Body mass index and breast cancer: analysis of a nation-wide population-based prospective cohort study on 1 393 985 Taiwanese women.

BACKGROUND: Asian women have a younger age at onset of breast cancer and a lower body mass index (BMI) than Western women. The link between obesity and risk of breast cancer in Asian women is still elusive. We aimed to investigate the effect of BMI on the risk of incident breast cancer in Taiwanese women. METHODS: A total of 1,393,985 women who had been cancer-free before recruitment and attended a nation-wide Taiwanese breast cancer-screening program between 1999 and 2009 were enrolled using a prospective cohort study. Obesity and other relevant variables (such as menopause status and other biochemical markers) were collected through in-person interviews, anthropometric measurements and blood samples at first screen. Incident breast cancers during follow-up were ascertained through the linkage of the cohort with the National Cancer Registry and the National Death Certification System. RESULTS: A total of 6969 and 7039 incident breast cancer cases were identified among women enrolled before and after menopause, respectively. Compared with a BMI range of 18.5-23.9 kg m(-)(2), the incremental level of BMI in the enrolled women before menopause revealed a lack of statistically significant association with the risk of incident breast cancer (adjusted hazard ratio=0.94, 0.98, 1.02, 1.01 and 0.82 for BMI <18.5, 24-26.9, 27-29.9, 30-34.9 and ⩾35, respectively), but the incremental level of BMI in the enrolled women after menopause led to a statistically significant incremental increase in the risk of breast cancer (adjusted hazard ratio=0.78, 1.19, 1.31, 1.53 and 1.65 for BMI <18.5, 24-26.9, 27-29.9, 30-34.9 and ⩾35, respectively) after adjusting for other explanatory risk factors. CONCLUSION: Obesity acts mainly as an influential promoter of the development of late-onset breast cancer after menopause in Taiwanese women.

An initial assessment of the feasibility and effectiveness of implementing diabetes shared care system in Taiwan--some experiences from I-Lan County.

Diabetes is the fifth leading cause of death in Taiwan and the burden of suffering is still increasing. Building a comprehensive and efficient health care system is crucial to improve the outcome of the diabetics. We implemented the first diabetes shared care system of Taiwan in I-Lan County since August 1996 under the support of Department of Health, the Executive Yuan. This county-wide system was named 'Lan-Yang Diabetes Shared Care System' by the regional steering committee. Regional guidelines for diabetes management were developed after extensive discussion. A multidisciplinary diabetes care team was organized through a training and certification process. Registered patients held diabetes passports to keep clinical record. Physicians of the system use shared referral protocols and sheets. By the end of June 1999, 99 medical professionals had completed their training for diabetes shared care and been certified. The shared care system awarded 26 clinics to hang the lamp signs with the system logo to make them distinguishable. Such clinics have now been available throughout 12 townships in I-Lan County. The number of registered patients carrying diabetes passport increased to 3484 and there was a community-based patient group in every township of I-Lan County. The amount of continuing diabetes clinical training delivered by the specialists to the primary care physicians and non-physician professionals increased to 1681 person-hours per year. The proportion of registered patients undertaking fundus examination within 1 year increased to 30.9%, checking urine micro-albumin to 28.0% and checking HbA(1c) 72.8%, respectively. Mean HbA(1c) value decreased from 8.7% in the first year to 7.9% in the third year. Our study showed that under the co-ordination by regional health bureau with integration of different levels of medical facilities, governmental sectors and non-governmental community resources, the diabetes shared care model is feasible in Taiwan. Through its implementation, quality of regional diabetes care has achieved preliminary improvement.

Cardiac beriberi among illegal mainland Chinese immigrants.

The most common symptoms of chronic beriberi due to thiamine deficiency include dyspnoea, fatigue, leg oedema, lower extremity weakness and numbness. When collapsed peripheral circulation, metabolic acidosis, or shock are present, the disease has advanced from chronic beriberi to pernicious or fulminating beriberi heart failure (Shoshin beriberi). We report two patients with fulminating beriberi; both of whom had been incarcerated at a detention centre for 5 months before hospitalization. A prolonged monotonous diet, low in thiamine, was a major risk factor in both patients. Thiamine deficiency should be considered for any patient with symptoms and signs compatible with beriberi.

