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Biomedical subjects

D R Smith

Publications and source records attributed to D R Smith.

At least 109 records · Page 6Linked to original sources
PubMed1998

Epidemiologic herd-level assessment of causative agents and risk factors for winter dysentery in dairy cattle.

OBJECTIVE: To test the association between exposure to bovine coronavirus (BCV) and outbreaks of winter dysentery (WD) in dairy herds and to examine other risk factors for outbreaks of WD in dairy herds. ANIMALS: 12 dairy herds in Ohio affected with WD (case herds). For each case herd, 2 unaffected herds from the same area were concurrently used as control herds. PROCEDURE: A case-control study was conducted, using herds as the unit of investigation. Multivariate logistic regression modeling was used to identify risk factors for contracting disease. RESULTS: 4 factors appeared to increase a herd's risk for WD: increase in herd prevalence of adult cows that had a fourfold or more increase in BCV serum IgG antibody titer; increase in herd prevalence of adult cows that had a fourfold or more increase in bovine viral diarrhea virus (BVDV) titer; housing cattle in tiestall or stanchion barns rather than free-stall facilities; and use of equipment to handle manure and subsequently handle feed. The adjusted population-attributable risk for these variables was 71, 43, 53, and 31%, respectively, and 99% overall, indicating that these variables had considerable impact on WD outbreaks for the study population. CONCLUSIONS AND CLINICAL RELEVANCE: In dairies in Ohio, recent herd exposure to BCV appeared to increase the risk for WD outbreaks. Some WD outbreaks might have been associated with acute BVDV infection. Certain housing and management practices may have increased the risk of an outbreak of WD.

Animals↗
PubMed1997

Immunologic aspects of neurologic and neuromuscular diseases.

Inflammatory disorders of the nervous and neuromuscular system are not uncommon despite the fact that immune privilege exists in much of the nervous system. Common immune-mediated neurologic diseases include multiple sclerosis, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, and idiopathic polymyositis. Environmental, genetic, and immunologic factors have been postulated to be involved in the pathogenesis of these diseases, but much remains to be elucidated about the specific identity and relative contributions of these factors. Several new therapies have become available for these diseases in the past few years, and many others are under investigation. Strategies that enhance the normal tolerance mechanisms of the immune system are being developed. In particular, strategies to block T(H)1-type responses or enhance T(H)2/3-type responses have generated interest.

Humans↗
PubMed1997

Increased interleukin 12 production in progressive multiple sclerosis: induction by activated CD4+ T cells via CD40 ligand.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system postulated to be a cell-mediated autoimmune disease in which interferon gamma (IFN-gamma) plays an important role. There is increased IFN-gamma secretion in MS, and IFN-gamma administration induces exacerbations of disease. We found that interleukin 12 (IL-12) was responsible for raised IFN-gamma secretion in MS as anti-IL-12 antibodies reversed raised anti-CD3-induced IFN-gamma in MS patients to normal levels. Furthermore, we found a marked increase in T cell receptor-mediated IL-12 secretion in progressive MS patients vs. controls (24.8 +/- 7.7 pg/ml vs. 1.5 +/- 1.0 pg/ml, P = 0.003) and vs. relapsing-remitting patients (3.7 +/- 1.4 pg/ml, P < 0.05). Investigation of the cellular basis for raised IL-12 demonstrated that T cells from MS patients induced IL-12 secretion from non-T cells, and that T cells from MS patients could even drive non-T cells from normal subjects to produce increased IL-12. Anti-CD40 ligand antibody completely blocked IL-12 secretion induced by activated T cells, and we found increased CD40 ligand expression by activated CD4+ T cells in MS patients vs. controls. The CD40 ligand-dependent Th1-type immune activation was observed in the progressive but not in the relapsing-remitting from of MS, suggesting a link to disease pathogenesis and progression and providing a basis for immune intervention in the disease.

Adult↗
PubMed1997

Immune deviation following pulse cyclophosphamide/methylprednisolone treatment of multiple sclerosis: increased interleukin-4 production and associated eosinophilia.

