Body mass, tobacco smoking, alcohol drinking and risk of cancer of the small intestine--a pooled analysis of over 500,000 subjects in the Asia Cohort Consortium.

BACKGROUND: The evidence for a role of tobacco smoking, alcohol drinking, and body mass index (BMI) in the etiology of small intestine cancer is based mainly on case-control studies from Europe and United States. SUBJECTS AND METHODS: We harmonized the data across 12 cohort studies from mainland China, Japan, Korea, Singapore, and Taiwan, comprising over 500,000 subjects followed for an average of 10.6 years. We calculated hazard ratios (HRs) for BMI and (only among men) tobacco smoking and alcohol drinking. RESULTS: A total of 134 incident cases were observed (49 adenocarcinoma, 11 carcinoid, 46 other histologic types, and 28 of unknown histology). There was a statistically non-significant trend toward increased HR in subjects with high BMI [HR for BMI>27.5 kg/m2, compared with 22.6-25.0, 1.50; 95% confidence interval (CI) 0.76-2.96]. No association was suggested for tobacco smoking; men drinking>400 g of ethanol per week had an HR of 1.57 (95% CI 0.66-3.70), compared with abstainers. CONCLUSIONS: Our study supports the hypothesis that elevated BMI may be a risk factor for small intestine cancer. An etiologic role of alcohol drinking was suggested. Our results reinforce the existing evidence that the epidemiology of small intestine cancer resembles that of colorectal cancer.

Effect of a self-help program for mothers of hemophilic children in Korea.

Mothers of hemophilic children are under stressful situations because of the characteristics of disease and inheritance. The purpose of this study was to evaluate the effect of the self-help group program for the mothers of hemophilic children. Fifty one mothers of hemophilic children were participated. The experiment group (n = 24) participated in the self-help group program for 5 weeks, while the control group (n = 27) received a self-help booklet only. Knowledge, self-efficacy, depression, parenting stress, and quality of life were evaluated using questionnaires. Data were analyzed using χ(2) -test, t-test, and analysis of covariance (ancova). The experiment and control groups were homogeneous in general characteristics and depending variables except knowledge (P < 0.05; P > 0.05, respectively). Knowledge, self-efficacy, and quality of life in the experiment group were increased after the program (P < 0.001). Especially, the knowledge in the experiment group was lower than the control group in pretest, but higher in the posttest (P < 0.001). Depression and parenting stress were reduced in the experiment group compared to the control group (P < 0.001). It is suggestive that the self-help group program can be a useful opportunity for mothers of hemophilic children to improve knowledge and self-efficay of child care and quality of life of themselves; to decrease depression and parenting stress. Extended application of the program to fathers or all family members may be needed to investigate in the future.

Profiling of differentially expressed genes in haemophilia A with inhibitor.

Inhibitor development is the most significant complication in the therapy of haemophilia A (HA) patients. In spite of many studies, not much is known regarding the mechanism underlying inhibitor development. To understand the mechanism, we analysed profiles of differentially expressed genes (DEGs) between inhibitor and non-inhibitor HA via a microarray technique. Twenty unrelated Korean HAs were studied: 11 were non-inhibitor and nine were HA with inhibitor (≥5 BU mL(-1)). Microarray analysis was conducted using a Human Ref-8 expression Beadchip system (Illumina) and the data were analysed using Beadstudio software. We identified 545 DEGs in inhibitor HA as compared with the non-inhibitor patients; 384 genes were up-regulated and 161 genes were down-regulated. Among them, 75 genes whose expressions were altered by at least two-fold (>+2 or <-2) were selected and classified via the PANTHER classification method. The expressions of signal transduction and immunity-related genes differed significantly in the two groups. For validation of the DEGs, semi-quantitative RT-PCR (semi-qRT-PCR) was conducted with the six selected DEGs. The results corresponded to the microarray data, with the exception of one gene. We also examined the expression of the genes associated with the antigen presentation process via real-time PCR. The average levels of IL10, CTLA4 and TNFα slightly reduced, whereas that of IFNγ increased in the inhibitor HA group. We are currently unable to explain whether this phenomenon is a function of the inhibitor-inducing factor or is an epiphenomenon of antibody production. Nevertheless, our results provide a possible explanation for inhibitor development.

