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Biomedical subjects

K Tomiyama

Publications and source records attributed to K Tomiyama.

At least 19 recordsLinked to original sources
PubMed2006

Ex vivo application of carbon monoxide in University of Wisconsin solution to prevent intestinal cold ischemia/reperfusion injury.

Carbon monoxide (CO), a byproduct of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. In vivo recipient CO inhalation at low concentrations prevented ischemia/reperfusion (I/R) injury associated with small intestinal transplantation (SITx). This study examined whether ex vivo delivery of CO in University of Wisconsin (UW) solution could ameliorate intestinal I/R injury. Orthotopic syngenic SITx was performed in Lewis rats after 6 h cold preservation in control UW or UW that was bubbled with CO gas (0.1-5%) (CO-UW). Recipient survival with intestinal grafts preserved in 5%, but not 0.1%, CO-UW improved to 86.7% (13/15) from 53% (9/17) with control UW. At 3 h after SITx, grafts stored in 5% CO-UW showed improved intestinal barrier function, less mucosal denudation and reduced inflammatory mediator upregulation compared to those in control UW. Preservation in CO-UW associated with reduced vascular resistance (end preservation), increased graft cyclic guanosine monophosphate levels (1 h), and improved graft blood flow (1 h). Protective effects of CO-UW were reversed by ODQ, an inhibitor of soluble guanylyl cyclase. In vitro culture experiment also showed better preservation of vascular endothelial cells with CO-UW. The study suggests that ex vivo CO delivery into UW solution would be a simple and innovative therapeutic strategy to prevent transplant-induced I/R injury.

Adenosine↗
PubMed2003

[Surgically treated mucoepidermoid carcinoma in a 6-year-old boy; report of a case].

A 6-year-old boy was admitted to our hospital with a history of recurrent obstructive pneumonia and hemoptysis. A chest computed tomography (CT) showed atelectasis in the left lower lobe. Angiograpy, which was performed for the suspicion of pulmonary sequestration, showed no feeding artery and revealed bleeding from the bronchial artery in the left lower lobe. As hemoptysis would not stop, an emergency left lower lobectomy was performed. Macroscopic examination of the resected specimen revealed a mass measuring 20 x 15 x 17 mm in the S8 proximal lung parenchyma, bronchiectasis, and an abscess in the distal lung parenchyma. Histopathologic examination determined the tumor was a mucoepidermoid carcinoma. Immunohistochemical staining revealed some tumor cells were positive for CA 19-9. The child has not had a recurrence 3 years postoperatively.

Bronchial Neoplasms↗
PubMed2002

Phenotypic resolution of spontaneous and D1-like agonist-induced orofacial movement topographies in congenic dopamine D1A receptor 'knockout' mice.

A novel system was used to assess the role of D(1)-like dopamine receptors in distinct topographies of orofacial movements in mice with congenic D(1A) receptor knockout. Under spontaneous conditions, vertical jaw movements in wild-types declined with time at a rate that was reduced in D(1A) mutants, while horizontal jaw movements emerged progressively in wild-types but not in D(1A) mutants; tongue protrusions were absent in D(1A) mutants, while incisor chattering was initially reduced in D(1A) mutants but rose subsequently to reach the level of wild-types. D(1A) receptors exert a topographically specific role in regulating individual spontaneous orofacial movements, and these involve interactions with psychomotor processes which 'sculpt' behavioural change over time. The anomalous D(1)-like agonist SK&F 83959, which fails to stimulate, and indeed inhibits the stimulation of adenylyl cyclase induced by dopamine, readily stimulated vertical jaw movements, tongue protrusions and incisor chattering, and these response topographies were absent in D(1A) mutants. These results suggest that D(1A) receptors may exert some form of permissive role over orofacial topographies initiated via a novel, putative D(1)-like site not linked to adenylyl cyclase, or that some D(1A) receptors might be coupled to a transduction system other than adenylyl cyclase.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2001

Topographical assessment and pharmacological characterization of orofacial movements in mice: dopamine D(1)-like vs. D(2)-like receptor regulation.

