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Biomedical subjects

M E Smith

Publications and source records attributed to M E Smith.

At least 199 records · Page 11Linked to original sources
PubMed1993

Systemic histiocytosis presenting as multiple sclerosis.

A patient resembling one with progressive multiple sclerosis in clinical presentation and by magnetic resonance imaging was studied in detail. Some features atypical for multiple sclerosis prompted a persistent search for an alternative cause. The diagnosis of a non-Langerhans systemic histiocytosis involving brain and bone was established and showed a partial response to radiation therapy. This patient illustrates the continued importance of a broad approach to the evaluation of possible multiple sclerosis, with particular attention to atypical features.

Biopsy↗
PubMed1993

Decomposition of recognition memory event-related potentials yields target, repetition, and retrieval effects.

Task manipulations and a subtractive analytic strategy were combined to decompose the positive-going amplitude shift of the event-related potential (ERP) that is elicited by previously studied words during recognition memory testing. Target stimuli elicited a robust posterior P3b subcomponent, but this effect is shown to be independent of the effects of prior study. Two study-related subcomponents were also identified. The earlier study effect reached peak amplitude about 400 msec after word onset and was elicited by repeated words regardless of whether the task required retrieval of information from secondary memory. This effect might reflect a repetition-related decline in the amplitude of the N400 component. The other study-related effect reached peak amplitude around 600 msec post-stimulus onset. This later effect overlapped temporally with the P3b, but it was not related to targetness. Rather, it was specifically related to task conditions that required retrieval from secondary memory. The identification of this third effect helps to clarify the functional significance of the ERPs observed during recognition memory testing.

Analysis of Variance↗
PubMed1993

Differential effect of interleukin-1 beta on Ia expression in astrocytes and microglia.

In an earlier study we demonstrated the inhibitory effect of interleukin-1 beta (IL-1 beta) on human leukocyte antigens (HLA) class II enhancement by interferon-gamma (IFN-gamma) in a human glioblastoma multiforme cell line. In this study we have examined the effect of IL-1 beta on IFN-gamma induced major histocompatibility complex (MHC) class II (Ia) in primary cultures of newborn murine astrocytes and microglial cells. Astrocytes expressed very low levels of Ia molecules under basal culture conditions but these molecules could be induced with IFN-gamma. IL-1 beta in doses ranging from 1 to 100 units/ml inhibited the level of IFN-gamma induced Ia expression on astrocytes, and this inhibition was dose-dependent (mean maximum inhibition of 53 +/- 5% in number of positive cells and 53 +/- 2.6% in mean fluorescence intensity in four separate experiments). IL-1 beta treatment had no effect on MHC class I induction by IFN-gamma in the astrocytes. In contrast, microglial cells expressed Ia molecules under basal culture conditions, and this expression was enhanced by IFN-gamma treatment. Both basal and IFN-gamma induced Ia expression on microglia were resistant to IL-1 beta treatment in doses ranging from 1 to 100 units/ml. These results indicate that Ia expression is differentially regulated on astrocytes and microglial cells and that IL-1 beta may have an important immune regulatory function in the central nervous system.

Animals↗
PubMed1993

Voice problems after pediatric laryngotracheal reconstruction: videolaryngostroboscopic, acoustic, and perceptual assessment.

Children with laryngotracheal stenosis undergo laryngotracheal reconstruction (LTR) to permit tracheostomy decannulation. We conducted voice assessments of 8 pediatric LTR patients with voice problems. Perceptual ratings and acoustic measures were taken in 5 patients and videolaryngoscopy/laryngostroboscopy was conducted in all 8. Results of perceptual evaluation were abnormal for hoarseness, breathiness and pitch. Acoustic analysis revealed a markedly decreased fundamental frequency of phonation, diminished frequency range, decreased vocal intensity, and shortened maximum phonation time. Videolaryngostroboscopic findings are summarized as follows: 2 patients had severe glottal insufficiency, 3 patients had vocal fold asymmetry in stiffness and position, and 3 patients demonstrated phonation using supraglottal structures. Use of the stroboscope contributed to diagnosis in 3 of 8 patients. Reverse (inhalatory) phonation was observed in three patients. Concomitant articulation problems were exhibited frequently. Sentence production was shortened by the decreased phonatory duration. When coupled with the abnormal voice quality, speech intelligibility was significantly affected. Voice problems following decannulation were observed to persist as a long-term difficulty in some LTR patients.

