PubMed Health⌕ Search

Biomedical subjects

N Ismail

Publications and source records attributed to N Ismail.

At least 19 recordsLinked to original sources

Behavior and the limits of genomic plasticity: power and replicability in microarray analysis of honeybee brains.

Transcription is slow relative to many post-transcriptional processes in the brain. Using the rich system of division of labor in the honeybee (Apis mellifera), we found extreme differences in the extent to which behavioral occupations of different durations were associated with gene-expression differences in the brain. Nursing and foraging, occupations lasting > 1 week, were associated with significant expression differences for nearly one-quarter of the genes tested (1208 of 5563 cDNAs tested; P < 0.01, anova), consistent with previous results. In contrast, transitional occupations, performed for 1-2 days after nursing and before the onset of foraging, were associated with either no differences (guards vs. undertakers; 19 cDNAs, fewer than the expectation of 56 false-positives) or few differences (comb builders vs. guards and undertakers; 248 cDNAs), but extensive differences relative to both nursing and foraging (> 500 cDNAs, all contrasts). Statistical power analysis indicated that expression differences of two-, 1.5- and 1.25-fold should have been detected in 100, 92 and 37% of cases, respectively. Replication of previous results at these magnitudes was 95, 71 and 51%, with no genes showing differences in the opposite direction. These results indicate that behavioral plasticity over different time-scales may be associated with substantial differences in the extent of genomic plasticity in the brain.

Animals↗

Making membrane proteins at the mammalian endoplasmic reticulum.

Whereas protein biogenesis at the endoplasmic reticulum is well understood in the case of secretory proteins and simple membrane proteins, much less is known about the synthesis of multi-spanning integral membrane proteins. While it is clear that the multiple membrane-spanning domains of these proteins must be inserted into the lipid bilayer during biosynthesis, the mechanism by which their integration is achieved and their subsequent folding/assembly are poorly defined. In this review, we summarize our current understanding of protein synthesis at the endoplasmic reticulum and highlight specific features that are relevant to the biogenesis of multi-spanning membrane proteins.

Animals↗

More antigen-dependent CD4(+) T cell / CD4(+) T cell interactions are required for the primary generation of Th2 than of Th1 cells.

Mechanisms controlling the Th1 / Th2 phenotype of a primary immune response are often discussed assuming that the generation of Th1 and Th2 cells from the common CD4(+) precursor T helper (pTh) involves an interaction of this pTh cell with an antigen-presenting cell (APC) in the form of a two-cell interaction. Other studies suggest that the outcome of this two-cell interaction is modified by the presence of other T cells. No study has analyzed primary immune responses generated in normal, non-TcR transgenic mice, following the administration of a non-infectious antigen administered without adjuvant. We show that the Th1 / Th2 phenotype of such a primary response, generated in lethally irradiated recipients reconstituted with a variety of unprimed spleen cells, depends conjointly on the amount of antigen and number of unprimed syngeneic CD4(+) T cells present, with higher amounts and numbers favoring the generation of Th2 cells. Our observations show how these quantitative variables control in an interdependent manner the Th1 / Th2 phenotype of a primary immune response, and bear upon the mechanism by which this phenotype is determined.

Animals↗

Vaccination against and treatment of tuberculosis, the leishmaniases and AIDS: perspectives from basic immunology and immunity to chronic intracellular infections.

The occurrence of infectious disease represents a failure of the immune system, a failure that must be prevented by effective vaccination or remedied by treatment. Vaccination against acute diseases such as smallpox and polio are very effective, due to the rapid and increased immune response of vaccinated individuals upon natural infection. In contrast, effective vaccination against intracellular pathogens that cause chronic diseases, such as the leishmaniases, tuberculosis and AIDS, has not been achieved. Clinical observations suggest cell-mediated, Th1 responses, exclusive of antibody production and the generation of Th2 cells, are optimally protective against these intracellular pathogens. Effective vaccination must ensure the generation of such a protective response. We explore here whether understanding very broad features of the regulation of the immune response can accommodate modern findings on the immunological features of these diseases, and provide a perspective within which strategies for effective vaccination and treatment can be developed.

AIDS Vaccines↗

A novel cytotoxic flavonoid glycoside from Physalis angulata.

A new flavonol glycoside, myricetin 3-O-neohesperidoside (1) was isolated from a cytotoxic MeOH extract of the leaves of Physalis angulata. Compound 1 showed remarkable cytotoxicity in vitro against murine leukemia cell line P-388, epidermoid carcinoma of the nasopharynx KB-16 cells, and lung adenocarcinoma A-549 with ED(50) values of 0.048, 0.50 and 0.55 microg ml(-1), respectively.

