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B Smith

Publications and source records attributed to B Smith.

At least 145 records · Page 8Linked to original sources
PubMed1998

Immunohistochemical characterization of immunoglobulin-containing cells and T cells in the colonic mucosa of healthy dogs.

OBJECTIVES: To quantitate numbers of immunoglobulin (Ig)-containing cells (IgA, IgG, and IgM) and T cells (CD3+, CD4+, and CD8+) in the colonic mucosa of healthy dogs, and to determine whether mean cell numbers differ among colonic regions. ANIMALS: 10 clinically normal young adult mixed-breed dogs. PROCEDURE: Endoscopically obtained specimens of ascending, transverse, and descending colonic mucosa were stained specifically for IgA, IgG, and IgM heavy chains and T-cell antigens, CD3+, CD4+, and CD8+, using immunoperoxidase techniques. Morphometric analysis, performed by light microscopy, was used to quantitate numbers in these standardized areas of colonic mucosa. Data analysis allowed determination of mean cell numbers in each colonic region, as well as comparison of mean cell numbers among colonic regions. RESULTS: The CD3+ and CD8+ T cells were the predominant immune cell types in all colonic regions. In the mucosa, CD3+ T cells were significantly (P < 0.05) more numerous than CD8+ T cells, and CD8+ T cells were significantly (P < 0.05) more numerous than CD4+ T cells. The IgA-containing cells were significantly (P < 0.05) more numerous than IgG-containing cells, whereas IgM-containing cells were least numerous (P < 0.05). Differences in mean cell counts among colonic regions were not significant for Ig-containing cells or T cells. CONCLUSIONS: Mean numbers of immune cells did not differ significantly among colonic regions in healthy dogs, although differences existed in mean populations of T cells and Ig-containing cells. The CD3+ and CD8+ T cells were the most numerous immune cell types in colonic mucosa. CLINICAL RELEVANCE: These quantitative data provide a basis for study of alterations in populations of mucosal immune cells and their possible contribution to the pathogenesis of gastrointestinal tract disease.

Animals↗
PubMed1998

A descriptive analysis of the Journal of Manipulative and Physiological Therapeutics, 1989-1996.

BACKGROUND: Two previous reports have summarized the content, institutional affiliations, academic training and funding sources for articles published in the Journal of Manipulative and Physiological Therapeutics (JMPT) from 1978-1986 and 1987-1988. OBJECTIVES: (a) to quantitatively assess the types of articles published in the JMPT from 1989-1996; (b) to identify the affiliations of contributors to the JMPT during this period; (c) to identify the academic backgrounds of contributors to the JMPT from 1989-1996; (d) to identify funding sources for scholarly works published in the JMPT during this period; (e) to identify the proportionate contributions of female authors; (f) to assess the proportion of articles contributed, i.e., foreign vs. domestic sources; and (g) to compare findings for the JMPT from 1989-1996 with similar data for 1978-1988. STUDY DESIGN: Survey of the contents of the JMPT from 1989-1996. METHODS: The contents of the 69 issues of the JMPT from 1989-1996 were reviewed by all authors. Characteristics extracted included category of the article, academic backgrounds of authors, institutional affiliations of authors, funding sources, gender of authors and nation(s) of origin of articles. RESULTS: The annual rate of published contributions to the Journal has more than doubled compared with its first 11 yr of publication, and the proportion of original data reports has grown slightly. Controlled and quasicontrolled clinical trials were 7 times more numerous (n = 28 articles) during the past 8 yr. Chiropractic colleges were the most frequently mentioned affiliation of authors, followed by private practice and nonchiropractic colleges. Collaborative articles submitted by authors at two or more chiropractic colleges grew from only 4 articles from 1978-1988 to 31 articles from 1989-1996. As in previous years, the National College of Chiropractic continued to be the most frequently mentioned academic affiliation of authors. The numbers of articles contributed by those holding scientific (e.g., PhD) and medical degrees have grown substantially. The number of articles mentioning financial support grew from 78 from 1978-1988 to 179 from 1989-1996, and 58 new funding sources were identified. The Foundation for Chiropractic Education and Research continues to be the most frequently mentioned source of funding. Of all articles published in the JMPT from 1989-1996, 21% were authored or coauthored by women. Of 1050 articles, 286 (27%) were authored or coauthored by individuals residing outside the United States of America. CONCLUSIONS: Substantial increases in scholarly activities within the chiropractic profession are suggested by the growth in scholarly products published in the discipline's most distinguished periodical. Increases in controlled outcome studies, collaboration among chiropractic institutions, contributions from nonchiropractors, contributions from nonchiropractic institutions and funding for research suggest a degree of professional maturation and growing interest in the content of the discipline.

