In situ localization of the genetic locus encoding the lysosomal acid lipase/cholesteryl esterase (LIPA) deficient in Wolman disease to chromosome 10q23.2-q23.3.
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Biomedical subjects
Publications and source records attributed to R A Anderson.
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The possible benefits of biological monitoring of large groups of people potentially exposed to environmental contaminants has become an area of much interest in recent years. Because chromite-ore processing residue has been found in some soils in northern New Jersey, urinary chromium monitoring of people in the community was evaluated as a potentially useful tool. In an attempt to identify those who could be exposed and to quantify the magnitude of exposure to the chromium in these soils, the New Jersey Department of Health (NJDOH) initiated a public health screening project. In 1992, the NJDOH proposed to evaluate over 4000 people who lived or worked near these sites. Volunteers were administered a questionnaire and were given a limited physical examination, and a single spot urine sample was collected. Because of the difficulties in using urinary chromium to assess low-level exposure and the potential implications of any regulatory decisions that could be based on the results of this project, a panel of experts was convened to evaluate the protocol. The panel consisted of five scientists and physicians with expertise in toxicology, dermatology, epidemiology, biological monitoring, and analytical chemistry. Like a World Health Organization group, the panel concluded that although urine biomonitoring can be useful in evaluating high levels of exposure to chromium, it is not reliable for assessing low-level exposure similar to that which may have occurred in northern New Jersey. The panel also noted that when urinary biomonitoring is to be used to assess the public's possible exposure, a large number of precautions must be taken to ensure the accuracy and usefulness of the results. The single most important recommendation was to collect a second, and perhaps a third, spot urine (or 24-h urine) sample before concluding that a person may be routinely overexposed. These suggestions are applicable to designing a biomonitoring program for nearly any environmental contaminant to which a community may be exposed. A review of scientific literature associated with biological monitoring of chromium is provided.
Chromium metabolism of lactating women was evaluated by measuring diet, breast milk, urine, and serum chromium in 17 subjects 60 d postpartum. Breast milk chromium concentration was similar for the 3 d of collection with a mean +/- SE concentration of 3.54 +/- 0.40 nmol/L (0.18 ng/mL). Dietary intake and urinary chromium values were also similar for each of the 3 collection days. Total chromium intake of lactating mothers (0.79 +/- 0.08 mumol/d) was greater than that of reference female subjects (0.48 +/- 0.02). There was a significant correlation (r = 0.84) between serum chromium and urinary chromium excretion. If a breast milk volume of 715 mL is assumed, chromium intake of exclusively breast-fed infants is < 2% of the estimated safe and adequate daily intake of 10 micrograms. In summary, breast milk chromium content is independent of dietary chromium intake and serum or urinary chromium values. Chromium intake also did not correlate with serum or urine chromium but there was a significant relationship between serum and urinary chromium concentrations.
Twenty-four castrated male pigs were used in a 2 x 2 treatment array to determine the main effects of and interactions between dietary chromium supplementation and pituitary porcine somatotropin (ppST) administration on growth performance and serum hormone and metabolite concentrations. The treatments were 1) control (basal diet); 2) chromium (basal diet+300 micrograms/kg diet added trivalent chromium as chromium picolinate); 3) ppST (100 micrograms/(kg body wt.d); and 4) chromium+ppST. Treatments were administered when pigs weighed between 30 and 60 kg. Blood was collected when pigs weighted 45 and 60 kg. All pigs treated with ppST exhibited improvements in growth performance (P < 0.05). Pigs given chromium showed no improvements in growth rate, feed efficiency or composition of gain. Measurements at 60 kg body weight revealed that ppST increased the cholesterol:HDL cholesterol ratio (P < 0.05). Chromium lowered serum insulin and glucose concentrations relative to controls (P < 0.05) and normalized the increase in glucose and insulin resulting from ppST treatment. No ppST x chromium interactions were noted, suggesting these changes in glucose and insulin metabolism are exerted through different mechanisms. These results indicate that chromium does not affect growth performance of young growing pigs. Chromium does normalize altered hormone and metabolite concentrations resulting from ppST treatment.