Animals↗

Determination of cis and trans isomers of monocrotophos in technical products by reversed-phase column liquid chromatography.

A simple reversed-phase column liquid chromatographic method for the determination of cis and trans isomers of monocrotophos (MCP) using a C18 column, aqueous acetonitrile as eluent and UV detection at 218 nm was developed. The method was used for quality assurance and to study the relative stabilities of cis and trans isomers in technical products of MCP.

Chromatography, Liquid↗

The Th1/Th2 nature of concurrent immune responses to unrelated antigens can be independent.

We tested the independence hypothesis, namely that the Th1/Th2 nature of concurrent immune responses, generated in the same secondary lymphoid organ to non-cross-reacting Ags, can be independently determined. Some infectious agents and some adjuvants contain modulatory molecules that affect the Th1/Th2 nature of immune responses in a non-Ag-specific manner. We therefore excluded infectious agents as Ags and the use of adjuvants to generate immune responses. We first show that the dose of xenogeneic RBC administered i.v. determines the Th1/Th2 nature of the splenic immune response. Low doses generate a virtually exclusive Th1 response, whereas a higher dose induces either a mixed Th1/Th2 or a predominantly Th2 response, and stimulates the production of specific Abs. We immunized individual mice simultaneously with a low dose of one kind of xenogeneic RBC and with a higher dose of another non-cross-reacting xenogeneic RBC and assessed the Th1/Th2 nature of the immune responses generated in the spleen to each kind of RBC. The Th1/Th2 nature of the response to each RBC in doubly immunized mice was indistinguishable from that of the corresponding immune response in singly immunized mice. We discuss the significance of our findings for understanding immune class regulation, and the possible reasons why such independence is not always seen.

Adjuvants, Immunologic↗

A valid ELISPOT assay for enumeration of ex vivo, antigen-specific, IFNgamma-producing T cells.

We describe an ELISPOT technique for the detection of antigen specific IFNgamma-producing T cells. The technique is performed on spleen cells plated directly ex vivo into ELISPOT trays without an in vitro pre-culture step. Thus, the assay is likely to reflect the in vivo activity of the cells. We have found that very high cell densities (at least 10(6) cells/well) are required for optimal detection of spot forming cells, and only at a high density of cells is the number of spots detected linearly related to the number of primed cells plated. If lower numbers of antigen primed cells are used, then unprimed spleen cells from syngeneic mice can be added to the well to increase the cell density. Under these conditions, we find that the number of spots is linearly proportional to the number of primed cells plated, even if these are well below a million cells/well. Experiments with MHC congenic mice indicate that the high density of spleen cells required to obtain optimal spot formation reflects a requirement for an MHC restricted function, probably efficient antigen presentation to T cells. The formation of IFNgamma spots is antigen dependent and abrogated by depleting the antigen primed cells of T cells. We conclude that this linear assay can be used to efficiently detect ex vivo antigen-specific IFNgamma-producing T cells.

Animals↗

Renal disease and hypertension in non-insulin-dependent diabetes mellitus.

Recent epidemiologic data demonstrate a dramatic increase in the incidence of end-stage renal disease (ESRD) in patients with non-insulin-dependent diabetes mellitus (NIDDM), thus dispelling the mistaken belief that renal prognosis is benign in NIDDM. Currently, the leading cause of ESRD in the United States, Japan, and in most industrialized Europe is NIDDM, accounting for nearly 90% of all cases of diabetes. In addition to profound economic costs, patients with NIDDM and diabetic nephropathy have a dramatically increased morbidity and premature mortality. NIDDM-related nephropathy varies widely among racial and ethnic groups, genders and lifestyles; and gender may interact with race to affect the disease progression. While the course of insulin-dependent diabetes mellitus (IDDM) progresses through well-defined stages, the natural history of NIDDM is less well characterized. NIDDM patients with coronary heart disease have a higher urinary albumin excretion rate at the time of diagnosis and follow-up. This greater risk may also be associated with hypertension and hyperlipidemia, and genes involved in blood pressure are obvious candidate genes for diabetic nephropathy. Hyperglycemia appears to be an important factor in the development of proteinuria in NIDDM, but its role and the influence of diet are not yet clear. Tobacco smoking can also be deleterious to the diabetic patient, and is also associated with disease progression. Maintaining euglycemia, stopping smoking and controlling blood pressure may prevent or slow the progression of NIDDM-related nephropathy and reduce extrarenal injury. Treatment recommendations include early screening for hyperlipidemia, appropriate exercise and a healthy diet. Cornerstones of management should also include: (1) educating the medical community and more widely disseminating data supporting the value of early treatment of microalbuminuria; (2) developing a comprehensive, multidisciplinary team approach that involves physicians, nurses, diabetes educators and behavioral therapists; and (3) intensifying research in this field.

