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Biomedical subjects

S Alexander

Publications and source records attributed to S Alexander.

At least 37 records · Page 2Linked to original sources

Neutrophil elastase promotes lung microvascular injury and proteolysis of endothelial cadherins.

Intestinal ischemia-reperfusion (I-R) is associated with lung injury and the acute respiratory distress syndrome. The hypothesis of this study was that intestinal I-R activates circulating neutrophils to promote elastase-mediated lung injury. Isolated rat lungs were perfused with blood or plasma obtained after intestinal I-R, and lung neutrophil retention and injury and bronchoalveolar lavage (BAL) elastase were measured. Perfusion with I-R blood caused lung neutrophil accumulation and injury and increased BAL elastase. These effects were attenuated by the elastase inhibitor L-658758. Interference with neutrophil adherence before gut reperfusion blocked BAL elastase accumulation. The role of endothelial junction proteins (cadherins) in I-R-elicited lung damage was also evaluated. Activated human neutrophils proteolyzed cadherins in human umbilical vein endothelial cells. Furthermore, plasma of patients with acute respiratory distress syndrome contained soluble cadherin fragments. The results of this study suggest that the elastase released by systemically activated neutrophils contributes to lung neutrophil accumulation and pulmonary microvascular injury. Elastase-mediated proteolysis of endothelial cell cadherins may represent the mechanism through which lung microvascular integrity is disrupted after intestinal I-R.

Animals

Molecular characterization of multiresistant strains of Salmonella typhi from South Asia isolated in Ontario, Canada.

Two hundred and fourteen isolates of Salmonella typhi submitted to our laboratory between 1992 and 1996 were tested for susceptibility to 20 antimicrobial agents. Forty-eight of the 214 isolates (22.4%), recovered from individuals who had travelled in South Asia, were multiresistant. Forty-four of the 48 isolates were resistant to ampicillin, chloramphenicol, tetracycline, streptomycin, sulfamethoxazole, trimethoprim, cotrimoxazole, ticarcillin, and piperacillin; the other four isolates were resistant to four to six agents. Forty-two of the multiresistant isolates belonged to Vi phage type E1, two isolates from the Punjab State belonged to phage type A, another from the Punjab State belonged to phage type E3, one isolate from Pakistan belonged to type M1, and one isolate from India belonged to type J1. Plasmids from 45 of 48 isolates showed a temperature-sensitive mechanism of transfer to Escherichia coli K-12 strains, characteristic of H1 incompatibility group plasmids. The majority of plasmids had an estimated molecular weight of 120 MDa and encoded both citrate utilization and mercury resistance. Plasmids from three isolates had an estimated molecular weight of 112-115 MDa; one of these isolates encoded citrate utilization but not mercury resistance. Analysis of isolates by pulsed-field gel electrophoresis after digestion with XbaI and SpeI indicated that the majority of multiresistant isolates shared a common restriction profile, while four isolates had unique patterns.

Adolescent

Profiles, occlusal plane relationships and spacing of teeth in the dentitions of 3 to 4 year old children.

A study of 1026, 3 to 4 year old children in nursery schools and day-care centers was done to assess the profile, occlusal relationships and the presence of spacing or crowding of teeth in south India. Males had a higher incidence of convex profiles, while females showed a higher incidence of straight profiles, but it was not statistically significant. Flush terminal planes was the most commonly observed molar relationship in both the sexes. Seventy-five percent of both the sexes showed presence of both physiologic and primate spaces in both the jaws; and 3% of the population under study were devoid of spacing and had closed dental arches. Comparison between the profiles and terminal plane relationships it was observed that convex profiles were significantly correlated with flush and distal step terminal planes in both the sexes.

Child, Preschool

The Dictyostelium discoideum beta-1,4-mannosyltransferase gene, mntA, has two periods of developmental expression.