A total of 12 healthy adult men were recruited to investigate the effect of exogenous melatonin on the sensitivity of the hypothalamo-pituitary axis to sex steroid negative feedback. The experiment consisted of a double-blind, randomized cross-over trial during which all subjects received 100 mg oral melatonin or placebo at 1600 h for 14 days. Midway through each of the two treatments (day 8), 100 mg testosterone propionate i.m. (TP) was given at 0900 h. Blood samples for the measurement of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, testosterone and melatonin were taken at 0900 h on days 1, 3, 5, and daily from days 8-14. An additional blood sample was taken 8 h after the administration of testosterone. The interval between the melatonin and placebo treatment periods was 2 months. The oral administration of melatonin caused a pharmacological increase in the blood plasma concentration of melatonin which was maximum at 2 h and still above normal at 24 h. The daily treatment thus resulted in persistently high circulating levels of melatonin for 14 days. This treatment had no significant effect on the secretion of LH, FSH, prolactin or testosterone based on the first week of each study (melatonin compared with placebo). The injection of TP caused a rapid 3 to 4-fold increase in the plasma concentrations of testosterone which was at a maximum at 8 h and had returned to baseline within 4 days, with a similar pattern in both the melatonin and placebo periods.(ABSTRACT TRUNCATED AT 250 WORDS)
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Signs and symptoms of Cr deficiency in the general population appear widespread due not only to suboptimal intake of dietary Cr but also the elevated consumption of simple sugars that increase Cr losses. A large percentage of the subjects with marginally impaired glucose tolerance or elevated circulating insulin respond to supplemental Cr. The mechanism of action of Cr in the potentiation of insulin activity as well as the exact structure of biologically active chromium is unclear but significant progress is being made. In summary, recent advances in chromium nutrition research strengthen the association of insufficient dietary chromium and risk factors maturity-onset diabetes and cardiovascular diseases and further document the role of chromium in the maintenance of optimal health.
Casein kinase I (CKI) is a class of protein kinases ubiquitous to all eukaryotic cells. Recently, cDNA clones encoding several bovine CKI isoforms have been sequenced that show high sequence identity to the HRR25 gene product of the budding yeast Saccharomyces cerevisiae; HRR25 is required for normal cellular growth, nuclear segregation, DNA repair, and meiosis. We have raised polyclonal antibodies to a human erythroid 34-kDa CKI and have sequenced a portion of this kinase. The amino acid sequence identifies the CKI as the alpha-CKI isoform, which is 62% identical to the HRR25 protein kinase. By use of immunofluorescence, the alpha-CKI has been localized to vesicular cytosolic structures and to the centrosome in interphase cells. As cells progress into mitosis, centrospheric staining increases and, in mitosis, alpha-CKI associates with kinetochore fibers. This localization suggests that alpha-CKI, like HRR25, plays a role in the segregation of chromosomes during mitosis and may be cell cycle-regulated both in humans and in yeast.
An explanation for the consistently documented finding of higher levels of high density lipoprotein-cholesterol in black men relative to white men was sought by comparing the frequency of restriction fragment length polymorphism markers present in blacks and in whites at the gene loci coding for the two major apolipoprotein constituents of high density lipoprotein, apolipoproteins AI and AII. The measurements were made in population-based samples of 45 to 54-year-old black (n = 190) and white (n = 370) subjects from the Minnesota Heart Survey for whom lipoprotein levels were available. The mean high density lipoprotein-cholesterol level for black men in the sample (47 +/- 1.5 mg/dl) was higher (P less than 0.05) than that for white men (42 +/- 0.9 mg/dl), while levels in women were not different between races. While the SacI and MspI markers at the apolipoprotein AI-CIII-AIV gene locus showed similar frequencies in blacks compared to whites, the degree of the linkage disequilibrium previously noted between these markers in white subjects was altered in blacks and the minor allele of the PstI marker at this locus was virtually absent in the black subjects (P less than 0.005 vs whites). For black men, there were significant associations of the M2 allele and the S2M2 haplotype at the apolipoprotein AI locus with lower high density lipoprotein-cholesterol levels. The results are consistent with the hypothesis that DNA sequence variations in the vicinity of the apolipoprotein AI-CIII-AIV gene locus are associated with the difference in high density lipoprotein-cholesterol levels between blacks and whites.
