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S Martin

Publications and source records attributed to S Martin.

At least 361 records · Page 20Linked to original sources
PubMed1995

Autoantibodies to the islet antigen ICA69 occur in IDDM and in rheumatoid arthritis.

Islet cell antigen (ICA) 69 is a newly-recognized islet cell antigen to which autoantibodies have been observed in prediabetic relatives of patients with insulin-dependent-diabetes mellitus (IDDM). Here we extend the earlier analysis of ICA69 antibodies to patients with recent-onset IDDM and to patients with other immune-mediated diseases. ICA69 antibodies were determined by Western blot using an affinity purified recombinant fusion protein of ICA69 and maltose binding protein. ICA69 antibody quantities were determined as titres using a titration curve of a standard serum as reference. Mean logarithmic ICA69 antibody titres were 3.4 (+/- 1.4) in 99 patients with acute IDDM compared to 2.8 (+/- 0.9) in 49 healthy blood donors (p < 0.001). A higher mean ICA69 antibody titre of 4.1 (+/- 0.8) was observed in 16 patients with rheumatoid arthritis in comparison to acute IDDM (p < 0.01) and healthy control subjects (p < 0.001). The percentage of sera with ICA69 antibody titres above the 2 SD level of normal subjects was 21% in IDDM, 31% in rheumatoid arthritis and 6% in healthy blood donors. None of the patients with autoimmune thyroid disease (n = 20), inflammatory bowel disease (n = 9) or multiple sclerosis (n = 7) had elevated ICA69 antibodies. In IDDM, presence of ICA69 antibodies persisted and the titre remained the same over 18 months of follow-up. The relationship of ICA69 antibodies to islet cell antibodies (ICA) or insulin autoantibodies (IAA) was tested. The production of ICA69 antibodies was not associated in diabetic patients with the presence of any of the two other autoantibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Acute and prolonged toxicity to aquatic organisms of new and existing chemicals and pesticides.

The relation of acute to prolonged toxicity of existing and new chemicals and active ingredients of numerous pesticides in the aquatic environment have been compared with their physico-chemical properties. The data had been presented to the authorities in behalf of the pesticide registrations, the notification of new chemicals or research projects. The ecotoxicity ratios are expressed as acute to prolonged ratios (APR). They are determined for fish and crustacea with existing and new chemicals and pesticides. In the case of the pesticides the data are subsummarized into fungicides, herbicides, insecticides. The variability of the APR is evaluated. According to the statistic evaluation of the data it must be summarized, that the toxic effects are often extremely specific and depend not only on the substance, but also on the aquatic species, the duration of the exposure, and the endpoint of the test. In general, a factor of 100 between the EC/LC50 of acute toxicity and NOEC of prolonged toxicity is scientifically justified. The data indicate that there is no significant correlation between lipophilic properties (logPow) or water solubility and toxicity in aquatic organisms. For that reason structure-activity relationships based on lipophilic properties of the substance cannot lead to reasonable results. It must be stated, that the prolonged ecotoxicity can not be exactly extrapolated from acute toxicity data on the basis of physico-chemical properties.

Animals↗
PubMed1995

Evaluation of an autologous red cell agglutination test, VetRED FIV, for the presence of FIV antibody in cats.

A commercially available whole blood agglutination test, VetRED FIV, used for the detection of antibodies to feline immunodeficiency virus (FIV), was evaluated. The test is based on the use of a synthetic peptide conjugated to a non-agglutinating anti-feline red blood cell monoclonal antibody. The amino acid sequence of the synthetic peptide was derived from the predicted sequence of the transmembrane protein of FIV. The sensitivity and specificity of VetRED FIV was 100% when 34 known FIV-positive and 15 known FIV-negative cats were tested. These cats were part of studies on experimentally induced FIV infection, with their FIV status confirmed by virus isolation. Further, VetRED FIV was compared with another commercially available test for FIV antibody, PetChek in a field trial on 548 feline blood samples received by a diagnostic laboratory. Of the test results 94.2% (516/548) were in agreement: 112 were positive by VetRED FIV and PetChek; 404 were negative by both tests and 32 were discordant. These 5.8% discordant samples producing VetRED FIV-positive/PetChek-negative or VetRED FIV-negative/PetChek-positive were further assessed by Western blot assay. In the field trial, the sensitivity and specificity of VetRED FIV was 97% and 97%, respectively, comparable to the 98% sensitivity and 99% specificity for PetChek. The results from the trial also confirm the relatively high overall prevalence of FIV in Australian cats predominantly among mature male cats in the 9-12 year age group. Given the simplicity of the VetRED FIV procedure, it is concluded that VetRED FIV is a useful addition to the available commercial tests for FIV infection.