Incidence of transitional cell carcinoma and arsenic in drinking water: a follow-up study of 8,102 residents in an arseniasis-endemic area in northeastern Taiwan.

A significant association between ingested arsenic and bladder cancer has been reported in an arseniasis-endemic area in southwestern Taiwan, where many households share only a few wells in their villages. In another arseniasis-endemic area in northeastern Taiwan, each household has its own well for obtaining drinking water. In 1991-1994, the authors examined risk of transitional cell carcinoma (TCC) in relation to ingested arsenic in a cohort of 8,102 residents in northeastern Taiwan. Estimation of each study subject's individual exposure to inorganic arsenic was based on the arsenic concentration in his or her own well water, which was determined by hydride generation combined with atomic absorption spectrometry. Information on duration of consumption of the well water was obtained through standardized questionnaire interviews. The occurrence of urinary tract cancers was ascertained by follow-up interview and by data linkage with community hospital records, the national death certification profile, and the cancer registry profile. Cox proportional hazards regression analysis was used to estimate multivariate-adjusted relative risks and 95% confidence intervals. There was a significantly increased incidence of urinary cancers for the study cohort compared with the general population in Taiwan (standardized incidence ratio = 2.05; 95% confidence interval (CI): 1.22, 3.24). A significant dose-response relation between risk of cancers of the urinary organs, especially TCC, and indices of arsenic exposure was observed after adjustment for age, sex, and cigarette smoking. The multivariate-adjusted relative risks of developing TCC were 1.9, 8.2, and 15.3 for arsenic concentrations of 10.1-50.0, 50.1-100, and >100 microg/liter, respectively, compared with the referent level of < or =10.0 microg/liter.

Product distribution and pre-steady-state kinetic analysis of Escherichia coli undecaprenyl pyrophosphate synthase reaction.

Undecaprenyl pyrophosphate synthase (UPPs) catalyzes the condensation of eight molecules of isopentenyl pyrophosphate (IPP) with farnesyl pyrophosphate (FPP) to generate C(55) undecaprenyl pyrophosphate. We investigated the kinetics and mechanism of this reaction pathway using Escherichia coli UPPs. With a variety of different ratios of enzyme to substrate and FPP to IPP in the presence or absence of Triton, different product distributions were found. In the presence of excess FPP, the intermediates (C(25)-C(50)) accumulated. Under a condition with enzyme and FPP in excess of IPP, instead of C(20)-geranylgeranyl pyrophosphate, C(20), C(25), and C(30) were the major products. The UPPs steady-state k(cat) value (2.5 s(-1)) in the presence of 0.1% Triton was 190-fold larger than in the absence of Triton (0.013 s(-1)). The k(cat) value matched the rate constant of each IPP condensation obtained from the enzyme single-turnover experiments. This suggested that the IPP condensation rather than product release was the rate-limiting step in the presence of Triton. In the absence of Triton, the intermediates formed and disappeared in a similar manner under enzyme single turnover in contrast to the slow steady-state rate, which indicated a step after product generation was rate limiting. This was further supported by a burst product formation. Judging from the accumulation level of C(55), C(60), and C(65), their dissociation from the enzyme cannot be too slow and an even slower enzyme conformational change with a rate of 0.001 s(-1) might govern the UPPs reaction rate under the steady-state condition in the absence of Triton.

Isolation and characterization of proteins that bind to galactose, lipopolysaccharide of Escherichia coli, and protein A of Staphylococcus aureus from the hemolymph of Tachypleus tridentatus.

