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Biomedical subjects

J Wuu

Publications and source records attributed to J Wuu.

At least 19 recordsLinked to original sources
PubMed2006

Effect of donepezil on motor and cognitive function in Huntington disease.

Striatal cholinergic dysfunction may be important in Huntington disease (HD). We studied whether donepezil improves chorea, cognition, and quality of life (QoL) in HD. Thirty patients were randomly assigned to treatment with donepezil or placebo. At the doses studied, donepezil did not improve chorea, cognition, or QoL. Adverse events were similar between both groups. Based on this small sample study, donepezil was not an effective treatment for HD.

Chorea↗
PubMed2004

MRI-derived entorhinal volume is a good predictor of conversion from MCI to AD.

With high-resolution quantitative magnetic resonance imaging (MRI) techniques, it is possible to examine alterations in brain anatomy in vivo and to identify regions affected in the earliest stages of Alzheimer's disease (AD). In the present study, 27 patients diagnosed with mild cognitive impairment (MCI) received a high-resolution MRI scan at baseline and were followed with yearly clinical evaluations. Ten of the 27 patients converted to AD during a 36-month period following the baseline clinical evaluation. Hippocampal and entorhinal cortex volumes derived from the baseline scan were compared to determine which of these two regions, known to be pathologically involved very early in the course of AD, could best differentiate MCI converters from non-converters. Although both entorhinal and hippocampal volumes were found to be independent predictors of the likelihood of conversion to AD, it was the right hemisphere entorhinal volume that best predicted conversion with a concordance rate of 93.5%.

Aged↗
PubMed2003

Maternal and gestational correlates of pregnancy prolactin and growth hormone in USA and China.

The objective of this study is to determine correlates of prolactin and growth hormone levels among pregnant women in the USA and China. We studied 304 pregnant Caucasian and 335 pregnant Chinese women. Levels of prolactin and growth hormone were measured at weeks 16 and 27 of gestation, and correlated with maternal, gestational and perinatal characteristics. Both growth hormone and, to a lesser extent, prolactin were inversely associated with pregnancy weight and body mass index, history of a previous live birth and newborn size, whereas educated women had higher levels of both hormones. Growth hormone levels were lower in women who gained more weight, smoked and had nausea and vomiting during pregnancy, whereas prolactin increased with longer total gestation. We found robust associations between maternal and newborn characteristics on the one hand and prolactin and growth hormone during pregnancy on the other.

Adult↗
PubMed2002

Huntington's disease: a randomized, controlled trial using the NMDA-antagonist amantadine.

OBJECTIVE: To examine the acute effects of the NMDA receptor antagonist amantadine on motor and cognitive function in Huntington's disease (HD). BACKGROUND: Chorea in HD and in the levodopa-induced dyskinesias of PD may be clinically indistinguishable. In PD, hyperphosphorylation of NMDA receptors expressed on striatal medium spiny neurons contributes to peak-dose dyskinesias, and drugs that block these receptors can diminish chorea severity. Because these spiny neurons are the primary target of the neurodegenerative process in HD, sensitization of NMDA receptors on residual striatal neurons might also participate in the generation of motor dysfunction in HD. METHODS: To evaluate this possibility, 24 patients with HD entered a double-blind placebo-controlled crossover study of amantadine with two 2-week arms. RESULTS: Chorea scores were lower with amantadine (usually 400 mg/d) than placebo, with a median reduction in extremity chorea at rest of 36% (p = 0.04) for all 22 evaluable patients and of 56% in the 10 individuals with the highest plasma drug levels. Improvement correlated with plasma amantadine concentrations (p = 0.01) but not CAG repeat length. Parkinsonian rating scores did not worsen and there was no consistent change in cognitive measures. Adverse event profile was benign. CONCLUSIONS: Results suggest that NMDA receptor supersensitivity may contribute to the clinical expression of choreiform dyskinesias in HD and that selective antagonists at that site can safely confer palliative benefit.

Adult↗
PubMed2002

Pregnancy and risk of renal cell cancer: a population-based study in Sweden.

