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M Syed

Publications and source records attributed to M Syed.

At least 19 recordsLinked to original sources

Is three selected parameters adequate to monitor rheumatoid arthritis?

This pilot study was done to choose which among the five core set criteria will have more discriminating ability and which is easy to administer in a clinical setting. Forty-eight patients recently diagnosed to have rheumatoid arthritis (RA) were recruited for the study. They were assessed by a rheumatologist in each visit (initial and after 2 months of treatment), for five core measures: patient assessment, pain (measured on VAS scale), number of tender joints, health assessment questionnaire (HAQ) score, and erythrocyte sedimentation rate (ESR). All patients were treated with methotrexate 7.5 mg per week and hydroxychloroquin 400 mg per day with adequate dose of NSAIDs. Patients with associated conditions like stroke, ischemic heart disease, and other physical comorbidity were excluded. They were categorized as 20, 50, and 70% improvement, if four of the five criteria occur. The Wilcoxon signed rank test and discriminant function analysis were done to identify the order of importance of measures on influencing the outcome. The ESR followed by patient improvement scale showed the least changes, while HAQ showed the highest changes. Discriminate function analysis has been carried out to see which factors influenced in grouping them for responses with post hoc analyses of finding the order of importance of these factors in classifying the response. Pain scale, ESR, HAQ score, patient improvement scale, and tender score were in the decreasing value of importance. The pain scale, HAQ, and ESR, which are more objective and discriminate measures, are useful as measures in RA.

Arthritis, Rheumatoid↗

Targeted expression of placental lactogen in the beta cells of transgenic mice results in beta cell proliferation, islet mass augmentation, and hypoglycemia.

The factors that regulate pancreatic beta cell proliferation are not well defined. In order to explore the role of murine placental lactogen (PL)-I (mPL-I) in islet mass regulation in vivo, we developed transgenic mice in which mPL-I is targeted to the beta cell using the rat insulin II promoter. Rat insulin II-mPL-I mice displayed both fasting and postprandial hypoglycemia (71 and 105 mg/dl, respectively) as compared with normal mice (92 and 129 mg/dl; p < 0.00005 for both). Plasma insulin concentrations were inappropriately elevated, and insulin content in the pancreas was increased 2-fold. Glucose-stimulated insulin secretion by perifused islets was indistinguishable from controls at 7.5, 15, and 20 mm glucose. Beta cell proliferation rates were twice normal (p = 0. 0005). This hyperplasia, together with a 20% increase in beta cell size, resulted in a 2-fold increase in islet mass (p = 0.0005) and a 1.45-fold increase in islet number (p = 0.0012). In mice, murine PL-I is a potent islet mitogen, is capable of increasing islet mass, and is associated with hypoglycemia over the long term. It can be targeted to the beta cell using standard gene targeting techniques. Potential exists for beta cell engineering using this strategy.

Animals↗

Gene Structure of the U2 snRNP-Specific A' Protein Gene from Salmo salar: Alternative Transcripts Observed.

The genomic sequence of the Atlantic salmon (Salmo salar) U2 snRNP-specific A' protein gene (U2A') was identified on a cosmid clone, and the exon/intron organization of a U2A' gene is described for the first time. The cosmid sequence includes 8 exons from which the 227 amino-terminal amino acids, of a total of 339 amino acids, are deduced. The cosmid cloning site was found in the 8th intron, which also contains a BglII minisatellite repeat region of unknown length. The 3' end of the gene was determined from a complementary DNA sequence. In the 234 amino-terminal amino acids the sequence identity is 84% to human and 49% to Arabidopsis thaliana. The phases of introns 1 to 8 are 1, 2, 0, 2, 0, 2, 0, and 1, respectively. The salmon U2A' gene was found by reverse transcription-polymerase chain reaction to be expressed in all 10 tissues tested, and in addition to the expected fragment of 695 bp, a smaller fragment of 615 bp was amplified in all tissues. Nucleotide sequencing of the fragments obtained showed that the smaller transcript lacks exon 6 and this results in frameshift of exon 7 and a truncated deduced polypeptide. This result may be explained by alternative splicing of the salmon U2A' gene. Different U2A' transcripts were found to exist also in human tissue.

Journal Article↗

Electrocardiographic presentation of blacks with first myocardial infarction does not explain race differences in thrombolysis administration.

BACKGROUND: Previous studies have suggested that thrombolysis is used less often in blacks than in whites. However, whether the greater prevalence of contraindications or less specific electrocardiographic manifestations of myocardial infarction (MI) account for this difference is unclear. METHODS AND RESULTS: We studied 498 consecutive patients (32% blacks) with first MI. Initial electrocardiograms were analyzed, blinded to race and outcome, for ST-segment deviation and bundle branch block to determine eligibility for thrombolysis. The relation of electrocardiographic eligibility for thrombolysis and actual use of thrombolysis in both races was explored. Among blacks, 45% received thrombolysis compared with 66% of whites (P <.001). A similar proportion of blacks and whites were eligible for thrombolysis (59% and 66% respectively, P =. 116), but 62% of electrocardiography-eligible blacks were treated with thrombolysis compared with 75% of whites (P =.016). After accounting for eligibility for electrocardiography and other clinical variables likely to affect the decision to administer thrombolysis by means of conditional logistic regression, blacks were still less likely to receive thrombolysis (relative risk 0.73; 95% confidence interval 0.55 to 0.97). CONCLUSIONS: We conclude that the differences in thrombolysis administration to blacks and whites are not accounted for by differences in electrocardiographic presentation or other measured variables. Unmeasured differences in clinical presentation of MI may explain racial differences in thrombolysis and merits further study.