Mutation spectrum and inhibitor risk in 100 Korean patients with severe haemophilia A.

Haemophilia A (HA) is an X-linked recessive bleeding disorder caused by defects in the F8 gene encoding the coagulation factor VIII. Mutation analysis in HA is important to confirm the diagnosis, genotype-phenotype correlations and for genetic counselling and family study. The aim of this study was to detect causative mutations of F8 in severe HA patients in Korea and to correlate the mutation type with the risk of inhibitor development. A total of 100 unrelated Korean patients with severe HA were enrolled for this study. The Nijeman modification of the Bethesda assay was used to determine the presence of inhibitor. Molecular analysis of F8 was performed using a combination of molecular techniques, including long-distance polymerase chain reaction, direct sequencing and multiplex ligation-dependent probe amplification (MLPA). We identified causative mutations in 98% of severe HA patients (98/100). Inv22 and Inv1 mutations were detected in 30 patients and one patient, respectively. A total of 59 unique mutations were identified in 69 non-inversion patients, including 24 novel mutations. The overall prevalence of inhibitor was 26%. Inhibitor risk was highest in patients with large deletion mutations identified using MLPA (100%). Among those with point mutations, the prevalence of inhibitor was highest when the mutation occurred in the A3 and C2 domains (60% and 50%, respectively). The molecular diagnostic strategy involving multiplex PCR, sequencing and dosage analyses identified causative mutations in most cases of severe HA. The high inhibitor risk was associated with large deletion mutations and point mutations in A3 and C2 domains.

Haemodynamics and cerebral oxygenation during arthroscopic shoulder surgery in beach chair position under general anaesthesia.

BACKGROUND: Patients undergoing surgery in beach chair position (BCP) are at risk of cerebral ischaemia. We determined the prevalence and risk factors of jugular venous bulb oxygen desaturation (SjvO(2) < 50%) in BCP. It was also examined whether regional cerebral tissue oxygen saturation (SctO(2) ) measured by near-infrared spectroscopy and SjvO(2) are interchangeable for assessment of cerebral oxygenation. METHODS: Fifty-six consecutive patients undergoing arthroscopic shoulder surgery in BCP were studied. Anaesthesia was intravenous with propofol and remifentanil (P/R) or inhalational with sevoflurane and 50% nitrous oxide (S/N) depending on provider choice. Mean arterial pressure (MAP), heart rate (HR), SjvO(2) , and SctO(2) were measured before (baseline; post-induction in supine position) and after the patients assumed BCP. Bland-Altman analysis was performed to measure the agreement between SctO(2) and SjvO(2) . RESULTS: SjvO(2) , SctO(2) , MAP, and HR decreased significantly when patients were raised into BCP. Jugular desaturation occurred in 41% of patients (56% with P/R vs. 21% with S/N anaesthesia, P = 0.0077). Risk factors for the desaturation included P/R anaesthesia [adjusted odds ratio (aOR) 4.76, 95% confidence interval (CI) 1.34-16.95, P = 0.016] and MAP < 50 mmHg (aOR 3.85, 95% CI 1.21-12.25, P = 0.023). Bland-Altman analysis showed a mean difference of -8.9% with 95% limit of agreement between -40.0% and 23.0%. The percentage error [1.96 standard deviation/mean of the reference method] was 48.5%. CONCLUSIONS: The incidence of jugular desaturation in BCP was 41%, and P/R anaesthesia and hypotension were associated with its occurrence while undergoing surgery under general anaesthesia. SctO(2) may not replace SjvO(2) for the determination of cerebral oxygenation.

Thiopental dose requirements for induction of anaesthesia and subsequent endotracheal intubation in patients with complete spinal cord injuries.

