Search PubMed⌕ Search

Biomedical subjects

S M Smith

Publications and source records attributed to S M Smith.

At least 289 records · Page 16Linked to original sources

Hemin enhances differentiation and maturation of cultured regenerated skeletal myotubes.

Satellite cells, isolated from marcaine-damaged rat skeletal muscle, differentiate in culture to form contracting, cross-striated myotubes. Addition of 20 microM hemin (ferriprotoporphyrin IX chloride) to the culture medium resulted in increases in the number, size, and alignment of myotubes; in the number of myotubes that exhibited cross-striations; and in the strength and frequency of myotube contractions. Hemin increased satellite cell fusion by 27%, but decreased cell proliferative rate by 30%. Hemin increased the specific activity of creatine kinase (CK), a sensitive indicator of muscle differentiation, by 157%. Separation of CK isoenzymes by agarose gel electrophoresis showed that hemin increased only the muscle-specific CK isoenzymes (MM-CK and MB-CK). Thus, hemin seems to duplicate some of the effects of innervation on cultured myotubes by increasing contraction frequency and strength, appearance of cross-striations, and muscle-specific isoenzymes. In contrast, 3-amino-1,2,4-triazole, an inhibitor of heme biosynthesis, decreased the number of cross-striated myotubes, the strength and frequency of myotube contractions, and CK activity. These inhibitory effects were reversed by hemin. Collectively, these results demonstrate a physiologically significant role for heme in myotube maturation.

Animals↗

The malate synthase gene of cucumber.

The complete sequences of a full-length cDNA clone and a genomic clone encoding the Cucumis sativus glyoxysomal enzyme malate synthase, have been determined. The sequences have enabled us to identify putative control regions at the 5' end of the gene, three introns, and possible alternative polyadenylation sites at the 3' end. The deduced amino acid sequence predicts a polypeptide of 64,961 molecular weight, which has 48% identity with that of Escherichia coli. Comparison of the sequence of malate synthase from cucumber with that from E. coli and with other glyoxysomal and peroxisomal enzymes, shows that a conserved C-terminal tripeptide is a common feature of those enzymes imported into microbodies.

Amino Acid Sequence↗

Conductance states activated by glycine and GABA in rat cultured spinal neurones.

The conductance properties of single Cl- channels activated by glycine and gamma-aminobutyric acid (GABA) were examined in rat spinal cord neurones grown in cell culture. The majority (85%) of spinal neurones were sensitive to both glycine and GABA as were most (83%) outside-out patches tested. Glycine and GABA activated multiple conductance state Cl- channels with linear current-voltage properties when the chloride activities of the solutions bathing both sides of the membrane were similar. Glycine activated six distinct conductance states with conductances of 14, 20, 30, 43, 64 and 93 pS, whereas GABA activated five states with conductances of 13, 20, 29, 39 and 71 pS. The 30 and 43 pS states and the 20 and 29 pS states were observed most frequently with glycine and GABA, respectively. As the values of the glycine- and GABA-activated conductance states form a geometric progression when arranged in ascending order, we concluded that the channels do not consist of a cluster of identical pores. Additional conductance states (50 and 100 pS) were activated by glycine occasionally. The similarity between the conductances of the states activated by the two transmitters is consistent with the proposal that they both activate the same type of Cl- channel.

Animals↗

Magnetic resonance imaging of adrenal cortical carcinoma.

Five cases of adrenal cortical carcinoma examined with magnetic resonance (MR) are presented. Clinical histories, computed tomographic (CT) scans, and final pathologic findings were reviewed in each case. All masses were hypointense compared to the liver on T1-weighted images and became hyperintense compared to the liver on T2-weighted images. Signal intensity of adrenal masses, fat, and liver were measured. Adrenal/liver and adrenal/fat signal intensity ratios were then calculated. All the masses were readily identified with MR. The MR also demonstrated displacement or invasion of adjacent organs, as well as liver metastases. The inferior vena cava was also identified in each case. Even though there were no consistent MR findings to diagnose adrenal cortical carcinomas accurately, superior blood vessel identification and multiplanar capabilities may make MR the imaging modality of choice in evaluating the extent of disease and in planning surgical excision.

