had significantly higher incidence rates of hypertension. These differences were greater among Blacks, who are also more concentrated in and less likely to move upward from the lower end of the occupational class matrix. CONCLUSIONS: Widening racial disparities in high blood pressure over the period of study may be partly attributable to characteristics associated with occupational class position and dynamics.

Adult↗

Double jeopardy: interaction effects of marital and poverty status on the risk of mortality.

The purpose of this paper is to examine the hypothesis that marital and poverty status interact in their effects on mortality risks beyond their main effects. This study examines the epidemiological bases for applying an additive rather than a multiplicative specification when testing for interaction between two discrete risk factors. We specifically predict that risks associated with being nonmarried and with being poor interact to produce mortality risks that are greater than each risk acting independently. The analysis is based on men and women who were ages 25-74 during the 1971-1975 National Health and Nutrition Examination Survey I (NHANES I) and who were traced successfully in the NHANES I Epidemiologic Follow-Up Study in 1982-1984. Overall, being both poor and nonmarried places nonelderly (ages 25-64) men, but not women, at risk of mortality greater than that expected from the main effects. This study shows that for all-cause mortality, marital and poverty status interact for men but less so for women; these findings exist when interaction is assessed with either a multiplicative or an additive standard. This difference is most pronounced for poor, widowed men and (to a lesser degree) poor, divorced men. For violent/accidental deaths among men, the interaction effects are large on the basis of an additive model. Weak main and interaction effects were detected for the elderly (age 65+).

Accidents↗

Linked lives, dependent demise? Survival analysis of husbands and wives.

Past research has found that married individuals have substantially lower risks of mortality than their single counterparts. This paper examines how household characteristics affect spouses' risks of mortality. A paired hazard rate model is estimated and tests are made to ascertain whether the estimated coefficients associated with risk factors differ between husbands' and wives' equations. Cigarette smoking, risk-avoidance behavior, poverty, and children are found to affect wives' and husbands' mortality in similar ways. Divorce, which can be interpreted as the termination of this shared household environment, is found to affect spouses differently.

Adult↗

Technical note: equine skeletal preservation techniques to enhance teaching effectiveness.

When the decision was made to euthanatize an acutely laminitic Thoroughbred broodmare, graduate students from the Department of Animal Sciences and Industry reconstructed the skeleton for use as a teaching tool. The reproductive and gastrointestinal tracts were removed and preserved in formalin. The hide, muscle, tendons, ligaments, and organs were removed, and the bones were boiled in water for > or = 48 h to remove all remaining tissue. After boiling, the bones were soaked in gasoline to remove fat from the marrow cavities and then soaked in a bleach/detergent mixture as a final cleaning step. The bones were allowed to dry for several weeks, then a semi-gloss clear lacquer was applied to aid in preservation. The bones were connected with 17-gauge wire and supported by two 1.91-cm galvanized steel rods on a mobile platform. The vertebral column was aligned on flexible copper tube with a 1.27-cm diameter. Additional support was provided for the head and neck by aluminum and steel rods extending from the front support. The final product is a complete, mobile skeleton that will be used as a teaching aid in equine classes. The skeleton serves a function for all levels of the cognitive learning domain. Examples of applications include memorization, identification, and location of bones; use in case studies for synthesis and demonstration of brainstorming efforts; and evaluation of joint ailments for more advanced levels of learning.

Animal Husbandry↗

Escherichia coli Rep protein and helicase IV. Distributive single-stranded DNA-dependent ATPases that catalyze a limited unwinding reaction in vitro.

Rep protein and helicase IV, two DNA-dependent adenosine 5'-triphosphatases with helicase activity, have been purified from Escherichia coli and characterized. Both enzymes exhibit a distributive interaction with single-stranded DNA as DNA-dependent ATPases in a reaction that is relatively resistant to increasing NaCl concentration and sensitive to the addition of E. coli single-stranded DNA binding protein (SSB). The helicase reaction catalyzed by each protein has been characterized using a direct unwinding assay and partial duplex DNA substrates. Both Rep protein and helicase IV catalyzed the unwinding of a duplex region 71 bp in length. However, unwinding of a 119-bp or 343-bp duplex region was substantially reduced compared to unwinding of the 71-bp substrate. At each concentration of protein examined, the number of base pairs unwound was greatest using the 71-bp substrate, intermediate with the 119-bp substrate and lowest using the 343-bp substrate. The addition of E. coli SSB did not increase the fraction of the 343-nucleotide fragment unwound by Rep protein. However, the addition of SSB did stimulate the unwinding reaction catalyzed by helicase IV approximately twofold. In addition, ionic strength conditions which stabilize duplex DNA (i.e. addition of MgCl2 or NaCl), markedly inhibited the helicase reaction catalyzed by either Rep protein or helicase IV while having little effect on the ATPase reaction. Thus, these two enzymes appear to share a common biochemical mechanism for unwinding duplex DNA which can be described as limited unwinding of duplex DNA. Taken together these data suggest that, in vitro, and in the absence of additional proteins, neither Rep protein nor helicase IV catalyzes a processive unwinding reaction.