BACKGROUND: Dose requirements of thiopental depend on patient characteristics and infusion rate. We determined thiopental dose requirements for induction of anaesthesia, and the effects of remifentanil on cardiovascular and bispectral index (BIS) responses to tracheal intubation in spinal cord-injured (SCI) patients undergoing general anaesthesia. METHODS: Twenty patients with traumatic complete SCI undergoing elective surgery were enrolled. Twenty patients without SCI served as control. Anaesthesia was induced with thiopental, followed by remifentanil 1 µg/kg and rocuronium 0.8 mg/kg, and maintained with 2% sevoflurane and 50% nitrous oxide in oxygen after tracheal intubation. Thiopental was administered at a rate of 50 mg/15 s until abolition of the eyelash reflex. Thiopental doses, BIS values, systolic arterial blood pressure (SAP), heart rate (HR) and plasma catecholamine concentrations were measured. RESULTS: Total thiopental dose required to abolish the eyelash reflex based on total body weight (BW) (5.26 ± 0.87 vs. 3.91 ± 1.07 mg/kg, P < 0.001) or lean BW (6.56 ± 1.37 vs. 5.24 ± 1.36 mg/kg, P < 0.01) were significantly smaller in the SCI group than in the control. SAP was decreased by induction of anaesthesia with thiopental and remifentanil, and increased by tracheal intubation in both groups. However, the peak SAP after intubation was smaller in the SCI patients. HR increased significantly above baseline values following intubation in both groups with no significant intergroup differences. Hypertension was more frequent in the control group. Norepinephrine concentrations remained unaltered following intubation in both groups. CONCLUSIONS: These results suggest that the dose requirements of thiopental for induction of general anaesthesia and subsequent tracheal intubation are reduced in the SCI patients.

Dose-related attenuation of cardiovascular responses to tracheal intubation by intravenous remifentanil bolus in severe pre-eclamptic patients undergoing Caesarean delivery.

BACKGROUND: The optimal dose of remifentanil to attenuate the cardiovascular responses to tracheal intubation in pre-eclamptic patients undergoing Caesarean delivery under general anaesthesia has not been established. We compared the effects of two low doses of remifentanil on the cardiovascular responses to tracheal intubation and neonatal outcomes. METHODS: Forty-eight women with severe pre-eclampsia were randomly assigned to receive either remifentanil 0.5 µg kg⁻¹ (R0.5 group, n=24) or 1 µg kg⁻¹ (R1.0 group, n=24) over 30 s before induction of anaesthesia using thiopental 5 mg kg⁻¹ and succinylcholine 1.5 mg kg⁻¹. Systolic arterial pressure (SAP), heart rate (HR), and plasma catecholamine concentrations were measured. Neonatal effects were assessed using Apgar scores and umbilical cord blood gas analysis. RESULTS: SAP was decreased by induction of anaesthesia and increased by tracheal intubation in both groups. The peak SAP after intubation was greater in the R0.5 group than in the R1.0 group, whereas it did not exceed baseline values in either group. HR increased significantly above baseline in both groups with no significant differences between the groups. Three subjects in the R1.0 group received ephedrine due to hypotension (SAP < 90 mm Hg). Norepinephrine concentrations remained unaltered after intubation and increased significantly at delivery with no significant differences between the groups. Neonatal Apgar scores and umbilical arterial and venous pH and blood gas values were comparable between the groups. CONCLUSIONS: Both doses of remifentanil effectively attenuated haemodynamic responses to tracheal intubation with transient neonatal respiratory depression in pre-eclamptic patients undergoing Caesarean delivery under general anaesthesia. The 1.0 µg kg⁻¹ dose was associated with hypotension in three of 24 subjects.

Altered cardiovascular responses to tracheal intubation in patients with complete spinal cord injury: relation to time course and affected level.

