M235T polymorphism of the angiotensinogen gene and hypertension in Chinese

OBJECTIVES: To compare the distributions of the genotypes and alleles of the M235T polymorphism of the angiotensinogen gene for hypertensive patients and normotensive controls. DESIGN: A study of association of genetic polymorphisms. SETTING: An outpatient clinic run by a university department handling referrals from primary care. PATIENTS: Two hundred and four subjects, 103 normal controls and 101 patients with newly diagnosed or documented hypertension. METHOD: Genomic DNA was extracted from peripheral blood leucocytes, amplified by polymerase chain reaction and digested with the restriction enzyme Tth 111 I. Methionine (M) and threonine (T) alleles were identified after electrophoresis. MAIN OUTCOME MEASURES: Prevalences of angiotensinogen genotypes and alleles for hypertensive patients and controls. Results: MM, TM and TT genotypes occurred in 3, 24 and 73% of controls and 1, 22 and 77% of hypertensive patients, respectively. The prevalences of the M and T alleles were 0.15 and 0.85 among controls and 0.12 and 0.88 among hypertensive patients. The prevalences of the angiotensinogen genotypes and alleles for controls and hypertensive patients did not differ significantly. CONCLUSIONS: Our findings differed from previous reports and suggested that this polymorphism is not associated with hypertension in this population.     

Statistical modeling of carcinogenic risks in dogs that inhaled 238PuO2

Combined analyses of data on 260 life-span beagle dogs that inhaled 238PuO2 at the Inhalation Toxicology Research Institute (ITRI) and at Pacific Northwest National Laboratory (PNNL) were conducted. The hazard functions (age-specific risks) for incidence of lung, bone and liver tumors were modeled as a function of cumulative radiation dose, and estimates of lifetime risks based on the combined data were developed. For lung tumors, linear-quadratic functions provided an adequate fit to the data from both laboratories, and linear functions provided an adequate fit when analyses were restricted to doses less than 20 Gy. The estimated risk coefficients for these functions were significantly larger when based on ITRI data compared to PNNL data, and dosimetry biases are a possible explanation for this difference. There was also evidence that the bone tumor response functions differed for the two laboratories, although these differences occurred primarily at high doses. These functions were clearly nonlinear (even when restricted to average skeletal doses less than 1 Gy), and evidence of radiation-induced bone tumors was found for doses less than 0.5 Gy in both laboratories. Liver tumor risks were similar for the two laboratories, and linear functions provided an adequate fit to these data. Lifetime risk estimates for lung and bone tumors derived from these data had wide confidence intervals, but were consistent with estimates currently used in radiation protection. The dog-based lifetime liver tumor risk estimate was an order of magnitude larger than that used in radiation protection, but the latter also carries large uncertainties. The application of common statistical methodology to data from two studies has allowed the identification of differences in these studies and has provided a basis for common risk estimates based on both data sets.     

Lysophosphatidylcholine acyltransferase activity in Saccharomyces cerevisiae: regulation by a high-affinity Zn2+ binding site

Variants of human pancreatic carboxypeptidase B (HCPB), with specificity for hydrolysis of C-terminal glutamic acid and aspartic acid, were prepared by site-directed mutagenesis of the human gene and expressed in the periplasm of Escherichia coli. By changing residues in the lining of the S1' pocket of the enzyme, it was possible to reverse the substrate specificity to give variants able to hydrolyse prior to C-terminal acidic amino acid residues instead of the normal C-terminal basic residues. This was achieved by mutating Asp253 at the base of the S1' specificity pocket, which normally interacts with the basic side-chain of the substrate, to either Lys or Arg. The resulting enzymes had the desired reversed polarity and enzyme activity was improved significantly with further mutations at residue 251. The [G251T,D253K]HCPB double mutant was 100 times more active against hippuryl-L-glutamic acid (hipp-Glu) as substrate than was the single mutant, [D253K]HCPB. Triple mutants, containing additional changes at Ala248, had improved activity against hipp-Glu substrate when position 251 was Asn. These reversed-polarity mutants of a human enzyme have the potential to be used in antibody-directed enzyme prodrug therapy of cancer.     

Right-hemispheric superiority in split-brain monkeys for learning and remembering facial discriminations

Twenty-six split-brain rhesus monkeys learned and remembered 8 go/no-go discriminations of monkey faces significantly better with the right hemisphere than with the left. Four discriminations required differentiating individual identity with expression held constant, and 4 required discriminating facial expression with identity held constant. There was no significant difference in the degree of laterality shown for these 2 types of problems. Female monkeys were more lateralized for learning to discriminate faces than were males. This sex difference in laterality was significant for learning but not for memory. Laterality for the facial discriminations was not significantly related to handedness of the monkeys. Overall, rhesus monkeys, like humans, show a right-hemispheric superiority for facial processing.     

Isolation and characterization of polyethylene wear debris associated with osteolysis following total shoulder arthroplasty

OBJECTIVE: As anorectic and bulimic patients present similar clinical and neurobiological symptoms, the purpose of this study was to compare brain glucose metabolism at rest in these patients. METHODS: Positron emission tomography with (18-F)-fluorodeoxyglucose was used to evaluate cerebral glucose metabolism (CMRglu) in 10 normal-weight bulimic women, in 10 underweight anorectic patients, and in 10 age- and sex-matched healthy volunteers. RESULTS: Absolute global cortical glucose activity was significantly lower in anorectic patients compared with bulimic and control subjects. Anorectic patients compared with normal control subjects also showed higher relative CMRglu in the inferior frontal cortex and in the basal ganglia, and putamen and caudate relative hypermetabolism when compared with bulimic patients. Thus, both eating disorder groups differed from control subjects in low relative parietal values of glucose. DISCUSSION: While absolute global metabolism seems to be related to weight loss, we can hypothesize either a common parietal cortex dysfunction in eating disorders or a particular sensitivity of this cortex to consequences of eating disturbances.