Studies on the effects of the antiandrogen cyproterone acetate on social encounters between pairs of male mice

An attempt was made in two experiments to reinvestigate the effects of the antiandrogen cyproterone acetate (CA) on mouse social behavior in a variety of ethologically-assessed paired encounters. The data confirm that CA reduces offense (threat and attack) in animals when both subjects receive the material but that CA has no such action in other pairings. This suggests that CA's major suppressive effect on "hostility" is expressed in mice via a reduction in "attack-promoting" pheromone production. Indeed, there was evidence in the more chronic study that CA, could augment (via a central mechanism?) offense in subjects paired with docile anosmic opponents. Changes in defense were largely responses to variations in the degree of attack to which animals were subjected. The antihormone also had actions on other aspects of behavior including sexual activity, social investigation and immobility in such tests. CA had a potent suppressive action on the weights of sex accessory glands. The data do not suggest that CA can be used as a specific antihostility agent.     

A survey and critical evaluation of a dual isotope (Dicopac) vitamin B12 absorption test

The results of all dual isotope tests (2142) carried out on 1989 patients, 807 males (40.6%) and 1182 females (59.4%), during a 10 year period (1976–1985 inclusive) in the Grampian Health Board Area (population 497,272) have been reviewed. Patient age ranged from 5–95 years with 45.5% over 60 years. The referring specialities were Gastroenterology (47.6%), Haematology (11.3%), Paediatries (2.1%) and all others (39.9%). According to the manufacturer's recommended criteria, results were classified as normal in 1054 (49.2%), abnormal in 659 (30.8%), equivocal in 337 (15.7%) and unsatisfactory in 92 (4.3%) tests. Vitamin B₁₂ malabsorption of ileal type was indicated in 544 tests (25.4%) and of gastric type in 115 (5.4%). Of the latter, 76 were related to pernicious anaemia, 10 to previous gastric surgery and 2 to gastric carcinoma. Of the 337 patients with equivocal results, 138 patients were reviewed and 115 (83.3%) found to have a documented cause for gastric malabsorption (96 pernicious anaemia and 19 previous gastric surgery). In 172 patients with proven pernicious anaemia the manufacturer's recommended criteria for gastric malabsorption were completely satisfied in only 76 (44.3%) but 167 (96.5%) had an excretion ratio 1.3 and 127 (73.8%) a ratio 1.7. Unsatisfactory tests were mainly due to incomplete urine collection (91.3%) or contamination with another isotope (5.4%).     

Automatic analysis of electro-encephalogram sleep spindle frequency throughout the night

A fully automatic method to analyse electro-encephalogram (EEG) sleep spindle frequency evolution during the night was developed and tested. Twenty allnight recordings were studied from ten healthy control subjects and ten sleep apnoea patients. A total of 22 868 spindles were detected. The overall mean spindle frequency was significantly higher in the control subjects than in the apnoea patients (12.5Hz against 11.7Hz, respectively; p<0.004). The proposed method further identified the sleep depth cycles, and the mean spindle frequency was automatically determined inside each sleep depth cycle. In control subjects, the mean spindle frequency increased from 12.0Hz in the first sleep depth cycle to 12.6Hz in the fifth cycle. No such increase was observed in the sleep apnoea patients. This difference in the spindle frequency evolution was statistically significant (p<0.004). The advantage of the method is that no EEG amplitude thresholds are needed.     

RELATIONSHIP OF HLA-DR EXPRESSION WITH REJECTION AND MONONUCLEAR CELL INFILTRATION IN RENAL ALLOGRAFT BIOPSIES

DNA methods have resulted in improved renal allograft survival rates in cadaveric renal transplantation. This paper describes the impact of DNA typing by PCR-SSP on a living-related renal transplant (LRRT) programme. It evaluates error rates in serology, acute rejections, graft function and survival rates between the two typing methods. Serological typing was carried out on CTS 120 antisera Class 1, 60 antisera Class 2, 72 antisera Terasaki Class 1 and 72 antisera Class 2 antigens. Low-resolution PCR-SSP typing was carried out by 24 primers for HLA-A, 48 for HLA-B and 24 for HLA-DR. Of the 585 transplants: 159 (Group I) were serology based; 172 were serology and PCR-SSP based for HLA-DR (Group II); and 254 were serology and PCR-SSP based for HLA-A and -B, and only PCR-SSP based for HLA-DR (Group III). Error rates in serology compared with PCR-SSP were 24% for HLA-A, 16% for HLA-B and 35% for HLA-DR. Acute rejections were 39%, 30% 26% in Groups I, II and III, respectively ( P= 0.02). Graft function of serum creatinine <1.5 mg/dl at 1 year was found in 26% of the Group I patients compared with 48% of those in Group III ( P <0.0001). One- and 3-year graft survival was 93% and 87% for Group II compared with 81% and 69% for Group I, respectively ( P= 0.0001). Matching by this combination of serology and PCR-SSP is not only economical for a developing country but also improves graft survival by 12% and 18% at 1 and 3 years, respectively.     

