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Biomedical subjects

R L Smith

Publications and source records attributed to R L Smith.

At least 289 records · Page 16Linked to original sources
PubMed1991

Purified staphylococcal culture medium stimulates neutral metalloprotease secretion from human articular cartilage.

Human articular cartilage released significantly increased levels of metal-dependent enzymes capable of degrading collagen, casein, and gelatin at a neutral pH following exposure to a sterile, purified fraction of Staphylococcus aureus culture medium. Neutral metalloprotease activity was determined by radiolabeled substrate assays and substrate gel analysis. The enzymes were activated with 4-aminophenylmercuric acetate and were inhibited by 1,10-phenanthroline and ethylenediamine tetraacetic acid. Protein immunoblots demonstrated that type I collagenase and stromelysin (matrix metalloproteinase III) secretion was increased following staphylococcal medium challenge. The profile of enzymatic activity induced by staphylococcal medium was directly comparable to that observed with interleukin-1, which was used as a positive control. The staphylococcal medium had no inherent proteolytic activity. Increased production of the neutral metalloproteases collagenase and stromelysin may significantly contribute to the extensive cartilage destruction noted in staphylococcal septic arthritis.

Cartilage, Articular↗
PubMed1991

Forward masking of the compound action potential: thresholds for the detection of the N1 peak.

A two-interval forced-choice method was developed that provides a rapid and objective computerized measurement of the threshold for detection of the N1 peak of the compound action potential (CAP) recorded in response to a probe tone. The CAP was recorded at the round window of anesthetized chinchillas and several gerbils. An adaptive threshold-tracking procedure was verified by comparing measured thresholds to those obtained from neurometric functions, which plot the proportion of correct detections of the probe as a function of probe intensity. The adaptive procedure was applied in a forward masking paradigm to study the growth of masking of the CAP as a function of masker intensity. Results indicate that growth of masking of the CAP more closely corresponds to that observed psychophysically, than does forward masking observed in the response of a single neuron. Implications for neural encoding mechanisms are discussed.

Acoustic Stimulation↗
PubMed1991

New isomeric classes of topically active ocular hypotensive carbonic anhydrase inhibitors: 5-substituted thieno[2,3-b]thiophene-2-sulfonamides and 5-substituted thieno[3,2-b]thiophene-2-sulfonamides.

A series of 5-substituted thieno[2,3-b]- and thieno[3,2-b)- and thieno[3,2-b)thiophene-2-sulfonamides was prepared and evaluated for topical ocular hypotensive activity in glaucoma models. The 5-substituents were varied to maximize both inhibitory potency against carbonic anhydrase and water solubility. At the same time, these substituents were varied in order to obtain compounds with the appropriate pKa to minimize pigment binding in the iris. All of these variables were optimized in the best compound, 5-[[(methoxyethyl)[(methoxyethyl)ethyl] amino]methyl]thieno[2,3-b]thiophene-2-sulfonamide hydrochloride (55).

Animals↗
PubMed1991

Topically active carbonic anhydrase inhibitors. 4. [(Hydroxyalkyl)sulfonyl]benzene and [(hydroxyalkyl)sulfonyl]thiophenesulfonamides.

For several decades a tantalizing goal for the treatment of primary open-angle glaucoma has been the development of a topically active carbonic anhydrase inhibitor. Recent results from several research groups indicate that considerable progress has been made toward this objective. In this report, we present the design and synthesis of (hydroxyalkyl)sulfonyl-substituted benzene- and thiophenesulfonamides. These compounds exhibit inhibition of carbonic anhydrase II in the nanomolar range and lower intraocular pressure in the alpha-chymotrypsinized rabbit model of ocular hypertension after topical instillation.

Administration, Topical↗
PubMed1991

A fibronectin receptor on Candida albicans mediates adherence of the fungus to extracellular matrix.

Binding of fibronectin, an extracellular matrix (ECM) protein, to Candida albicans was measured, and adherence of the fungus to immobilized ECM proteins, fibronectin, laminin, types I and IV collagen, and subendothelial ECM was studied. 125I-labeled fibronectin was inhibited from binding to the fungus by unlabeled human plasma fibronectin and by Arg-Gly-Asp (RGD), Gly-Arg-Gly-Glu-Ser-Pro (GRGESP), and Gly-Arg-Gly-Asp-Thr-Pro (GRGDTP), but binding was not inhibited by Gly-Arg-Gly-Asp-Ser-Pro. Soluble fibronectin, RGD, GRGESP, and GRGDTP also inhibited fungal adherence to the individual immobilized ECM proteins in a complex pattern, but only soluble fibronectin (10(-7) M) inhibited fungal adherence to subendothelial ECM. Thus, C. albicans possesses at least one type of cell surface receptor for binding soluble fibronectin that can be inhibited with peptides. This receptor apparently is used to bind the fungus to immobilized ECM proteins and to subendothelial ECM and may play a role in the initiation of disseminated disease by bloodborne fungi by providing for adherence of the microorganisms to ECM proteins.

