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T Kihara

Publications and source records attributed to T Kihara.

At least 109 records · Page 6Linked to original sources

Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion.

BACKGROUND AND PURPOSE: Neutrophils have been implicated in the pathogenesis of ischemia-reperfusion injury. The aim of the present study was to evaluate the correlation between neutrophil infiltration into ischemic tissues and brain injury after transient focal ischemia. METHODS: We evaluated the effects of depletion of circulating neutrophils by administration of an antineutrophil monoclonal antibody (RP3) on brain edema formation, infarct size, and neutrophil infiltration (myeloperoxidase [MPO]-quantified) in rats with 1 hour of middle cerebral artery (MCA) occlusion. RESULTS: In the cerebral cortex perfused by the anterior cerebral artery (ACA area), there was a significant increase in MPO activity only 24 hours (P < .05) after reperfusion. In the cerebral cortex perfused by the middle cerebral artery (MCA area) and caudate putamen, MPO activity was significantly increased at 12 (MCA area, P < .01; caudate putamen, P < .05), 24 (MCA area, P < .05; caudate putamen, P < .01), and 72 hours (MCA area, P < .01; caudate putamen, P < .05) and returned to near-normal level by 168 hours after reperfusion. Brain MPO activity after transient MCA occlusion correlated well with the appearance of neutrophils. Depletion of neutrophils by RP3 treatment completely inhibited the increase in MPO activity in the ischemic brain after 24 hours of reperfusion. In addition, treatment with RP3 significantly attenuated the postischemic increase in brain water content at 24 hours after reperfusion. RP3 also significantly reduced the size of infarct area. CONCLUSIONS: These results indicate that the increase in brain MPO activity after transient focal ischemia virtually reflects the neutrophil infiltration and that neutrophil infiltration into the ischemic brain is implicated in postischemic brain injury.

Animals↗

Effect of adjuvant-induced arthritis on hepatic drug metabolism in rats.

1. Hepatic drug metabolism was investigated in normal, adjuvant-induced arthritic (AA), indomethacin-treated AA and prednisolone-treated AA rats. The contents of P450 and b5 and the activities of NADH-b5 reductase (fp2), NADPH-ferrihaemoprotein reductase, P450 mixed function oxidase, FAD-monooxygenase and several enzymes involved in conjugation were remarkably lower in AA than in normal rats. 2. Many of the decreased enzyme activities were restored to normal levels by the continuous administration (3 weeks) of indomethacin or prednisolone, which improved the arthritic states of the animals. However, the restoration of FAD-monooxygenase activity by the administration of indomethacin or prednisolone was incomplete. The P450 and b5 contents and the fp2 activity in prednisolone-treated AA rats were also significantly lower than those in normal rats. 3. These findings indicate that the ability of the liver to metabolize drugs (both oxidation and conjugation) in AA rats is greatly decreased and that a long series of the treatment of AA rats with anti-inflammatory drugs is required to restore several enzyme activities.

Animals↗

[Flow cytometric DNA analysis on renal cell carcinoma--a study of 116 cases on fresh surgical specimens].

DNA ploidy was investigated using flow cytometry on fresh surgical specimens from 116 cases with renal cell carcinoma. DNA diploid tumor was observed in 39 cases (33.6%) and aneuploid in 77 cases (66.4%). DNA aneuploid group was further classified into 3 subgroups by DNA index (D.I.); near-diploid group (D.I.: 0.8-1.2, 21.6%), near-tetraploid group (D.I.: 1.8-2.2, 12.9%) and other aneuploid group (31.9%). DNA ploidy pattern correlated with clinical stages and histological grading, indicating significantly a higher incidence of DNA diploid in cases in stage I and grade 1. DNA clonal heterogeneity was observed in 48.1%, and homogeneously diploid was in 28.6% of 77 cases who were analyzed more than 2 specimens. Incidences of DNA heterogeneity and homogeneous diploid correlated with the number of analyzed specimens and our results showed that more than 4 specimens were necessary to diagnose the DNA ploidy patterns. The near-tetraploid group was shown to have an extremely poor prognosis compared with the diploid group and the other aneuploid group. There were no significant difference between the diploid group and the aneuploid group in terms of the early prognosis, however, the incidence of disease recurrence was significantly higher in the aneuploid group. Our results demonstrated that DNA ploidy was an useful prognostic factor in the evaluation of patients with renal cell carcinoma.

