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Biomedical subjects

Shigeki Yamada

Publications and source records attributed to Shigeki Yamada.

At least 19 recordsLinked to original sources

Adult-onset Still's disease in a patient over 80 years old successfully treated with low-dose methotrexate therapy.

We report on an 83-year-old Japanese woman with adult-onset Still's disease (AOSD), with marked hypercytokinemia (serum levels of ferritin (Fer) and interleukin (IL)-18 were markedly high). On seeing older patients with fever of unknown origin (FUO), particularly Asians, AOSD should be considered. Reduced doses of oral prednisolone following intravenous methylprednisolone (mPSL) therapy caused a flare-up of AOSD and led to Pneumocystis carinii (jeroveci) pneumonia. Low-dose methotrexate (MTX) therapy was administered as a steroid-sparing agent with good response. Our case suggests that in very elderly people, as in younger patients, MTX is useful for controlling AOSD with marked hypercytokinemia, and avoiding corticosteroid-induced adverse effects.

Aged, 80 and over↗

Comparison of percutaneous coronary intervention with medication in the treatment of coronary artery disease in hemodialysis patients.

It has been reported that percutaneous coronary intervention (PCI) is beneficial for coronary artery disease (CAD) among the general population. However, its effects in patients who are on hemodialysis (HD) remain unclear. A prospective cohort study was performed to clarify whether PCI has a therapeutic advantage over medical therapy among HD patients with CAD. A follow-up study to 5 yr was conducted among 259 HD patients with ischemic heart disease. Mean follow-up was 39 mo. Patients were divided into three groups: 122 patients without significant stenosis, 88 patients who had significant stenosis and were treated with PCI, and 49 patients who had significant stenosis and were treated with medication only. The primary end point was cardiac death, and the secondary end point was all-cause death. The results showed that the 5-yr cardiac survival rate was 41.6% in the medication group, 77.1% in the PCI group (P = 0.0006), and 84.5% in the nonstenosis group (P < 0.0001). The 5-yr all-cause survival rate was 19.3% in the medication group, 48.4% in the PCI group (P = 0.004), and 64.3% in the nonstenosis group (P < 0.0001). Even after adjustment for other risk factors, effects of PCI on the risk for cardiac and all-cause death remained significant and independent (odds ratio 0.14; 95% confidence interval 0.08 to 0.25, P = 0.0006; and odds ratio 0.37; 95% confidence interval 0.26 to 0.54, P = 0.0062, respectively). Results were consistent when the therapeutic effect of PCI or medication was analyzed using propensity-matched patients. These data suggested that PCI could improve the prognosis of HD patients with CAD. PCI would be recommended for HD patients with CAD.

Aged↗

Search on chromosome 17 centromere reveals TNFRSF13B as a susceptibility gene for intracranial aneurysm: a preliminary study.

BACKGROUND: Our previous studies have shown a significant linkage of intracranial aneurysms (IAs) to chromosome 17. METHODS AND RESULTS: Nine genes (TNFRSF13B, M-RIP, COPS3, RAI1, SREBF1, GRAP, MAPK7, MFAP4, and AKAP10) were selected from 108 genes that are located between D17S1857 and D17S1871 by excluding 99 genes that were pseudogenes, hypothetical genes, or well-characterized genes but not likely associated with IA. Direct sequencing of all coding and regulatory regions in 58 cases (29 pedigree probands and 29 unrelated nonpedigree cases) was performed. Deleterious changes were found only in TNFRSF13B, K154X, and c.585 to 586insA in exon4. The association of IA with TNFRSF13B was further studied in 304 unrelated cases and 332 control subjects. Rare nonsynonymous changes, a splicing acceptor site change and a frame shift, were found in unrelated cases (2.3%; 14 of 608) more frequently than in control subjects (0.8%; 5 of 664; P=0.035). The association study using single-nucleotide polymorphisms in an unrelated case-control cohort revealed a protective haplotype (odds ratio 0.69, 95% confidence interval 0.52 to 0.92, P=0.012) compared with the major haplotype after adjustment for covariates. CONCLUSIONS: We propose that TNFRSF13B is one of the susceptibility genes for IA.

Adult↗

Association analysis of common variants of ELN, NOS2A, APOE and ACE2 to intracranial aneurysm.

