Biomedical subjects

T Tani

Publications and source records attributed to T Tani.

At least 145 records · Page 8Linked to original sources

PubMed1998

Role of EDRF in pulmonary circulation during sustained hypoxia.

The pulmonary artery pressure (PAP) response to hypoxia is characterized by an initial vasoconstriction followed by vasodilation. Pulmonary vessels can release endothelium-derived relaxing factor (EDRF), which is considered to be nitric oxide (NO), but the role of EDRF in the regulation of normal and hypoxic pulmonary vascular tone is still uncertain. We designed this study to address the in vivo role of EDRF in vasodilation during sustained hypoxia. We studied the effects of an EDRF-synthesis inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), on the pulmonary vascular response to sustained hypoxia (10% O2, 20 min) in normoxic (N) and chronically hypoxic (CH) rats. Biphasic PAP response was observed in N rats, whereas PAP was unchanged in CH rats during sustained hypoxic exposure. The L-NAME-induced PAP increase during normoxia was greater in CH than in N rats, suggesting that basal EDRF plays an important role in attenuating the severity of pulmonary hypertension in CH rats. Administration of L-NAME increased the initial increment in PAP by acute hypoxia and shifted the PAP response upward throughout sustained hypoxia, while still showing the biphasic pattern, in N rats. In contrast, PAP increased acutely and remained elevated with little recovery in the late phase in CH rats. The inducible NO synthase messenger RNA (mRNA) expression and protein showed greater increases in the lungs of CH than in N rats. These results suggest that EDRF release during sustained hypoxia may partly contribute to the roll-off in PAP response during sustained hypoxia in N rats, and that augmented EDRF may prevent a further increase in PAP during chronic hypoxia.

Alkalosis↗

PubMed1998

Extracorporeal endotoxin removal by polymyxin B immobilized fiber cartridge: designing and antiendotoxin efficacy in the clinical application.

We have developed an extracorporeal hemoadsorption cartridge, the PMX cartridge, to eliminate endotoxin from peripheral blood circulation. As an adsorbent, a polymyxin B covalently immobilized fiber (PMX-F) was developed. After the optimization of the condition of immobilization, fixed polymyxin B maintained its ability to adsorb endotoxin and its bactericidal activity. PMX-F could detoxify many kinds of endotoxin in vitro. Fixed polymyxin B was estimated to interact with the lipid A portion of endotoxin. Utilization of fibrous adsorbents enabled us to design the PMX cartridge with a large surface area and low blood pressure drop in the blood flow compartment and to apply it safely to the direct hemoperfusion procedure. In Japan, the PMX cartridge is now being clinically applied as one of the therapeutical interventions for sepsis, septic shock, and septic multiple organ failure. In multicenter clinical studies, the blood endotoxin level has been significantly decreased. Accompanied with elimination of endotoxin, hemodynamic abnormalities such as low blood pressure and low systemic vascular resistance were significantly improved. In more recent multicenter studies, the average number of failed organs; severity of illness score, such as Goris score; and vasopressor dosage were significantly decreased. The PMX cartridge is expected to be effective in the intervention for the treatment of septic shock. Endotoxin may be one of the therapeutical targets for the treatment of sepsis.

Adolescent↗

PubMed1998

Blood purification therapy in cancer treatment.

It is well known that cancer patients have specific and nonspecific immunosuppressive substances in their sera that depress cellular immunity. Plasma exchanges have been attempted to remove these immunosuppressive factors and improve the immunity to cancer. Double infiltration plasmapheresis has also been attempted and has been found to remove the immunosuppressive substances efficiently without a large volume substitution. Using these methods, an improvement in performance status and clinical symptoms and reduction of tumor size have been observed. Cancer chemotherapy has several severe side effects. Double filtration plasmapheresis is also clinically applied as a surplus carcinostatic drug adsorption method to alleviate systemic adverse reactions.

Adsorption↗

PubMed1998

Reactivation of sea-urchin sperm flagella induced by rapid photolysis of caged ATP.