Adult↗

[Present situation in self-injection therapy with interferon-alpha for patients with renal cell carcinoma].

Interferon-alpha (IFN alpha) is often used for the treatment of renal cell carcinomas. The injections are frequently self-administered at home. To assess how this therapy was accepted by the patient we sent out a questionnaire. For the past 2 years until March 1993, this therapy was performed in our department on 52 patients, of whom 45 were selected for the study. All patients were informed of their disease and consented to the necessity of this treatment. Thirty-eight patients answered this questionnaire. Almost all patients injected this agent mainly by themselves. These findings suggested that they regarded this therapy as a strategy to be executed by themselves for the treatment of carcinoma. The main toxic symptoms in this therapy were asthenia, fever and loss of appetite. Leukocytopenia occurred in about half of the patients, of whom 1 patient required medication because of a rapid decrease in the white blood cell count shortly after inception of this therapy. The treatment was discontinued in 50% of the patients because of these adverse effects. Systemic toxicity disappeared after cessation of IFN alpha administration. Additionally, over 80% of the patients expressed concern about effectiveness, the duration and high cost of this therapy. The patients had to be repeatedly instructed about the method of disposing used needles and syringes. This study revealed that self injection of IFN alpha, which required strict management particularly at the initiation, can be performed at home. However, countermeasures must be taken against the side actions and an optimum regimen of IFN alpha should be established as soon as possible.

Adult↗

Differential effects of ceruletide on amphetamine-induced behaviors and regional dopamine release in the rat.

This study concerned the effects of ceruletide, a cholecystokinin (CCK)-related peptide, on amphetamine-stimulated behaviors (hyperlocomotion and stereotypy) and amphetamine-induced dopamine (DA) release from the striatum and the nucleus accumbens of the rat. Also, behavioral alterations due to ceruletide administration were compared with the change in DA release from these areas. Ceruletide 160 micrograms/kg s.c., attenuated hyperlocomotion induced by amphetamine, 1 mg/kg and 3 mg/kg s.c., but had no effect on amphetamine-induced stereotypy. Results from in vivo microdialysis experiments showed that s.c. administration of ceruletide caused a significant inhibition of the amphetamine-induced increase in DA release in the nucleus accumbens but not in the striatum. These neurochemical inhibitory effects of ceruletide disappeared completely with bilateral subdiaphragmatic vagotomy. However, infusion of 1 microM of ceruletide into the nucleus accumbens through the dialysis probe had no effect on amphetamine-induced DA release. These results suggest that the inhibitory effect of peripheral administration of ceruletide on amphetamine-induced hyperlocomotion is closely related to the change in DA release from the nucleus accumbens. In the nucleus accumbens, systemically administered ceruletide acts initially on the peripheral organs and influences the activity of DA terminals via an unknown path related to the vagus. Ceruletide had different actions on the dopaminergic system in the striatum and that in the nucleus accumbens.

Amphetamine↗

Developmental toxicity of caffeine in the larvae of Xenopus laevis.

To examine the developmental toxicity of caffeine, Xenopus larvae just after hatching, were continuously exposed to 100-2,000 mg/L caffeine for 48 hours. Caffeine interfered with development of Xenopus larvae at a concentration of 100 mg/L and above in a concentration-dependent manner. Characteristic external abnormalities, such as shortened body with wavy fins, were observed, the severity of which was clearly concentration dependent. These larvae were frequently accompanied by abnormal body flexure and edema in the fin. Light microscopy revealed that exposure to caffeine induced severe damage in the myotome and neural tube, and at higher concentrations, the epidermal tissue was also affected. Myoblasts showed wide intercellular spaces, and their cytoplasm lost uniform staining. Ultrastructural studies of myoblasts revealed distinct myofibril disorganization and degeneration, and mitochondrial alterations. In the neural tube, cells at the dorsal part of tube showed wide intercellular spaces and some of them were segregated to the peripheral region. Furthermore, vacuole-like structures of various sizes appeared in the white matter. The outer layer of epithelial cells in the epidermis were vacuolated and swollen. With regard to the pathogenesis of myofibril damage, caffeine appeared to cause a disturbance of intracellular calcium regulation, by releasing calcium ions from the sarcoplasmic reticulum, and the mitochondrial changes observed in myotomal cells were considered to be reflective of this increased intracellular calcium ion levels. It is speculated that caffeine interferes with cell adhesion in the myotome and neural tube by affecting calcium ion regulation.