Animals↗
PubMed1995

Immunogenicity of the yeast recombinant p17/p24:Ty virus-like particles (p24-VLP) in healthy volunteers.

In this Phase I study, immunisation with the yeast-derived p24 virus-like particles Ty p24-VLP (3 x 100 or 3 x 500 micrograms subcutaneously) in 16 healthy male subjects elicited p24 antibody responses in 4 of 16 (25%) subjects. After a fourth, intramuscular, immunisation (500 micrograms), p24 antibody responses were detected in 11 of 15 (70%) subjects. In addition to p24 antibody responses, T cell proliferative responses were also observed, although no HLA restricted p24-specific cytotoxic T cell responses were detected. The results demonstrate that Ty p24-VLP is immunogenic and well-tolerated in healthy male subjects.

AIDS Vaccines↗
PubMed1995

A comparison of outpatient and inpatient anterior cruciate ligament reconstruction surgery.

The feasibility of outpatient anterior cruciate ligament (ACL) surgery has not been reported in the literature. We evaluated outpatient ACL surgery by comparing outpatient versus inpatient pain control, narcotic consumption, postoperative complications, recovery time, and cost analysis. Thirty-seven ACL reconstructions were performed in 37 patients over a 16-month period. Twenty-five of the patients had surgery performed as outpatients and 12 as inpatients. One of the outpatients required hospitalization because of excessive nausea and vomiting and another for urinary retention. Only 2 of the 25 outpatients (8%) believed that they should have been hospitalized for pain control. Based on a visual analog scale, pain severity, pain frequency, and pain relief were measured, and no statistically significant difference (P < .05) was noted between the groups, although the data suggested that the inpatients were slightly more comfortable. There were no differences in rehabilitation or in regaining full range of motion of the operated knee. Also, the only postoperative complication in both groups occurred in an inpatient who developed arthrofibrosis. Cost analysis showed that outpatient ACL reconstruction was cost effective. The average inpatient cost was $9,220 (2.4 hospital days) compared with the average outpatient cost of $3,905. This reflected a savings of 58%. These results show that outpatient ACL reconstruction surgery is possible in the appropriate patient without harm to the patient and with a significant cost savings.

Adult↗
PubMed1995

FAS-induced apoptosis is mediated via a ceramide-initiated RAS signaling pathway.

Fas receptor-induced apoptosis plays critical roles in immune homeostasis. However, most of the signal transduction events distal to Fas ligation have not been elucidated. Here, we show that Ras is activated following ligation of Fas on lymphoid lines. The activation of Ras is a critical component of this apoptotic pathway, since inhibition of Ras by neutralizing antibody or a dominant-negative Ras mutant interfered with Fas-induced apoptosis. Furthermore, ligation of Fas also resulted in stimulation of the sphingomyelin signalling pathway to produce ceramides, which, in turn, are capable of inducing both Ras activation and apoptosis. This suggests that ceramides acts as second messengers in Fas signaling via Ras. Thus, ligation of the Fas molecule on lymphocyte lines induces activation of Ras via the action of ceramide, and this activation is necessary, but not sufficient, for subsequent apoptosis.

Animals↗
PubMed1995

Implications for viral uncoating from the structure of bovine enterovirus.

We have determined the crystal structure of a bovine enterovirus, revealing that the topologies of the major capsid proteins and the overall architecture of the virion are similar to those of related picornaviruses. The external loops joining beta-strands are truncated and the canyon region is partially filled by an extension of the VP3 G-H loop giving the viral capsid a relatively smooth appearance. These changes may have implications for cell attachment. In spite of these differences the virus maintains a hydrophobic pocket within VP1, occupied by a specific 'pocket factor' which appears to be myristic acid. These observations support the proposal that a kinetic equilibrium exists between occupied and unoccupied pocket states, with occupation inhibiting uncoating.

Animals↗
PubMed1995

Histocompatibility testing for kidney transplantation: an update.