Sea-urchin sperm flagella in a state of rigor were reactivated by rapid photolysis of caged ATP. After a time lag of 11-17 ms, all bends in the axonemes present during rigor began to be propagated towards the tip as if their propagation had not been interrupted. This result suggests that the site-specific activity of dyneins along the length of the axoneme is preserved even during rigor states when ATP is absent and that regulation of the activity can be restarted immediately with a new cycle of ATP turnover. During the starting transient, pre-existing rigor waves in the distal region were propagated without a change in the maximal shear angle until they disappeared at the tip. This was more evident when the rapid reactivation was triggered in high-viscosity solution, in which only the form of new bends was greatly affected by viscous load. After reactivation, the velocity of microtubule sliding increased and reached a plateau within 28 ms. This time course reflects the rate of force generation by dynein in situ.

Adenosine Triphosphate↗

PubMed1998

Actions of the novel oral antidiabetic agent HQL-975 in genetically obese diabetic db/db mice.

The hypoglycemic effect of the novel oral agent 3-[4-12-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl]-2S-propyla mino-propionic acid (HQL-975) was examined in db/db mice with genetically obese non-insulin dependent diabetes mellitus (NIDDM). The oral administration of HQL-975 at 3.5 and 35.3 mg/kg/d for 7 d decreased the plasma glucose level of these mice in a dose-dependent manner. HQL-975 also significantly decreased the plasma triglyceride, total cholesterol, non-esterified fatty acid and insulin levels. In the oral glucose tolerance test, HQL-975-treated mice showed improved glucose tolerance and decreased endogenous insulin secretion. HQL-975 increased glycemic response to exogenous insulin in the mice. In the HQL-975-treated db/db mice adipocytes, the glucose uptake, insulin binding, and GLUT4 expression were increased compared with those in untreated db/db mice adipocytes. These results indicate that HQL-975 improved insulin action in db/db mice through receptor and post-receptor effects. In conclusion, HQL-975 is a new oral antidiabetic agent with a hypoglycemic effect which is associated with an insulin-sensitizing effect. This agent may therefore be effective for the treatment of NIDDM.

3T3 Cells↗

PubMed1998

Effect of muscarinic agonist on overflow incontinence induced by bilateral pelvic nerve transection in rats.

The effect of bethanechol, a muscarinic agonist, was studied by cystometrography in conscious rats with bilateral pelvic nerve (PN) lesions. In sham-operated rats, the transvesical infusion of saline elicited regularly micturition. The micturition was abolished by the bilateral PN transection, resulting in overflow incontinence. Bethanechol (30 mg/kg), administered orally to denervated rats, significantly increased the micturition frequency. Therefore, the micturition seems to be largely dependent upon muscarinic receptors of the bladder, and the finding supports the clinical effect of bethanechol. Moreover, this animal model may be useful for studying the overflow incontinence from detrusor failure of neuropathic origin.

Administration, Oral↗

PubMed1998

Pharmacological studies on the novel antiallergic drug HQL-79: I. Antiallergic and antiasthmatic effects in various experimental models.

The effects of oral administration of 4-benzhydryloxy-1-[3-(1H-tetrazol-5-yl)-propyl]piperidine (HQL-79), a newly synthesized antiallergic drug, in various experimental allergic and asthmatic models were investigated. HQL-79 markedly inhibited immediate hypersensitivity reactions such as passive cutaneous anaphylaxis in rats, antigen-induced bronchoconstriction and nasal vascular permeability in actively sensitized guinea pigs, like epinastine and ketotifen did. Airway eosinophilia in repeatedly antigen-exposed guinea pigs was suppressed by chronic administration of HQL-79 for 2 weeks. In another experiment, the antigen-induced late asthmatic response (LAR) in metyrapone-treated guinea pigs was also ameliorated by chronic treatment with HQL-79. Moreover, HQL-79 partially inhibited the toluene diisocyanate-induced delayed-type hypersensitivity (DTH) reaction in mice when administered chronically during the immunization period. The corticosteroid dexamethasone inhibited the airway inflammatory responses in guinea pigs and the DTH in mice. These results indicate that HQL-79 has potent inhibitory effects on the immediate hypersensitivity reactions, and when administered chronically, it also inhibits airway eosinophilia, LAR and DTH, similarly to corticosteroids.

Animals↗

PubMed1998

Pharmacological studies on the novel antiallergic drug HQL-79: II. Elucidation of mechanisms for antiallergic and antiasthmatic effects.