Abnormalities, Drug-Induced↗

A carcinoid tumor of the rectum removed by strip biopsy.

In a 29-year-old male complaining of constipation, total colonoscopy revealed a 5 mm yellowish submucosal tumor at a distance of 6 cm from the anal ring. The histologic diagnosis of specimens obtained by biopsy was rectal carcinoid tumor and transanal ultrasonography revealed the tumor localization within the submucosal layer in the rectum. A strip biopsy was performed. Histopathological examination confirmed the diagnosis and ascertained complete excision. Rectal carcinoid tumors should be removed completely and strip biopsy may be a suitable procedure for removal of rectal submucosal tumors less than 10 mm in diameter.

Adult↗

Influence of potassium concentration in microdialysis perfusate on basal and stimulated striatal dopamine release: effect of ceruletide, a cholecystokinin-related peptide.

The in vivo microdialysis method was used to study the effect of the cholecystokinin-related peptide, ceruletide, on extracellular levels of dopamine (DA) in the striatum following perfusion with various K+ concentrations. Increasing the K+ concentration in the perfusate from 4 to 15 or 17.5 mM did not change basal DA release or release evoked by electrical stimulation of the medial forebrain bundle (MFB). However, when the perfusing solution contained 20 or 30 mM K+, dose-dependent reductions of both basal and MFB-stimulated DA release occurred. Subcutaneous administration of ceruletide at 160 micrograms/kg had no influence on the basal or MFB-stimulated DA release with 4 or 15 mM K+ in the perfusate. However, after perfusion with 17.5 mM K+, ceruletide significantly attenuated the basal and MFB-stimulated DA release. Carbachol (10 microM) locally applied via the dialysis probe also attenuated MFB-stimulated DA release after perfusion with 17.5 mM K+. From these results, we conclude that under appropriate depolarization of striatal DA terminals, ceruletide induces further depolarization and inactivation of nigrostriatal DA terminals. The present data suggest that this effect may be mediated via intrinsic cholinergic neurons in the striatum.

Animals↗

A granular cell tumor of the buccal mucosa--a case report.

In the oral region, granular cell tumors often occur in the tongue, but rarely in the buccal mucosa. A case of granular cell tumor in the right buccal mucosa of a 74 year-old female is described. An elastic-hard solid mass about 1 cm in diameter was palpated under the right buccal mucosa. It was well-defined from the proximal tissues and adhered to part of the buccal mucosa. As a result of a biopsy, the diagnosis of a granular cell tumor was made. The tumor was resected together with the surrounding tissues under local anesthesia. Histopathological examination revealed large tumor cells with eosinophilic, PAS-positive fine granules under the hyperplastic epithelium. The granular cells stained negatively with PTAH, but positively with S-100 protein. Electron microscopic observations revealed a number of lysosomes of various sizes and densities within the cytoplasm of the tumor cells.

Aged↗

Ceruletide, a CCK-like peptide, attenuates dopamine release from the rat striatum via a central site of action.

