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N Hamel

Publications and source records attributed to N Hamel.

26 records · Page 2Linked to original sources
PubMed1999

Prevalence and penetrance of BRCA1 and BRCA2 gene mutations in unselected Ashkenazi Jewish women with breast cancer.

BACKGROUND: Approximately 2.0%-2.5% of Ashkenazi Jewish women carry one of three founding mutations in the BRCA1 and BRCA2 genes, and each mutation is associated with a high lifetime risk of invasive breast cancer. We investigated the extent to which these three mutations contribute to breast cancer incidence in the Ashkenazi Jewish population. METHODS: We ascertained 457 Jewish women with prevalent cases of breast cancer who were unselected for age or family history of the disease; 412 of these women were tested for the three founder mutations (case patients). Control subjects consisted of 360 non-Jewish women with breast cancer (control patients) and 380 healthy Jewish women with no history of cancer (control subjects). RESULTS: Mutations were found in 48 (11.7%) of 412 Jewish case patients. Forty-six of 48 mutations occurred in women with early-onset breast cancer (<50 years) or a history of ovarian or early-onset breast cancer in a first-, second-, or third-degree relative. The estimated penetrance to age 70 years for breast cancer was 59.9% for the BRCA1 gene mutations and 28.3% for the BRCA2 gene mutation. Compared with Jewish control subjects, the relative risk (RR) of breast cancer for first-degree relatives of mutation carriers was 5.16 (95% confidence interval [CI] = 3.14-8. 48), but risk was also increased for relatives of noncarriers (RR = 1.66; 95% CI = 1.18-2.33). The RR of prostate cancer for first-degree relatives of Jewish case patients was 3.36 (95% CI = 1. 49-7.56). CONCLUSIONS: Approximately 12% of breast cancers in the Ashkenazi Jewish population are attributable to mutations in the BRCA1 or BRCA2 gene. Genetic testing may be useful when Jewish women with breast cancer are diagnosed before age 50 years or have a close relative with ovarian or early-onset breast cancer. An association between breast and prostate cancers was observed in our study population.

Aged↗
PubMed1996

Circulating progenitor cells in human ontogenesis: response to growth factors and replating potential.

We have measured the number of progenitor cells circulating in fetal (17-32 weeks of gestation), perinatal (36 weeks of gestation), and adult (30-50 years old) blood. The progenitor cells at each ontogenetic stage were also characterized in terms both of the minimal combinations of growth factors they required to form maximal numbers of colonies in vitro and of their self-replication potential, as measured by the number of secondary and tertiary progenitor cells each could generate. The number of progenitor cells circulating in fetal and perinatal blood can be measured by directly plating the unfractionated blood. In this assay, fetal blood contains half the number of progenitor cells detected in perinatal blood (18.0 +/- 16.4 versus 40.88 +/- 0.63, p < 0.01), and the number of progenitor cells in adult blood is below the level of detection of the assay (< 1/8 microliter of blood). To compare the number of progenitor cells in all three stages of human development, progenitor cell counts were performed on blood mononuclear cells enriched by density separation. In this case, the light density cell fractions from fetal and neonatal blood contained the same number of progenitor cells (300/10(5) cells), numbers that were 10-fold higher than those observed with adult blood (30/10(5) cells). Circulating fetal-neonatal erythroid and multipotential progenitor cells were found to differ from their adult counterparts in terms of their response to growth factors and their self-renewal ability. In fact, the number of cytokines required to observe maximal colony formation increased with the ontogenetic stage of the cells. No differences were found in the frequency of primary colonies containing progenitor cells or in the mean number of secondary progenitor cells per primary colony in cultures of fetal, neonatal, or adult blood. Differences between the three ontogenetic stages, however, were found with respect to the number of sequential replatings that were possible. In fact, although both secondary granulocyte-macrophage (GM) and mixed-cell colonies derived from fetal cells gave rise to tertiary colonies, only perinatal secondary mixed-cell colonies grew in tertiary cultures, and no growth was observed in tertiary cultures of adult cells. These results suggest that the greater amplification of progenitor cells observed in liquid culture of fetal/neonatal versus adult blood is due both to a higher proliferative capacity of neonatal progenitor cells (up to two replatings versus one) and to a higher frequency in these samples of mixed-cell colony-forming cells (CFC) (37.7 +/- 7.3 versus 2.0 +/- 0.7/10(5) light density cells, respectively). Because of the high numbers of progenitor cells circulating in the fetus, as well as their high proliferative capacity, it is predicted that if blood could be harvested directly in utero, fetal blood would be as good a source of stem cells for transplantation as perinatal placental/cord blood. Circulating fetal stem cells would, therefore, represent an ideal target for gene therapy and in utero autologous transplantation.