Histocompatibility testing prior to kidney transplantation is an established necessity. Recipient sensitization to HLA specificities affects the efficacy of the lymphocytotoxic cross-match and influences the achievable HLA mismatch. Within Europe most cadaver donor kidneys are allocated on the basis of minimum histocompatibility mismatch contrasting with the North American system which allows for exchange of kidneys only where there is no detectable donor/recipient mismatch. There is also a contrast between the immunosuppression protocols used in these continents with, in general, more aggressive regimens used in North America. In the 1990s there has been considerable refinement in the techniques available to histocompatibility laboratories for definition of HLA phenotypes and genotypes and some obstacles to successful transplantation have been overcome. We review some of these changes with particular reference to our own experience.

Antibodies↗
PubMed1995

Alteration of the amino acid substrate specificity of clostridial glutamate dehydrogenase by site-directed mutagenesis of an active-site lysine residue.

Two residues, K89 and S380, thought to interact with the gamma-carboxyl group of the substrate L-glutamate, have been altered by site-directed mutagenesis of clostridial glutamate dehydrogenase (GDH). The single mutants K89L and S380V and the combined double mutant K89L/S380V were constructed. All three mutants were satisfactorily overproduced in soluble form. However, only the K89L mutant was retained by the dye column normally used in purifying the wild-type enzyme. All three mutant enzymes were purified to homogeneity and tested for substrate specificity with 24 amino acids. The single mutant S380V showed no detectable activity. The alternative single mutant K89L showed an activity towards L-glutamate that was decreased nearly 2000-fold compared with wild-type enzyme, whereas the activities towards the monocarboxylic substrates alpha-aminobutyrate and norvaline were increased 2- to 3-fold. A similar level of activity was obtained with methionine (0.005 U/mg) and norleucine (0.012 U/mg), neither of which give any activity with the wild-type enzyme under the same conditions. The double mutant showed decreased activity with all substrates compared with the wild-type GDH. In view of its novel activities, the K89L mutant was investigated in greater detail. A strictly linear relationship between reaction velocity and substrate concentration was observed up to 80 mM L-methionine and 200 mM L-norleucine, implying very high Km values. Values of kcat/Km for L-methionine and L-norleucine were 6.7 x 10(-2) and 0.15 s-1 M-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Levels of circulating intercellular adhesion molecule-1 and -3 but not circulating endothelial leucocyte adhesion molecule are increased in patients with rheumatoid vasculitis.

The aim of this study was to investigate whether levels of circulating adhesion molecules reflect vascular inflammation in rheumatoid vasculitis (RV). Levels of circulating intercellular adhesion molecule-1 (cICAM-1), c-ICAM-3 and circulating endothelial leucocyte adhesion molecule (cE-selectin) were determined in 14 patients with RV and compared to 47 patients with rheumatoid arthritis (RA) and 100 healthy donors (HD). Enzyme-linked immunosorbent assays were used to quantify cICAM-1, cICAM-3 and cE-selectin. We found that in RV significantly (P < 0.0001) elevated levels of cICAM-1 and cICAM3, but not cE-selectin, were found when compared with RA patients. Levels > 2 S.D. above the mean level of HD were present for cICAM-1, cICAM-3 and cE-selectin in 57, 71 and 21%, respectively of patients with RV and 2, 21 and 44%, respectively of the RA patients. Increased levels of both cICAM-1 and cICAM-3 were found in 43% of the RV patients and in none of the RA patients. Comparison of the serum levels of patients studied in an active and inactive phase of RV revealed significantly lower levels of cICAM-3 levels in the inactive phase. In conclusion we find that determination of cICAM-1 and cICAM-3 may be useful as a marker of vascular inflammation in patients with RV.

Aged↗
PubMed1995

The bovine herpesvirus 1 maturational proteinase and scaffold proteins can substitute for the homologous herpes simplex virus type 1 proteins in the formation of hybrid type B capsids.

We determined the nucleotide sequence of a 3.5-kb region of the bovine herpesvirus 1 (BHV-1) genome which contained the complete BHV-1 homologs of the herpes simplex virus type 1 (HSV-1) UL26 and UL26.5 genes. In HSV-1, the UL26 and UL26.5 open reading frames encode scaffold proteins upon which viral capsids are assembled. The UL26-encoded protein is also a proteinase and specifically cleaves both itself and the UL26.5-encoded protein. The overall BHV-1-encoded amino acid sequence showed only 41% identity to the HSV-1 sequences and was most divergent in the regions defined to be involved in the scaffolding function. We substituted the proteins encoded by the BHV-1 homologs of the UL26 and UL26.5 open reading frames, expressed in baculovirus, for the corresponding HSV-1 proteins in an in vitro HSV-1 capsid assembly system. The proteins expressed from the BHV-1 UL26 and UL26.5 homologs facilitated the formation of hybrid type B capsids indistinguishable from those formed entirely with HSV-1-encoded proteins.