The effects of 4-benzhydryloxy-1-[3-(1H-tetrazol-5-yl)-propyl]piperidine (HQL-79), a newly developed antiallergic drug, on various chemical mediators and on chemical mediator release were investigated. Orally administered HQL-79 strongly inhibited the histamine-induced skin reaction in rats, and histamine- and 5-hydroxytryptamine (5-HT)-induced bronchoconstriction in guinea pigs. HQL-79 inhibited antigen-induced release of leukotriene (LT) B4, LTC4, histamine and prostaglandin (PG) D2 from the chopped lung tissues of actively sensitized guinea pigs. On the other hand, release of PGE2, one of the bronchoprotective prostanoids, was significantly enhanced by HQL-79. In an in vivo experiment, chronic administration of HQL-79 clearly reduced PGD2 contents and enhanced PGE2 contents in the lungs of repeatedly antigen-exposed guinea pigs. In biochemical studies, HQL-79 inhibited mouse spleen PGD synthase in a concentration-dependent manner. None of the antiallergics such as epinastine, terfenadine, oxatomide and cetirizine inhibited the PGD synthase. HQL-79 did not affect PGE synthase in sheep vesicular gland microsomes. These results suggest that antiallergic and antiasthmatic effects of HQL-79 could be ascribed to antihistaminic- and anti-5-HT effects, chemical mediator release inhibition, PGE2-release enhancement and PGD synthase inhibition. It is considered, in particular, that the differential modulation of PGD2 and PGE2 production is a conspicuous pharmacological feature of HQL-79.

Animals↗

PubMed1998

Effects of the novel oral antidiabetic agent HQL-975 on glucose and lipid metabolism in diabetic db/db mice.

The antidiabetic effects of 3-¿4-[2-(5-methyl-2-phenyl-oxazol-4- yl)ethoxy]phenyl¿-2S-propylamino-propionic acid (CAS 185679-16-7, HQL-975), a novel oral agent, on a genetically obese non-insulin-dependent diabetes mellitus (NIDDM) model (db/db mice) were examined. HQL-975 administration (3.7-34.1 mg/kg/d for 7 days) decreased the levels of plasma glucose, triglyceride, total cholesterol, non-esterified fatty acid and insulin in the mice. In an intraperitoneal glucose tolerance test (IPGTT), HQL-975 administration decreased the fasting plasma glucose level and improved the glucose tolerance in the mice. The HQL-975 administration also significantly increased the glycogenesis and lipogenesis from 14C-glucose in liver, but did not alter the glycogenesis in the diaphragm or the lipogenesis in adipose tissues at 2 h after the glucose loading. In the HQL-975-treated db/db mice, the radioactivity of 14C-glucose incorporated into hepatic glycogen was higher than that incorporated into hepatic total lipids. After the administration of HQL-975 (34.1 mg/kg/d for 7 days) to db/db mice, the hepatic hexokinase and fatty acid synthetase activities were significantly increased, the glycogen synthase I activity was increased but not significantly, and the glucose-6-phosphatase and the phosphoenolpyruvate carboxykinase activities were decreased. These results suggest that HQL-975 increases the hepatic glucose utilization and decreases the hepatic glucose production. Since hepatic glycogenesis is regulated by glucose itself but not by insulin in normoglycemic ICR mice, HQL-975 is thought to enhance the effect of glucose on the stimulation of hepatic glycogenesis. It is concluded that the enhancement of the hepatic glucose utilization played an important role in the hypoglycemic action of HQL-975.

Animals↗

PubMed1998

Diagnostic value of cervical somatosensory evoked potentials recorded from the intervertebral discs after median and ulnar nerve stimulation in cervical spondylotic myelopathy.

We have studied the cervical somatosensory evoked potentials (CSEPs) recorded referentially from serial intervertebral discs after stimulation of the median nerve or the ulnar nerve at the wrist in cervical spondylosis. In seven unilateral radiculopathies, the CSEPs evoked by stimulation on the asymptomatic side normally consisted of the P1-N1 and the P2-N2 components, which represented the potentials arising from the white matter and the gray matter, respectively. Of 21 myelopathies, the CSEPs revealed the white matter involvement with conduction block identified by abrupt P1-N1 amplitude reduction in 7, the gray matter involvement identified by P2-N2 amplitude reduction in 3, or a combination of both in 11. The CSEPs were useful not only for determining the level responsible for myelopathy but also for localizing the lesion in the transverse plane of the spinal cord.