Adolescent↗
PubMed1993

Absorption and disposition of a new antiarrhythmic agent bidisomide in man.

Absorption and disposition of bidisomide were studied in 12 healthy male subjects after a 20-min iv (1 mg/kg; N = 6) infusion and oral (2 mg/kg; N = 6) administration of the 14C-labeled drug. The oral absorption profile of unlabeled bidisomide was also studied after administration of a solution by a nasoenteric tube to different sites of the gastrointestinal tract (stomach, duodenum, jejunum, and ileum). The systemic availability was 61%. Absorption was slow initially and then rapid, achieving peak plasma concentrations between 2 and 4 hr. Less than complete systemic availability was attributed to incomplete absorption rather than first-pass metabolism. When the drug solution was delivered directly to the stomach, two distinct peak plasma levels were found. This was attributed to the more rapid absorption of bidisomide in the duodenum and ileum (and/or possibly colon). Following an iv dose, plasma levels of the drug declined with mean half-lives of 0.11, 2.0, and 12 hr for alpha, beta, and gamma phases, respectively, and a plasma clearance of 380 mL/min. The percentages of the dose recovered as bidisomide in urine and feces were 19 +/- 1 and 29 +/- 4 for the iv dose and 9.1 +/- 0.9 and 48 +/- 5 for the oral dose. Bidisomide did not exhibit substantial enantioselective pharmacokinetics in plasma regardless of the route of administration. The mean urinary excretion of the (-) enantiomer was, however, slightly higher than that of the (+) enantiomer, with (-)/(+) enantiomeric ratios of 1.2 and 1.3 after iv and oral administration, respectively. The enantiomeric ratio of bidisomide recovered in the feces was approximately 1.

Absorption↗
PubMed1993

Involvement of cytochromes in the anaerobic biotransformation of tetrachloromethane by Shewanella putrefaciens 200.

Shewanella putrefaciens 200 is an obligate respiratory bacterium that can utilize a variety of terminal electron acceptors, e.g., NO3-, NO2-, Fe(III), and trimethylamine N-oxide, in the absence of O2. The bacterium catalyzed the reductive transformation of tetrachloromethane (CT) under anaerobic conditions. The only identified product was trichloromethane (CF), but CF production was not stoichiometric. No dichloromethane, chloromethane, or methane was produced. A chloride mass balance indicated that fully dechlorinated products were not formed. Studies with [14C]CT suggested that a portion of the transformed CT reacted with biomass to form unidentified soluble and insoluble products. Intermediate production of a trichloromethyl radical can explain observed product distribution without significant CO2 formation. Evidence suggests that respiratory c-type cytochromes are responsible for the dehalogenation ability of S. putrefaciens 200. Previous growth under microaerobic conditions ([O2], < 2.5 microM) results in (i) a 2.6-fold increase in specific heme c content and (ii) a 2.3-fold increase in specific rates of anaerobic CT transformation. Manipulation of heme content by growth on iron-free medium or medium amended with delta-aminolevulinic acid showed that CT transformation rates increase with increases in specific heme c content. Transformation of CT is inhibited by CO. Dehalogenation studies with periplasmic, cytoplasmic, and membrane fractions indicated that only periplasmic and membrane fractions possessed dehalogenation ability. Cytochromes c were the predominant cytochromes present. Membranes were also found to contain smaller amounts of cytochrome b. Observed CT transformation patterns are consistent with a cometabolic description involving fortuitous CT reduction by reduced c-type cytochromes.

Biotransformation↗
PubMed1993

Orientation of the cleavage site of the herpes simplex virus glycoprotein G-2.

