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The aim of this study was to evaluate whether anti-beta2 glycoprotein-I antibody (anti-beta2GPI) of the IgG or IgM classes is associated with the development of pregnancy-induced hypertension (PIH) or preeclampsia in the Japanese population. In a case-controlled cohort study, peripheral blood was obtained at 8-14 weeks of gestation from a consecutive series of 1155 women. The case group comprised 36 patients who later developed PIH during the pregnancy. Of the 36 PIH patients, 13 had severe PIH, 18 had preeclampsia and 11 had severe preeclampsia. One hundred and eleven age- and parity-matched women whose pregnancies ended in normal delivery without obstetric complications were selected as controls. We found that a titer of anti-beta2GPI IgG>or=1.0 U/ml was a risk factor for severe PIH (P=0.023, OR 5.7 95%CI 1.4-22.8). In addition, titers of anti-beta2GPI IgM>or=1.2 U/ml was found to be a risk factor for PIH (P=0.001, OR 8.8 95%CI 1.6-47.5). In women positive for anti-beta2GPI but negative for lupus anticoagulant, anti-cardiolipin, phosphatidylserine-dependent anti-prothrombin, or kininogen-dependent anti-phosphatidylethanolamine antibodies, the presence of anti-beta2GPI was not a significant risk factor for development of PIH or preeclampsia. In conclusion, the presence of anti-beta2GPI antibody represents a risk factor for developing PIH and severe PIH. This finding supports the utility of anti-beta2GPI determination as one of the laboratory criteria for anti-phospholipid syndrome classification. The usefulness of anti-beta2GPI measurement among women without other anti-phospholipid antibodies requires further study.

Background: Pregnancy-induced hypertension (PIH) is a common cause of perinatal mortality. It is believed to result from the interaction of several factors, including those related to the blood coagulation system. We performed genotyping and subgroup analyses to determine if the 4G/5G genotypes of the plasminogen activator inhibitor-1 gene (PAI-1) play a role in the pathogenesis of PIH, and to evaluate possible interactions of the PAI-1 polymorphisms with those of the angiotensinogen gene (AGT) and the endothelial nitric oxide synthase gene (NOS3). Methods: An association study of PAI-1 polymorphism, and subgroup analyses of common variants of AGT and NOS3, among 128 patients with PIH and 376 healthy pregnant controls. Results: No significant differences were found between the cases and controls in the frequencies of allele 4G or the 4G/4G genotype. In subgroup analyses, after adjustment for multiple comparison, a significant association with the AGT TT genotype was found among women with the PAI-1 4G/4G genotype, and an association with the NOS3 GA+AA genotype was found among women with the 5G/5G or 4G/5G genotypes. Conclusions: Our findings suggest that there are at least 2 pathways in the pathogenesis of severe PIH. However, with respect to early prediction and prevention of severe PIH, although the PAI-1 4G/4G genotype alone was not a risk factor for severe PIH, the fact that PAI-1 genotypes are associated with varying risks for severe PIH suggests that PAI-1 genotyping of pregnant women, in combination with other tests, may be useful in the development of individualized measures that may prevent severe PIH.

STUDY DESIGN A sex- and age-matched case-control study with genotyping of the FokI variant of the vitamin D receptor gene (VDR) was carried out. OBJECTIVES To facilitate the early prediction, prevention, and treatment of ossification of the posterior longitudinal ligament (OPLL) of the spine, we analyzed the FokI variant of VDR and past body mass indexes, histories of past illness, family history, and body pliability along with lifestyle factors. SUMMARY OF BACKGROUND DATA Many possible genetic and environmental risk factors for OPLL have been suggested, including male sex, high body mass index, diabetes mellitus, trauma, hormonal imbalance, and dietary and sleeping habits and genetic variants. METHODS Both a self-administered questionnaire and whole blood samples were obtained from 63 patients with OPLL and 126 sex-, age-, and hospital-matched controls free of backbone diseases were randomly selected from hospital patients. VDR genotyping was carried out using PCR-RFLP methods. After univariate analysis, multivariate and subgroup analyses according to the VDR genotype was applied to clarify the confounding relationship between VDR genotype and other possible risk factors. RESULTS A multivariate analysis revealed that the VDR FF genotype, family history of myocardial infarction, high body mass index at age 40, long working hours, and working with night shift to be independent potent risk factors for OPLL. CONCLUSION The risk of developing OPLL may possibly be reduced gradually and effectively by removing or minimizing the effect of such lifestyle factors one at a time through targeted preventive intervention.