BACKGROUND AND PURPOSE: Previous studies have shown positive evidence of linkage of the intracranial aneurysm (IA) at chromosome 7q11, 17cen, 19q13, and Xp22. These regions contain elastin (ELN), nitric oxide synthetase 2A (NOS2A), apolipoprotein E (APOE), and angiotensin-I converting enzyme 2 (ACE2), which are considered to be promising candidate genes for IA. We aimed to examine the association of single-nucleotide polymorphisms (SNPs) with IA in these candidate genes. METHODS: To identify polymorphisms in NOS2A and ACE2, all exons and exon-intron boundaries were screened by direct sequencing in 30 randomly selected controls. The program tagSNPs was used to select an optimal set of haplotype-tagging SNPs. For ELN and APOE, SNPs were selected from previous reports. These selected SNPs were then genotyped in 362 cases with IA and 332 residential area matched controls. THESIAS software was used to investigate the association of alleles and haplotypes with IA by adjusting with covariates. RESULTS: We genotyped 8 SNPs in ELN, 8 SNPs in NOS2A, 3 epsilon alleles in APOE and 1 SNP in ACE2. No alleles or haplotypes of 4 candidate genes revealed any significant association with IA. CONCLUSIONS: Investigated polymorphisms in this study were not associated with IA.

Adult↗

History of blood transfusion before 1990 is a risk factor for stroke and cardiovascular diseases: the Japan collaborative cohort study (JACC study).

BACKGROUND: We have previously shown novel evidence that history of blood transfusion is a risk factor for mortality from subarachnoid hemorrhage. This study was conducted to assess history of transfusion as a risk factor for other hemorrhagic stroke or ischemic stroke and cardiovascular diseases. STUDY DESIGN AND METHODS: A total of 88,312 Japanese participants (36,823 men and 51,489 women), aged 40-79 years, without history of stroke, heart disease or cancer, completed a questionnaire including history of transfusion under the JACC Study from 1988 to 1990. Participants were followed up annually until deceased, or when they moved away from the surveyed community, or at the end of 1999. The underlying causes of death were determined according to the International Classification of Diseases, 10th revision (ICD-10). RESULTS: Total follow-up person-years were 871,437 (males 359,437, females 512,000). During this 10-year period, 309 died from intracerebral hemorrhage, 587 from ischemic stroke and 472 from coronary heart disease. The multivariate relative risks of a transfusion history were 2.16 (95% CI 1.42-3.27, p < 0.001) for intracerebral hemorrhage, 1.63 (95% CI 1.18-2.27, p = 0.004) for ischemic stroke and 1.66 (95% CI 1.17-2.36, p = 0.005) for coronary heart disease, after adjustment for conventional cardiovascular risk factors. CONCLUSION: A transfusion history was associated with increased mortality from stroke and coronary heart disease.

Adult↗

Churg-Strauss syndrome associated with hypersensitivity to acetaminophen.

Acetaminophen is a widely used antipyretic drug. We describe a 64-year-old Japanese woman who developed typical Churg-Strauss syndrome after frequent use of acetaminophen. Following the ingestion of acetaminophen, she exhibited various allergic reactions such as asthmatic attacks, pyrexia and petechiae on legs. In the lymphocyte transformation test, a positive reaction to acetaminophen was detected. A muscle biopsy revealed massive extravascular eosinophil infiltration and a necrotizing vasculitis. Hypersensitivity to acetaminophen may be implicated in the development of Churg-Strauss syndrome in this case.

Acetaminophen↗

Genome-wide scan for Japanese familial intracranial aneurysms: linkage to several chromosomal regions.

BACKGROUND: Genetic factors have an important role in the pathogenesis of intracranial aneurysm (IA). The results of previous studies have suggested several loci. METHODS AND RESULTS: From 29 IA families with > or =3 individuals affected by IA, we used nonparametric (model-free) methods for linkage analyses, using GENEHUNTER and Merlin software. Genome-wide linkage analyses revealed 3 regions on chromosomes 17cen (maximum nonparametric logarithm of the odds score [MNS] = 3.00, nominal P=0.001), 19q13 (MNS=2.15, nominal P=0.020), and Xp22 (MNS=2.16, nominal P=0.019). We tested 4 candidate genes in these regions: the microfibril-associated protein 4 gene (MFAP4) and the promoter polymorphism of the inducible nitric oxide synthase gene (NOS2A) on chromosome 17cen, the epsilon genotypes of the apolipoprotein E gene (APOE) on chromosome 19q13, and the angiotensin I converting enzyme 2 gene (ACE2) on chromosome Xp22. Associations of their polymorphisms with IA were evaluated by a case-control study (100 cases: 29 probands from IA families and 71 unrelated subjects with IAs, 100 unrelated control subjects [unaffected members with IAs and absence of family history of IAs]). However, the case-control study showed that none of the polymorphisms of the examined genes had associations with IA. CONCLUSIONS: A genome-wide scan in 29 Japanese families with a high degree of familial clustering revealed 1 suggestive linkage region on chromosome 17cen and 2 potentially interesting regions on chromosomes 19q13 and Xp22. These regions were consistent with previous findings in various populations.

