PubMed Health⌕ Search

Biomedical subjects

T Suga

Publications and source records attributed to T Suga.

At least 37 records · Page 2Linked to original sources

Endothelial dysfunction in the klotho mouse and downregulation of klotho gene expression in various animal models of vascular and metabolic diseases.

The human aging process is associated with vascular endothelial dysfunction. However, humoral factors which might protect against endothelial dysfunction during aging have not yet been identified. We recently identified the klotho gene as a possible regulator of human aging. In the present study using the klotho-deficient heterozygous mouse, we examined whether the Klotho protein is a humoral factor protecting against endothelial dysfunction. We further cloned rat klotho cDNA and investigated whether klotho mRNA expression in rat kidney is altered under pathological conditions such as hypertension, hyperlipidemia, renal failure, and inflammatory stress. The Klotho protein itself, or its metabolites, promotes endothelial NO production in aorta as well as arterioles, and klotho mRNA in kidney is downregulated under sustained circulatory stress.

Acetylcholine↗

Gastric varices with splenic vein occlusion treated by splenic arterial embolization.

A 53-year-old man was admitted to our hospital in August 1997 with enlarged gastric varices. Computed tomography (CT) showed splenic vein occlusion, gastric varices, and extra-gastric wall collateral veins. Color flow images of gastric varices were clearly visualized, and the velocity in the gastric varices was 19.6 cm/s via endoscopic color Doppler ultrasonography (ECDUS). The patient was diagnosed with gastric varices according to angiographic findings of splenic vein occlusion, and splenic arterial embolization was performed. Two weeks after the splenic arterial embolization, CT showed peripheral areas of low attenuation in the spleen, due to splenic infarction, with 70% of the spleen volume showing low attenuation. Eight months after the splenic arterial embolization, ECDUS revealed a decrease in gastric variceal color flow images, with the velocity in the gastric varices being 10.3 cm/s.

Chronic Disease↗

Early mutation of precore (A1896) region prior to core promoter region mutation leads to decrease of HBV replication and remission of hepatic inflammation.

To evaluate the relationship between mutations and clinical courses, we investigated precore (preC) and core promoter (CP) mutations and serum HBV DNA levels in HBe-antibody-positive HBV carriers. Fifty-six asymptomatic carriers (ASC), 29 patients with chronic hepatitis who showed normal ALT levels for more than two years (CH-ASC), 31 patients with chronic hepatitis (CH), and 32 patients with hepatocellular carcinoma (HCC) were studied. Almost all patients (99.2%) had mutations in either CP or preC. Mutation only in preC (A1896) was present in 52.2% with ASC, 25.0% with CH-ASC, 16.1% with CH, and 8.0% with HCC, and was significantly higher in ASC (P < 0.01). The patients with only preC mutation showed low HBV DNA levels in each clinical stage. The mutation of preC (A1896) prior to the mutation of CP might control the replication of HBV, which leads to the remission of hepatitis.

Adult↗

Endoscopic pancreatic sphincter balloon dilation for effective retrieval of pancreatic duct stone.

To facilitate pancreatic stone retrieval, four patients with chronic pancreatitis and pancreatic stones underwent endoscopic pancreatic sphincter balloon dilation (EPSBD) rather than pancreatic sphincterotomy. Extracorporeal shock wave lithotripsy combined with endoscopic removal was carried out in three patients. Stone removal following EPSBD was completely successful in all four patients. Patients showed no severe complications during the dilation procedure. In one patient, to prevent pancreatitis, an endoscopic nasopancreatic drain was placed for 1 week after EPSBD. Compared with pancreatic sphincterotomy, EPSBD can be performed safely in patients with chronic pancreatitis to assist in the extraction of pancreatic duct stones. Use of the EPSBD procedure in cases of chronic pancreatitis provides a useful approach to improve endoscopic clearance of pancreatic duct stones.

Aged↗

Pleural amyloidosis in a patient with intractable pleural effusion and multiple myeloma.