To determine whether the C677T polymorphism of the methylenetetrahydrofolate reductase ( MTHFR) gene and the Leiden mutation of coagulation factor V (FV) are associated with recurrent spontaneous abortion (RSA) of unexplained etiology in Japanese participants, the genotypes of the two polymorphisms were determined and compared between cases of unexplained RSA and normal pregnant controls. Eighty-three Japanese participants, consisting of 45 women with explained RSA and 38 women with unexplained RSA, and 174 controls were recruited in the study. The frequencies of the T677 allele/TT genotype were not significantly different among women with explained RSA (35.6%/13.3%), women with unexplained RSA (34.2%/7.9%), primigravid controls (35.1%/11.7%), and multigravid controls (39.7%/16.5%). In the cases of unexplained RSA, the frequencies of the T677 allele and TT genotype tended to increase according to the number of previous spontaneous abortions, but the increase was without statistical significance: the frequencies of the T677 allele and TT genotype in women with two abortions were 18.2% and 0%, whereas in women with three abortions the frequencies were 38.0% and 9.5%, and in women with four or more abortions the frequencies were 50.0% and 16.7%, respectively. In addition, no Leiden mutation of FV was detected in the women with RSA or the controls. Neither T677 of the MTHFR nor the Leiden mutation of FV was associated with unexplained RSA in the Japanese population.

To assess the association between the egogram and hypertension in pregnancy (HP), a case-control study was carried out. Seventy-one HP cases, primiparous aged 20 to 34 years, and 109 controls, were enrolled among pregnant women who visited our hospitals for obstetrical care. Data from a self-administered questionnaire containing a Self Grow-Up Egogram (SGE) were subjected to univariate and multivariate analyses with prepregnancy body mass index (BMI) and angiotensinogen (AGT) genotype. The mean +/- standard error of total scores for the critical parent (CP) scale were 9.7 +/- 0.5 for cases and 8.3 +/- 0.3 for controls, those for the nurturing parent (NP) scale were 13.6 +/- 0.4 for cases and 13.4 +/- 0.3 for controls, those for the adult (A) scale were 11.3 +/- 0.5 for cases and 10.9 +/- 0.3 for controls, those for the free child (FC) scale were 12.3 +/- 0.3 for cases and 13.8 +/- 0.3 for controls, and those for the adapted child (AC) scale were 10.2 +/- 0.4 for cases and 8.5 +/- 0.4 for controls. A low FC scale score (FCor = 10) and a high AC scale score (AC10) were significantly associated with HP ( p0.05; p0.01, respectively). In the multivariate analysis, FCor = 10, AC10, prepregnancy BMIor = 24, and homozygosity of the T235 allele genotype of the AGT gene were detected as the potent independent risk factors for HP. The odds ratios were 2.2, 2.8, 4.0, and 2.5, respectively. The present results suggest that a low FC score and a high AC score may be potent, independent risk factors for HP.

The relation between dietary habits and the risk of ossification of the posterior longitudinal ligaments of the spine (OPLL) was investigated in a case-control study conducted in Japan from 1998 to 2001. Prevalent OPLL cases (n = 69) were identified and individually matched by age and sex with community controls (n = 138) randomly selected from the general population in Hokkaido. A self-administered food-frequency questionnaire was used to assess habitual dietary intake. The odds ratio (OR) and its 95% confidence interval (CI) were estimated, using conditional logistic regression models to compute the OR adjusted for a history of diabetes mellitus. We found that frequent consumption of pickles (salted products) was significantly associated with an increased risk of OPLL, with an adjusted OR of 1.6 (95% CI, 1.1 to 2.2). The adjusted OR for nondaily consumers of rice was 3.0 (95% CI, 2.4 to 3.7). Frequent consumption of chicken (adjusted OR, 0.5; 95% CI, 0.3 to 0.98) and soy foods (adjusted OR, 0.4; 95% CI, 0.2 to 0.7) was significantly associated with a decreased risk of OPLL. Our findings suggest that dietary habits may constitute independent risk factors for OPLL. Further studies will be needed to prospectively determine the relationship between dietary habits and OPLL risk.