A novel procedure for the assessment of orofacial movement topographies in mice was used to study, for the first time, the individual and interactive involvement of dopamine D(1)-like vs. D(2)-like receptors in their regulation. The dopamine D(1)-like receptor agonists A 68930 ([1R,3S]-1-aminomethyl-5,6-dihydroxy-3-phenyl-isochroman) and SK&F 83959 (3-methyl-6-chloro-7,8-dihydroxy-1-[3-methyl-phenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine) each induced vertical jaw movements with tongue protrusions and incisor chattering. The dopamine D(1)-like receptor antagonists SCH 23390 ([R]-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) and BW 737C ([S]-6-chloro-1-[2,5-dimethoxy-4-propylbenzyl]-7-hydroxy-2-methyl-1,2,3,4-tetrahydroisoquinoline) antagonised these responses, while the dopamine D(2)-like receptor antagonist YM 09151-2 (cis-N-[1-benzyl-2-methyl-pyrrolidin-3-yl]-5-chloro-2-methoxy-4-methylaminobenzamide) attenuated those to SK&F 83959 and released horizontal jaw movements. These findings suggest some role for a dopamine D(1)-like receptor that is coupled to a transduction system other than/additional to adenylyl cyclase, and for dopamine D(1)-like:D(2)-like receptor interactions, in the regulation of individual orofacial movement topographies in the mouse. This methodology will allow the use of knockout mice to clarify the roles of individual dopamine receptor subtypes in their regulation.

Animals↗
PubMed2001

Hemoglobin-vesicles as oxygen carriers: influence on phagocytic activity and histopathological changes in reticuloendothelial system.

Hemoglobin-vesicles (HbV) have been developed for use as artificial oxygen carriers (particle diameter, 250 nm) in which a purified Hb solution is encapsulated with a phospholipid bilayer membrane. The influence of HbV on the reticuloendothelial system was studied by carbon clearance measurements and histopathological examination. The HbV suspension ([Hb] = 10 g/dl) was intravenously infused in male Wistar rats at dose rates of 10 and 20 ml/kg, and the phagocytic activity was measured by monitoring the rate of carbon clearance at 8 hours and at 1, 3, 7, and 14 days after infusion. The phagocytic activity transiently decreased one day after infusion by about 40%, but it recovered and was enhanced at 3 days, showing a maximum of about twice the quiescent level at 7 days, and then returned to the normal value at 14 days. The initial transient decreased activity indicates a partly, but not completely, suppressed defensive function of the body. The succeeding increased phagocytic activity corresponds to the increased metabolism of HbV. The histopathological examination with anti-human Hb antibody, hematoxylin/eosin, and oil red O stainings showed that HbV was metabolized within 7 days. Hemosiderin was very slightly confirmed with Berlin blue staining at 3 and 7 days in liver and spleen, though they completely disappeared at 14 days, indicating that the heme metabolism, excretion or recycling of iron proceeded smoothly and iron deposition was minimal. Electron microscopic examination of the spleen and liver tissues clearly demonstrated the particles of HbV with a diameter of about 1/40 of red blood cells in capillaries, and in phagosomes as entrapped in the spleen macrophages and Kupffer cells one day after infusion. The vesicular structure could not be observed at 7 days. Even though the infusion of HbV modified the phagocytic activity for 2 weeks, it does not seem to cause any irreversible damage to the phagocytic organs. These results offer important information for evaluating the safety issues of HbV for clinical use.

Animals↗
PubMed2001

The psychopharmacology-molecular biology interface: exploring the behavioural roles of dopamine receptor subtypes using targeted gene deletion ('knockout').

