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Articles by A. Weiss
Total Records ( 2 ) for A. Weiss
  A. Weiss , M. Boaz , Y. Beloosesky , R. Kornowski and E. Grossman
  Aims  Obesity is linked to increased morbidity and mortality risk in both the general population and in patients with diabetes mellitus; however, recent reports suggest that, in hospitalized elderly individuals, the association between body mass index (BMI) and mortality may be inverse. The present study sought to investigate the association between BMI and survival in hospitalized elderly individuals with diabetes mellitus.

Methods  The medical records of 470 patients (226 males, mean age of 81.5 ± 7.0 years) admitted to an acute geriatric ward between 1999 and 2000 were reviewed. Of the 140 patients with diabetes mellitus, 122 had more than 6 months of follow-up and were included in this analysis. Patients were followed up until 31 August 2004. Mortality data were extracted from death certificates.

Results  During a mean follow-up of 3.7 ± 1.6 years, 69 (56.6%) subjects died, 31 (25.4%) from cardiovascular causes. Those who died from any cause had lower baseline BMI than those who survived (24.0 ± 4.0 vs. 27.1 ± 4.3 kg/m2; < 0.0001). Similarly, those who died of cardiovascular causes had lower baseline BMI than those who did not (23.7 ± 3.6 vs. 25.9 ± 4.5, = 0.01). BMI was inversely associated with all-cause [relative risk (RR) 0.89, 95% confidence interval (CI) 0.83-0.96, P = 0.002] and cardiovascular death (RR 0.83, 95% CI 0.74-0.93, P = 0.002) even after controlling for age, sex, smoking, dyslipidaemia and reason for hospital admission.

Conclusions  In very elderly subjects with diabetes mellitus, increased BMI was associated with reduced mortality risk.

  L. Y Hsu , Y. X Tan , Z Xiao , M Malissen and A. Weiss

ZAP-70 is critical for T cell receptor (TCR) signaling. Tyrosine to phenylalanine mutations of Y315 and Y319 in ZAP-70 suggest these residues function to recruit downstream effector molecules, but mutagenesis and crystallization studies reveal that these residues also play an important role in autoinhibition ZAP-70. To address the importance of the scaffolding function, we generated a zap70 mutant mouse (YYAA mouse) with Y315 and Y319 both mutated to alanines. These YYAA mice reveal that the scaffolding function is important for normal development and function. Moreover, the YYAA mice have many similarities to a previously identified ZAP-70 mutant mouse, SKG, which harbors a distinct hypomorphic mutation. Both YYAA and SKG mice have impaired T cell development and hyporesponsiveness to TCR stimulation, markedly reduced numbers of thymic T regulatory cells and defective positive and negative selection. YYAA mice, like SKG mice, develop rheumatoid factor antibodies, but fail to develop autoimmune arthritis. Signaling differences that result from ZAP-70 mutations appear to skew the TCR repertoire in ways that differentially influence propensity to autoimmunity versus autoimmune disease susceptibility. By uncoupling the relative contribution from T regulatory cells and TCR repertoire during thymic selection, our data help to identify events that may be important, but alone are insufficient, for the development of autoimmune disease.

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