Biomedical subjects

T Kihara

Publications and source records attributed to T Kihara.

At least 19 recordsLinked to original sources

PubMed1998

Stimulation of alpha4beta2 nicotinic acetylcholine receptors inhibits beta-amyloid toxicity.

We examined the effects of nicotinic receptor agonists against beta amyloid (Abeta) cytotoxicity to rat cortical neurons. Administration of nicotine protected against Abeta-induced neuronal death. This neuroprotection was blocked by dihydro-beta-erythroidine, an alpha4beta2 nicotinic receptor antagonist. Furthermore, incubation with cytisine, a selective alpha4beta2 nicotinic receptor agonist, inhibited Abeta cytotoxicity. These results suggest that alpha4beta2 nicotinic receptor activation plays an important role in neuroprotection against Abeta cytotoxicity.

Alkaloids↗

PubMed1998

Neuromagnetic fields preceding unilateral movements in dextrals and sinistrals.

Movement-related magnetic fields were recorded with a whole-head magnetoencephalographic system in three dextrals and three sinistrals during right or left index finger extension. The motor field (MF) demonstrated an asymmetrical isofield map pattern with larger field reversal over the contralateral hemisphere for dominant hand movement and an almost symmetrical pattern for non-dominant hand movement in each subject. The equivalent current dipole moment of the MF for the contralateral hemisphere was significantly larger than the ipsilateral hemisphere for dominant hand movement, and almost equal for both hemispheres for non-dominant hand movement. These results were congruent for both dextrals and sinistrals, suggesting a more important role of the hemisphere contralateral to the dominant hand in unilateral voluntary movement, regardless of handedness.

Brain↗

PubMed1998

Dopamine D2-type agonists protect mesencephalic neurons from glutamate neurotoxicity: mechanisms of neuroprotective treatment against oxidative stress.

Oxidative stress, a process in which neurotoxic oxygen free radicals cause dopaminergic neuronal degeneration, has been implicated in the degenerative process in Parkinson's disease. Glutamate-induced neurotoxicity is a model of oxidative stress. We demonstrated that preincubation with D2-type dopamine agonists bromocriptine and quinpirole provides neuroprotection against glutamate-induced neurotoxicity in cultured rat mesencephalic neurons. Simultaneous administration of D2 agonists, however, did not provide neuroprotection. The protective effects were dependent on the duration of preincubation and were blocked by a D2 antagonist and a protein synthesis inhibitor. Furthermore, preincubation with D2 agonists provided neuroprotection against toxicity induced by calcium overload and exposure to superoxide anions. Confocal microscopic analysis, using 2,7-dichlorofluorescin diacetate, revealed that bromocriptine preincubation suppressed the action of radicals on neurons. These findings indicate that dopamine D2 agonists provide protection mediated not only by the inhibition of dopamine turnover but also via D2-type dopamine receptor stimulation and the subsequent synthesis of proteins that scavenge free radicals.

Animals↗

PubMed1998

Partial purification and characterization of sphingosine N-acyltransferase (ceramide synthase) from bovine liver mitochondrion-rich fraction.

Sphingosine N-acyltransferase (ceramide synthase, E.C. 2.3.1.24) was solubilized from bovine liver mitochondrion-rich fraction with n-octyl beta-D-thioglucoside as the detergent and partially purified by sequential chromatography on columns of DE-32, shingosine affinity, and Sepharose CL-6B. The partially purified preparation migrated on SDS-polyacrylamide gel electrophoresis as two major protein bands of 62 and 72 kDa. The molecular mass of the enzyme estimated by gel filtration was 240-260 kDa, suggesting that the partially purified enzyme is present in a subunit form or simply has an aggregative nature. The specific activity of the final preparation for the condensation of sphingosine with stearoyl-CoA increased by 98.7-fold compared with the starting material. The optimal pH value for the ceramide synthesis was 7.5. The partially purified enzyme had an apparent Km of 146 microM and a Vmax of 11.1 nmol/min/mg protein for stearoyl-CoA. The Km and Vmax values toward sphingosine were 171 microM and 11.3 nmol/min/mg protein, respectively. Interestingly, sphinganine was also a good substrate for this enzyme, and the Km and Vmax values were 144 microM and 8.5 nmol/min/mg protein, respectively.

