Biomedical subjects

K Tomiyama

Publications and source records attributed to K Tomiyama.

At least 37 records · Page 2Linked to original sources

PubMed1999

[Effect of ondansetron hydrochloride injection and tablet against nausea and vomiting in lung cancer patients receiving carboplatin].

We investigated the efficacy of combination of ondansetron hydrochloride injection and tablet against nausea and vomiting in 22 lung cancer patients (total number of chemotherapy courses: 23) receiving chemotherapy of single-dose carboplatin (CBDCA) at a dose of 302.2 +/- 31.9 mg/m2. For suppressing emesis, the patients were given 4 mg of ondansetron injection on the day of CBDCA injection (Day 1), and 4 mg/day of ondansetron tablet for Days 2 to 5. The following results were obtained 5 days after the administration of carboplatin. 1) Control of nausea graded 'Good' or better counted for 95% or higher of all cases for each day of the chemotherapy. A complete nausea suppression rate was seen in 91.3%, 81.0%, 71.4%, 63.6% and 71.4% from Day 1 to Day 5, respectively. 2) Control of vomiting graded 'Major' control or better was achieved in 95% or more of all cases, for each day. The complete vomiting suppression rate observed from Day 1 to Day 5 was 91.3%, 78.3%, 65.2%, 69.6% and 91.3%, respectively. 3) Inhibitory effect on nausea and vomiting for each day of Days 1 to 5 graded as 'Effective' or better was shown in 90% or higher of all cases; based on overall judgement for Days 1 to 5, all cases were graded as 'Effective' or better. 4) The proportion of cases which was evaluated as 'Can eat most of the meal' was 88.0%, 73.9%, 50.7%, 50.7% and 65.2% from Days 1 to 5, respectively, against 95.7% prior to the start of chemotherapy. 5) No adverse drug reaction or abnormal clinical laboratory values were seen along with ondansetron. 6) In conclusion, combined treatment with ondansetron injection and tablet was considered clinically useful in control of nausea and vomiting during administration of carboplatin, and may also be useful for out-patient chemotherapy.

Adult↗

PubMed1998

Phenotypic and functional modulation of T cells in vivo by extrathymic T cells when T cells with MHC class II disparity were injected into athymic nude mice.

TCRhigh cells are generated by the mainstream of T cell differentiation in the thymus, whereas TCRint cells (or NK1.1+ T cells) are generated extrathymically in the liver and by an alternative intrathymic pathway. It is still unknown how these T cell populations interact in vivo with each other. To investigate the interaction of TCRint cells with TCRhigh cells, we used congenitally athymic nude (B6-nu/nu) mice which carry only TCRint cells in all immune organs. When TCRhigh cells from B6-C-H-2bm12 (bm12) mice (i.e. I-Abm12) were injected into B6-nu/nu mice (i.e. 1-Ab), the expanding T cell population was a mixture of TCRhigh cells of donor origin and TCRint cells of recipient origin. However, 9 Gy-irradiated nude mice permitted a full expansion of TCRhigh cells which expressed the IL-2Ralpha+beta+ phenotype, namely, they were at the most activated state. These mice died of acute graft-versus-host disease (GVHD) within 5 days. On the other hand, non-irradiated nude mice suppressed the expansion of TCRhigh cells of donor origin and such TCRhigh cells continued to have the IL-2Ralpha(+/-)beta+ phenotype. These mice could survive but showed signs of chronic GVHD thereafter. In both situations, CD4+alphabeta T cells expanded irrespective of donor or recipient origin. These results suggest that TCRint cells in the recipient mice possess a regulatory function in relation to donor TCRhigh cells; as a result, fully activated TCRhigh cells acquired the IL-2Ralpha+beta+ phenotype and injured the host, but TCRhigh cells suppressed in vivo remained as the IL-2Ralpha(+/-)beta+ phenotype and only partially injured the host.

Animals↗

PubMed1998

Requirement of the IL-2 receptor beta chain for the development of Vgamma3 dendritic epidermal T cells.

