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Biomedical subjects

T Horiguchi

Publications and source records attributed to T Horiguchi.

At least 19 recordsLinked to original sources

Cyclooxygenase-2 mediates the development of cortical spreading depression-induced tolerance to transient focal cerebral ischemia in rats.

We examined the role of cyclooxygenase-2 in the development of ischemic tolerance induced by cortical spreading depression against transient, focal brain ischemia. Cortical spreading depression was continuously induced for 2 h with topical KCl (13+/-1 depolarizations/2 h) in male Wistar rats. At 1, 2, 3, 4, and 5 days following recovery, the middle cerebral artery was transiently occluded for 120 min. Four days later, the animals were killed and infarct volume was determined. Additionally, cyclooxygenase-2 levels in the cerebral cortex and 15 deoxy-Delta(12, 14) PGJ2 levels in cerebrospinal fluid were determined at these times with Western blotting and immunoassay, respectively. Infarct volume was reduced compared with non-cortical spreading depression control animals (274.3+/-15.3 mm3) when cortical spreading depression was performed 3 and 4 days before middle cerebral artery occlusion (163.9+/-14.2 mm3, 154.9+/-14.2 mm3) but not at 1, 2 and 5 days (280.4+/-17.3 mm3, 276.3+/-16.9 mm3 and 268.5+/-17.3 mm3). Cyclooxygenase-2 levels increased most dramatically starting at 2 days, peaked at 3 days, and started to return toward baseline at 4 days after cortical spreading depression. 15 Deoxy-Delta(12, 14) PGJ2 levels increased from 134.7+/-83 pg/ml at baseline to 718+/-98 pg/ml at 3 days. Administration of N-[2-cyclohexyloxy-4-nitrophenyl] methanesulphonamide (10 mg/kg, i.v.), a selective cyclooxygenase-2 inhibitor, at 1 h prior to middle cerebral artery occlusion in cortical spreading depression preconditioned animals did not affect infarct volume (162.6+/-62.1 mm3). However, administration of N-[2-cyclohexyloxy-4-nitrophenyl] methanesulphonamide given three times prior to middle cerebral artery occlusion prevented the reduced infarct volume induced by cortical spreading depression preconditioning (272.9+/-63.2 mm3). Administration of L-nitro-arginine methyl ester (4 mg/kg, i.v.) prior to cortical spreading depression blocked increases in cyclooxygenase-2 normally seen at 3 and 4 days. We conclude that NO-mediated cyclooxygenase-2 upregulation by cortical spreading depression protects the brain against ischemic damage.

Animals↗

Novel excitatory neuropeptides isolated from a prosobranch gastropod, Thais clavigera: The molluscan counterpart of the annelidan GGNG peptides.

The GGNG peptides are excitatory neuropeptides identified from earthworms, leeches and polychaeta. Two structurally related peptides were purified and characterized from a mollusk, Thais clavigera (prosobranch gastropod). The peptides designated as Thais excitatory peptide-1 (TEP-1) (KCSGKWAIHACWGGN-NH2) and TEP-2 (KCYGKWAMHACWGGN-NH2) are pentadecapeptides having one disulfide bond and C-terminal GGN-NH2 structures, which are shared by most GGNG peptides. TEP augmented the motilities of Thais esophagus and penial complex. TEP-like immunoreactivity is distributed in both the neurons of the central nervous system and nerve endings in the penial complex. Thus, the involvement of TEP in the contraction of the digestive and reproductive systems is suggested. Substitution of amino acids in TEP revealed that two tryptophan residues in TEP are important for maintaining bioactivity.

Amino Acid Sequence↗

Age-dependent synuclein pathology following traumatic brain injury in mice.