Amino Acid Sequence↗
PubMed1995

Interpreting the new illness question in the UK census for health research on small areas.

STUDY OBJECTIVE: The study aimed to identify the various factors that seem to influence the average response to the new census question on limiting, long standing illness at the small area level, to assess the extent to which the new questions adds to information already available in the census and elsewhere, and to discuss how useful the data are likely to be for those planning health and social services. DESIGN: This was a cross sectional analysis of the relationship between rates of limiting, long standing illness (standardised for age and sex) and a large number of indicators of health and socioeconomic status at the small area level. SETTING: The study used data relating to 4985 small areas covering the whole of England. The average population was about 10 000. PARTICIPANTS: The 1991 census of population was addressed to the entire population of England. MAIN RESULTS: There are wide variations in the levels of self reported long standing illness between small areas, 70% of which are explained by demographic factors. Variation in age/sex standardised responses to the new census question at the small area level can largely be explained by census data on self reported disability among those of working age, standardised mortality ratio, and by indicators of socioeconomic circumstances relating to social class, ethnicity, and the elderly living alone. These does not seem to be a significant reporting bias due to underemployment. CONCLUSION: Unlike the disability question in the census, the standardised, self reported long standing limiting illness ratio covers the entire population and it is not skewed towards men. Although the variable is a synthesis of the health and social determinants of perceived morbidity, it does not provide much information that was not already available. In addition, it is available every 10 years only and thus may be rather inaccurate as an indicator of relative need towards the end of the decade. Moreover, in future censuses, individuals' answers might be influenced by the knowledge that their responses will affect the volume of resources allocated to the area in which they live.

Adolescent↗
PubMed1995

Proprotein convertases (PC1/PC3 and PC2) in normal and neoplastic human tissues: their use as markers of neuroendocrine differentiation.

By immunocytochemistry and immunoblotting, we examined normal and neoplastic human tissues with polyclonal antibodies raised against selected peptide regions of proprotein convertase-2 and -3 (PC2 and PC3), two proteases that have been shown to selectively cleave neuroendocrine precursor molecules at pairs of basic residues. Immunoreactivity for both enzymes was detected in neuroendocrine cells of pituitary, gut, pancreas, thyroid, and adrenals and in tumors thereof, but was absent in thyroid follicular cells, parathyroids, adrenal cortex, testes, and a number of nonneuroendocrine tissues, both normal and tumorous. Although both PCs were virtually universal concomitants of the neuroendocrine system, cells with a neural phenotype (e.g. pheochromocytes and Merkel cells) predominantly contained PC2, whereas classic endocrine cells contained mostly PC3. PC3 immunoreactive cells were abundant all along the gastrointestinal tract, whereas PC2 was highly expressed only in the pyloric antrum and proximal third of duodenum. Double immunostaining experiments revealed colocalization of PC3 with virtually all gastrointestinal peptides, whereas PC2 immunoreactivity was mostly expressed in gastrin, cholecystokinin, and somatostatin cells. Noticeably, the proportion of glucagon-producing cells immunoreactive for PC3 was high in the gut and low in pancreatic islets and glucagonomas, whereas the reverse occurred for PC2. At the ultrastructural level, immunostaining was confined to the mature dense core granules, the site of storage of granins and peptide hormones. With the exception of parathyroid cells, PC2 and/or PC3 expression correlated with the occurrence of granins, canonical markers of the secretory granules. Immunoblotting experiments confirmed the identity of the immunocytochemical reactivities. It is concluded that PC2 and PC3 are highly sensitive markers of neuroendocrine differentiation and have distinct distribution patterns, and that antibodies to these enzymes may play an important role in the analysis of tumors.

Aspartic Acid Endopeptidases↗
PubMed1995

Gender related pharmacokinetics of diltiazem in healthy subjects.