RGD-grafted thermoreversible polymers to facilitate attachment of BMP-2 responsive C2C12 cells

The purpose of this study was to design thermoreversible biomaterials for enhanced adhesion of bone morphogenetic protein-2 (BMP-2)-responsive cells. Peptides containing the arginine-glycine-aspartic acid (RGD) sequence were conjugated to N-isopropylacrylamide (NiPAM) polymers via amine-reactive N-acryloxysuccinimide (NASI) groups. In monolayer cultures, the adhesion of BMP-2-responsive C2C12 cells to RGD-grafted NiPAM/NASI surfaces was significantly higher than adhesion on ungrafted NiPAM/NASI surfaces. Although the morphology of cells adhered to RGD-grafted NiPAM/NASI surfaces was comparable to cells adhered on tissue culture polystyrene (TCPS), long-term cell growth was limited on the NiPAM/NASI surfaces, even for RGD-grafted surfaces. Treatment of C2C12 cells with recombinant BMP-2 induced dose-dependent osteoblastic differentiation as assessed by alkaline phosphatase (ALP) activity. In the absence of BMP-2, cells cultured on NiPAM/NASI polymers (either grafted with RGD peptide or not) expressed significantly higher levels of ALP activity than the cells cultured on TCPS, indicating that the polymer surfaces induced some osteoblastic activity in C2C12 cells without the need for BMP-2. We conclude that NiPAM-based thermoreversible biomaterials, despite their limited ability to support cell growth, allowed an enhanced expression of the chosen osteogenic marker (ALP) by C2C12 cells in vitro.     

Sensitivities of Human Monocytes and Epithelial Cells to Pneumolysin Are Different

The Streptococcus pneumoniae pore-forming toxin, pneumolysin, is an important virulence factor in pneumococcal pneumonia. The effect of pneumolysin on human lung epithelial and monocyte cell viability was compared. Pneumolysin caused a dose-dependent loss of viability of human lung epithelial (A549 and L132) and monocyte (U937 and THP-1) cell lines. Analysis of the dose-response curves revealed similar log 50% inhibitory concentration (pIC(50)) values for A549, L132, and THP-1 of 0.12+/- 0.1, 0.02+/- 0.04, and 0.12+/- 0.13 hemolytic units (HU), respectively, but U937 cells showed a significantly greater pIC(50) of 0.42+/- 0.12 HU. Differentiation of A549 and L132 with phorbol ester or THP-1 with gamma interferon had no effect on their sensitivity to pneumolysin. However, a significant decrease in the potency of pneumolysin against U937 cells followed gamma interferon treatment. The Hill slopes of the inhibition curves were greater than unity, indicating that pneumolysin may act with positive cooperativity. Analysis of pneumolysin-treated THP-1 cells by electron microscopy revealed membrane lesions of between 100 and 200 nm in diameter.     

Detection of Trisomy 12 and Centromeric Alterations in CLL by Interphase- and Metaphase-FISH

We have studied trisomy 12 in chronic lymphocytic leukemia (CLL) by fluorescence in situ hybridization (FISH) with an -satellite centromeric probe for chromosome 12 on both dividing and non-dividing cells. Trisomy for chromosome 12 was demonstrated in four of these patients (15.3%) using FISH on interphase cells. The percentage of trisomic cells ranged from 10% to 65% of nuclei. The hybridization signals in the trisomic and disomic nuclei were of a broadly similar size and nature. Interestingly, three of the remaining CLL patients, who exhibited disomy for chromosome 12, showed a marked difference in size of the hybridization signals in interphase nuclei. This was also demonstrated in metaphase spreads. In addition, metaphase FISH studies revealed a supernumerary marker chromosome in three out of 26 patients with CLL.     

Identification of two different mutations in the PDS gene in an inbred family with Pendred syndrome

Recently the gene responsible for Pendred syndrome (PDS) was isolated and several mutations in the PDS gene have been identified in Pendred patients. Here we report the occurrence of two different PDS mutations in an extended inbred Turkish family. The majority of patients in this family are homozygous for a splice site mutation (1143-2A-->G) affecting the 3' splice site consensus sequence of intron 7. However, two affected sibs with non-consanguineous parents are compound heterozygotes for the splice site mutation and a missense mutation (1558T-->G), substituting an evolutionarily conserved amino acid. The latter mutation has been found previously in two Pendred families originating from The Netherlands, indicating that the 1558T-->G mutation may be a common mutation.