Epidemiological findings indicate that hormonal influences may play a role in the etiology of renal cell cancer (RCC). The possible effect of childbearing remains enigmatic; while some investigators have reported a positive association between number of births and renal cell cancer risk, others have not. A case-control study, nested within a nation-wide Fertility Register covering Swedish women born 1925 and later, was undertaken to explore possible associations between parity and age at first birth and the risk of renal cell cancer. Among these women a total of 1465 cases of RCC were identified in the Swedish Cancer Register between 1958 and 1992 and information on the number of live childbirths and age at each birth was obtained by linkage to the Fertility Database. For each case, five age-matched controls were randomly selected from the same register. Compared to nulliparous women, ever-parous women were at a 40% increased risk of RCC (Odds Ratio [OR]=1.42; 95% CI 1.19-1.69). The corresponding OR for women of high parity (five or more live births) was 1.91 (95% CI 1.40-2.62). After controlling for age at first birth among parous women, each additional birth was associated with a 15% increase in risk (OR=1.15; 95% CI 1.08-1.22). The observed positive association between parity and renal cell cancer risk is unlikely to be fully explained by uncontrolled confounding, but warrants further evaluation in large studies, with allowance for body mass index.

Adult↗
PubMed2002

Correlates of pregnancy oestrogen, progesterone and sex hormone-binding globulin in the USA and China.

The objective of this study is to examine perinatal correlates of oestradiol (E2), oestriol (E3), progesterone and sex hormone-binding globulin (SHBG) among pregnant women in the USA and China. Three hundred and four Caucasian women in Boston and 335 Chinese women in Shanghai were studied. Levels of E2, E3, progesterone and SHBG were measured in maternal blood at weeks 16 and 27 of gestation, and correlated with maternal, gestational and perinatal characteristics. Height, weight and body mass index (BMI) before pregnancy is inversely associated with E2 and SHBG, whereas E3 is inversely associated with height and progesterone is inversely associated with weight and BMI. A previous live birth is associated with lower E2 and SHBG in the index pregnancy. Total gestation duration is inversely associated with E2, E3 and progesterone, whereas weight gain during pregnancy is inversely associated with progesterone and SHBG. In the US, pregnancies with female fetuses are characterized by significantly reduced progesterone. Pregnancy hormones are associated with several maternal, gestational and neonatal characteristics.

Adult↗
PubMed2001

Coexpression of granulocyte colony stimulating factor and its receptor in primary ovarian carcinomas.

Immunohistochemistry was used to determine the expression of granulocyte colony-stimulating factor (G-CSF) and its receptor (G-CSFR) in primary ovarian carcinomas. The expression of G-CSFR was observed in the malignant cells of each of the 46 primary carcinomas examined; G-CSF was coexpressed in both the malignant epithelial cells and the stroma of 56.5% of the specimens. Thus the majority of ovarian carcinomas harbor both potential autocrine and paracrine G-CSF axes. In 37% of the samples, G-CSF was expressed only within stromal cells, suggesting that only a potential paracrine system is in place. In a preliminary, retrospective, evaluation, the survival of patients whose tumors expressed only the apparent paracrine loop was significantly worse than patients whose tumors expressed both potential autocrine and paracrine G-CSF-based regulatory loops (14.5 vs. 42.5 months, respectively). Studies on the potential function of G-CSF were performed using the G-CSFR-expressing OVCAR-3 ovarian carcinoma line. As a single agent, rhG-CSF failed to stimulate [3H]-thymidine incorporation in these cells, but enhanced the mitogenic action of epidermal growth factor (EGF) in a dose-dependent manner. Thus, potential autocrine and/or paracrine loops involving G-CSF and its receptor occur in over 90% of primary ovarian carcinomas, and may act to modulate the action of growth factors.

Cell Survival↗
PubMed2001

Breast cancer risk in women who have had children with different partners.

