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Biomedical subjects

S D Reid

Publications and source records attributed to S D Reid.

At least 19 recordsLinked to original sources

Depression and its associated factors among patients attending chronic disease clinics in southwest Trinidad.

This study determined the prevalence of depression and associated factors, among patients attending chronic disease clinics in Southwest Trinidad. This was a cross-sectional survey using a sample of consecutive patients at four large clinics. To determine the presence of depression, an interviewer-applied modified Zung Scale was validated The modified Zung scale, at the cut-off index of 60, has a sensitivity of 60% and a specificity of 94%. Seven hundred and thirty-four completed questionnaires were received, a response rate of 76%. The patients were primarily Indo-Trinidadian (70%), over 50 years (76.4%) and female (72.3%). The prevalence of depression was 28.3%. There were statistically significant differences in the level of depression by age, gender, educational level achieved and occupation (p < 0.05). There were also statistically significant differences in the level of depression by the number of presenting complaints, the number of chronic diseases, the presence of arthritis, the presence of diabetes mellitus with another chronic disease and the presence of ischaemic heart disease (p < 0.05). No significant differences were found with respect to ethnicity (p = 0.97) or the presence of diabetes mellitus by itself (p = 0.34). Results of logistic regression indicate that the independent predictors of depression (p < 0.05) were the level of education achieved, those with higher levels of education had less depression; the number of presenting complaints, those with more presenting complaints were more likely to be depressed and the presence of arthritis and female gender. It is imperative that policy be developed to address the mental health problems of patients attending these chronic disease clinics.

Adolescent↗

Substance abuse among first admissions to the psychiatric unit of a general hospital in Trinidad.

Admissions for first episode of psychiatric illness provide information on service utilization which can be used to improve service delivery. The present study reviews the use of in-patient general psychiatric services in southern Trinidad using data from first admissions in one year, specifically to determine service utilization by substance-abusing patients. Case files of all admissions to the psychiatric unit of the San Fernando General Hospital in one year were reviewed and analyzed for demographic data, substance abuse, diagnosis and associated features of the admission. Significant rates of substance abuse were found among first admissions. Of 123 new patients, 43.1% were diagnosed with a substance abuse disorder, 56.6% of whom had a comorbid psychiatric disorder. Patients with substance abuse problems tended to be young males. The substance most commonly abused was alcohol (26.8%) and alcohol abusers were more likely to be of East Indian descent. Management within this mental health catchment area needs to address identification, early intervention and prevention of substance abuse among psychiatric patients. It is proposed that both hospital and community-based substance abuse interventions should be employed in the management of acute psychiatric patients.

Adult↗

HIV seroprevalence and risk factors in female substance abusers seeking rehabilitation in Trinidad and Tobago.

Crack cocaine use, especially among females, is associated with risky sexual behaviour. Data from 122 female substance abusers admitted to a rehabilitation centre in Trinidad and Tobago between 1996 and 2002 were retrospectively reviewed to determine Human Immunodeficiency Virus (HIV) seroprevalence and other associated risk factors. HIV seroprevalence was 19.7%, eight times higher than in the general population. Factors significantly associated with HIV infection were use of crack cocaine, low educational attainment and diagnosis of a sexually transmitted infection. Other factors associated with risky sexual behaviour were common--use of cocaine in combination with alcohol (65.6%), psychiatric illness (28.7%) and a history of sexual abuse (83%). Female substance abusers, especially female crack addicts are at high risk of acquiring and transmitting HIV. Rehabilitation programmes should include HIV prevention interventions which specifically target all risk factors including trauma counselling, skills development and screening for sexually transmitted infections.

Adolescent↗

Multilocus analysis of extracellular putative virulence proteins made by group A Streptococcus: population genetics, human serologic response, and gene transcription.

Species of pathogenic microbes are composed of an array of evolutionarily distinct chromosomal genotypes characterized by diversity in gene content and sequence (allelic variation). The occurrence of substantial genetic diversity has hindered progress in developing a comprehensive understanding of the molecular basis of virulence and new therapeutics such as vaccines. To provide new information that bears on these issues, 11 genes encoding extracellular proteins in the human bacterial pathogen group A Streptococcus identified by analysis of four genomes were studied. Eight of the 11 genes encode proteins with a LPXTG(L) motif that covalently links Gram-positive virulence factors to the bacterial cell surface. Sequence analysis of the 11 genes in 37 geographically and phylogenetically diverse group A Streptococcus strains cultured from patients with different infection types found that recent horizontal gene transfer has contributed substantially to chromosomal diversity. Regions of the inferred proteins likely to interact with the host were identified by molecular population genetic analysis, and Western immunoblot analysis with sera from infected patients confirmed that they were antigenic. Real-time reverse transcriptase-PCR (TaqMan) assays found that transcription of six of the 11 genes was substantially up-regulated in the stationary phase. In addition, transcription of many genes was influenced by the covR and mga trans-acting gene regulatory loci. Multilocus investigation of putative virulence genes by the integrated approach described herein provides an important strategy to aid microbial pathogenesis research and rapidly identify new targets for therapeutics research.

