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J Wuu

Publications and source records attributed to J Wuu.

31 records · Page 2Linked to original sources

Diet and cancer of the prostate: a case-control study in Greece.

The nutritional aetiology of prostate cancer was evaluated in Athens, Greece, through a case-control study that included 320 patients with histologically confirmed incident prostate cancer and 246 controls without history or symptomatology of benign prostatic hyperplasia or prostate cancer, treated in the same hospital as the cases for minor diseases or conditions. Among major food groups, milk and dairy products as well as added lipids were marginally positively associated with risk for prostate cancer. Among added lipids, seed oils were significantly and butter and margarine non-significantly positively associated with prostate cancer risk, whereas olive oil was unrelated to this risk. Cooked tomatoes and to a lesser extent raw tomatoes were inversely associated with the risk for prostate cancer. In analyses focusing on nutrients, rather than foods, polyunsaturated fats were positively and vitamin E inversely associated with prostate cancer. We conclude that several nutrition-related processes jointly contribute to prostate carcinogenesis.

Age Factors↗

Diet and benign prostatic hyperplasia: a study in Greece.

OBJECTIVES: To evaluate the nutritional etiology of benign prostatic hyperplasia (BPH) by conducting a case-control study in Athens, Greece. Despite the high morbidity and substantial human suffering produced by BPH, little research has been undertaken concerning the nutritional etiology of this disease. METHODS: The study sample consisted of 184 patients with histologically confirmed BPH and 246 control patients without clinical evidence of prostate disease. All patients and controls were permanent residents of the greater Athens area. The data were modeled through unconditional logistic regression. RESULTS: Among the food groups, fruits were inversely related to BPH risk, with a logistic regression-derived odds ratio of 0.79 per quintile increase and 95% confidence interval 0.67 to 0.93. Increased consumption of both butter and margarine was positively associated with BPH risk, and a marginally significant positive association was also evident for seed oils. No overall association was found with respect to consumption of olive oil. In analyses evaluating the role of nutrients rather than foods, zinc, an element selectively concentrated in the prostate gland, was significantly positively associated with BPH risk. CONCLUSIONS: Our study provides evidence that, among added lipids, butter and margarine may increase the risk of BPH, and fruit intake may reduce this risk. Dietary zinc may play an important role in the etiology of BPH.

Case-Control Studies↗

Hormones and hair patterning in men: a role for insulin-like growth factor 1?

BACKGROUND: Androgens are important in hair growth and patterning, whereas growth hormone substitution enhances their effect in growth hormone-deficient men. No previous study has jointly evaluated the function of sex steroids, sex hormone-binding globulin (SHBG), and insulin-like growth factor (IGF-1) in determining hair patterning in men. OBJECTIVE: We assessed the relationship between circulating hormone measurements and both head and chest hair patterning in a sample of elderly men. METHODS: Fifty-one apparently healthy men older than 65 years of age were studied cross-sectionally. Head and chest hair patterning was assessed by a trained interviewer. Morning blood samples from all subjects were used for measurements of testosterone, estradiol, dehydroepiandrosterone sulfate, SHBG, and IGF-1. RESULTS: Results were obtained from logistic regression models, adjusting simultaneously for all the measured hormones and age. Men with higher levels of testosterone were more likely to have vertex baldness (odds ratio [OR] = 2.5, 95% confidence interval [CI: 0.9 to 7.8] per 194 ng/dL increment of testosterone). In addition, for each 59 ng/mL increase in IGF-1, the odds of having vertex baldness doubled (95% CI [1.0 to 4.6]). Those who were found to have higher circulating levels of SHBG were less likely to have dense hair on their chest (OR = 0.4, 95% CI [0.1 to 0.9] per 24 nmol/L increment in SHBG]). CONCLUSION: Testosterone, SHBG, and IGF-1 may be important in determining hair patterning in men.

Aged↗

Childbearing at older age and endometrial cancer risk (Sweden).