The fetal antigen hypothesis suggests that the lowered risk of breast cancer in parous women may be afforded by the development of antibodies to fetal antigens that are structurally similar to mammary cancer antigens. It has previously been hypothesized that the likelihood of developing such antibodies may be higher among women who have had children with more than 1 partner. Utilizing information on parenthood and breast cancer available in nationwide Swedish registers, we undertook a case-control study nested within a nation-wide cohort to address this issue. Number of partners fathering a child was categorized as 1, 2 and 3 or more. All analyses were restricted to subjects with 2 or more births and encompassed a total of 20,881 women with breast cancer and 111,989 control women. In an unadjusted analysis, the risk of breast cancer was somewhat lower (odds ratio [OR] = 0.94, 95% confidence interval [CI] 0.89-0.99) in women who had had children with 2 different partners compared with women who had had children conceived with the same partner. After adjustment for parity, age at first birth and educational level, however, the risk of breast cancer was slightly elevated (OR = 1.09, 95% CI: 1.03-1.15). Among women who had had children with 3 or more different men, the pattern was similar. The present results provide no support for the hypothesis that greater antigenic exposure afforded by having children with more than 1 man may reduce the risk of breast cancer. It remains possible, however, that pregnancy may influence breast cancer risk through some immunologic mechanism; further testing of the fetal antigen hypothesis may require development of relevant laboratory measures.

Adult↗
PubMed2001

Chromosome aberrations in lymphocytes of residents living in buildings constructed with radioactively contaminated rebars.

Using the G-banding technique, we examined lymphocytes from 90 individuals (43 males and 47 females, median age 31 years) living in buildings constructed with radioactively contaminated rebars. Forty-five nonexposed control subjects (22 males and 23 females, median age 30 years), matched to the radiation-exposed individuals by sex and age, were selected for comparison. At least 500 metaphases were checked for each individual. All recognizable structural aberrations of chromosomes or chromatids were recorded. After adjusting for age and smoking status, both the percentage of cells with aberrant chromosomes (PCAC) and the number of aberrant chromosomes per 100 cells (NAC) were found to be significantly higher in the radiation-exposed females than in the control females (p < 0.05 for PCAC and NAC). This difference, however, was not observed in the comparison of radiation-exposed and control males. This suggests a possible interaction between sex and radiation exposure in their effects on chromosome aberrations.

Adolescent↗
PubMed2001

Influence of timing of administration of 5-fluorouracil to donors on bone marrow engraftment in nonmyeloablated hosts.

We evaluated the engraftment and the cell cycle status of marrow cells at various times after 5-fluorouracil (5-FU) administration. 5-FU (150 mg/kg) was given to donor male BALB/c mice at 1, 2, 6, or 12 days prior to marrow harvest. The donor cells were then assessed in host nonmyeloablated female mice. Bone marrow engraftment of marrow treated with 5-FU was evaluated and compared to marrow treated with diluent (phosphate-buffered saline) at 3 and 10 weeks after marrow infusion. Our data show a rapid induction of an engraftment defect 1 day after 5-FU, persistence of this defect through day 6, and a recovery by day 12. Experiments using hydroxyurea (which selectively kills cells in the S phase) to determine the cell cycle status indicated that cells that engrafted in post-5-FU marrow were noncycling at days 1, 2, and 12 but cycling at day 6. Post-5-FU bone marrow was also analyzed in vitro by colony assays and its cycling status determined by 3H-thymidine suicide assay. High-proliferative-potential colony-forming cells (HPP-CFCs) and low-proliferative-potential colony-forming cells (LPP-CFCs) decreased rapidly 1 day after 5-FU, with a nadir observed at day 6 for HPP-CFCs and day 2 for LPP-CFCs. By day 12, LPP-CFCs showed a total recovery, but HPP-CFCs were still defective. Significant numbers of HPP-CFCs were cycling, mostly at days 6 and 8 after 5-FU, whereas LPP-CFCs appeared quiescent except at day 2. These results emphasize the importance of timing if post-5-FU marrow is used for gene therapy or marrow transplantation.