Synucleins (Syn), a family of synaptic proteins, includes alpha-Syn, which plays a pivotal role in Parkinson's disease and related neurodegenerative diseases (synucleinopathies) by forming distinct brain pathologies (Lewy bodies and neurites). Since traumatic brain injury (TBI) is a poorly understood risk factor for Parkinson's disease, we examined the effects of TBI in the young and aged mouse brain on alpha-, beta-, and gamma-Syn. Immunohistochemical analysis showed that brains from sham-injured young and aged mice had normal alpha- and beta-Syn immunoreactivity (IR) in neuropil of cortex, striatum, and hippocampus with little or no gamma-Syn IR. At 1 week post TBI, the aged mouse brain showed a transient increase of alpha- and beta-Syn IR in the neuropil as well as an induction of gamma-Syn IR in subcortical axons. This was associated with strong labeling of striatal axon bundles by antibodies to altered or nitrated epitopes in alpha-Syn as well as by antibodies to inducible nitric oxide synthase. However, these TBI-induced changes disappeared by 16 weeks post TBI, and altered Syn IR was not seen in young mice subjected to TBI nor in alpha-Syn knockout mice while Western blots confirmed that TBI induced transient alterations of alpha-Syn in the mouse brains. This model of age-dependent TBI-induced transient alterations in alpha-Syn provides an opportunity to examine possible links between TBI and mechanisms of disease in synucleinopathies.

Aging↗

Vitamin E ointment at high dose levels suppresses contact dermatitis in rats by stabilizing keratinocytes.

OBJECTIVE: The pharmacological effect of vitamin E ointment at high dose levels was investigated in rats and mice during the development of contact dermatitis. MATERIALS AND METHODS: Allergic or irritant contact dermatitis was induced in sensitized or unsensitized animals by topical application of chemical agent(s). Cultured keratinocytes were prepared from dorsal skin of rats. RESULTS: The vitamin E ointment at 20-40% suppressed allergic and irritant contact dermatitis, exerting a comparable effect to that of 0.5% prednisolone ointment. Microscopic findings revealed that 20% vitamin E ointment reduced the keratinocyte damage, whereas 0.5% prednisolone was ineffective. The protective action of vitamin E on keratinocyte damage was also confirmed in a cell culture experiment. Furthermore, 20% vitamin E ointment blocked down-regulation of skin barrier function induced by contact dermatitis, although 0.5% prednisolone ointment was inactive. CONCLUSIONS: These results indicate that 20% vitamin E ointment suppresses contact dermatitis by stabilizing keratinocytes, concomitantly with novel, interesting properties.

Administration, Topical↗

Effects of suplatast tosilate on airway inflammation and airway hyperresponsiveness.

Suplatast tosilate (IPD) is a Th2 cytokine inhibitor that lowers the titer of the IgE antibody through specific inhibition of the production of IL (interleukin)-4 and IL-5 by T cells and inhibits tissue infiltration by eosinophils. In this clinical trial, suplatast tosilate (300 mg/day) was administered orally for 4 weeks to 25 patients (13 patients with atopic asthma, 12 patients with nonatopic asthma) whose bronchial asthma was staged in step 1 or step 2 according to the Guidelines for Prevention and Management of Bronchial Asthma, 1998. Before and after administration, the parameters of airway inflammation, that is, peripheral blood eosinophils count, serum level of eosinophil cationic protein (ECP), ECP level in induced sputum, airway hyperresponsiveness (Dmin), and morning peak expiratory flow (PEF), were measured. The peripheral blood eosinophil count, serum level of ECP, and ECP level in induced sputum decreased significantly. Of these parameters, the ECP level in induced sputum was the most sensitive. Furthermore, suplatast tosilate significantly inhibited Dmin. These results were especially significant in patients with atopic asthma. Suplatast tosilate was considered to have inhibited airway eosinophilic inflammation through decreases in peripheral blood eosinophils counts and in ECP levels in induced sputum, which resulted in inhibition of airway hyperresponsiveness.

Adult↗

Intra-ischemic hypothermia attenuates intercellular adhesion molecule-1 (ICAM-1) and migration of neutrophil.