Adrenal Cortex↗

Norepinephrine turnover in iron deficiency: effect of two semi-purified diets.

The effects of two dietary treatments on norepinephrine turnover in iron deficiency were examined. These studies were designed to bridge the gap between previous studies of poor thermoregulation in iron deficiency which used a diet (HMW, Hubbel-Mendel-Wakeman formulation) relatively high in fat (46% of calories) and moderate in carbohydrate (46% of calories) and the more recent studies of thermogenesis in iron deficiency which use the AIN-76 recommended diet which is relatively low in fat (11% of calories) and high in carbohydrate (67% of calories). Iron deficient rats grew less well and had depressed thyroid hormone concentrations regardless of dietary treatment group. The HMW diet significantly increased norepinephrine turnover in heart in iron deficient animals relative to AIN diet but had no effect in controls. Brown adipose tissue norepinephrine turnover was threefold higher in HMW rats fed a low iron diet, and only 67 percent higher in control rats. This study demonstrates that certain modest macronutrient manipulations affect norepinephrine content and turnover more in iron deficient than controls. However, abnormalities in thyroid hormone concentrations persist in iron deficient animals regardless of these dietary treatments.

Adipose Tissue, Brown↗

The effects of alcohol, expectancy, and sensation seeking on driving risk taking.

Using a cover story of the effects of alcohol on perceptual and motor abilities, two levels of alcohol consumed (moderate and none), two levels of alcohol expectancy (moderate and none), and two levels of sensation seeking (high and low) were combined to determine their effect on risk taking in a driving simulator. Ninety-six subjects were randomly assigned to eight conditions. Dependent variables were lane changes-cars passed and time at maximum speed. Results on lane-changes-cars passed indicated greater risk-taking in driving by high sensation seekers. Interaction of alcohol expectancy and sensation seeking indicated high sensation seekers took more risks when they believed they had consumed alcohol. Low sensation seekers became more cautious in driving when they believed they had consumed alcohol. Alcohol consumed did not produce a significant main effect or interaction.

Adult↗

Plasma cell dyscrasia: a case of POEMS syndrome with a unique dermatologic presentation.

POEMS (polyneuropathy, organomegaly [hepatosplenomegaly or lymphadenopathy], endocrinopathy, M protein, and skin changes) syndrome is an uncommon plasma cell dyscrasia with diverse manifestations, including lymphadenopathy as well as those that comprise the acronym. Dermatologic changes may include hyperpigmentation, thickened skin, hypertrichosis, and papular angiomas. These changes are believed to result from humoral products of the plasma cell clone and frequently resolve with treatment of the neoplasm. We describe a man with typical POEMS syndrome with a unique skin lesion: a large, sharply circumscribed, pigmented plaque on the anterior chest wall centered over a plasmacytoma of the sternum. Results of histologic examination showed a proliferation of capillaries of varying size, enlarged fibroblasts, and increased amounts of collagen and proteoglycan from the dermis to the periosteum. Because the outer cortex of the sternum was eroded, peptide mediators of vascular and fibroblast proliferation may have diffused directly from the plasma cell lesion into the tissues of the chest wall.

Adult↗

Synthesis and characterization of a series of diarylguanidines that are noncompetitive N-methyl-D-aspartate receptor antagonists with neuroprotective properties.

