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Biomedical subjects

R L Smith

Publications and source records attributed to R L Smith.

At least 271 records · Page 15Linked to original sources
PubMed1992

A theoretical basis for conditional probability analyses of neural discharge activity.

A theory has been developed which allows the estimation of the probability density of a discharge, given that an arbitrary condition is fulfilled. It is shown that the common methods for the evaluation of a post-stimulus time (PST) histogram and a hazard function can be considered as special applications of this theory. Whereas the usual hazard function shows how the probability of a discharge depends on the time elapsed since the last discharge, generalized hazard functions proposed in the present paper allow to reveal also the influence of the last but one discharge, the last but two discharge, and so on. In contrast to the usual method for the estimation of a hazard function, the applicability of the procedures proposed here is not restricted to stationary discharge activity. Some elementary applications are illustrated by analysing simulated discharge activity mimicing the response of a single auditory-nerve fiber to a high-intensity tone burst.

Action Potentials↗
PubMed1992

The exogenous origin of trimethylamine in the mouse.

Although it is now generally regarded that the origin of urinary trimethylamine (TMA) is via the action of intestinal microflora on precursors such as choline, little direct evidence exists. The normal production of urinary TMA was shown to be absent in germ-free mice and greatly reduced in antibiotic-pretreated animals. Cohabitation of germ-free mice with conventional animals restored their ability to excrete TMA. This study invokes a fundamental role for the intestinal microflora in the provision of TMA from precursors within the food.

Animals↗
PubMed1992

Activation of second-messenger pathways reactivates latent herpes simplex virus in neuronal cultures.

Herpes simplex virus type 1 (HSV-1) establishes latent infections in neurons of sympathetic and sensory ganglia in humans, and reactivation of latent virus results in recurrent disease. Previously, we reported establishment of latent HSV-1 infections in neuronal cultures derived from rats, monkeys, and humans; reactivation occurs following nerve growth factor (NGF) deprivation. The processes controlling HSV latency are not understood. Using the in vitro neuronal latency system, we have shown that latent HSV-1 reactivated in response to stimulation of at least two second-messenger pathways. Stimulation of cAMP-dependent pathways by several mechanisms or activation of protein kinase C by phorbol myristate acetate (PMA) resulted in reactivation of latent HSV-1. The reactivation kinetics following treatment with activators of protein kinase A and C were accelerated compared with those following NGF deprivation. 2-Aminopurine, which inhibits NGF-stimulated protein kinases and other classes of protein kinases, but does not effect protein kinase A or C, blocked reactivation produced by NGF deprivation or treatment with a cAMP analog, but not reactivation by PMA treatment. These results demonstrate that latent HSV-1 reactivates in neurons in vitro in response to activation of second-messenger pathways.

Cell Line↗
PubMed1992

Ionic coupling among cells in the organ of Corti.

Gap junctions have been demonstrated morphologically among the supporting cells of the mammalian organ of Corti but, in contradistinction to reptiles, evidence for their existence between the supporting cells and hair cells is equivocal. The literature is ambiguous with respect to electrical coupling and dye coupling among the supporting cells, and no coupling of either kind has been demonstrated for the hair cells. We found strong coupling of both kinds among the supporting cells in the cochleas of live Mongolian gerbils and a less stable coupling between the supporting cells and the outer hair cells. The electrical coupling was established by recording alternating receptor potentials in the hair cells and following their decrement in the population of Hensen's cells; the dye coupling, by injecting Lucifer yellow electrophoretically into the hair cells or the supporting cells and investigating its spread to the neighboring cells. The electrical recordings were made by means of microelectrodes filled with either 1.5 or 3 M KCl or 1 M LiCl with 6% Lucifer yellow, the latter used for dye injection. The electrode resistances ranged from about 20 to 60 M omega in the first instance, and from about 50 to 110 M omega, in the second. The electrodes were inserted into the organ of Corti through scala media according to the method of Dallos, Santos-Sacchi and Flock (1982) modified by us. The alternating potential in Hensen's cells was usually larger than in the outer tunnel of Corti and remained practically constant up to the outer margin of the Hensen's-cell population. Its phase was the same as in the outer hair cells. When the dye was injected into a Hensen's cell, it always spread to neighboring Hensen's cells and often to Deiter's cells. Dye injected into outer hair cells (identified according to anatomical and physiological criteria) also spread to Deiter's and Hensen's cells and, usually, to other outer hair cells. Stained cells were identified in surface preparations and, on two occasions, in serial sections from plastic embedded cochleas.