The aim of this study was to investigate the gender-related pharmacokinetic differences after a single oral dose of diltiazem (120 mg) in 12 healthy subjects (6 males and 6 females). Kinetic parameters were calculated from serum concentrations obtained by means of a specific HPLC method. The total area under the concentration-time curve (AUC0-infinity) was 917.03 +/- 342.13 ng.h-1/ml for females and 1,192.97 +/- 329.93 ng.h-1/ml for males. Peak serum levels (Cmax) were 181.29 +/- 48.03 ng/ml and 194.29 +/- 93.81 for females and males, respectively. The time to reach maximum concentration (Tmax) was 2.2 +/- 0.8 h for both. The biological elimination t1/2 was 4.58 +/- 2.08 h and 5.59 +/- 2.44 h, showing an elimination rate (kel) of 0.174 +/- 0.062 h-1 and 0.149 +/- 0.075 h-1, and a mean residence time (MRT) of 8.56 +/- 1.94 h and 8.88 +/- 2.78 h for females and males, respectively. Male subjects showed higher values than females, but no significant difference was observed when comparing pharmacokinetic parameters by gender. Diltiazem was well tolerated by all subjects.

Adult↗
PubMed1995

Can practice patterns and outcomes be successfully altered? Examples from cardiovascular medicine. The Clinical Quality Improvement Network (CQIN) Investigators.

OBJECTIVE: To offer an attributive opinion of recent improvements in acute myocardial infarction (AMI) practice patterns and patient outcomes in the culture of an active health care research program. DATA SOURCES: Review of original clinical data from five sequential, consecutively enrolled, AMI patient cohorts at the University of Alberta Hospitals from 1987-93. DATA SYNTHESIS: Early cohorts had low use of trial-proven efficacious therapies for AMI, particularly among high risk older and female patients. Over time, there were continuous and marked increases in the use of efficacious therapies and decreased use of nonefficacious therapies, with a parallel decrease in mortality among high risk patients. CONCLUSIONS: In a large tertiary care hospital between 1987 and 1993 the use of evidence-based AMI therapy and survival in high risk patients significantly increased. The continuity and large size of these improvements in AMI practice patterns, compared with similar populations reported in the contemporary literature, suggest it is unlikely they were due to chance. Rather, intercurrent repeated measurement and reporting of key health care performance indicators, and initiation of explicit critical path AMI practice guidelines provide a more likely explanation. Future studies by a network of community and university investigators will test whether these findings are true for a broad AMI population and whether similar practice definition and improvement tools are effective for other cardiac problems, including the management of congestive heart failure.

Adult↗
PubMed1995

Shear strength of ceramic brackets bonded to etched or unetched enamel.

The purpose of this study was to compare the shear bond strengths and enamel surface morphology after debonding a polycrystalline ceramic bracket (Transcend 2000) bonded with a light-cured resin cement (Transbond) without enamel etching or by etching for 15 seconds with 10% or 37% phosphoric acid and 10% maleic acid. Forty extracted noncarious human premolars were used. The buccal enamel surfaces were used and the teeth randomly divided in to four groups of 10 teeth each: Group 1: No enamel etching; Group 2: Enamel etching for 15 seconds with 10% phosphoric acid; Group 3: Enamel etching for 15 seconds with 37% phosphoric acid; and Group 4: Enamel etching for 15 seconds with 10% maleic acid. The brackets were bonded to the etched enamel surfaces according to manufacturers' instructions except the etching time variations. All specimens were stored in distilled water for 24 hours and then thermocycled for 300 cycles between 5 degrees C and 55 degrees C. The specimens were mounted in dental stone and placed in the Instron at a crosshead speed of 0.5 mm/min using a knife-edged blade. Immediately after debonding, the enamel surface and bracket-enamel interface were evaluated visually and with a stereomicroscope. Representative samples were then examined with the SEM. ANOVA and Student-Newman-Keuls tests were performed. The results (in MPa) were: Group 1:11.83 (+3.9); Group 2: 28.80 (+12.6); Group 3: 26.25 (+5.3); Group 4: 18.06 (+6.9). Groups 2 and 3 were statistically significantly different (p<0.0001) from Groups 1 and 4. Groups 2 vs. 3 or 1 vs. 4 were not statistically different. Debonding occurred mainly at the bracket-resin interface in all groups, except Group 2 which displayed two samples with enamel cohesive failures and two fracturing the bracket. The SEM evaluation revealed that after debonding, the group etched with the 37% phosphoric acid gel had the roughest enamel surface and was the only group to present enamel fractures. Bracket bonding with unetched enamel and enamel etched with 10% phosphoric acid gel should be clinically investigated using the products tested.

Acid Etching, Dental↗