Four diarylguanidine derivatives were synthesized. These compounds were found to displace, at submicromolar concentrations, 3H-labeled 1-[1-(2-thienyl)cyclohexyl]piperidine and (+)-[3H]MK-801 from phencyclidine receptors in brain membrane preparations. In electrophysiological experiments the diarylguanidines blocked N-methyl-D-aspartate (NMDA)-activated ion channels. These diarylguanidines also protected rat hippocampal neurons in vitro from glutamate-induced cell death. Our results show that some diarylguanidines are noncompetitive antagonists of NMDA receptor-mediated responses and have the neuroprotective property that is commonly associated with blockers of the NMDA receptor-gated cation channel. Diarylguanidines are structurally unrelated to known blockers of NMDA channels and, therefore, represent a new compound series for the development of neuroprotective agents with therapeutic value in patients suffering from stroke, from brain or spinal cord trauma, from hypoglycemia, and possibly from brain ischemia due to heart attack.

Animals↗

In-vitro and in-vivo activity of cefpirome (HR 810) against methicillin-susceptible and -resistant Staphylococcus aureus and Streptococcus faecalis.

With cefpirome (HR 810) the MICs for both methicillin-resistant Staphylococcus aureus (MRSA) and for Streptococcus faecalis were 8.0 mg/l. At 4 x MIC, cefpirome killed MRSA as rapidly as did vancomycin while for enterococci, cefpirome, vancomycin or ampicillin alone were not bactericidal. However, all agents were bactericidal when combined with 2 mg/l of gentamicin, although gentamicin combined with cefpirome showed a smaller decrease in cfu/ml than the combination with ampicillin or vancomycin. A mouse thigh infection model was developed in which the thigh muscle was infected with bacteria and either no therapy or concurrent antibiotic therapy was initiated. On the subsequent day, the entire thigh muscle was quantitatively cultured. In this model, the numbers of enterococci at the infection site at 24 h were reduced by 2.1 logs with no treatment, 2.6 with cefpirome (25 mg/kg/day), 2.8 with ampicillin (150 mg/kg/day), and 2.7 with vancomycin (25 mg/kg/day). For MRSA the reductions were 1.1 logs with no therapy, 2.8 with vancomycin, and 3.0 with cefpirome. The apparent enhanced in-vivo activity of cefpirome for MRSA argues for further evaluation of this antibiotic for treatment of MRSA and other Gram-positive cocci, including enterococci.

Aminoglycosides↗

Activities and physiological states of male and female Tabanus sackeni.

Male and female Tabanus sackeni Fairchild (Diptera: Tabanidae) were collected on a road, dipping at pools of water on a road, and at uv-light traps; females were also caught in Malaise traps. Most males at uv-light traps were collected just before sunrise. Most females at uv-light traps were collected in the evening and most had recently taken a bloodmeal. Malaise-trapped females showed a distinct crepuscular peak of host-seeking activity. Crop volumes were variable in these host-seeking females; many had large crops. Crop volumes were small in individuals of both sexes collected dipping or on the road. Many dipping females were gravid. By examining how physiological states and the behaviour of individuals changed according to trap type, we are able to make inferences about the timing and importance of a number of unobserved activities. A link between uptake of water and sugar feeding was apparent and we postulate that mating takes place in the early morning, just before sunrise.

Animals↗

Caesium ions: a glycine-activated channel agonist in rat spinal cord neurones grown in cell culture.

1. The chloride (Cl-) currents activated by caesium ions (Cs+), glycine and gamma-aminobutyric acid (GABA) were compared following their application to rat neurones that had been grown in cell culture. Recordings were made using the whole-cell patch clamp technique under voltage clamp conditions. 2. In spinal cord neurones, bicuculline methiodide antagonized GABA-activated currents more effectively than Cs+ - or glycine-activated currents. However, strychnine was more effective at blocking the currents activated by Cs+ or glycine than those activated by GABA. 3. Of the 3 agonists, only GABA activated currents in cells from the intermediate lobe of the rat pituitary. 4. In spinal neurones the size of the currents activated by 70 mM Cs+ was correlated to the size of the currents activated by 15 microM glycine (P less than 0.005; n = 10, Spearman's rank correlation), but there, was no significant correlation between the size of the currents activated by these agents and 10 microM GABA. 5. The joint application of glycine and Cs+ activated currents that were approximately twice as big as the sums of the currents activated by separate applications of the same doses. This synergism was consistent with Cs+ acting at the same receptor as glycine (7 microM glycine being equivalent to 31 +/- 7 mM Cs+). 6. It was concluded that Cs+ activates the same Cl- channel as the inhibitory neurotransmitter glycine.