Pleural involvement of systemic amyloidosis has been rarely reported. We report a case with multiple myeloma presenting an intractable right pleural effusion, in which pleural amyloidosis was diagnosed through pleural biopsy using a Cope needle. The diagnosis of pleural amyloidosis is important, because its refractory pleural effusion should be treated with pleurodesis. Since closed pleural biopsy using a Cope needle is much less invasive than thoracoscopy, the former should be attempted first whenever pleural amyloidosis is suspected.

Aged↗

Adhesions from flexor tendon surgery: an animal study comparing surgical techniques.

Intraoperative and postoperative hemorrhage has long been considered a cause of tendon adhesion and, thus, scarring and poor surgical results. To prevent such problems bipolar coagulators are commonly used during surgery to help achieve hemostasis. Surgical lasers also have been reported to help limit bleeding and scar formation. Very little is known regarding the relationship between hemorrhage and/or direct tendon tissue effects and tendon adhesions with the use of these modalities. We compared 3 different surgical techniques (meticulous sharp scalpel dissection, scalpel dissection plus bipolar coagulation, and CO(2) laser dissection) and used chicken flexor tendons to biomechanically and histologically assess the amount of adhesion formation after each procedure. Our findings show that bipolar coagulation and CO(2) laser application are both associated with significantly increased adhesion formation in tendon surgery compared with sharp dissection alone and that the meticulous, conventional sharp dissection technique is the best method to control adhesion formation. These conclusions have relevance to clinical tendon surgery.

Animals↗

Decreased insulin production and increased insulin sensitivity in the klotho mutant mouse, a novel animal model for human aging.

We have recently identified a novel gene, klotho (kl), which may suppress several aging phenotypes. A defect of kl gene expression in the mouse results in a syndrome resembling human aging, such as arteriosclerosis, skin atrophy, osteoporosis, and pulmonary emphysema. To determine whether mouse homozygotes for the kl mutation (kl/kl) show abnormal glucose metabolism, an oral glucose tolerance test (OGTT) was performed at 6 to 8 weeks of age. Blood glucose levels during the OGTT were significantly lower in kl/kl mice versus wild-type mice. The insulin content of the pancreas was significantly lower in kl/kl mice compared with wild-type mice. Decreased insulin production was also supported by Northern blot analysis showing lower levels of insulin mRNA in kl/kl mice. To examine how lower blood glucose levels may exist in kl/kl mice despite decreased insulin production, insulin tolerance tests (ITTs) were performed. The glucose decline following insulin injection was more severe in kl/kl mice versus wild-type mice, suggesting that insulin sensitivity was higher in kl/kl mice versus wild-type mice. In kl/kl mice, an augmented expression of GLUT4 in skeletal muscle was demonstrated by both Northern blot analysis and Western blot analysis. Thus, we conclude that insulin production is decreased and insulin sensitivity is increased in the klotho mouse, a novel animal model for human aging.

Adrenocorticotropic Hormone↗

Disruption of the klotho gene causes pulmonary emphysema in mice. Defect in maintenance of pulmonary integrity during postnatal life.

Homozygous mutant klotho (KL(-/-)) mice exhibit multiple phenotypes resembling human aging. In the present study, we focused on examining the pathology of the lungs of klotho mice and found that it closely resembled pulmonary emphysema in humans both histologically and functionally. Histology of the lung of KL(-/-) mice was indistinguishable from those of wild-type littermates up to 2 wk of age. The first histologic changes appeared at 4 wk of age, showing enlargement of the air spaces accompanied by destruction of the alveolar walls, and progressed gradually with age. In addition to these changes, we observed calcium deposits in type I collagen fibers in alveolar septa and degeneration of type II pneumocytes in 8- to 10-wk-old KL(-/-) mice. Pulmonary function tests revealed prolonged expiration time in KL(-/-) mice, which is comparable with the pathophysiology of pulmonary emphysema. The expression level of messenger RNA for type IV collagen, surfactant protein-A and mitochondrial beta-adenosine triphosphatase was significantly increased in KL(-/-) mice, which may represent a compensatory response to alveolar destruction. Additionally, the heterozygous mutant klotho mice also developed pulmonary emphysema late in life, around 120 wk of age. These findings indicate that klotho gene expression is essential to maintaining pulmonary integrity during postnatal life. The klotho mutant mouse is a useful laboratory animal model for examining the relationship between aging and pulmonary emphysema.