Adult↗
PubMed1996

Nuclear genes associated with a single Brassica CMS restorer locus influence transcripts of three different mitochondrial gene regions.

Previous studies have shown that the mitochondrial orf224/atp6 gene region is correlated with the Polima (pol) cytoplasmic male sterility (CMS) of Brassica napus. We now extend this correlation by showing that the effects of nuclear fertility restoration on orf224/atp6 transcripts cosegregate with the pol restorer gene Rfp1 in genetic crosses. We also show, however, that the recessive rfp1 allele, or a very tightly linked gene, acts as a dominant gene, designated Mmt (modifier of mitochondrial transcripts), in controlling the presence of additional smaller transcripts of the nad4 gene and a gene possibly involved in cytochrome c biogenesis. A common sequence, TTGTGG, maps immediately downstream of the 5' termini of both of the transcripts specific to plants with the Mmt gene and may serve as a recognition motif in generation of these transcripts. A similar sequence, TTGTTG, that may be recognized by the product of the alternate allele (or haplotype), Rfp1, is found within orf224 just downstream of the major 5' transcript terminus specific to fertility restored plants. Our results suggest that Rfp1/ Mmt is a novel nuclear genetic locus that affects the expression of multiple mitochondrial gene regions, with different alleles or haplotypes exerting specific effects on different mitochondrial genes.

Base Sequence↗
PubMed1993

Tracer disequilibrium in CO2 compartments during NaH14CO3 infusion.

The failure of labeled CO2 to equilibrate between extracellular and intracellular CO2 compartments may influence the accuracy of substrate oxidation measurements during infusion of carbon-labeled tracers because it may generate errors in estimate of fixation of labeled CO2 derived from control experiments in which labeled bicarbonate is infused. In this study, normal volunteers received a 14-hour overnight primed continuous infusion of NaH14CO3. Over the last 4 hours of the study, steady-state conditions were achieved in the specific activities (SAs) of expired 14CO2 and plasma urea, which was used as a probe for hepatic intracellular CO2 SA. Plasma urea SA was approximately 17% lower than expired CO2 SA (46.4 +/- 5.6 v 56.8 +/- 3.9 disintegrations per minute.mumol-1, P < .02). Fractional 14CO2 recovery was 94.8% +/- 0.8%; when corrected for failure to equilibrate with intracellular CO2, fractional recovery was 89.5% +/- 1.9%. These data indicate that compartmentalization of CO2 may occur in humans. The duration of our experiments, required because of the long half-life of plasma urea, may have minimized the apparent magnitude of compartmentalization. Furthermore, it is possible that compartmentalization in extrahepatic tissues could be of either lesser or greater magnitude than that which we observed in liver. Whether this phenomenon contributes to incomplete recovery of 14CO2 during NaH14CO3 infusion cannot be determined from our results. Additional studies using different experimental approaches will be required to better measure CO2 compartmentalization.

Adolescent↗
PubMed1991

Increased dietary branched-chain amino acids do not improve growth in developing rats with chronic biliary obstruction.

We studied dietary branched-chain amino acid enrichment in cholestatic weanling rats. Growth was assessed with body weight, muscle weight and nitrogen balance. Systemic metabolic measurements that reflect liver function were evaluated, including plasma ammonia, albumin, amino acids, glucose, triglyceride and branched-chain ketoacids, as well as urinary carnitine excretion. Twenty-two rats underwent bile-duct ligation at 14 d of age. At weaning, 11 rats were fed a control diet and 11 an isoenergetic, isonitrogenous branched-chain amino acid-enriched diet for 3 wk, each with a sham-operated, pair-fed control. Body weights were similar in all four groups. Changes due to bile-duct ligation and not affected by the diet manipulation included lower plasma glucose, nitrogen balance and muscle weight, and higher triglyceride concentration, carnitine excretion and liver weight. Changes due to ligation that were normalized by dietary manipulation included plasma albumin, ammonia and total amino acid concentrations. The ratio of branched-chain to aromatic amino acids was decreased in ligated animals fed both diets; however, branched-chain amino acids were lower in the two groups fed more branched-chain amino acids.

Administration, Oral↗