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Biomedical subjects

K Noguchi

Publications and source records attributed to K Noguchi.

At least 379 records · Page 21Linked to original sources

Synthesis and bioactivity of propranolol analogues with a rigid skeleton. I.

The synthesis of two kinds of propranolol analogues, A and B, with a rigid skeleton was investigated. The compounds were designed to help identify the conformation involved in beta-adrenergic receptor-propranolol interaction. The key intermediate, 2-hydroxy.2,3-dihydronaphtho[1,8-bc]pyran (5), was obtained starting from acenaphthenone (1). On sequential dehydration, hydroboration, and oxidation, 5 gave 2,3-dihydronaphtho[1,8-bc]pyran-3-one (8), which was converted to compound A. Compound 5 was also derived to 2-formyl-2,3-dihydronaphtho[1,8-bc]pyran (13) via the 2-vinyl compound (12). Condensation of nitromethane with 13 followed by reduction and alkylation produced the desired compound B. The beta-blocking activities of A and B were examined.

Adrenergic beta-Antagonists↗

Comparative effects of arotinolol, labetalol and propranolol on regional myocardial dysfunction induced by flow-limiting coronary stenosis in anesthetized dogs.

Effects of arotinolol, a combined alpha- and beta-adrenoceptor blocking agent, on regional myocardial dysfunction produced by severe coronary stenosis in anesthetized dogs were examined and compared with those of labetalol and propranolol. Doses of these three antagonists were selected to produce a comparable degree of the negative chrono- and inotropic effect but a different potency of alpha-adrenoceptor blockade (labetalol greater than arotinolol). Regional myocardial function measured as segment shortening (%SS) was decreased to around 2-3% by constriction of the left circumflex coronary artery (LCX), and then drug or saline was administered i.v. The stenosis of LCX was released 30 min after the administration. No significant alteration in hemodynamic and contractility parameters was seen as compared to the predrug value up to at least 30 min after saline i.v. Arotinolol and propranolol both reduced heart rate and peak positive left ventricular dP/dt (LVdP/dt) without a significant change in LCX flow. Concomitantly, %SS distal to a coronary stenosis was significantly improved by arotinolol and propranolol. On the other hand, labetalol significantly reduced LCX flow probably due to systemic hypotension and failed to improve %SS in the ischemic area, although the agent markedly decreased heart rate and LVdP/dt. These results indicate that arotinolol improves impaired regional myocardial function distal to a coronary stenosis in a similar manner with propranolol.

Adrenergic beta-Antagonists↗

Characteristics of cardiovascular effects of the venom of habu (Trimeresurus flavoviridis) in rats.

Characteristics of the cardiovascular effects of habu venom were studied in vivo and in vitro in rats. Aortic pressure (AoP), heart rate (HR) and renal cortical blood flow (RCBF) assessed by a laser-Doppler flowmeter were measured in anesthetized rats. Administration of habu venom (0.2-1.6 mg/kg, i.v.) dose-dependently produced a fall in AoP without a marked change in HR. RCBF decreased significantly along with the decline in AoP. Heated habu venom (70 degrees C for 5 min) or the residual venom by dialysis produced similar hemodynamic responses to nonheated crude habu venom. Although habu antivenin significantly reduced the effects of habu venom, indomethacin, aprotinin, atropine, captopril and chlorpheniramine did not. Methylprednisolone significantly attenuated these effects. Habu venom (10(-5) to 3 x 10(-4) g/ml) produced dose-dependent relaxations of the isolated rat aorta preparations precontracted with norepinephrine or KCl, which were not affected by indomethacin, nordihydroguaiaretic acid, p-bromophenacyl bromide, mepacrine, methylene blue or de-endothelialization. These results indicate that habu venom, particularly its heat-stable component(s) which has at least more than 10,000 molecular weight, produces hypotensive and vasorelaxant effects in rats, and suggest that eicosanoids, kinins, histamine, ACh, and endothelium are scarcely involved in these effects.

Animals↗

Effect of polyoxyethylene-modified superoxide dismutase on recovery of myocardial dysfunction after coronary stenosis in dogs.

The effects of superoxide dismutase modified with polyoxyethylene (SOD-POE) on impairment of myocardial segment shortening (SS) during coronary stenosis plus pacing-induced tachycardia (CSPT) and the recovery after reperfusion was examined in anesthetized dogs. SOD-POE or saline was administered i.v. 30 min before reperfusion. Changes in hemodynamic variables and SS by CSPT were similar in both groups. However, the SOD-POE group showed improved recovery of SS compared with the control group. Results indicate that oxygen-derived free radicals may partially be involved in the genesis of myocardial dysfunction after CSPT-induced regional ischemia.

Animals↗

Persistent primitive hypoglossal artery associated with arteriovenous malformation--case report.