BACKGROUND: We determined cardiovascular responses to tracheal intubation in relation to the time since injury in patients with different levels of spinal cord injury. METHODS: Two hundred and fourteen patients with complete cord injury were studied. They were either quadriplegics (>C7, n=71) or paraplegics (20 yr. Twenty patients with no cord injury served as controls. Systolic arterial pressure (SAP), heart rate (HR), and plasma catecholamine concentrations were determined. RESULTS: Intubation did not affect SAP in the quadriplegics regardless of the time post-injury, but it significantly increased SAP in all paraplegics. Moreover, the pressor response was enhanced in the paraplegics who were 10 yr or more since injury (P<0.05). HR increased significantly in all groups; the magnitude of the increase was less only in acute quadriplegics compared with controls. Plasma concentrations of norepinephrine increased in every group except for the quadriplegics within 4 weeks of injury. The maximum increases in SAP, HR, and norepinephrine from awake baseline values were smaller in the quadriplegics than in the paraplegics (P<0.01). CONCLUSIONS: The cardiovascular and catecholamine responses to intubation change as a function of the time elapsed and the level of the cord injury. In this study, the pressor response to tracheal intubation was abolished in the quadriplegics but not in paraplegics; indeed, it was enhanced at 10 yr or more since injury in this group.

Epstein-Barr virus antibody level and gastric cancer risk in Korea: a nested case-control study.

BACKGROUND: Few cohort studies have investigated Epstein-Barr virus (EBV) infection before the occurrence of gastric cancer. METHODS: Among 14,440 cohort participants, 100 incident gastric cancer cases were individually matched to two controls. Epstein-Barr virus antibodies IgG and IgA against viral capsid antigen (VCA), EBV nuclear antigen (EBNA) antibody IgG, and early antigen (EA) antibody IgG were measured using enzyme immunoassays (EIAs). RESULTS: The highest titres of VCA IgG (odds ratio (OR): 1.37, 95% confidence interval (CI): 0.62-3.06) or EBNA IgG (OR: 0.87, 95% CI: 0.51-1.46) were not associated with gastric cancer risk. CONCLUSION: Higher levels of VCA IgG or EBNA IgG were not associated with increased risk of gastric adenocarcinoma in Koreans.

Cardiovascular and arousal responses to laryngoscopy and tracheal intubation in patients with complete spinal cord injury.

BACKGROUND: We aimed to determine whether the autonomic and arousal responses to laryngoscopy and tracheal intubation were altered in patients with spinal cord injury (SCI). METHODS: One hundred and sixteen patients with traumatic complete SCI were grouped according to the time elapsed after the injury (<3 days and >9 months) and the level of injury (above T5 and below T5): acute high (AH, n=25), chronic high (CH, n=26), acute low (AL, n=20), and chronic low (CL, n=45). Twenty-five patients without SCI served as a control group. Bispectral index (BIS) response, systolic arterial pressure (SAP), heart rate (HR), and plasma concentrations of catecholamines and arginine vasopressin were measured. RESULTS: Both CH and CL groups showed a greater reduction in BIS values after induction of anaesthesia with thiopental compared with controls (P<0.05). However, BIS values after intubation increased similarly in all groups from the value measured just before laryngoscopy. SAP increased in the AL and CL and control groups but not in the AH and CH groups. HR increased significantly in all groups; though to a lesser degree in the AH compared with the other groups. Plasma norepinephrine concentrations increased in all except the AH group, but vasopressin concentrations were unchanged. CONCLUSIONS: The arousal response to laryngoscopy and tracheal intubation as measured by BIS is not altered in SCI, but cardiovascular and catecholamine responses may be changed depending on time elapsed and the level of the injury. However, an identical dose of thiopental may reduce BIS value after intubation more profoundly in patients with chronic SCI.

Effects of remifentanil on cardiovascular and bispectral index responses to endotracheal intubation in severe pre-eclamptic patients undergoing Caesarean delivery under general anaesthesia.