The precise roles of protein glycosylation in multicellular development are poorly understood. We have characterized the mntA gene from Dictyostelium discoideum which encodes the beta-1,4-mannosyltransferase enzyme that catalyzes the reaction: GDP-Man + dolichol-PP-GlcNAc2 --> dolichol-PP-GlcNAc2-Man + GDP. This gene has a central role in the synthesis of the lipid-linked oligosaccharide precursor which becomes the core of all asparagine-linked (N-linked) glycans. The mntA gene contains a single small intron and encodes a 493 aa protein with a predicted molecular size of 56 kDa. It is located 5' to the repE gene on chromosome IV and is transcribed in the opposite orientation to repE with which it shares a 585 bp of upstream intergenic region. The predicted mntA gene product shares 38% homology with the S. cerevisiae ALG1 gene product. The MntA protein has a region homologous to the putative dolichol-binding region in the yeast ALG1 protein, but it is located in a different part of the molecule. Northern analysis revealed that the expression of the mntA gene is regulated during multicellular development with two periods of mRNA accumulation. The mntA gene product has a classical endoplasmic reticulum retention motif, and is the first Dictyostelium gene encoding a protein that is active in this organelle. The identification of this gene will allow expanded studies of the role of N-linked glycans in multicellular development.

Amino Acid Sequence

Differential developmental expression of the rep B and rep D xeroderma pigmentosum related DNA helicase genes from Dictyostelium discoideum.

DNA helicases are essential to many cellular processes including recombination, replication and transcription, and some helicases function in multiple processes. The helicases encoded by the Xeroderma pigmentosum (XP) B and D genes function in both nucleotide excision repair and transcription initiation. Mutations that affect the repair function of these proteins result in XP while mutations affecting transcription result in neurological and developmental abnormalities, although the underlying molecular and cellular basis for these phenotypes is not well understood. To better understand the developmental roles of these genes, we have now identified and characterized the rep B and rep D genes from the cellular slime mold Dictyostelium discoideum . Both genes encode DNA helicases of the SF2 superfamily of helicases. The rep D gene contains no introns and the rep B gene contains only one intron, which makes their genomic structures dramatically different from the corresponding genes in mammals and fish. However the predicted Dictyostelium proteins share high homology with the human XPB and XPD proteins. The single copy of the rep B and D genes map to chromosomes 3 and 1, respectively. The expression of rep B and D (and the previously isolated rep E) genes during multicellular development was examined, and it was determined that each rep gene has a unique pattern of expression, consistent with the idea that they have specific roles in development. The pattern and extent of expression of these genes was not affected by the growth history of the cells, implying that the expression of these genes is tightly regulated by the developmental program. The expression of the rep genes is a very early step in development and may well represent a key event in the initiation of development in this organism.

Amino Acid Sequence

Cost, work, reimbursement, and the pediatric nephrologist in the United States Medicare/End-Stage Renal Disease Program.

The American Academy of Pediatrics, the American Society of Pediatric Nephrology, and the Renal Physicians Association combined their efforts to perform a survey of the work involved in providing care to children with end-stage renal disease (ESRD). These data document that the work of delivering care to infants and children on dialysis takes longer and is more intense than the care provided to adult patients. These data were presented to the American Medical Association Specialty Society Relative Value Scale Update Committee (RUC) to justify higher payment for pediatric ESRD care using previously developed monthly capitation payment Current Procedural Terminology codes based on patient age. Relative Work Units of 13.25 for infants (0-2 years), 9.13 for children (2-12 years), 6.47 for adolescents (12-19 years), and 5.24 for adults (> 19 years) were recommended by the RUC to Medicare. A suggested description of services for pediatric dialysis patients covered by the monthly capitated payment was developed.

Adolescent

Cytomegalovirus infections following renal transplantation--effects on antiviral prophylaxis: a report of the North American Pediatric Renal Transplant Cooperative Study.