Aging↗

Involvement of hepatocyte growth factor on hepatocarcinogenesis induced by peroxisome proliferators.

Hepatocyte growth factor (HGF) has been known to enhance the growth of normal hepatocytes, but also to inhibit the growth of neoplastic cells. This article examines the involvement of HGF in the hepatocarcinogenesis caused by peroxisome proliferators (PPs). Up to 78 wk after male F-344 rats were orally given (4-chloro-6-[2,3-xylidino]-2-pyrimidinylthio) acetic acid (Wy-14,643), the hepatocarcinomas and (pre)neoplastic nodules in the livers were observed. At that time, the content of HGF and the expression of HGF mRNA in the liver tumors were significantly decreased. These changes were observed also in the liver of rats treated with other PPs, such as dehydroepiandrosterone and di(2-ethylhexyl)phthalate, but were not observed in tumors induced by genotoxic carcinogens (diethylnitrosamine-phenobarbital). In in vivo experiments, the formation of preneoplastic lesions and the tumors caused by Wy-14,643 administration were markedly suppressed by i.v.-injection of HGF in a dose-dependent manner. In the colony assay using (pre)neoplastic cells from livers of Wy-14,643-treated rats, HGF inhibited the colony formation of (pre)neoplastic cells in a dose-dependent manner. These findings may indicate that decreases in hepatic HGF levels are common and specific events induced by PPs, but not by genotoxic carcinogens, and that those changes play an important role in the promotion of neoplastic or preneoplastic cell growth induced by PPs.

Animals↗

Phosphorylation of 13 kDa nuclear protein in hepatocarcinomas induced by peroxisome proliferators.

Peroxisome proliferators (PPs) are nongenotoxic compounds causing the emergence of hepatocellular carcinoma in rodents, but the mechanisms of the hepatocarcinogenesis have been unclear. The authors examined the changes in phosphorylation of nuclear proteins after treatment with (4-chloro-6-[2,3-xylidino]-2-pyrimidinylthio) acetic acid (Wy-14,643). Wy-14,643 (0.1% w/w in diet) was given orally to male F-344 rats for up to 80 wk. In the hepatocarcinomas induced by Wy-14,643, phosphorylation of 13 kDa nuclear protein (NP 13), which was resistant to alkaline treatment, was significantly increased. NP 13 phosphorylation gradually increased, dependent on treatment period. Furthermore, in the hepatocarcinomas induced by other PP, di(2-ethylhexyl)phthalate, increase in NP13-phosphorylation was also observed. Therefore, NP 13-phosphorylation may relate to development of preneoplastic or neoplastic lesions induced by PPs.

Animals↗

Nuclear hypersegmentation precedes the increase in blood eosinophils in acute eosinophilic pneumonia.

In this case of acute eosinophilic pneumonia (AEP), eosinophils with hypersegmented nuclei emerged in the blood before the increase of eosinophil count. An 18-year-old woman complaining of fever, cough and dyspnea was admitted because of diffuse ground-glass opacities in her chest roentgenogram. On admission, her blood cell count revealed a marked increase of neutrophils. Although the number of eosinophils was normal, some of them contained three- or four-lobed nuclei. She was diagnosed to have AEP through bronchoalveolar lavage and transbronchial lung biopsy. The combination with acute clinical course, pulmonary infiltration and the presence of hypersegmented eosinophils in blood may imply the diagnosis of AEP.

Acute Disease↗

Alternate numbness in the upper extremities as the initial symptom of basilar migraine: an electrophysiological evaluation using EEG power topography.

