Use of an intravascular T1 contrast agent to improve MR cine myocardial-blood pool definition in man

The feasibility of improving myocardial/blood pool contrast in MR cine images through use of an intravascular contrast agent (Ferumoxtran, Advanced Magnetics, Inc., Cambridge, MA) was tested in four subjects. The contrast-to-noise ratio (CNR) demonstrated a trend toward improvement in the short axis and improved significantly in the long axis cine by an average of 128% (P < .05). Image intensity gradients at the myocardial/blood pool interface increased significantly in both the short and long axis (P < .01). It is expected that larger image intensity gradients at the endocardial border should improve the capabilities of automated segmentation algorithms, reducing the uncertainty and need for manual editing.     

Recurrent gains of 1q, 8 and 12 in the Ewing family of tumours by comparative genomic hybridization

Comparative genomic hybridization (CGH) was used to detect copy number changes of DNA sequences in the Ewing family of tumours (ET). We analysed 20 samples from 17 patients. Fifteen tumours (75%) showed copy number changes. Gains of DNA sequences were much more frequent than losses, the majority of the gains affecting whole chromosomes or whole chromosome arms. Recurrent findings included copy number increases for chromosomes 8 (seven out of 20 samples; 35%), 1q (five samples; 25%) and 12 (five samples; 25%). The minimal common regions of these gains were the whole chromosomes 8 and 12, and 1q21-22. High-level amplifications affected 8q13-24, 1q and 1q21-22, each once. Southern blot analysis of the specimen with high-level amplification at 1q21-22 showed an amplification of FLG and SPRR3, both mapped to this region. All cases with a gain of chromosome 12 simultaneously showed a gain of chromosome 8. Comparison of CGH findings with cytogenetic analysis of the same tumours and previous cytogenetic reports of ET showed, in general, concordant results. In conclusion, our findings confirm that secondary changes, which may have prognostic significance in ET, are trisomy 8, trisomy 12 and a gain of DNA sequences in 1q.     

Passing of gallstones via the urethra: a complication of laparoscopic cholecystectomy

The phenotype of high K (HK) red blood cells, which is an autosomal recessive, was found in dog groups from 10 of 13 breeds or populations in Japan. The incidence of HK was 26 to 38% in the San'in-Shiba, Shinshu-Shiba and Akita breeds, and the gene frequencies of HK ranged from 0.513 to 0.612. The highest incidence (42%) was found in the Jindo breed from Korea, and the gene frequency was 0.652. Two other groups from Korea also possessed this HK variation. However, although HK cells were not found in dogs from Taiwan, Indonesia, Mongolia and Sakhalin, Russia, the HK phenotype is clearly distributed now throughout Japan and Korea.     

The HLA-DQ7 and -DQ8 associations in DR4-positive rheumatoid arthritis patients. A combined analysis of data available in the literature

Several different lines of evidence have demonstrated that inherited susceptibility to rheumatoid arthritis (RA) is associated with the DRB1 genes encoding the HLA-DR4 and HLA-DR1 molecules. A contrasting hypothesis has recently been proposed, suggesting that, in general, the DRB1 locus is associated with protection to RA and that the RA-associated DRB1 alleles are not responsible for the primary disease association but merely permissive for the susceptibility conferred by the HLA-DQ alleles with which they are in linkage disequilibrium. We have performed a critical review of the literature on the HLA association in RA with special emphasis on studies in which both an HLA-DR and -DQ association has been investigated. Our analyses provide strong evidence against the hypothesis that HLA-DQ molecules play a major role in the general susceptibility to RA. Thus, the strongest association in rheumatoid arthritis is with DRB1 genes rather than DQB1 genes.     