In the absence of selective agonists and antagonists able to discriminate between individual members of the D1-like and D2-like families of dopamine receptor subtypes, functional parcellation has remained problematic. 'Knockout' of these subtypes by targeted gene deletion offers a new approach to evaluating their roles in the regulation of behaviour. Like any new technique, 'knockout' has associated with it a number of methodological limitations that are now being addressed in a systematic manner. Studies on the phenotype of D1(A/1), D(1B/5), D2, D3 and D4 'knockouts' at the level of spontaneous and agonist/antagonist-induced behaviour are reviewed, in terms of methodological issues, neuronal implications and potential clinical relevance. Dopamine receptor subtype 'knockout' is a nascent technology that is now beginning to fulfil its potential. It is being complemented by more systematic phenotypic characterisation at the level of behaviour and additional, molecular biologically-based approaches.

Animals↗
PubMed2001

Homogeneous epithelial gamma delta T cell repertoire of the skin is shaped through peripheral selection.

In contrast to the T cell receptor (TCR) diversity of major alpha beta T cells in lymphoid tissues, epithelial T cells of the murine skin, called dendritic epidermal T cells (DETC), express exclusively an invariant gamma delta TCR. Fetal thymic precursors of DETC immigrate to the skin before birth, and in adult mice T cells expressing the canonical gamma delta TCR identical to that of DETC are not found in other lymphoid or epithelial tissues. Here, we show that DETC precursors migrate to the gut as well as to the skin during fetal periods, but preferentially survive and expand in the skin after birth. We propose that similar to the thymic selection of the diverse alpha beta T cell repertoire, 'peripheral selection' of the homogeneous epithelial gamma delta T cell repertoire may be mediated by TCR signaling upon the recognition of the self-ligand, because the ligand for the DETC TCR was expressed only in the skin.

Animals↗
PubMed2001

Differential diagnosis of a lateral cervical cyst and solitary cystic lymph node metastasis of occult thyroid papillary carcinoma.

We present a case of solitary cystic lymph node metastasis from an occult thyroid papillary carcinoma mimicking a lateral cervical cyst, and a case of thyroid papillary carcinoma with a true lateral cervical cyst. Based on a comparison of the radiographical findings of the two cases, differential diagnosis between cystic lymph node metastasis of papillary carcinoma and branchial cyst is discussed.

Adult↗
PubMed2001

[Approaches to sella turcica in endoscopic pituitary surgery].

Recent advances in endoscopic sinus surgery suggested the potential for its surgical application to pituitary surgery. A number of institutions have reported the advantage of endoscope use in pituitary surgery, which is now widely accepted, but approaches to the sella vary in the literature. We retrospectively studied sella approaches in endoscopic pituitary surgery as rhinologists. Subjects included 6 cases of pituitary adenoma and 2 cases of Rathke's cleft cyst. A both-nostril transnasal transsphenoidal approach, our standard technique, was used in 6 cases. This approach consisted of elevation of mucoperiosteal flaps, resection of the vomer and sphenoid anterior wall, and opening of the sellar floor. Elevated mucoperiosteal flaps were used to close of the sella after tumor resection. All tumors were removed and no significant postoperative complications occurred. We found the both-nostril transnasal approach to be easy and time-saving and provided surgeon with a broad surgical field necessary to treat large tumors and accidental cases. Postoperative observation of the sella was easy for wide opening of the anterior wall of the sphenoid sinus. In our experience with reoperation, we quickly accessed the sella and easily removed tumors in the second operation. Our technique therefore has an advance in treatment of recurrence. The both-nostril transnasal approach involves the same procedures as median drainage of the sphenoid sinus, so our technique may have advantages in preventing mucocele of the sphenoid sinus as a late complication of transsphenoidal surgery. The transnasal transsphenoidal approach via both nostrils is preferable rhinologically.

Adenoma↗
PubMed2000

Magnetic resonance angiography evaluation of basilar artery stenosis in patients with vertebrobasilar insufficiency.