Acyl Coenzyme A↗

PubMed1998

Effect of interleukin 1 beta-induced fever on hepatic drug metabolism in rat.

1. A fever-induced model in rat was created by repeated injection of interleukin 1 beta (IL-1 beta) in the cerebroventricle and the influence of fever on hepatic drug metabolism was investigated. Fever apparently decreased the content of cytochrome P450 (CYP) and the activities of NADPH-ferrihaemoprotein reductase (fp2), aminopyrine N-demethylase, aniline hydroxylase, FAD-monooxygenase, p-nitrophenol UDP-glucuronosyl-transferase and glutathione S-transferase. Immunoblot analysis of the CYP isozymes indicated that CYP2C11 and CYP3A were extensively decreased in the IL-1 beta-induced fevered rat. 2. Repeated administration (5 days) of mefenamic acid in the fevered rat could not restore the activities of fp2, aminopyrine N-demethylase and aniline hydroxylase to control levels, although their hyperthermic state had been improved. The CYP content in the mefenamic acid-treated fevered rat was also lower than that in the control. 3. These findings suggest that fever impairs the hepatic drug-metabolizing capacity (both oxidation and some conjugations) and that the fever-induced impairments are partially retained, even if the hyperthermia has been offset by the administration of antipyretics.

Aminopyrine N-Demethylase↗

PubMed1998

[Frameless registration for chest SPECT and X-ray CT image by volume matching].

Image registration of functional (SPECT) and morphological (X-ray CT/MRI) images has been studied in order to improve the accuracy and the quality of the image diagnosis. This paper describes a new registration method for chest SPECT and X-ray CT images. Presented method is a frameless and automatic registration method which calculates a transformation matrix between two coordinate systems of image data by an optimization method. This registration method uses similar physical characteristics of X-ray CT and transmission CT image. The three-dimensional overlap of the body region is used for image matching. Precision evaluation and visual image evaluation were conducted. The result of the precision evaluation with a phantom and clinical data suggested the clinically acceptable robustness in registration procedure. Visual evaluation of registered images confirmed the usefulness of this method in clinical applications.

Algorithms↗

PubMed1997

BDNF prevents NO mediated glutamate cytotoxicity in cultured cortical neurons.

The effects of brain-derived neurotrophic factor (BDNF) on glutamate-induced cytotoxicity were examined using primary cultures of rat cortical neurons. BDNF induced TrkB tyrosine phosphorylation in rat cultured cortical neurons. The cell viability was significantly reduced when cultures were briefly exposed to glutamate and incubated with normal medium for 24 h. Glutamate cytotoxicity was prevented by MK-801, which is a non-competitive blocker of N-methyl-D-aspartate and N(omega)-nitro-L-arginine, which is a blocker of nitric oxide synthetase. Delayed neurotoxicity was also induced by ionomycin, a calcium ionophore, and nitric oxide (NO) donors such as S-nitrosocysteine (SNOC) and 3-morpholinosydnonimine (SIN-1). Incubating cultures with BDNF for 10 min to 24 h protected cortical neurons against glutamate neurotoxicity. The protective effects of BDNF against glutamate cytotoxicity were dependent on both its concentrations and incubation time. BDNF also prevented the ionomycin-, SNOC-, and SIN-1 induced cytotoxicity. These results indicate that BDNF protects cultured cortical neurons from NMDA receptor-mediated glutamate neurotoxicity by reducing cytotoxic action of NO.

Animals↗

PubMed1997

Identification and activation of profollipsin, a latent precursor form of porcine follipsin.