Vgamma3 TCR cells develop in the fetal thymus and migrate to the skin as dendritic epidermal T cells (DETC). Fetal Vgamma3 thymocytes differentiate from immature heat stable antigen (HSA)high cells to mature HSAlow cells and the latter subset predominantly expresses IL-2 receptor beta chain (IL-2Rbeta). In this study, the role of IL-2Rbeta in the development of Vgamma3 cells was determined in IL-2Rbeta-deficient mice. There was a moderate reduction of mature HSAlow Vgamma3 thymocytes in IL-2Rbeta-deficient mice. Small numbers of Vgamma3 DETC were detected in the fetal skin of IL-2Rbeta-deficient mice, but they were absent in newborn and adult mice. These results suggest that IL-2Rbeta may transduce the crucial signal for survival and/or expansion of Vgama3 cells in the fetal thymus and in the fetal skin. In normal mice, IL-15 but not IL-2 mRNA was expressed in the fetal epidermis and exogenous addition of low concentration of IL-15 to fetal skin organ culture induced proliferation of Vgamma3 DETC. The dependence of fetal Vgamma3 DETC on the expression of IL-2Rbeta and the presence of IL-15 mRNA in the fetal epidermis imply an essential role of IL-15 signaling through IL-2Rbeta in the selective localization of this gammadelta T cell subpopulation in the skin.

Animals↗

PubMed1998

Effect of zinc sulfate on sensorineural olfactory disorder.

We administered zinc sulfate to patients with sensorineural (post-viral, post-traumatic, or unknown aetiology) olfactory disorder and examined its effects. The patients were divided into three groups by method of treatment: zinc sulfate only, combination of zinc sulfate and the usual therapy, or the usual therapy. For disorders of post-viral and unknown aetiologies, there were no significant differences in improvement among the three groups. However, for post-traumatic olfactory disorder, the zinc sulfate groups had significantly higher improvement rates than did the group that received the usual therapy. The difference between post-traumatic and post-viral olfactory disorders in the effect of zinc sulfate therapy appeared to depend on the pathology of the associated lesions. In cases of post-traumatic olfactory disorder, regenerative capacity is retained in the olfactory epithelium because the blast cells of olfactory receptor cells remain intact. However, for post-viral olfactory disorder, the lack of olfactory receptor cells and blast cells due to viral infection results in loss of regenerative capacity. We also determined pre-treatment serum zinc concentrations in those patients who planned to be treated with zinc sulfate. Pre-treatment serum zinc concentration was not significantly related to improvement rates.

Craniocerebral Trauma↗

PubMed1998

Effect of growth factor on GTPase-activating protein (Ras GAP) in Chinese hamster ovary cells.

GTPase-activating proteins (GAPs) stimulate the hydrolysis of GTP bound to small G-proteins and regulate the signal transduction pathway. Changes in the expression of p21-Ras p120-GAP induced by growth factor treatment were examined in cultured Chinese hamster ovary (CHO) and human choriocarcinoma (BeWo) cells. Expression of p120-GAP and GAP activity were measured. Fetal bovine serum induced a significant increased level of GAP in CHO cells, but did not increase GAP in BeWo cells. The results suggest that growth factors affect Ras GAP expression in CHO cells, while they do not in other cells such as BeWo cells.

Animals↗

PubMed1998

Dentinal tubule occlusion with lanthanum fluoride and powdered apatite glass ceramics in vitro.

To simulate hypersensitive dentin, the smear layer and dentinal plugs of bovine root dentin specimens were removed by immersion in 10% phosphoric acid, polishing with hydroxyapatite particles, and ultrasonic cleansing. The fluoride-tannic acid-lanthanum-apatite (FTLA) group was treated with acidulated phosphate fluoride (APF) containing tannic acid followed by rubbing with a paste of lanthanum chloride (LaCl3) and powdered apatite glass ceramics. The treated specimens were immersed in a remineralizing solution that mimics saliva for 6 weeks. The SEM observations revealed that the treated surfaces of the FTLA group were completely covered with fine spherical compounds and the dentinal tubules were occluded with plugs to a depth of about 3 microns. Fluoride and lanthanum were detected to a depth of over 20 microns by EPMA observation. After the remineralization, the surface of FTLA-treated specimen did not have any opened tubules and showed a remarkable increase in the number of fine spherical deposits in the dentinal tubules. These results suggest that the reaction products produced by sequential treatment with acidic fluoride and LaCl3 and powdered apatite glass ceramics are able to effectively occlude dentinal tubules.

Acidulated Phosphate Fluoride↗

PubMed1998

Clinical study of olfactory disturbance.

The clinical records of 889 patients with olfactory disturbance who had been examined at the Olfaction Clinic, Osaka City University Hospital, Japan from January 1982 to December 1996 were studied in order to investigate the relationship between the patients' characteristics and their prognoses. Aetiologically the characteristic variables of "head trauma" and "congenital" had the greatest influence on prognosis, representing poor recovery. The patients with "rhinitis" and "head trauma" showed faster improvement of olfactory disturbance in "females", "those with short duration of olfactory disorder" and "those with high olfactory acuity before treatment". None of the characteristic variables influenced prognosis in the patients with "viral infection". Age did not significantly influence prognosis. Improvement was recognized in most patients within 6 months. Hence, we should treat patients with olfactory disturbance for at least this length of time.