Amino Acid Sequence↗

Progression of dreams of crack cocaine abusers as a predictor of treatment outcome: a preliminary report.

This study tested the hypotheses that a) the dream content of crack cocaine abusers in Trinidad and Tobago changes during abstinence, and b) the change in dream content can be used to predict treatment outcome. The sample comprised 46 consecutive patients who completed a 3-month residential treatment program and were followed up after 6 months. Dreams and associated emotions were recorded during the first month of inpatient treatment and at 6 months follow-up. Forty-one (89.1%) patients reported drug dreams during the first month, mainly of using the drug. Twenty-eight (60.9%) had drug dreams at 6 months follow-up, mainly of using or refusing the drug. There was an abstinence rate of 56.5% at 6 months. A better treatment outcome was associated with having drug dreams at 6 months follow-up (p < .05) and dreams of refusing the drug (p < .05). Findings support the need to further explore the progression of dreams during treatment as a predictive tool.

Adult↗

Parallel evolution of virulence in pathogenic Escherichia coli.

The mechanisms underlying the evolution and emergence of new bacterial pathogens are not well understood. To elucidate the evolution of pathogenic Escherichia coli strains, here we sequenced seven housekeeping genes to build a phylogenetic tree and trace the history of the acquisition of virulence genes. Compatibility analysis indicates that more than 70% of the informative sites agree with a single phylogeny, suggesting that recombination has not completely obscured the remnants of ancestral chromosomes. On the basis of the rate of synonymous substitution for E. coli and Salmonella enterica (4.7 x 10(-9) per site per year), the radiation of clones began about 9 million years ago and the highly virulent pathogen responsible for epidemics of food poisoning, E. coli O157:H7, separated from a common ancestor of E. coli K-12 as long as 4.5 million years ago. Phylogenetic analysis reveals that old lineages of E. coli have acquired the same virulence factors in parallel, including a pathogenicity island involved in intestinal adhesion, a plasmid-borne haemolysin, and phage-encoded Shiga toxins. Such parallel evolution indicates that natural selection has favoured an ordered acquisition of genes and the progressive build-up of molecular mechanisms that increase virulence.

DNA, Bacterial↗

The control of T cell responses by dendritic cell subsets.

Dendritic cells are known as the most efficient antigen-presenting cell type to activate naïve T cells; however, they are able to do more than just efficiently present antigen to T cells. They are key modulators of the immune response that can influence Th cell differentiation by preferentially inducing Th type 1 or 2 cell responses, and the differential polarisation of CD4(+) T cells appears to be mediated by discrete dendritic cell subsets.

Animals↗

Identification and characterization of the scl gene encoding a group A Streptococcus extracellular protein virulence factor with similarity to human collagen.

Group A Streptococcus (GAS) expresses cell surface proteins that mediate important biological functions such as resistance to phagocytosis, adherence to plasma and extracellular matrix proteins, and degradation of host proteins. An open reading frame encoding a protein of 348 amino acid residues was identified by analysis of the genome sequence available for a serotype M1 strain. The protein has an LPATGE sequence located near the carboxy terminus that matches the consensus sequence (LPXTGX) present in many gram-positive cell wall-anchored molecules. Importantly, the central region of this protein contains 50 contiguous Gly-X-X triplet amino acid motifs characteristic of the structure of human collagen. The structural gene (designated scl for streptococcal collagen-like) was present in all 50 GAS isolates tested, which together express 21 different M protein types and represent the breadth of genomic diversity in the species. DNA sequence analysis of the gene in these 50 isolates found that the number of contiguous Gly-X-X motifs ranged from 14 in serotype M6 isolates to 62 in a serotype M41 organism. M1 and M18 organisms had the identical allele, which indicates very recent horizontal gene transfer. The gene was transcribed abundantly in the logarithmic but not stationary phase of growth, a result consistent with the occurrence of a DNA sequence with substantial homology with a consensus Mga binding site immediately upstream of the scl open reading frame. Two isogenic mutant M1 strains created by nonpolar mutagenesis of the scl structural gene were not attenuated for mouse virulence as assessed by intraperitoneal inoculation. In contrast, the isogenic mutant derivative made from the M1 strain representative of the subclone most frequently causing human infections was significantly less virulent when inoculated subcutaneously into mice. In addition, both isogenic mutant strains had significantly reduced adherence to human A549 epithelial cells grown in culture. These studies identify a new extracellular GAS virulence factor that is widely distributed in the species and participates in adherence to host cells and soft tissue pathology.