Animals↗
PubMed1992

Regulation of phycobilisome structure and gene expression by light intensity.

The cyanobacterium Agmenellum quadruplicatum PR-6 (Synechococcus sp PCC 7002) was grown turbidostatically in white light at three levels of irradiance: 20, 200, and 1260 microeinsteins per square meter per second. Phycobilisomes were isolated from each culture and analyzed by absorbance, gel electrophoresis, and electron microscopy. The ratio of phycocyanin to allophycocyanin decreased 1.8-fold from the lowest to highest irradiance. This change was due entirely to an approximately 2.5-fold decrease in one structural unit of rod domains, the complex of phycocyanin, and a 33-kilodalton linker polypeptide (LR33). For a given irradiance, phycobilisomes from cells grown on ammonium as the nitrogen source had 10 to 20% more phycocyanin than those from nitrate cultures. Total RNA was isolated from all cultures and probed with gene fragments specific to phycocyanin and allophycocyanin subunits and LR33. The relative level of RNAs encoding phycocyanin and allophycocyanin was found to vary with light intensity in parallel with the phycobiliprotein ratio. Hence, the light-harvesting capacity of phycobilisomes is directly regulated by relative levels of phycobiliprotein mRNA. The LR33 transcript occurs as a 3' extension on about 10% of phycocyanin transcripts. The ratio of RNA encoding LR33 to that encoding phycocyanin did not vary with irradiance, although the protein ratio changed 1.7- to twofold between extremes. Based on these and other observations, we propose that the LR33 protein is constitutively synthesized at a rate higher than that required to complex with available phycocyanin.

Journal Article↗
PubMed1992

Effect of an arginine-glycine-aspartic acid-containing peptide on hematogenous candidal infections in rabbits.

The adherence of Candida albicans yeast cells to the subendothelial extracellular matrix, fibronectin, laminin, and type I and IV collagen was tested. Fibronectin (10(-7) M) and a peptide, PepTite-2000 (Telios Pharmaceuticals Inc., San Diego, Calif.), containing the sequence arginine-glycine-aspartic acid (RGD) inhibited Candida adherence to these targets by greater than 90%. When C. albicans was perfused over ex vivo rabbit aortic endothelium, there was no significant difference in the amount of adherence in the presence or absence of the RGD-containing peptide. However, the RGD-containing peptide reduced the number of Candida organisms present in liver, brain, heart, and kidneys (P less than 0.05) of rabbits 4 h after intravenous inoculation of 5 x 10(7) C. albicans yeast cells. The peptide also reduced the number of macroscopic Candida abscesses in the kidneys of rabbits 72 h after intravenous inoculation of 10(7) C. albicans yeast cells (P less than 0.05). Inhibition of Candida adherence in vitro and in vivo may occur because the peptide blocks a fungal receptor that is necessary for adherence.

Animals↗
PubMed1992

Inhibition of existing denitrification enzyme activity by chloramphenicol.

Chloramphenicol completely inhibited the activity of existing denitrification enzymes in acetylene-block incubations with (i) sediments from a nitrate-contaminated aquifer and (ii) a continuous culture of denitrifying groundwater bacteria. Control flasks with no antibiotic produced significant amounts of nitrous oxide in the same time period. Amendment with chloramphenicol after nitrous oxide production had begun resulted in a significant decrease in the rate of nitrous oxide production. Chloramphenicol also decreased (greater than 50%) the activity of existing denitrification enzymes in pure cultures of Pseudomonas denitrificans that were harvested during log-phase growth and maintained for 2 weeks in a starvation medium lacking electron donor. Short-term time courses of nitrate consumption and nitrous oxide production in the presence of acetylene with P. denitrificans undergoing carbon starvation were performed under optimal conditions designed to mimic denitrification enzyme activity assays used with soils. Time courses were linear for both chloramphenicol and control flasks, and rate estimates for the two treatments were significantly different at the 95% confidence level. Complete or partial inhibition of existing enzyme activity is not consistent with the current understanding of the mode of action of chloramphenicol or current practice, in which the compound is frequently employed to inhibit de novo protein synthesis during the course of microbial activity assays. The results of this study demonstrate that chloramphenicol amendment can inhibit the activity of existing denitrification enzymes and suggest that caution is needed in the design and interpretation of denitrification activity assays in which chloramphenicol is used to prevent new protein synthesis.