A latent protease has been identified in column fractions obtained during the purification of the porcine ovarian serine protease follipsin. The latent enzyme was readily activated by trypsin treatment. The trypsin-activated enzyme was purified using a benzamidine-Sepharose 6B column and was shown to be composed of two distinct, covalently associated polypeptides with Mr of 45000 and 32000. This polypeptide chain composition, together with its substrate specificity, inhibition profile using various protease inhibitors, cross-reactivity with anti-follipsin antibody, and ability to activate single-chain precursor tissue plasminogen activator, indicated its identity as porcine follipsin. The activation of the enzyme with trypsin was found to occur by the hydrolysis of an internal peptide bond resulting in a two-chain structure. Thus, we conclude that the latent enzyme is the inactive precursor form (profollipsin) of follipsin. The present study also shows that the follicular fluid of porcine ovary contains a profollipsin-activating enzyme activity.

Animals↗

PubMed1997

Nicotinic receptor stimulation protects neurons against beta-amyloid toxicity.

beta-Amyloid (A beta), a major constituent of senile plaques in Alzheimer's disease (AD), is thought to contribute to the neurodegeneration. We examined the effects of nicotinic receptor agonists on A beta cytotoxicity in cultured rat cortical neurons. The number of viable neurons decreased significantly when cultures were exposed to synthetic A beta peptides (25-35). Concomitant administration of nicotine with A beta markedly reduced the number of dead cells. This nicotine-induced neuroprotection was dependent on the concentration. When hexamethonium or mecamylamine, nicotinic antagonist, was added, neuroprotective effect of nicotine was blocked, which indicates that effect of nicotine was mediated by nicotinic receptors. In addition, a selective alpha7-receptor antagonist, alpha-bungarotoxin (alpha-BTX), blocked the neuroprotective effect of nicotine. Furthermore, incubation with 3-(2,4)-dimethoxybenzylidene anabaseine (DMXB), a selective alpha7-receptor agonist, protected against A beta-induced neuronal death. These results suggest that alpha7-receptor activation plays an important role in neuroprotection against A beta cytotoxicity. This study suggests that nicotinic receptor stimulation, especially alpha7-receptor activation, may be able to protect neurons from degeneration induced by A beta and may have effects that counter the progress of AD.

Amyloid beta-Peptides↗

PubMed1997

A prospective randomized study of glutamine-enriched parenteral compared with enteral feeding in postoperative patients.

Plasma amino acids were measured in 17 postoperative subjects randomly assigned to receive for > or = 5 d tube feeding or total parenteral nutrition (TPN) that had identical energy, nitrogen, and glutamine contents. Subjects required gastric or pancreatic surgery for malignancy and were well-matched for age and body mass index. Tube feeding or TPN began on postoperative day 1 and advanced in daily 25% increments to meet goals of 105 kJ . kg body wt-1 . d-1, 1.5 g protein . kg body wt-1 . d-1, and 0.3 g glutamine . kg body wt-1 . d-1. Delivered energy, nitrogen, and glutamine were closely matched on day 4. Nitrogen balance and plasma proteins did not differ significantly between feeding groups. Total indispensable amino acids, branched-chain amino acids, and glutamine declined 25% on postoperative day 1 compared with preoperative day 0. Indispensable and branched-chain amino acid concentrations were restored with 5 d of either tube feeding or TPN. Glutamine concentrations did not differ significantly by feeding group, though a trend suggested that glutamine recovered more slowly in the tube-fed than in the TPN-fed subjects. Plasma amino acids otherwise reflected formula composition with ratios of valine to leucine of 1.24 and 3.69 mumol/L in subjects receiving 5 d of tube feeding or TPN, respectively. These findings suggest that glutamine-enriched tube feeding and TPN can result in similar profiles for most plasma amino acids at carefully matched doses.

Adolescent↗

PubMed1997

Endoscopic diagnosis of hookworm disease of the duodenum.