Amino Acid Sequence↗

Cytokine regulation of CD44 expression on rat intestinal epithelial cells.

CD44 comprises a family of type I transmembrane glycoproteins that is expressed on a wide range of cells including those of epithelial, lymphoid and myeloid lineage. Although expression of CD44 in the small intestine is typically localised in the crypts of Lieberkuhn, we have reported the expression of CD44 on mature, intestinal villus epithelial cells during the development of small bowel allograft rejection. The mechanisms underlying CD44 up-regulation are unknown, although it may be influenced by localised cytokine production. This study used flow cytometry to assess the effects of recombinant IFN-gamma and TNF-alpha on CD44 expression and hyaluronan binding by the rat small intestinal epithelial cell lines, RIE and IEC 6. IFN-gamma upregulated CD44 expression on RIE (155% of unstimulated control) and IEC 6 (209% of unstimulated control) cells, whereas TNF-alpha had no effect. IFN-gamma had no qualitative effect on CD44, as binding of the ubiquitously expressed extracellular matrix polysaccharide hyaluronan was unchanged. RIE and IEC 6 cells expressed the 82 kDa and 130 kDa major isoforms of CD44, however cytokine stimulation did not affect the expression of these, nor did stimulation induce the expression of other variants. In summary, these findings demonstrate that CD44 expression by intestinal epithelial cells can be regulated by cytokines, yet their ability to bind hyaluronan and the isoform of the expressed CD44 remains unaltered. It appears that localised inflammatory conditions and cytokine production may modify epithelial cell expression of CD44, however the physiological role for such a response has yet to be elucidated.

Alternative Splicing↗

Pseudodementia in a twenty-one-year-old with bipolar disorder and vitamin B12 and folate deficiency.

A twenty-one-year-old female known to suffer from bipolar type I disorder developed features of a pseudodementia. Following prompt initial response to treatment with antidepressants, there was an early recurrence of cognitive impairment. Blood investigations confirmed a macrocytic anaemia and vitamin B12 and folate deficiencies. There was dramatic resolution of cognitive impairment after vitamin replacement. This suggested the occurrence of a reversible nutritional dementia and reinforced the need to rule out secondary organic causes of psychiatric symptoms even in patients previously diagnosed with a primary psychiatric disorder.

Adult↗

Sequence diversity of flagellin (fliC) alleles in pathogenic Escherichia coli.

To study the molecular evolution of flagellin, the protein subunit specifying flagellar (H) antigens, the fliC genes from 15 pathogenic strains of Escherichia coli were amplified by PCR and sequenced. Comparison of fliC sequences of H6 and H7 strains revealed that alleles have a mosaic structure indicating the occurrence of past horizontal transfer of DNA segments between strains. The close similarity of H7 sequences also indicates the exchange of an entire fliC H7 allele between distant clonal lineages. In addition, the ratio of silent substitutions to amino acid replacements suggests that a short segment in the central region of fliC has been under positive selection in the divergence of H6 and H7 alleles. Phylogenetic analysis demonstrates that the fliC sequences of O157:H7 and O55:H7 serotypes are nearly identical and highly divergent from those of E. coli strains expressing H6 and H2 flagellar antigens. A nonmotile clone of sorbitol-fermenting O157 has rapidly accumulated multiple mutations in fliC, presumably as a result of the silencing of flagellin expression.

Alleles↗

Drug use, sexual behaviour and HIV risk of the homeless in Port-of-Spain, Trinidad.

Data were collected from 88 homeless persons in Port-of-Spain, Trinidad to assess HIV risk. 68% of the sample were engaging in unprotected sex with multiple partners, 25% were exchanging sex for money, and 29.5% were regularly smoking crack cocaine. Many had two or more of these behaviours that put them at high risk of HIV infection. Females were significantly more likely to be sex traders, to engage in bisexual behaviour and to have a history of psychiatric illness. The relationship between psychiatric illness and HIV risk behaviours among homeless female persons is explored. Educational interventions are suggested to reduce the public health risks in this population.