Diabetes Mellitus, Type 2↗

Blunt hepatic injury in adolescents: age makes a difference.

This analysis of mortality from blunt hepatic injury was performed to define outcome in the adolescent age group in relation to that recorded for children and adults. Children (age 0-10 years) were selected from a multi-institutional trauma registry, adults (age > or = 21 years) from the registry of a Level I trauma center, and adolescents (age 11-20 years) from both. Groups were compared by injury frequency, proportion of severe hepatic injuries (code 864.03 or 864.04 in the International Classification of Diseases, Adapted for Use in the United States 9-CM), immediate laparotomy, mortality, and cause of death. Children had the lowest proportion of severe injury and overall mortality. Torso trauma was the primary cause of death in only three children. Adolescent injury patterns were similar to those of adults in the proportion of severe visceral disruption and incidence of fatal torso trauma. Immediate laparotomy was employed almost twice as commonly in adults as in adolescents. The 64 per cent of adolescents who did not undergo laparotomy had a lower mortality than those who did. Conversely, the 36 per cent of adults without exploration had a significantly higher mortality, which usually occurred before laparotomy could be initiated. Increasing hepatic injury severity brought increasing mortality; however, the cause of death differed with age. Although the incidence of severe liver injury did not differ between adolescents and adults, management and outcome did. These data indicate that individualized management based on overall patient status remains the best approach to care of these injuries.

Adolescent↗

Use of erythropoietin, active vitamin D3 metabolites, and alkali agents in predialysis patients.

Studies in rats with renal ablation indicate that anemia lessens, whereas its vigorous correction with recombinant human erythropoietin (r-HuEPO) worsens systemic and glomerular hypertension, factors known to promote progression of chronic renal failure (CRF). However, in human studies, use of r-HuEPO in predialysis patients has not been associated with worsening renal function, provided blood pressure control is achieved. Histological evidence of bone disease is common in early renal failure, and deficits in calcitriol synthesis seem to be an important factor in the pathogenesis of secondary hyperparathyroidism (HPTH) in early CRF. Reports to data, on the use of low dose active vitamin D metabolites in predialysis patients, indicate either a reversible decline or no decline in renal function. Adynamic bone disease, however, may ensure during such therapy if excessive reductions in serum intact parathyroid hormone concentrations occur. Recent data suggest that chronic metabolic acidosis decreases albumin synthesis, increases muscle proteolysis, and induces negative nitrogen balance in patients with CRF. Despite these experimental data, the clinical relevance of correction of metabolic acidosis in end-stage renal disease (ESRD) is still not defined. Even though therapy of metabolic acidosis in the adult patient with CRF remains conjectural at this time, reports indicate that its correction might lead to healing of osteomalacia and osteopenia, and possibly may decrease protein degradation and improve growth in children with CRF.

Acidosis↗

Bulimia: implications for the practising dentist.

The incidence of eating disorders appears to be increasing, with the dental practitioner potentially being the first healthcare worker to make a diagnosis, due to the characteristic dental signs of tooth substance loss. It is therefore important that members of the dental team are aware of the dental sequelae of anorexia and bulimia and are able to offer advice and treatment to sufferers.

Anorexia↗

Death from pelvic fracture: children are different.

This study compares outcome from pelvic fractures in children with that of adults. Data for 23,700 children registered in the National Pediatric Trauma Registry (NPTR) were compared with those of 10,720 adults recorded over 5 years in the registry of our level I trauma center. Patients were categorized by open versus closed fracture and by fracture type as defined by a modification of the Key and Conwell system. Outcome was evaluated by mortality rate and incidence of fracture-induced fatal exsanguination. The 722 pelvic fractures recorded in the NPTR represent 3% of the population and is half the frequency represented by the 532 adults evaluated (P < .001). The overall mortality rate was 5% for children and 17% for adults. Two children died of fracture-related exsanguination; there were 18 such deaths among the adults. Pelvic ring disruption was encountered more commonly among adults, and was associated with a significantly higher mortality rate. Patients with initial hemodynamic instability were more likely to die, although children less so than adults. The authors conclude that children do not die of pelvic fracture-associated hemorrhage as often as adults. Massive blood loss in the child occurs most commonly from solid visceral injury rather than from pelvic vascular disruption.

Adult↗