Authorship↗
PubMed1998

Evaluation of mild lameness in horses trotting on a treadmill by clinicians and interns or residents and correlation of their assessments with kinematic gait analysis.

OBJECTIVE: To estimate sensitivity and accuracy of subjective evaluation of mild lameness in horses during treadmill locomotion and to correlate subjective evaluation with kinematic analysis. ANIMALS: 19 lame and 5 clinically normal horses. PROCEDURE: Lameness was evaluated by subjective score and kinematic analysis before and after palmar digital nerve block (PDNB). Evaluations were made by 6 clinicians and 7 interns or residents. Within- and between-observer agreement analyses (kappa values) were calculated and compared, using a Student's t-test. Pearson's product-moment correlation coefficients were calculated between clinician's change in score and the change in kinematic variables after PDNB. RESULTS: Within-observer agreement was within the range expected for conditions of moderate diagnostic difficulty. Within-observer agreement was higher for clinicians than for interns or residents. Between-observer agreement was acceptable for scores within 1 value of each other. Between-observer agreement of change in lameness score after PDNB was poor. When kinematic variables were ranked with each clinician's subjective change in score, only 2 were among the top 3 for the majority of clinicians. Asymmetry of vertical head movement between contralateral forelimb stance phases and the point of maximum hoof height during swing decreased as lameness subjectively improved. CONCLUSION: Mild lameness may be difficult to evaluate during treadmill locomotion. Although clinicians were more repeatable in their subjective evaluation of lameness than interns or residents, they were not more reliable at detecting the true state of lameness. CLINICAL RELEVANCE: Lack of agreement between clinician scoring of mild lameness emphasizes the need to use more objective measures for quantifying lameness.

Animals↗
PubMed1997

Membrane-type matrix metalloproteinases 1 and 2 exhibit broad-spectrum proteolytic capacities comparable to many matrix metalloproteinases.

Soluble proenzyme forms of the catalytic domains of membrane-type matrix metalloproteinases 1 and 2 (MT1-MMP and MT2-MMP) and a form of MT1-MMP containing the catalytic and hemopexin domains were expressed as soluble recombinant proteins. Purified, activated forms of the MT-MMP were shown to degrade fibronectin, tenascin, nidogen, aggrecan and perlecan. Only MT2-MMP showed activity against laminin. MT1-MMP retaining the hemopexin domain was able to specifically cleave native type-I and type-III collagens into the 3/4-1/4 fragments typical of the specific collagenases. The catalytic domain alone did not retain this activity. The MT-MMP did not degrade interleukin-1beta, but, similarly to many other MMP, could process a pro [tumor necrosis factor (TNF) alpha] fusion protein to release mature TNF. However, the latter was subsequently degraded into smaller fragments. These results demonstrate that, in addition to their ability to activate other MMP, such as progelatinase A/proMMP2 and procollagenase-3/proMMP13, MT-MMP degrade a number of extracellular matrix macromolecules. Their location at the surface of cells implies that they could play a significant role in the modulation of cell-matrix interactions.

Aggrecans↗
PubMed1997

Activation of progelatinase B (proMMP-9) by active collagenase-3 (MMP-13).

Human progelatinase B was activated by collagenase-3 in a time-dependent fashion. Activation proceeded through an intermediate form of Mr 86,000 to the final active form of Mr 82,000. N-terminal amino acid sequence determination demonstrated that the Glu40-Met41 peptide bond was initially hydrolysed followed by cleavage of the Arg87-Phe88 peptide bond releasing the rest of the propeptide domain which was accompanied by the achievement of maximal enzymatic activity as revealed using a quenched fluorescent substrate. Kinetic analysis of activation revealed that the rates were dependent on the concentration of the proenzyme as well as active collagenase-3. Active gelatinase B did not contribute to the activation rate of the proenzyme initiated by collagenase-3 and our results indicate that progelatinase B activation proceeds via bimolecular cleavage with collagenase-3 involving sequential cleavage of the propeptide in two steps. The activation rates were not dependent on C-terminal domain interactions between progelatinase B and collagenase-3, as assessed using wild-type and C-terminal deletion mutants of both enzymes. Since elevated levels of both gelatinase B and collagenase-3 have been observed in arthritis and breast cancer pathology these enzymes may well form a proteolytic cascade in these diseases which allows rapid turnover of the extracellular matrix.