Aged↗

Biclonal extramedullary plasmacytoma arising in the peritoneal cavity: report of a case.

We report a rare case of extramedullary plasmacytoma, which arose either in the ileum or the ileal mesentery. A 70-year-old woman presented with a high fever and symptoms of bowel obstruction. Computed tomography and magnetic resonance imaging showed a large heterogeneous tumor in the peritoneal cavity. Serum immunoelectrophoresis revealed a biclonal increase of IgA-Kappa and IgG-Kappa. At surgery, we found that the parenchyma of the fragile tumor had firm communication with the ileal mesentery, and the cavity of the tumor communicated with the ileal lumen. After a temporary regression following surgery and chemotherapy, the tumor grew rapidly. Although there was no evidence of progression to multiple myeloma, the patient died of cachexia less than 4 months after surgery.

Aged↗

Parathyroid adenoma without hyperparathyroidism.

A 45-year-old female patient was admitted to our hospital presenting with a right anterior cervical tumor that was elastic, hard, painless and 3.5 x 3.5 cm in size. Laboratory data including serum calcium level, thyroid and parathyroid hormonal functions revealed no abnormalities. Further examination, consisting of computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography (US) and radioisotope (RI)-imaging demonstrated that it was a solid tumor located behind the right thyroid lobe. The tumor, whose origin was unclear, was successfully removed with right thyroid lobectomy. Macroscopically, it appeared as reddish solid tumor consisting of small cystic lesions storing chocolate-colored mucous. Immunohistology confirmed that there was proliferation of chief cells with positive parathyroid hormone (PTH) staining. Thus the tumor was diagnosed as parathyroid adenoma despite a lack of clinical evidence for hyperparathyroidism. The reason for the lack of clinical features of hyperparathyroidism in this adenoma still remains unclear, however, there might be inactivation of hormone excretion, possibly due to insufficiency of blood supply. This was a very rare case of parathyroid adenoma exhibiting no clinical evidence of hyperparathyroidism.

Adenoma↗

Unilateral active adrenal tuberculosis featuring persistent intermittent fever.

The adrenal gland is one of the organs which tuberculosis infects. In most clinical settings bilateral adrenal tuberculosis has been clarified after adrenal insufficiency is overt. On the contrary, active adrenal tuberculosis is rarely detected during the survey of infectious disease. A 68-year-old man was admitted because of intermittent fever. The fever had continued for the last 3 months. The intermittent fever was accompanied with leukocytosis and elevation of C-reactive protein. Serum soluble interleukin-2 receptor was 1920 U/ml, and beta2-microglobulin was 4.0 mg/l. Bacterial cultures of blood, sputa, urine, bone marrow and cerebrospinal fluid did not show any particular bacteria. Mycobacterium tuberculosis was negative in culture of sputa, and there was no tuberculin reaction. Plasma ACTH and serum cortisol were 18.5 pmol/l and 527.0 nmol/l, respectively. Abdominal CT scan showed right adrenal mass with a size of 28 x 20 mm, which was low density and had a well-encapsulated homogenous appearance. After the adrenalectomy, histology verified active adrenal tuberculosis. The intermittent fever disappeared, and white blood cells and C-reactive protein normalized. These findings indicate an atypical, rare case of unilateral, active adrenal tuberculosis closely linked to intermittent fever, and without any other organ involvement.

Acute Disease↗

Risk factors for fatal subarachnoid hemorrhage: the Japan Collaborative Cohort Study.

BACKGROUND AND PURPOSE: The present study aimed to identify risk factors for mortality due to subarachnoid hemorrhage (SAH) using a comprehensive questionnaire from the Japan Collaborative Cohort (JACC) Study, a Japan-wide population-based prospective study. METHODS: A total of 109,293 individuals (45,551 men and 63,742 women, aged 40 to 79 years) free of stroke at entry participated in the JACC Study between 1988 and 1990. Participants were followed up annually until they died or moved away from the surveyed community, or until the end of 1999. A diagnosis of death from SAH was based on the International Classification of Diseases, 10th revision (ICD-10). The age-adjusted univariate and multivariate hazard ratios (HR) and 95% confidence intervals (CI) of various factors were calculated in sex-stratified and sex-specific analyses using the Cox proportional hazards regression model. RESULTS: A total of 244 individuals (88 men and 156 women) died from SAH during the follow-up of 1 086 963 person-years. Our univariate analyses confirmed that preference for salty foods and history of blood transfusion, as well as hypertension, family history of stroke, cigarette smoking, heavy alcohol consumption, and low BMI, had statistically significant associations with mortality due to SAH. Multivariable analyses revealed that history of blood transfusion was an independent significant risk factor (HR=4.2 [95%CI, 2.1 to 8.5]) for men, while preference for salty foods or heavy drinking were not. CONCLUSIONS: History of blood transfusion was found to be an independent risk. The association between SAH and blood transfusion warranted further study.