Post-transplant cytomegalovirus (CMV) infections are a source of significant morbidity. However, the extent of the problem and the benefits of various antiviral prophylactic therapies remain incompletely understood. The North American Pediatric Renal Transplant Cooperative Study registry was screened to identify patients hospitalized for CMV infections during the 1st post-renal transplant year between 1987 and 1993. Using a control group of transplant recipients, we performed a retrospective analysis of risk factors for CMV disease among these hospitalized patients and studied the effects of various viral prophylactic strategies on CMV risk, clinical manifestations, and outcome. We identified 142 patients hospitalized with CMV infections, the majority of which included major organ involvement. A CMV-positive kidney donor was the most significant risk factor for hospitalization [odds ratio (OR) = 5.2, P<0.0001] irrespective of recipient age or CMV immune status. As opposed to antiviral agents (acyclovir, ganciclovir) or pooled IgG, prophylaxis with enriched anti-CMV IgG significantly reduced the risk of CMV hospitalization (OR = 0.31, P = 0.03). The prophylactic use of antiviral agents was associated with a decreased risk of major organ involvement during the CMV infection (OR = 0.34, P<0.005). Among the patients with CMV, the 3-year graft survival was significantly better for those who received any form of prophylaxis compared with those who received none (88% vs. 52%, P<0.001). Our findings suggest a role for combined CMV-enriched IgG and antiviral agent prophylaxis for post-transplant CMV disease. Such an approach could diminish the incidence and severity of CMV infection and appears to have an independent favorable effect on graft outcome.

Adolescent

Age-related increase in muscle sympathetic nerve activity is associated with abdominal adiposity.

Tonic sympathetic nerve activity (SNA) increases with age, but the mechanisms are unknown. There is evidence that SNA is positively related to total and abdominal body fat, which also increase with age. We tested the hypotheses that 1) the elevation in SNA with age is partially accounted for by higher abdominal and/or total body fat and 2) skeletal muscle is a target of the adiposity-related sympathetic effects. Direct microneurographic recordings of skeletal muscle SNA (MSNA) were obtained during supine rest in 16 older (64 +/- 1 yr, means +/- SE) and 16 young (24 +/- 1 yr) adult males. Central body fat was estimated by waist circumference (WC) and fat mass (FM) by hydrostatic weight. MSNA, WC, and FM were higher in the older vs. young males (44 +/- 2 vs. 22 +/- 2 bursts/min, 91 +/- 2 vs. 79 +/- 1 cm, and 19 +/- 2 vs. 9 +/- 1 kg, respectively; all P < 0.0001). Although univariate correlations were high for MSNA and both WC (r = 0.77) and FM (r = 0.75), stepwise multiple regression analysis revealed WC to be the best predictor of MSNA (R2 = 0.60, P < 0.0001), with FM explaining only an additional 2% of the variance (not significant). Statistically covarying for WC reduced but did not eliminate the difference in adjusted age-group means for MSNA (39 +/- 3 vs. 26 +/- 2 bursts/min, P = 0.003). We conclude that 1) the elevated SNA in older adults is partially related to higher body fat, particularly in the abdominal region, and 2) skeletal muscle is a target of the adiposity-related sympathetic effects observed with aging.

Abdomen

Prevalence of malocclusion and periodontal status in Tibetan school children of Kushalnagar, Mysore district.

A representative sample of 817 Tibetan school children aged 7 to 17 years of Mysore district were examined for malocclusion, gingival bleeding and calculus, using plane mouth mirror, sickle explorer and periodontal probes, under natural light. A very slight increase in malocclusion was noted in school girls, in addition to the statistically significant increase in gingival bleeding among 8-13 years and 17 year old girls and 7-10 years and 15-16 year old boys. Moreover, a highly statistically significant increase in calculus was perceived amongst girls. The present study thus showed an increasing demand for preventive and therapeutic dental treatment in these children and early identification of such individuals at risk, can lead to better disease management.

Adolescent

Helminth fauna of Anas undulata, Anas erythrorhyncha, Anas capensis and Anas smithii at Barberspan, South Africa.