Carbon↗
PubMed1992

Bone signal abnormalities in the posterolateral tibia and lateral femoral condyle in complete tears of the anterior cruciate ligament: a specific sign?

Thirty-two patients with acute, complete tears of the anterior cruciate ligament (ACL) proved at surgery underwent examination with magnetic resonance (MR) imaging. Bone impaction sites were present in the posterolateral tibial plateau in 30 patients (94%) and in the lateral femoral condyle (LFC) in 29 patients (91%). The bone abnormalities had low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with the signal intensity of normal marrow. It is assumed that the bone changes occur during injury when the LFC impacts into the posterior tibia, either during the initial rotary subluxation or as the LFC recoils to return to anatomic alignment. Only one of six partial ACL tears had a bone signal change. In patients with acute knee injury, bone impaction sites in the posterolateral tibia and the LFC suggest that a complete ACL tear is present.

Anterior Cruciate Ligament Injuries↗
PubMed1992

Iliotibial band friction syndrome: MR imaging findings.

Six patients with clinical histories and physical examination results consistent with iliotibial band friction syndrome (ITBFS) were examined with magnetic resonance (MR) imaging. Ill-defined decreased signal intensity on T1-weighted images and increased signal intensity on T2-weighted images was present deep to the iliotibial band, adjacent to the lateral femoral epicondyle. Axial fast imaging with steady-state precession (FISP) gradient-echo sequences were essential in differentiating the ill-defined signal intensity abnormality associated with ITBFS from fluid in the lateral knee joint. None of these patients were found to have lateral meniscal tears, and all responded to conservative measures directed at treating ITBFS. The authors conclude that MR imaging may be useful in confirming or establishing the diagnosis of ITBFS in patients with the appropriate clinical history and distal lateral thigh or lateral knee pain.

Adolescent↗
PubMed1992

The role of bronchoscopy in the diagnosis of pulmonary tuberculosis in patients at risk for HIV infection.

The present study was undertaken to clarify the role of bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) in the diagnosis of pulmonary tuberculosis in patients at risk for human immunodeficiency virus (HIV) infection. We retrospectively identified 31 patients at risk for HIV who proved to have Mycobacterium tuberculosis on culture of at least one pulmonary specimen. All had pulmonary symptoms but initial sputum smears negative for acid-fast bacilli (AFB). All underwent fiberoptic bronchoscopy (FOB), including BAL and TBB; postbronchoscopy sputum was also collected in 19 patients. A specimen was considered to yield an immediate diagnosis when positive for AFB either on smear or histologic study; granulomas alone were considered positive when no other causes were identified. Overall, an immediate diagnosis was made by bronchoscopic specimens in 15 (48 percent) of 31 cases. TBB was the sole positive specimen in seven patients (23 percent). For comparison, similar specimens from 40 patients in whom M avium complex (MAC) grew on culture were also evaluated. An immediate identification of AFB was made in only four patients (10 percent). We conclude that the finding of AFB on staining of any pulmonary specimen is highly suggestive of tuberculosis, rather than MAC, and warrants institution of antituberculosis therapy. Of all bronchoscopic specimens, TBB provides the highest yield for an immediate diagnosis of tuberculosis.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Pulmonary disposition of gallium-67 in patients with Pneumocystis pneumonia: an analysis using bronchoalveolar lavage.