Craniocerebral Trauma↗

PubMed1997

Phosphorylation of H-ras proteins by protein kinase A.

Protein phosphorylation is one of several representative post-translational modifications. Cyclic AMP-dependent protein kinase (PKA) plays the crucial and varying role of signal transduction. On the other hand, ras proteins plays an important role in cell proliferation and growth. Although a previous report showed that H-ras protein was phosphorylated by PKA, the stoichiometry was not determined, so we investigated the stoichiometry of phosphorylation of the protein by PKA. H-ras cDNA inserted into a pGEX-2T expressing vector produced high levels of recombinant H-ras (rH-ras) in a fusion protein with glutathione S-transferase. rH-ras was obtained after cleavage by thrombin. Phosphorylation of ras protein by the catalytic subunit of PKA was performed, and the radioactivity was counted after SDS-PAGE and autoradiography. The results indicate that less than 0.1 mol of phosphate was incorporated per mol of H-ras protein, and suggest that H-ras protein could not be a physiologically meaningful substrate for PKA.

Cyclic AMP-Dependent Protein Kinases↗

PubMed1997

[Carinal resection for primary lung cancer--with special attention to a modified double-barrel method].

Carinal resection for primary lung cancer was clinically evaluated. Carinal resection was performed in 18 patients, 17 males and one female, with a mean age of 64 years. Nine patients underwent carinal reconstruction and the other 9 sleeve or wedge pneumonectomy. The carinal reconstruction was of the montage type in one patient, the one-stoma type in 2, and the modified double-barrel method in 6. The modified double-barrel method is a technique that we developed by adding bronchial end-to-side anastomosis to the tracheobronchial end-to-end anastomotic site. A pedicled intercostal muscle flap was used for covering the anastomotic site. The postoperative respiratory complications after carinal reconstruction were anastomosis failure in 4 patients (pin-hole in 3) and respiratory failure in 2. However, no anastomosis stricture occurred, and recovery was satisfactory. There were no respiratory complications after pneumonectomy. One patient had renal failure before surgery and died of multiple organ failure 23 days after a montage type carinal reconstruction. The other 17 patients did well and could be discharged from the hospital and the overall mortality rate was 5.6%. No anastomosis stricture occurred in the modified double-barrel method. By carinal reconstruction covering of the anastomotic site is mandatory to prevent fatal postoperative complications.

Adenocarcinoma↗

PubMed1996

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor impairs cell p4fferentiation in cultured adipogenic cells (3T3-L1).

Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, inhibits the synthesis of mevalonic acid. We examined the effect of lovastatin on the differentiation of the fibroblast/adipocyte cell line (3T3-L1). Lovastatin inhibits the differentiation of 3T3-L1 cells in a dose-dependent fashion. The inhibitory effect of lovastatin was partially reversed by adding exogenous mevalonic acid to the 3T3-L1 cells. Exogenous cholesterol (15 micrograms/ml) did not prevent lovastatin inhibition of adipocyte conversion. The isoprenoids, farnesol and geraniol, partially prevented lovastatin inhibition of adipocyte conversion but squalene did not prevent lovastatin inhibition of adipocyte conversion. We conclude that the inhibitory effect of lovastatin was partially due to the blockade of the pathway leading to synthesis of isoprenoids, which are downstream products of mevalonic acid.

3T3 Cells↗

PubMed1996

Existence of a small population of IL-2R beta hi TCRint cells in SCG and MRL-lpr/lpr mice which produce normal Fas mRNA and Fas molecules from the lpr gene.

Mice carrying the lpr gene, SCG and MRL-lpr/lpr mice, were used to characterize the phenotype and lpr gene of abnormally proliferating T cells in these mice. A major population which expanded in these mice were T cells expressing intermediate (int) levels of T cell receptor (TCR) (and CD3) and the phenotype of interleukin-2 receptor (IL-2R) beta lo alpha- (possibly abnormal TCRint cells). The levels of TCRhi cells of thymic origin (generated through the mainstream of T cell differentiation in the thymus) profoundly decreased after the onset of disease. However, a small population of normal TCRint cells (i.e. IL-2R beta hi alpha-) were also found to exist in all tested organs. For example, the majority of abnormal IL-2R beta lo TCRint cells were CD4-8- CD2-, while normal IL-2R beta hi TCRint cells were a mixture of single-positive cells (mainly CD8+), CD4-8- cells and CD2+ cells. Moreover, normal TCRint cells preferentially produced normal Fas mRNA and Fas molecules from the lpr gene. This phenomenon explains the leaky appearance of normal Fas mRNA and Fas molecules in mice carrying the lpr gene. It is suggested that a small population of IL-2R beta hi TCRint cells are resistant to the lpr genetic abnormality.