OBJECTIVES: Several studies have found an inverse association between older age at last birth and endometrial cancer risk. A nested case-control study was undertaken to examine the influence of this and other aspects of reproductive patterns on the risk of developing endometrial cancer. METHODS: Among women born in 1925 and later, 4,839 eligible patients were identified in the Swedish Cancer Register. For each case, five individually age-matched controls were randomly selected from a population-based Fertility Register. Relative risks were estimated from odds ratios obtained from conditional logistic regression analyses. RESULTS: Compared to uniparous women, childless women were at a higher risk of endometrial cancer (odds ratio [OR] = 1.38, 95% confidence interval [CI] = 1.25-1.52). This association was stronger in younger (< 50 years) than in older (50+ years) women. At all ages of first birth, a delivery was associated with a reduced risk of endometrial cancer that slowly diminished with time. Among parous women, the risk decreased by almost 20% for each additional live birth (OR = 0.81, CI = 0.78-0.84). In an analysis limited to women with two or more births that compared the independent effects of age at first and at last birth, only older age at last birth was associated with a lowered risk of endometrial cancer. The risk decreased at a rate of about 15% per five-year delay of last birth. CONCLUSIONS: Endometrial cancer is often referred to as the prototype hormonally-determined disease in women. However, our findings give further support to the hypothesis that a birth may not only affect risk through hormonal influences, but possibly also through mechanical shedding of cells that have undergone malignant transformation.

Adult↗

Clearance kinetics of CD34+ cells from peripheral blood: an independent predictor of hematologic recovery after high-dose chemotherapy and hematopoietic stem cell transplantation.

We measured the concentration of CD34+ cells in peripheral blood (PB) (1/2) h prior to and (1/2), 1, 3, 6, and 12 h following hematopoietic stem cell (HSC) infusion in 34 breast cancer patients treated with high-dose chemotherapy (HDC). The decrease in these concentrations over time enabled us to determine the clearance kinetics of CD34+ cells from PB. The absolute number of CD34+ cells in PB generally peaked at (1/2) h after infusion, then rapidly declined from 1 to 3 h post infusion and continued to fall until 12 h post transplant, but more slowly. In univariate analysis, CD34+cells/kg infused, CFU-GM/kg infused, the CD34+ count at (1/2) h, and the 12-h clearance of CD34+ cells from PB were predictors of hematologic recovery, as were each of the two phases of clearance when the slope was divided into rapid and slow phases (from (1/2) to 3 and from 3 to 12 h post transplant, respectively). We then stratified our population by the number of CD34+ cells/kg infused. In group 1, patients received </=7.5 x 10(6) CD34+ cells/kg; in group 2, >7.5 x 10(6) CD34+ cells/kg. After adjusting for CD34+ cells injected, age, and purged or unpurged graft in multivariate analysis, the 12 h clearance remained a predictor of hematologic recovery in group 1. In addition, the second phase of clearance (from 3 to 12 h after infusion) was an even better predictor than the 12 h clearance. In group 2, however, no statistically significant correlation was observed, even with the number of HSC injected. Results suggest that rapidity of clearance of CD34+cells from PB is an independent indicator of hematologic recovery in patients receiving lower doses of CD34+ cells. When the cell dose injected is over a threshold, PB clearance correlations with hematologic recovery are masked.

Adult↗

The fluctuating phenotype of the lymphohematopoietic stem cell with cell cycle transit.

The most primitive engrafting hematopoietic stem cell has been assumed to have a fixed phenotype, with changes in engraftment and renewal potential occurring in a stepwise irreversible fashion linked with differentiation. Recent work shows that in vitro cytokine stimulation of murine marrow cells induces cell cycle transit of primitive stem cells, taking 40 h for progression from G0 to mitosis and 12 h for subsequent doublings. At 48 h of culture, progenitors are expanded, but stem cell engraftment is markedly diminished. We have investigated whether this effect on engraftment was an irreversible step or a reversible plastic feature correlated with cell cycle progression. Long-term engraftment (2 and 6 mo) of male BALB/c marrow cells exposed in vitro to interleukin (IL)-3, IL-6, IL-11, and steel factor was assessed at 2-4-h intervals of culture over 24-48 h using irradiated female hosts; the engraftment phenotype showed marked fluctuations over 2-4-h intervals, with engraftment nadirs occurring in late S and early G2. These data show that early stem cell regulation is cell cycle based, and have critical implications for strategies for stem cell expansion and engraftment or gene therapy, since position in cell cycle will determine whether effective engraftment occurs in either setting.

