Characterization of type I 5 alpha-reductase activity in DU145 human prostatic adenocarcinoma cells

Each amino acid is represented by a vector of numerical measurements for the attributes of volume, area, hydrophilicity, polarity, hydrogen bonding, shape, and charge. Inter-residue distances are then calculated according to common metrics, and we introduce a new clustering objective function derived from information-theoretic considerations. The arguments of the function are the inter-object distances of the things to be clustered: in this case the amino acids. By means of approximating the solution of an integer programming problem, then, the residues are partitioned into clusters. The clusters obtained are compared with groups obtained in substitution/mutation studies and found to be similar. Thus, probably the strongest and most objective evidence to date is supplied for believing that physico-chemical properties account for the viability of substitutions and that the important similarities/differences are explained by a relatively small and simple set of properties.     

Measurement error and results from analytic epidemiology: dietary fat and breast cancer

BACKGROUND: International correlational analyses have suggested a strong positive association between fat consumption and breast cancer incidence, especially among post-menopausal women. However, case-control studies have been taken to indicate a weaker association, and a recent, pooled cohort analysis reported little evidence of an association. Differences among study results could be due to differences in the populations studied, differences in the control for total energy intake, recall bias in the case-control studies, and dietary measurement error biases. Existing measurement error models assume either that the sample data used to validate dietary self-report instruments are without measurements error or that any such error is independent of both the true dietary exposure and other study subject characteristics. However, growing evidence indicates that total energy and, presumably, both total fat and percent energy from fat are increasingly underreported as percent body fat increases. PURPOSE: A relaxed dietary measurement model is introduced that allows all measurement error parameters to depend on body mass index (weight in kilograms divided by the square of height in meters) and incorporates a random underreporting quantity that applies to each dietary self-report instrument. The model was applied to results from international correlational analyses to determine whether the differing associations between dietary fat and postmenopausal breast cancer can be explained by measurement errors in dietary assessment. METHODS: The relaxed measurement model was developed by use of data on total fat intake and percent energy from fat from 4-day food records (4DFRs) and food-frequency questionnaires (FFQs) from the original Women's Health Trial. This trial was a randomized, controlled, feasibility study of a low-fat dietary intervention carried out from 1985 through 1988 in Cincinnati (OH), Houston (TX), and Seattle (WA) among 303 women (184 intervention and 119 control) who were 45-69 years of age. The relaxed model was used to project results from the international correlational analyses onto 4DFR and FFQ fat-intake categories. RESULTS AND CONCLUSIONS: If measurement errors in dietary assessment are overlooked entirely, the projected relative risks (RRs) for breast cancer based on the international data vary substantially across percentiles of total fat intake. The projected RR for the 90% versus the 10% fat-intake percentile is 3.08 with the 4DFR and 4.00 with the FFQ. If random (i.e., noise) aspects of measurement error are acknowledged, the projected RR for the same comparison is reduced to 1.54 with the 4DFR and 1.42 with the FFQ. If both systematic and noise aspects of measurement error are acknowledged, the projected RR is reduced to about 1.10 with either instrument. Acknowledgment of measurement error also leads to a projected RR of about 1.10 for the 90% versus the 10% percentile of percent energy from fat with either dietary instrument. IMPLICATIONS: Dietary self-report instruments may be inadequate for analytic epidemiologic studies of dietary fat and disease risk because of measurement error biases.     

The importance of geriatrics to family medicine: a position paper by the Group on Geriatric Education of the Society of Teachers of Family Medicine

The role of geriatrics and geriatricians in family medicine remains unsettled. Despite a rapidly aging population, a tremendous shortage now exists of faculty with interest and expertise in geriatrics. Relatively few family practice residents choose to enter geriatric fellowship programs, and federal funding for such programs has been reduced. Despite accreditation requirements, residency programs are not always able to provide the range of geriatric experiences needed to properly prepare graduates to provide care for the broad range of older patients. Medical students' exposure to geriatrics remains limited. The Group on Geriatric Education of the Society of Teachers of Family Medicine believes that family medicine faculty must recognize and be committed to the notion that geriatrics is integral to family medicine. Both undergraduate and residency training programs should emphasize experience with geriatric patients in multiple settings. In particular, the nursing home should not be the main focus of geriatric training. The small number of certified geriatric faculty will be able to provide leadership, but a broad range of faculty must become involved in teaching geriatrics. Faculty development activities and continuing education programs to foster the necessary expertise will be essential to the accomplishment of this task.     

Bovine IgG2a antibodies to Haemophilus somnus and allotype expression

AIMS/BACKGROUND: To characterise clinically a large kindred segregating retinitis pigmentosa and sensorineural hearing impairment in an autosomal dominant pattern and perform genetic linkage studies in this family. Extensive linkage analysis in this family had previously excluded the majority of loci shown to be involved in the aetiologies of RP, some other forms of inherited retinal degeneration, and inherited deafness. METHODS: Members of the family were subjected to detailed ophthalmic and audiological assessment. In addition, some family members underwent skeletal muscle biopsy, electromyography, and electrocardiography. Linkage analysis using anonymous microsatellite markers was performed on DNA samples from all living members of the pedigree. RESULTS: Patients in this kindred have a retinopathy typical of retinitis pigmentosa in addition to a hearing impairment. Those members of the pedigree examined demonstrated a subclinical myopathy, as evidence by abnormal skeletal muscle histology, electromyography, and electrocardiography. LOD scores of Zmax = 3.75 (theta = 0.10), Zmax = 3.41 (theta = 0.10), and Zmax = 3.25 (theta = 0.15) respectively were obtained with the markers D9S118, D9S121, and ASS, located on chromosome 9q34-qter, suggesting that the causative gene in this family may lie on the long arm (q) of chromosome 9. CONCLUSIONS: These data indicate that the gene responsible for the phenotype in this kindred is located on chromosome 9 q. These data, together with evidence that a murine deafness gene is located in a syntenic area of the mouse genome, should direct the research community to consider this area as a candidate region for retinopathy and/or deafness genes.     

Production of the 19-kDa antigen of Mycobacterium tuberculosis in Escherichia coli and its purification

The 19-kDa antigen (19Ag) of Mycobacterium tuberculosis (Mt) is a lipoprotein which is released from the organism during growth. In order to study the possible involvement of this antigen in the host protective response against Mt infection, it would be helpful to obtain high-level production of 19Ag from a recombinant organism. We have found that overexpression of the native 19Ag gene in Escherichia coli or yeast leads to products which are aggregated and insoluble. By site-directed mutagenesis of the 19Ag lipoprotein leader sequence, we have generated a mutant gene which directs the production of 19Ag into the periplasmic space of E. coli, from where it can be easily purified in high yield. 19Ag obtained from this mutant construct lacks the lipid-modified N-terminal Cys residue found in the native 19Ag, and is not glycosylated, but is otherwise indistinguishable from 19Ag isolated from Mt culture supernatant.