Hookworm is one of the most common parasites in the world, but can be missed on stool examination. We report a 31-year-old man who was complaining of epigastric discomfort, with laboratory findings of iron-deficiency anemia and eosinophilia. He was found to be infected with hookworm (Ancylostoma duodenale), which was directly detected and retrieved from the duodenum with biopsy forceps during upper gastrointestinal endoscopy. We eliminated his infection successfully by the Damaso de Rivas-Kihara modified method and oral administration of pyrantel pamoate. This report indicates that it is important to check carefully even in the distal duodenum at routine upper gastrointestinal endoscopy whenever parasitic disease is suspected but is hard to diagnose because of a limited number of eggs in feces.

Adult↗

PubMed1997

[Utility of prostate specific antigen (PSA) density in detecting prostate cancer in men showing gray zone serum PSA levels].

The efficacy of prostate specific antigen density (PSAD) in diagnosing prostate cancer was assessed in 98 patients with serum prostate specific antigen (PSA) levels between 2 and 10 ng/ml who had a pathological diagnosis made by prostate biopsy or transurethral resection of the prostate. Of the 98 patients, 22 (22%) had prostate cancer. The PSA (based on a cut-off value of 4.5 ng/ml) had a sensitivity and positive predictive value (PPV) of 82% and 38%, respectively, for diagnosing prostate cancer, while the results for PSAD (based on a cut-off value of 0.13) were 91% and 61%. The PSAD was more efficient than the PSA levels and was also superior to digital rectal examination (DRE) combined with transrectal ultrasonography (TRUS), for which the sensitivity and PPV were 73% and 39%, respectively. Six (11%) out of 57 patients who were normal on DRE and TRUS had prostate cancer. In these 57 patients, the PSA (cut-off value: 4.5 ng/ml) had a sensitivity of 50% and PPV while the values for PSAD (cut-off value: 0.13) were 83% and 36% respectively. The PSAD could effectively detect even impalpable prostate cancer not visible on TRUS.

Aged↗

PubMed1997

[Bladder carcinoma presenting with hypercalcemia: a case report].

A 47-year old woman was referred to our hospital with nausea, vomiting and the loss of body weight. Pelvic computed tomography and magnetic resonance imaging revealed an invasive bladder tumor on the left lateral wall, accompanied with calcification. Laboratory examination revealed marked hypercalcemia (20.6 mg/dl) and elevated serum parathyroid hormone-related protein-intact (29.9 pmol/l), which was apparently produced by the tumor. Treatment with pamidronate and colloid infusion resulted in normocalcemia. Anterior pelvic exenteration was performed. Histopathological diagnosis was transitional cell carcinoma > adenocarcinoma, G3, pT4pN2M0, stage IV. She died of cancer 7 months postoperatively.

Carcinoma, Transitional Cell↗

PubMed1997

[Pheochromocytoma of the left retroperitoneal paraganglion associated with torsade de pointes: a case report].

A 54-year-old woman developed torsade de pointes with secondary QT prolongation due to hypokalemia and hypomagnesemia. Her serum K and Mg levels were 2.5 mEq/l and 1.5 mg/dl, respectively. This electrolyte imbalance was due to intentional overdosing of metolazone. Attacks of torsade de pointes occurred three times in the intensive care unit and were corrected by intravenous lidocaine administration. Her serum K level was corrected using KCl infusion, restoring the normal QT interval. Routine computed tomography found a left retroperitoneal paraganglioma. Urinary and serum catecholamine examination revealed extremely high values of epinephrine and norepinephrine. The diagnosis was pheochromocytoma in the left retroperitoneal paraganglion. The tumor which was removed measured 70 x 65 x 60 mm in size. Microscopic examination revealed the characteristic patterns of pheochromocytoma.

Diuretics↗

PubMed1997

[A case of xanthogranuloma of the urinary bladder].

A case of xanthogranuloma of the urinary bladder is reported. A 68-year-old man was referred to our hospital for the evaluation of microscopic hematuria. At that time, he did not have an abdominal tumor and ultrasonography showed no abnormality of the kidneys and the bladder wall. Two months later, he was admitted with the chief complaints of perineal discomfort and non tender fist size mass was palpable in the lower abdomen. Ultrasonography, computed tomographic scan and magnetic resonance imaging MRI demonstrated a supravesical mass which was strongly suspected as urachal tumor. Total cystectomy with urachal resection was performed. The histological diagnosis was xanthogranuloma. The patient has been in good health without recurrence, 4 years after surgery. We discuss xanthogranuloma of the urinary bladder in the literature.

