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Tetsuo Nishikawa

Publications and source records attributed to Tetsuo Nishikawa.

At least 19 recordsLinked to original sources
PubMed2006

Prevalence of primary aldosteronism: should we screen for primary aldosteronism before treating hypertensive patients with medication?

The present review examines various reports describing prevalence of primary aldosteronism (PA) among hypertensives and the screening method of PA to better understand the current concepts used for diagnosing and managing PA among clinicians as well as specialists. Here, we describe and compare the prevalence of PA in Japan, which is well known to induce various vascular complications due to hyperaldosteronemia, resulting in cerebral infarction, myocardial infarction and renal failure, with that in another Asian area, US, European countries, Australia and Africa. The incidence rates for PA among hypertensives were recently reported to be widely raged between 3.2% and 20%. Those discrepancies are due in part to the completely different characteristics of the starting subjects used for studying the prevalence. Moreover, the criteria for screening PA among hypertensives, including aldosterone-renin ratio (ARR), and confirmatory tests for definitely diagnosing PA, such as saline infusion test are varied. We had already reported that a diagnosis of PA was made in 61 (6%) of the 1,020 hypertensive patients during the past five years, from 1995 until 1999. In our study, only 18% of the patients showed a serum K level of 3.3 mEq/l or less. Thus, many clinicians seem to misdiagnose PA as essential hypertension, because of absence of hypokalemia. Finally, we describe highlight key evidence for optimal methods for screening and definitely diagnosing PA among hypertensive patients in order to avoid misjudgment before or after treating hypertensive patients.

Aldosterone↗
PubMed2006

Normal delivery following an uneventful pregnancy in a Japanese acromegalic patient after discontinuation of octreotide long acting release formulation at an early phase of pregnancy.

We report a 35-year-old woman with active acromegaly despite pituitary surgery and irradiation who received continuous octreotide LAR treatment for the control of GH excess until discovery of her pregnancy. The patient delivered a healthy boy following an uneventful pregnancy after discontinuing octreotide LAR as soon as possible at the early phase of pregnancy. Despite a substantial maternal-fetal transfer of octreotide, postnatal development was normal at 3 years of age. In almost all previously described cases, octreotide was discontinued after pregnancy was confirmed. No side-effects of mother or fetus have been reported. Octreotide treatment in pregnancy seems to be feasible and safe. Due to the still-limited number of reported cases treated with octreotide LAR, the potential benefits of octreotide LAR treatment should be weighed carefully against its possible risks.

Acromegaly↗
PubMed2005

Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.

By analyzing 1,780,295 5'-end sequences of human full-length cDNAs derived from 164 kinds of oligo-cap cDNA libraries, we identified 269,774 independent positions of transcriptional start sites (TSSs) for 14,628 human RefSeq genes. These TSSs were clustered into 30,964 clusters that were separated from each other by more than 500 bp and thus are very likely to constitute mutually distinct alternative promoters. To our surprise, at least 7674 (52%) human RefSeq genes were subject to regulation by putative alternative promoters (PAPs). On average, there were 3.1 PAPs per gene, with the composition of one CpG-island-containing promoter per 2.6 CpG-less promoters. In 17% of the PAP-containing loci, tissue-specific use of the PAPs was observed. The richest tissue sources of the tissue-specific PAPs were testis and brain. It was also intriguing that the PAP-containing promoters were enriched in the genes encoding signal transduction-related proteins and were rarer in the genes encoding extracellular proteins, possibly reflecting the varied functional requirement for and the restricted expression of those categories of genes, respectively. The patterns of the first exons were highly diverse as well. On average, there were 7.7 different splicing types of first exons per locus partly produced by the PAPs, suggesting that a wide variety of transcripts can be achieved by this mechanism. Our findings suggest that use of alternate promoters and consequent alternative use of first exons should play a pivotal role in generating the complexity required for the highly elaborated molecular systems in humans.

Base Sequence↗
PubMed2005

A discriminant model constructed by the support vector machine method for HERG potassium channel inhibitors.