To assess the usefulness of evaluating basilar arterial flow by magnetic resonance angiography (MRA), MRA results for patients with vertebrobasilar insufficiency (VBI) were compared with those for age-matched individuals with no vestibular disorders. The presence of stenosis in the basilar artery, its severity and the presence of complications associated with atherosclerosis in the two groups were statistically compared. Analyses revealed significant differences in the incidence of stenosis, its severity, and the incidence of complications between the two groups. These findings suggest that MRA is valuable for the estimation of vertebrobasilar hemodynamics. MRA evaluation of basilar artery stenosis appears to be suitable for identifying a high-risk group among VBI patients, since basilar artery stenosis can result in serious disabilities.

Aged↗
PubMed2000

Functional alteration of granulocytes, NK cells, and natural killer T cells in centenarians.

The immune system in centenarians was characterized as elevated levels in the proportion and number of granulocytes, NK cells, and extrathymic T cells (including NKT cells) in the peripheral blood. Conventional T cells, abundant in youth, were decreased in proportion and number. In addition to this numerical change in centenarians, the function was significantly altered in comparison with that in middle-aged subjects. The phagocytic function and cytokine production of granulocytes in centenarians increased whereas the production of superoxides from granulocytes decreased. This tendency was almost the same in both healthy and unhealthy centenarians. IFN gamma production by NK and extrathymic T cells in centenarians seemed to be augmented and resulted in an elevated level of serum IFN gamma. Possibly due to the effect of this endogenous IFN gamma, the proportion of CD64(+) (Fc gamma RI) cells among granulocytes was elevated. The expansion of CD64 antigens on granulocytes is known to be regulated by IFN gamma and to be associated with their induction of phagocytosis. These results suggest that the immune system of centenarians is not merely impaired, but altered in terms of the number and functions of granulocytes, NK cells, NKT cells.

Adult↗
PubMed1999

Phosphorylation of extracellular signal-regulated kinases 1 and 2 in 3T3-L1 adipocytes by stimulation of beta(3)-adrenoceptor.

Recent studies have revealed that activated extracellular signal-regulated kinases (ERKs) 1 and 2 by the stimulation of beta(3)-adrenoceptors played a critical role in cell survival in brown adipocytes. On the other hand, phosphorylation of ERK1/2 via beta(3)-adrenoceptors and its physiological and pathological significance in white adipocyte has remained uncertain despite the increasing significance of functioning white adipocytes. Accordingly, we here studied phosphorylation of ERK1/2 caused by the stimulation of beta(3)-adrenoceptors in 3T3-L1 adipocytes, and the roles of phosphorylated ERK1/2 in lipolysis. Phosphorylation of ERK1/2 was induced by a selective beta(3)-adrenoceptor agonist, DL-4-[2'-¿2-hydroxy-2-(3-chlorophenyl)ethylamino¿propyl] phenoxyacetic acid sodium salt sesquihydrate (BRL37344), in 3T3-L1 adipocytes in a time- and dose-dependent manner. The phosphorylation of ERK1/2 by BRL37344 was sensitive to the cyclic AMP (cAMP)-dependent protein kinase inhibitor, N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide (H89). To elucidate the roles of phosphorylated ERK1/2 in lipolysis, the effect of a selective inhibitor of ERK1/2 phosphorylation, 2'-amino-3'-methoxyflavone (PD98059), was examined. This inhibitor did not alter the lipolytic action caused by BRL37344, even at concentrations sufficient to block phosphorylation of ERK1/2, suggesting that ERK1/2 play no role in the lipolysis caused by BRL37344 in 3T3-L1 adipocytes.

3T3 Cells↗
PubMed1999

Cytotoxic pathways in the skin allograft rejection by CD4+ T cells.