Multiple sclerosis (MS) is postulated to be a Th1-type cell-mediated autoimmune disease. Thus therapies that decrease T cell interferon (IFN)-gamma production or increase interleukin (IL)-4 production would be expected to have an ameliorating effect on MS. Some progressive MS patients receiving pulse cyclophosphamide therapy developed peripheral blood eosinophilia. We investigated whether cyclophosphamide-treated patients had immune deviation toward Th2 responses. We measured cytokine production in patients receiving either monthly intravenous methylprednisolone (MP), intravenous cyclophosphamide plus methylprednisolone (CY/MP), methotrexate, IFN-beta1b, in untreated MS patients, and in healthy controls. Minimal IL-4 was secreted in untreated patients (129 +/- 62 pg/ml), methotrexate-treated patients (99 +/- 79 pg/ml), and healthy controls (50 +/- 13 pg/ml). A marked increase in IL-4 was observed in CY/MP patients (1,503 +/- 291 pg/ml). Patients treated with MP (418 +/- 160 pg/ml) or IFN-beta1b (425 +/- 167 pg/ml) showed small increases. Eosinophilia in CY/MP-treated patients (6.0 +/- 0.7%) correlated with increased IL-4. IL-10 production was also increased in CY/MP-treated patients. Both CY/MP- and MP-treated groups had decreased production of IFN-gamma compared with untreated MS. These findings demonstrate pronounced immune deviation favoring Th2-type responses after pulse cyclophosphamide therapy.

Adult↗
PubMed1997

Abnormal expression of the p53 tumor suppressor gene in the conjunctiva of patients with pterygium.

PURPOSE: To determine whether pterygium is a disorder of abnormal growth by examining the expression of the p53 gene in the conjunctiva of patients with pterygium. METHODS: Immunostaining for abnormal expression of p53 was performed using mouse monoclonal antibody to human p53, pAb 240, on six eyes with primary pterygium and two eyes with recurrent pterygium. RESULTS: In three of the eight eyes with pterygium, specimens were positive for abnormal expression in the epithelium of the pterygium and in the superior bulbar conjunctiva. CONCLUSION: Abnormal p53 expression in the epithelium of primary and recurrent pterygium specimens suggests that pterygium is a growth disorder rather than a degeneration.

Antibodies, Monoclonal↗
PubMed1997

Outcome-based assessment of endolymphatic sac surgery for Meniere's disease.

This study reports the preliminary results of an outcomes approach to analysis of the effectiveness of endolymphatic sac decompression (ELSD). Using the medical outcomes survey's 36-item, short-form health survey (SF-36), we assessed the quality of life in 33 patients with disabling Meniere's disease undergoing ELSD for medically intractable vertigo. Results indicate that patients with 1995 American Academy of Otolaryngology--Head and Neck Surgery (AAO/HNS) class A or B outcomes showed no significant difference from population norms on the SF-36, whereas patients with AAO/HNS classes C to E outcomes scored significantly below norms. Six patients who were given the SF-36 preoperatively scored consistently below population norms. Postoperatively, they showed a statistically significant improvement and were statistically equal to norms. These findings suggest that the SF-36 is a good measure of the quality of life impairment in patients with disabling Meniere's disease. In addition, SF-36 scores correlated well with the 1995 AAO/HNS classification.

Adult↗
PubMed1997

Multiplex sequencing of 1.5 Mb of the Mycobacterium leprae genome.

The nucleotide sequence of 1.5 Mb of genomic DNA from Mycobacterium leprae was determined using computer-assisted multiplex sequencing technology. This brings the 2.8-Mb M. leprae genome sequence to approximately 66% completion. The sequences, derived from 43 recombinant cosmids, contain 1046 putative protein-coding genes, 44 repetitive regions, 3 tRNAs, and 15 tRNAs. The gene density of one per 1.4 kb is slightly lower than that of Mycoplasma (1.2 kb). Of the protein coding genes, 44% have significant matches to genes with well-defined functions. Comparison of 1157 M. leprae and 1564 Mycobacterium tuberculosis proteins shows a complex mosaic of homologous genomic blocks with up to 22 adjacent proteins in conserved map order. Matches to known enzymatic, antigenic, membrane, cell wall, cell division, multidrug resistance, and virulence proteins suggest therapeutic and vaccine targets. Unusual features of the M. leprae genome include large polyketide synthase (pks) operons, inteins, and highly fragmented pseudogenes.

Amino Acid Sequence↗
PubMed1997

Complete genome sequence of Methanobacterium thermoautotrophicum deltaH: functional analysis and comparative genomics.

