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Biomedical subjects

S C Smith

Publications and source records attributed to S C Smith.

At least 55 records · Page 3Linked to original sources
PubMed2000

Evidence for an accessory protein function for Toll-like receptor 1 in anti-bacterial responses.

Members of the Toll-like receptor (TLR) family are components of the mammalian anti-microbial response, signaling with a domain closely related to that of IL-1 receptors. In this report the expression and function of TLR1, a TLR of unknown function, are examined. TLR1 is expressed by monocytes, as demonstrated using a novel mAb. Monocytes also express TLR2. TLR1 transfection of HeLa cells, which express neither TLR1 nor TLR2, was not sufficient to confer responsiveness to several microbial extracts. However, cotransfection of TLR1 and TLR2 resulted in enhanced signaling by HeLa cells to soluble factors released from Neisseria meningitidis relative to the response with either TLR alone. This phenomenon was also seen with high concentrations of some preparations of LPS. The N. meningitidis factors recognized by TLR1/TLR2 were not released by N. meningitidis mutant in the LpxA gene. Although LpxA is required for LPS biosynthesis, because cooperation between TLR1 and TLR2 was not seen with all LPS preparations, the microbial component(s) TLR1/2 recognizes is likely to be a complex of LPS and other molecules or a compound metabolically and chemically related to LPS. The functional IL-1R consists of a heterodimer; this report suggests a similar mechanism for TLR1 and TLR2, for certain agonists. These data further suggest that mammalian responsiveness to some bacterial products may be mediated by combinations of TLRs, suggesting a mechanism for diversifying the repertoire of Toll-mediated responses.

Acyltransferases↗
PubMed2000

Bridging the treatment gap.

The leading cause of death and disability in the United States today is cardiovascular disease (CVD). The main risk factor, hypercholesterolemia, is grossly undertreated, although it is widely appreciated that lowering cholesterol levels is key to reducing the incidence of CVD. Cholesterol-lowering therapy decreases total mortality, cardiovascular events, the need for revascularization procedures, and hospitalization costs. A 25-35% reduction of low-density lipoprotein (LDL) indicates significant benefits with regard to morbidity and mortality. Unfortunately, most patients who are candidates for cholesterol-lowering treatment do not receive it. Wider use of lipid-lowering agents could, in fact, make a significant difference in patient outcomes. There is strong interest on the part of consumers in over-the-counter (OTC) cholesterol-lowering products that may help them reduce their risk of developing heart disease and live healthier lives. Surveys estimate that half of all patients with high cholesterol would like to have an OTC statin product made available. Increased availability of cholesterol-lowering therapies as well as changes in physician prescribing practices could benefit a broad spectrum of the population that is currently untreated or undertreated. Current prescribing practices and guidelines have not resulted in widespread use of these therapies; therefore, outcomes for CVD prevention remains suboptimal. The proposed advantages of making statins available over-the-counter include their known efficacy, dose consistency, and proven safety profile.

Adult↗
PubMed2000

Preoperative factors predisposing to early postoperative atrial fibrillation after isolated coronary artery bypass grafting.

An analysis of 183 patients in sinus rhythm who underwent coronary artery bypass grafting was conducted to determine the association of multiple preoperative factors, including an elevated left ventricular end-diastolic pressure, with early postoperative atrial fibrillation. An association with advanced age, a history of atrial fibrillation, and preoperative digoxin use was found, but not with an elevated left ventricular end-diastolic pressure, irrespective of left ventricular systolic function.

Age Factors↗
PubMed2000

Isosmotic media prevent edema in amphibian larvae without cardiac function.

The absence of cardiac and circulatory function causes severe edema in amphibian embryos. Analyzing the roles of embryonic and larval circulation in respiration may thus be confounded by the increased diffusion distance and decreased surface area/volume ratio caused by edema. Similarly, detailed morphological analyses of embryos/larvae with defective circulatory or renal function is difficult or impossible due to the gross morphological anomalies engendered by edematous swelling. To circumvent these problems, two media have been developed which are isosmotic with the plasma of a common experimental amphibian species (Ambystoma mexicanun). These media are remarkably effective in preventing fluid accumulation in embryos and larvae lacking heart function and, when used in slightly lower concentrations, cause no apparent harm to embryos and larvae with normal circulation for periods up to 3 weeks. These media should prove useful for a variety of studies on the developmental physiology of the circulatory system and possibly also when examining the development of renal function and ionoregulation.

Ambystoma mexicanum↗
PubMed2000

Putting prevention into daily practice.