Study design A sex- and age-matched case-control study was carried out. Objectives To facilitate early prediction, prevention, and treatment of ossification of the posterior longitudinal ligament of the spine, the authors analyzed histories of past illness, past body mass indexes, and body pliableness by nature, adjusted for other factors considered to be risk factors. Summary of background data The cause of ossification of the posterior longitudinal ligament of the spine has not yet been elucidated in detail, although many possible causative factors have been suggested, including gender, diabetes mellitus, trauma, hormonal imbalance, and dietary habits. Methods A self-administered questionnaire was obtained from 69 patients with ossification of the posterior longitudinal ligament of the spine and 138 sex- and age-matched control participants who were free of spinal disease, randomly selected from participants in a health checkup in a town. After univariate analysis, a stepwise method was applied to select significant factors in multivariate analysis. Results A multivariate analysis revealed that the following three indicators were independent potent risk factors for ossification of the posterior longitudinal ligament of the spine: history of diabetes mellitus, history of lumbago, and maximum body mass index before manifestation > or =25, after adjustment for other possible lifestyle risk factors. Conclusion Excessive weight gain between 20 and 40 years of age, diabetes mellitus, and lumbago were found to be independent risk factors for ossification of the posterior longitudinal ligament of the spine. Follow-up studies, including the addition of hospital-based control participants and analysis of genetic polymorphisms, will be needed in the future.

Hypertension in pregnancy (HP) is a multifactorial disease manifested due to a complex combination of environmental factors and several predisposing genes including factors in the renin angiotensin system. The aim of this study was to assess the association between the A1166C variant of the angiotensin II type 1 receptor (AT1) gene and severe HP. We carried out association studies and multivariate analyses including other candidate causal factors of HP such as the M235T variant of the angiotensinogen (AGT) gene, prepregnancy body mass index (BMI), and family history of hypertension in Japanese subjects. One hundred and fourteen patients with severe HP and 291 normal pregnancy controls were genotyped. Among primiparous subjects, the frequency of "AC+CC genotype of AT1" was significantly higher in severe HP than in the controls. A multivariate analysis with "AC+CC genotype of AT1" and "TT genotype of AGT" revealed that these were independently associated with primiparous severe HP. However, when "family history of hypertension" and "prepregnancy BMIor =25" were added as factors examined in the multivariate analysis, only "TT genotype of AGT" and "family history of hypertension" were found to be independent potent factors. The present results suggest that the C1166 allele of the AT1 gene may be concerned with the predisposition to essential hypertension independently of the T235 allele of the AGT gene.

Hypertension in pregnancy (HP), including preeclampsia (PE), is known to be a multifactorial disease. Recently, an Ile105Val variant of the glutathione S-transferase P1 gene ( GSTP1) was shown to be associated with PE in The Netherlands. We therefore performed an association study of the Ile105Val variant comparing 131 patients with HP and 327 normal pregnant controls in Japan. We analyzed the data in the context of other risk factors before pregnancy. The frequency of the Ile/Val+Val/Val genotype of the GSTP1 was not significantly different between the HP (26%) patients and the controls (28%). However, in primiparous patients, the frequency was significantly different in elderly pregnancy (63% in severe HP vs. 18% in controls; P < 0.05), in the subgroup with the MM+MT genotypes of the angiotensinogen gene (50% in severe HP vs. 26% in controls; P < 0.05), and in the subgroup with the GA+AA genotypes of the endothelial nitric oxide synthase gene (42% in severe HP vs. 13% in controls; P < 0.05). These results suggest that this variant of the GSTP1 may play a role in the manifestation of HP together with other independently and/or synergistically acting factors, particularly in primiparous pregnancy.