A case of basilar migraine (BM) with alternate numbness as the initial symptom is described. The patient's chief complaint was alternate numbness in the right and left upper extremities. After angiography the patient fell into a drowsy state, followed by excitation, and finally confusion. The EEG power topography showed slow alpha, theta and delta power in the right occipital area, and alternatively in the right and left parietal area. These findings suggest that the cause of BM is not only based on a vasoconstriction mechanism, but also cortical spreading depression. BM should be suspected as a cause of sensory symptoms.

Adolescent↗

Gastrointestinal stromal tumors of the small intestine that expressed c-kit protein.

We report two patients with gastrointestinal stromal tumors (GISTs) of the small intestine that expressed c-kit protein (CD117). One was a 68-year-old woman with epigastralgia and vomiting. A submucosal tumor of the upper jejunum was detected, and partial resection was carried out. The histology revealed a GIST negative for CD34 but positive for CD117. The other was a 42-year-old woman with progressive anemia, melena and lower abdominal pain. Intussusception was detected, and a partial resection was carried out. A submucosal tumor of the lower jejunum was noted. The histology revealed a GIST positive for both CD34 and CD117.

Adult↗

[PL granule-induced pneumonia requiring mechanical ventilation].

PL granule is one of the most common forms of composite medicine for colds in Japan, including acetaminophen. We report a case of PL granule-induced pneumonia that required mechanical ventilation. A 72-year old man who had been prescribed amiodarone for more than one year before for arrhythmogenic right ventricular dystrophy, repeatedly took PL granules at one-week intervals because of sneezing and fever. He then underwent acute respiratory failure. He needed mechanical ventilation for severe hypoxemia, but recovered with glucocorticoid pulse therapy. Because the blastoid transformation test using his peripheral blood lymphocytes was positive on stimulation with PL granules, but negative on amiodarone stimulation, he was diagnosed as having drug (PL granule)-induced pneumonia. Only one case of PL granule-induced pneumonia and seven of acetaminophen-induced pneumonia have been reported. None of these patients needed mechanical ventilation. PL granule-induced pneumonia should be treated cautiously because of possible acute exacerbation.

Aged↗

Pulmonary nocardiosis during immunosuppressive therapy for idiopathic pulmonary fibrosis.

Nocardiosis is a subacute or chronic suppurative infection caused by Nocardia species. Although it is more common in immunocompromised hosts, idiopathic pulmonary fibrosis (IPF) has not been recognized as a predisposing factor for nocardial infection. We report a case of IPF, in which pulmonary nocardiosis developed during treatment with prednisolone and cyclophosphamide. The risk of pulmonary nocardiosis may be increased in cases of IPF on immunosuppressive therapy. Since IPF often accompanies lung carcinoma, it is important to correctly differentiate nocardiosis from carcinoma.

Aged↗

Wy-14,643, a peroxisome proliferator, inhibits compensative cell proliferation and hepatocyte growth factor mRNA expression in the rat liver.

Previously, we found that a peroxisome proliferator significantly reduced hepatic and plasma hepatocyte growth factor (HGF) levels in male F-344 rats, and that the growth of preneoplastic or neoplastic cells induced by this peroxisome proliferator was markedly inhibited by HGF. Here, we examined the effects of [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid (Wy-14,643), a peroxisome proliferator, on cell proliferation and HGF mRNA levels in the liver of rats after stimulation of compensative cell proliferation. After 2 weeks of treatment with Wy-14,643, hepatic DNA synthesis caused by partial hepatectomy was decreased by 50% compared with untreated controls. DNA synthesis was maintained at the same reduced level for up to 10 weeks. During this period, hepatic HGF mRNA level was also much lower in Wy-14,643-treated rats than untreated controls. Therefore Wy-14,643, a peroxisome proliferator, would inhibit the growth of normal hepatocytes, and then produce an advantageous circumstance for the selective growth of neoplastic or preneoplastic cells.

Animals↗