Amino Acid Sequence↗
PubMed1997

Human phosphodiesterase 4A: characterization of full-length and truncated enzymes expressed in COS cells.

The type 4 phosphodiesterase (PDE) family comprises four enzymes (4A, 4B, 4C and 4D) that are characterized by their specificity for cAMP and selective inhibition by the anti-depressant drug rolipram (4-[3-(cyclopentoxyl)-4-methoxyphenyl]2-pyrrolidone). In common with other PDEs, they consist of a central conserved domain associated with catalytic activity in addition to two N-terminal upstream conserved regions (UCR1 and UCR2) that are unique to the type 4 enzymes. We have isolated a 2 kb cDNA encoding a full-length type 4A PDE{HSPDE4A4B[Bolger, Michaeli, Martins, St.John, Steiner, Rodgers, Riggs, Wigler and Ferguson (1993) Mol. Cell. Biol. 13, 6558-6571]} from a human frontal cortex cDNA library. Northern blot analysis showed that the major PDE4A mRNA of 4.5 kb was widely distributed in different human tissues. The recombinant PDE4A expressed in COS cells had a molecular mass of approx. 117 kDa as revealed by SDS/PAGE/Western blotting with a PDE4A-specific antibody and was specific for cAMP with a Km of 4.8 microM. The enzyme activity was potently inhibited by R-rolipram (IC50 204 nM) and showed a 2.7-fold stereoselectivity over the S enantiomer. Analysis of the kinetics of inhibition indicated that R-rolipram did not behave as a simple competitive inhibitor. Dixon replots suggested that there was more than one mode of interaction consistent with the detection in the enzyme of a high-affinity binding site for R-rolipram with a Kd of 2.3 nM. Truncation of the PDE4A enzyme by deletion mutagenesis showed that neither of the UCRs was required for catalytic activity and identified an approx. 71 kDa core enzyme with a K(m) for cAMP of 3.3 microM. In contrast with the full-length PDE4A, R-rolipram behaved as a simple competitive inhibitor of this form of the enzyme with decreased potency (IC50 1022 nM) and no stereoselectivity. In addition, no high-affinity rolipram-binding site was detected in the truncated enzyme, indicating that this interaction involves sequences upstream of the catalytic domain of the enzyme.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1997

The role of the C-terminal domain of human collagenase-3 (MMP-13) in the activation of procollagenase-3, substrate specificity, and tissue inhibitor of metalloproteinase interaction.

Recombinant human procollagenase-3 and a C-terminal truncated form (Delta249-451 procollagenase-3) have been stably expressed in myeloma cells and purified. The truncated proenzyme could be processed by aminophenylmercuric acetate via a short-lived intermediate form (N-terminal Leu58) to the final active form (N-terminal Tyr85). The kinetics of activation were not affected by removal of the hemopexin-like C-terminal domain. The specific activities of both collagenase-3 and Delta249-451 collagenase-3 were found to be similar using two quenched fluorescent substrates, but Delta249-451 collagenase-3 failed to cleave native triple helical collagens (types I and II) into characteristic one- and three-quarter fragments. It was noted, however, that the beta1,2(I) chains of type I collagen were susceptible to Delta249-451 collagenase-3, which indicates that the catalytic domain displays telopeptidase activity, thereby generating alpha1,2(I) chains that are slightly shorter than those in native type I collagen. It can be concluded that the C-terminal domain is only essential for the triple helicase activity of collagenase-3. Binding of procollagenase-3 and active collagenase-3 to type I collagen is mediated by the C-terminal domain. Both collagenase-3 and Delta249-451 collagenase-3 hydrolyzed the large tenascin C isoform, fibronectin, recombinant fibronectin fragments, and type IV, IX, X, and XIV collagens; thus, these events were independent from C-terminal domain interactions. In contrast, the minor cartilage type XI collagen was resistant to cleavage. Kinetic analysis of the mechanism of inhibition of wild-type and Delta249-451 collagenase-3 by wild-type and mutant tissue inhibitors of metalloproteinase (TIMPs) revealed that the association rates for complex formation were influenced by both N- and C-terminal domain interactions. The C-terminal domain of wild-type collagenase-3 promoted increased association rates with the full-length inhibitors TIMP-1 and TIMP-3 and the hybrid N.TIMP-2/C.TIMP-1 by a factor of up to 33. In contrast, the association rates for complex formation with TIMP-2 and N.TIMP-1/C.TIMP-2 were only marginally affected by C-terminal domain interactions.