Gallium-67 localizes to the cellular fraction of bronchoalveolar lavage (BAL) fluid in patients with sarcoidosis, idiopathic pulmonary fibrosis, as well as normal subjects. To further study 67Ga disposition in BAL fluid, 11 patients with Pneumocystis carinii pneumonia (PCP) and 8 patients with a variety of other lung diseases, underwent BAL 24 hr after 67Ga injection. Compared to the non-PCP patients, PCP patients had high uptake gallium scans at 24 and 72 hr, and showed significantly increased radioactivity in both unfractionated lavage and in the acellular, supernatant fraction of BAL. The mean ratio of total supernatant/cell pellet radioactivity was also higher in patients with PCP (1.23 +/- 0.27 versus 0.24 +/- 0.05, p less than 0.01). Supernatant radioactivity correlated with the presence of neutrophil alveolitis, but not with BAL transferrin concentrations. We conclude that neutrophil alveolitis in PCP promotes 67Ga accumulation in the acellular fraction of BAL fluid. However, the high uptake 67Ga scans observed in PCP patients without neutrophil alveolitis suggest that the mechanism of pulmonary uptake of 67Ga is not fully elucidated by BAL fluid analysis alone.

Adult↗
PubMed1992

Inhibition of interleukin 1 induced chondrocyte protease activity by a corticosteroid and a nonsteroidal antiinflammatory drug.

We report that administration of the corticosteroid, methylprednisolone (PRED) inhibited interleukin 1 (IL-1) induction of chondrocyte caseinolytic activity (25-55%) and collagenolytic activity (15-24%). The nonsteroidal antiinflammatory drug (NSAID), naproxen (NAP) had no effect on either enzyme activity over a therapeutic range (7-30 micrograms/ml) but at 120 micrograms/ml inhibited IL-1 induced caseinolytic and collagenolytic activity by 17 and 19%, respectively. However, PRED (2 micrograms/ml) in combination with NAP (30 micrograms/ml) significantly increased the inhibition of caseinolytic activity (p less than 0.001) compared to that observed with PRED (2 micrograms/ml) alone. The suppression of IL-1 induced collagenolytic activity noted with PRED in combination with NAP did not exceed that observed with PRED alone.

Adrenal Cortex Hormones↗
PubMed1991

Cloning, primary sequence, and chromosomal mapping of a human flavin-containing monooxygenase (FMO1).

cDNA clones that code for a pig and human flavin-containing monooxygenase (FMO) have been isolated. The full-length sequence of the human cDNAs revealed that they encode a polypeptide of 532 amino acid residues containing putative FAD- and NADP-binding sites. The deduced amino acid sequence has 88 and 86% identity, respectively, with the pig and rabbit "hepatic" forms of FMO, but is only 58% similar to the rabbit "pulmonary" FMO, and thus represents the human ortholog of the "hepatic" form of FMO. However, as this FMO is present in low abundance in human adult liver, the general term "hepatic" for this form of the enzyme is misleading, and thus we propose the name FMO1 to describe this human FMO and its mammalian orthologs. Northern blot analysis demonstrated that human FMO1 mRNA is more abundant in fetal than in adult liver, indicating that in man the enzyme is subject to developmental regulation. Southern blot hybridization of human genomic DNA suggests that the protein is encoded by a single gene, which has been designated FMO1 and mapped to chromosome 1.

Amino Acid Sequence↗
PubMed1991

Localization of tyrosine hydroxylase and olfactory marker protein immunoreactivities in the human and macaque olfactory bulb.

These studies utilized specific antisera to examine the distribution and characteristics of tyrosine hydroxylase and olfactory marker protein in the olfactory bulb of the human and macaque monkey. The macaque displayed immunoreactive profiles to both antisera comparable to those described previously for other mammals. Olfactory marker protein antiserum labeled the olfactory nerve layer and glomeruli. Within the glomeruli, labeled processes were interdigitated with unlabeled processes believed to be the postsynaptic dendrites of olfactory bulb neurons. Tyrosine hydroxylase antisera labeled somata surrounding the glomeruli as well as putative dendritic processes with the glomerular neuropil. It appeared that only a subset of juxtaglomerular neurons were immunoreactive. A similar pattern was observed in the human for both antibodies. Fascicles of olfactory marker protein immunoreactive olfactory nerves often coursed long distances into the olfactory bulb prior to arborizing within a glomerulus. The data suggest that olfactory receptor cell axons destined for specific glomeruli fasciculate into bundles prior to reaching the target glomeruli. The immunoreactivity in the human to tyrosine hydroxylase was qualitatively similar to the macaque and other mammals although the number of labeled somata and intraglomerular processes appeared lower. As in the macaque, it appeared that only a subset of juxtaglomerular neurons were labeled.

