CTLA-4 is required for the induction of high dose oral tolerance

Mucosal and systemic administrations of high dose antigens induce long- lasting peripheral T cell tolerance. We and others have shown that high dose peripheral T cell tolerance is mediated by anergy or deletion and is preceded by T cell activation. Co-stimulatory molecules B7-1 (CD80)/B7-2 (CD86) and their counter-receptors CD28/CTLA-4 play pivotal roles in T cell activation and immune regulation. In the present study, we examined the roles of the B7 co-stimulation pathway in the generation of high dose peripheral T cell tolerance. We found that blocking B7:CD28/CTLA-4 interaction at the time of tolerance induction partially prevented T cell tolerance, whereas selective blockade of B7:CTLA-4 interaction completely abrogated peripheral T cell tolerance induced by either oral or i.p. antigens. These results suggest that CTLA-4-mediated feedback regulation plays a crucial role in the induction of high dose peripheral T cell tolerance.      

Activation of apoptosis associated with enforced myc expression in myeloid progenitor cells is dominant to the suppression of apoptosis by interleukin-3 or erythropoietin

The inappropriate expression of c-myc in cells deprived of growth factors has recently been implicated in the activation of programmed cell death (apoptosis). The studies described here examine the ability of interleukin-3 (IL-3) or erythropoietin (Epo) to suppress apoptosis that occurs in association with enforced myc expression during cell cycle arrest of a murine IL-3-dependent myeloid progenitor cell line, 32D. G1 arrest was observed when culturing 32D cells to high density in medium supplemented with IL-3, or at subconfluent densities in medium supplemented with Epo. Under both conditions, endogenous c-myc expression was downregulated and viability was maintained. In clones of cells in which c-myc is constitutively expressed from a retroviral vector, enforced c-myc expression was associated with the activation of apoptosis at high cell densities. Similarly, enforced c-myc expression was deleterious to cell survival when these cells were cultured in Epo, as apoptosis was evident within 6 hours. The results support the concept that inappropriate c-myc expression activates apoptosis and that neither IL-3 nor Epo can suppress this program under these conditions.     

Accuracy of the precordial V-Quick patch in persons with cardiac or pulmonary disease

The aim of this study was to demonstrate the equivalence of 12-Lead Electrocardiograms (EKG) obtained with the new V-Quick patch and traditional tab-style electrodes. Using a within-subject design, a convenience sample of 100 subjects with either cardiac or pulmonary disease underwent two 12-lead EKGs, one with the traditional tab-style electrodes and one with the precordial patch. Computer-generated measurements of waveform axes and amplitude were obtained for both EKGs. Comparison of mean and 95% confidence intervals revealed no significant differences in Q, R or S wave amplitude across the six precordial leads. Furthermore, a four-factor ANOVA found no significant difference (p > 0.05) in the Q, R and S wave amplitude between the type of electrode, gender and type of disease. A subset of 29 EKGs read by three experts found intra- (.90) and inter-rater (.84) reliability to be strong. In conclusion, the precordial V-Quick patch provided equivalent EKGs to those obtained using standard tab-style electrodes.     

Guideline recommendations for treatment of schizophrenia: the impact of managed care

BACKGROUND: Medicaid-managed care has been shown to reduce the number and length of psychiatric hospitalizations, but little is known about the clinical and social consequences of such managed care programs. The purpose of this study was to compare the treatment of schizophrenia for disabled Medicaid beneficiaries who were and were not enrolled in managed care. METHODS: This was a prospective observational study of patients who sought care for a psychiatric crisis from June 7, 1997, to May 13, 1999. Patients were followed up for 6 months. Inpatient and outpatient mental health facilities in Massachusetts were studied. The participants included 420 adult Medicaid beneficiaries, aged 24 to 64 years, who were treated for schizophrenia; 784 eligible beneficiaries were originally contacted and invited to participate (53.6% response). A private managed behavioral health care organization administered the Medicaid mental health benefit for about half the patients in the study. The other half were enrolled in the dually insured fee-for-service Medicare/Medicaid plan. The main outcome measures were adherence to the Schizophrenia Patient Outcomes Research Team treatment recommendations from inpatient and outpatient medical records, self-reported quality of interpersonal interactions between patient and clinician, self-reported care experiences and outcomes, and clinician-reported outcomes. RESULTS: There were no differences between the managed care plan and the unmanaged fee-for-service plan in adherence to the schizophrenia treatment guidelines. However, much outpatient care in both programs was inconsistent with treatment guidelines. Inpatient treatment was far more likely to conform to guidelines than outpatient treatment. Patient ratings of their care were positive and not different between plans. Clinical outcome and health-related quality of life were not different between plans. CONCLUSIONS: A major change in Massachusetts in the way mental health care is organized and financed had neither a negative nor a positive effect on care quality. However, adherence to nationally accepted guidelines for care was only modest, suggesting a need to improve the delivery of treatment to the most disabled highest-risk adults with schizophrenia.     

Childhood autoimmune cytopenia secondary to unsuspected common variable immunodeficiency

Immune thrombocytopenic purpura and autoimmune hemolytic anemia are typically idiopathic processes without underlying systemic illness. Four children with autoimmune cytopenia had low immunoglobulin levels that led to the diagnosis of common variable immunodeficiency. Routine screening of immunoglobulins is suggested for children with chronic or recurrent immune thrombocytopenic purpura and autoimmune hemolytic anemia.     

Elevated sperm chromosome aneuploidy and apoptosis in patients with unexplained recurrent pregnancy loss

OBJECTIVE: To evaluate sperm chromosome aneuploidy and semen quality in 24 partners of women with unexplained recurrent pregnancy loss and to analyze the data in relation to sperm apoptosis data. METHODS: Semen quality parameters and sperm chromosome aneuploidy for chromosomes X, Y, 13, 18, and 21 were evaluated in the recurrent pregnancy loss patients, fertile controls, and a control group of men from the general population. RESULTS: The mean aneuploidy rate in the recurrent pregnancy loss group was 2.77 +/- 0.22, significantly higher (P <.005) than in either the general population (1.48 +/- 0.12) or in fertile (1.19 +/- 0.11) control groups. In the recurrent pregnancy loss patients, the percentage of aneuploid sperm was correlated to the percentage of apoptotic sperm (r =.62, P <.001). Normal morphology was diminished in the patient group, compared with the general population group (P <.01) and the donor group (P <.001). CONCLUSIONS: These data indicate that some recurrent pregnancy loss patients have a significant increase of sperm chromosome aneuploidy, apoptosis, and abnormal sperm morphology. This study demonstrates a new possible cause of recurrent pregnancy loss.