The future holds promise for expanding preventive therapies to reduce cardiovascular risk. These preventive concepts are supported by sound science and strong evidence from multiple randomized clinical trials. To be successful, the health care system must continue to provide financial resources to support physicians and other health care providers in preventive cardiovascular efforts. In the long run, this support should result in a decrease in the need for expensive high-technology, acute-care interventions. Health care provider teams involving physicians, nurses, and other providers will be necessary to ensure the success of these measures, and they must be integrated into the expanding network of inpatient and outpatient delivery systems. Finally, programs to train fellows, residents, and medical students in preventive skills will provide the basis for expanded application of cardiovascular risk therapies and contribute to the ultimate widespread success in decreasing the morbidity and mortality from cardiovascular disease.

Adult↗
PubMed2000

Use of food labels and beliefs about diet-disease relationships among university students.

OBJECTIVE: The purpose of this study was to measure the reported use of nutrition information on food labels by a population of university students and to determine if label users differed from non-users in terms of gender and specific beliefs related to label information and diet-disease relationships, specifically fat and heart disease and fibre and cancer. DESIGN: A single-stage cluster sampling technique was used. Data was obtained using a self-administered, validated questionnaire. SETTING: The present investigation took place at the University of Saskatchewan, Canada in the autumn of 1997. SUBJECTS: : A total of 553 students in randomly selected classes in the College of Arts and Science took part in the survey (92% response rate). The sample consisted of roughly equal numbers of males and females, most between the ages of 18 and 24. RESULTS: There were approximately equal numbers of label users and non-users among males, while label users outnumbered non-users by almost four to one among females. The importance of nutrition information on food labels was the only belief that differed significantly between label users and non-users for both sexes. For females, no other beliefs distinguished label users from non-users. However, for males, significant differences were found between label users and non-users on the beliefs that nutrition information is truthful and that a relationship between fibre and cancer exists. CONCLUSIONS: Females appear to use food labels more often than do males. The only consistently observed difference between label users and non-users (male and female) was that users believed in the importance of nutrition information on food labels while non-users did not.

Adolescent↗
PubMed2000

Identification of a Salmonella typhimurium genomic region involved in invasion of HeLa and Henle-407 epithelial cells.

To identify the invasion determinant, a cosmid library was constructed by cloning a genomic library of Salmonella typhimurium 82/6915 into a cosmid vector, pLA2917. A genomic region involved in invasion of cultured HeLa and Henle-407 cells was subcloned into plasmid pGEM-7Z. E. coli strain DH1 carrying pSV6235 consisting of a S. typhimurium 4.6 kb genomic region in pGEM-7Z showed invasion of cultured HeLa and Henle-407 cells. Nested sequential deletions were introduced into the 4.6 kb genomic region of pSV6235. The E. coli recombinants which contained less than 1.5 kb deletions from the 5' end (SmaI site) of the genomic region invaded the cells as effectively as DH1 (pSV6235). The invasion of the recombinants carrying over 2.0 kb deletions from the end of pSV6235 was significantly inactivated compared to DH1 (pSV6235). Restriction enzyme analysis showed that the 3.1 kb fragment from the 3' end of the 4.6 kb genomic region was distinguished from the Salmonella pathogenicity I genes of S. typhimurium such as the inv, spa, and hil regions showing invasion of the cultured eukaryotic cells.

Cell Line↗
PubMed2000

Detection of a novel campylobacter cytotoxin.

The culture filtrates from 10 Campylobacter species were screened for the presence of cytotoxins on a variety of selected tissue culture cell lines. Some Campylobacter jejuni strains showed no effects on tissue culture cell lines compared with other C. jejuni strains, especially C. jejuni 81116, which consistently produced a cytotoxin that was lethal to tissue culture cells. It was observed that CHO cells were the most sensitive cell line in detecting campylobacter cytotoxins. Samples containing the culture filtrate of C. jejuni 81116 prepared at various growth stages were used to determine the subcellular location of the cytotoxin. This C. jejuni 81116 cytotoxin appears to be a heat-stable toxin that is secreted from the cell during stationary phase; cytotoxin activity can be abolished with proteolytic enzymes.

Animals↗
PubMed2000

Effect of sex, hemodynamics, body size, and other clinical variables on the corrected thrombolysis in myocardial infarction frame count used as an assessment of coronary blood flow.