In this study, we report the isolation and characterization of three novel hemolymph proteins that are believed to be involved in the innate immune response of horseshoe crabs, Tachypleus tridentatus. They include two closely related proteins, one that binds to the protein A of Staphylococcus aureus (PAP) and another that binds to the lipopolysaccharide of Escherichia coli (LBP). PAP binds specifically to staphylococcal protein A (SpA) with a K(D) of 3.86 x 10(-5) M, whereas LBP binds to lipopolysaccharide (LPS) with a K(D) of 1.03 x 10(-6) M. Both PAP and LBP are glycoproteins with an apparent molecular mass of about 40 kDa. N-terminal sequences of PAP and LBP showed 61.9 and 72.2% identity, respectively, to tachylectin-3, a lectin isolated from the amebocyte of T. tridentatus, previously characterized by its affinity to the O-antigen of LPS and blood group A antigen (Muta, T., and Iwanaga, S. (1996) Curr. Opin. Immunol. 8, 41-47). The third protein, a galactose-binding protein (GBP), was found to bind tightly to Sepharose CL-4B and could only be eluted from the column matrix with chaotropic agents, such as 4 M urea or 2 M guanidine hydrochloride. Further analysis indicated that GBP binds to D(+)-galactose with a K(D) of 2.47 x 10(-7) M. N-terminal sequence analysis showed that GBP shared a 50% identity with lectin L-6, identified in the granules of amebocyte of T. tridentatus. (Gokudan, S., Muta, T., Tsuda, R., Koori, K., Kawahara, T., Seki, N., Mizunoe, Y., Wai, S. N. , Iwanaga, S., and Kawabata, S. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 10086-10091). Lectin-L6 and tachylectin-3 are nonglycosylated intracellular proteins with about half the molecular mass of PAP, LBP, and GBP. GBP also binds to PAP and LBP with K(D) values of 1.25 x 10(-7) and 1.43 x 10(-8) M, respectively, and this binding is enhanced about 10-fold upon the addition of SpA and LPS to form the GBP.PAP.SpA and GBP.LBP.LPS complexes, respectively.

On the biosynthesis of alternating alpha-2,9/alpha-2,8 heteropolymer of sialic acid catalyzed by the sialyltransferase of Escherichia coli Bos-12.

Escherichia coli Bos-12 synthesizes a heteropolymer of sialic acids with alternating alpha-2,9/alpha-2,8 glycosidic linkages (1). In this study, we have shown that the polysialyltransferase of the E. coli Bos-12 recognizes an alpha-2,8 glycosidic linkage of sialic acid at the nonreducing end of an exogenous acceptor of either the alpha-2,8 homopolymer of sialic acid or the alternating alpha-2,9/alpha-2,8 heteropolymer of sialic acid and catalyzes the transfer of Neu5Ac from CMP-Neu5Ac to this residue. When the exogenous acceptor is an alpha-2,8-linked oligomer of sialic acid, the main product synthesized is derived from the addition of a single residue of [14C]Neu5Ac to form either an alpha-2,8 glycosidic linkage or an alpha-2,9 glycosidic linkage at the nonreducing end, at an alpha-2, 8/alpha-2,9 ratio of approximately 2:1. When the acceptor is the alternating alpha-2,9/alpha-2,8 heteropolymer of sialic acid, chain elongation takes place four to five times more efficiently than the alpha-2,8-linked homopolymer of sialic acid as an acceptor. It was found that the alpha-2,9-linked homopolymer of sialic acid and the alpha-2,8/alpha-2,9-linked hetero-oligomer of sialic acid with alpha-2,9 at the nonreducing end not only failed to serve as an acceptor for the E. coli Bos-12 polysialyltransferase for the transfer of [14C]Neu5Ac, but they inhibited the de novo synthesis of polysialic acid catalyzed by this enzyme. The results obtained in this study favor the proposal that the biosynthesis of the alpha-2, 9/alpha-2,8 heteropolymer of sialic acid catalyzed by the E. coli Bos-12 polysialyltransferase involves a successive transfer of a preformed alpha-2,8-linked dimer of sialic acid at the nonreducing terminus of the acceptor to form an alpha-2,9 glycosidic linkage between the incoming dimer and the acceptor. The glycosidic linkage at the nonreducing end of the alternating alpha-2,9/alpha-2,8 heteropolymer of sialic acid produced by E. coli Bos-12 should be an alpha-2,8 glycosidic bond and not an alpha-2,9 glycosidic linkage.

Use of nonautologous microencapsulated fibroblasts in growth hormone gene therapy to improve growth of midget swine.