Amino Acid Sequence↗
PubMed1991

Characterization of lip expression in Salmonella typhimurium: analysis of lip::lac operon fusions.

Strains of Salmonella typhimurium which have an auxotrophic requirement for lipoic acid were isolated by mutagenesis with the transposable element Mu dJ. The chromosomal location of these insertion mutations was determined to be at 14 map units by bacteriophage P22-mediated cotransduction. The lip gene is transcribed in the clockwise direction relative to the S. typhimurium genetic map. Strains with lip::lac operon fusions were used to characterize the transcriptional activity of the lip promoter. Transcription of the lip gene is not regulated by catabolite repression or lipoic acid concentration. The data indicate that the lip gene product is expressed constitutively at a low level.

Amino Acids↗
PubMed1991

Metabolism of verapamil in a family pedigree with deficient N-oxidation of trimethylamine.

The oxidative N-dealkylation of verapamil has been studied in a family of five members with two propositi with an inherited deficiency of trimethylamine N-oxidation (fish-odour syndrome). The results were assessed for possible co-segregation of the trimethylamine N-oxidation phenotype and any observed deficiency in oxidative N-dealkylation. The general pattern of metabolism of verapamil in the five subjects studied was similar to that reported in earlier investigations. Moreover, there were no differences between the two affected subjects and other family members with respect to the metabolic pattern. It is concluded that there is no functional segregation with respect to the mechanisms controlling trimethylamine N-oxidation and verapamil N-dealkylation.

Adult↗
PubMed1991

In situ measurement of methane oxidation in groundwater by using natural-gradient tracer tests.

Methane oxidation was measured in an unconfined sand and gravel aquifer (Cape Cod, Mass.) by using in situ natural-gradient tracer tests at both a pristine, oxygenated site and an anoxic, sewage-contaminated site. The tracer sites were equipped with multilevel sampling devices to create target grids of sampling points; the injectate was prepared with groundwater from the tracer site to maintain the same geochemical conditions. Methane oxidation was calculated from breakthrough curves of methane relative to halide and inert gas (hexafluroethane) tracers and was confirmed by the appearance of 13C-enriched carbon dioxide in experiments in which 13C-enriched methane was used as the tracer. A Vmax for methane oxidation could be calculated when the methane concentration was sufficiently high to result in zero-order kinetics throughout the entire transport interval. Methane breakthrough curves could be simulated by modifying a one-dimensional adevection-dispersion transport model to include a Michaelis-Menten-based consumption term for methane oxidation. The Km values for methane oxidation that gave the best match for the breakthrough curve peaks were 6.0 and 9.0 microM for the uncontaminated and contaminated sites, respectively. Natural-gradient tracer tests are a promising approach for assessing microbial processes and for testing in situ bioremediation potential in groundwater systems.

Carbon Isotopes↗
PubMed1991

Excess mortality in critically ill patients with nosocomial bloodstream infections.

To determine the excess mortality attributable to hospital-acquired bloodstream infections, we applied the acute physiology and chronic health evaluation (APACHE) II classification to 34 critically ill patients with this complication. The study included primary bloodstream infections, defined by a positive blood culture at least three days after hospitalization, in the absence of any other apparent source of infection. The most frequent blood isolates included Staphylococcus aureus (39 percent), Gram-negative rods (24 percent), and Candida albicans (15 percent); the spectrum of blood isolates suggested that most infections were related to intravascular catheters. In a control group of intensive care unit patients (n = 384), the death rate predicted by APACHE II was similar to the observed death rate (35.3 vs 37.8 percent). In a subgroup of control patients (n = 34), chosen for APACHE II scores that matched the patients with bloodstream infections, predicted and observed death rates were also similar (53.1 vs 52.9 percent). For patients with bloodstream infections, however, observed mortality (82.4 percent) significantly exceeded the predicted value (54.1 percent, p = 0.025). We conclude that critically ill patients who develop nosocomial bloodstream infections are at greater risk of death than patients with comparable severity of illness without this complication. The difference between the observed and predicted death rates, 28 percent, represents the excess mortality associated with bloodstream infection in critically ill patients.