Amino Acid Sequence↗
PubMed1997

Analysis of the contribution of the hinge region of human neutrophil collagenase (HNC, MMP-8) to stability and collagenolytic activity by alanine scanning mutagenesis.

Analysis of the hinge region of neutrophil collagenase by alanine scanning mutagenesis revealed that this sequence motif has a pronounced effect on the stability and collagenolytic activity of the active enzyme. The mutagenesis of the amino acid residues in the P1' position of the two autoproteolytically cleaved peptide bonds (Leu243 and Ile248) to Ala showed that the mutant enzymes were more resistant to autoproteolysis. However, these mutants were not completely stable and autoproteolysis occurred mainly at the Ala239-Ile240 peptide bond and the half-life of the active enzyme was increased by 50%. In contrast, mutagenesis of Pro247 --> Ala (P1 of the minor cleavage site Pro247-Ile248) lead to increased susceptibility of the enzyme to autoproteolysis. However, when the other P1 position Gly242 was altered to Ala no effect on stability was observed. The analysis of the ability of the mutant active enzymes to hydrolyse 14C-type I collagen was assessed and our results demonstrate that the hinge sequence motif of neutrophil collagenase is important for collagenolytic activity. The alteration of the Gly242-Leu-Ser-Ser-Asn-Pro-Ile-Gln-Pro247 sequence motif to Gly242-Ala-Ala-Ala-Ala-Pro-Ala-Ala-Pro247 showed that the collagenolytic activity was reduced by 68.4%. In addition, mutagenesis of the downstream sequence motif Pro247-Thr-Gly-Pro-Ser-Thr-Pro-Lys-Pro258 to Pro247-Ala-Ala-Pro-Ala-Ala-Pro-Ala-Pro258 had an even more marked effect on the collagenolytic activity, which was reduced by 87.4%. When the Pro residues in the hinge motif (Pro247, Pro250, Pro253 and Pro256) were altered to Ala the collagenolytic activity dropped to 1.5% of the value observed for wild-type enzyme.

Alanine↗
PubMed1997

Dexamethasone prevents apoptosis in a neonatal rat model of hypoxic-ischemic encephalopathy (HIE) by a reactive oxygen species-independent mechanism.

It has previously been shown, in a neonatal rat model of hypoxic-ischemic encephalopathy (HIE), that neuronal injury can be attenuated by pretreatment with dexamethasone. The mechanism by which dexamethasone exerts this protective effect is not known. Using the same neonatal rat model of HIE, we found pretreatment with dexamethasone to have no effect on the generation of superoxide radical, products of lipid peroxidation, peroxynitrite-mediated tissue damage or bcl-2 protein expression. However, dexamethasone did inhibit the induction of c-fos transcription seen following HIE, and subsequent evidence of apoptosis. We conclude that it is possible to limit hypoxic-ischemic neuronal injury, despite the continued production of reactive oxygen species, by interventions which block the cascade of events culminating in apoptosis. The involvement of apoptosis in the neuronal injury of HIE, if confirmed in acutely asphyxiated human infants, suggests that there may be a post-injury 'window of opportunity' for neuroprotective interventions.

Aldehydes↗
PubMed1997

Long-term psychosocial outcome in typical absence epilepsy. Sometimes a wolf in sheeps' clothing.

