Linda L. Darga

5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and the risk of acute lymphoblastic leukemia (ALL) in Filipino children.

5,10‐Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism. Polymorphisms at the C677T and A1298C loci are associated with reduced activity; consequently more folate substrates are shunted toward thymidylate and DNA synthesis. Several studies have reported a reduced risk of developing ALL in children with MTHFR polymorphisms. The objective of this study was to determine the association between MTHFR polymorphisms and ALL in Filipino children.

MOLECULAR SYSTEMATICS AND CLINAL VARIATION IN MACAQUES

ABSTRACT . Gene frequency data were gathered on seven genetic loci from 17 populations of ten species of macaques from known geographic areas. The data were analyzed via two computer methods, each generating dendrograms depicting phylogenetic relationships. These relationships are discussed in terms of the traditional taxonomy of macaques. M. fasciculariS, M. mulatta, M. Cyctopis and M. fuscata form a closely related assemblage. M. speeiosa , the Celebes and pig-tailed macaques are the most divergent groups. The Celebes populations are joined together and form an assemblage with the M. nemestrina groups, a geographically reasonable union. Clinal patterns of genetic variation suggest the operation of natural selection.

Genetic determinants of bone mass do not relate with breast cancer risk in US white and African-American women

IntroductionThe association between high bone mass and increased breast cancer risk has been established. Identification of polymorphisms and the resultant variant receptors suggests the possibility of differential effects on hormone responsive genes when complexed with the hormones. Both estrogen receptor-α (ER) and vitamin D receptor (VDR) polymorphisms have been associated with bone density. Thus, we examined these polymorphisms for association with increased breast cancer risk among US African-American and white women.MethodsA case–control study was conducted to measure ER and VDR polymorphisms and radial bone mineral density (BMD) in African-American and white women, and to examine the association between polymorphisms, bone density and breast cancer risk. Genotypes and bone density were obtained from 412 women (220 cases and 192 controls, with equal distribution between the two ethnic groups).ResultsWe found no evidence for an association between either the ER or VDR genotypes and breast cancer risk. Also, there was no difference in the risk of breast cancer by genotypes after adjusting for ethnicity. The addition of age, sex and ethnicity-specific BMD (Z-scores) did not significantly change the odds ratio for breast cancer.ConclusionsOur data suggest that the polymorphisms investigated had no effect on risk of breast cancer in this population. Thus, we found no evidence to support our hypothesis that breast cancer cases and controls would have a different distribution of ER and VDR genotypes. Furthermore, the polymorphisms were not associated with differences in bone mass and its relationship with breast cancer risk.

Biochemical Evidence on the Phylogeny of Anthropoidea

Anthropoidea is the suborder of Primates which includes New and Old World monkeys, apes, and humans. The term “Anthropoidea” was introduced by Mivart and has received general acceptance since Simpson (1945) included it in his classification of mammals (Simons, 1972). However, questions have arisen regarding the monophyletic nature of Anthropoidea. Since the fossil record relating to higher primate origins remains incomplete, there is reasonable doubt that the three superfamilies of Anthropoidea (Ceboidea, Cercopithecoidea, and Hominoidea) descended from a common “stem stock” (Schwartz et al., 1978). Although Simons (1976) views Anthropoidea as a monophyletic assemblage, he notes (1972) that the earliest putative ancestors of Ceboidea, Cercopithecoidea, and Hominoidea do not seem to resemble one another as much as one would expect if all had emerged from a single segment of Paleocene-Eocene lower primates.

Quality of life as a predictor of weight loss in obese, early-stage breast cancer survivors.