Adenosine Triphosphatases↗

In vitro activity of sparfloxacin and three other fluoroquinolones against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis.

Fluoroquinolones are variably active against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE). The purpose of this study was to test the in vitro susceptibility of 50 isolates each of MRSA and MRSE to four of the new fluoroquinolones--sparfloxacin, ciprofloxacin, ofloxacin and norfloxacin--and to see if resistance could be induced in five susceptible strains of each species by serial passages with increasing concentrations of drug. A standard microdilution technique was used to determine minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of each drug for each isolate. Agar dilution plates were also prepared containing concentrations of drug varying from one-half of the reported MIC to 128 times the reported MIC, and microorganisms persisting were serially passaged. Initially, 98% of the strains of MRSA were susceptible to the fluoroquinolones. MBCs were essentially identical to MICs. Similarly, 96% of the strains of MRSE were susceptible. Following exposure to increasing concentrations of each fluoroquinolone, resistance appeared to emerge less rapidly to sparfloxacin and ofloxacin than to norfloxacin and ciprofloxacin.

Anti-Infective Agents↗

Correct folding of alpha-lytic protease is required for its extracellular secretion from Escherichia coli.

alpha-Lytic protease is a bacterial serine protease of the trypsin family that is synthesized as a 39-kD preproenzyme (Silen, J. L., C. N. McGrath, K. R. Smith, and D. A. Agard. 1988. Gene (Amst.). 69: 237-244). The 198-amino acid mature protease is secreted into the culture medium by the native host, Lysobacter enzymogenes (Whitaker, D. R. 1970. Methods Enzymol. 19:599-613). Expression experiments in Escherichia coli revealed that the 166-amino acid pro region is transiently required either in cis (Silen, J. L., D. Frank, A. Fujishige, R. Bone, and D. A. Agard. 1989. J. Bacteriol. 171:1320-1325) or in trans (Silen, J. L., and D. A. Agard. 1989. Nature (Lond.). 341:462-464) for the proper folding and extracellular accumulation of the enzyme. The maturation process is temperature sensitive in E. coli; unprocessed precursor accumulates in the cells at temperatures above 30 degrees C (Silen, J. L., D. Frank, A. Fujishige, R. Bone, and D. A. Agard. 1989. J. Bacteriol. 171:1320-1325). Here we show that full-length precursor produced at nonpermissive temperatures is tightly associated with the E. coli outer membrane. The active site mutant Ser 195----Ala (SA195), which is incapable of self-processing, also accumulates as a precursor in the outer membrane, even when expressed at permissive temperatures. When the protease domain is expressed in the absence of the pro region, the misfolded, inactive protease also cofractionates with the outer membrane. However, when the folding requirement for either wild-type or mutant protease domains is provided by expressing the pro region in trans, both are efficiently secreted into the extracellular medium. Attempts to separate folding and secretion functions by extensive deletion mutagenesis within the pro region were unsuccessful. Taken together, these results suggest that only properly folded and processed forms of alpha-lytic protease are efficiently transported to the medium.

Bacterial Outer Membrane Proteins↗

Taurine depletion and cardiovascular disease in adult cats fed a potassium-depleted acidified diet.

Although low plasma taurine concentrations have been associated with congestive cardiomyopathy in cats, the cause of taurine depletion in cats consuming adequate quantities of taurine is unknown. Taurine depletion and cardiovascular disease (cardiomyopathy and thromboembolism) developed unexpectedly in 3 of 6 healthy adult cats during a potassium-depletion study. Plasma taurine concentration decreased significantly (P less than 0.05) and rapidly over an 8-week period (from 98 to 36 nmol/ml) in 6 cats that consumed a potassium-deficient diet (0.20% potassium, dry matter basis) that was acidified with 0.8% ammonium chloride, despite containing dietary taurine concentrations (0.12% dry matter basis) in excess of amounts currently recommended. Taurine concentrations were significantly lower in cats fed the acidified diet than in 6 cats fed a potassium-deficient diet that was not acidified (36 nmol/ml vs 75 nmol/ml) after 8 weeks. In addition, plasma taurine concentrations did not decrease over a 6-month period in 8 cats that were fed a potassium-replete diet with acidifier. Plasma taurine concentrations were lowest in 3 cats that died of cardiovascular disease in the group receiving potassium-deficient, acidified diets. These data indicated an association between taurine and potassium balance in cats and suggested that development of taurine depletion and cardiovascular disease may be linked to concurrent potassium depletion.

Ammonium Chloride↗

In vitro comparison of cilofungin alone and in combination with other antifungal agents against clinical isolates of Candida species.

Cilofungin, a lipopeptide antifungal agent, was tested for in vitro activity alone and in combination with ketoconazole, itraconazole, flucytosine and amphotericin B against 102 clinical isolates of Candida species. At 48 hours all isolates of Candida albicans, Candida tropicalis, Candida paratropicalis and Candida glabrata were inhibited by less than or equal to 5 meg/ml of cilofungin. In contrast, the MIC90 for Candida krusei was 10 mcg/ml and for Candida parapsilosis greater than 40 mcg/ml. The interaction of combinations of cilofungin with amphotericin B, itraconazole, ketoconazole and flucytosine was additive or indifferent at 48 hours for 100%, 88%, 78% and 70% of all Candida species isolates, respectively. Overall, cilofungin demonstrated good activity in vitro against most Candida species isolates.