We sought to perform a tree-based analysis of lifestyle risk factors for hypertension in pregnancy (HP) with univariate and multivariate analyses. Seventy-eight HP patients and 199 normal controls were recruited from primiparous women 20 to 34 years of age. Data from angiotensinogen (AGT) genotyping and data from a self-administered questionnaire about lifestyle were subjected to univariate and multivariate analyses. By dividing the subjects into two subgroups--those who possessed "the TT genotype of AGT" and "body mass index (BMI) < 24" and those who did not--we were able to examine the acquired risk factors for HP during pregnancy in these two groups. Multivariate analysis selected "mentally stressful condition" and "no antenatal training during pregnancy" in the former group, and "poorly balanced diet" in the latter group. Determination of factors obvious before pregnancy, such as genotype or prepregnancy BMI, may be useful for devising effective individualized strategies for preventing HP.

Hypertension in pregnancy (HP), including preeclampsia, is known to be a multifactorial disease. Recently, a Glu298Asp variant of the endothelial nitric oxide synthase gene (NOS3) was identified as being associated with coronary spasm and myocardial infarction, whereas it has been reported that endothelial nitric oxide synthase plays a role in HP. We therefore performed an association study of the Glu298Asp variant with HP among 152 HP patients and 335 normal pregnant control individuals, in the context of other risk factors before pregnancy. The frequency of the variant GA+AA NOS3 genotypes was significantly higher in the patients (0.23) than in the controls (0.12) (P0.01). Multivariate analysis revealed that family history of hypertension, TT genotype of the angiotensinogen gene (AGT), GA+AA NOS3 genotype, and prepregnancy body mass indexor = 24 were independent potent risk factors, after adjustment for maternal age and parity. The odds ratios of the factors were 2.7, 2.3, 2.2, and 2.1, respectively. Our results suggested that the Asp298 of NOS3 is a potent, independent risk factor for HP.

Antiphospholipid antibody (aPL) is associated with thromboembolism. There is scant evidence of a relationship between the aPL profile and serious adverse pregnancy outcome. The aim of this study was to assess whether aPL measurements during early pregnancy were useful in predicting a serious adverse pregnancy outcome. In this prospective study, we measured aPLs, including lupus anticoagulant (LA), IgG, IgM, IgA anticardiolipin antibody (aCL), IgG, IgM phosphatidylserine-dependent antiprothrombin antibody, and IgG kininogen-dependent antiphosphatidylethanolamine antibody (aPE) during the first trimester in a consecutive series of 1155 women. The 99 th percentile cut-off values in each aPL were determined using samples from 105 women who did not exhibit any pregnancy morbidity. We assessed the predictive risk of a serious adverse pregnancy outcome adjusted for confounding factors. We found that IgG aCL was associated with developing pregnancy-induced hypertension (PIH) (odds ratio 11.4, 95% CI 2.7-48); IgG aPE with PIH (8.3, 2.4-29), severe PIH (20.4, 4.5-91), and premature delivery (PD) (12.7, 3.1-50); and LA with PD (11.0, 2.8-44) and low birth weight (8.0, 2.1-31). The combinations of IgG aPE plus IgG aCL (17.5, 4.7-66.7) or IgG aPE plus LA (22.2, 5.4-909) measurements predicted severe PIH with 30.8% sensitivity and 99.2% specificity. We conclude that aPL measurements during early pregnancy may be useful in predicting adverse pregnancy outcome.

To clarify whether the homozygous deletion (DD) genotype of angiotensin-converting enzyme gene ( ACE) is a genetic risk factor for preeclampsia in Japanese women, we performed ACE genotyping in patients with preeclampsia and healthy pregnant women, and analyzed the relationship between preeclampsia and ACE genotype, taking into account some well-known contributing factors for preeclampsia, such as primiparity, positive family history of hypertension, prepregnancy body mass index < 24, and heterozygosity and homozygosity of T235 (MT+TT) genotypes of the angiotensinogen ( AGT) gene. Among all of the subjects, the frequency of the DD genotype was not different between patients with preeclampsia and controls (16% and 12%, respectively). Regarding primiparity, prepregnancy body mass index < 24, and MT+TT genotypes of AGT, no significant differences in the frequency of the DD genotype of ACE were found between patients with preeclampsia and controls, although in a subgroup positive for family history of hypertension, the frequency of the DD genotype tended to be higher in patients with preeclampsia (25%) than in controls (8%; p = 0.061). Carrying the DD genotype may have some influence on the pathogenesis of preeclampsia, perhaps through effects on placental hypoxia or the interaction of hypertensive disease and atherosclerosis, although this influence may not be strong. Additional studies using a larger number of patients and analyses that include other genetic and environmental factors will be necessary to confirm these results.