OBJECTIVES: To determine whether young adults in whom typical absence epilepsy has been diagnosed in childhood have greater psychosocial difficulties than those with a non-neurologic chronic disease and to decide which seizure-related factors predict poor psychosocial outcome. DESIGN: Population-based, inception cohort study. SETTING: The only tertiary care pediatric hospital in the province of Nova Scotia. PATIENTS: All children in whom typical absence epilepsy or juvenile rheumatoid arthritis (JRA) was diagnosed between January 1, 1997, and December 31, 1985, who were aged 18 years or older at follow-up in March 1994 to April 1995. Patients with typical absence epilepsy were identified from centralized electroencephalographic records for Nova Scotia, and those with JRA were identified from discharge diagnoses from the only children's hospital in Nova Scotia. MAIN OUTCOME MEASURE: Patients participated in a structured interview that assessed psychosocial function. RESULTS: Fifty-six (86%) of the 65 patients with absence epilepsy and 61 (80%) of the 76 patients with JRA participated in the interview. The mean age of the patients at the interview was 23 years. Terminal remission occurred in 32 (57%) of the patients with typical absence epilepsy but in only 17 (28%) of the patients with JRA. Factor analysis identified 5 categories of outcome: academic-personal, behavioral, employment-financial, family relations, and social-personal relations. Patients with typical absence epilepsy had greater difficulties in the academic-personal and in the behavioral categories (P < .001) than those with JRA. Those with ongoing seizures had the least favorable outcome. Most seizure-related factors showed minimal correlation with psychosocial functioning. CONCLUSION: Young adults with a history of typical absence epilepsy, particularly those without remission of their seizures, often have poor psychosocial outcomes, considerably worse than those with JRA.

Adolescent↗
PubMed1997

An exploratory study of male recovering substance abusers living in a self-help, self-governed setting.

Adult men (n = 132; 92% of the population) with histories of alcohol/drug use disorders were interviewed upon their entry to 11 Oxford Houses located in the state of Illinois. Individuals still in residence at a six-month follow-up (n = 48) were reinterviewed; prior to the follow-up interview, 42 men had left voluntarily and 42 men had been evicted for abuse or disruptive behavior. The men remaining in residence tended to be older (M age = 37 years), were disproportionately African American (56%), and were less pessimistic about their future. At the intake interview, individuals who would be evicted reported a lower expectation for abstinence social support from the other residents in Oxford House. The Oxford House model of social support for recovery from alcohol and drug dependence appears to help some residents maintain sobriety.

Adult↗
PubMed1997

Investigation of pharmacokinetics and of possible adverse effects in infants exposed to tricyclic antidepressants in breast-milk.

We have studied ten breast-feeding mothers who were prescribed tricyclic antidepressant drugs and have also compared their infants' development with a similar group (n = 15) who were bottle-fed. Concentrations of tricyclic drugs in maternal plasma and urine, in fore-milk and hind-milk and in infant plasma (n = 6) and urine (n = 9) were measured by gas chromatography (GC) and by an enzyme immunoassay (EIA). The fat concentration in milk was also measured. Infants health and development were monitored by physical examination and by the Bayley Scales of Infant Development up to 30 months. The amounts of tricyclic drugs and their principal metabolites in maternal plasma were significantly correlated with the oral dose and with the amounts in breast-milk. Drug concentrations in fore-milk, but not in hind-milk, increased in line with its fat content, which was maximal in hind-milk. Correlations between gas chromatographic and enzyme immunoassays of maternal samples were high provided that the values for amitriptyline and nortriptyline were excluded; immunoreactivities to these compounds were abnormally high, suggesting that metabolites were also being measured by EIA. The daily doses of drugs ingested by breast-fed infants were about 1% of the maternal dose/kg and the immunoassay detected very small amounts of tricyclics in infants' plasma and urine. No acute toxic effects were found in the ten medicated breast-fed infants and there was no evidence of developmental delays in comparison with bottle-fed infants. Although the number of subjects in this study is small, when taken in conjunction with other published findings, we have not found any reason to prevent mothers who are taking established tricyclic antidepressants from breast-feeding their babies if they want to do so.

Animals↗
PubMed1997

Induction of apoptosis in neoplastic cells by depletion of vitamin B12.

