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Biomedical subjects

Tetsuo Nishikawa

Publications and source records attributed to Tetsuo Nishikawa.

At least 37 records · Page 2Linked to original sources
PubMed2004

Integrative annotation of 21,037 human genes validated by full-length cDNA clones.

The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.

Alternative Splicing↗
PubMed2004

Effect of cyclic mechanical stretch and titanium particles on prostaglandin E2 production by human macrophages in vitro.

Early implant instability has been proposed as a critical factor in the onset and progression of aseptic loosening and periprosthetic osteolysis in total joint arthroplasties. Previous in vitro studies have reported that macrophages stimulated with cyclic mechanical strain release inflammatory mediators. Little is known, however, about the response of these cells to mechanical strain with particles, which is often a component of the physical environment of the cell. We therefore studied the production of prostaglandin E(2) (PGE(2)), an important mediator in aseptic loosening and periprosthetic osteolysis in total joint arthroplasties, for human macrophages treated with mechanical stretch alone, titanium particles alone, and mechanical stretch and particles combined. A combination of mechanical stretch and titanium particles resulted in a statistically synergistic elevation of levels of PGE(2) compared with the levels found with either stretch or particles alone. Exposure of human macrophages to mechanical stretch with particles upregulated the expression of cyclooxygenase (COX)-2 mRNA but not COX-1 mRNA, this expression resulting in a 97-fold increase in PGE(2) production compared to the nonstimulated cells. The current study is the first to investigate the effects of mechanical stretch with particles on cultured macrophages and include an investigation of the time course of PGE(2) production and COX-2 mRNA expression. Our results suggest that, while mechanical strain may be one of the primary factors responsible for macrophage activation and periprosthetic osteolysis, mechanical strain with particles load may contribute significantly to the osteolytic potential of macrophages in vitro. The synergistic effect observed between mechanical stretch and particles could accelerate implant loosening and implies that reduction in either cyclic mechanical strain or wear debris load would lead to a reduction of osteolysis.

Cyclooxygenase 2↗
PubMed2004

Prospective study on the prevalence of secondary hypertension among hypertensive patients visiting a general outpatient clinic in Japan.

Secondary hypertension (SH) including endocrine hypertension has been reported to be uncommon. We estimated the prevalence of SH among hypertensive patients. We prospectively studied 1,020 hypertensive patients. As an initial screening, we measured plasma aldosterone concentration, plasma renin activity, serum cortisol concentration and plasma catecholamine concentration and conducted abdominal ultrasonography (US). As a secondary screening, we performed furosemide plus upright test, captopril renography, dexamethasone suppression test, 24-h urine catecholamine measurement and abdominal CT. Finally, primary aldosteronism with the exception of idiopathic hyperaldosteronism, pheochromocytoma, and Cushing's syndrome were diagnosed by histopathological examination of surgical specimens. Idiopathic hyperaldosteronism was clinically diagnosed by adrenocorticotrophic hormone (ACTH)-stimulated adrenal venous sampling and renovascular hypertension by renal arteriography. There were 61 patients with primary aldosteronism, 5 with renovascular hypertension, 11 with Cushing's syndrome, 10 with preclinical Cushing's syndrome and 6 with pheochromocytoma, and the prevalence of SH was 9.1% among 1,020 hypertensive patients. In 76 (82%) of 93 patients with SH, hypertension was cured or improved after unilateral adrenalectomy, transsphenoidal pituitary adenectomy or percutaneous transluminal angioplasty. With the exception of US and CT, all initial and secondary screening tests were found to be sensitive and specific for differentiating SH from essential hypertension (EH). In conclusion, the measurement of various hormone concentrations was very sensitive for ruling out SH--a condition for which, in the present study, there were few specific signs or symptoms--while CT and US examinations were not always useful for differentiating SH from EH. The prevalence of curable SH among hypertensive subjects was higher in this study, which was conducted by our simple method of screening tests, than in previous reports. Hypertensive patients should be screened for SH and the underlying disease treated appropriately to avoid long-term use of antihypertensive drugs and risks of atherosclerotic complications.