Adolescent↗

Antagonistic roles for phospholipase D activities in B cell signaling: while the antigen receptors transduce mitogenic signals via a novel phospholipase D activity, phosphatidylcholine-phospholipase D mediates antiproliferative signals.

Cross-linking of the Ag receptors on B cells induces DNA synthesis and proliferation. Butanol trap experiments suggest that one or more phospholipase D activities play a key role in this process. Although phosphatidylcholine-phospholipase D has been shown to play a central role in the transduction of proliferative responses for a wide variety of calcium-mobilizing receptors, we show that the Ag receptors are not coupled to this phospholipase. In addition, phosphatidylcholine-phospholipase D is not stimulated under conditions that mimic T cell-dependent B cell activation. In contrast, ATP, which inhibits surface Ig (sIg)-mediated DNA synthesis in murine B cells via P2-purinoceptors, activates phosphatidylcholine-phospholipase D. Phosphatidylcholine-phospholipase D is therefore associated with antiproliferative signal transduction in mature B cells, but it does not transduce early signals associated with sIg-mediated growth arrest or apoptosis in immature B cells. Mitogenic stimulation of sIg is, however, coupled to a novel nonphosphatidylcholine-hydrolyzing phospholipase D activity. The resultant sIg-generated phosphatidic acid, unlike the phosphatidylcholine-derived phosphatidic acid generated via the purinoceptors, is converted to diacylglycerol. These data provide the first evidence that while the novel sIg-coupled phospholipase D and resultant diacylglycerol generation may play a role in B cell survival and proliferation, phosphatidylcholine-phospholipase D may transduce, via phosphatidic acid, negative immunomodulatory signals in mature B lymphocytes.

1-Butanol↗

A phosphorylcholine-containing filarial nematode-secreted product disrupts B lymphocyte activation by targeting key proliferative signaling pathways.

Filarial nematodes infect more than 100 million people in the tropics, causing elephantiasis, chronic skin lesions, and blindness. The parasites are long-lived as a consequence of being able to evade the host immune system, but an understanding of the molecular mechanisms underlying this evasion remains elusive. In this study, we demonstrate that ES-62 (2 microg/ml), a phosphorylcholine (PC)-containing glycoprotein released by the rodent filarial parasite Acanthocheilonema viteae, is able to polyclonally activate certain protein tyrosine kinase and mitogen-activating protein kinase signal-transduction elements in B lymphocytes. Although this interaction is insufficient to cause B lymphocyte proliferation per se, it serves to desensitize the cells to subsequent activation of the phosphoinositide-3-kinase and Ras mitogen-activating protein kinase pathways, and hence also to proliferation, via the Ag receptor. The active component of ES-62 appears to be PC, a molecule recently shown to act as an intracellular signal transducer, as the results obtained with ES-62 are broadly mimicked by PC alone. As PC-containing secreted products (PC-ES) are also released by human filarial parasites, our data suggest that PC-ES, by interfering with B cell function, could play a role in prolonging filarial infection in parasitized individuals.

Amino Acid Sequence↗

CD44 expression in rejecting rat small bowel allografts.

CD44 is a widely expressed cell surface protein that recognizes multiple ligands and is involved in extra- and intercellular adhesion. The precise role of CD44 in immune interactions is currently unknown, but it is believed to be a homing receptor involved in lymphocyte trafficking and inflammatory responses. This study investigated CD44 expression in intestinal tissue after heterotopic rat small bowel transplantation and assessed the effect of transplantation on intestinal epithelial cell proliferation using an antibody to the nuclear activation Ag Ki67. Lamina propria and intestinal epithelial cell expression of CD44 was graded blindly by five observers, and villus epithelial cells were noted as being positive or negative for Ki67 staining. CD44 expression was high in the lamina propria of both allografted and isografted animals; however, there was no significant difference between the two groups. In contrast, the expression of CD44 on the villus epithelium was greater in allografted animals and progressed toward the villus tips as rejection developed, declining thereafter because of loss of villus integrity. Ki67 positivity was also greater in allografted animals but did not progress toward the villus tip. This is the first reported observation of CD44 expression on intestinal epithelium that is not restricted to the crypts. The findings indicate the involvement of CD44 in the rejection process and demonstrate changes in the proliferative profile of rejecting small intestinal epithelium. Further studies into adhesion molecules, such as CD44, may help to improve understanding of graft failure and promote the development of new therapeutic approaches for controlling and preventing graft rejection.

Animals↗