BACKGROUND: Two major mechanisms of T cell-mediated cytotoxicity are known: perforin-dependent and Fas-dependent cytotoxic pathways. Previous studies in vitro demonstrated that CD4+ cytotoxic T lymphocytes use the Fas pathway as a primary cytotoxic mechanism, but the cytotoxic mechanisms used by CD4+ T cells in vivo are unclear. METHODS: We examined the cytotoxic pathways of CD4+ T cells in vivo using a skin allograft model, in which athymic nu/nu mice were transplanted with skin allografts and reconstituted with purified CD4+T cells. Fas-deficient and perforin-deficient mice and anti-tumor necrosis factor (TNF)-alpha monoclonal antibody were used for inactivating each cytotoxic pathway in vivo. RESULTS: The skin allografts from Fas-deficient mice were readily rejected by the athymic mice reconstituted with purified CD4+ T cells. Perforin-deficient CD4+ T cells could also reject Fas-deficient skin allografts. Furthermore, in vivo treatment with anti-TNF-alpha monoclonal antibody did not prevent the allograft rejection by CD4+ T cells in the absence of both Fas and perforin pathways. CONCLUSIONS: These results indicate participation of undefined mechanisms other than Fas, perforin, and TNF-alpha pathways in CD4+ T cell-mediated cytotoxicity in vivo.

Animals↗
PubMed1999

Fentanyl increases dopamine release in rat nucleus accumbens: involvement of mesolimbic mu- and delta-2-opioid receptors.

The effects of the mu-receptor agonist fentanyl on extracellular levels of dopamine in rat nucleus accumbens were studied in awake animals by in vivo brain microdialysis. Fentanyl dose-dependently increased the levels of dopamine when given intravenously (microg/kg) or via a microdialysis probe placed into the ventral tegmental area or the nucleus accumbens (nmol). The effect of fentanyl given into the nucleus accumbens was blocked by systemic administration of the non-selective opioid receptor antagonist naloxone and by accumbens administration of D-Phe-Cys-Tyr-D-Trp-Om-Thr-Phe-Thr-NH2 (nmol), a mu-opioid receptor antagonist, and naltrindole (nmol), a non-selective delta-opioid receptor antagonist, in a dose-dependent manner. The delta2-opioid receptor antagonist, naltriben (nmol), also blocked the effects of fentanyl, whereas the delta1-opioid receptor antagonist, (E)-7-benzylidenenaltrexone (nmol), was ineffective. When marginally effective doses of D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH2 and naltriben were given simultaneously, the effect of fentanyl was nearly fully blocked; the pretreatment itself had no effect. Administration of the mu-opioid receptor agonist [D-Ala2, N-Me-Phe4,Gly5-ol]-enkephalin (nmol), the delta1-opioid receptor agonist [D-Pen2,5]-enkephalin (nmol) or the delta2-opioid receptor agonist [D-Ala2,Glu4]-deltorphin (nmol) into the nucleus accumbens enhanced the amount of accumbal dopamine. This study provides evidence that not only activation of delta1- and delta2-opioid receptors, but also activation of mu-opioid receptors in the nucleus accumbens increases the release of accumbal dopamine in freely moving rats. We suggest that the effect of intra-accumbens administration of fentanyl upon accumbal release of dopamine is either due to the simultaneous activation of mu-opioid receptors and delta2-opioid receptors or due to activation of mu-opioid receptors that interact with delta2-opioid receptors in a complex manner.

Analgesics, Opioid↗
PubMed1999

Both wortmannin and simvastatin inhibit the adipogenesis in 3T3-L1 cells during the late phase of differentiation.

As we reported previously, both wortmannin and lovastatin inhibit the differentiation in 3T3-L1 cells when these drugs were applied during the insulin-induced cell differentiation. In the present study, 3T3-L1 cells were treated with wortmannin and simvastatin after the completion of the insulin-stimulation, and differentiation was found to be significantly decreased by these drugs. This suggests intracellular signaling pathways play roles in the differentiation of 3T3-L1 cells even after the completion of the insulin-stimulation and also suggests that not only the early phase (day 0 to day 2) but also the late phase (day 2 to day 4) of differentiation is important for the differentiation of the cells.

3T3 Cells↗