Adult↗

Effect of delay on racial differences in thrombolysis for acute myocardial infarction.

OBJECTIVE: To analyze the effect of delay times on racial differences in thrombolysis for acute myocardial infarction. BACKGROUND: Lower rates of thrombolytic therapy in blacks with acute myocardial infarction have recently been reported, but the reasons for this disparity are unknown. We hypothesized that lower rates of thrombolysis are caused by delay in presentation after symptom onset. METHODS: From November 1992 through November 1996, consecutive patients with a first acute myocardial infarction presenting to a large, urban teaching hospital were prospectively enrolled. Delay times were determined retrospectively from review of medical records. Patients were prospectively followed up for in-hospital cardiac events and death. A multivariable regression model was built to relate presentation times and other variables to thrombolysis administration. RESULTS: A total of 395 patients were included in the study, of which 33% were black. Symptom onset to emergency department presentation and door-to-needle times were significantly longer in blacks. Thrombolysis was administered significantly less often in blacks compared with whites (47% vs 68%, P =.001). Black race and age above 60 years were independently associated with delayed presentation and prolonged door-to-needle times. Black race, time to presentation, and non-Q-wave myocardial infarction were independently associated with not receiving thrombolysis. In-hospital mortality rates were similar in both groups. CONCLUSIONS: Blacks presented later than whites for first acute myocardial infarction. Late arrival strongly influenced the rate of thrombolysis administration. Lower rates of thrombolysis and prolonged door-to-needle times were apparent in blacks after adjustment for delay times and other clinical factors, a finding that merits further investigation.

Adult↗

The structure and expression of the Salmo salar Ran gene.

The Ran protein is a highly conserved GTPase factor of the Ras-family of proteins. It is involved in the transport of proteins and RNA through the nuclear pores. cDNA sequences of Ran genes from different organisms are available but no vertebrate genomic sequence as yet. We have isolated a genomic cosmid clone of the Ran1 gene of Atlantic salmon (Salmo salar) and found that the gene is about 2.2 kb and has got 5 introns. Its gene structure was compared to those of Caenorhabditis elegans and Arabidopsis thaliana and one intron was found to be conserved in position. Two different Ran transcripts were identified in salmon, indicating that there are two Ran genes, Ran1 and Ran2. Both transcripts were found in all ten salmon tissues tested, though Ran1 to a higher degree.

Amino Acid Sequence↗

Identification of a novel putative SINE sequence in a Salmo salar cosmid clone.

A novel putative SINE sequence was found in a randomly selected cosmid clone of Salmo salar. The sequence (cSSML032Alu, GenBank accession number: L77085) was found to have 78% identity in 212 bp, with one Salvelinus namaycush AluI satellite sequence (GenBank accession number: U27096) and 69% identity in 197 bp, with another AluI satellite sequence from S. namaycush (GenBank accession number: U27091). Colony hybridization of cSSML032Alu to a salmon cosmid library indicated its dispersed presence in the genome, with a copy number in the range of a few thousand. Direct terminal repeats of nine bases and a potential poly(A) tail remnant identified in the S. salar cSSML032Alu sequence indicate a possible ancient retroposon unit.

Journal Article↗

Atresia coli inherited in Holstein cattle.

A mating plan was designed to test the genetic hypothesis that atresia coli is inherited as an autosomal recessive at a single locus with two alleles. Matings between 8 putative carrier sires and 56 putative carrier dams resulted in 59 normal and 8 atresia coli calves, which was not different from the expected number of 8.1 affected calves. One case of atresia coli was observed among 628 calves born concurrently in the herd. All of the affected calves born from planned and contemporary matings were inbred, and their dominance relationships with each other were greater than zero, which is complementary evidence of pairs of alleles in common among affected calves. In planned matings, 7 of the 39 pregnancies diagnosed during the first 40 d of gestation of putative carriers produced affected calves. In contemporary matings, for pregnancies diagnosed before d 41 of gestation, there were 1 affected and 295 normal calves. Atresia coli in Holstein calves was associated with putative carrier parents. Retrospective analysis of early pregnancy diagnosis in dams was inconclusive in evaluating the role of palpation on atresia coli in genetically predisposed calves.

Animals↗

Incidence of atresia coli and relationships among the affected calves born in one herd of Holstein cattle.