HERG attracts attention as a risk factor for arrhythmia, which might trigger torsade de pointes. A highly accurate classifier of chemical compounds for inhibition of the HERG potassium channel is constructed using support vector machine. For two test sets, our discriminant models achieved 90% and 95% accuracy, respectively. The classifier is even applied for the prediction of cardio vascular adverse effects to achieve about 70% accuracy. While modest inhibitors are partly characterized by properties linked to global structure of a molecule including hydrophobicity and diameter, strong inhibitors are exclusively characterized by properties linked to substructures of a molecule.

Animals↗
PubMed2005

Total hip arthroplasty in severe congenital factor VII deficiency: successful use of recombinant activated factor VII for hemostasis.

Congenital factor VII (FVII) deficiency is a rare hemorrhagic disorder, and, in affected patients, surgery is likely to cause excessive bleeding. In this article, we report the first case of total hip arthroplasty in a patient with severe congenital FVII deficiency in which recombinant activated factor VII (rFVIIa, NovoSeven) was successfully used to manage bleeds. The patient was a 68-year-old woman with severe congenital FVII deficiency, who suffered from a hemorrhagic arthrosis of her left hip joint. We administered rFVIIa as intermittent bolus infusions both perioperatively and postoperatively; dosing was based on the results of a preoperative rFVIIa challenge test. During surgery and the 3-day postoperative treatment period, we observed normal hemostasis with no excessive bleeding or complications.

Aged↗
PubMed2005

Human renal mesangial cells produce aldosterone in response to low-density lipoprotein (LDL).

Systemic aldosterone plays an important role in the development of the microvascular disease and glomerular damage of the kidney in patients with diabetes mellitus and hyperlipidemia. Here, we investigated the possibility of local production of aldosterone in the kidney, using human primary glomerular mesangial cells. These cells produced both pregnenolone and aldosterone measured by specific radioimmunoassay and/or gas chromatography/mass spectrometry (GC/MS) methods. The production of both steroids was significantly stimulated by treatment with LDL, while angiotensin II had a synergistic effect. Adrenocorticotropic hormone (ACTH) and (Bu)2cAMP, on the other hand, failed to stimulate aldosterone production by these cells, suggesting that the local production of this steroid by mesangial cells is regulated differently from that of adrenal zona glomerulosa cells. Mesangial cells expressed the mRNA of the LDL receptor and steroidogenic enzymes, such as P450scc, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 21-hydroxylase and CYP11B2. Mesangial cells also expressed mRNA of the mineralocorticoid receptor (MR), and LDL stimulated its abundance by three-fold, while spironolactone, a completive antagonist of aldosterone, completely abolished this LDL effect. Since MR is a known mineralocorticoid-responsive gene as well as an intracellular receptor molecule for this steroid, these results suggest that locally produced aldosterone is biologically active, stimulating the transcription rates of the mineralocorticoid-responsive genes by activating the MR in mesangial cells. These pieces of evidence indicate that human mesangial cells are an aldosterone-producing tissue in which LDL plays a major regulatory role. Therefore, human renal mesangial endocrine system may contribute to local aldosterone concentrations and effects in the renal glomerulus independently of the systemic renin--angiotensin--aldosterone system and may participate in the development and progression of glomerular damage in several pathologic conditions.

3-Hydroxysteroid Dehydrogenases↗
PubMed2005

Impaction bone grafting with hydroxyapatite: increased femoral component stability in experiments using Sawbones.

BACKGROUND: Substantial bone loss and bone defects increase the amount of allografting required in hip revision surgery. Thus, the use of a synthetic material to limit the amount of allograft tissue required for impaction grafting is desirable. We evaluated the potential of hydroxyapatite (HA) mixtures to provide initial mechanical stability to a polished tapered femoral stem. MATERIAL AND METHODS: We determined the initial stability of a polished tapered femoral stem after reconstructing a cavitary femoral bone defect by impaction bone grafting with cement in Sawbones composite femurs. Three types of graft material were tested for their ability to improve initial rotational stability. The graft materials investigated were pure allograft, a mixture of 50% allograft and 50% hydroxyapatite (HA), and pure HA. RESULTS: We found a statistically significant difference between the three groups as regards torsional micromotion and failure load. INTERPRETATION: Our findings suggest that reconstruction of femoral bone defects with pure HA or a mixture of allograft and HA provides adequate initial stability for femoral revision arthroplasty using impaction grafting.