Adult↗
PubMed1991

Topography and morphology of retinal ganglion cells in Falconiforms: a study on predatory and carrion-eating birds.

The topographic distribution of retinal ganglion cells and their cell body size have been studied in five Falconiform species, including predatory (chilean eagle Buteo fuscenses australis, and sparrow hawk Falco sparverius) and carrion-eating (chimango caracara Milvago chimango; condor Vultur gryphus, and black vulture Coragyps atratus) birds. All these species had a well defined nasal fovea and a horizontal streak. Instead of a temporal fovea as in eagles and hawks, an afoveate temporal area is present in chimango, condor, and vulture. The highest ganglion cell density was found in the nasal fovea of Falco and Buteo with 65,000 and 62,000 cells/mm2, respectively. A negative correlation between ganglion cell density and cell body size was found in all the species studied. The specializations of the temporal retina showed a rather homogenous population of medium sized neurons, while the nasal foveas showed a homogeneous population of smaller ganglion cells. Finally, the peripheral retina showed a heterogeneous population of large, medium, and small ganglion cells. Predatory behavior appears to be closely related to foveal specializations, and is best exemplified in the eagle and hawk and to a lesser extent in the chimango.

Animals↗
PubMed1991

Comparative effects of the diastereoisomers, quinine and quinidine in producing phenocopy debrisoquine poor metabolisers (PMs) in healthy volunteers.

1. A single oral dose (50 mg) of quinidine significantly increased the debrisoquine metabolic ratio in six healthy volunteers. For four of the volunteers the metabolic ratio changed to that typical of the poor metaboliser (PM) phenotype. 2. The effect of quinidine in producing debrisoquine oxidation "poor metaboliser" phenocopies persisted for at least 3 days but had disappeared by 1 week. 3. The debrisoquine metabolic ratios for the same six subjects were not significantly altered by the oral administration of quinine (200 or 400 mg), the diastereoisomer of quinidine. 4. The plasma pharmacokinetic parameters of both nortriptyline and desipramine in healthy volunteers were all changed to those more typical of the debrisoquine PM phenotype following the concomitant administration of quinidine (50 mg). 5. It is concluded that quinidine, but not its diastereoisomer quinine, is a potent selective inhibitor of the in vivo oxidation of debrisoquine and can produce an artifactual PM phenocopy in persons who are phenotypically extensive metaboliser (EM) phenotype status. The clinical implications of this observation are discussed.

Adult↗
PubMed1991

The pharmacokinetics of racemic verapamil in patients with impaired renal function.

The pharmacokinetics of verapamil were studied in patients with renal failure who were undergoing maintenance hemodialysis and in normal subjects after an IV infusion of 10 mg and a single oral dose of 120 mg. Plasma levels of verapamil and its active metabolite, norverapamil, were analyzed by a sensitive and specific HPLC procedure. Severe renal failure requiring hemodialysis did not change the time course of verapamil and norverapamil plasma concentrations after either the IV or oral dose. The terminal elimination rate constant, clearance, volume of distribution, and bioavailability of verapamil were not significantly different between the two groups of subjects. In addition, the apparent maximal plasma concentration, terminal elimination rate constant, and area under the curve for norverapamil were similar in patients with renal failure and normal subjects. The study showed that the plasma disposition of verapamil and norverapamil was not affected in patients with impaired renal function. Furthermore, this study does not indicate that any change in dosage is necessary when single doses of verapamil are administered to patients with renal failure.

Administration, Oral↗