During the synthesis of glycoprotein G-2 (gG-2) of herpes simplex virus type 2, the 104,000-Da gG-2 precursor (104K precursor) is cleaved to generate the 72K and the 31K intermediates. The 72K product is processed to generate the mature gG-2 (molecular mass, 108,000 Da), while the 31K product is additionally processed and secreted into the extracellular medium as the 34K component (H. K. Su, R. Eberle, and R. J. Courtney, J. Virol. 61:1735-1737, 1987). In this study, the orientations of the 31K and 72K products on the 104K precursor were determined by using two antipeptide sera produced in rabbits and a monoclonal antibody, 13 alpha C6, directed against gG-2. The sera prepared against synthetic peptides corresponding to the terminal amino acid residues 67 to 78 and an internal peptide at amino acids 247 to 260 of gG-2 recognized the 104K precursor and the 31K cleavage product but not the 72K intermediate. In contrast, 13 alpha C6 detected the 72K cleavage product and the uncleaved precursor but not the 31K cleavage component. The epitope recognized by 13 alpha C6 was mapped within amino acids 486 to 566. These results suggest that the 31K cleavage product is derived from the amino-terminal portion of the 104K precursor molecule and that the 72K intermediate is derived from the carboxyl terminus. In support of our model described above for the synthesis of gG-2, antibodies recognizing either of the cleavage products reacted with the uncleaved precursor but not with the other cleavage product. By using partial endo-beta-N-acetylglucosaminidase H analysis, two N-linked glycosylation sites were found on each of the cleavage products. The distribution of the N-linked glycosylation sites and the reactivities of the antipeptide sera allowed the cleavage region on the precursor to be mapped to within amino acids 260 to 437.

Antibodies, Monoclonal↗
PubMed1993

Service utilization patterns as determinants of capitation rates.

OBJECTIVE: In a capitation payment system, the ability to project service requirements and cost is critical. The types and levels of services needed by persons with serious mental illness vary. The purpose of this study was to identify different patterns of service utilization and patient characteristics and costs associated with them. METHODS: Service use by 55 clients participating in a psychosocial-habilitation outpatient program at a hospital-based community mental health center was tracked for one year. Treatment cost for all services was calculated for each patient. RESULTS: Cluster analysis indicated that for persons with serious mental illness who enter community treatment, there appear to be four distinct patterns of service use: low, moderate, moderately high, and high. The groups were differentiated only by the presence of a disability (among the moderately high users) and a history of frequent inpatient treatment (among the high users). The two highest-use groups represented about one-third of the total sample but consumed more than three-fourths of the total resources. CONCLUSIONS: The lack of significant group differences on most clinical variables may make it difficult to develop capitation rates for subgroups of persons with serious mental illness. Service use may be determined by factors other than clinical need.

Activities of Daily Living↗
PubMed1993

Genomic elements involved in transcriptional regulation of the rabbit surfactant protein-A gene.