Adrenal Gland Diseases↗
PubMed2003

Complete sequencing and characterization of 21,243 full-length human cDNAs.

As a base for human transcriptome and functional genomics, we created the "full-length long Japan" (FLJ) collection of sequenced human cDNAs. We determined the entire sequence of 21,243 selected clones and found that 14,490 cDNAs (10,897 clusters) were unique to the FLJ collection. About half of them (5,416) seemed to be protein-coding. Of those, 1,999 clusters had not been predicted by computational methods. The distribution of GC content of nonpredicted cDNAs had a peak at approximately 58% compared with a peak at approximately 42%for predicted cDNAs. Thus, there seems to be a slight bias against GC-rich transcripts in current gene prediction procedures. The rest of the cDNAs unique to the FLJ collection (5,481) contained no obvious open reading frames (ORFs) and thus are candidate noncoding RNAs. About one-fourth of them (1,378) showed a clear pattern of splicing. The distribution of GC content of noncoding cDNAs was narrow and had a peak at approximately 42%, relatively low compared with that of protein-coding cDNAs.

Chromosomes, Human, 21-22 and Y↗
PubMed2003

Salusins: newly identified bioactive peptides with hemodynamic and mitogenic activities.

The discovery of endogenous bioactive peptides has typically required a lengthy identification process. Computer-assisted analysis of cDNA and genomic DNA sequence information can markedly shorten the process. A bioinformatic analysis of full-length, enriched human cDNA libraries searching for previously unidentified bioactive peptides resulted in the identification and characterization of two related peptides of 28 and 20 amino acids, which we designated salusin-alpha and salusin-beta. Salusins are translated from an alternatively spliced mRNA of TOR2A, a gene encoding a protein of the torsion dystonia family. Intravenous administration of salusin-alpha or salusin-beta to rats causes rapid, profound hypotension and bradycardia. Salusins increase intracellular Ca2+, upregulate a variety of genes and induce cell mitogenesis. Salusin-beta stimulates the release of arginine-vasopressin from rat pituitary. Expression of TOR2A mRNA and its splicing into preprosalusin are ubiquitous, and immunoreactive salusin-alpha and salusin-beta are detected in many human tissues, plasma and urine, suggesting that salusins are endocrine and/or paracrine factors.

Adenosine Triphosphatases↗
PubMed2003

Reconstruction of the iliofemoral ligament with an artificial ligament for recurrent anterior dislocation of total hip arthroplasty.

An 86-year-old woman underwent 4 revisions of hip arthroplasty and showed good position of both acetabular and femoral components. This was confirmed by roentgenographic measurements in the prone position. However, poor anterior acetabular covering after posterior inclination of the pelvis associated with lumbar kyphosis was observed in the standing position. Therefore, we reconstructed the iliofemoral ligament using a Leeds-Keio ligament to prevent anterior dislocation. At the 12-month follow-up evaluation, hip stability was confirmed, and the hip showed no further dislocation.

Aged↗
PubMed2003

[Changes in the prevalence of intestinal parasites among Japanese expatriates in developing countries].