Adult↗

PubMed1997

Activation of c-Jun N-terminal kinase during ischemia and reperfusion in mouse liver.

We have generated a mouse model for hepatic ischemia in which surgical subcutaneous transposition of the spleen allows hepatic ischemia to be applied without affecting other tissues. Using this mouse model we investigated the relationship between the length of ischemic periods in the liver and subsequent liver function; furthermore, we assayed the activation of c-Jun N-terminal kinase (JNK) during ischemia and reperfusion. Although prior to this study only the activated form of JNK was known to be translocated to the nucleus, we found that JNK translocates to the nucleus during ischemia without activation and is then activated during reperfusion. These results suggest a novel mechanism of JNK activation.

Animals↗

PubMed1997

Structure and expression of the gsa-1 gene encoding a G protein alpha(s) subunit in C. elegans.

The heterotrimeric guanine nucleotide-binding proteins (G proteins) act as switches in the signal transduction from cell surface receptors to a variety of effectors. Among them, Gs proteins stimulate adenylate cyclase activities and regulate ion channels in mammals. We identified the gsa-1 gene encoding a G protein alpha subunit in the nematode Caenorhabditis elegans. The predicted product consists of 375 amino acid residues, 66% of which are identical with those of a mammalian Gs(alpha) subunit. The gsa-1 gene was physically mapped near the left end of chromosome I. A gsa-1/lacZ fusion gene was expressed in many cells in embryos, larvae and adults, including neurons, body wall muscle cells and muscle cells of the pharynx and the vulva. The results presents a basis for genetic studies of the gsa-1 gene.

Amino Acid Sequence↗

PubMed1997

Expression of type IV collagen alpha1(IV)-alpha6(IV) polypeptides in normal and developing human kidney and in renal cell carcinomas and oncocytomas.

Type IV collagen trimer is a major component of basement membranes (BMs). It is composed of polypeptides named alpha1(IV)-alpha6(IV) chains. Chains alpha1,2(IV) are widely expressed in BMs while alpha3(IV)-alpha6(IV) are more restricted in human tissues. We have now studied by immunohistochemical means the distribution of collagen IV chains in fetal and adult human kidney, in oncocytomas, in renal cell carcinomas (RCCs) and their metastases and in experimental xenografts of human tumors. alpha1,2(IV) chains were found in all BMs of fetal and adult kidney as well as of renal tumors, while alpha3(IV)-alpha6(IV) chains were found in BMs of distal segments of developing and mature tubules. alpha3(IV)-alpha5(IV) chains were seen also in BMs of developing fetal glomeruli after the capillary loop stage. Most of the RCCs and their metastases showed occasional expression of alpha3(IV)-alpha6(IV) with papillary variants showing only expression of alpha5(IV) chain. There was a distinct expression of alpha3(IV)-alpha5(IV) chains in BMs of 3 oncocytomas. In 2 of them a variable expression of the alpha6(IV) chain was seen. In 3 of 4 xenografts, immunoreactivity for human-specific monoclonal antibody (MAb) for alpha1,2(IV) was seen in the BM-like structures. No alpha3-alpha6(IV) was seen in any of the xenografts, while polyclonal antiserum for type IV collagen presented immunoreactivity in BMs of all xenografts. Our results show that oncocytomas and most of the RCCs express scarce variants of type IV collagen containing alpha3(IV)-alpha6(IV) chains. In experimental xenograft tumors, both implanted RCC cells and host stromal cells have a capacity to produce type IV collagen.

Adenoma, Oxyphilic↗

PubMed1997

An enzyme-linked immunosorbent assay for detecting proteolytic activity of hepatitis C virus proteinase.

An ELISA method for the quantitation in vitro of HCV serine proteinase activity was developed. A peptide substrate, Ac-Gly-Glu-Ala-Gly-Asp-Asp-Ile-Val-Pro-Cys-Ser-Met-Ser-Tyr-Thr-Trp-Thr-L ys (biotin) -OH (Sub-1), was hydrolyzed by a recombinant NS3 proteinase fused with maltose binding protein (MBP-NS3) into a product with a free amino moiety at the N-terminus. The product was immobilized, and the amino moiety was analyzed by digoxigenin labeling followed by immunological reaction with anti-digoxigenin-alkaline phosphatase conjugate and then the colorimeteric reaction. This method is suited for the high throughput screening of inhibitors, and the screening can be accelerated by automatic operation.