A case of persistent primitive hypoglossal artery (PPHA) associated with arteriovenous malformation (AVM) is reported. A 46-year-old male suddenly developed severe headache followed by transient unconsciousness and was admitted to our hospital 2 hours later. A computed tomographic scan showed subarachnoid hemorrhage. Angiograms revealed an AVM in the left cerebellar hemisphere and an ipsilateral PPHA. The AVM was completely removed and he was discharged 1 month after surgery without neurological deficit. Only three cases of PPHA associated with intracranial AVM have been reported in the literature. One patient died of rebleeding from the AVM before surgery, and another was conservatively treated because the AVM was too large for resection. The remaining one was surgically treated only by ligation of the feeding arteries. Ours is the first case treated by total removal of the AVM. Since these four cases, including ours, account for 3.0% of 134 cases of PPHA reported, PPHA associated with AVM is considered rare.

Cerebral Angiography↗

[Two cases of idiopathic retroperitoneal fibrosis effectively treated with steroid therapy].

Two cases of idiopathic retroperitoneal fibrosis (IRPF) were reported. The first case, in a 72-year old man, was admitted for hydronephrosis with indistinct origin. Following percutaneous nephrostomy, biopsy of retroperitoneal tissue was performed, and IRPF was diagnosed. The treatment consisted of bilateral ureterolysis, intraabdominal transposition of ureters and oral administration of prednisolone for 3 months. The second case, in a 51-year-old woman, was admitted for the evaluation of severe azotemia. As ovarian carcinoma and its ureteral invasion was suspected, simple hysterectomy and bilateral ovariectomy were performed. Typical histological finding of IRPF was also observed. Oral administration of prednisolone has been continued for two years. Recurrence of IRPF has not been observed in these two cases for over two years.

Aged↗

[A case of double bronchogenic cysts in the mediastinum].

A 42-year-old house wife had suffered from abnormal mass lesion in the right pulmonary hilum on her chest X-ray film. MRI showed another mediastinal mass between IVC and descending aorta with high T1 and T2 intensity. Thoracic CT done before MRI missed the latter lesion because only upper mediastinal scanning had been performed. At operation subcarinal and right paraesophageal cysts were successfully removed. Histological examination of the subcarinal cyst showed ciliated pseudostratified columnar epithelium lining, and its thin wall consisted of partly smooth muscle bundle, lymph node, calcification, inflammatory cell infiltration and hemorrhage. The paraesophageal cyst lined by a ciliated pseudostratified columnar epithelium, and the wall consisted of mostly fibrous connective tissue with partly smooth muscle bundle. Although the both cysts were diagnosed as bronchogenic origin, definitive bronchial glands and cartilage could not be recognized. The postoperative course was uneventful. This is the first case report of mediastinal double bronchogenic cysts appeared in the Japanese literature.

Bronchogenic Cyst↗

[Eel calcitonin treatment on patients with urogenital carcinoma for relief of pain from metastatic bone lesions].

Forty-seven patients of advanced urogenital carcinoma with bone metastasis were treated with eel calcitonin (CT) to relieve severe pain from metastatic bone lesions. Patients were 45 males and 2 females with a mean age of 72.9. CT was administered intravenously at a daily dose of 160 units for 10 days. The efficacy of CT on relief of pain was estimated using a mark sheets filled by each patient and his or her doctor. And also the amount of analgesics given to patients before and after the administration of CT were checked. CT was effective on 77% of patients to reduce severe bone pain, especially on osteoblastic lesions metastasized from prostatic carcinoma. CT administration decreased the amount of analgesics in 37% of the cases. As toxicity, nausea and vomiting which stopped the CT administration were observed in only one From these results, we conclude that CT is quite useful drug for relief of severe bone pain from metastatic lesions in patients with urogenital carcinoma.

Aged↗

Alleviation of myocardial dysfunction and abnormal lactate metabolism during coronary stenosis in dogs by ICI 118,551.

Hemodynamic parameters, segment shortening in the ischemic myocardium and cardiac lactate extraction were estimated in the presence of a critical coronary stenosis, before and after administration of the selective beta 2-adrenoceptor antagonist, ICI 118,551, or the beta 1-adrenoceptor antagonist, atenolol, to anesthetized dogs. ICI 118,551 (0.2 and 0.5 mg/kg i.v.) and atenolol (0.2 mg/kg i.v.) produced significant decreases in both heart rate (by 6, 14 and 20% of the predrug value, respectively) and maxLVdP/dt (by 15, 26 and 24% of the predrug value, respectively). ICI 118,551 (0.5 mg/kg) and atenolol significantly improved the impaired shortening of the myocardial segment when compared with the change seen after saline administration. ICI 118,551 at both doses and atenolol significantly increased depressed cardiac lactate extraction while saline did not. Increasing heart rate by pacing abolished the beneficial effects of ICI 118,551 and atenolol on ischemic myocardial segment shortening and lactate metabolism. The data suggest that not only beta 1- but also beta 2-adrenoceptor blockade may contribute to the amelioration of myocardial ischemia in a model of coronary stenosis.