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The mutagenic potential of chronic treatments of male CF-1 mice with ethanol and delta 9-tetrahydrocannibinol (THC), and their comutagenic potential with a known mutagenic agent, Trenimon, were examined. This was accomplished by measuring the frequency of dominant lethal mutations arising from mating of treated males with nontreated females. Adult male mice were treated with 5% (v/v) ethanol as part of a liquid diet (28% ethanol-derived calories) for five weeks; 10 mg/kg body weight (p.o.) THC every two days for five weeks; a single injection of Trenimon (0.125 mg/kg, i.p.) on day 28 of diet treatment; and all combinations of treatments. The control group was pair-fed a liquid diet in which isocaloric sucrose replaced ethanol; these males were also given sesame oil (vehicle for THC) and saline (vehicle for Trenimon) on the same schedule as that for the treated males. Neither body weights nor hematocrits were adversely affected by any treatment. Both ethanol and Trenimon treatments resulted in a small (8-9%; p less than 0.05) decrease in testicular weight. The effect of combined treatment with ethanol and Trenimon was roughly additive. Treatment with THC had no effect on testicular weight. Seminal vesicle weights were not affected by any treatment. Treatments were without significant effect on fertility, as measured by the frequency of males producing pregnancies. Ethanol and Trenimon treatments produced approximately 3- and 7-fold increases, respectively in the frequencies of preimplantational loss over that seen for the control group (7.3%), resulting in significant ethanol and Trenimon effects (p less than 0.001). No interactive effects of ethanol and Trenimon treatments were noted. Frequencies of dead fetuses per pregnancy in the ethanol- and Trenimon-treated groups were increased approximately 2.5- and 4-fold, respectively, over the control value of approximately 16%. However, the effect of combined treatments was not greater than that due to Trenimon alone, resulting in Trenimon and ethanol effects (p less than 0.001) and ethanol-Trenimon interaction (p less than 0.001). The calculated mutation index resulting from each treatment yielded significant (p less than 0.001) ethanol- and Trenimon-induced effects. In contrast to effects of ethanol and Trenimon treatments, THC, given alone, or in combination with ethanol and/or Trenimon, had no effect on either preimplantational loss, fetal mortality or the resulting mutation index. The data suggest that chronic ethanol treatment, at levels resulting in minimal fertility impairment, increases the frequency of dominant lethal mutations. In contrast, chronic treatment with THC, as administered in the present study, appears to be without effect.(ABSTRACT TRUNCATED AT 400 WORDS)
A new patient having clinical, pathologic and biochemical features of the exceedingly rate B1 variant of GM2-gangliosidosis is described. This patient, of northern European (non-Ashkenazi) ancestry, is the first affected child of this ethnic background available for molecular genetic analysis; thus, she represented an opportunity to identify a new mutation associated with this phenotype or, conversely, to further characterize the DN allele of the hexosaminidase alpha gene (G533-greater than A) as a more widely distributed mutation not previously observed in this gene pool. As a means of rapid analysis, we report a strategy for PCR amplification and direct DNA sequencing of exon 5 of the hexosaminidase alpha gene, the most frequent site of mutations in this condition. With this technique, the father of the affected child was determined to be heterozygous for the DN allele, while the mother was found to have only the normal sequence in this region. This observation further extends the known geographic and ethnic distribution of this mutation, and suggests the likelihood that the DN allele has been derived by multiple independent mutational events.