Amino Acid Sequence↗

PubMed1997

Hypoxia, but not reoxygenation, induces interleukin 6 gene expression through NF-kappa B activation.

Interleukin (IL) 6 is one of major mediators of inflammation, and IL-6 gene activation during hypoxia/reoxygenation has been implicated in the pathogenesis of ischemia/reperfusion injury. However, molecular events involved in IL-6 gene expression during hypoxia/reoxygenation remain to be identified. We have previously shown that NF-kappa B plays an essential and indispensable role in the transcriptional activation of the IL-6 gene induced by various stimuli, including IL-1 and tumor necrosis factor-alpha. We show here that hypoxia, but not reoxygenation, induces the activation of NF-kappa B through the degradation of a major inhibitor of NF-kappa B, I kappa B alpha. This hypoxia-induced NF-kappa B activation resulted in the kappa B-dependent transcriptional activation of the IL-6 gene. Interestingly, the time course of hypoxia-induced NF-kappa B activation was rather slow as compared with those of NF-kappa B activation induced by other stimuli, such as IL-1: a significant NF-kappa B activation was not observed before 1 hr of hypoxia treatment and persisted for up to 7 hr of hypoxia treatment. However, hypoxia-induced NF-kappa B activation was not inhibited by cycloheximide, which indicates that hypoxia directly triggers NF-kappa B activation. Furthermore, while hypoxia is unlikely to generate reactive oxygen intermediates, pretreatment of cells with antioxidants such as N-acetyl cysteine and alpha-tocopherol inhibited NF-kappa B activation induced by hypoxia. Thus, we discuss possible implications of these results for a postulated role of reactive oxygen intermediates in NF-kappa B activation.

Animals↗

PubMed1997

Bacterial translocation as a cause of septic shock in humans: a report of two cases.

While bacterial translocation has been reported to occur under numerous conditions in animal models, there has been no paper to date focusing on bacterial translocation as a direct cause of septic shock in humans. We present herein the cases of two patients who developed septic shock believed to have been directly caused by bacterial translocation. Neither of the patients had a focus of infection, the intestinal walls were intact in gross appearance, and the peritoneal cavity had not been contaminated by surgery. Moreover, in both patients, the same organisms were detected in the blood, ascites fluid, and mesenteric lymph nodes, and bacilli were found in the intestinal wall.

Aged↗

PubMed1997

Benign cervical teratoma in an adult: report of a case.

Cervical teratomas are rarely encountered in adults. We report herein the case of a 21-year-old woman who was admitted to our hospital for surgical treatment of a neck tumor, 7.5 x 4.5 x 2.7 cm in size, located in the left lower pole of the thyroid. Ultrasonography (US) and computed tomography (CT) revealed a multicystic tumor. The levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and squamous cell carcinoma-related antigen (SCC) in the cystic fluid were extremely elevated in contrast to the normal levels found in the serum. The tumor was completely excised and histological examination revealed it to be composed of elements derived from the three germ layers, confirming a diagnosis of benign cystic teratoma.

Adult↗

PubMed1997

A pancreatic pseudocyst with pancreatic pleural effusion: report of a case.

A 54-year-old man with a 30-year history of chronic alcoholism was admitted to our hospital suffering from dyspnea and left-sided chest pain. A chest radiograph revealed pleural effusion. Computed tomography revealed a pancreatic pseudocyst in the tail of the pancreas spreading out to the posterior mediastinum and the left pleural cavity. The laboratory findings of pleural effusion were as follows: amylase, 118,400 IU/1; protein, 4.6 g/dl; class I in cytology. Despite a reduction in the pleural effusion by conservative therapy, left back pain and a recurrence of the pleural effusion were observed after oral intake was re-initiated. A distal pancreatectomy and ligation of the pancreaticopleural fistula were thus performed on the 75th hospital day. The patient made a complete recovery from pancreatic pleural effusion and has now been well for 9 years.

Chronic Disease↗