BACKGROUND: We examined the effects of remifentanil on cardiovascular and bispectral index (BIS) responses to tracheal intubation and neonatal outcomes in pre-eclamptic patients undergoing Caesarean delivery under general anaesthesia. METHODS: Forty-two women with severe pre-eclampsia were randomly assigned to receive either remifentanil 1 microg kg(-1) (n=21) or saline (n=21) over 30 s before induction of anaesthesia using thiopentone 4 mg kg(-1) and suxamethonium 1.5 mg kg(-1). Mean arterial pressure (MAP), heart rate (HR) and BIS values as well as plasma catecholamine concentrations were measured. Neonatal effects were assessed using Apgar scores and umbilical cord blood gas analysis. RESULTS: Induction with thiopentone caused a reduction in MAP and BIS in both remifentanil and control groups. Following the tracheal intubation MAP and HR increased in both groups, the magnitude of which was lower in the remifentanil group. BIS values also increased, of which magnitude did not differ between the groups. Norepinephrine concentrations increased significantly following the intubation in the control, while remained unaltered in the remifentanil group. The neonatal Apgar scores at 1 min were significantly lower in the remifentanil group than in the control. However, Apgar scores at 5 min, and umbilical artery and vein blood gas values were similar between the groups. CONCLUSIONS: These results suggest that a single bolus of 1 microg kg(-1) remifentanil effectively attenuates haemodynamic but not BIS responses to tracheal intubation in pre-eclamptic patients undergoing Caesarean delivery under general anaesthesia. However, its use was associated with maternal hypotension and neonatal respiratory depression requiring resuscitation.

Anaesthetic requirement and stress hormone responses in patients undergoing lumbar spine surgery: anterior vs. posterior approach.

BACKGROUND: The intensity of nociceptive stimuli reflects the severity of tissue injury. The anaesthetic requirement and stress hormonal responses were determined to learn whether they differ according to different surgical approaches (anterior vs. posterior) during the spinal surgery. METHODS: Patients undergoing lumbar spine surgery without neurological deficits were divided into two groups: one having posterior (n=13) and the other having anterior fusion (n=13). The end-tidal sevoflurane concentrations (ET(SEVO)) required to maintain the bispectral index score at 40-50 were determined. Mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), serum osmolality and plasma concentrations of catecholamines, cortisol and vasopressin (AVP) were measured. RESULTS: There were no differences in MAP, HR, CVP and serum osmolality between the groups. ET(SEVO) was higher in the anterior than in the posterior group (P<0.05). The plasma concentrations of norepinephrine and cortisol increased in both groups during the surgery, whereas those of epinephrine remained unchanged. AVP concentrations increased during the surgery in the anterior group, and remained unaltered in the posterior group. The anterior group needed more analgesics (P<0.01) during the first 1 h after the operation. CONCLUSIONS: The anterior approach required a deeper level of anaesthesia while undergoing spinal surgery and more use of post-operative analgesics than the posterior approach. It was also associated with a more pronounced AVP release during the surgery.

Identification of mutations in the F9 gene including exon deletion by multiplex ligation-dependent probe amplification in 33 unrelated Korean patients with haemophilia B.

Haemophilia B (HB) is a rare X-linked recessive bleeding disorder caused by a mutation in the F9 gene. The aims of this study were to characterize the mutation spectrum of F9 in Korean patients with HB to establish the optimal molecular diagnostic strategy and to find genotype-phenotype correlations. Study subjects consisted of 33 unrelated Korean patients with HB. We performed polymerase chain reaction (PCR) amplification and direct sequencing of all exons and flanking sequences of F9. When large deletion was suspected from PCR failure, exon dosage test using multiplex ligation-dependent probe amplification (MLPA) was performed. We identified disease-causing mutations in 32 out of 33 patients by direct sequencing analyses (mutation detection rate, 97%). A total of 28 unique mutations were detected, including 7 novel ones. Six mutations were recurrent but observed in no more than two patients. In the remaining one patient, exon 1 was not amplified, and MLPA analysis confirmed a large deletion involving exon 1. The genotype-phenotype correlations between the type of mutation and the severity of factor deficiency were not consistent, as has been previously reported. One patient developed inhibitor, and he was the patient with exon 1 deletion. Based on our results from 33 Korean patients with HB, which showed no hotspot for mutations, direct sequencing of all exons with flanking sequences is needed as the first-line test. MLPA can be a feasible platform at clinical laboratories to detect large deletion mutations in suspected cases.

An extract of Polygonum multiflorum protects against free radical damage induced by ultraviolet B irradiation of the skin.