Animals↗

Ciprofloxacin therapy for methicillin-resistant Staphylococcus aureus infections or colonizations.

Thirty patients were treated for colonization or for skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus. Three treatment regimens were evaluated, each progressively more aggressive. Our regimen was 750 mg of ciprofloxacin twice daily for 5 days, the second regimen was 750 mg of ciprofloxacin twice daily for 10 to 14 days, and the final regimen was 750 mg of ciprofloxacin twice daily plus 300 mg of rifampin twice daily for 21 days. It appears that ciprofloxacin alone produced an initial eradication rate in at least one site in 50% of the patients, regardless of whether the treatment was for 5 or up to 14 days. All of the patients with eradication became recolonized within 1 week posttherapy. When rifampin was combined with ciprofloxacin, the eradication rate was 100% when the isolates were susceptible to both agents, and these patients remained free of methicillin-resistant S. aureus at 1-week and 1-month follow-ups.

Ciprofloxacin↗

D-lactic acid measurements in the diagnosis of bacterial infections.

Body fluids suspected of bacterial infection were cultured and examined for the presence of D-lactic acid, a specific bacterial metabolite. We examined 206 patients and 264 specimens. D-Lactic acid was found in concentrations of greater than or equal to 0.15 mM in 11 of 11 infected and 6 of 40 noninfected ascitic fluids, 6 of 6 infected and 4 of 33 noninfected pleural fluids, 4 of 4 infected and 0 of 13 noninfected synovial fluids, and 26 of 27 infected and 2 of 130 noninfected cerebrospinal fluids. The overall sensitivity was 79.7%, and the specificity was 99.5% when the D-lactic acid concentration was at least 0.15 mM. The most important clinical utility of the D-lactic acid measurement appears to be for patients with bacterial infection in various body compartments and in patients who have already received antimicrobial therapy. An elevation in D-lactic acid may indicate the presence of bacterial infection even when cultures are negative.

Ascitic Fluid↗

Diagnosis of Mycobacterium bacteremia in patients with acquired immunodeficiency syndrome by direct examination of blood films.

Thirty acquired immunodeficiency syndrome patients with mycobacterial bacteremia documented by Du Pont Isolator (Du Pont Co., Wilmington, Del.) blood cultures underwent microscopic examination of buffy coat blood smears. Of 30 patients, 14 were culture positive for Mycobacterium avium-Mycobacterium intracellulare complex and 1 was positive for M. tuberculosis. Of 15 culture-positive patients, 13 had identifiable organisms on Kinyoun- or auramine-stained direct blood smears.

Acquired Immunodeficiency Syndrome↗

Effect of intravenous vancomycin on renal function.

In the past, vancomycin has been reported to cause renal failure during intravenous administration; however, more recently, such renal toxicity is alleged not to occur because of increased purity of the vancomycin preparations. In this study, 23 patients were prospectively examined during intravenous vancomycin administration for changes in renal function. Vancomycin was administered for an average of 15 days. The blood urea nitrogen (BUN) changes averaged +1.7 mg/dl and the creatinine changes averaged +0.06 mg/dl. Since the accuracy of the serum creatinine determination was +/- 0.3 mg/dl, clinically significant deterioration of renal function occurred in 4 patients or 17%. Even among these 4 patients with documented worsening of renal function, we suspect that deterioration was related to the infection being treated. With close monitoring of dosing, the propensity of vancomycin to cause nephrotoxicity may be less than once thought.

Adult↗

Recombinant interferon-gamma primes alveolar macrophages cultured in vitro for the release of leukotriene B4 in response to IgG stimulation.

