Multiple lesions of the mandible.
Explore the source record for details and available documents.
Biopsy↗
Biomedical subjects
R L Smith
Publications and source records attributed to R L Smith.
The fish odour syndrome: biochemical, familial, and clinical aspects.
OBJECTIVES: To study the biochemical, familial, and clinical features of the fish odour syndrome among subjects with suspected body malodour. DESIGN: Subjects who responded to a newspaper article were screened for the fish odour syndrome by interview and biochemical tests. Families of subjects with the syndrome were tested if possible. SETTING: St Mary's Hospital, London, and some interviews at subjects' homes. SUBJECTS: 187 subjects (28 males) with suspected body malodour, of whom 156 (19 males) underwent biochemical tests. Five families of six of the subjects with the fish odour syndrome agreed to further tests. MAIN OUTCOME MEASURES: Amounts of trimethylamine and trimethylamine N-oxide in urine collected over 24 hours under normal dietary conditions and for eight hours after oral challenge with 600 mg trimethylamine. RESULTS: The fish odour syndrome was diagnosed in 11 subjects: the percentage of total trimethylamine excreted in their urine samples that was oxidised to trimethylamine N-oxide was < 55% under normal dietary conditions and < 25% after oral challenge with trimethylamine (in normal subjects > 80% of trimethylamine was N-oxidised). Parents of six of the subjects with the syndrome were tested: all showed impaired N-oxidation of excreted trimethylamine (< 80%) after oral challenge, indicating that they were heterozygous carriers of the allele for the syndrome. The syndrome was associated with various psychosocial reactions including clinical depression. CONCLUSIONS: The fish odour syndrome can be inherited in an autosomal recessive fashion. It should be considered as a possible causative factor in patients complaining of body malodour.
Adolescent↗
Functional methionines in the collagen/gelatin binding domain of plasma fibronectin: effects of chemical modification by chloramine T.
Chemical modification of plasma fibronectin (pFn) or its 40-kDa collagen/gelatin binding (CGB) domain by low concentrations of chloramine T (CT), a methionine-specific oxidant, caused decreased binding affinity between pFn or the isolated CGB domain and Sepharose-immobilized denatured collagen or a Texas Red-labeled CNBr fragment CB7 from the alpha 1 chain of type I collagen. Kds obtained by fluid-phase fluorescence polarization binding assays increased upon oxidation about 17-fold for pFn and by 4-fold for the CGB domain. Comparison of CT-oxidized and native CGB domains by endogenous tryptophan fluorescence and CD spectra gave no indication of conformational changes. delta GH2O, the free energy of unfolding at infinite denaturant dilution, derived from guanidinium chloride denaturation curves, differed by less than 0.7 kcal/mol for the oxidized and native CGB domains, indicating essentially equivalent conformational stabilities. We show here that methionyl residues found at positions 412, 432, and 446 are the sites of the oxidative modification. Modification protection experiments carried out in the presence of gelatin demonstrated specific protection of otherwise oxidizable methionyl residues and preservation of high-affinity binding. These results implicate methionyl residues as functional in contributing to high-affinity binding interaction between fibronectin and gelatin.
Amino Acid Sequence↗
Immunohistochemical analyses of the human olfactory bulb.
These studies explore the distribution of putative neuroactive peptides in the human olfactory bulb. Localization of synaptophysin-, serotonin-, cholecystokinin-, substance P-, and somatostatin-like staining was examined by immunocytochemical protocols. The results provide new insights into the composition and laminar segregation of subpopulations of neurons and neuronal processes in the human olfactory bulb. The prominent synaptophysin-like immunoreactivity observed in the glomeruli of the human olfactory bulb is consistent with the notion that the density of synapses, and hence the density of synaptic vesicles, is highest in the glomeruli. Serotonin-like immunoreactivity suggested a variable innervation of glomeruli ranging from a dense tangled ball of fibers within the glomerulus to a sparse innervation by a single immunoreactive fiber. There was no evidence of serotonin-like immunoreactive cell bodies in either the olfactory bulb proper, anterior olfactory nucleus, or proximal regions of the lateral olfactory tract. Cholecystokinin-like immunoreactivity was limited to fibers found largely in the juxtaglomerular region of the glomerular layer. In the deeper layers of the olfactory bulb, cholecystokinin-like immunoreactive fibers did not show any of branching or arborization that was evident in the juxtaglomerular region. Substance P-like immunoreactivity was seen in varicose fibers distributed in all of the human olfactory bulb laminae. In addition, stained multipolar neurons were found in the area of the anterior olfactory nucleus. Somatostatin-like immunoreactivity was similar to that of substance P in that a plexus of stained fibers was found in all laminae of the olfactory bulb. Also, somatostatin-like immunoreactive cell bodies were found in the area of the anterior olfactory nucleus. However, as compared to substance P, somatostatin had a less dense plexus of immunoreactive fibers in the olfactory bulb. These results increase our understanding of the fundamental organization of the human olfactory system. The current data, coupled with prior studies, provide a foundation from which to study the cellular pathology of diseases with known olfactory system sequelae such as Alzheimer's, Parkinson's, and schizophrenia.