Ceruletide (CLT), a cholecystokinin-like peptide was given subcutaneously or via the perfusate to rats to clarify the site of action (peripheral vs. central location) of CLT, using in vivo microdialysis techniques. Striatal dopamine (DA) release induced by haloperidol (HPD) was significantly inhibited by subcutaneously administered CLT (160 micrograms/kg) when given with a perfusate containing 15 mM K+. Subdiaphragmatic vagotomies failed to block the inhibitory effect of CLT. CLT (10(-15)-10(-11) M) locally applied, via a dialysis tube, produced an inhibitory effect on HPD-induced DA release in the striatum in a dose-dependent manner. The inhibitory effect of CLT given subcutaneously on DA release was antagonized by both locally applied proglumide and systemically administered L-365,260. These findings suggest that systemically administered CLT can directly act on the striatal neurons via CCK-B receptors and produce an inhibitory effect on DA release in the striatum under appropriate depolarization.

Animals↗

Activation of human natural killer cells by the protein-bound polysaccharide PSK independently of interferon and interleukin 2.

The protein-bound polysaccharide PSK was tested for the ability to activate human natural killer (NK) cells. When blood lymphocytes and purified CD3-CD16+ large granular lymphocytes (LGL) were treated in vitro overnight with PSK, they demonstrated enhanced NK cell activity against K562. The PSK-activated killer cells also lysed NK-resistant targets and freshly isolated autologous and allogeneic tumor cells. The PSK effect was observed with concentrations that could be obtained in the blood of cancer patients receiving oral administration of PSK. PSK-induced enhancement of NK activity was not abrogated by monoclonal antibodies (mAb) that neutralized interferon (IFN) alpha, IFN gamma, or interleukin-2 (IL-2). In addition, mAb reactive with p55 (alpha chain) or p75 (beta chain) glycoproteins of IL-2 receptors had no effects on PSK-enhanced NK activity even when used simultaneously. These results indicate that the PSK could activate human NK cells independently of IFN and IL-2/IL-2R systems.

Adenocarcinoma↗

Ultrastructural study of M cells from colonic lymphoid nodules obtained by colonoscopic biopsy.

The present study was undertaken to investigate ultrastructurally the epithelium covering lymphoid nodules obtained from colonoscopic biopsies of the human colon and rectum. Colonoscopy using the dye spraying contrast method was performed in nine patients who showed x-ray evidence of lymphonodular hyperplasia. Fifty-two colonoscopical biopsy specimens of lymphoid nodules were obtained from the ascending, transverse, and descending colon and rectosigmoid region. All specimens were observed by light and electron microscopy. Light microscopy disclosed large lymphoid follicles protruding into the lumen with a "dome-type" configuration. These extended to the lamina propria of the mucosa and were associated with a massive lymphoid aggregation extending as far as the muscularis mucosa from the submucosa. The epithelium covering these nodules contained a few goblet cells and many lymphocytes. Observation of the elevated surface at the apex by scanning electron microscopy revealed M cells with sparse microvilli in the dome epithelium surrounded by crypts. Transmission electron microscopy disclosed M cells enfolding many immature or mature lymphocytes and plasmocytes. The M cells had cytoplasmic microvilli (so-called "microfolds") on their surfaces, well-developed tubulovesicular systems, and vacuoles in the cytoplasm. The basic structure of the M cells as observed by scanning and transmission electron microscopy was the same as that of M cells in the Peyer's patches of humans and mice. The apical surface of the colonic lymphoid follicles in Crohn's disease patients was associated with erosions observed by scanning electron microscopy. The erosions proved to be the naked surface of the dome after removal of the epithelium, and many holes from 2.0 to 6.0 microns in diameter were observed on the naked surface. At high magnification, lymphocytes were seen projecting from holes (18%) on the naked surface of the dome. These ultrastructural findings indicate that human colonic lymphoid follicles are very similar to those seen in other species.

Adult↗

Preparation and pharmacological evaluation of 4-(1,4-benzoquinon-2-yl)-4-phenylbutanamides as potential cerebral protective agents.

A new series of 4-(1,4-benzoquinon-2-yl)-4-phenylbutanamides (2) were synthesized for evaluation of their pharmacological activities. All these compounds synthesized showed significant antilipidperoxidation (ALP) activities with brain homogenate in rats and some of them possessed a protective effect against hypobaric hypoxia in mice. Especially, a thiomorpholine derivative (2l, SUN-4757) showed a wide efficacy spectrum to a variety of experimental screening assays designed for cerebral protective agents, and it had a high LD50 value.