In order to study the prevalence of intestinal parasites among Japanese expatriates of developing countries, we conducted fecal specimen examinations annually from 1995 to 2000. Fecal specimens were collected from Japanese expatriates of each area: Asia, the Middle East, East Europe, Africa and Latin America. The specimens were fixed with 10% formalin in the local area, and then examined in Japan. We used the formalin-ether sedimentation method to find protozoan cysts or helminth eggs. In 1995, the infection ratio was 3.0% (N = 981), decreasing to 2.4% (N = 1,275) in 1996, 2.3% (N = 1,620) in 1997 and 1.6% (N = 1,574) in 1998. However, the ratio began to increase in 1999 (2.0%, N = 1,713) and 2000 (2.5%, N = 1,806). The ratio in Africa was the highest in each year, followed by Asia and Latin America. Heterophyidae (51 cases), Giardia lamblia (42) and Trichuris trichiura (30) were detected most frequently. In Egypt, the ratio of Heterophyidae rose by 28.8% in 2000. This was the prime reason for the increase in the overall ratio of infections worldwide. Most of the Japanese infected with Heterophyidae in Egypt had ingested dried mullet roe. This may explain the reason for the increase in the infection ratio there. Although the prevalence of intestinal parasites among Japanese expatriates in developing countries is decreasing, those who eat fish in these areas are still at risk. In order to eradicate intestinal parasitosis from this group, we must continue preventive measures such as health education.

Adult↗
PubMed2003

Plasma orexin-A levels in obstructive sleep apnea-hypopnea syndrome.

STUDY OBJECTIVES: Orexin and orexin receptors are present in the CNS. The effects of orexin peptides have been uniformly reported as excitatory, and the posterior hypothalamus containing orexin neurons has been implicated in arousal state control. Therefore, it is probable that the orexin system may have a neuromodulatory effect on arousal states. The aim of the present study was to investigate the relationship between plasma orexin-A levels and arousals from sleep in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). DESIGN: An analysis was conducted in 30 male patients with OSAHS, which had been diagnosed by polysomnography by the presence of an apnea-hypopnea index (AHI) of > 5, and 20 male age-matched and body mass index (BMI)-matched control subjects. RESULTS: Plasma orexin-A levels were higher in patients with OSAHS compared with those in control subjects (p < 0.05). Plasma orexin-A levels correlated positively, but weakly, with the arousal index (r = 0.51; p < 0.05) and the AHI (r = 0.52; p < 0.05). However, plasma orexin-A levels did not relate to age, BMI, Epworth sleepiness scale, PaO(2), PaCO(2), minimum arterial oxygen saturation (SaO(2)) during sleep, or mean SaO(2) during sleep. Plasma orexin-A levels can be a measure of both AHI and arousal index. CONCLUSION: These results suggested that the orexin system may be involved in arousal mechanisms in patients with OSAHS.

Carrier Proteins↗
PubMed2002

cDNA macroarray analysis of gene expression in synoviocytes stimulated with TNFalpha.

Gene expression of synoviocytes stimulated with tumor necrosis factor-alpha (TNFalpha) was studied by macroarray analysis to elucidate the cellular response and identify new biological functions of known and unknown genes. 10035 cDNA clones were used to make cDNA macroarrays of representative genes. Synoviocytes expressed large amounts of fibronectin and collagen mRNA. Statistical analysis of the macroarray data revealed 26 genes, including six new genes, which underwent significant alteration of gene expression in response to TNFalpha stimulation. These findings suggest that the synoviocyte response to TNFalpha stimulation forms the basis of development of various aspects of the pathophysiology of rheumatoid arthritis.

Amino Acid Sequence↗
PubMed2002

Increased reflex activation of the peroneus longus following application of an ankle brace declines over time.

Two experiments were performed to document the time-dependent characteristics of the peroneus longus short latency stretch reflex amplitude following application of an ankle brace. In Experiment 1, stretch reflexes were induced in 15 weightbearing subjects during an unbraced condition and braced condition. In Experiment 2, stretch reflexes were induced in 15 weightbearing subjects before and after 3 h of wearing the brace. In Experiment 1. the amplitude of the stretch reflex increased in the braced condition by about 25% relative to the non-braced condition (p = 0.006). In Experiment 2 the amplitude of the stretch reflex increased about 18% immediately after application of the brace relative to the non-braced condition (p = 0.037). After 3 h, the stretch reflex amplitude was not different from that of initial non-braced condition. Given the importance of the peroneus longus muscle in ankle complex stability, further attention should be directed to whether the increased stretch reflex gain can be exploited during rehabilitation from ankle complex injuries. The findings provide a framework by which the effect of ankle braces on ankle joint proprioception, muscle activation profiles and balance may be physiologically interpreted.