The complete 1,751,377-bp sequence of the genome of the thermophilic archaeon Methanobacterium thermoautotrophicum deltaH has been determined by a whole-genome shotgun sequencing approach. A total of 1,855 open reading frames (ORFs) have been identified that appear to encode polypeptides, 844 (46%) of which have been assigned putative functions based on their similarities to database sequences with assigned functions. A total of 514 (28%) of the ORF-encoded polypeptides are related to sequences with unknown functions, and 496 (27%) have little or no homology to sequences in public databases. Comparisons with Eucarya-, Bacteria-, and Archaea-specific databases reveal that 1,013 of the putative gene products (54%) are most similar to polypeptide sequences described previously for other organisms in the domain Archaea. Comparisons with the Methanococcus jannaschii genome data underline the extensive divergence that has occurred between these two methanogens; only 352 (19%) of M. thermoautotrophicum ORFs encode sequences that are >50% identical to M. jannaschii polypeptides, and there is little conservation in the relative locations of orthologous genes. When the M. thermoautotrophicum ORFs are compared to sequences from only the eucaryal and bacterial domains, 786 (42%) are more similar to bacterial sequences and 241 (13%) are more similar to eucaryal sequences. The bacterial domain-like gene products include the majority of those predicted to be involved in cofactor and small molecule biosyntheses, intermediary metabolism, transport, nitrogen fixation, regulatory functions, and interactions with the environment. Most proteins predicted to be involved in DNA metabolism, transcription, and translation are more similar to eucaryal sequences. Gene structure and organization have features that are typical of the Bacteria, including genes that encode polypeptides closely related to eucaryal proteins. There are 24 polypeptides that could form two-component sensor kinase-response regulator systems and homologs of the bacterial Hsp70-response proteins DnaK and DnaJ, which are notably absent in M. jannaschii. DNA replication initiation and chromosome packaging in M. thermoautotrophicum are predicted to have eucaryal features, based on the presence of two Cdc6 homologs and three histones; however, the presence of an ftsZ gene indicates a bacterial type of cell division initiation. The DNA polymerases include an X-family repair type and an unusual archaeal B type formed by two separate polypeptides. The DNA-dependent RNA polymerase (RNAP) subunits A', A", B', B" and H are encoded in a typical archaeal RNAP operon, although a second A' subunit-encoding gene is present at a remote location. There are two rRNA operons, and 39 tRNA genes are dispersed around the genome, although most of these occur in clusters. Three of the tRNA genes have introns, including the tRNAPro (GGG) gene, which contains a second intron at an unprecedented location. There is no selenocysteinyl-tRNA gene nor evidence for classically organized IS elements, prophages, or plasmids. The genome contains one intein and two extended repeats (3.6 and 8.6 kb) that are members of a family with 18 representatives in the M. jannaschii genome.

Anaerobiosis↗
PubMed1997

Errors and correlates in parental recall of child immunizations: effects on vaccination coverage estimates.

OBJECTIVE: We evaluated the accuracy of parental recall of children's immunization histories as compared with provider records and examined how errors in parental recall correlate with sociodemographic characteristics. DESIGN: The validation study was part of a population-based household survey designed to assess immunization levels among Texas children under age 2 years. For 72% (n = 3278), interviewers used vaccination records from the parent to copy dates for the diphtheria and tetanus toxoids and pertussis vaccine (DTP), oral polio vaccine (OPV), and measles, mumps, and rubella (MMR) shots. For parents without shot records (n = 1216), interviewers asked about each vaccine, whether the child had received the shot, how many, and at what age. Of these, 85% (n = 1029) were validated with health provider records. RESULTS: Measured against provider records, only 34% of parents accurately recalled the number of DTP shots a child had. More often (42%) parents underestimated the number of DTP shots than overestimated (24%). Agreement between parental recall and provider records was high (83%) for the single dose of MMR. Accuracy of parents' recall did not differ by race/ethnicity, education level, or type of health insurance coverage, but decreased as child's age increased. Having a vaccination record at home was associated with a higher immunization status. Hispanic, lower educated, and uninsured parents were more likely to have a vaccination record than non-Hispanic, higher educated, and privately insured parents. DISCUSSION: Validity of parental recall of children's immunization histories depends on the vaccine and the age of the child, which is highly correlated with the number of shots parents must recollect. Results suggest that inclusion of parent recall information from vaccination surveys underestimates DTP:OPV:MMR coverage. This underestimation is consistent across economic and race/ethnic groups. Thus, community surveys based on cards and recall should provide reliable conclusions about which groups need intensive program efforts. For the routine monitoring of vaccination coverage, reasonable estimates can be obtained by combining parent-held record and parent recall data. Caution is required when comparing coverage estimates from different surveys since the source of information and method of derivation will produce widely varying coverage rates.