PURPOSE/OBJECTIVES To investigate whether quality of life (QOL) assessed before weight loss intervention predicts weight loss and, in turn, what the effect of weight loss is on QOL measures after 12 months in early-stage breast cancer survivors. DESIGN A clinical trial of a weight loss intervention in breast cancer survivors. SETTING Community-wide recruitment in Detroit, MI. SAMPLE 39 breast cancer survivors (body mass index = 30-44 kg/m2), within three years of initial diagnosis and at least three months after chemotherapy or radiation therapy. METHODS Participants were randomized to one of three weight loss methods or a control group. The Functional Assessment of Cancer Therapy-Anemia (FACT-An) QOL questionnaire was administered at baseline and after the intervention. MAIN RESEARCH VARIABLES Six subscales of the FACT-An and weight change. FINDINGS Modest but statistically significant associations were found for the physical and functional subscales of the FACT-An with weight loss for 39 subjects who completed 12 months of the study. Those reporting relatively impaired physical or functional QOL at baseline lost more weight, which accounted for 8%-9% of the weight loss variance beyond that resulting from the diet arm assignment. At 12 months, greater weight loss was associated with significant improvements in overall FACT-An score and in the physical, functional, fatigue, and anemia subscales (p < 0.05). CONCLUSIONS Relatively low physical function at baseline was not a barrier to weight loss; indeed, it may have been a motivating factor in adherence to the weight loss intervention. Weight loss was associated with improvement in several QOL subscale measures in breast cancer survivors, but the emotional and social subscales were not affected. IMPLICATIONS FOR NURSING Counseling for weight loss that includes recommendations for exercise should not be withheld for patients with relatively low physical functioning.

Immunodiffusion systematics of the primates. Part V. The Platyrrhini.

Evolutionary relationships between New World monkeys and marmoset genera and the place of the Ceboidea within the primates are considered in terms of the immunological specificity of ceboid proteins. Antigenic distances between the New World primates are measured using antisera produced in rabbits to nine ceboid genera: Alouatta, Aotes, Ateles, Callicebus, Cebus, Chiropotes, Lagothrix, Saimiri and Saguinus. A cladogram constructed on the basis of increasing degrees of antigenic distance between branches depicts Ceboidea as a monophyletic assemblage within which Alouatta is grouped with the Atelinae genera, Lagothrix and Ateles, Chiropotes joins Cacajao and Cebus joins Saimiri. The joining of the cebid genera Aotes and Callicebus with callithricid genera Callimico and Saguinus into a single complex lineage suggests that Cebidae is a paraphyletic or polyphyletic taxon. A phylogenetic taxonomy for Platyrrhini is proposed.

The Bearing of Molecular Data on the Cladogenesis and Times of Divergence of Hominoid Lineages

The analysis of amino acid sequence data by the maximum parsimony method can provide valuable insights into the evolutionary processes which shaped the hominoid radiation and the emergence of Homo. Recent discoveries of hominine and ramapithecine fossils from East Africa and Asia have stimulated reevaluation of the evolutionary history of Anthropoidea, especially of that branch leading to Homo sapiens (Johanson and White, 1979; Greenfield, 1980).

Radial bone density and breast cancer risk in white and African-American women

A number of different models for assessing individual risk of breast cancer use known risk factors such as age, age at menarche, age at first live birth, previous breast biopsies, and family history. High bone mass in white women is also associated with an increased breast cancer risk; however, bone mass as a risk factor has not been studied in African-American women. We conducted a case-control study to evaluate bone mineral density as a risk factor for breast cancer in white and African-American women. We recruited 221 women with newly diagnosed breast cancer from a comprehensive breast cancer center at a large university hospital, and 197 control women who were frequency matched for ethnicity and age. Odds ratios were based on proximal and distal radial bone density measured by peripheral bone densitometry (Norland pDEXA) and expressed as a standardized “Z-score” (age and ethnicity specific). Logistic regression models were fitted controlling for body mass index, menopausal status, age, and HRT use (ever/never and duration). With proximal bone density Z-score included in the model as a continuous variable, a one-unit increase in radial shaft bone density increased the risk of breast cancer by 25% (p=0.02). When proximal bone density Z-score was analyzed as a dichotomous variable (≤0, >0) the odds ratio was 1.98 (95% CI, 1.32 to 2.97); that is, having an above average proximal bone density (age-specific) doubles the risk of breast cancer. There were no significant interactions with, and no appreciable confounding effects by, other covariates. An above-average radial shaft Z-score is a significant risk factor for breast cancer in both white and African-American women. The present study extends the association between bone mass and breast cancer risk to African-Americans, and suggests another potential application for bone density testing.