Animals↗

Parity and the risk of pancreatic cancer: a nested case-control study.

Smoking is the only generally accepted risk factor for pancreatic cancer. Reproductive history has in recent studies been associated with pancreatic cancer, but with contradictory results. In order to evaluate a possible association between age at first birth and the number of births and pancreatic cancer, we conducted a nested case-control study by linking 2 Swedish nationwide registries: the Cancer Registry and The Fertility Registry. Among women born between 1925 and 1970, 1,015 patients with pancreatic cancer were compared with 5,073 age-matched controls. No association between pancreatic cancer and number of births was found. Age at first birth was inversely related with the risk of pancreatic cancer (OR per 5 years = 0.90; 95% CI 0.83-0.97; p = 0.01), an association mainly confined to women with a diagnosis of pancreatic cancer before 50 years of age (OR per 5 years = 0.85; 95% CI 0.73-1.00; p = 0.04). This trend remained after adjustment for parity, but was less prominent. Young age at first birth and high parity in Sweden are, however, associated with an increased frequency of smoking, thus at least some of the increased risk for pancreatic cancer in women with young age at first birth is likely to be explained by smoking acting as a confounder.

Adolescent↗

Lymphohematopoietic engraftment in minimally myeloablated hosts.

The concept that myeloablation to open space was a prerequisite for marrow stem cell engraftment has been challenged by studies showing high rates of engraftment in nonmyeloablated mice (Stewart et al, Blood 81:2566, 1993; Quesenberry et al, Blood Cells 20:97, 1994; Brecher et al, Blood Cells 5:237, 1979; Saxe et al, Exp Hematol 12:277, 1984; and Wu et al, Exp Hematol 21:251, 1993). However, relatively large numbers of marrow cells were necessary to achieve high long-term donor percentages. We have demonstrated, using a BALB/c male/female marrow transplant model and detecting male DNA in host tissues by Southern blot or fluorescent in situ hybridization, that exposure to doses of irradiation that cause minimal myeloablation (50 to 100 cGy) leads to very high levels of donor chimerism, such that relatively small numbers of marrow cells (10 to 40 million) can give donor chimerism in the 40% to 100% range. Studies of radiation sensitivity of long-term engrafting cells have shown that 100 cGy, although not myelotoxic, is stem cell toxic, and indicate that the final host:donor ratios are determined by competition between host and donor stem cells. These data indicate that low levels of irradiation should be an effective approach to nontoxic marrow transplantation in gene therapy or in attempts to create allochimerism to treat such diseases as cancer, sickle cell anemia, or thalassemia.

Animals↗

The role of cell cycle regulatory proteins, cyclin D1, cyclin E, and p27 in thyroid carcinogenesis.

The cell cycle is controlled in part by cyclin-dependent kinases (CDKs), which are activated by forming complexes with cyclins. CDKs phosphorylate certain substrates to facilitate the proliferating cells through the cell cycle. CDK inhibitors (CDKIs) such as p27 inhibit cyclin-CDK complexes and function as a negative cell cycle regulator. The overexpression of the positive regulators (cyclins) or the underexpression of the negative regulators including p27 has been seen in a variety of neoplasms, but their role and interaction in thyroid carcinogenesis is yet to be established. We studied the expression of cyclins D1 and E, and the CDKI, p27 by immunohistochemistry in 116 cases, including 59 cases of follicular variant of papillary carcinoma (FVPC) and 57 cases of follicular adenoma (FA). The positive staining was divided into four grades: 1+ if less than 10%, 2+ if 11% to 25%, 3+ if 26% to 50%, and 4+ if greater than 50% of the nuclei of tumor cells stained positively. Cyclin D1 expression was seen in 37 (63%) FVPC and 34 (60%) FA. Cyclin E-positive cells were seen in 51 (86%) FVPC and 47 (82%) FA. No significant differences in the grade of cyclins D1 (P = .261) and E (P = .284) staining was seen between FVPC and FA. Of the 59 FVPC, 53 (89%) showed p27-positive cells; of these, 33 were 1+, nine were 2+, seven were 3+ and only four were 4+ positive. Conversely, all 57 FA were p27 positive, 53 were 4+, and four were 3+ positive. This difference in the grade of p27 staining between FVPC and FA was statistically significant (P < .001). This study shows a significant underexpression of p27 in FVPC compared with FA, suggesting that a decrease in p27 expression plays a more important role than overexpression of cyclins D1 and E alone in thyroid carcinogenesis and that p27 immunostaining may be helpful in the diagnosis of FVPC.

