Erythroid failure in Diamond-Blackfan anemia is characterized by apoptosis

Programmed cell death, also known as apoptosis, is frequently initiated when cells are deprived of specific trophic factors. To investigate if accelerated apoptosis contributes to the pathogenesis of Diamond- Blackfan anemia (DBA), a rare pure red blood cell aplasia of childhood, we studied the effect of erythropoietin (epo) deprivation on erythroid progenitors and precursors from the bone marrow of DBA patients as compared with hematologically normal controls. Apoptosis in response to epo deprivation was evaluated by enumeration of colony-forming unit- erythroid (CFU-E)- and burst-forming unit-erythroid (BFU-E)-derived colonies in plasma clot semisolid culture and by the identification of typical DNA oligosomes by gel electrophoresis from marrow mononuclear cells in liquid culture. In all DBA patients there was a marked decrease in CFU-E- and BFU-E-derived colony formation compared with normal controls at comparable time points of epo deprivation, with a complete loss of CFU-E-derived colonies in semisolid culture by 9 hours of epo deprivation versus 48 hours in controls. The BFU-E-derived colony response to epo deprivation displayed a similar pattern of decrement. Apoptotic changes assessed by the presence of characteristic DNA fragmentation began in the absence of epo deprivation and were readily detected within 3 hours of epo deprivation in DBA cultures versus 9 hours in controls. We conclude that DBA is characterized by accelerated apoptosis as measured by the loss of erythroid progenitor clonogenicity and increased progenitor and precursor DNA fragmentation leading to the formation of characteristic oligosomes, consistent with an intrinsic erythroid-progenitor defect in which increased sensitivity to epo deprivation results in erythroid failure.     

A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras-transformed rat intestinal epithelial cells

BACKGROUND & AIMS: Constitutive expression of cyclooxygenase 2 (COX-2) has been found in 85% of colorectal cancers. Ras mutations are found in 50% of colorectal adenocarcinomas. The aim of this study was to determine the role of COX-2 in ras-induced transformation in rat intestinal epithelial (RIE) cells. METHODS: Cell growth was determined by cell counts. The expression of COX-2 was examined by Northern and Western analyses. For tumorigenicity assays, cells were inoculated into dorsal subcutaneous tissue of athymic nude mice. DNA-fragmentation assays were performed to detect apoptosis. RESULTS: The expression of COX-2 was increased in RIE-Ras cells at both messenger RNA (9-fold) and protein (12-fold) levels. Prostaglandin I2 levels were elevated 2.15-fold in RIE-Ras cells. Serum deprivation further increased COX-2 expression 3.8-fold in RIE-Ras cells. Treatment with a selective COX-2 antagonist (SC58125) inhibited the growth of RIE-Ras cells through inhibition of cell proliferation and by induction of apoptosis. SC-58125 treatment reduced the colony formation in Matrigel by 83.0%. Intraperitoneal administration of SC-58125 suppressed RIE-Ras tumor growth in nude mice by 60.3% in 4 weeks. SC-58125 treatment also induced apoptosis in RIE-Ras cells as indicated by increased DNA fragmentation. CONCLUSIONS: Overexpression of COX-2 may contribute to tumorigenicity of ras-transformed intestinal epithelial cells. Selective inhibition of COX-2 activity inhibits growth of ras-transformed intestinal epithelial cells and induces apoptosis. (Gastroenterology 1997 Dec;113(6):1883-91)     

An analysis of nodular deposits on soft contact lenses.

Approximately 6.8 percent of soft contact lens wearers develop multiple nodular deposits on the front surface of their soft contact lenses. It was the purpose of this investigation to evaluate the role of calcium in the newly formed and mature deposits. Nodular deposits were examined using scanning electron microscopy and Energy Dispersive X-ray (EDX) analysis for calcium content. Any deposit which did not demonstrate the presence of calcium was sectioned, and the individual section re-examined by EDX analysis. Our results indicate that calcium was present in all but three of 72 nodular deposits investigated. The calcium was finely distributed throughout the deposits in a non-crystalline pattern, especially in the basal layers. Sections of the deposits also were examined at the light microscope level for the presence of lipids, calcium, and polysaccharides (mucin). All deposits stained positively for lipids, but polysaccharides were more evident in newer deposits. These results may indicate that both calcium and polysaccharides are involved in the genesis of nodular deposits.     

Selecting a database for literature searches in nursing: MEDLINE or CINAHL?

This study compares the usefulness of the MEDLINE and CINAHL databases for students on post-registration nursing courses We searched for nine topics, using title words only Identical searches of the two databases retrieved 1162 references, of which 88% were in MEDLINE, 33% in CINAHL and 20% in both sources The relevance of the references was assessed by student reviewers The positive predictive value of CINAHL (70%) was higher than that of MEDLINE (54%), but MEDLINE produced more than twice as many relevant references as CINAHL The sensitivity of MEDLINE was 85% (95% CI 82–88%), and that of CINAHL was 41% (95% CI 37–45%) To assess the ease of obtaining the references, we developed an index of accessibility, based on the holdings of a number of Irish and British libraries Overall, 47% of relevant references were available in the students' own library, and 64% could be obtained within 48 hours There was no difference between the two databases overall, but when two topics relating specifically to the organization of nursing were excluded, references found in MEDLINE were significantly more accessible We recommend that MEDLINE should be regarded as the first choice of bibliographic database for any subject other than one related strictly to the organization of nursing     

Juvenile amyopathic dermatomyositis

We report a 15-year-old girl with a 10-year-old history of typical skin features of dermatomyositis (DM) without evidence of muscle involvement. Amyopathic dermatomyositis(ADM) is defined by the presence of biopsy confirmed classic cutaneous findings of dermatomyositis in the absence of any clinical or laboratory signs of muscle disease for at least 2 years after onset of skin pathology. To exclude muscle involvement muscle enzymes should be normal; moreover additional use of magnetic resonance imaging and muscle ultrasound is currently being proposed. It is as yet undetermined. whether early aggressive immunosuppressive treatment of ADM might prevent the development of myositis at a later date or influence the course of the skin disease. In a paediatric patient with ADM we advocate a more expectant attitude with careful and regular monitoring for possible development of muscle disease.     

Factors that may explain interstate differences in certificate-of-need decisions.

A major difficulty in conducting studies of the impact of certificate-of-need programs is in accounting for interstate differences in program characteristics. This paper addresses this problem by examining the empirical relationship between various characteristics of certificate-of-need programs and program decisions, measured in terms of the approvals of hospital capital projects. Aggregate data on capital expenditure approvals and net bed change approvals for 28 States are correlated with an index of each State's regulatory characteristics that was developed in an earlier study. In addition, a multivariate model of certificate-of-need approvals is estimated in which certain measures associated with the need for hospital capital in a State are introduced, along with the indices of regulatory characteristics, to explain interstate differences in regulatory characteristics, to explain interstate differences in program decisions. The results of this analysis indicate that although regulatory characteristics are significantly correlated with the relative number of new beds approved, they have little correlation with total capital expenditure approvals. Moreover, variables reflecting the need for new hospital capital in a State, such as past population growth and existing hospital capacity, appear to be more important than regulatory characteristics in explaining the relative amount of capital approvals.