Methionine synthase, a critical enzyme in deoxyribonucleotide biosynthesis for DNA replication, requires vitamin B12 as a cofactor. We have tested the hypothesis that depletion of cells of vitamin B12 would block growth of neoplastic cells and divert them into apoptosis and could form the basis of a new therapeutic strategy for cancer treatment. Using nitrous oxide to inactivate vitamin B12 we show that, in a variety of cell lines in vitro, methionine synthase is rapidly inhibited, the cells cease proliferation and undergo apoptosis. The kinetics of cell death, once started, are similar to those observed following methotrexate treatment or serum withdrawal. This is the first observation of apoptosis being induced following depletion of an essential metabolite as opposed to the more conventional strategy of adding a toxic drug to damage cells thereby triggering apoptosis. Moreover, vitamin B12 depletion has no effect on the nonproliferating cell population.

Journal Article↗
PubMed1997

Risk factors and medical follow-up of drug users tested for hepatitis C--can the risk of transmission be reduced?

Of 1728 patients attending a regional drug and alcohol clinic, 202 were considered at risk of hepatitis C virus (HCV). Forty-nine per cent (99/202) agreed to testing-67% (67) were HCV antibody positive. Age and a history of needle sharing was the significant factor associated with positive HCV status. Patients on methadone maintenance medication were more-likely to have been HCV positive, but significantly (p = 0.005) less likely to have shared needles in the previous year. Seventy-three per cent (49/67) attended for follow-up at a "liver clinic". Fifty per cent were infected with genotype 1a. Eighteen patients were biopsied and all were abnormal, ranging from mild hepatitis to severe fibrotic hepatitis. Attendance for medical follow-up was poor, which emphasizes the importance of preventative measures such as methadone maintenance programmes for reducing the spread of HCV.

Journal Article↗
PubMed1997

A key for freshwater invertebrates using fuzzy logic.

MOTIVATION: This paper summarizes a biological key using a fuzzy logic expert system. This approach allows the user to make some errors, be uncertain about some answers and not answer questions if unsure, but have an opportunity to identify unknown specimens correctly. This approach was adopted in order to develop a 'forgiving' key for users with little or no prior knowledge of identification. The system was implemented using a multi-media expert system builder, 'Matcher', operating in a Microsoft Windows environment. RESULTS: The paper reports the design issues for a key to identify freshwater invertebrates to family level and describes the types of questions used within the key, the fuzzy inference engine, the structure of the system and the methodology adopted for testing it. Following this, an empirical test is reported of the hypothesis that a fuzzy logic expert system can improve identification accuracy for a sample of intended users. Finally, the discussion considers the practicalities of using such a system as an aid to organism identification.

Algorithms↗
PubMed1997

Pain relief with oral cannabinoids in familial Mediterranean fever.

Cannabinoids have analgesic and, possibly, anti-inflammatory properties but their clinical use has been restricted by legislation. This is the first United Kingdom report of the controlled use of a standardised pharmaceutical preparation of cannabinoids in capsular form. The therapy was assessed in a patient with familial Mediterranean fever, who presented with chronic relapsing pain and inflammation of gastrointestinal origin. After determining a suitable analgesic dosage, a double-blind placebo-controlled cross-over trial was conducted using 50 mg tetrahydrocannabinol daily in five doses in the active weeks and measuring effects on parameters of inflammation and pain. Although no anti-inflammatory effects of tetrahydrocannabinol were detected during the trial, a highly significant reduction (p < 0.001) in additional analgesic requirements was achieved. Future study designs can now incorporate prescribable forms of cannabinoids but the choice of previous cannabis users only as patients has clinical limitations. Cannabis naive patients would tolerate controlled investigations but may generate medicolegal problems.

Administration, Oral↗
PubMed1997

Rehospitalisation for asthma within 12 months: unequal rates on the basis of gender in two hospitals.

BACKGROUND: High asthma morbidity has been reported in certain demographic groups in geographical areas of low socioeconomic status (SES). AIM AND METHODS: We tested for an ecological association between the gender of people being frequently hospitalised for asthma and the SES of the area in which they lived, using a cross-sectional study. RESULTS: Women represented 75% of the readmission population at The Queen Elizabeth Hospital (TQEH--low SES hospital) and 55% at Modbury Hospital (moderate-high SES hospital). Women at TQEH were significantly more likely to have one readmission within 12 months and over 30 times more likely to have two or more readmissions than women at Modbury Hospital. CONCLUSION: The ecological association observed in this study needs to be confirmed elsewhere in Australia.

Adolescent↗