Angina Pectoris↗

Different GTP-binding proteins mediate regulation of calcium channels by acetylcholine and noradrenaline in rat sympathetic neurons.

In dissociated neurons of rat superior cervical ganglion (SCG), noradrenaline (NA) and acetylcholine (ACh) suppressed Ca2+ currents elicited by depolarizations to 0 mV from -60 mV. With GTP-gamma-S in patch electrodes, ACh and NA caused persistent inhibition of Ca2+ currents. Pretreatment of SCG cells with pertussis toxin abolished the action of ACh but not of NA. The results suggest that ACh and NA reduce the Ca2+ currents in SCG cells through different G proteins.

Acetylcholine↗

Postnatal ontogeny of POMC gene expression in the rat pituitary: an analysis by in situ hybridization histochemistry.

Postnatal development of proopiomelanocortin gene expression in the rat pituitary was examined using in situ hybridization histochemistry. In adult rats, a very high density of hybridization signals was seen in the intermediate lobe of the pituitary, while only a moderate density occurred in the anterior lobe. No evidence of hybridization was detected in the posterior lobe. At birth, both the intermediate and anterior lobes had low to moderate frequencies of hybridization signals but a rapid rise to moderate density was noted by the 8th postnatal day. Radioactive labelling in the intermediate lobe continued to increase sharply with age to reach a plateau at postnatal day 28, while hybridization signals in the anterior lobe levelled off at postnatal day 8 with no subsequent rise in density.

Aging↗

Hypersensitivity pneumonitis induced by toluene diisocyanate: sequelae of continuous exposure.

A 41-year-old automobile paint sprayer showed the clinical features of hypersensitivity pneumonitis 1 week after he had begun to work with paint materials containing toluene diisocyanate. His symptoms began 6 to 8 hours after exposure to the agent and spontaneously disappeared by the next morning. He had diffuse, fine reticulonodular shadows on a chest roentgenogram and a restrictive impairment of pulmonary function. Immunoglobulin G antibody to toluene diisocyanate-human serum albumin was present in bronchoalveolar lavage fluid and sera: IgA antibody was present only in bronchoalveolar lavage fluid. Also, the patient had sensitized bronchoalveolar lymphocytes to toluene diisocyanate-human serum albumin. The histologic findings suggested hypersensitivity pneumonitis. The results of bronchoalveolar lavage, which was repeated on four separate occasions, showed lymphocytosis and a predominance of suppressor-cytotoxic T cells. The findings from serial determinations of humoral antibodies showed no changes consistent with the results of clinical and laboratory studies. In contrast, blastogenic responses of bronchoalveolar lymphocytes to toluene diisocyanate markedly decreased, and the patient showed clinical improvement despite continued exposure to the agent.

Adult↗

The detection of platelet-activating factor in inflamed human gingival tissue.

Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine; PAF) is a biologically active lipid, like the prostaglandins, which mediates allergic and inflammatory reactions. Aggregation of washed rabbit platelets was induced by a lipid prepared from inflamed gingiva. The mobility of the active lipid was coincident with that of authentic PAF on thin-layer chromatography. The aggregation was dose-dependent and inhibited by pretreatment with a specific PAF antagonist, ONO 6240, but not by indomethacin or creatine phosphate/creatine phosphokinase, which inhibit the platelet aggregation due to arachidonic acid or ADP, respectively. Thus the active lipid was identified as PAF; the amount of PAF detected was 118.1 +/- 79.7 pg/50 mg tissue (n = 6, mean +/- SD), the amount in normal tissue being 13.0 +/- 11.3 pg/50 mg tissue (n = 6). There was therefore a significant difference between the tissues. Lyso PAF, the metabolite of PAF with acetylhydrolase, was not detectable in either gingival tissue. Thus PAF was produced more in inflamed gingival tissue than in normal tissue; PAF may be involved in the occurrence and maintenance of periodontal disease.

Adult↗

B cell hyperresponsiveness to interleukin 2 and the age-associated decline in murine lupus.