Black or African American↗
PubMed1997

The impact of public assistance factors on the immunization levels of children younger than 2 years.

OBJECTIVES: This study examined how children's immunization status varied with enrollment in the Women, Infants, and Children (WIC); Aid to Families with Dependent Children (AFDC); food stamp; and Medicaid programs. METHODS: A statewide survey was used to determine the percentage of children less than 2 years of age who were up to date for diphtheria, tetanus, and pertussis; polio; and measles, mumps, and rubella vaccines. RESULTS: WIC and uninsured children were more likely and AFDC and Medicaid children less likely to be up to date than others. CONCLUSIONS: The higher immunization status of WIC and uninsured children suggests that integrating immunization practices with government programs may be effective.

Aid to Families with Dependent Children↗
PubMed1997

Aviation spatial orientation in relationship to head position, altitude interpretation, and control.

INTRODUCTION: Recently, a visually driven neck reflex was identified as causing head tilt toward the horizon during VMC flight. If this is the case, then pilots orient about a fixed rather than moving horizon, implying current attitude instruments inaccurately present spatial information. The purpose of this study was to determine if the opto-kinetic cervical neck reflex has an effect dependent on passive (autopilot) or active control of the aircraft. Further, findings could help determine if the opto-kinetic cervical reflex is characteristic of other flight crewmembers. METHODS: There were 16 military pilots who flew two 13-min VMC low-level routes in a large dome flight simulator. Head position in relation to aircraft bank angle was recorded by a head tracker device. During one low-level route, the pilot had a supervisory role as the autopilot flew the aircraft (passive). The other route was flow manually by the pilot (active). RESULTS: Pilots consistently tilted the head to maintain alignment with the horizon. Similar head tilt angles were found in both the active and passive flight phases. However, head tilt had a faster onset rate in the passive condition. CONCLUSION: Results indicate the opto-kinetic cervical reflex affects pilots while actively flying or in a supervisory role as the autopilot flies. The consistent head tilt angles in both conditions should be considered in attitude indicator, HUD, and HMD designs. Further, results seem to indicate that non-pilot flight crewmembers are affected by the opto-kinetic cervical reflex which should be considered in spatial disorientation and airsickness discussions.

Aerospace Medicine↗
PubMed1996

Ion microscopy imaging of 10B from p-boronophenylalanine in a brain tumor model for boron neutron capture therapy.

Boron neutron capture therapy (BNCT), a binary treatment modality that can potentially irradiate tumor tissue within cellular dimensions, is critically dependent on the preferential delivery of 10B to individual neoplastic cells. In this study, ion microscopy was used to quantitatively evaluate the selectivity of p-boronophenylalanine-fructose (BPA-F) in the rat 9L gliosarcoma brain tumor model. With a spatial resolution of approximately 0.5 microm, ion microscopy images show that BPA-F delivers 3.5 times more boron to the main tumor mass [99 +/- 36 microg/g tissue (mean +/- SD)] than to the contiguous normal brain (27 +/- 12 microg/g tissue). A similar, but lower, accumulation was observed away from the main tumor mass in small clusters of neoplastic cells (47 +/- 15 microg/g tissue) invading the surrounding brain (16 +/- 8 microg/g tissue). These findings establish for the first time the selectivity of BPA-F to the neoplastic cells invading the normal brain and provide a much-needed baseline measurement of the distribution of a clinically approved BNCT drug. Given the propensity for malignant brain tumors to infiltrate the surrounding normal brain, these observations have particular significance for clinical trials of BNCT for human glioblastoma multiforme using the drug BPA-F.

Animals↗
PubMed1996

Mexican papita viroid: putative ancestor of crop viroids.

The potato spindle tuber disease was first observed early in the 20th century in the northeastern United States and shown, in 1971, to be incited by a viroid, potato spindle tuber viroid (PSTVd). No wild-plant PSTVd reservoirs have been identified; thus, the initial source of PSTVd infecting potatoes has remained a mystery. Several variants of a novel viroid, designated Mexican papita viroid (MPVd), have now been isolated from Solanum cardiophyllum Lindl. (papita güera, cimantli) plants growing wild in the Mexican state of Aguascalientes. MPVd's nucleotide sequence is most closely related to those of the tomato planta macho viroid (TPMVd) and PSTVd. From TPMVd, MPVd may be distinguished on the basis of biological properties, such as replication and symptom formation in certain differential hosts. Phylogenetic and ecological data indicate that MPVd and certain viroids now affecting crop plants, such as TPMVd, PSTVd, and possibly others, have a common ancestor. We hypothesize that commercial potatoes grown in the United States have become viroid-infected by chance transfer of MPVd or a similar viroid from endemically infected wild solanaceous plants imported from Mexico as germplasm, conceivably from plants known to have been introduced from Mexico to the United States late in the 19th century in efforts to identify genetic resistance to the potato late blight fungus, Phytophthora infestans.