Adult↗
PubMed2002

Mini review: surgical indications for adrenal incidentaloma.

The detection of an adrenal mass as an incidental finding has become so frequent that this trend is considered to be an endocrine epidemic. In these adrenal incidentalomas, a difficult problem is to distinguish between benign and malignant primary or secondary tumors. Another major problem in the management of patients with incidentally discovered adrenal mass is whether and when the mass puts the patient at increased risk of an adverse outcome. A Japanese government-supported study conducted by Professor Miyachi's research committee reviewed the records of all university hospitals and hospitals possessing more than 200 beds in Japan and found 2106 Japanese patients with adrenal incidentaloma during the year 1999. They comprised 1095 males (52%) and 1011 females (48%), mostly distributed between 50 and 59 years of age. The tumor size ranged mostly from 1.1 to 2.0 cm. Almost half (50.3%) of all the incidentalomas were diagnosed as non-functional adenomas, and 5.6% were primary or secondary malignant tumors. In conclusion, accurate assessment of tumor size is an important consideration during preoperative evaluation of adrenal tumors in order to rule out malignancy. Careful evaluation of endocrine functions of the hypothalamic-pituitary-adrenal axis is necessary before surgical treatment in patients with adrenal incidentaloma. Patients with adrenal incidentaloma should be carefully followed, especially regarding size and hormonal conditions.

Adrenal Gland Neoplasms↗
PubMed2002

Unique cases of unilateral hyperaldosteronemia due to multiple adrenocortical micronodules, which can only be detected by selective adrenal venous sampling.

Primary aldosteronism is classified as aldosterone-producing adenoma (APA), idiopathic hyperaldosteronism (IHA), unilateral adrenal hyperplasia (UAH), primary adrenal hyperplasia (PAH), adrenal cancer, and glucocorticoid-remediable aldosteronism. We describe here 4 cases of primary aldosteronism due to unilateral hyperaldosteronemia, demonstrating unique histopathologic findings, such as unilateral multiple adrenocortical micronodules in the affected adrenals. Thirty-three patients with primary aldosteronism were consecutively admitted; 27 of them were treated by unilateral adrenalectomy. Four of them also had unilateral adrenal hypersecretion of aldosterone by selective adrenal venous sampling and adrenocortical multiple micronodules without an adenoma. These patients had hyporeninemic hyperaldosteronism with normokalemic hypertension. In these patients, furosemide plus upright test failed to increase plasma renin activity (PRA); the ratio of plasma aldosterone concentration (PAC) to PRA at 90 minutes after captopril administration was similar to that in patients with IHA and APA. Aldosterone concentrations were increased in each unilateral adrenal vein, and poorly encapsulated multiple adrenocortical micronodules from 2 to 3 mm in diameter were microscopically detected in the resected adrenal glands. Immunohistochemical analysis of steroidogenic enzymes, including cholesterol side chain cleavage, 3beta-hydroxysteroid dehydrogenase, 21-hydroxylase, 17alpha-hydroxylase, and 11beta-hydroxylase, indicated that the cortical cells within these micronodules were active in aldosterone production, while the non-nodular zona glomerulosa cells were inactive. We conclude that the clinical and pathologic characteristics of our 4 cases with unilateral multiple adrenocortical micronodules (UMN) are distinct from those of APA, IHA, UAH, and PAH. Furthermore, unilateral hyperaldosteronemia induced by UMN may be frequently misdiagnosed, because standard imaging tests, which cannot always detect tiny abnormalities of adrenals, showed "normal adrenal glands" in these patients. Thus, primary aldosteronism due to UMN should be carefully examined for differential diagnosis of each form of hyperaldosteronemia.

Adenoma↗