In young NZB x NZW (B/W) F1 mice there was a population of B cells that were hyperresponsive to interleukin 2 (IL-2) and that proliferated but did not differentiate, even in the absence of a prior activation signal, and hence were already stimulated in vivo and were prepared to respond to IL-2. These B cells belonged to the population that was nonadherent to the Sephadex G-10 (G-10) column. We found that such hyperresponsiveness was progressively reduced with the aging of these mice. This event did not appear to be related to the age-associated changes of IL-2 receptors on B cells, since the IL-2-binding ability and the density of IL-2 receptor alpha expressed on B cells in culture did not differ between the young and the old mice. Studies suggested that two major mechanisms are responsible for the age-associated decline in the IL-2 responsiveness of B cells. First, the capacity of IL-2 hyperresponsiveness of such B cells decreases in B/W F1 mice with aging, probably through further activation and differentiation of the B cells. Second, the G-10 adherent, but not nonadherent, B cells from the aged mice inhibit the IL-2 response of G-10 nonadherent B cells. The G-10 adherent B cells from the old mice also inhibited the IL-2 production of T cells from the young B/W F1 mice. Taken together, it appears that young B/W F1 mice bear a population of B cells already stimulated so that they can respond to IL-2 without prior stimuli. With aging, activation of the B cells progresses and they appear to down-regulate the IL-2 hyperresponse of B cells and the IL-2 synthesis by T cells.

Aging↗

Preproenkephalin gene expression in the rat spinal cord after noxious stimuli.

The trans-synaptically activated biosynthesis of the preproenkephalin (PPE) mRNA in the dorsal horn of the rat lumbar spinal cord was examined by an in situ hybridization histochemical technique. As a nociceptive stimulus, a small amount of formalin was injected into the right hindpaw, and quantitative and qualitative changes of PPE-mRNA expression were determined by emulsion autoradiography. Formalin injection was found to result in a significant increase in the number and signal intensity of neurons expressing PPE-mRNAs in the superficial and deep layers of the ipsilateral spinal dorsal horn. Expression of PPE-mRNA increased within 1 h after formalin injection in neurons of deep layers, but gradually for at least 24 h in neurons in the superficial layers. These results at the level of the spinal cord showed that differential responses of PPE neurons related to the pain sensation occurred trans-synaptically after nociceptive stimulation applied to the periphery.

Animals↗

In situ hybridization analysis of the somatostatin-containing neuron system in developing cerebellum of rats.

We used in situ hybridization histochemistry to examine the postnatal development of the somatostatin (SRIF) synthesizing system in the cerebellum of rats. There are numerous hybridizing neurons from 1 to 9 days after birth. These occur throughout the cerebellum including the developing medulla and cortex except in the external granular cell layer. The lateral cerebellar nucleus also contains SRIF gene-containing cells. The intensity of the signals for SRIF mRNA in the cerebellum decreases with age. There is a drastic decrease in SRIF mRNA in the lateral cerebellar nucleus. SRIF cells cannot be detected in the lateral cerebellar nucleus of adult rats, whereas a small, yet significant number of SRIF cells are scattered in the cerebellar medulla. However, the cerebellum of adult rats still contains a significant number of labeled cells in the granular cell layer, although the intensity for SRIF mRNA decreases from 14 days after birth to adulthood. SRIF gene-expressing cells in the cerebellar cortex are located primarily in the granular cell layer and appear to correspond to Golgi cells judging from their characteristic features. These results are consistent with our previous immunohistochemical study on the decrease of SRIF immunoreactivity in the cerebellum of adult rats. These findings, together with a recent study of transient SRIF receptor-expressing cells in the developing cerebellum suggest that SRIF acts during cerebellar development.

Aging↗

Prepro-VIP and preprotachykinin mRNAs in the rat dorsal root ganglion cells following peripheral axotomy.

Using in situ hybridization histochemistry, we examined the expression of prepro-vasoactive intestinal polypeptide (VIP) mRNAs and preprotachykinin (PPT) mRNAs which coded for substance P (SP) in the rat dorsal root ganglion (DRG) following spinal nerve transection. VIP mRNAs increased dramatically in the DRG neurons after transection of the peripheral branch of the spinal nerve (sciatic nerve), whereas PPT mRNAs showed a gradual decrease for a few weeks. Dorsal rhizotomy or axotomy of the central branch of DRG cells had little influence on VIP-mRNAs and no effect on PPT mRNA expression. These results demonstrated an activation of VIP biosynthesis in the DRG neurons due to axotomy of the peripheral branch, which was opposite to the reaction of PPT mRNA to the same treatment.

Animals↗

Gallium-67 uptake in the salivary glands in chronic graft-versus-host disease after bone marrow transplantation.

Ga-67 citrate scans were performed in a 17-year-old female patient after bone marrow transplantation for acute lymphoblastic leukemia. Ga-67 accumulated in salivary glands in which chronic graft-versus-host disease (GVH) was demonstrated pathologically. Ga-67 scan may be a sensitive and noninvasive test for detecting and monitoring the Sicca syndrome induced by chronic GVH.

Adolescent↗