Expression of the surfactant protein-A (SP-A) gene is lung specific and is developmentally and hormonally regulated in fetal lung tissue. Cyclic AMP analogs and glucocorticoids stimulate transcriptional activity of the SP-A gene in fetal rabbit lung tissue in culture; an additive effect is observed when the agents are added in combination. To analyze the genomic regions that regulate SP-A promoter activity, fusion genes comprised of -1766, -991, -378, and -47 basepairs (bp) of DNA flanking the 5'-end of the SP-A gene, the transcription initiation site, and 20 bp of exon I linked to the human GH (hGH) structural gene were subcloned into a replication-defective human adenovirus vector and transfected into differentiated rat type II cells in primary culture. SP-A promoter activity was analyzed by RIA of hGH protein in the culture medium. In type II cells transfected with SP-A-1766:hGH and SP-A-991:hGH fusion genes, hGH production was induced 30- to 40-fold by (Bu)2AMP (Bt2cAMP; 1 mM). When type II cells were transfected with the SP-A-378:hGH fusion gene, basal levels of expression were reduced by more than 50%; however, Bt2cAMP caused an 11-fold increase in hGH production. In type II cells transfected with the SP-A-47:hGH fusion gene, basal levels of hGH production were essentially undetectable, and no stimulatory effect of Bt2cAMP was apparent. Cyclic AMP stimulation of expression of the SP-A-1766:hGH, SP-A-991:hGH, and SP-A-378:hGH fusion genes was limited to type II pneumonocytes in primary culture and was absent in two lung adenocarcinoma cell lines (NCl-H358 and A549), which do not express SP-A, and in cAMP-responsive adrenal Y1 cells. Mutations of a putative cAMP-responsive element (TGACCTCA) at -261 bp revealed its functional importance in mediating cAMP regulation of SP-A gene expression. Unexpectedly, dexamethasone (Dex; 10(-7) M) antagonized the stimulatory effect of Bt2cAMP on expression of SP-A:hGH fusion genes containing from -378 to -1766 bp of 5'-flanking DNA as well as that of a fusion gene construct containing -991 bp of 5'-flanking DNA, the first exon, the first intron, and 20 bp of the second exon (SP-A-991+670:hGH). The inhibitory effect of Dex was dose dependent, with half-maximal inhibition occurring at a Dex concentration of 8 x 10(-10) M. The inhibitory effect of Dex was prevented by the glucocorticoid receptor antagonist RU486.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1992

Reactivation of latent herpes simplex virus by excimer laser photokeratectomy.

We tested whether excimer laser photorefractive and phototherapeutic keratectomy may reactivate latent herpes simplex and cause recurrent keratitis in mice. Two of ten latently infected mice that were treated with ten excimer laser pulses to the corneal epithelium shed herpes simplex virus type 1, as did four of ten mice that were treated with 50 excimer laser pulses. Ocular shedding of herpes simplex virus was detected in four of ten mice that were treated with ethylenediamine-tetraacetic acid (EDTA) scraping of the corneal epithelium without laser keratectomy, and in six of ten mice on which combined EDTA-facilitated epithelial removal was performed followed by the application of ten excimer laser pulses. In both EDTA-treated groups, viral shedding was prolonged and 18 of 20 mice developed marked corneal opacification or neovascularization, or both. Corneal photoablation with the excimer laser may induce reactivation of latent herpes simplex virus, even in mice with clear and smooth-appearing corneas, and should be considered in the differential diagnosis of humans with persistent corneal epithelial defects after refractive or therapeutic excimer procedures.

Animals↗
PubMed1992

Using gadolinium-enhanced magnetic resonance imaging lesions to monitor disease activity in multiple sclerosis.

The highly variable clinical course and the lack of a direct measurement of disease activity have made evaluation of experimental therapies in multiple sclerosis (MS) difficult. Recent studies indicate that clinically silent lesions can be demonstrated by magnetic resonance imaging (MRI) in patients with mild relapsing-remitting MS. Thus, MRI may provide a means for monitoring therapeutic trials in the early phase of MS. We studied 12 patients longitudinally for 12 to 21 months with monthly gadolinium (Gd)-enhanced MRIs. The data have been used to identify the most effective design of a clinical trial using Gd-enhanced lesions as the outcome measure. Frequent ( > 1/mo) Gd-enhancing lesions were observed in 9 of the 12 patients, indicating that the disease is active even during the early phase of the illness. The frequency of the lesions was not constant; there was marked fluctuation in lesion number from month to month. However, the magnitude of the peak number of lesions and the frequency of the peaks varied among patients. Because of this variability, the most effective use of Gd-enhancing lesions as an outcome measure in a clinical trial was a crossover design with study arms of sufficient duration to allow accurate estimation of lesion frequency. Monitoring Gd-enhancing lesions may be an effective tool to assist in the assessment of experimental therapies in early MS.

Adult↗
PubMed1992

EAE cerebrospinal fluid augments in vitro phagocytosis and metabolism of CNS myelin by macrophages.