Amphotericin B↗

Cerebrospinal fluid endothelin-1 and endothelin-3 levels in normal and neurosurgical patients: a clinical study and literature review.

Endothelins are a family of structurally related, potent, long-lasting vasoconstrictor peptides. There are no established normal human levels of endothelin-1 or endothelin-3 in the cerebrospinal fluid. We measured cerebrospinal fluid endothelin-1 and endothelin-3 levels in five groups of patients: normal controls, patients with subarachnoid hemorrhage and cerebral vasospasm, patients with severe head injuries, patients undergoing temporal lobectomy for intractable epilepsy, and a patient with a gunshot injury to the thoracic spine. Endothelin-3 levels were significantly elevated in patients with subarachnoid hemorrhage and may participate in cerebral vasospasm and subsequent neurologic deterioration.

Adult↗

Incidence of Listeria monocytogenes in meat production environments of a South Island (New Zealand) mutton slaughterhouse.

The results of a survey conducted at a South Island, New Zealand, abattoir are presented. Two-hundred-and-eighteen samples taken from ovine carcasses and the environment were analysed. The traditional cold enrichment, i.e. 4 degrees C for up to 16 weeks, was used. No isolations of listeriae were made from freshly dressed carcasses or from surfaces with which meat makes contact. However, seven isolates of Listeria monocytogenes were obtained from cold rooms operating at 5 degrees C and which are used to store carcasses. Also, a single isolate of L. ivanovii was obtained from a mesh screen strainer of the waste water treatment plant located near the works. The study indicates that ovine carcasses can be prepared free of L. monocytogenes, that cold rooms may be a source of these microorganisms and it also reconfirms that listeriae can be found in soil and fodder of animal paddocks adjacent to the abattoir.

Abattoirs↗

Open depressed skull fracture missed on computed tomography: a case report.

A case of an open depressed skull fracture that was missed on standard computed tomographic (CT) scan is presented. The fracture was seen on a CT generated lateral scout film, and after repositioning the gantry, further CT images clearly showed the fracture and underlying brain injury. The authors recommend that all patients with head trauma undergoing head CT have either a CT generated lateral scout film or a lateral skull radiograph to assess the vertex of the skull, an area poorly visualized on standard axial images.

Adult↗

Collinear nutrients and the risk of colon cancer.

The relationship between colon cancer risk and the relative contributions of fat and caloric intake are assessed. A lack of consensus exists regarding the role of each of these dietary factors in the development of colon cancer. This lack of agreement originates from the high correlations between the nutrients, as well as the manner in which researchers treat these dietary variables in their analyses. Four proposed methods are evaluated which attempt to address the collinearity problem in nutritional epidemiology: (1) exclude one or more collinear variables, (2) use the proportion of calories consumed attributable to each dietary component, (3) use a regression-adjustment approach to purge the collinearity correlated nutrients, and (4) ridge regression. Diagnostic tests are reported which assess the degree of collinearity on data collected for a case-control study of colon cancer conducted in Utah between 1979 and 1983. Using logistic regression analyses, we apply each of these methods to case-control data. We find that the risks associated with fat and caloric consumption are extremely sensitive to a priori analytic decisions made by epidemiologist about the underlying collinearity problem.

Case-Control Studies↗

Patterns of economic change surrounding the death of a spouse.

The timing of economic changes near the death of a spouse is not well understood. Using multiple regression analysis and longitudinal data from the Panel Study of Income Dynamics, the economic situations of middle-aged and older widows and widowers were compared to those of otherwise similar intact couples over an 11-year period. The analysis shows that all four widowed groups had fewer economic resources 5 years after the death than did their married counterparts. Yet, each group took very different economic paths to get to this point. For example, older widows and widowers begin the analysis with significantly lower income-to-needs ratios 5 years prior to the death, while middle-aged widows experience more economic change near the time of the death. These findings suggest that both middle-aged and older cohorts of widowed individuals may have made consumption choices over the life cycle that differ from those made by their intact counterparts.

Age Factors↗

Solid waste scavenger community: an investigation in Bangkok, Thailand.

A solid waste scavenger community at On-Nooch dump site in Bangkok was investigated. The purpose was to identify the dimensions of the public health risk to this group of people and their community due to exposure to hazardous conditions from waste materials. A cross-sectional descriptive study utilizing field surveys and measurements was performed. The demographic, socioeconomic, health related and environmental characteristics of this community were examined. Health complaints and injuries were inventoried among scavengers. Prevalence of childhood respiratory illness was high especially in those households where smoking was present. Intestinal helminthic and protozoan infection in children were detected. Six individuals with possible HIV infection and a number of Hepatitis B anti-genemia were found among male respondents. An appreciable proportion of respondents fell below normal when tested for lung function. Air pollution measurements showed acceptable ambient air levels except for particulate matters. Water quality was low for both potable and nonpotable water.

Adolescent↗