Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.     

Hemorrhagic and nonhemorrhagic brain lesions: evaluation with 0.35-T fast MR imaging

Two fast magnetic resonance (MR) imaging techniques, advanced Fourier and partial-flip imaging, were used at 0.35 T to examine 21 patients with suspected intracranial lesions; the results were quantitatively compared with a conventional spin-echo study. Both of the fast MR techniques yielded a fourfold reduction in imaging time per section. The advanced Fourier sequence showed contrast that was identical to the conventional spin-echo study with signal-to-noise ratios of 58% and 57% for the first and second echoes, respectively. The partial-flip sequence showed a contrast of 109% and 57% for lesions versus substantia alba, and 107% and 78% for substantia grisea versus substantia alba relative to the first and second echoes of the conventional spin-echo study. The partial-flip sequence was particularly sensitive to magnetic susceptibility; this produced artifacts that may undermine the usefulness of partial flip for routine screening in certain parts of the brain. However, this susceptibility significantly improved the detection of intracranial hemorrhage when compared with the spin-echo sequence, particularly when combined with phase mapping of the partial-flip study.     

Effects of metyrapone on hypothalamic-pituitary-adrenal axis and sleep in women with post-traumatic stress disorder.

BACKGROUND: Metyrapone blocks cortisol synthesis which results in removal of negative feedback, a stimulation of hypothalamic corticotropin releasing factor (CRF) and a reduction in delta sleep. We previously reported a diminished delta sleep and hypothalamic-pituitary-adrenal (HPA) response to metyrapone in men with post-traumatic stress disorder (PTSD). In this study, we aimed to extend these findings to women. METHODS: Three nights of polysomnography were obtained in 17 women with PTSD and 16 controls. On day 3, metyrapone was administered throughout the day up until bedtime. Plasma adrenocorticotropic hormone (ACTH), cortisol, and 11-deoxycortisol were obtained the morning following sleep recordings the day before and after metyrapone administration. RESULTS: There were no significant between-group differences in hormone concentration and delta sleep at baseline. Relative to controls, women with PTSD had decreased ACTH and delta sleep responses to metyrapone. Decline in delta sleep was associated with the magnitude of increase in ACTH across groups. CONCLUSIONS: Similar to our previous findings in men, the ACTH and sleep electroencephalogram response to metyrapone is attenuated in women with PTSD. These results are consistent with a model of downregulation of CRF receptors in an environment of chronically increased CRF activity or with enhanced negative feedback regulation in PTSD.     

Genetic linkage of the tricho-dento-osseous syndrome to chromosome 17q21

Tricho-dento-osseous syndrome (TDO), MIM# 190320, is transmitted as a highly penetrant autosomal dominant trait that is characterized by variable clinical expression. The principal clinical features include kinky/curly hair in infancy, enamel hypoplasia, taurodontism, as well as increased thickness and density of cranial bones. Possible genetic linkage has been reported for TDO with the ABO blood group locus, but the gene defect remains unknown. We have identified four multiplex families (n = 63, 39 affected, 24 unaffected) from North Carolina segregating TDO. We previously have excluded a major locus for TDO in the ABO region for these families. Utilizing a genome-wide search strategy, we obtained conclusive evidence for linkage of the TDO syndrome locus to markers on chromosome 17q21 (D17S791, Z max = 10.54, Theta = 0.00) with no indication of genetic heterogeneity. Multipoint analysis suggests the TDO locus is located in a 7 cM chromosomal segment flanked by D17S932 and D17S941. This finding represents the first step towards isolation and cloning of the TDO gene. Identification of this gene has important implications for understanding normal and abnormal craniofacial development of hair, teeth and bone.      

Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy

The Bethlem myopathy is a rare autosomal dominant proximal myopathy characterized by early childhood onset and joint contractures. Evidence for linkage and genetic heterogeneity has been established, with the majority of families linked to 21q22.3 and one large family linked to 2q37, implicating the three type VI collagen subunit genes, COL6A1 (chromosome 21), COL6A2 (chromosome 21) and COL6A3 (chromosome 2) as candidate genes. Mutations of the invariant glycine residues in the triple-helical domain-coding region of COL6A1 and COL6A2 have been reported previously in the chromosome 21-linked families. We report here the identification of a G-->A mutation in the N-terminal globular domain-coding region of COL6A3 in a large American pedigree (19 affected, 12 unaffected), leading to the substitution of glycine by glutamic acid in the N2 motif, which is homologous to the type A domains of the von Willebrand factor. This mutation segregated to all affected family members, to no unaffected family members, and was not identified in 338 unrelated Caucasian control chromosomes. Thus mutations in either the triple-helical domain or the globular domain of type VI collagen appear to cause Bethlem myopathy.      