Adult↗
PubMed1991

Bronchoalveolar lavage neutrophilia seen in Pneumocystis pneumonia presenting with pneumothorax.

Spontaneous pneumothorax is a known complication of Pneumocystis carinii pneumonia (PCP) in patients with acquired immunodeficiency syndrome. From a series of 61 patients with PCP, we identified two cases, not associated with aerosolized pentamidine, that presented with spontaneous pneumothorax and cystic changes seen on chest radiographs. Bronchoalveolar lavage cell findings were remarkable for very elevated neutrophil counts in both cases, suggesting a possible inflammatory cause for the observed cystic changes.

Adult↗
PubMed1991

Mechanical overload of a single compartment induces early degenerative changes in the rabbit knee: a preliminary study.

The purpose of this experiment was to determine whether mechanical overload of a single compartment of the knee in rabbits via proximal tibial osteotomy could produce early changes consistent with degenerative arthritis. Ten New Zealand white female rabbits were allocated into two groups. Group 1 (five animals) underwent a right 20 degrees valgus proximal tibial osteotomy to overload the lateral compartment of the knee. Group 2 (five animals) underwent a tibial osteotomy without malalignment (sham controls). The osteotomies were stabilized with a mini AO/ASIF plate and screws, allowing early mobilization. The left leg in each animal was left intact and served as a control. Animals were sacrificed after 3 months. Histological grading of the cartilage was performed according to Mankin et al. The mean histological gradings for the right minus the left knee were the same for the lateral and medial compartments in the 0 degrees sham osteotomy group. However, the mean histological grading of the "overloaded" lateral compartment was 2.4 times greater than the medial compartment in the 20 degrees valgus osteotomy group. These findings suggest that histological evidence of degenerative changes can be surgically induced in the rabbit knee by creating a biomechanical overload of one compartment.

Animals↗
PubMed1991

Preservation of aortic valve in type A aortic dissection complicated by aortic regurgitation.

Two hundred fifty-two patients underwent operation for type A aortic dissection at Stanford University Medical Center from 1963 to 1987 and Duke University Medical Center from 1975 to 1988. Sixty-seven percent had an acute type A dissection and 33% had a chronic type A dissection. In addition to repair or replacement of the ascending aorta, 121 patients (48%) required an aortic valve procedure. Valve resuspension was performed in 46 (39 acute type A and 7 chronic type A), with an operative mortality rate of 13% +/- 5% (+/- 70% confidence limits), and aortic valve replacement in 75 (36 acute type A and 39 chronic type A), with an operative mortality rate of 20% +/- 5% (p = not significant versus resuspension). The operative mortality rate for patients requiring only repair or replacement of the ascending aorta was 32% +/- 4%. Indications for valve replacement included coexistent (nonacute) aortic valve disease, Marfan's syndrome, annuloaortic ectasia, and cases in which successful resuspension could not be accomplished. The overall actuarial survival rate for all patients was 59% +/- 3% (+/- 1 standard error of the mean), 40% +/- 4%, and 25% +/- 5% at 5, 10, and 15 years, respectively. Survival rates at these same times for patients with valve resuspension were 67% +/- 8%, 52% +/- 10%, and 26% +/- 19%, respectively; for patients who required aortic valve replacement, these survival rates were 70% +/- 5%, 39% +/- 8%, and 21% +/- 11%; finally, patients who received only an ascending aortic procedure had survival probabilities of 51% +/- 5%, 37% +/- 6%, and 23% +/- 6% (p = not significant versus resuspension versus aortic valve replacement). Multivariate analysis showed advanced age (p less than 0.001), previous cardiac or aortic operation (p less than 0.001), more preoperative dissection complications (p = 0.002), and earlier operative date (p = 0.038) to be the only significant, independent factors that increased the likelihood of early or late death. The type of aortic valve procedure (resuspension versus aortic valve replacement versus none) was not a significant predictor of mortality. Two of 46 patients with valve resuspension required late aortic valve replacement (freedom from aortic valve replacement: 100% and 80% +/- 13% at 5 and 10 years, respectively), as did 4 of 75 patients with initial aortic valve replacement (freedom from repeat aortic valve replacement: 98% +/- 2% and 73% +/- 13%, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1990

Septic arthritis. Staphylococcal induction of chondrocyte proteolytic activity.