BACKGROUND: Compared with the conventional Thrombolysis In Myocardial Infarction (TIMI) flow grade system, the corrected TIMI frame count (CTFC) quantifies coronary blood flow in a more reproducible fashion. The purpose of this study was to determine if the CTFC is affected by sex, body size, hemodynamics, or other selected clinical variables. METHODS AND RESULTS: CTFC was measured in 534 coronary arteries from 200 consecutive patients referred for coronary angiography. CTFC in each artery was related to patient variables (sex, age, race, and body surface area), clinical variables (cardiac rhythm, medication use, diabetes, hypertension, hypercholesterolemia, smoking, and left ventricular hypertrophy), angiographic variables (wall motion abnormality in each coronary artery distribution, left ventricular ejection fraction, percent stenosis in the artery, and presence of collaterals), and hemodynamic variables (aortic systolic and diastolic blood pressure and left ventricular end-diastolic pressure). By multivariate analysis, CTFC in all arteries was significantly associated with aortic systolic and diastolic pressures and body surface area. In addition, there were significant associations between CTFC and age and sex in some but not all arteries. Although significant, the absolute change in CTFC associated with these variables was small. CONCLUSIONS: CTFC provides a quantitative assessment of coronary blood flow that varies only a small amount in association with body size, systemic arterial pressure, age, and sex.

Age Factors↗
PubMed2000

Apoptosis is a rare event in first-trimester placental tissue.

OBJECTIVE: The aim of this study was to confirm our previous findings of an increase in the incidence of placental apoptosis with increasing gestational age by means of transmission electron microscopic assessment of first-trimester placental tissue. We also wanted to challenge the validity of terminal uracil nick end-labeling staining for the assessment of placental apoptosis. STUDY DESIGN: The incidence of apoptosis was quantified with hematoxylin and eosin staining and terminal uracil nick end-labeling staining in 6 first-trimester placental samples, 5 second-trimester placental samples, and 7 third-trimester placental samples. These results were then compared with the results that were obtained by quantifying apoptosis in 6 first-trimester placental samples with transmission electron microscopy. RESULTS: Our previous hematoxylin and eosin-staining findings of a rise in apoptosis with increasing gestational age were confirmed. Transmission electron microscopy confirmed the low incidence of apoptosis in first-trimester placental tissue. Terminal uracil nick end-labeling staining produced incongruous results. CONCLUSION: Our earlier findings of a low incidence of apoptosis in first-trimester placental tissue have been confirmed by transmission electron microscopy, which remains the criterion standard in the assessment of apoptosis. Our findings discredit terminal uracil nick end-labeling staining for the assessment of placental apoptosis.

Apoptosis↗
PubMed2000

Folate affects apoptosis in human trophoblastic cells.

Effects of folate deficiency on the rate of apoptosis in human cytotrophoblastic cells has been investigated. Apoptosis was determined in cytotrophoblastic cells after culture in 1. control medium, 2. folate-free medium and 3. folate-free medium plus 10% fetal calf serum. Apoptosis rates in cells cultured in mediums 2 and 3 were significantly higher than those cultured in the control medium (P<0.02 and P<0.03, respectively). In conclusion, human cytotrophoblastic cells show a significantly increased rate of apoptosis in vitro after culture in a folate-free medium. Possible explanations for the association between folate deficiency and pregnancy complications are suggested.

Apoptosis↗
PubMed2000

Evaluation and treatment of thermal injuries.

An estimated 1 to 2 million Americans suffer burn injuries each year. The majority of these are minor; however, approximately 70,000 individuals sustain injuries severe enough to require admission to a hospital or burn center for treatment.

Airway Obstruction↗
PubMed1999

Calcium channel blockers and mortality in elderly patients with myocardial infarction.

BACKGROUND: Although calcium channel blockers are a useful therapy in relieving angina, lowering blood pressure, and slowing conduction of atrial fibrillation, growing evidence has cast doubt on their safety in patients with coronary disease. OBJECTIVE: To examine the association between calcium channel blocker therapy at hospital discharge and mortality in a population-based sample of elderly patients hospitalized with acute myocardial infarction. DESIGN: Retrospective cohort study using data from medical charts and administrative files. SETTING: All acute care hospitals in 46 states. PATIENTS: All Medicare patients with a principal diagnosis of acute myocardial infarction consecutively discharged from the hospital alive during 8-month periods between 1994 and 1995 (N = 141,041). MAIN OUTCOME MEASURE: Mortality at 30 days and 1 year. RESULTS: Calcium channel blockers were widely prescribed at hospital discharge to elderly patients with myocardial infarction between 1994 and 1995 (n = 51,921), the most commonly prescribed being diltiazem (n = 21,175), nifedipine (n = 12,670), amlodipine (n = 11,683), and verapamil (n = 3639). After adjusting for illness severity and concomitant medication use, patients who were prescribed calcium channel blockers at hospital discharge did not have increased risk for 30-day or 1-year mortality, with the exception of the few (n = 116) treated with bepridil. Bepridil differs from other calcium channel blockers because of its tendency to prolong repolarization, and its association with proarrhythmic effects in elderly patients. CONCLUSION: We did not identify a mortality risk in a large consecutive sample of elderly patients with myocardial infarction, which supports the need for additional prospective trials examining calcium channel blocker therapy for ischemic heart disease.

Aged↗