Adhesion of neutrophil to the endothelium and subsequent transmigration has been reported to contribute to progression of focal ischemia. Hypothermia has been known to attenuate ischemic insult through various mechanisms of action. The authors evaluated the effect of hypothermia on expression of intercellular adhesion molecule-1 (ICAM-1) protein and on transmigration of neutrophil with immunohistochemical method. Transient focal ischemia model in rats was employed, and animals received 2 h of either normothermic or hypothermic ischemia. To confirm the effectiveness of hypothermia on neuroprotection, cortical infarct area was compared between the two groups. Our results demonstrated that hypothermia reduced both the number of microvessels expressing ICAM-1 and that of neutrophils migrating into ischemic tissue. Comparison of cortical infarct area showed persistent protective effect. This study indicates that reduction of ICAM-1 expression and subsequent reduction of migrating neutrophil in hypothermia can contribute to attenuation of ischemic damage.

Animals↗

Cerebral microaneurysms found incidentally during aneurysm surgery.

Not uncommonly, cerebral microaneurysms are found incidentally during surgery for another previously diagnosed cerebral aneurysm(s). The frequency and angiographic characteristics of such incidental microaneurysms are retrospectively summarized. Seventeen patients were identified as harboring incidental microaneurysms, comprising 4.9% of the whole series. The middle cerebral artery (MCA) was the most frequent location (seven cases, 41%) of these microaneurysms. There was a tendency for MCA microaneurysms to be contiguous to a previously known, larger aneurysm at the same location. Neurosurgeons as well as interventional neuroradiologists should be aware of the possible presence of these incidental microaneurysms while treating patients with a cerebral aneurysm(s). Although the actual clinical implications of these incidental microaneurysms have not been elucidated, the few additional risks to patients already surgically exposed for the treatment of another aneurysm, along with the possible benefit of preventing their rupture and growth, would justify the surgical treatment of these microaneurysms.

Adult↗

Potential fascial dome made by the upper leaf of the phreno-esophageal membrane.

We describe the configuration and size of the artificial fascial dome created in 57 cadavers. This dome protrudes into the thoracic cavity from the esophageal hiatus. This dome was a potential space realized by finger dissection (i.e., a specific but common surgical procedure during surgery of the upper part of the stomach). The vagus nerves penetrated the top of the dome and ran down along the esophagus. The height of the ventral wall of the dome ranged from 10-60 mm, while the dorsal wall was 10-40 mm longer than the ventral one since the dorsal wall attached to the lower, dorsal limb of the esophageal hiatus. Accordingly, the dorsal wall separated the "thoracic" aorta from the "abdominal" esophagus. We considered that the upper leaf of the phreno-esophageal membrane forms the fascial dome, although the lower leaf of the membrane was not identified in this study. According to the results, we proposed a schematic representation of the phreno-esophageal membrane.

Aged↗

A display of hypomania in a depressed male in response to fluvoxamine.

The present report describes the behavioural and psychological changes in a 55-year-old depressed male who displayed hypomania after the use of fluvoxamine in addition to other antidepressant medications. The patient experienced his first major depressive episode after the bankruptcy of his company. When fluvoxamine was prescribed at a dose of 50 mg/day in addition to sulpiride at 150 mg/day and a 50 mg dose of trazodone before sleep seven months after admission, grinning and a violation of ward rules occurred repeatedly. The patient became verbally aggressive to the staff and addicted to gambling and alcohol. Six days after the cessation of fluvoxamine, his condition remitted. None of the neuromuscular abnormalities indicative of serotonin syndrome appeared during the episode. Upon review of previous reports on manic switches induced by SSRIs and other antidepressants, we speculate that the fluvoxamine accounted for his hypomania.

Bipolar Disorder↗

[Clinical significance of serum KL-6 in pulmonary sarcoidosis].