Animals↗

Reversal of alpha-methyltyrosine-induced hypoactivity by 6-(R)-5,6,7,8-tetrahydro-L-erythrobiopterin (R-THBP) in mice.

The effects of peripheral administration of 6-(R)-5,6,7,8-tetrahydro-L-erythrobiopterin dihydrochloride (R-THBP), a natural cofactor for tyrosine and tryptophan hydroxylases, were investigated in mice treated with a competitive inhibitor of tyrosine hydroxylase, alpha-methyltyrosine (alpha-MT). A subcutaneous dose of 250 mg/kg of alpha-MT decreased markedly both ambulatory activity and cerebral contents of norepinephrine, dopamine and their metabolites in mice. An intraperitoneal dose of 100 mg/kg of R-THBP, which did not alter ambulatory activities in normal mice, improved the hypoactivity in alpha-MT-treated mice. Moreover, R-THBP at intraperitoneal doses of 60 and 100 mg/kg inhibited the impairment of cerebral catecholamine metabolism induced by alpha-MT in mice. We suggest that the reversal of the alpha-MT effects by R-THBP might be due to reactivation of tyrosine hydroxylase in the central nervous system.

Animals↗

Remarkable improvement of growth and developmental retardation in Crohn's disease by parenteral and enteral nutrition therapy.

The patient, an 18-yr-old male (admission ht 153 cm, wt 30 kg), had been suffering from growth arrest and intermittent abdominal pain since he was 13 yr old, which was left untreated. Examinations on admission disclosed almost normal pituitary function, while levels of testosterone and somatomedin C were low. Roentgenological examination revealed extensive skip-stenotic lesions and longitudinal ulcers in the ileum, diagnostic of Crohn's disease. Therapy involving high-caloric parenteral and enteral alimentation resulted in a marked increase in both ht and wt, and improvement in roentgenological and colonoscopical findings. The interrelation between Crohn's disease and malnutrition with reference to some reports in the literature is discussed.

Adolescent↗

Allergic granulomatosis and angiitis of Churg-Strauss. A case of high serum level of eosinophil cationic protein.

We report a case of allergic granulomatosis and angiitis of Churg-Strauss. The patient is a 40-year-old woman who satisfied the clinico-pathological triad of asthma, tissue and blood eosinophilia, and granulomatous vasculitis. We also measured serum eosinophil cationic protein (ECP) levels in this patient. In the active stage, the serum ECP level was higher than in healthy controls, declining in the remission stage, a finding suggesting that ECP is involved in the pathogenesis and course of Churg-Strauss disease.

Adult↗

Studies of variant palatal rugae in normal and corticosteroid-treated mouse embryos.

Fourteen- and 15-day mouse embryos treated with triamcinolone on day 11 of gestation were examined for the presence of variant rugae. Nontreated mouse embryos served as controls. Variant rugae found were classified into five types. All five types of variations (bifurcation, division, supernumerary, shortness and cross) were observed in triamcinolone-treated embryos, and shortness was most frequently seen. Supernumerary, bifurcation and division were ranked next, following by cross. Variant, rugae, except the cross, were also observed in non-treated embryos in low frequencies, but more than one-half of them were the bifurcation of the second ruga. Divided rugae ranked next, and supernumerary and shortness were found occasionally. Except for the bifurcated and supernumerary rugae, the greater part of the variant rugae were found in the fifth and fourth ruga in the triamcinolone-treated groups and in the fifth ruga in the nontreated groups. As the incidence of variant rugae in the triamcinolone-treated embryos was significantly higher than that in the nontreated, it was regarded as one of the changes induced by the corticoid. Based on the characteristic features of the rugal region, it is speculated that the formation of variant rugae is associated with the disturbance of normal epithelial-mesenchymal interaction which may be controlled by the nerve fibers appearing at the time of rugal formation. The relationship between the increased appearance of variant rugae and the failure of palatal shelf elevation was examined, but no direct evidence was obtained.

Abnormalities, Drug-Induced↗