Adult↗
Sequence and topology of the CorA magnesium transport systems of Salmonella typhimurium and Escherichia coli. Identification of a new class of transport protein.
The CorA Mg2+ transport systems of Salmonella typhimurium and Escherichia coli mediate both influx and efflux of Mg2+. The product of the CorA locus is sufficient for mediation of Mg2+ influx while product(s) of the unlinked CorBCD loci allow CorA to mediate efflux in addition to influx. The nucleotide sequences of the S. typhimurium and E. coli CorA loci have been determined. The locus in each species consists of a single gene expressing a protein with gel molecular masses of 42 kDa (S. typhimurium) and 39 kDa (E. coli). The predicted amino acid sequences of these proteins are each 316 amino acids in length, are 98% identical, and lack homology to any known protein. Although CorA is an integral membrane protein by biochemical criteria, its predicted amino acid sequence contains 28% charged amino acid. Membrane localization of CorA was shown to be dependent on the Sec pathway in E. coli. Hydropathy analysis predicts two C-terminal hydrophobic sequences of sufficient length to span the membrane bilayer. The membrane topology of CorA was determined by constructing deletion derivatives of CorA and genetically fusing them to BlaM or LacZ cassettes. The enzymatic activities of these hybrid proteins indicate that the N-terminal 235 amino acid residues of the CorA protein are located within the periplasmic space, comprising a single periplasmic domain. The C-terminal region of CorA is composed of three membrane-spanning segments rather than the two suggested by hydropathy plots, thus depositing the C terminus within the cytoplasm. This topology suggests that CorA functions as an oligomer since three membrane loops are most likely insufficient for any sort of membrane pore or channel. Its lack of homology to known proteins and its topology indicate that the CorA Mg2+ transporter represents a new class of membrane transport system.
Amino Acid Sequence↗
Selective inhibition of ras-dependent transformation by a farnesyltransferase inhibitor.
To acquire transforming potential, the precursor of the Ras oncoprotein must undergo farnesylation of the cysteine residue located in a carboxyl-terminal tetrapeptide. Inhibitors of the enzyme that catalyzes this modification, farnesyl protein transferase (FPTase), have therefore been suggested as anticancer agents for tumors in which Ras contributes to transformation. The tetrapeptide analog L-731,735 is a potent and selective inhibitor of FPTase in vitro. A prodrug of this compound, L-731,734, inhibited Ras processing in cells transformed with v-ras. L-731,734 decreased the ability of v-ras-transformed cells to form colonies in soft agar but had no effect on the efficiency of colony formation of cells transformed by either the v-raf or v-mos oncogenes. The results demonstrate selective inhibition of ras-dependent cell transformation with a synthetic organic inhibitor of FPTase.
Alkyl and Aryl Transferases↗
Dimethylamine formation in man.
Trimethylamine N-oxide, a common food component, has been identified as a major source of urinary dimethylamine in man. The potential pathophysiological consequences of exposure to dietary derived dimethylamine are raised.
Administration, Oral↗
Pulmonary granulomata. A complication of intravesical administration of bacillus Calmette-Guerin for superficial bladder carcinoma.
Intravesical administration of bacillus Calmette-Guerin (BCG) is an effective treatment for superficial carcinoma of the bladder. The authors report a pulmonary complication characterized by miliary infiltration on chest roentgenogram and caseating granulomata on lung biopsy specimens. This case and three prior reports suggest that this complication may be a form of hypersensitivity rather than true BCG infection.
Administration, Intravesical↗
Pregnanes from defensive glands of a belostomatid bug.