Animals↗
PubMed2001

Bigger is better: maternal and neonatal predictors of hematopoietic potential of umbilical cord blood units.

Umbilical cord blood (CB) is a useful stem cell source for patients without matched family donors. CB banking is expensive, however, because only a small percentage of the cord units stored are used for transplantation. In this study, we determined whether maternal factors, such as race, age, and smoking status have an effect on laboratory parameters of hematopoietic potential, such as viability, cell counts, CD34+ cell counts, and CFU-GM. We studied the effect of neonatal characteristics such as birth order, birth weight, gestational age, and sex of the baby on the same laboratory parameters. Race and maternal age had no effect on these laboratory parameters. In multivariate analysis, babies of longer gestational age had higher cell counts, but lower CD34+ cell counts and CFU-GM. Bigger babies had higher cell counts, more CD34+ cells, and more CFU-GM. Women with fewer previous live births also produced cord units with higher cell counts, CFU-GM, and CD34+ cell counts. Specifically, each 500 g increase in birth weight contributed to a 28% increase in CD34+ cell counts, each week of gestation contributed to a 9% decrease in CD34+cell counts, and each previous birth contributed to a 17% decrease in CD34+ cell counts (all P < 0.05). These data may be used to select the optimal cord blood donors and allow CB banks efficient resource allocation.

Adult↗
PubMed2001

Childbearing and the risk of parathyroid adenoma--a dominant cause for primary hyperparathyroidism.

OBJECTIVES: To explore possible associations between the reproductive history amongst women and the risk of parathyroid adenoma (PA). DESIGN: Two nationwide Swedish registries. The Fertility Register included data on more than 3.4 million livebirths between 1943 and 1992 amongst Swedish females born 1925-72. The Cancer Register encompasses more than 1800 women with a diagnosis of PA 1960 until 1992. SETTING: All women resident in Sweden 1960-92. SUBJECTS: Cases were all 1800 women born 1925-72 reported to the Swedish Cancer Registry with a histopathological diagnosis of PA. Five controls were selected at random for each case by matching for the month and year of birth. Conditional logistic regression was used to estimate relative risks of PA. MAIN OUTCOMES: Parathyroid adenoma. RESULTS: High parity (four or more live births) was associated with an increased risk of PA. Amongst women with a diagnosis of PA before menopause (i.e. the age of 50 years) there was an increased risk of PA with younger age at first childbirth. Nulliparous women were at increased risk for PA before menopause, and at decreased risk after menopause. CONCLUSIONS: There is an association between childbearing and the risk of PA, which has not previously been demonstrated, but the underlying biological mechanisms remain to be determined.

Adenoma↗
PubMed2000

Effect of ex vivo cytokine treatment on human cord blood engraftment in NOD-scid mice.

Umbilical cord blood transplantation is considered an alternative to traditional bone marrow transplantation for patients who do not have matched sibling donors. In this study, we examined the effects of ex vivo treatment of human cord blood cells with cytokine mixtures and assessed the ability of treated cells to engraft in NOD-scid mice. We incubated the cord blood with a four-factor cytokine mixture of interleukin (IL)-3, IL-6, IL-11 and stem cell factor, or with a two-factor cytokine mixture of thrombopoietin and flt-3. Incubation of cord blood for 48 h with either cytokine mixture did not affect progenitor cell number or proliferative potential as measured by the high proliferative potential (HPP) assay. Cytokine-treated cord blood injected into irradiated NOD-scid mice resulted in multilineage human engraftment. Overall, incubation with cytokines resulted in variable levels of engraftment with different cord blood samples. Incubation of cord blood with the four-factor cytokine mixture resulted in increased survival of irradiated NOD-scid recipients. These results demonstrate that short-term ex vivo treatment of human progenitor cells gives variable results on in vivo multipotential capabilities.

Animals↗
PubMed2000

Duration of gestation and prostate cancer risk in offspring.