Adult↗

Absence of linkage of familial intracranial aneurysms to 7q11 in highly aggregated Japanese families.

BACKGROUND AND PURPOSE: We sought to test the linkage of familial intracranial aneurysms (FIAs) to the ELN (elastin) locus in chromosome 7q11 reported previously. METHODS: Intracranial aneurysm (IA) probands were searched from patient records or neurosurgeons' recalls in collaborating hospitals. Members of the participating probands' families who had unknown affection status were screened by MR angiography and diagnosed by digital subtraction angiography. Inclusion criteria of families for genetic analyses were as follows: at least 3 alive affected members or 2 alive affected members with at least 1 unaffected member (>or=60 years). Linkage to the ELN locus was tested with the use of GENEHUNTER by parametric and nonparametric methods. To exclude false-negatives in the linkage analysis, the lowest 5% limits of logarithms of the odds (LOD) and nonparametric LOD (NPL) scores for individual families and for the total set of families were simulated on assumption that the ELN locus is linked to FIAs. RESULTS: Questionnaires were sent to 885 patients, and 563 responded. Seventy-nine probands were positive for family history. One hundred thirty-four family members of unknown affection status were screened. A total of 14 families with 64 members met the criteria. Linkage to the ELN locus was discarded in 11 families and was inconclusive for 3 families. The total LOD and total NPL scores for 14 families were -8.04 and -0.643, respectively. Our conclusion did not change even when the values of penetrance were changed or only affected members were analyzed. CONCLUSIONS: The majority of aggregated IA Japanese families may not have a genetic linkage to chromosome 7q11.

Adult↗

A case of primary esophageal tuberculosis diagnosed by identification of Mycobacteria in paraffin-embedded esophageal biopsy specimens by polymerase chain reaction.

We present a case of primary esophageal tuberculosis diagnosed by polymerase chain reaction (PCR) of paraffin-embedded esophageal biopsy specimens. A 42-year-old Japanese woman visited our clinic because of dysphagia. Radiologic and endoscopic examinations revealed a stenotic lesion with reddish mucosa and multiple ulcers in the middle esophagus. There was no associated lesion outside the esophagus. Histological and bacteriological studies of esophageal biopsy specimens and gastric aspirates did not give a definitive diagnosis. However, mycobacterial DNA was detected by PCR of paraffin-embedded esophageal biopsy specimens. She then was diagnosed as having primary esophageal tuberculosis. The esophageal mucosal lesion almost healed after 1 month of antituberculosis medication with residual annular stenosis which was resolved later by endoscopic balloon dilation.

Adult↗

Elimination kinetics of quinaprilat and perindoprilat in hypertensive patients with renal failure on haemodialysis.

Objective of the present study was to investigate the elimination kinetics of quinaprilat and perindoprilat, the active metabolites of angiotensin-converting enzyme (ACE) inhibitors quinapril and perindopril, in hypertensive patients with renal failure under haemodialysis to evaluate the appropriate duration of off-dose of these drugs before starting of low-density lipoprotein (LDL) apheresis. The informed consent was received from 12 hypertensive patients with renal failure, who were under haemodialysis (42 to 62 years). The patients received oral administration of quinapril (10 mg) or perindopril (2 mg) once a day for four weeks. First, to evaluate the dialyzability of each metabolite, blood samples were collected before and after haemodialysis one week after the repeated doses. Second, to evaluate the elimination kinetics of quinaprilat or perindoprilat, blood samples were collected at 24, 72, 120, 192 and 240 h after the final administration. Plasma concentrations of quinaprilat and perindoprilat were measured by high-performance liquid chromatography (HPLC) and radioimmunoassay, respectively. Pharmacokinetic parameters were determined by a model-dependent method. Values of haemodialysis clearance (CL(HD)) and extraction ratio (ER) were 51.5+/-30.2 ml/min and 0.35+/-0.21 for quinaprilat and 108.1+/-5.9 ml/min and 0.75+/-0.04 for perindoprilat, respectively. The terminal elimination half-lives of quinaprilat and perindoprilat were 60.7+/-2.1 and 79.9+/-14.0 h, respectively. The dialyzability of perindoprilat was much higher than that of quinaprilat probably due to low protein binding potency. The present study suggests that hypertensive patients receiving chronic therapy with quinapril or perindopril on haemodialysis should be withdrawn for at least 2 to 3 weeks before LDL apheresis.