We investigated whether the level of serum KL-6 could be an activity marker for pulmonary sarcoidosis. In 33 patients with pulmonary sarcoidosis, the relationships between serum KL-6 levels and diagnostic imaging, serum angiotensin-converting enzyme (ACE) levels, serum lysozyme levels, steroid therapy, and prognosis were evaluated. There were no significant differences in the level of serum KL-6 when the patients were divided on the basis of radiographic findings, but the level of serum KL-6 was markedly elevated in some patients with stage-II pulmonary sarcoidosis. There was a significant correlation between serum KL-6 levels and the following two parameters: serum ACE and lysozyme levels. Among patients with a high initial level of serum KL-6, pulmonary sarcoidosis tended to become exacerbated within one year. Steroid therapy significantly decreased the level of serum KL-6, suggesting that the level of serum KL-6 could be an activity indicator for pulmonary sarcoidosis. Immunohistochemical staining by anti-KL-6 antibody revealed that KL-6 was localized in proliferating type-II alveolar epithelial cells.

Adult↗

[Clinical utility and safety of diagnostic thoracoscopy].

The increasing use of thoracoscopy performed under local anesthesia has made contributions to the diagnosis of pleural disease with effusion. During the past 7 years, we have performed 100 such thoracoscopy procedures using a flexible fiberoptic bronchoscope. On the basis of our clinical findings, we are able to discuss the utility and safety of this procedure. The causes of pleural effusion were carcinomatous pleurisy in 72 cases, tuberculosis pleurisy in 15 cases, infection without tuberculosis in 4 cases, malignant pleural mesothelioma in 8 cases and one case of asbestosis. The success rate of thoracoscopic pleural biopsies were 97% for carcinomatous pleurisy, 100% for malignant pleural mesothelioma and 86% for tuberculosis pleurisy. This procedure was performed with no serious effect on blood pressure, oxygen saturation, monitored ECG or BGA data, and with no serious complications. Therefore, we concluded that this method is very useful for the diagnosis of pleural effusions and has few complications.

Adult↗

Post-ischemic hypothermia delayed neutrophil accumulation and microglial activation following transient focal ischemia in rats.

Following ischemia, inflammation has been demonstrated to be involved in the progression of the tissue damage. Intra-ischemic hypothermia has been shown to attenuate the adverse activities of neutrophils and microglia. We investigated whether neutrophil accumulation and/or microglial activation is attenuated in post-ischemic hypothermia following transient focal ischemia in rats. After 1 h of ischemia, the neutrophil accumulation and the microglial activation was evaluated immunohistochemically. Percent infarct area was compared at 1, 2, 3, 5, and 7 days after ischemia/reperfusion. In hypothermia, the neutrophil accumulation was delayed but not attenuated. In normothermia, the accumulation reached the peak at 2 days after ischemia. The peak shifted to 3 days in hypothermia. Similarly, the microglial activation was delayed in hypothermia. Comparison of the infarct area showed significant protection by hypothermia at 1 and 2 days after reperfusion. However, hypothermia failed to show significant protection after 3 days and later. These results show that the delayed neutrophil accumulation and the microglial activation can be responsible for the loss of persistent protection in post-ischemic hypothermia.

Animals↗

Three-dimensional reconstruction of transcription termination factor rho: orientation of the N-terminal domain and visualization of an RNA-binding site.

The Escherichia coli rho transcription termination protein is a hexameric helicase, and is believed to function by separating an RNA-DNA hybrid. Unlike hexameric DNA helicases, where a single strand of DNA passes through the central channel, it has been proposed that the RNA wraps around the outside of the ring. We have generated a three-dimensional reconstruction of rho, and localized a tRNA molecule bound to the primary RNA-binding site to the outside of the ring. An atomic structure of the N-terminal domain of rho fits into our reconstruction uniquely, with the residues involved in RNA-binding on the outside of the ring. Although rho shares a common structural core with the F1-ATPase and other hexameric helicases, there has been a divergence in function due to rho's N-terminal domain, which has no homology to other helicases.