Achieving therapeutic goals in insulin-using diabetic patients with non-insulin-dependent diabetes mellitus: A weight reduction-exercise-oral agent approach

Non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes in the civilized world. Its consequences include microvascular and macrovascular disease, both of which appear to evolve from a common background of obesity and physical inactivity. The current study was undertaken in obese patients with NIDDM to see whether improvements could be made in glycemic control as well as in many cardiovascular risk factors (obesity, hypertension, lipid abnormalities, and physical inactivity) that are typical of this condition. Fifteen obese insulin-using patients with NIDDM (average body mass index, 34.0) were treated with a 500-calorie formula diet for eight to 12 weeks. Administration of insulin and diuretics was discontinued at the onset of the study. A eucaloric diet was begun at eight to 12 weeks and maintained until Week 24. A behaviorally oriented nutrition-exercise program was instituted at the beginning of the study. Glipizide or placebo was added (randomized) at Week 15 if the fasting plasma glucose level in patients exceeded 115 mg/dl. Patients lost an average of 22 pounds over the course of 24 weeks. Frequency and duration of physical activity increased significantly from baseline, as did the maximal oxygen consumption rate. Glycemic control by 15 weeks (without insulin) was similar to baseline (with insulin). With the addition of glipizide at Week 15, both fasting plasma glucose and glucose tolerance improved significantly. This improvement was not observed with placebo. In addition, both systolic and diastolic blood pressure decreased by about 10 mm Hg. There were no significant changes in the levels of serum lipids or glycosylated hemoglobin. In conclusion, a multifaceted intervention program, employing weight reduction, exercise, diet, and glipizide therapy, can be instituted in insulin-using patients with NIDDM, with improvement in glycemic control and in certain risk factors (hypertension, obesity, physical inactivity) for cardiovascular disease.

A Study of the Efficacy and Safety of Moexipril in Mild to Moderate Hypertension.

This placebo-controlled, double-blind, multicenter study examined the efficacy, safety, and tolerability of the angiotensin-converting enzyme inhibitor, moexipril, in lowering blood pressure in mildly to moderately hypertensive patients. Patients were initially randomized into four groups, two of which received moexipril 7.5 mg per day and two received moexipril 15 mg per day, for first 12 weeks of treatment. Patients then entered a withdrawal phase with one of the groups in each dose category continuing that dose of moexipril and one receiving placebo for 12 more weeks. From 223 patients randomized initially, 190 completed the 12-week withdrawal phase. In the two dosage groups from baseline to 12 weeks, sitting diastolic blood pressure decreased from 101.1 to 92.8 mm Hg for the 7.5-mg group and from 100.7 to 91.3 mm Hg for the 15-mg group (p > 0.05 baseline to week 12 in both groups) with a significant difference between those groups attained at week 12 only (p = 0.03). By the end of the withdrawal phase (24-week evaluation), the group that continued to receive 7.5 mg moexipril decreased diastolic blood pressure by 8.2 mm Hg, whereas the corresponding placebo group decreased diastolic blood pressure by 3.7 mm Hg. Although the difference between these two groups was not significant at the 24-week end point, all other time points differed significantly between groups at p ≤ 0.017. Similarly, whereas the corresponding placebo group had a mean reduction in diastolic blood pressure of 4.6 mm Hg, the group that continued 15 mg of moexipril showed a mean diastolic blood pressure reduction of 10.6 mm Hg (p > 0.001 between groups). No comparison between the two moexipril dosage groups was significant, however, during the withdrawal phase. These results during medication withdrawal indicate that moexipril is effective in significantly lowering diastolic blood pressure.