Administration, Oral↗

[An efficacy study of a TPN kit with multivitamin addictive in the HPN].

When home parenteral nutrition (HPN) is instituted, one should aim at reducing the risk of infections, simplifying the operation, and improving the patient's QOL, while considering the differences between the hospital and home. As for simplification of the operation, the problem is who and when to prepare the TPN while paying attention to the stability of multivitamins. Recently, a TPN kit that includes multivitamins and does not need a syringe or an injection needle to add vitamins to the TPN preparation was launched. Accordingly, we conducted a study to examine the simplicity of the procedure and usefulness of the product on the basis of time required to add other components to the TPN preparation, as assessed by questionnaire. The subjects of the study were medical care providers as well as patients on HPN and their families. The time required for TPN admixtures was significantly shorter compared with the conventional method. According to the questionnaire, the storability and easiness of the procedure were particularly highly appreciated. This product has the advantage that sterility can be maintained at home, that contamination with foreign bodies can be reduced, and that it can be stored at room temperature. Since it can be preserved in preparation for natural disasters and can be carried around during travel, it is expected to improve the QOL of patients on HPN and their families.

Drug Storage↗

[An efficacy study of a TPN kit with multivitamin additive in the HPN].

When home parenteral nutrition (HPN) is instituted, one should aim at reducing the risk of infections, simplifying the operation, and improving the patient's QOL, while considering the differences between the hospital and home. As for simplification of the operation, the problem is who and when to prepare the TPN while paying attention to the stability of multivitamins. Recently, a TPN kit that includes multivitamins and does not need a syringe or an injection needle to add vitamins to the TPN preparation was launched. Accordingly, we conducted a study to examine the simplicity of the procedure and usefulness of the product on the basis of time required to add other components to the TPN preparation, as assessed by questionnaire. The subjects of the study were medical care providers as well as patients on HPN and their families. The time required for TPN admixtures was significantly shorter compared with the conventional method. According to the questionnaire, the storability and easiness of the procedure were particularly highly appreciated. This product has the advantage that sterility can be maintained at home, that contamination with foreign bodies can be reduced, and that it can be stored at room temperature. Since it can be preserved in preparation for natural disasters and can be carried around during travel, it is expected to improve the QOL of patients on HPN and their families.

Humans↗

Vasculogenic mimicry and pseudo-comedo formation in breast cancer.

Tumors require a blood supply for growth and hematogenous metastases. Until recently, most research in this area has focused on the role of angiogenesis, the recruitment of new vessels into a tumor from preexisting vessels. Previously, in a study of breast cancer (IBC), in which we used established inflammatory breast cancer (IBC) xenografts (WIBC-9) originating from a patient with IBC (Shirakawa et al., Cancer Res 2001:61:445-451), we reported observing vasculogenic mimicry (VM), a condition in which bloodstreams within cancer tissue are not accompanied by a lining of endothelial cells (ECs) (Shirakawa et al., Cancer Res 2002:62:560-566). In the present study, we examined 331 surgically resected breast cancer specimens for evidence of VM, using immunohistochemistry and laser-captured microdissection (LCM) followed by nested reverse transcriptase polymerase chain reaction (RT-PCR). Surprisingly, 7.9% (26 specimens) of the 331 specimens exhibited evidence of VM. Of these 26 VM specimens, 84.6% (22 specimens) exhibited pseudo-comedo formation. RT-PCR analysis of 8 microdissected typical VM specimens revealed expression of Tie-2, Flt-1, thrombin receptor and CD31 in 63, 50, 0 and 0% of specimens, respectively. In contrast, results of RT-PCR analysis of 8 specimens from non-VM tumors were negative for expression of these genes. The 26 VM cases tended to have a higher percentage of hematogenous recurrence (p = 0.059) and a lower percentage of 5-year survival (p = 0.071) than the 305 non-VM cases. However, there were no significant differences in tumor size, lymph node metastasis, estrogen receptors or progesterone receptors between the 2 groups (p > 0.1). Our results suggest that the existence of VM increases the likelihood of hematogenous metastases and is in inverse proportion to prognosis.

Antigens, CD↗