Previous studies from this laboratory have shown that CNS myelin is phagocytized and metabolized by cultured rat macrophages to a much larger extent when myelin is pretreated with serum containing antibodies to myelin constituents than when it is left untreated or pretreated with non-specific serum. In this study the effect of cerebrospinal fluid (CSF) from rabbits with experimental allergic encephalomyelitis (EAE) in promoting myelin phagocytosis was examined. Fourteen rabbits were immunized with purified myelin in Freund's complete adjuvant, seven of which developed clinical EAE symptoms. Serum and CSF were collected from EAE and control rabbits, and the CSF was centrifuged to remove cells. Sera and CSF from these rabbits and from Freund's adjuvant-immunized controls and untreated controls were measured for IgG content by radial diffusion assay, their myelin antibody characteristics were analyzed by immunoblots, and the ability of these serum and CSF samples to promote myelin phagocytosis when used for myelin opsonization was examined. The ability of a CSF sample to enhance radioactive myelin uptake and phagocytosis by cultured macrophages as measured by the appearance of radioactive cholesterol ester was linearly proportional to its total IgG titer, and correlated approximately both with clinical symptoms of the animal and the presence of antibody against the myelin constituents myelin basic protein, proteolipid protein, and galactocerebroside. The cholesterol esterification activities of EAE sera correlated to a lesser extent with IgG levels and clinical symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Beta-endorphin and corticotropin immunoreactivity and specific binding in the neuromuscular system of obese-diabetic mice.

Immunoreactivity for two derivatives of pro-opiomelanocortin, beta-endorphin and alpha-melanocortin (or corticotropin), was demonstrated, using a conventional immunoperoxidase method, in some of the intramuscular nerves in muscle sections from obese diabetic (ob/ob) mice and homozygous lean (+/+) mice. The endplate regions were visualized in the sections by staining for acetylcholinesterase reaction product. The proportion of muscle endplates with beta-endorphin-immunoreactive motor nerves was approximately 2.5-fold higher in soleus and extensor digitorum longus muscles and approximately 1.5-fold higher in the diaphragm of the obese (ob/ob) mice compared to the normal lean mice. The proportion of muscle endplates with alpha-melanotropin-immunoreactive motor nerves was between 30 and 53% lower, depending on the muscle type, in the ob/ob mice compared to the lean mice. The muscles of ob/ob and lean mice were investigated for the presence of specific binding sites for [125I]beta-endorphin and for [125I]corticotropin, using autoradiography. Some muscle fibres in soleus, extensor digitorum longus and diaphragm in both the ob/ob and the lean mice exhibited specific binding sites for the radioactive ligands. The binding sites were distributed over the entire surface in these muscle fibres. In the ob/ob mice the number of muscle fibres with specific [125I]beta-endorphin binding sites was six-fold higher in soleus and approximately 10-fold higher in extensor digitorum longus and diaphragm, than in the corresponding muscles of the lean mice. In contrast, the number of muscle fibres with specific [125I]corticotropin binding sites was similar in obese (ob/ob) and lean mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

91Zr NMR characterisation of phases in transformation toughened zirconia.

A detailed 91Zr NMR investigation is presented of the five component (cubic, monoclinic, tetragonal, orthorhombic and delta) phase mixture in the transformation toughened engineering ceramic, magnesia-partially-stabilised zirconia (MgPSZ). The phases are distinguished on the basis of the quadrupole interaction displayed in the powder pattern of the 91Zr(1/2, -1/2) transition. This paper reports: (i) the first characterisation of the magnesia-fully-stabilised cubic phase at the eutectic composition (13.5 mol% MgO); (ii) the observation of a poorly ordered tetragonal phase on fast cooling ZrO2 (9.3 mol% MgO) from the cubic phase field at 1720 degrees C, and the subsequent growth and ordering of the tetragonal phase precipitates due to further annealing; (iii) the observation of the (partial) transformation of the cubic phase to the ordered delta-phase (Mg2Zr5O12) on annealing MgPSZ at 1100 degrees C for 8 h; and (iv) the observation of the transformation of the tetragonal phase into the orthorhombic phase after cooling in liquid nitrogen, and the reverse transformation after heating to 600 degrees C.

Crystallization↗