Thirty-four species of gastrointestinal helminths were found in 25 Anas undulata, 21 Anas erythrorhyncha, ten Anas capensis and seven Anas smithii collected at Barberspan, South Africa. Excluding four new taxa, 11 new African records, and 14, 11, 12 and nine new host records were established for Anas undulata, Anas erythrorhyncha, Anas capensis and Anas smithii, respectively. The helminth community included 13 cosmopolitan species, seven species known only from the holarctic, one species known only from the south Pacific and 13 new or unidentified species that appear to be restricted to Africa. The infection levels of the common helminth species in the mainly carnivorous Anas capensis and Anas smithii, were generally much higher than those of species infecting Anas undulata or Anas erythrorhyncha.

Animals

A comparison of the helminth communities in Anas undulata, Anas erythrorhyncha, Anas capensis and Anas smithii at Barberspan, South Africa.

Examination of the helminth communities in 25 yellow-billed ducks (Anas undulata), 21 red-billed ducks (Anas erythrorhyncha), ten Cape teal (Anas capensis) and seven Cape shovellers (Anas smithii) that had overwintered at Barberspan, revealed differences in community structure. Infracommunities in yellow-billed and red-billed ducks were characterized by low diversity and high eveness, and generally consisted of less than 100 helminths per duck. Similarity values (mean percent similarity and mean Jaccard's coefficients) were low. In contrast, infracommunities in Cape teal and Cape shovellers were more diverse, displayed low eveness values and consisted of far greater numbers of helminths. Mean similarity values for the infracommunities in Cape teal and Cape shovellers were much higher than those in yellow-billed or red-billed ducks. The component communities in all four duck hosts were species rich. Those in yellow-billed and red-billed ducks, however, consisted predominantly of satellite species and no core species were present, whereas those in Cape teal and Cape shoveller included several core species. Cape teal and Cape shovellers each had a group of recurrent species but there was not much of a tendency for species to co-occur in yellow-billed and red-billed ducks. Multivariate analysis revealed a greater similarity between the communities in Cape teal and Cape shovellers than between the latter and the communities in yellow-billed or red-billed ducks. Communities in Cape teal and Cape shovellers could be distinguished from each other by the presence or absence of particular cestode species. The communities in these two species could be distinguished from those in yellow-billed or red-billed ducks by a suite of cestode species that was absent in the latter two. Two recurrent groups, consisting of eight and two species, were identified in the compound community. Each group consisted of species found predominantly in Cape teal and Cape shovellers. Patterns seen in the helminth communities of the various hosts reflected differences in diet, but other factors, including feeding behaviour, spatial segregation and host specificity, may also have had an effect.

Animals

Genioglossis muscle electrical activity and associated arch dimensional changes in simple tongue thrust swallow pattern.

Twenty schoolchildren between the age groups of 12-14 years with permanent dentition were the subjects of this study. Group A comprised of ten subjects with Angle's Class I occlusion. Group B consisted of ten subjects having Angle's Class I occlusion with anterior open bite and simple tongue thrust swallow pattern. Evaluation of electrical activity of genioglossus muscle and associated arch dimensional changes were performed in both groups A and B. Frequency of electrical activity of the genioglossus muscle and duration of swallow was found to be significantly higher in tongue thrusters than in the normal subjects. No statistically significant changes were observed in both upper and lower arches of Groups A and B in terms of bimolar and bipremolar width and palatal depth. A significant increase in the extent of anterior teeth proclination in the upper arch in the tongue thrust individuals was attributed to the effect of the increased frequency of electrical activity of the genioglossus muscle and prolonged duration of swallow.

Adolescent

Arteriovenous malformation of the mandible--report of a case.

An eight-year-old girl was referred for the management of recurrent bleeding from the lower, left gingival region and a diffused swelling on the left side of her face. Doppler study and carotid angiogram were suggestive of an arteriovenous malformation. Segmental mandibular resection was performed after ligation of the left external carotid artery. Post-operative period was uneventful and there has been no recurrence of the lesion till date.

Arteriovenous Malformations

repE--the Dictyostelium homolog of the human xeroderma pigmentosum group E gene is developmentally regulated and contains a leucine zipper motif.

