Naoki Yamada

Methylenetetrahydrofolate reductase variant and schizophrenia/depression

Patients with methylenetetrahydrofolate reductase (MTHFR) deficiency often show psychiatric manifestations. Since a common variant of the MTHFR gene, T677(Ala), responsible for the thermolabile MTHFR with less than 50% specific MTHFR activity, has been reported, we examined whether the T677 allele is associated with psychiatric disorders in an unrelated Japanese population consisting of 297 schizophrenics, 32 patients with major depression, 40 patients with bipolar disorder, and 419 controls. The genotype homozygous for the T677 allele was significantly frequently observed in schizophrenics with an odds ratio of 1.9 (P = 0.0006), and in patients with major depression with an odds ratio of 2.8 (P = 0.005). Our data suggest associations of the MTHFR gene variant with schizophrenia and depression in the Japanese.

Human papillomavirus infections among Japanese women: age-related prevalence and type-specific risk for cervical cancer

To obtain baseline data for human papillomavirus (HPV) screening and vaccination in Japan, we analyzed HPV DNA data from 2282 Japanese women (1517 normal cytology, 318 cervical intraepithelial neoplasia [CIN] grade 1, 307 CIN2–3, and 140 invasive cervical cancer [ICC]) that visited the University of Tsukuba Hospital or Ibaraki Seinan Medical Center Hospital for screening or treatment of cervical diseases between 1999 and 2007. An L1‐based PCR method was used for individual HPV genotyping. The most common HPV types in ICC were, in order of decreasing prevalence, HPV16 (40.5%), HPV18 (24.4%), HPV52 (8.4%), HPV58 (3.1%), and HPV33 (3.1%). Based on the comparison of HPV type distributions between normal cytology and CIN2–3 and ICC, estimated risk of disease progression varied considerably by genotype: HPV16, HPV18, HPV31, HPV33, HPV35, HPV52, and HPV58 (prevalence ratio, 1.92; 95% confidence interval 1.58–2.34); other oncogenic types (0.31, 95% confidence interval 0.19–0.50); and non‐oncogenic types (0.09, 95% confidence interval 0.03–0.43). HPV16 and/or HPV18, including coinfections with other types, contributed to 67.1% of ICC and 36.2% of CIN2–3 among Japanese women. More importantly, the overall prevalence of HPV16 and/or HPV18 varied greatly according to the womens age: highest in women aged 20–29 years (ICC, 90.0%; CIN2–3, 53.9%), decreasing with age thereafter, and lowest in women aged 60 years or older (ICC, 56.3%; CIN2–3, 25.0%). In conclusion, type‐specific HPV testing may help identify Japanese women at high risk of progression to CIN2–3 and cancer. In Japan, current HPV vaccines are estimated to provide approximately 70% protection against ICC and may be more useful in reducing the incidence of cervical cancer and precancer in young women of reproductive age. (Cancer Sci 2009; 100: 1312–1316)

The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia

AbstractPreeclampsia is associated with thrombosis of the intervillous or spiral artery. A deletion/insertion polymorphism (4G or 5G) in the promoter of the plasminogen activator inhibitor type 1 (PAI-1) gene is suggested to be involved in regulating the synthesis of the inhibitor, 4G allele, being associated with the enhanced gene expression and plasma PAI-1 levels. We assessed the association between preeclampsia and the 4G/5G polymorphism of the PAI-1 gene in 115 preeclamptic patients, 210 pregnant controls, and 298 healthy volunteer controls. The frequency of the homozygotes for the 4G allele was significantly higher in the patients than in the control pregnant women (P = 0.04) or in the healthy volunteers (P = 0.02). The 4G allele frequency was also significantly higher in the patients than in the control group of pregnant women (P = 0.03) and in the healthy volunteers (P = 0.02). These results suggest that the presence of the 4G/4G genotype of the PAI-1 gene is one of the risk factors for preeclampsia.