Binding Sites↗

Synthesis and biological evaluation of novel 9-functional heterocyclic coupled 7-deoxy-9-dihydropaclitaxel analogue.

Novel 9-functional heterocyclic coupled 7-deoxy-9-dihydropaclitaxel analogues 17 and 22-24 synthesized from a natural taxoid 5-cinnamoyltriacetyltaxicin-I (3) and their biological evaluation in tubulin assembly activity and cytotoxicity in vitro against several human tumor cell lines are first presented. The biologically tested results show that 17, 22 and 23 are inactive in tubulin assembly assay and have no more remarkable cytotoxicities against human tumor cell lines SK-OV3, WIDR and MCF-7, though 22 and 23 exhibit more potent cytotoxicity against human liver cancer and human esophagus cancer cell lines (BEL-7402 and ECa-109) than paclitaxel.

Antineoplastic Agents, Phytogenic↗

Postischemic hypothermia attenuates apoptotic cell death in transient focal ischemia in rats.

Hypothermia confers potent neuroprotection against ischemic injury. Attenuation of apoptosis by hypothermia can be one of the responsible mechanisms. In this study, in situ DNA nick-end labeling (TUNEL) and immunostaining of Bax protein were performed to evaluate the effect of postischemic hypothermia on apoptotic cell death, employing rodent transient focal ischemia. Animals received 1 hour of transient focal ischemia. Brain temperature was maintained at 37.5 +/- 0.5 degrees C during ischemia. Immediately after reperfusion, animals were assigned to either a normothermic or hypothermic group. In hypothermia, animals were cooled and brain temperature was lowered to 34.5 +/- 1.0 degrees C. Prolonged hypothermia was maintained for 16 hours and animals rewarmed. In both groups, TUNEL and immunostaining of Bax was performed. In normothermia, the number of TUNEL positive cells reached the peak at 2 days after ischemia and decreased gradually. In hypothermia, the peak was shifted to 3 days after ischemia. The number of TUNEL positive cells in hypothermia was persistently below that of normothermia. Similarly, in hypothermia, immunostaining of Bax showed attenuated immunoreactivity compared with that in normothermia. In conclusion, postischemic hypothermia reduced both the number of TUNEL positive cells and immunoreactivity of Bax, which may be one of the responsible mechanisms with which hypothermia exerts neuroprotection.

Animals↗

Usefulness of serum carboxy-terminal telopeptide of type I collagen (ICTP) as a marker of bone metastasis from lung cancer.

BACKGROUND: Serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) is a metabolite of type I collagen comprising 90% or more of organic substances in bone. Its usefulness as a marker of bone metastasis from malignant tumors is expected. METHOD: We measured ICTP to evaluate its clinical usefulness for diagnosis of bone metastasis in 140 patients with lung cancer. For comparison, serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21-1), gastrin-releasing peptide precursor (ProGRP), alkaline phosphatase and calcium were simultaneously measured. ICTP was measured by double-antibody radioimmunoassay. RESULTS: ICTP was significantly higher in patients with bone metastasis from lung cancer than in the group without bone metastasis, patients with other pulmonary diseases or healthy control subjects and showed excellent sensitivity and specificity, indicating that this marker is highly useful for complementary diagnosis of bone metastasis from lung cancer. Moreover, the survival duration was significantly shorter in the ICTP-positive group than in the ICTP-negative group, suggesting that ICTP can be a prognostic factor in lung cancer. CONCLUSION: It is suggested that measurement of ICTP is worthwhile as a serological diagnostic method of bone metastasis from lung cancer. Moreover, since repeated measurements are possible, this measure was considered very helpful in complementary diagnosis of bone metastasis and also as a standard to determine the timing of examinations such as bone scintigraphy.

Adenocarcinoma↗