We have cloned and characterized the Dictyostelium discoideum repE gene, a homolog of the human xeroderma pigmentosum (XP) group E gene which encodes a UV-damaged DNA binding protein. The repE gene maps to chromosome 4 and it is the first gene identified in Dictyostelium that is homologous to those involved in nucleotide excision repair and their related XP diseases in humans. The predicted protein encodes a leucine zipper motif. The repE gene is not expressed by mitotically dividing cells, and repE mRNA is first detected during the aggregation phase of development when the cells have ceased dividing and replicating genomic DNA. The mRNA level plateaus by the time the developing cells have entered multicellular aggregates and remains at the same steady-state level for the remainder of development. In addition, we have demonstrated that the level of mRNA is very low in developing cells. These observations suggest that repE may play a regulatory role in development. The data indicate that potential developmental roles for XP-related genes can be profitably studied in this system.

Amino Acid Sequence

PsB multiprotein complex of Dictyostelium discoideum. Demonstration of cellulose binding activity and order of protein subunit assembly.

The differentiated spores of Dictyostelium are surrounded by an extracellular matrix, the spore coat, which protects them from environmental factors allowing them to remain viable for extended periods of time. This presumably is a major evolutionary advantage. This unique extracellular matrix is composed of cellulose and glycoproteins. Previous work has shown that some of these spore coat glycoproteins exist as a preassembled multiprotein complex (the PsB multiprotein complex) which is stored in the prespore vesicles (Watson, N., McGuire, V., and Alexander, S (1994) J. Cell Sci. 107, 2567-2579). Later in development, the complex is synchronously secreted from the prespore vesicles and incorporated into the spore coat. We now have shown that the PsB complex has a specific in vitro cellulose binding activity. The analysis of mutants lacking individual subunits of the PsB complex revealed the relative order of assembly of the subunit proteins and demonstrated that the protein subunits must be assembled for cellulose binding activity. These results provide a biochemical explanation for the localization of this multiprotein complex in the spore coat.

Animals

Evaluation of a patient teaching skills course disseminated through staff developers.

Effective Patient Teaching (EPT), a course designed to improve health professionals' and health professions students' teaching skills, reliably produces gains in participants' skills when presented by its developers. The objective of this dissemination research study was to investigate whether, using a 'training of trainers' approach, seven nurses with staff development responsibilities in five different sites could teach EPT with similar effectiveness. The evaluation included pre- and post-course analysis of audiotaped patient education sessions conducted by 48 health professional participants who took EPT from one of the trainers in their home institutions. Post-course participant satisfaction surveys were also administered. EPT resulted in teaching skill improvements in four of five sites, and overall teaching skills scores improved significantly (P < 0.01). EPT can improve participants' teaching skills when taught by health professional trainers with staff development responsibilities who have recently received EPT training.

Clinical Competence

Prospective study of the SI-40NB foldable silicone intraocular lens.

PURPOSE: To evaluate the surgical performance and postoperative outcomes of 100 consecutive implantations of the new AMO PhacoFlex SI-40NB foldable intraocular lens (IOL). SETTING: Concord Hospital and Dalcross Private Hospital, Sydney, Australia. METHODS: This prospective study comprised 100 consecutive patients who had endocapsular phacoemulsification cataract surgery with implantation of the AMO SI-40NB IOL, which has a silicone optic and poly(methyl methacrylate) (PMMA) haptics. Patients were excluded if trabeculectomy was performed concomitantly. The main outcome measures were control of folding, ease of implantation, centration, intraoperative and postoperative complications, and visual acuity. A minimum of 4 months follow-up was planned. RESULTS: Mean follow-up was 4.3 months +/- 2.1 (SD) (range 1 to 12 months). The lens permitted excellent control of folding and insertion, as well as excellent centration at surgery and 4 months. There was one lens-related intraoperative complication because of crimping of the trailing lens haptic. Postoperative complications were minimal, and 92% of patients achieved a visual acuity of 20/20 or better at 1 and 4 months. Excluding the eyes with retinal pathology, 100% achieved 20/20 or better at 4 months. CONCLUSION: The AMO SI-40NB three-piece silicone IOL with PMMA haptics provided excellent operative control, centration, and visual outcome and is suitable for small incision cataract surgery.

Aged