Over the last decades, the incidence of ultraviolet B (UVB)-related skin problems has been increasing. Damages induced by UVB radiation are related to mutations that occur as a result of direct DNA damage and/or the production of reactive oxygen species. We investigated the anti-oxidant effects of a Polygonum multiflorum thumb extract against skin damage induced by UVB irradiation. Female SKH-1 hairless mice were divided into three groups: control (N = 7), distilled water- (N = 10), and P. multiflorum extract-treated (PM, N = 10) groups. The PM (10 g) was extracted with 100 mL distilled water, cryo-dried and 9.8 g was obtained. The animals received a topical application of 500 microL distilled water or PM extract (1, 2, 4, 8, and 16%, w/v, dissolved in distilled water) for 30 min after UVB irradiation (wavelength 280-320 nm, 300 mJ/cm(2); 3 min) of the dorsal kin for 14 days, and skin immunohistochemistry and Cu,Zn-superoxide dismutase (SOD1) activity were determined. SOD1 immunoreactivity, its protein levels and activities in the skin were significantly reduced by 70% in the distilled water-treated group after UVB irradiation compared to control. However, in the PM extract-treated groups, SOD1 immunoreactivity and its protein and activity levels increased in a dose-dependent manner (1-16%, w/v, PM extract) compared to the distilled water-treated group. SOD1 protein levels and activities in the groups treated with 8 and 16%, w/v, PM extract recovered to 80-90% of the control group levels after UVB. These results suggest that PM extract strongly inhibits the destruction of SOD1 by UV radiation and probably contains anti-skin photoaging agents.

Risk factors for the development of NIDDM in Yonchon County, Korea.

OBJECTIVE: To determine the risk factors for the development of NIDDM in Yonchon County of Korea. RESEARCH DESIGN AND METHODS: We studied 1,193 Korean nondiabetic subjects at baseline who participated in a 2-year follow-up study on diabetes in Yonchon County. A 75-g oral glucose tolerance test was performed 2 years after the baseline examination. Age, sex, and anthropometric and metabolic characteristics at baseline were analyzed simultaneously as potential predictors of conversion to NIDDM. We also designed a nested case-control study to determine the role of hyperinsulinemia and/or hyperproinsulinemia in the conversion to NIDDM in patients with newly developed diabetes and control subjects matched for age, sex, BMI, and waist-to-hip-ratio. RESULTS: At 2 years, 67 subjects developed diabetes, as defined by World Health Organization criteria. The age-adjusted incidence was significantly higher in men (6.4%) than in women (3.0%), and the incidence increased as age increased in both sexes. Multiple logistic regression analysis revealed age, male sex, and fasting and 2-h glucose levels to be significant risk factors for the development of NIDDM, whereas waist-to-hip ratio and BMI were not. In a nested case-control study, baseline proinsulin but not insulin levels were significantly higher in subjects who progressed to NIDDM than in those who did not. CONCLUSIONS: In the Korean population, beta-cell dysfunction, as measured by high proinsulin levels, seems to be associated with subsequent development of NIDDM, whereas regional and general obesity and fasting insulin levels, which may be a surrogate for insulin resistance, were not.

Alcohol consumption, glutathione S-transferase M1 and T1 genetic polymorphisms and breast cancer risk.

To evaluate the potential association between GSTM1 and GSTT1 genotypes and development of breast cancer, a hospital based case-control study was conducted in a South Korean study population consisting of 189 histologically confirmed incident breast cancer cases and their 189 age-matched control subjects with no present or previous history of cancer. A multiplex polymerase chain reaction method was used for the genotyping analyses and statistical evaluations were performed by unconditional logistic regression model. The GSTM1 null genotype was significantly associated with breast cancer risk in premenopausal women [odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1-3.7], but not in the postmenopausal women (OR = 0.9, 95% CI = 0.5-1.9), nor in all women grouped together (OR = 1.3, 95% CI = 0.8-1.1). The GSTT1 null genotype posed a similar risk of breast cancer with an OR of 1.6 (95% CI = 1.0-2.5) for the total breast cancer group, OR of 1.7 (95% CI = 0.9-3.2) for pre-menopausal women, and OR of 1.3 (95% CI = 0.6-2.8) for post-menopausal women. The breast cancer risk associated with concurrent lack of both GSTM1 and GSTT1 genes was 2.2 (95% CI = 1.1-4.5), and the risk increased as the number of null genotype increased (P for trend = 0.03). When the data were stratified by the known risk factors of breast cancer, a significant interaction was observed between the GSTM1 genotypes and alcohol consumption (P for interaction = 0.03). An especially remarkable risk of breast cancer was observed for alcohol-consuming premenopausal women lacking both the GSTM1 and GSTT1 genes (OR = 5.3, 95% CI = 1.0-27.8) compared to those with both of the genes. Our findings thus suggest a novel gene-environment interaction which plays an important role in the individual susceptibility to breast cancer. p6

