Interactions of human hMSH2 with hMSH3 and hMSH2 with hMSH6: examination of mutations found in hereditary nonpolyposis colorectal cancer

Mutations in the human mismatch repair protein hMSH2 have been found to cosegregate with hereditary nonpolyposis colorectal cancer (HNPCC). Previous biochemical and physical studies have shown that hMSH2 forms specific mispair binding complexes with hMSH3 and hMSH6. We have further characterized these protein interactions by mapping the contact regions within the hMSH2-hMSH3 and the hMSH2-hMSH6 heterodimers. We demonstrate that there are at least two distinct interaction regions of hMSH2 with hMSH3 and hMSH2 with hMSH6. Interestingly, the interaction regions of hMSH2 with either hMSH3 or hMSH6 are identical and there is a coordinated linear orientation of these regions. We examined several missense alterations of hMSH2 found in HNPCC kindreds that are contained within the consensus interaction regions. None of these missense mutations displayed a defect in protein-protein interaction. These data support the notion that these HNPCC-associated mutations may affect some other function of the heterodimeric complexes than simply the static interaction of hMSH2 with hMSH3 or hMSH2 with hMSH6.     

Growth, voluntary food intake and digestion in farmed temperate and tropical deer

Growth and voluntary feed intake (VFI) in grazing temperate farmed deer species are influenced by the feeding value of the forage and the stage of the deer's seasonal cycle. Liveweight gain (LWG) of growing red deer was greater when perennial ryegrass (0.80)/white clover (0.20) pasture was grazed at 10 cm than 5 cm surface height, but venison production by one year of age was still low. Chicory and red clover were of superior feeding value for deer than perennial ryegrass-based pastures, increasing LWG of young red and hybrid (0.25 elk; 0.75 red deer) deer during summer and autumn, due to higher VFI and to higher organic matter digestibility. Relative to perennial ryegrass, chicory disintegrated faster in the rumen, with very low rumination time and faster rumen outflow rates of liquid and particulate matter. Inputs of red clover and chicory substantially increased venison carcass weights at one year of age from grazing red and hybrid stags. In indoor pen feeding studies, red deer were shown to have a seasonal cycle of digestive function, with greater rumen mean retention time (MRT) and greater rates of rumen ammonia production in summer than in winter. It was deduced that the purpose of the digestive cycle was to maintain apparent digestibility constant as VFI increased during summer. Tropical sambar deer were also shown to have seasonal cycles in growth and VFI that were of reduced amplitude compared with red deer. Peak VFI and growth occurred in autumn and minimum VFI and growth occurred in spring. Feed conversion (kg DM eaten/kg LWG) was more efficient for sambar than for red deer, due to lower VFI and lower heat production, but there was no difference between species in digestive efficiency.     

Muscle mass and fat mass in relation to bone mineral density in very old men and women: the Framingham Heart Study

Aim of the study was investigate the cross-sectional relationship between body composition and bone mineral density (BMD) in very old men and women. The study sample consisted of 504 women and 285 men, aged 72-93 yr, participating in examination 22 (1992-1993) of the Framingham Heart Study. Total body BMD, regional BMD, and soft-tissue body composition was measured by dual-energy X-ray absorptiometry. Both muscle mass and percentage body fat were positively associated with total body BMD in women. After adjustment for age, physical activity, smoking status, estrogen use, and thiazide use, BMD increased with increasing tertile of muscle mass (p = 0.007) and with increasing tertile of percentage body fat (p = 0.0001) in women. In men muscle mass, not percentage body fat, was positively associated with BMD. After adjustment for potential confounders, BMD remained associated with muscle mass only (p = 0.02). These results were similar for leg BMD and arm BMD. The study suggests that the influence of muscle and fat mass on bone mineral density is different between very old men and women.     

Perioperative specific management of blood volume loss in craniosynostosis surgery

Accurate assessment and replacement of blood loss and fluid-electrolyte deficit during craniosynostosis repair is difficult owing to patient size and the diversity of surgical technique. Forty-three patients undergoing primary craniosynostosis repair over a 10-year period were studied retrospectively to determine blood loss and fluid deficit and to assess blood transfusion practices during both intraoperative and postoperative periods. Blood loss was calculated on the basis of estimated red cell mass (ERCM) and fluid-electrolyte imbalance was investigated with blood samplings. Blood transfusion was considered appropriate if the postoperative or posttransfusion ERCM was within 12% of the preoperative value. Estimated fluid requirement (EFR) was used in 4 ml kg(-1) h(-1) except for neonates. Intraoperatively, 80% of all patients were appropriately managed with respect to blood transfusion and EFR. Postoperatively only 20% of the patients receiving transfusions were transfused appropriately. In 23.3% of these patients (10/43) unexpected respiratory distress developed immediately after their recovery from the anesthesia. With the measurement of estimated blood volume and allowable blood loss, appropriate transfusion could be achieved for the successful treatment of the primary craniosynostosis.     

Designing the MPC105 PCI bridge/memory controller

The MPC105 peripheral component interconnection bridge/memory controller provides a platform-specification-compliant bridge between Power PC microprocessors and the PCI bus. With it, designers can create systems using peripherals already designed for a variety of standard PC interfaces. This bridge chip also integrates a secondary cache controller and high-performance memory controller that supports DRAM or synchronous DRAM and ROM or flash ROM     

Assessing disability after head injury: improved use of the Glasgow Outcome Scale

OBJECTIVE: The objective of this study was to assess somatic and inherited androgen receptor gene mutations in families with only one affected individual. METHODS: Molecular genetic analysis of the androgen receptor gene in DNA derived from blood leukocytes from 30 families with single-strand conformation analysis, direct sequencing, and restriction fragment analysis was performed. RESULTS: In 22 families the mothers and all investigated grandmothers were heterozygous carriers. However, within the sisters and aunts, both heterozygous carriers and noncarriers were present. In eight families a de novo mutation was characterized. In three of these patients indication for somatic mosaicism was found. CONCLUSIONS: De novo mutations occur at a high rate within the androgen receptor gene (8 of 30 = 26.7%); a high proportion (3 of 8) arise after the zygote stage. Thus only direct analysis of the underlying mutation of the androgen receptor gene in the proband and his or her family can provide the basis for genetic counseling.     

The synthesis of symmetrical and unsymmetrical P1/P1' cyclic ureas as HIV protease inhibitors

Cyclic urea SD146, a potent HIV protease inhibitor bearing a flat resistance profile, possessed poor solubility and bioavailability, which precluded further development of the compound. In an effort to improve upon the pharmacokinetic profile of the compound, several analogs modified at the P1/P1' residues were prepared and evaluated. Several of those compounds displayed significant improvement of physical properties.     

Optimization of signal detection in SPECT

Parallel-hole collimators of varying design are discussed, using the display signal-to-noise ratio of R.F. Wagner et al. (Med. Phys., vol.6, p.83-94, 1979) to obtain contrast-detail diagrams and analytical expressions for the signal-to-noise ratio in SPECT (single-photon-emission computed tomography). It is concluded: (1) that the detectability of deeply embedded small objects (more than ~10 cm deep) may be improved only slightly by improvements in the resolution and geometric efficiency of parallel-hole collimators; (2) that a long-bore collimator outperforms a low-energy general-purpose collimator for objects smaller than ~2 cm, but only to a minor degree; and (3) that for improvement of small object detectability by SPECT, the most fruitful technological pursuit would probably involve development of focused collimators.