Arthroplasty, Replacement, Hip↗
PubMed2005

Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries.

We have developed an in silico method of selection of human full-length cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries. Fullness rates were increased to about 80% by combination of the oligo-capping method and ATGpr, software for prediction of translation start point and the coding potential. Then, using 5'-end single-pass sequences, cDNAs having the signal sequence were selected by PSORT ('signal sequence trap'). We also applied 'secretion or membrane protein-related keyword trap' based on the result of BLAST search against the SWISS-PROT database for the cDNAs which could not be selected by PSORT. Using the above procedures, 789 cDNAs were primarily selected and subjected to full-length sequencing, and 334 of these cDNAs were finally selected as novel. Most of the cDNAs (295 cDNAs: 88.3%) were predicted to encode secretion or membrane proteins. In particular, 165(80.5%) of the 205 cDNAs selected by PSORT were predicted to have signal sequences, while 70 (54.2%) of the 129 cDNAs selected by 'keyword trap' preserved the secretion or membrane protein-related keywords. Many important cDNAs were obtained, including transporters, receptors, and ligands, involved in significant cellular functions. Thus, an efficient method of selecting secretion or membrane protein-encoding cDNAs was developed by combining the above four procedures.

5' Flanking Region↗
PubMed2005

Clinical usefulness of the thickness of preperitoneal and subcutaneous fat layer in the abdomen estimated by ultrasonography for diagnosing abdominal obesity in each type of impaired glucose tolerance in man.

For this study we enrolled 1,615 males who were admitted to our hospital for a general health check-up. Plasma glucose (PG) and insulin were measured during 75 g OGTT, and abdominal obesity was assessed by ultrasonography in all subjects. We divided them into several groups: normal glucose tolerance (NGT), high-normal glucose tolerance (h-NGT) who showed >10.0 nmol/l at 1 hr PG among those with NGT, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG + IGT, and DM, according to the results of 75 g OGTT. The aim of the present study was to clarify the clinical characteristics of pre-diabetic disorders relating to metabolic syndrome by comparing various parameters including body mass index (BMI), blood levels of various lipids and abdominal wall fat index (AFI) calculated from the thickness of preperitoneal (Pmax) and subcutaneous (Smin) fat layer in the abdomen estimated by ultrasonography with insulin sensitivity determined by homeostatic model assessment (HOMA-IR) in each type of abnormal glucose regulation as classified by PG changes in 75 g OGTT. We also investigated the relationship between insulin secretion capability and insulin sensitivity to delineate the characteristics of each type of abnormal glucose regulation, and compared the area under the insulin curve (AUCins) and the time axis, and the ability of early insulin secretion by glucose loading (insulinogenic index: I.I.) in each type of abnormal glucose regulation. There was a significant positive correlation between HOMA-IR and Smin or Pmax, suggesting that Smin and Pmax may reflect insulin sensitivity. Abdominal obesity, which was diagnosed from the data of AFI, was present in the h-NGT and IFG + IGT groups, suggesting that those groups belong to the clinical entity of metabolic syndrome. HOMA-IR was higher in IFG than in IGT, although I.I. was reduced and AUCins was increased in IFG as well as in IGT. h-NGT demonstrated a slightly lower I.I. and higher AUCins, compared with IGT. IFG demonstrated much stronger insulin resistance than IGT, although I.I. was reduced and AUCins was increased in IFG and IGT. Thus, it is suggested that insulin sensitivity may partly account for the difference in pathogenesis between IFG and IGT; and that h-NGT, which showed abdominal obesity assessed as AFI by ultrasonography, should be recognized as a disease state of metabolic syndrome with impaired glucose regulation.

Abdomen↗
PubMed2005

[Liddle syndrome].

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Diagnosis, Differential↗