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As the biologically active component of glucose tolerance factor (GTF), the essential trace mineral chromium is now being marked to athletes. GTF potentiates insulin activity and is responsible for normal insulin function. Thus, insulin's effects on carbohydrate, fat, and protein metabolism are dependent upon the maintenance of adequate chromium stores. Due to excessive chromium loss and marginal chromium intake, athletes may have an increased requirement for chromium. Therefore, in some circumstances the dietary supplementation of a chromium compound may be efficacious. The restoration and maintenance of chromium stores via supplementation would promote optimal insulin efficiency, necessary for high-level athletic performance. However, potential anabolic effects of enhanced insulin function would likely be marginal, and reports of short-term anabolic increases from the supplementation of an organic chromium compound need to be confirmed.
Cinnamon and Brewer's yeast extracts have been shown to potentiate the action of insulin in isolated adipocytes. In this study, isolated rat epididymal adipocytes were used to evaluate the influence of bovine serum albumin on insulin activity as affected by cinnamon and Brewer's yeast extracts. Albumin at 0.01-0.1% decreased the insulin stimulatory effects of cinnamon from 11.8- to 5.3-fold and 2% albumin decreased this effect to near control levels. Conversely, the insulin-enhancing properties of Brewer's yeast remained low in the presence of less than 0.25% albumin but subsequently increased 2.8-, 4.8- and 5.6-fold in the presence of 0.25, 0.50 and 1.0% albumin, respectively. In the absence of added insulin, increased activity of the insulin-stimulated utilization of glucose by both extracts was observed but only Brewer's yeast extract displayed additive effects when tested at higher insulin levels. Due to the inhibitory and enhancing effects of albumin on the insulin activity of cinnamon and Brewer's yeast, respectively, it is suggested that the effects of albumin be assessed when evaluating the insulin-enhancing effects of other substances using isolated adipocytes.
The effects of supraphysiological levels of testosterone, used for male contraception, on sexual behavior and mood were studied in a single-blind, placebo-controlled manner in a group of 31 normal men. After 4 weeks of baseline observations, the men were randomized into two groups: one group received 200 mg testosterone enanthate (TE) weekly by im injection for 8 weeks (Testosterone Only group), the other received placebo injections once weekly for the first 4 weeks followed by TE 200 mg weekly for the following 4 weeks (Placebo/Testosterone group). The testosterone administration increased trough plasma testosterone levels by 80%, compatible with peak testosterone levels 400-500% above baseline. Various aspects of sexuality were assessed using sexuality experience scales (SES) questionnaires at the end of each 4-week period while sexual activity and mood states were recorded by daily dairies and self-rating scales. In both groups there was a significant increase in scores in the Psychosexual Stimulation Scale of the SES (i.e. SES 2) following testosterone administration, but not with placebo. There were no changes in SES 3, which measures aspects of sexual interaction with the partner. In both groups there were no changes in frequency of sexual intercourse, masturbation, or penile erection on waking nor in any of the moods reported. The Placebo/Testosterone group showed an increase in self-reported interest in sex during testosterone treatment but not with placebo. The SES 2 results suggest that sexual awareness and arousability can be increased by supraphysiological levels of testosterone. However, these changes are not reflected in modifications of overt sexual behavior, which in eugonadal men may be more determined by sexual relationship factors. This contrasts with hypogonadal men, in whom testosterone replacement clearly stimulates sexual behavior. There was no evidence to suggest an alteration in any of the mood states studied, in particular those associated with increased aggression. We conclude that supraphysiological levels of testosterone maintained for up to 2 months can promote some aspects of sexual arousability without stimulating sexual activity in eugonadal men within stable heterosexual relationships. Raising testosterone does not increase self-reported ratings of aggressive feelings.