Aged↗

PubMed1996

Change in ascorbate radical production in an irradiated experimental tumor with increased tumor size.

We have reported that ascorbate radical (Asc.-) could serve as an indicator of the amount of hydroxyl radical and superoxide produced by irradiation in vivo. Using this method, we investigated the relationship between tumor size and Asc.- production after irradiation (10 Gy) and between tumor size and the radical-scavenging ability of WR-2721 (300 mg/kg). Asc.- was measured in normal muscle and SCC-VII tumors transplanted into mice (n = 6). In tumors, the increase in Asc.- significantly decreased with increasing tumor size (r = -0.483; P < 0.05). The increase in Asc.- production after irradiation was more inhibited by WR-2721 in normal muscle tissue than in tumor tissue at various sizes. In tumors, the increase in Asc.- was less inhibited by WR-2721 with increasing tumor size. These results demonstrate that the increase in radical production after irradiation and drug distribution decreased with increasing tumor size and that WR-2721 has excellent differential protection. This method is expected to measure changes in the amounts of local hydroxyl radical and superoxide modified by a change of tumor environment or drug administration.

Amifostine↗

PubMed1996

NF-kappa B is induced in the nuclei of cultured rat aortic smooth muscle cells by stimulation of various growth factors.

We investigated whether induction of transcription factor NF-kappa B is involved in the proliferation of cultured rat aortic smooth muscle cell using electrophoretic mobility shift assay and immunocytochemistry. NF-kappa B was induced in the nucleus in a dose-dependent manner when the smooth muscle cells were stimulated by various growth factors such as PDGF-BB, bFGF, EGF and IGF-1, but not growth inhibitors such as TGF-beta and IFN-gamma. Among growth factors, PDGF-BB and bFGF, more potent growth stimulators, induced higher kappa B binding activity than EGF or IGF-1. These evidences were also supported by the results obtained with immunocytochemistry. Immunocytochemistry also showed that the induced NF-kappa B contained p50 and p65. These results suggest that NF-kappa B induction may be involved in the proliferation of vascular smooth muscle cell.

Animals↗

PubMed1996

Role of platelet-activating factor and thromboxane A2 in radical production during ischemia and reperfusion of the rat brain.

Oxygen radicals produced by activated neutrophils have been involved in brain injury during ischemia-reperfusion. Platelet-activating factor (PAF) is a candidate as one of the mediators of neutrophil activation during cerebral ischemia-reperfusion. Recent evidence indicates that PAF-induced neutrophil activation is mediated by thromboxane A2 (TXA2). To study the role of PAF and TXA2 in radical production during cerebral ischemia-reperfusion, we evaluated the effects of a PAF antagonist, Y-24180, and a TXA2 antagonist, S-1452, on radical formation in rats with 1 h middle cerebral artery (MCA) occlusion. In the present study, we employed a new electron spin resonance (ESR) method coupled with brain microdialysis. The method uses the endogenous ascorbyl radical (AR) concentration as a marker of oxygen radicals and requires no spin-trapping agents. In the vehicle controls, extracellular AR from the ischemic brain cortex decreased during MCA occlusion. Following reperfusion, AR significantly increased at 30 mm and 1 h, returned to near the basal levels at 2 h, and increased again at 24 h after reperfusion. In the rats treated with S-1452 or Y-24180, AR decreased during MCA occlusion to the same extent as in the vehicle control. However, pretreatment with Y-24180 or S-1452 significantly attenuated the increase in extracellular AR after reperfusion, while it exerted no effect on the changes in extracellular ascorbate or tissue pO2 throughout the experimental period. In conclusion, PAF and TXA2 might contribute to cerebral ischemia-reperfusion injury by increasing the generation of oxygen radicals.

Animals↗