The capacity of interferon-gamma to regulate the generation and release of leukotriene B4 (LTB4) from human alveolar macrophages of normal nonsmoking individuals was evaluated. When alveolar macrophages were incubated for 60 min with heat aggregated IgG (HAIgG), they generated and released 5.7 +/- 1.7 ng of LT B4 per 10(6) cells compared to 1.9 +/- 0.4 ng from cells incubated with buffer alone, P = 0.02. When alveolar macrophages were preincubated with interferon-gamma for 24 h before activation for 60 min with heat-aggregated IgG, the soluble IgG aggregates became a significantly more effective stimulus for LTB4 release, 17.0 +/- 3.9 ng/10(6) cells, P = 0.001, compared to cells incubated in the absence of interferon-gamma and challenged with HAIgG. Interferon-gamma did not alter the response to A23187. This effect of interferon-gamma was both time and dose dependent; it also was specific since neither interferon-alpha nor interferon-beta had a regulatory effect on the release of LTB4 from cells in response to challenge with HAIgG. Preincubation of the alveolar macrophages with interferon-gamma augmented the density of IgG1 receptors by 81.5 +/- 17.3%; neither interferon-alpha nor interferon-beta effected this parameter. Furthermore, monomeric IgG1 blocked HAIgG induced LTB4 release from alveolar macrophages primed with interferon-gamma. Therefore, at least one of the mechanisms by which interferon-gamma primes alveolar macrophages for the production and release of LTB4 in response to stimulation by aggregates of IgG is that of increasing the number of receptors for this stimulus.

Antigens, Differentiation↗

Molecular approaches to vertebrate limb morphogenesis.

It has long been proposed that concentration gradients of morphogens provide cues to specify cell fate in embryonic fields. Recent work in a variety of vertebrate systems give bona fide evidence that retinoic acid, the biologically active form of vitamin A, is a candidate for such a morphogen. In the developing chick wing, for example, locally applied retinoic acid triggers striking changes in the pattern along the anteroposterior axis. Instead of giving rise to a wing with the normal 234 digit pattern, wing buds treated with retinoic acid develop a 432234 mirror-image symmetrical digit pattern. For this review, we focus on three aspects of limb morphogenesis. (1) We summarize the experimental evidence supporting the notion that retinoic acid is a candidate morphogen. (2) Limb buds contain high levels of cellular retinoic-acid-binding protein (CRABP). Using order of magnitude calculations, we evaluate how the concentration of CRABP might affect the occupancy state of the retinoic acid receptor. (3) We discuss the spatio-temporal expression pattern of homeobox-containing genes in the developing limb and speculate about the possibility that retinoic acid influences the pattern of expression of homeobox genes.

Animals↗

Mesangiopathic glomerulonephritis in Zuni (New Mexico) Indians.

Zuni is a Pueblo Indian village having more than a sixfold greater incidence of nondiabetic end-stage renal disease than the rest of the United States. Renal biopsy specimens from 44 patients with nondiabetic renal disease were subdivided into two groups. In group 1, 21 patients with asymptomatic microscopic hematuria revealed a mild mesangiopathic glomerulonephritis in 18 cases. The predominantly staining immunoglobulin was IgM in ten specimens and IgA in eight specimens. In group 2, 23 patients with symptomatic renal disease presented with nephrotic range proteinuria (11), renal insufficiency (eight), and hypertension (four). A mesangiopathic glomerulonephritis was diagnosed in 16 cases, and in 11 was IgA predominant. Three cases of membranoproliferative glomerulonephritis occurred in group 2. Five cases revealed focal glomerulosclerosis without immune deposits (three in group 1 and two in group 2). More than half (57%) of the patients undergoing biopsy were related. Cases of symptomatic nondiabetic renal disease showed a significant tendency to cluster among the members of four families, suggesting a hereditary influence in the pathogenesis of immune-mediated glomerulonephritis in the Zuni.

Adolescent↗