Adenocarcinoma, Follicular↗

Cell cycle analysis and synchronization of pluripotent hematopoietic progenitor stem cells.

Hematopoietic stem cells purified from mouse bone marrow are quiescent with less than 2% of Lin- Hoechst(low)/Rhodamine(low) (Lin- Ho(low)/Rho(low)) and 10% to 15% of Lin-/Sca+ cells in S phase. These cells enter proliferative cycle and progress through G1 and into S phase in the presence of cytokines and 5% heat-inactivated fetal calf serum (HI-FCS). Cytokine-stimulated Lin- Ho(low)/Rho(low) cells took 36 to 40 hours to complete first division and only 12 hours to complete each of 5 subsequent divisions. These cells require 16 to 18 hours to transit through G0/G1 period and 28 to 30 hours to enter into mid-S phase during the first cycle. Up to 56% of Lin- Rho(low)/Ho(low) cells are high-proliferative potential (7 factor-responsive) colony-forming cells (HPP-CFC). At isolation, HPP-CFC are quiescent, but after 28 to 30 hours of culture, greater than 60% are in S phase. Isoleucine-deprivation of Lin- Ho(low)/Rho(low) cells in S phase of first cycle reversibly blocked them from entering into second cycle. After the release from isoleucine-block, these cells exhibited a G1 period of less than 2 hours and entered into mid-S phase by 12 hours. Thus, the duration of G1 phase of the cells in second cycle is 4 to 5 times shorter than that observed in their first cycle. Similar cell cycle kinetics are observed with Lin-/Sca+ population of bone marrow cells. Stem cell factor (SCF) alone, in the presence of HI-FCS, is as effective as a cocktail of 2 to 7 cytokines in inducing quiescent Lin-/Sca+ cells to enter into proliferative cycle. Aphidicolin treatment reversibly blocked cytokine-stimulated Lin-/Sca+ cells at G1/S boundary, allowing their tight synchrony as they progress through first S phase and enter into second G1. For these cells also, SCF alone is sufficient for their progression through S phase. These studies indicate a very short G1 phase for stem cells induced to proliferate and offer experimental approaches to synchronize murine hematopoietic stem cells.

Animals↗

Monitoring versus interim analysis of clinical trials: a perspective from the pharmaceutical industry.

The definitions of "interim analysis" and "monitoring" of clinical trials are often ambiguous in the current literature. The resulting confusion can lead to erroneous conclusions and misguided decisions, especially when activities that are operational or observational are evaluated in a probabilistic sense as inferential. The authors seek to define "interim analysis" and "monitoring" in a mutually exclusive fashion. These definitions will then provide the opportunity to review and categorize existing clinical trial practices and procedures. This will clarify such issues as "when to look" and "when to pay a price" (e.g., test size and power) and characterize such issues in the context of pharmaceutical industry drug development.

Bayes Theorem↗

Prevalence of CCR5 and CCR2 HIV-coreceptor gene polymorphisms in Belgium.

Polymorphisms of the chemokine receptor genes CCR5 and CCR2 are associated with resistance to HIV-1 infection or delayed progression to AIDS. Few data are available on their combined prevalence in healthy subjects; we therefore examined the occurrence of CCR5-Delta32 and CCR2-64I polymorphisms in a sample of 310 healthy Belgians. Allele frequencies were 0.119 and 0.074 for CCR5-Delta32 and CCR2-64I, respectively. Genotype distributions for both polymorphisms were found to be in accordance with Hardy-Weinberg equilibrium, but a significant (p = 0.002) linkage disequilibrium between CCR5-Delta32 and CCR2-64I was observed. The high prevalence of CCR5-Delta32 and CCR2-64I in Belgians may need to be taken into account in the design of studies of antiretroviral treatments.

Belgium↗