Autosomal recessive hydrocephalus due to congenital stenosis of the aqueduct of Sylvius

Isolated hydrocephalus due to congenital stenosis of the aqueduct of Sylvius is almost always an X‐linked recessive inherited condition. We describe a brother and sister with isolated hydrocephalus from congenital aqueductal stenosis. We believe that these two occurrences represent a rare autosomal recessive form of this abnormality. In assessing a first known occurrence of hydrocephalus with stenosis of the aqueduct of Sylvius in a family, the rare possibility of autosomal inheritance must be considered in genetic counselling. Copyright

Brain Natriuretic Peptide (BNP) and Cyclic Guanosine Monophosphate (cGMP) Levels in Normal Pregnancy and Preeclampsia

Objective: Our purpose was to evaluate plasma levels of brain natriuretic peptide (pBNP) and cyclic guanosine monophosphate (pcGMP) in preeclamptic patients and controls.

Association analysis of nine missense polymorphisms in the coagulation factor V gene with severe preeclampsia in pregnant Japanese women.

AbstractThe Leiden mutation in the coagulation factor V (F5) gene associated with preeclampsia in Caucasians has not been found in Japanese populations. We examined the association of 20 missense polymorphisms in the F5 gene in 133 pregnant Japanese women with preeclampsia and in 224 unrelated, healthy, pregnant Japanese women. Among nine polymorphisms identified in the subjects, the M385T and R485K polymorphisms were associated with preeclampsia (P = 0.05 and P = 0.02, respectively). Haplotype analysis indicated that the R485K polymorphism is truly associated with preeclampsia, whereas the association of the M385T polymorphism is due to linkage disequilibrium. Taken together with reports that the R485 allele yields poor factor V function in comparison with that of the K485 allele and that the F5 Leiden mutation is associated with preeclampsia in Caucasian populations, the findings of the present study suggest that the F5 gene is associated with preeclampsia in pregnant Japanese women.

Antepartum Assessment of Fetal Cystic Lymphangioma by Magnetic Resonance Imaging

Few reports of fetal cystic lymphangioma have described assessment in utero by magnetic resonance imaging (MRI). We evaluated a fetus with cystic lymphangioma by this method. Complementing the characteristic features of cystic lymphangioma in ultrasonographic images, prenatal MRI provided a detailed view of anatomic relationships of cysts to surrounding tissues in this case. This anatomic evaluation facilitated planning of perinatal management and choice of manner of delivery. We found MRI very helpful in antepartum assessment of fetal cystic lymphangioma.

Second-Trimester Maternal Pregnancy-Associated Plasma Protein A and Inhibin A Levels in Fetal Trisomies

Objective: The aim of this study was to determine whether fetal trisomy is associated with altered levels of second-trimester maternal pregnancy-associated plasma protein A (PAPP-A) and inhibin A. Methods: Maternal serum PAPP-A and inhibin A concentrations were measured at 15–17 weeks of gestation in 14 singleton pregnancies with fetal trisomy and in 56 matched pregnant controls. Results: PAPP-A levels in the trisomy group were significantly lower than in controls. The inhibin A level with fetal trisomy 21 was slightly higher than the control group, but levels were not different between trisomies 18 and 13 and controls. Conclusion: Fetal trisomies 21, 18, and 13 are associated with a reduction in second-trimester maternal PAPP-A levels; trisomies 18 and 13 are not associated with increased inhibin A levels, unlike trisomy 21.

Transplacental exposure to antipsychotic drugs during pregnancy and megacystis in the fetus

Urinary retention is an adverse effect of antipsychotic drugs that has not been previously reported in the fetus. We have diagnosed megacystis in a fetus possibly caused by transplacental exposure to the antipsychotic drugs being administered to the mother. Two weeks after the mother stopped taking the drugs, the size of the enlarged fetal urinary bladder returned to normal. Sonographic examination of the neonate revealed an anatomically normal urinary tract, with a normal bladder capacity and urination. Copyright

Undifferentiated Carcinoma with Osteoclast-Like Multinucleated Giant Cells Arising in an Ovarian Mature Cystic Teratoma

Malignant transformation is an unusual complication of mature cystic teratomas. Squamous cell carcinomas and adenocarcinomas are predominant among these malignant tumors. We present a 70-year-old Japanese woman with a giant ovarian tumor (30 × 23 × 9 cm) and multiple peritoneal dissemination. The huge tumor was filled with necrotic and fatty tissue and coagula accompanied with hair balls histologically diagnosed as undifferentiated carcinoma with multinucleated giant cells arising in an ovarian mature cystic teratoma. The residual disseminated tumors grew very rapidly and occupied the whole abdominal cavity again 3 weeks after the surgery. The patient died 5 weeks after the operation.