We report herein that cartilage proteolytic activity increased in bovine and rabbit articular cartilage after treatment with a purified staphylococcal culture medium or intraarticular infection with Staphylococcus aureus. Staphylococcal culture medium increased the release of gelatinolytic, collagenolytic, and caseinolytic activity into the medium of isolated chondrocytes or cartilage organ culture. The proteolytic activities were determined in assays using radiolabeled substrate and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Staphylococcal culture medium was proteolytically inactive by both assay techniques. RNA synthesis of isolated chondrocytes was unaffected by staphylococcal culture medium, whereas overall protein synthesis was inhibited by 84%. An analysis of extracts of Staphylococcus aureus-infected rabbit knee cartilage by substrate gels showed increased gelatinolytic and caseinolytic activity compared with extracts of uninfected knee cartilage. Our data suggest that the rapid loss of proteoglycan and persistent degradation of cartilage in staphylococcal septic arthritis is due to the production and activation of chondrocyte proteases.

Animals↗
PubMed1990

Stimulation of adult chondrocyte metabolism by a thyroid-derived factor.

This paper reports the effects of adding partially purified bovine thyroid calcitonin, thyrocalcitonin, to adult bovine articular cartilage cells. Thyrocalcitonin stimulated chondrocyte proliferation fourfold under low serum (0.5%) culture conditions. In serum-free medium, thyrocalcitonin stimulated cell proliferation more than twofold. With high-density cultures in serum-free medium, chondrocyte glycosaminoglycan (GAG) synthesis was stimulated 60% by thyrocalcitonin. Cell-associated radioactivity was increased twofold. In contrast to thyrocalcitonin, addition of human and salmon calcitonin peptides as well as the thyroid hormones T3 and T4 had no effect on adult cartilage cell proliferation or GAG synthesis. The data reported here suggest the existence of a thyroid-derived factor, independent of calcitonin peptides or thyroid hormones, which stimulates adult articular chondrocyte metabolism.

Animals↗
PubMed1990

Quantitation and relative distribution of extracellular matrix in Staphylococcus epidermidis biofilm.

The relationship between adherence of bacteria to foreign bodies and their deposition of extracellular matrix was examined on glass and suture material. To quantitate bacterial adherence, uptake of [3H]thymidine into bacterial DNA was analyzed. Corresponding amounts of extracellular matrix were measured by a new technique using [14C]glucose incorporation. This study shows that [14C]glucose preferentially labeled bacterial strains in proportion to biofilm production. The ratio of 3H14C in high biofilm producers was 0.9 and in low producers it was 3.7. Radioactive identification of organisms as high and low producers was confirmed by electron microscopy. The results presented here show that production and accumulation of biofilm over time is a stable characteristic in different strains of S. epidermidis. The use of ratios reflecting radiolabeling of bacteria and biofilm by [3H]thymidine and [14C]glucose, respectively, is a quantitative yet simple technique to assess extracellular matrix of different strains of S. epidermidis.

Animals↗
PubMed1990

Glucosaminidase, galactosaminidase, and glucuronidase in the growth plate.

The activities of glucosaminidase, galactosaminidase, and glucuronidase were determined in fractions of bovine growth plate cartilage. Glucosaminidase and galactosaminidase activities were lowest in the area corresponding to the reserve cartilage and increased from the upper to the lower portions of the hypertrophic zones of the growth plate, reaching a maximum in the calcifying cartilage. Glucuronidase activity showed a distinct spike of activity in the calcifying cartilage. The spatial distribution of these activities suggests a role in calcification and in the dissolution of the extracellular matrix at the chondro-osseous junction of the growth plate.

Animals↗
PubMed1990

Phosphorylase kinase isozymes and phosphorylase in denervated skeletal muscles.

The effects of motor denervation on levels of phosphorylase kinase isozymes and phosphorylase were investigated in rat epitrochlearis, hemidiaphragm, and soleus muscles. Amounts of the proteins were measured after quantitative immunoprecipitation and found to be decreased by as much as 70% 2 weeks after denervation. Unexpectedly, denervation had little, if any, effect on the relative proportions of the two phosphorylase kinase isozymes. Phosphorylase and phosphorylase kinase were decreased by essentially the same extent after denervation, and the effects of denervation were comparable in all three muscles. The decreases in these enzymes explain, at least in part, the marked alterations in glycogen metabolism that occur after motor denervation.

Animals↗