Relationship between the Val158Met polymorphism of catechol O-methyl transferase and breast cancer.

A case-control study was performed to assess the potential influence of catechol O-methyl transferase (COMT) genotype on the risk of breast cancer in Korean women. One hundred and sixty-three histologically confirmed incident breast cancer cases and 163 age- and menopausal status-matched control individuals with no present or previous history of cancer were selected as study subjects. COMT genetic polymorphism was determined by gel electrophoresis after NlaIII enzyme digestion of amplified DNA. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression after adjustment for known or suspected risk factors of breast cancer. Women with at least one COMT lower enzyme activity associated allele (COMT-L) were at elevated risk for breast cancer (OR = 1.7, 95% CI = 1.04-2.78) compared with those homozygous for high enzyme activity associated COMT-H alleles. Among women with low (> or = 23.1) body mass index the COMT-L allele containing genotypes posed a marginally significant increased risk of breast cancer compared to the COMT-HH genotype (OR = 1.8, 95% CI = 0.95-3.48). Women with at least one COMT-L allele who had experienced a full-term pregnancy when aged over 30 years or were nulliparous had 2.7-fold increased risk; however, this increase did not reach statistical significance (OR = 2.7, 95% CI = 0.64-11.35). Furthermore, never-drinking and never-smoking women with at least one COMT-L allele were at increased risk of breast cancer compared to those with COMT-HH genotype with ORs of 2.0 (95% CI = 1.23-3.38) and 1.7 (95% CI = 1.04-2.62), respectively. These results are consistent with studies showing that COMT genotype of lower enzyme activity might be related to increase in risk of breast cancer, and extend this finding to Korean women.

Changes of pyridoxal kinase expression and activity in the gerbil hippocampus following transient forebrain ischemia.

In the previous study, we observed chronological alterations of glutamic acid decarboxylase (GAD), which is the enzyme converting glutamate into GABA. GAD isoforms (GAD65 and GAD67) differ substantially in their interactions with cofactor pyridoxal 5'-phosphate, which is catalyzed by pyridoxal kinase (PLK). In the present study, we examined the chronological changes of PLK expression and activity in the hippocampus after 5 min transient forebrain ischemia in gerbils. PLK immunoreactivity in the sham-operated group was detected weakly in the hippocampus. Ischemia-related change of PLK immunoreactivity in the hippocampus was significant in the hippocampal cornu ammonis (CA1)region, not in the hippocampal CA2/3 region and dentate gyrus. PLK immunoreactivity was observed in non-pyramidal GABAergic neurons at 30 min to 3 h after ischemic insult. At 12 h after ischemic insult, PLK immunoreactivity was shown in many CA1 pyramidal cells as well as some non-pyramidal cells. At this time point, PLK immunoreactivity and protein content was highest after ischemia. Thereafter, PLK immunoreactivity and protein content is decreased time-dependently by 4 days after ischemic insult. Four days after ischemia, some astrocytes expressed PLK in the CA1 region. The specific PLK activity was not altered following ischemic insult up to 2 days after ischemic insult. Thereafter, the specific PLK activity decreased time-dependently. However, total activity of PLK was significantly increased 12-24 h after ischemic insult, and thereafter total activity of PLK decreased. Therefore, we suggest that the over-expression of PLK in the CA1 pyramidal cells at 12 h after ischemia may induce increase of GAD in the CA1 pyramidal cells, which plays an important role in delayed neuronal death via the increase of GABA or enhancement of GABA shunt pathway.