The aquatic bug Abedus herberti (Hemiptera: Belostomatidae) secretes a mixture containing four pregnanes (desoxycorticosterone (I), pregnenolone (II), progesterone (III), and 3 alpha-hydroxy-pregn-5-en-20-one (IV)) from its cephalic glands. Pregnanes had previously been characterized from the defensive glands of aquatic beetles (Dytiscidae) and shown to be deterrent to fish. It may be specifically under predation pressure from fish that A. herberti and Dytiscidae evolved their comparable defenses.
Animals↗
The effects of bone cement powder on human adherent monocytes/macrophages in vitro.
This study reports the effects of Simplex bone cement powder (BC) on the proliferation and production of bone resorbing factors in vitro by human adherent monocytes/macrophages. Adherent peripheral blood cells were isolated from seven healthy individuals and exposed to a dispersion of BC powder (1 mg/mL), phytohemagglutinin (PHA, 40 micrograms/mL), or medium alone at different periods of cell incubation (days 0-2, 0-7, 5-7, or 10-12). Cell proliferation was quantified by incorporation of 3H-thymidine uptake. Culture supernatants were evaluated for levels of interleukin 1-like activity (IL-1) by murine thymocyte proliferation assay, prostaglandin E2 (PGE2) by radioimmunoassay, lysosomal enzyme activity (N-acetyl-beta-D-glucosaminidase and beta-glucuronidase using fluorometry, and collagen and casein degrading activity using radioactive substrates. Human adherent peripheral blood cells showed a proliferative response to PHA that coincided with cell maturation; BC did not inhibit PHA-induced cell proliferation of either adherent or nonadherent blood cells, indicating the non-toxic nature of these particles at the concentrations tested. BC stimulated increased release of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase; the levels of PGE2, IL-1, collagenase, and caseinase were unchanged.
Adult↗
Adherence of Candida albicans to immobilized extracellular matrix proteins is mediated by calcium-dependent surface glycoproteins.
The adherence of Candida albicans to the extracellular matrix proteins type I collagen and fibronectin (Fn) is dependent upon the presence of extracellular calcium. In the absence of calcium, 14 +/- 3% of yeast cells added to type I collagen adhered, whereas 62 +/- 3% of yeast cells adhered in the presence of 2 mM calcium. EDTA and EGTA reduced C. albicans adherence in a dose-dependent manner. Calcium, and to a lesser extent, cesium and magnesium, enhanced yeast cell adherence. The fluorescent probe, terbium (Tb+3), bound to the surface of yeast cells in a dose-dependent manner demonstrating the presence of cationic metal-binding sites on the yeast cell surface. When extracts of C. albicans yeast cells were applied to columns of Fn or gelatin coupled to agarose, two surface proteins of C. albicans were specifically eluted with 10 mM EDTA, 2% alpha-methylmannopyranoside or an Arg-Gly-Asp-containing peptide. The fungal proteins had relative molecular masses of 60,000 and 105,000 in the unreduced state. The proteins were present in the cell membrane as well as the cell wall and were demonstrated to be glycoproteins by their ability to bind concanavalin A. Immunoblot analysis of yeast extracts demonstrated that anti-integrin antibodies to the human fibronectin, vitronectin and complement receptor cross-reacted with the Candida 60 kDa glycoprotein. Thus, calcium-dependent fungal cell wall glycoproteins likely related to integrins may be receptors responsible for yeast cell adherence to host tissue such as the extracellular matrix.
Amino Acid Sequence↗
Physiological overshoot and the compound action potential.
The sensitivity of the compound action potential (CAP) of the auditory nerve of the Mongolian gerbil (Meriones unguiculatus) to an added signal was studied as a function of the state of adaptation to a masker. The masker consisted of a train of tone bursts. A signal was added to one of the bursts and the threshold for detecting the signal was determined using a two-interval forced-choice technique. With a signal at the same frequency as the masker, there was little or no change in threshold with increasing adaptation to the masker, i.e., with the signal applied at masker onset or later on in the train. With a signal at a different frequency, considerably higher thresholds were obtained in the unadapted state than in the adapted state, a situation that appeared to resemble psychophysical overshoot phenomena. However, the interpretation of this result was complicated by the observation that the CAP response to a two-frequency stimulus is a sum of two slightly desynchronized waveforms arising from different cochlear regions. Synchronizing the two waveforms reduced the 'overshoot', but still resulted in higher thresholds in the unadapted state. The differences in threshold are accounted for by considering the changing signal-to-noise ratios at different states of adaptation. Possible relationships to psychophysically observed overshoot are discussed.
Acoustic Stimulation↗
Narrative skills in 4-year-olds with normal, impaired, and late-developing language.