Unplanned pregnancy in Portugal

Cyclo 3 Fort is used in the treatment of chronic venous insufficiency. In this study, the effects of Cyclo 3 Fort, 2, 10 and 50 mg/kg, were studied in cheek pouch preparations from diabetic hamsters. The mean arteriolar diameter in animals receiving Cyclo 3 Fort, 10 and 50 mg/kg, was significantly greater than in control animals (p < 0.05), and the mean venule diameter was significantly lower in animals receiving the 50 mg/kg dose than in the control group. This suggests that Cyclo 3 Fort, 50 mg/kg/day, has a venotonic effect in diabetic animals. The venoarteriolar reflex was studied by measuring the internal diameter of arterioles during venular occlusion. The reflex was impaired in animals treated with either placebo or 2 mg/kg, but this was reversed by treatment with Cyclo 3 Fort, 10 and 50 mg/kg.     

Visualization of mitochondria with green fluorescent protein in cultured fibroblasts from patients with mitochondrial diseases

cDNAs for green fluorescent protein (GFP) and for a GFP fusion protein containing the presequence of human ornithine transcarbamylase (pOTC-GFP) were transfected into cultured human fibroblasts. GFP cDNA gave diffuse fluorescence throughout the cytoplasm and the nucleus, whereas pOTC-GFP cDNA gave mitochondria-associated fluorescence. Fluorescent mitochondrial structures could be classified into five patterns: thread-like mitochondria, fine thread-like ones, rod-like ones, granular ones, and granular ones with weak cytosolic fluorescence. pOTC-GFP mutants resulted in a loss of mitochondrial fluorescence and an appearance of weak fluorescence throughout the cytoplasm. pOTC-GFP cDNA was transfected into fibroblasts from patients with various mitochondrial diseases. Higher ratios of fibroblasts with granular mitochondria and those with fine thread-like ones were observed in a patient with Reye's syndrome and a patient with Kearns-Sayre syndrome. Weak cytosolic fluorescence was sometimes observed in fibroblasts from these patients. This method will be useful to analyze mitochondrial structural alterations and disorders of mitochondrial protein import.     

Pegylated peptides. V. Carboxy-terminal PEGylated analogs of growth hormone-releasing factor (GRF) display enhanced duration of biological activity in vivo

In the present study, human growth hormone-releasing factor (hGRF) and analogs were successfully pegylated at the carboxy-terminus using a novel solid- and solution-phase strategy. Following synthesis, these pegylated hGRF analogs were evaluated for in vitro and in vivo biological activity. Specifically, hGRF (1-29)-NH2, [Ala15]-hGRF (1-29)-NH2, [desNH2Tyr1, D-Ala2, Ala15]-hGRF(1-29)-NH2 and [His1, Val2, Gln8, Ala15, Leu27]-hGRF(1-32)-OH were each C-terminally extended using a Gly-Gly-Cys-NH2 spacer (previously demonstrated not to alter intrinsic biological activity), and then monopegylated via coupling to an activated dithiopyridyl-PEG reagent. PEG moieties of 750, 2000, 5000 or 10,000 molecular weight (MW) were examined to determine the effect of polymer weight on activity. Initial biological evaluations in vitro revealed that all C-terminally pegylated hGRF analogs retained high growth hormone (GH)-releasing potencies, regardless of the MW of PEG polymer employed. Two of these pegylated hGRF analogs, [desNH2Tyr1, D-Ala2, Ala15]-hGRF (1-29)-Gly-Gly-Cys(NH2)-S-Nle-PEG5000 and [His1, Val2, Gln8, Ala15, Leu27]-hGRF(1-32)-Gly-Cys(NH2)-S-Nle-PEG5000, were subsequently evaluated in both pig and mouse models and found to be highly potent (in vivo potency range = 12-55-fold that of native hGRF). Relative to their non-pegylated counterparts, these two pegylated hGRF analogs exhibited enhanced duration of activity.     

The use of laser and phototherapy in the comprehensive treatment of malignant tumors and leukemia in children

The report deals with the development of procedures, evaluation of laser application and prevention of complications involved in intensive chemoradiation therapy of neoplasms of hemopoietic and lymphoid tissue in childhood. The clinical data on 548 patients, aged 2 months-15 years, with leukemia and solid tumor were evaluated. Laser application for treatment of different complications of chemoradiation therapy of pediatric leukemia proved a valuable innovation. It had a pronounced antiinflammatory and analgetic effect, promoted tissue regeneration processes and cut down the duration of complication treatment drastically.