Eighteen cases of atresia coli were observed in the University of Illinois Holstein herd from 1974 through August 1983 in 2367 births. The overall incidence of the abnormality was .76% during this period. All of the affected calves were related to one another, and 15 of them were inbred. More calves were born with atresia coli from dams in which pregnancy was diagnosed prior to d 41 of gestation than from dams in which pregnancy was diagnosed later. Early pregnancy diagnosis in dams may contribute, but was not essential, to atresia coli in Holstein calves. Thirteen of the affected calves were males. The proportion of calves aborted or born dead among the affected calves was greater than expected from the incidence of aborted or born dead among contemporary calves.

Animals↗

Effects of cisapride on isolated guinea pig colon.

Effects of cisapride were studied on the whole segments and muscle strips isolated from the guinea pig ascending colon. In whole segment preparations, external application of cisapride (0.4-10 microM) produced relaxation and inhibited spontaneous and evoked intraluminal pressure changes. Intraluminal application (1-10 microM) increased the pressure response. In many circular muscle strips (18 preparations out of 20), cisapride (0.3-1 microM) increased the mechanical activity, particularly when the pH was lowered, associated with an increased spike activity. However, this action was relatively weak, and in some preparations (2 preparations out of 20), almost no effect was observed. At higher concentrations (more than 1-5 microM), cisapride reduced the muscle tone and nerve-mediated contractions. The cisapride effect could be demonstrated in the presence of atropine (0.5 microM) and serotonin (5 microM). It was concluded that cisapride has direct inhibitory as well as excitatory actions. There was a tendency for the excitatory action to appear at a lower concentration than for the inhibitory action.

Acetylcholine↗

Structural analysis of mouse S-antigen.

Mouse S-antigen clones were isolated from a mouse retinal cDNA library using a bovine S-antigen cDNA probe. The largest clone (MSC-242) comprised 1532 bp and contained the entire coding sequence. The nucleotide sequence homology between the mouse and bovine coding regions was 84%, while non-coding regions appeared to be more divergent. The deduced amino acid sequence indicated that the mouse S-antigen had 403 residues and its molecular ratio was 44,930. An overall amino acid sequence similarity of 84% was observed between the mouse and bovine proteins. This degree of similarity dropped to 60% and 47% at the N and the C termini, respectively. The local homology with alpha-transducin observed in the bovine proteins, including the putative phosphoryl and rhodopsin binding sites, was conserved in the mouse as well. There was no overall sequence similarity with other proteins listed in the National Biomedical Research Foundation (NBRF) protein sequence database. Among the uveitopathogenic sites for experimental autoimmune uveitis (EAU), peptides N and M were identical to their bovine counterparts. Peptides 3 and K, however, were more divergent. The short repeats within these peptides were conserved.

Amino Acid Sequence↗

A genetic association between bovine serum and colostrum lysozyme levels.

Serum and colostrum lysozyme activity was determined in primiparous cows employing a lysoplate method described elsewhere. Samples from 336 animals were collected over a 5-year period from a research station. The animals were sired by 20 elite bulls, one of which (1893) is probably heterozygous for a dominant high lysozyme level gene. The resulting two-population split of high and low level offspring from 1893 is also consistent for the present cow material both in serum and colostrum. A highly significant overall correlation (P less than 0.01) between serum and colostrum lysozyme was estimated. Positive correlation was also found within families and this was particularly high for 1893. No association between serum and colostrum lysozyme activity could be detected when high level animals were excluded. This means that the genetic association between lysozyme activity in the two body fluids is solely dependent upon the major gene described. Consequently, selection of bulls for serum lysozyme activity will influence the colostrum or milk lysozyme activity in the cow population, provided that the major gene is present in the population.

Animals↗

Some properties of the lysozymes in serum and colostrum from cows with high and low lytic power against Micrococcus lysodeikticus.

Previous work has uncovered a dominant gene for high bacteriolytic activity of bovine serum against the test bacterium Micrococcus lysodeikticus. This major gene effect is also fully expressed in colostrum. In the present study the lytic power of serum and colostral whey from high and low level cows was subjected to a degree of characterization. It was found that the enzyme activities studied exhibited properties in accordance with those defined for a lysozyme (EC 3.2.1.17), i.e. (1) lysis of a suspension of M. lysodeikticus, (2) basic protein (pI = 10.0 and pI = 10.3 for bovine serum lysozyme (BSL) and bovine colostrum lysozyme (BCL), respectively), (3) molecular weight (MW) approximately 16 000 for both BSL and BCL, (4) liberation of free reducing sugars during action on cell wall peptidoglycan (the kinetics of BSL and BCL differed strongly), and (5) fairly heat stable, especially at acidic pH and relative labile at alkaline pH (BCL was far more sensitive to heating at alkaline pH than was BSL). The dramatic differences in activity between high and low level animals might be due to a major genetic mechanism influencing the amount of, or the activity of, circulating enzyme molecules, rather than a structural gene coding for a certain enzyme with a particular specific activity. This is also supported by the high correlation between the lytic capacity of BSL and BCL in spite of the different properties of these lysozymes (i.e. in respect of pI, enzyme kinetics and heat stability) reported in the present study.

Animals↗