Two groups of children who were slow in expressive language development (SELD) at age 2 and a matched group of toddlers with normal language were re-evaluated at age 4. Assessment included measures of productive syntactic skills in spontaneous speech and narrative abilities in a standard story retelling task. Four-year-olds who continued to perform below the normal range in sentence structure production scored significantly lower than their normally speaking peers on all measures of narrative skill. Children who were slow to begin talking at age 2 but who, by age 4, had moved into the normal range in basic sentence structure production showed no statistically significant differences, in terms of several of the measures of narrative ability, from either normally speaking 4-year-olds or from the group with persistent delay. The implications of these findings for the management of early language delay and its relation to school learning disability are discussed.
Age Factors↗
Organization of the genes necessary for hydrogenase expression in Rhodobacter capsulatus. Sequence analysis and identification of two hyp regulatory mutants.
A 25 kbp DNA fragment from the chromosome of Rhodobacter capsulatus B10 carrying hydrogenase (hup) determinants was completely sequenced. Coding regions corresponding to 20 open reading frames were identified. The R. capsulatus hydrogenase-specific gene (hup and hyp) products bear significant structural identity to hydrogenase gene products from Escherichia coli (13), from Rhizobium leguminosarum (16), from Azotobacter vinelandii (10) and from Alcaligenes eutrophus (11). The sequential arrangement of the R. capsulatus genes is: hupR2-hupU-hypF-hupS-hupL-hupM-hu pD-hupF-hupG-hupH-hupJ-hupK-hypA- hypB-hupR1- hypC-hypD-hypE-ORF19-ORF20, all contiguous and transcribed from the same DNA strand. The last two potential genes do not encode products that are related to identified hydrogenase-specific gene products in other species. The sequence of the 12 R. capsulatus genes underlined above is presented. The mutation site in two of the Hup- mutants used in this study, RS13 and RCC12, was identified in the hypF gene (deletion of one G) and in the hypD gene (deletion of 54 bp), respectively. The hypF gene product shares 45% identity with the product of hydA from E. coli and the product of hypF from R. leguminosarum. Those products present at their N-terminus a Cys arrangement typical of zinc-finger proteins. The G deletion in the C-terminal region of hypF in the RS13 mutant prevented the expression of a hupS::lacZ translational fusion from being stimulated by H2 as it is observed in the wild-type strain B10. It is inferred that the HypF protein is a factor involved in H2 stimulation of hydrogenase expression.
Amino Acid Sequence↗
A comparison of N1 of the whole nerve action potential and wave i of the brain-stem auditory evoked response in Mongolian gerbil.
The present study seeks to provide empirical support for the assumption that wave i of the gerbil brain-stem auditory evoked response (BAER) corresponds to N1 of the whole nerve action potential (WNAP) by comparing the latency and amplitude of BAER wave i and WNAP N1. Fourteen 3-month old gerbils were anesthetized with Nembutal and Urethane-Dial. Normothermia was maintained by a homeothermic blanket system. BAERs were recorded with Grass needle electrodes placed subdermally. The WNAP was recorded with a silver wire placed in the round window niche. WNAP and BAER were simultaneously recorded with a passband of 100-10,000 Hz. Responses consisted of 500 sweeps, and two responses were obtained for each condition. Clicks were 25-microseconds electrical pulses. Tonebursts were shaped with a Hanning window, with 1-ms rise and fall times. Toneburst frequencies included 1, 2, 4, 8, and 16 kHz. For each stimulus, responses were obtained at levels of 30, 50, 70, and 90 dB pSPL. SPL was measured near the entrance to the ear canal with an Etymotic ER-7C probe microphone. Dependent variables were the latency and amplitude of N1 of the WNAP and wave i of the BAER. The latencies of wave i and N1 were very similar. Mean (across animal) latencies of N1 and wave i were within 70 microseconds for all six stimuli (clicks, tonebursts) and all four levels. Latency/intensity function slopes for N1 and wave i were also very similar, with both dependent variables showing an increasing latency/intensity function slope with decreasing toneburst frequency. The N1/wave i amplitude ratio was computed.(ABSTRACT TRUNCATED AT 250 WORDS)
Acoustic Stimulation↗
Effect of treated-sewage contamination upon bacterial energy charge, adenine nucleotides, and DNA content in a sandy aquifer on Cape Cod.