Beckman EL-ISE电解质分析仪准确性及故障的分析判断

0 引言为了克服离子选择电极（ISE）法的微量电位信号极易受环境温度变化及电子噪声的干扰问题,该仪器采用了参考电极,把参考电极与其测定电极装在同一测量室内,保持其相同的物理环境,使干扰源对所有电极的影响相同. 以内参液作为参考电极的测量对象,测得一个参考电极电位值,再测样品的电极电位值,二者相抵就消除了所叠加的干扰信号.     

Sirolimus reduces the incidence of acute rejection episodes despite lower cyclosporine doses in caucasian recipients of mismatched primary renal allografts: a phase II trial. Rapamune Study Group

BACKGROUND: The novel agent sirolimus (SRL; Rapamune; rapamycin) inhibits the immune response by a mechanism distinct from those of calcineurin antagonists or antimetabolites. This randomized, controlled, multicenter, single blind, phase II trial examined the combination of SRL, steroids, and full versus reduced doses of cyclosporine (CsA) for prophylaxis of acute renal allograft rejection. METHODS: A total of 149 recipients of mismatched cadaveric- or living-donor primary renal allografts were randomized into six groups. Three groups received placebo or 1 or 3 mg/m2/day SRL, as well as steroids and full-dose CsA (Sandimmune). Three groups received steroids, reduced-dose CsA (target trough level 50% of full-dose range), and 1, 3, or 5 mg/m2/day SRL. RESULTS: The incidence of biopsy-proven acute rejection episodes within the first 6 months after transplant was reduced from 32.0% in the control group to 8.5% in patients receiving SRL (1 or 3 mg/m2/day) and full-dose Sandimmune CsA (P=0.018). Similar low rates of acute rejection episodes were observed among non-African-Americans, but not African-Americans, treated with SRL and reduced-dose Sandimmune CsA. Despite the augmented immunosuppression, 1-year patient and graft survival rates did not differ significantly across groups. Adverse effects attributable to CsA, including hypertension and new-onset diabetes mellitus, were not exacerbated by SRL. Except for an increased incidence of pneumonia among patients receiving full-dose CsA and 3 mg/m2/day SRL, the incidences of opportunistic infections were similar in all treatment groups. Although SRL produced more frequent, but reversible, hematological and lipid abnormalities, it had no apparent nephrotoxic effects to exacerbate CsA-induced renal dysfunction. CONCLUSIONS: SRL in combination with CsA and steroids not only lowers the incidence of biopsy-proven acute renal allograft rejection episodes, but also may permit CsA sparing, at least among Caucasian patients, without an increased risk of rejection.     

Delta sleep response to metyrapone in post-traumatic stress disorder.

Metyrapone blocks cortisol synthesis, which results in the stimulation of hypothalamic cortiocotropin-releasing factor (CRF) and a reduction in delta sleep. We examined the effect of metyrapone administration on endocrine and sleep measures in male subjects with and without chronic PTSD. We hypothesized that metyrapone would result in a decrease in delta sleep and that the magnitude of this decrease would be correlated with the endocrine response. Finally, we utilized the delta sleep response to metyrapone as an indirect measure of hypothalamic CRF activity and hypothesized that PTSD subjects would have decreased delta sleep at baseline and a greater decrease in delta sleep induced by metyrapone. Three nights of polysomnography were obtained in 24 male subjects with combat-related PTSD and 18 male combat-exposed normal controls. On day 3, metyrapone was administered during normal waking hours until habitual sleep onset preceding night 3. Endocrine responses to metyrapone were measured in plasma obtained the morning following sleep recordings, the day before and after administration. Repeated measures ANOVAs were conducted to compare the endocrine and sleep response to metyrapone in PTSD and controls. PTSD subjects had significantly less delta sleep as indexed by stages 3 and 4, and total delta integrated amplitude prior to metyrapone administration. There were no differences in premetyrapone cortisol or ACTH levels in PTSD vs controls. PTSD subjects had a significantly decreased ACTH response to metyrapone compared to controls. Metyrapone caused an increase in awakenings and a marked decrease in quantitative measures of delta sleep that was significantly greater in controls compared to PTSD. The decline in delta sleep was significantly associated with the magnitude of increase in both 11-deoxycortisol and ACTH. The results suggest that the delta sleep response to metyrapone is a measure of the brain response to increases in hypothalamic CRF. These data also suggest that the ACTH and sleep EEG response to hypothalamic CRF is decreased in PTSD.