Base Sequence↗
PubMed1996

Application of experimental design techniques to optimize a competitive ELISA.

This paper describes the application of experimental design techniques to optimize a sensitive ELISA for a hapten molecule with a calibration range of 0-1000 pg/ml. Ten factors that were expected to affect the assay performance were initially screened, followed by factorial experiments to delineate the effects of the critical factors identified at the screening stage. Assay performance was evaluated using a unique rating system based on standard curve reproducibility, assay detection limits and the use of desirability functions. This rating system allowed multiple responses to be evaluated simultaneously. It was found that the substrate incubation time and enzyme label lot played an important role, while dilutions of the enzyme label and the anti-hapten antibody showed significant interaction. These observations were in good agreement with optimal assay conditions based on historical data collected over a period of two to three years. Application of experimental design techniques enabled us to confirm the significance of the factors affecting the assay within a three month period, with a minimum number of experiments. In addition, information on interaction between factors were determined.

Animals↗
PubMed1996

A diet containing myristoleic plus palmitoleic acids elevates plasma cholesterol in young growing swine.

The objective of this study was to test the effect of a novel fatty acid mixture, enriched with myristoleic and palmitoleic acids, on plasma lipoprotein cholesterol concentrations. Weanling pigs were assigned to one of six groups and each group received a diet differing in fatty acid composition. Diets were fed for 35 days and contained 10 g added cornstarch/100 g (to provide baseline data) or 10 g added fatty acids/100 g. For those diets containing added fatty acids, extracted lipids contained 36% myristoleic plus palmitoleic acid combined (14:1/16:1 diet), 52% palmitic acid (16:0 diet), 51% stearic acid (18:0 diet), 47% oleic acid (18:1 diet), or 38% linoleic acid (18:2 diet). With the exception of the cornstarch diet, all diets contained approximately 30% myristic acid. There were no significant differences in weight gain across treatment groups (P = 0.22). All diets caused a significant increase in triglycerides and in total, low density lipoprotein, high density lipoprotein, and very low density lipoprotein cholesterol. The increase in total plasma cholesterol from pretreatment values was greatest in pigs fed the 14:1/16:1 and 18:1 diets. However, the increase in low density lipoprotein cholesterol from the pretreatment concentration was greatest in the 14:1/16:1-fed pigs. Increases in very low density lipoprotein cholesterol above pretreatment concentrations were lowest in 16:0-fed pigs and greatest in 18:1-fed pigs. Dietary fatty acids elicited changes in plasma fatty acids which generally were reflective of the diets, although the 18:0 diet did not alter plasma fatty acid concentrations and the 16:0 diet increased plasma 16:0 only at the end of the study. These results demonstrated that the combination of myristoleic plus palmitoleic acids increased plasma cholesterol in young pigs, suggesting that fatty acid chain length, rather than degree of unsaturation, is primarily responsible for the effects of fatty acids on circulating lipoprotein cholesterol concentrations.

Animals↗
PubMed1996

What is the denominator for contrast normalisation?

The perceived speed of 1 c/deg sinusoidal gratings of contrast 0.02 was measured in the presence of high contrast (0.50) 1 c/deg sinusoidal gratings (called modifiers). The modifiers drifted or were counterphase modulated at various temporal frequencies. The presence of a modifier with temporal frequencies (0 and 3 Hz) lower than the low contrast moving grating decreased its perceived speed while the presence of modifiers with higher temporal frequencies (8, 12 and 16 Hz) increased its perceived speed. A modifier of the same temporal frequency (6 Hz) as the standard grating had no effect upon the perceived speed of the low contrast gratings. Moving modifiers are more effective than counterphase flickering modifiers in biasing the perceived speed of low contrast gratings if they move in the same direction as the test grating and less effective if they move in the opposite direction. Finally, a modifier presented in an annulus surrounding the test grating is more effective than a modifier presented in a circular patch above or below the test grating in raising the perceived speed of low contrast gratings. This suggests that perceived speed depends on the ratio of low and high temporal frequency signals averaged over a significant area of the visual field.

Humans↗