Kadambari K. Namboodiri

Nonsteroidal antiinflammatory drugs and breast cancer

We examined the association of nonsteroidal antiinflammatory drugs and breast cancer risk in a case-control study of 511 breast cancer patients and 1,534 population control subjects. The relative risk of breast cancer was reduced in women using these compounds at least 3 times per week for > or = 1 year [odds ratio (OR) = 0.66; 95% confidence interval (CI) = 0.52-0.83]. Odds ratios were similar for use of ibuprofen (0.57) or aspirin per se (0.69). Breast cancer risk declined with increasing exposure, and the greatest risk reduction (40%; odds ratio = 0.60; 95% CI = 0.40-0.91) occurred at the highest level of use (daily intake for > or = 5 years). These results indicate that nonsteroidal antiinflammatory drugs may have chemopreventive potential against the development of breast cancer.

Increased Red-Cell Sodium-Lithium Countertransport in Normotensive Sons of Hypertensive Parents

MOST investigators would agree that both heredity and environment are important determinants in the development of essential hypertension. Among the environmental factors, dietary sodium has a prom...

A family with hereditary ataxia: HLA typing

In a previously unreported family with olivopontocerebellar atrophy, the kindred contained over 600 individuals in five generations. Of 83 offspring of affected individuals who are over 38.8 years of age (the mean age of the onset of disease in this family), 47 had ataxia; there was autosomal dominant transmission. Clinical findings included lower bulbar palsies, hyperreflexia, ataxia, incoordination, scanning and explosive speech, and, in some, slow motor-nerve conduction velocities. There was cortical and cerebellar atrophy of pontine nuclei, inferior olives, and XII nuclei, and loss of Purkinje cells in the cerebellum. Seventy-three individuals of the III and IV generations were typed for HLA histocompatibility antigens. A maximum lod score of 1.97 was found at male recombination fraction 0.18 and female recombination fraction 0.36. When the lod score values reported in other studies were combined with the values in this family, the maximum lod score was found to be 4.681 at a recombination frequency of 0.22.

Evidence for a Possible Major Gene Effect in Absolute Finger Ridge Count

Dermatoglyphics, as defined by finger ridge count, is considered a classic example of polygenic inheritance in man. A set of data containing samples from both Caucasian and Japanese populations are analyzed by fitting a mixture of normal distributions, utilizing maximum likelihood estimation. The results are homogeneous over all subsets of the data and suggest that a single major autosomal locus with two additive alleles may account for over half the variation of the quantitative phenotype absolute finger ridge count. Existence of this locus awaits confirmation by pedigree or linkage analyses.

Segregation and Linkage Analyses of Dopamine-β-Hydroxylase Activity

Dopamine- β - h rydroxylase (DBH) activity in serum was measured by spectro-photometric methods in 95 persons of a large family (HGAR 2), along with 27 polymorphic ma

Family aggregation of high density lipoprotein cholesterol. Collaborative lipid research clinics program family study.

High density lipoprotein cholesterol data on a population-based random sample of 858 white and 72 black probands and their 3935 white and 205 black relatives were collected from nine North American clinics using a common protocol and standardized methodology. Familial associations were examined within clinics for whites and pooled across clinics for blacks. The influence of covariates and varying family size on correlations was examined using several sets of transformed and adjusted values and a variety of weighting schemes. Parent-offspring and sibling correlations were significant in most cases, but spouse correlations were not, suggesting a stronger influence of shared genes than shared environment on high density lipoprotein cholesterol. Adjustment for covariates tended to weaken the correlations, but the effect of variable family size was imperceptible. Although pairs involving pediatric offspring or siblings tended to show higher correlation than their adult counterparts, the differences were not significant. All correlations except father-daughter and brother-brother were homogeneous across clinics in whites. There was no asymmetry in parent-child correlations by the sex of the offspring, but the pooled mother-child correlation was significantly higher than father-child values, suggesting a possible maternal influence on high density lipoprotein cholesterol. No heterogeneity in correlations in high density lipoprotein cholesterol was detected between blacks and whites except for mother-son pairs.

Linkage relationships of Lp and Ag serum lipoproteins with 25 polymorphic markers

SummaryLinkage relations of Lp and Ag serum lipoproteins with 25 polymorphic marker systems are examined in a large kindred of over 100 persons. The results indicate that Lp and ESD are probably closely linked and so the Lp locus may also be assigned to chromosome 13. No significant linkage is detected between Ag and the other marker systems.

Coagulation factor XIII: a useful polymorphic genetic marker.

SummaryThe plasmas of two groups of subjects were examined for blood coagulation Factor XIII-A (FXIII-A, F13A) by electrophoresis in agarose using a Tris-EDTA-borate buffer to separate the common variants, F13A*1, F13A*2, and F13A*3. Dimeric subunits were visualized in UV light as monodansyl cadaverine bound to casein at the position of the transglutaminase activity representing F13A. One test group consisted of 307 members of three large Caucasian families. The other consisted of 148 consecutive patients whose plasmas had been sent to the clinical laboratory for determination of prothrombin time. Segregation analysis and father-to-son transmission confirmed that F13A is inherited as an autosomal co-dominant trait. The allelic frequencies in the random sample were F13A*1=0.82 and F13A*2=0.18. This sample included both blacks and whites, and the gene frequencies were not significantly different in the two races. The gene frequencies among the unrelated spouses of the three white families were A*1=0.75, A*2=0.24, A*3=0.01. Genetic equilibrium was present in both groups.The degree of polymorphism, the availability of blood, the ease of assessment, the absence of selective pressure, and the uniformity of gene frequencies in two major American ethnic groups make F13A a very useful marker for linkage studies and paternity testing. F13A has been provisionally assigned to chromosome 6. Linkage analysis of our family data did not provide evidence of linkage to two chromosome 6 markers, properdin factor B (BF) and glyoxalase 1 (GLO). The highest lod score (Z) was between F13A and the Kidd (Jk) blood group (Z=0.68 at Θ-0.24).

Linkage relationships of biochemical markers to Q- and C-band variants in a large black kindred

SummaryLod scores are reported for 86 biochemical to cytogenetic marker comparisons in a Black kindred. Analysis with unconfirmed locus assignments resulted in 12 exclusions of close linkage.