Weekly doxorubicin in the treatment of patients with AIDS-related Kaposi''s sarcoma. AIDS Clinical Trials Group

It has been shown that the X-ray-sensitive Chinese hamster V79 mutants (V-E5, V-C4 and V-G8) are similar to ataxia-telangiectasia (A-T) cells. To determine whether the AT-like rodent cell mutants are defective in the gene homologous to A-T (group A, C or D), human chromosome 11 was introduced to the V-E5 and V-G8 mutant cells by microcell-mediated chromosome transfer. Forty independent hybrid clones were obtained in which the presence of chromosome 11 was determined by in situ hybridization. The presence of the region of chromosome 11q22-23 was shown by molecular analysis using polymorphic DNA markers specific for the ATA, ATC and ATD loci. Seventeen of the obtained monochromosomal Chinese hamster hybrids contained a cytogenetically normal human chromosome 11, but only twelve hybrid cell lines were shown to contain an intact 11q22-23 region. Despite the complementation of the X-ray sensitivity by a normal chromosome 11 introduced to A-T cells (complementation group D), these twelve Chinese hamster hybrid clones showed lack of complementation of X-ray and streptonigrin hypersensitivity. The observed lack of complementation does not seem to be attributable to hypermethylation of the human chromosome 11 in the rodent cell background, since 5-azacytidine treatment had no effect on the streptonigrin hypersensitivity of the hybrid cell lines. These results indicate that the gene defective in the AT-like rodent cell mutants is not homologous to the ATA, ATC or ATD genes and that the human gene complementing the defect in the AT-like mutants seems not to be located on human chromosome 11.     

Outcome of type I acute aortic dissection operated after 70 years of age. A retrospective study of operated dissection of the aorta in the over 70 years old]

OBJECTIVE: To evaluate the different short-term complications after in vitro fertilization and embryo transfer. DESIGN: a retrospective study on 7 years in the fertility clinic of an university hospital. MATERIALS AND METHODS: Short-term medical complications were analysed after 1500 transvaginal ultrasonographically guided oocyte retrievals. RESULTS: Ovarian hyperstimulation syndrome (1.8%), pelvic infections (0.4%), intraperitoneal bleeding (0.2%) and adnexal torsions (0.13%) were observed. One case of adnexal torsion occurred during pregnancy (0.18%). Two unusual case of bowel endometriosis were encountered (0.13%). CONCLUSIONS: Short-term medical complications after in vitro fertilization and embryo transfer are rare (2.8%). This contrast with the high rate of multifetal pregnancies which increases maternal and perinatal morbidity and mortality and must be considered as the major complication of in vitro fertilization treatment.     

Genomic footprinting of the yeast zinc finger protein Rme1p and its roles in repression of the meiotic activator IME1

The zinc finger protein Rme1p is a negative regulator of the meiotic activator IME1 in Saccharomyces cerevisiae . Prior studies have shown that Rme1p binds in vitro to a site near nt -2030 in the IME1 upstream region, but a genomic mutation in that site has little effect on repression of IME1 . To identify Rme1p binding sites in vivo , we have examined the binding of Rme1p to genomic sites through in vivo footprinting. We show that Rme1p binds to two sites in the IME1 upstream region, near nt -1950 and -2030. Mutations in both binding sites abolish repression of chromosomal IME1 by Rme1p, whereas a mutation in either single site causes partial derepression. Therefore, both Rme1p binding sites are essential for repression of IME1 . Prior studies have shown that repression by Rme1p depends upon RGR1 and SIN4 , which specify RNA polymerase II mediator subunits that are required for normal nucleosome density. We find that RGR1 and SIN4 are not simply required for Rme1p to bind to DNA in vivo . These results suggest that Rme1p functions directly as a repressor of IME1 and that Rgr1p and Sin4p are required for DNA-bound Rme1p to exert repression.     

Are current methods of measurement of erythropoietin (EPO) in human plasma or serum adequate for the diagnosis of polycythaemia vera and the assessment of EPO deficiency?

Current methodology for the immunoassay of erythropoietin (EPO) in human plasma or serum is reviewed, with an emphasis on measurement of EPO concentrations in the low and normal ranges, analytical interference and blood sampling requirements. In only 2 out of 8 research or in-house immunoassays reported since 1987 was there evidence that patients with polycythaemia vera (PV) could be identified, PV being an EPO-independent form of polycythaemia in which EPO concentrations are low in untreated cases. The same was true for only 1 out of 13 currently available kit methods. Remarkable differences in sample stability have been observed with different methods. Measurement of EPO in serum is recommended in most published articles. However, only EDTA plasma seems to be acceptable for the one generally available method with proven high diagnostic sensitivity for PV. It is concluded that most EPO assay methods have not been shown to be adequate for the measurement of the low EPO concentrations, and thus have poor diagnostic sensitivity for PV. It is inferred that they might not be appropriate to assess states of EPO deficiency. Only when a sufficiently sensitive diagnostic method becomes generally available will it be possible to define the various causes of low EPO concentrations. As in other fields of polypeptide hormone measurement, further developments in the field of EPO assay may be expected to be important in diagnostic medicine.     

A clinical evaluation of transdermal therapeutic system fentanyl for the treatment of cancer pain

PROBLEM: Circulating inflammatory cytokines have been implicated in the pathogenesis of preeclampsia. To test this hypothesis, we measured plasma levels of immunoreactive tumor necrosis factor (TNF)-alpha and -beta, interleukin (IL)-1 alpha and -beta, and IL-6 and -10 in women with preeclampsia, in women with transient gestational hypertension, and throughout normal pregnancy. METHOD OF STUDY: Enzyme-linked immunosorbent assays were used and subjected to extensive validation studies. RESULTS: The median concentration of plasma TNF-alpha was increased by twofold in women with preeclampsia compared with that in normal third-trimester pregnancy (P < 0.001) and in women with gestational hypertension (P < 0.04). The median concentration of plasma IL-6 was increased by threefold in women with preeclampsia compared with that in normal third-trimester pregnancy (P < 0.001) and increased twofold compared with that in women with gestational hypertension (P < 0.1). There were no significant differences observed in the levels of plasma IL-1 beta and IL-10 between the preeclamptic and other subject groups. The level of IL-1 beta, but not the levels of IL-10, TNF-alpha, or IL-6, was significantly changed during normal pregnancy compared with the nonpregnant condition manifesting an overall decline (P < 0.04). TNF-beta and IL-1 alpha were not detected in any samples, possibly because of the low sensitivity of these particular immunoassays. CONCLUSION: Elevated levels of TNF-alpha and IL-6 may contribute to the putative endothelial dysfunction of preeclampsia.