Animals↗

PubMed1996

Apoptosis in the normal olfactory epithelium of the adult guinea pig.

Among nerve cells of vertebrates, the olfactory epithelia are uncommon in their capacity for cell turnover. Apoptosis is well known to play a key role in maintaining homeostasis in continuously renewing tissues. We examined whether true apoptosis occurred in the normal olfactory epithelia of healthy adult guinea pigs using nucleic acid labeling. Subsequently, apoptosis was recognized in olfactory nerve cells, indicating that apoptosis might play a role in turnover of the olfactory epithelium.

Animals↗

PubMed1995

Wortmannin, a specific phosphatidylinositol 3-kinase inhibitor, inhibits adipocytic differentiation of 3T3-L1 cells.

The effect of wortmannin, which inhibits phosphatidylinositol 3-kinase (PI 3-kinase), on adipocytic differentiation of 3T3-L1 cells was examined. The extent of differentiation was evaluated by the staining of adipocytes with Oil Red O and measurement of glycerol 3-phosphate dehydrogenase (GPDH) activity. Wortmannin, at over 100 nM, significantly inhibited adipogenesis of cells treated with isobutyl-methylxanthine, dexamethasone, and insulin with an IC50 value about 50 nM. These results suggest that PI 3-kinase plays a role in adipocytic differentiation of 3T3-L1 cells.

1-Methyl-3-isobutylxanthine↗

PubMed1995

In vivo microdialysis evidence for transient dopamine release by benzazepines in rat striatum.

The effects of benzazepine derivatives on extracellular levels of dopamine (DA) and L-3,4-dihydroxy-phenylacetic acid (DOPAC) in the dorsal striatum of freely moving rats were studied using in vivo microdialysis. Direct injection of SKF-38393 (0.5 or 1.5 micrograms/0.5 microliter), a selective D1 receptor agonist, into the striatum through a cannula secured alongside a microdialysis probe produced a rapid dose-dependent transient increase in striatal DA efflux and a more gradual reduction in efflux of DOPAC. The rapid increase in DA efflux was not affected by infusion of tetrodotoxin (TTX; 2 microM) or Ca(2+)-free Ringer's solution and occurred after either enantiomer of SKF-38393. A TTX-insensitive increase in DA level similar to that induced by SKF-38393 was also seen after other benzazepines acting as agonists (SKF-75670 and SKF-82958, each 1.5 micrograms in 0.5 microliter) and antagonists (SCH-23390, 1.5 micrograms in 0.5 microliter) at the D1 receptor and after (+)-amphetamine. These effects were inhibited by infusion of nomifensine (100 microM). It is concluded that the transient increases in striatal DA efflux seen after intrastriatal injection of SKF-38393 and other benzazepines are not mediated by presynaptic D1 receptors but by an amphetamine-like action on the dopamine transporter.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Opposite effects of midazolam and beta-carboline-3-carboxylate ethyl ester on the release of dopamine from rat nucleus accumbens measured by in vivo microdialysis.

This report describes the effects of midazolam and beta-carboline-3-carboxylate ethyl ester (beta-CCE) on extracellular concentrations of dopamine in the nucleus accumbens of freely moving rats measured by in vivo microdialysis. The two compounds had opposite effects, midazolam (0.075 and 0.15 mg/kg i.v.) dose dependently decreasing, and beta-CCE (3 and 10 mg/kg i.p.) dose dependently increasing, dialysate concentrations of dopamine. Flumazenil (6 micrograms/kg i.v.) did not affect the efflux of dopamine but it prevented the effects of both midazolam and beta-CCE on dopamine efflux. N6-Cyclohexyladenosine (0.1, and 1 mg/kg i.p.), a selective adenosine A1 agonist, dose dependently increased the efflux of dopamine. This effect was blocked by 8-cyclopentyl-1,3-dipropylxanthine (25 mg/kg i.p.), a selective adenosine A1 receptor antagonist, a dose which given alone did not affect dopamine efflux; responses to midazolam were not affected. 3,7-Dimethyl-1-propargylxanthine (1 and 3 mg/kg i.p.), a selective adenosine A2 receptor antagonist, did not mimic the effects of beta-CCE. The results suggest that midazolam and beta-CCE modulate dopamine release in the nucleus accumbens by an action at the benzodiazepine binding site associated with the GABAA receptor complex.

Adenosine↗

PubMed1994

[Methods for intracerebral injection].

