Differential effects of interleukin-4 in peptide induced autoimmunity

BALB/c mice immunized with multimeric DWEYSVWLSN develop IgG1 anti-DNA antibodies and glomerular immunoglobulin deposits, leading us to investigate the role of IL-4 in this model of antigen induced lupus. Splenocytes from DWEYSVWLSN immunized mice secreted IL-4 but not gamma-interferon. Following peptide immunization, IgG1 anti-peptide and anti-DNA antibodies were significantly higher in IL-4 wild type mice, while IgM and IgG3 anti-DNA levels were significantly higher in IL-4 knockout mice. Titers of IgG anti-laminin and anti-histone, but not anti-Sm/RNP and anti-cardiolipin antibodies, were significantly higher in the IL-4 wild type group. Glomerular immunoglobulin deposition was substantially decreased in IL-4 knockout mice. We conclude that while IL-4 does not materially affect the generation of some autoantibody responses associated with peptide induced autoimmunity, IL-4 deficiency inhibits kidney immunoglobulin deposition. The effect of IL-4 on humoral autoimmunity in lupus is complex, and is dependent on genetic background, the antigenic trigger and stage of disease.     

The management of incidental findings of reduction mammoplasty specimens

Reduction mammoplasty is one of the most commonly performed procedures in plastic surgery. Occasionally, there are findings reported by pathologists that are unfamiliar to the treating surgeon. The aim of the present study was to determine the types of pathologies encountered in reduction mammoplasty specimens. From this list of diagnoses, a best practice guideline for management will be organized to better assist plastic surgeons in the management of patients with incidental findings on pathology reports. A total of 441 pathology reports from patients who underwent bilateral or unilateral reduction mammoplasty in the past three years were identified. A list of 21 different pathologies was generated from the pathology reports, along with supplemental data from recent texts and articles. Occult carcinomas were encountered in two cases (0.45%) and high-risk lesions were found in three cases (0.68%) at the authors’ institution. An algorithm was then constructed to organize the pathologies according to risk of malignancy and assign them to a management guideline. There are many different lesions encountered incidentally in reduction mammoplasty specimens that may or may not confer some cancer risk. It is important for plastic surgeons to know which lesions need closer follow-up to provide the best care for their patients.     

Pharmacophore-based predictive model generation for potent antimalarials targeting haem detoxification pathway

Pharmacophore hypotheses were developed for molecules having antimalarial activities targeting the haem detoxification pathway of the malaria parasite. A training set consisting of 23 compounds was selected to generate these hypotheses, and their activities were evaluated for haem polymerization inhibition and against chloroquine-sensitive (3D7) as well as chloroquine-resistant (K1) strains of p. falciparum. The models were cross-validated by Fischer’s randomization test at a 95% confidence level. The model developed against chloroquine-resistant malaria parasites was found to yield the best predictions among the three models.     

EnteropathognicEscherichia coli diarrhea in hospitalized children at Delhi

Prevalence of enteropathogenicE. coli (EPEC) in 4178 cases of acute diarrhea in hospitalised children of <2 years old admitted during 1980–1985 was studied.E. coli in pure culture was obtained from 15·5% of the stool samples. Of the isolates 58·8% were typable, however, only 43·2% belonged to known EPEC serotypes. The commonest serotype, was 020 (21·1%), followed by 018 (20·7%), 026 (8·8%), 0119 (8·4%), 0125 (7·7%), 086 (6·1%) and others. Majority of the serotypes were obtained from males and in the age group >6–12 months.     

BAFF overexpression and accelerated glomerular disease in mice with an incomplete genetic predisposition to systemic lupus erythematosus

OBJECTIVE: To determine whether overexpression of BAFF can accelerate the development of systemic lupus erythematosus-associated end-organ disease in hosts with an underlying autoimmune diathesis. METHODS: We introduced a BAFF transgene (Tg) into autoimmune-prone B6.Sle1 and B6.Nba2 mice and evaluated these mice for serologic autoimmunity and renal pathology. RESULTS: B6.Sle1.BAFF and B6.Nba2.BAFF mice, but not non-Tg littermates, frequently developed severe glomerular pathology by 3 months of age. Age-matched B6.BAFF mice, despite renal Ig deposits and increases in B cells and Ig production similar to those in B6.Sle1.BAFF and B6.Nba2.BAFF mice, did not develop glomerular pathology. In B6.Sle1.BAFF and B6.Nba2.BAFF mice, severity of glomerular disease did not obligately correlate with circulating levels of IgG anti-chromatin and/or anti-double-stranded DNA antibodies or with amounts of these autoantibodies deposited in the kidneys. Even in mice with severe glomerular disease, renal tubulointerstitial infiltrates were very limited, and increased proteinuria was not detected. CONCLUSION: BAFF-driven effects on glomerular pathology may be mediated, at least in part, by autoantibodies with specificities other than chromatin and/or by autoantibody-independent means. There is an uncoupling of BAFF-driven precocious glomerular pathology from concomitant development of clinically apparent renal disease, strongly suggesting that BAFF overexpression works in concert with other factors to promote overt renal disease.     

Social inequalities and children's height in Trinidad and Tobago

OBJECTIVE: The aim of the study was to report the association of socio-economic factors with child's height. DESIGN: Cross-sectional study based on a representative national sample of government schools. SETTING: Trinidad and Tobago in 1999. SUBJECTS: A total of 2608 boys and girls mean age 5.8 y, range 4.38-6.99 y and 3080 mean age 8.6 y, range 7.00-10.44 y olds. OUTCOME: Measurement of height and a questionnaire completed by parents. In the analysis height was expressed as standard deviation scores (s.d.s.) based on the British height curves (1990) or height below -1.5 s.d.s. RESULTS: Ethnicity, parental heights, birthweight, maternal age at child's birth and number of children in the family were the main factors associated with children's height. Lack of piped water supply in the home was the only socio-economic factor consistently associated with height (mean difference in s.d.s. adjusted only for age group, gender and ethnicity -0.192, 95% CI -0.257 to -0.127 and in addition adjusted for the variables listed above -0.080, 95% CI -0.141 to -0.019). Parental education, household overcrowding and employment status were weakly associated with height in the partially adjusted model only. Analysis of severe growth failure gave similar results. CONCLUSION: The impact of socio-economic factors on height is marginal in Trinidad and Tobago. As socio-economic factors may have an impact on a broad range of health indicators, height and rates of undernutrition should not be used as sole criteria for assessing progress in decreasing health differentials caused by social inequalities.     

Cytotoxic cucurbitacin constituents from Sloanea zuliaensis

A new cucurbitacin D analogue, 2-deoxycucurbitacin D (1), as well as cucurbitacin D (2) and 25-acetylcucurbitacin F (3) were isolated from Sloanea zuliaensis. Compound 1 was found only in the young leaves of the plant and not in the mature leaves, and its structure was established using spectroscopic means. Compounds 1-3 demonstrated potent cytotoxic activity against breast (MCF-7), lung (H-460), and central nervous system (SF-268) human cancer cell lines.