Changes in adenylate energy charge (ECA) and in total adenine nucleotides (A(T) and DNA content (both normalized to the abundance of free-living, groundwater bacteria) in response to carbon loading were determined for a laboratory-grown culture and for a contaminated aquifer. The latter study involved a 3-km-long transect through a contaminant plume resulting from continued on-land discharge of secondary sewage to a shallow, sandy aquifer on Cape Cod, Mass. With the exception of the most contaminated groundwater immediately downgradient from the contaminant source, DNA and adenylate levels correlated strongly with bacterial abundance and decreased exponentially with increasing distance downgradient. ECAS (0.53 to 0.60) and the ratios of ATP to DNA (0.001 to 0.003) were consistently low, suggesting that the unattached bacteria in this groundwater study are metabolically stressed, despite any eutrophication that might have occurred. Elevated ECAS (up to 0.74) were observed in glucose-amended groundwater, confirming that the metabolic state of this microbial community could be altered. In general, per-bacterium DNA and ATP contents were approximately twofold higher in the plume than in surrounding groundwater, although ECA and per-bacterium levels of A(T) differed little in the plume and the surrounding uncontaminated groundwater. However, per-bacterium levels of DNA and A(T) varied six- and threefold, respectively, during a 6-h period of decreasing growth rate for an unidentified pseudomonad isolated from contaminated groundwater and grown in batch culture.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenine Nucleotides↗
Expression of 92-kD type IV collagenase/gelatinase (gelatinase B) in osteoarthritic cartilage and its induction in normal human articular cartilage by interleukin 1.
We report here that a 92-kD gelatinolytic metalloproteinase is expressed as protein and mRNA in human osteoarthritic cartilage, but not in normal adult articular cartilage. Western immunoblotting demonstrated that the 92-kD gelatinolytic activity corresponded to 92-kD type IV collagenase/gelatinase (gelatinase B); mRNA for gelatinase B was identified by Northern blotting. Chondrocytes from normal cartilage also exhibited mRNA for 72-kD type IV collagenase/gelatinase (gelatinase A), tissue collagenase, and stromelysin-1, and these mRNAs were increased in osteoarthritic cartilage. Regional analysis of osteoarthritic cartilage samples from four individuals revealed that gelatinase B mRNA was expressed in grossly fibrillated areas; two of four nonfibrillated cartilage samples failed to exhibit the mRNA, but did have increased levels of mRNA for other neutral metalloproteinases. IL-1 alpha treatment of normal human cartilage explants or isolated chondrocytes induced increased levels of gelatinase B and increased mRNA for tissue collagenase and stromelysin-1. Under identical conditions, mRNA levels for gelatinase A were not increased indicating that regulation of this enzyme in human articular chondrocytes is distinct from that of other metalloproteinases. Our data showing expression of gelatinase B in fibrillated cartilage suggest that it is a marker of progressive articular cartilage degradation in osteoarthritis.
Adult↗
Production and hormonal regulation of insulin-like growth factor binding proteins in bovine chondrocytes.
Linear growth results from proliferation and differentiation of chondrocytes within the growth plates and is regulated, in part, by the insulin-like growth factors (IGFs). IGF binding proteins (IGFBPs) also appear to play a significant, but yet unclear, role. To examine IGFBP production by chondrocytes, we isolated bovine chondrocytes from adult articular, fetal articular, and fetal growth plate cartilage, and maintained them in primary culture as high-density monolayers or encapsulated in alginate beads. Cells were cultured in serum-free conditions with human GH (hGH), insulin, hIGF-I, or hIGF-II. Human IGF-I resulted in higher DNA content in all three of the chondrocyte types. Conditioned medium samples were analyzed for IGFBPs by Western ligand blotting. Chondrocytes released IGFBPs of 24, 29, 33, 39, and 43 kilodaltons (kDa). Deglycosylation and immunoblotting identified the 39/43-kDa doublet as IGFBP-3 and the 33-kDa band as IGFBP-2. All chondrocyte types released 29- and 24-kDa IGFBP bands constitutively. Adult articular chondrocytes increased production all IGFBPs in response to IGF-I, but particularly the 29-kDa band (17-fold increase). Fetal articular chondrocytes showed a similar pattern, but with less of an increase when treated with IGF-I. Fetal growth plate chondrocytes primarily showed increases in IGFBP-3 and the 24-kDa form (4.7- and 2.7-fold, respectively) in response to IGF-I. Although the role of IGFBPs in IGF mediation of articular and growth plate chondrocyte metabolism requires further research, we show here that bovine chondrocytes produce IGFBPs, and the IGFs regulate this production.
Animals↗