We report a case of pulmonary intravascular lymphoma of large B cell type in a 72-year-old woman. She had a one-month history of fever and dry cough before admission. Chest X-ray revealed ground glass shadow in both lung fields, and the high-resolution CT disclosed centrilobular distribution of ground glass opacities. Transbronchial lung biopsy demonstrated large lymphoid cells in the capillaries of alveolar septa. The tumor cells showed strong immunohistochemical reactivity to CD 20. After combined treatment with CHOP and rituximab, clinical symptoms, laboratory and radiological findings were improved. As with diffuse large B cell lymphoma, CHOP chemotherapy plus rituximab may prove useful as a standard regimen for pulmonary intravascular lymphoma.

BACKGROUND: Although the average age of onset of ossification of the posterior longitudinal ligamen of the spine (OPLL) is at around 50 years, the onset of the symptoms is insidious and the progression is very slow. The etiology of OPLL has not been elucidated in detail. Previous studies have suggested that a high-salt diet and low consumption of animal protein, glucose intolerance and high body mass are risk factors for OPLL. However, there is little information about the relationship between OPLL and life styles in the prime of life (between 30 and 50 years). METHODS: To facilitate early prediction and prevention of OPLL, we analyzed life styles such as sleeping habit, physical exercise, smoking, alcohol drinking and hangover in subjects in the prime of life. Self-administered questionnaires were obtained from patients with OPLL and their sex- and age-matched controls. Sixty-nine patients diagnosed with OPLL within 3 years previously and 138 sex- and age-matched controls without backbone diseases, randomly selected from participants in a health checkup in a local town, were enrolled. RESULT: Moderate amount of sleep (6-8 hours vs. 5 hours or shorter and 9 hours or longer; odds ratio [OR] = 0.18, 95% confidence interval [CI] = 0.06, 0.54) and a regular sleeping habit (i.e., going to bed and getting up at regular time) (OR=0.44, 95% CI=0.22, 0.90) were associated with a decreased risk o OPLL even after adjusting for other factors. On the other hand, moderate physical exercise (once a week or more v.s. less than once a week: OR=0.97, 95% CI=0.42, 2.26), smoking (OR=1.41, 95% CI=0.67, 2.97), drinking (OR=1.08, 95% CI=0.53, 2.20) and hangover (OR=1.12, 95% CI=0.43, 2.94) in the prime of life showed no correlation with risk of OPLL. CONCLUSION: Good sleeping habits in the prime of life may decrease the risk of OPLL.

In order to determine whether maternal smoking before or during pregnancy, or both, is associated with a reduced risk for preeclampsia in Japanese subjects, we conducted a case-control study that took other risk factors for preeclampsia into consideration. Seventy-one preeclampsia patients were matched with 142 controls for parity and age. Information from a self-administered questionnaire and clinical data such as maternal age, parity, family history of hypertension, prepregnancy body mass index (BMI), and pregnancy outcomes were analyzed. No significant difference was found between the groups in smoking rates before and during pregnancy (38.0 and 18.3% in preeclampsia patients and 38.0 and 16.9% in controls, respectively). However, classification of the subjects according to the presence of "prepregnancy high body mass (BMI > or = 24)" revealed a significant association between maternal smoking before pregnancy and preeclampsia in women with a prepregnancy high body mass (a smoking rate of 47.6% in patients with preeclampsia and 7.1% in controls, p < 0.05). This result suggests that there is a clear racial difference in the manifestation of preeclampsia with respect to the effect of smoking and that early intervention, particularly before pregnancy, to get obese women to stop smoking may be effective for preventing preeclampsia.