The aim of the present study was to investigate the expression activity, both in vitro and in vivo, of the porcine growth hormone complementary DNA (pGH cDNA) in porcine fetal fibroblast (PFF) cells. The pGH gene had been constructed inside the bicistronic retroviral vector PSN and subsequently transfected into PFF cells further encapsulated with immunoprotective microcapsules. This would provide a way to evaluate the improvement in growth performance of Tao-Yuan swine by the use of nonautologous microencapsulated fibroblasts carrying the pGH cDNA via the technique of somatic gene therapy. Results from Southern blot analysis confirmed that the full length of the pGH cDNA was completely integrated into the genome of the PFF cells after they had been infected one to four times using a PSN retroviral vector. Moreover, Northern blot analysis showed that high transcription activity was present in clones infected twice, and exogenous pGH secretion was found when the pGH-infected PFF had been further cultured for 48 hr in vitro and subjected to immunoblot assay. Encapsulation of the pGH-PFF with an alginate-poly-L-lysine-alginate membrane did not show any deterioration in their proliferation and survival both in vitro and in vivo. The pGH gene in encapsulated recombinant fibroblasts was fully expressed after it had been transplanted into the peritoneal cavity of the Tao-Yuan swine, and reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed on the microcapsules retrieved 1 month later. The feasibility of pGH gene therapy to improve midget Tao-Yuan swine growth enhancement is further supported by the fact that transplantation of the encapsulated recombinant fibroblast cells resulted in a much more significant increase in weight gain than in those swine in either the age-matched untreated control group or in those that had been transplanted with uncapsulated recombinant PFF cells (10.56 +/- 1.01 kg versus 6.95 +/- 0.94 and 5.27 +/- 1.30 kg; p < 0.05). These experimental data suggest that growth hormone gene therapy did provide an alternative approach for growth improvement in midget Tao-Yuan swine.

The porcine sperm motility inhibitor is identical to beta-microseminoprotein and is a competitive inhibitor of Na+,K(+)-ATPase.

We have isolated a small porcine seminal protein called SMI-1. Our results from peptide sequence, amino acid composition and mass spectral analyses reveal that SMI-1 is identical to porcine beta-microseminoprotein, a protein with unknown function. We also report here that this protein inhibits competitively the activity of Na+,K(+)-ATPase purified from porcine cerebral cortex in a dose-dependent manner. The inhibitory effect could be reversed by the addition of ATP. The half-maximal inhibition was achieved at an inhibitor concentration of 90 microM.

Partial reversion of transformed phenotype of B104 cancer cells by antisense nucleic acids.

We used antisense RNA to inhibit the expression of oncogene neu and investigated the effects of diminished neu expression on the phenotypes of B104 cells containing activated oncogene neu. Antisense MT-neu and pSV-neo plasmids were cotransfected into neuroblastoma B104 cells. Southern analysis showed the integration of anti-neu DNA into B104 cells. The expression of neu was inhibited up to 90% as quantitated by immunoprecipitation. The growth rate and the potential to differentiate in these transfectants were not affected as compared to the parental cell lines. The ability to grow in soft agar was inhibited more than 90% in these transfectants. Our results indicated that antisense-RNA against a specific oncogene can decrease the tumorigenicity of tumor cells but may not be able to revert it to normal cells completely.

Release of the p53-induced repression on thymidine kinase promoter by single p53-binding sequence.

Herpes simplex thymidine kinase (TK) promoter was shown to be repressed by the wild-type p53. Using a model system that the p53-binding site was linked to the thymidine kinase promoter, we demonstrated that single p53-specific binding site was sufficient to abolish the repression. On the contrary, the mutant p53 had the opposite effects on the HSV-TK promoter in BHK cells. The results suggest that the p53-binding site may act as an enhancer to regulate the gene expression in a novel way in vivo.

Insulin-like growth factor I stimulates transcription of the c-jun proto-oncogene in Balb/C 3T3 cells.

Treatment of quiescent Balb/c 3T3 cells with insulin-like growth factor I (IGF I) resulted in the stimulation of proto-oncogene c-jun transcription. Cells exposed to cycloheximide and IGF I together showed super-induction of c-jun transcripts. Nuclear run-off assay revealed that IGF I up-regulated c-jun only while cycloheximide was present. The stability of c-jun mRNA was markedly increased in the cells treated with IGF I. These results suggest that IGF I controls the expression of c-jun by increasing the transcriptional activity and stabilizing the existing transcripts.

The effects of glucocorticoid hormone on the expression of c-jun.

The effects of glucocorticoid hormone on the expression of c-jun in the fibroblasts were studied. The expression of c-jun was repressed by dexamethasone in the NIH3T3 cells, but not in the transformed B104-1 or EJ-Ras cells. The repression was not relieved by the addition of cycloheximide.