This large population-based nested case-control study investigated the importance of perinatal characteristics as risk factors for prostate cancer in later life in a cohort of men who were born between 1889 and 1941 in Stockholm, Sweden. Eight hundred and thirty-four prostate cancer cases over 18 years of age and of singleton birth were identified from the cohort between 1958 and 1994. For each case, singleton males born live to the first four mothers admitted after the case's mother were selected as potential controls; 1880 eligible controls were included in the study. For each study subject, we obtained data on mother's parity, pre-eclampsia or eclampsia before delivery, age at delivery, and socioeconomic status, as well as child's birth length and weight, placental weight, and gestational age. Odds ratio (OR) estimates and 95% confidence intervals (CIs) were derived from logistic regression analyses. We found no statistically significant differences between cases and controls with respect to maternal age, socioeconomic status, or parity. Birth weight, birth length, and placental weight were also not significantly related to prostate cancer risk. Pregnancy toxemia (OR = 0.33; 95% CI, 0.07-1.45) and longer gestation age were associated with a reduced risk of prostate cancer; the OR estimate was 0.94 (95% CI, 0.89-0.99) for each 1-week prolongation of the duration of gestation. Our results suggest that birth size indicators are not important risk factors for prostate cancer in later life. In addition, our data on gestation age indicate that the late in utero environment may be as important as the early in utero environment in the modulation of prostate cancer risk in offspring.

Aged↗
PubMed2000

Lifestyle factors and insulin-like growth factor 1 levels among elderly men.

Insulin-like growth factor 1 (IGF-1) is a potentially important determinant of disease; hence epidemiological identification of factors that influence circulating IGF-1 is merited. We therefore analysed data collected in Greece to determine the relationship between anthropometric, lifestyle and dietary variables and serum levels of IGF-1 among elderly men. We identified 51 men with prostate cancer, 50 men with benign prostatic hyperplasia, and 52 apparently healthy elderly men (controls), all matched for age (+/- 1 year). These 153 men provided blood specimens and were interviewed using a validated lifestyle and food frequency questionnaire. We performed multivariate linear regression to identify potential predictors of circulating IGF-1. After controlling for age, body mass index, smoking habits, alcohol drinking and coffee consumption, each 5 cm increase in height predicted a 13.0% increase in IGF-1 (95% CI 0.4-27.2%) among the controls and a 11.3% increase in IGF-1 (95% CI 4.5-18.6%) among the entire study group. None of the investigated dietary factors (total fat, carbohydrate, protein, dairy products, tomatoes, calcium) were strongly related to IGF-1 levels. The positive association between IGF-1 and height integrates the empirical evidence linking IGF-1 and height with prostate cancer risk.

Aged↗
PubMed1999

Gender of offspring and maternal breast cancer risk.

A high total number of full-term pregnancies is associated with a reduced risk of breast cancer, though pregnancy transiently increases the risk of the disease. However, little attention has been given to a possible association of breast cancer risk with the gender of offspring, even though male fetuses have been associated with several factors linked to a low breast cancer risk, namely, pregnancy toxemia, increased levels of alpha-fetoprotein (AFP) and increased levels of sex hormone-binding globulin. We used data from linked Swedish registries to study the relative importance of male and female offspring as risk correlates of subsequent breast cancer in the mothers. In a nested case-control study, case patients were 2,328 women who had one or more live-born children delivered between 1973 and 1989 and who were subsequently diagnosed with breast cancer during this period. For comparison, 10,256 control subjects, matched to cases by birth year, were randomly selected from among the eligible women. Number of boys was inversely associated and number of girls positively associated with breast cancer risk. Neither of these trends was significantly different from the null value, but the difference between the 2 trends was marginally significant (p=0.06). Moreover, women who gave birth to 2 or more boys but no girls were at significantly lower risk for breast cancer in comparison to women who gave birth to 2 or more girls but no boys; the odds ratio was 0.78 (95% CI 0.64-0.95). The apparently protective effect of pregnancies with male fetuses was limited to women younger than 40 years. Endocrine or other metabolic processes specifically associated with a male rather than a female fetus may impart relative protection against the occurrence of breast cancer during the childbearing period.

Adolescent↗