In behavioral studies, seeking the regional site of action of centrally acting drugs, injections are normally made directly into a restricted area of the brain using a microsyringe inserted in a guide cannula that had been implanted previously. This paper describes conventional methods for injecting a drug into the rat brain. The common technique used in brain dialysis studies is to apply the drugs focally into the brain by infusing them through the dialysis probe. One of the main problems of this technique is the difficulty in estimating actual doses of the drugs administered. The present paper also describes a microdialysis probe in combination with a microinjection tube to examine changes in the release and metabolism of dopamine within the area where the drugs were injected under experimental conditions similar to those used in behavioral studies. Using this method, we demonstrated the characteristic difference between two benzamide D2-receptor antagonists YM-09151-2 and l-sulpiride on dopamine release in rat striatum.

Animals↗

PubMed1993

Preferential distribution of V beta 8.2-positive T cells in the central nervous system of rats with myelin basic protein-induced autoimmune encephalomyelitis.

To determine the role of encephalitogenic T cells in the formation of lesions in the central nervous system (CNS), experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats by immunization with either myelin basic protein (MBP) or the synthetic peptide which corresponds to the 87-100 sequence of guinea pig MBP, and T cells expressing T cell receptor (TcR) V beta 8.2, V beta 8.5, V beta 10 and V beta 16 in the lymphoid organs and CNS were localized and quantified by flow cytometry (FCM) and immunohistochemistry. In normal rats, the percentage of T cells expressing these V beta phenotypes to the total number of TcR alpha beta+ T cells, as determined by FCM, ranged from 5% to 10% in the lymph node. V beta 16+ T cells were the most predominant population among the four V beta subsets tested. Essentially the same findings were obtained from the analysis of the lymphoid organs of rats with EAE which had been induced by immunization with the same two antigens. In sharp contrast, 15-20% of the T cells isolated from lesions of MBP-induced EAE expressed V beta 8.2. Thus, the percentage of V beta 8.2+ T cells in the EAE lesions was threefold higher than that in the lymph node, while the proportions of V beta 8.5+, V beta 10+ and V beta 16+ T cells were about the same in both organs. The predominance of V beta 8.2+ T cells in EAE lesions was confirmed by counts of immunohistochemically stained T cells in the spinal cord. Moreover, it was revealed that (i) the predominance of V beta 8.2+ T cells was greatest during the development of EAE and became less obvious at the recovery state, and (ii) at the peak stage of EAE, approximately 85% of V beta 8.2+ T cells were distributed in the parenchyma while 15% were in the perivascular space of the CNS vessels. These findings indicate that encephalitogenic T cells which express V beta 8.2 infiltrate the CNS at a very early stage of EAE and become the predominant population in infiltrating T cells, and further suggest that encephalitogenic T cells, not only recruit inflammatory cells in the CNS, but also cause neural tissue damage, such as demyelination.

Amino Acid Sequence↗

PubMed1993

Rejection of cultured keratinocyte allografts in presensitized mice.

The fate of cultured keratinocyte (KC) allografts remains controversial. Although prolonged survival of cultured KC allografts in naive mice has been reported, the detailed mechanisms remain undetermined. Furthermore, it was also reported that in the human cultured KC allografts do not survive permanently, and they are rapidly replaced by recipient cells. In the present study, we have addressed this issue and obtained findings that cultured KC allografts survive for a prolonged period in naive mice under the conditions in which reepithelization by recipient cells is prevented. However, the same cultured KC allografts were rejected when they were grafted onto recipients primed with allogeneic spleen cells or full-thickness skin grafts. To clarify the mechanisms behind these findings, the allostimulatory ability of cultured KC and their susceptibility to alloreactive cytotoxic T cells were examined in vitro. In a mixed epidermal cell-lymphocyte reaction, cultured KC were unable to induce allospecific proliferative responses of naive T cells. On the other hand, primed T cells from presensitized mice showed weak but significant proliferative responses against allogeneic KC. It also was confirmed that cultured KC are susceptible to lysis by alloreactive cytotoxic T cells. These data indicate that prolonged survival of cultured KC allografts in naive mice is attributable to a defect in the afferent, but not the efferent, phase of the rejection process that is caused by the weak allostimulatory ability of cultured KC. This assumption was also supported by the finding that spleen cells from the recipient mice bearing long-surviving KC allografts retain in vitro responsiveness against stimulator cells syngeneic to the grafted KC. Taken together, these findings indicate that long-term survival of cultured KC allografts in naive mice may be due solely to the weak allostimulatory ability of cultured KC, but not to loss of susceptibility to alloreactive cytotoxic T cells after culture of KC or induction of tolerance in the recipient mice bearing KC allografts.

3T3 Cells↗