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Biomedical subjects

Y Kitamura

Publications and source records attributed to Y Kitamura.

At least 289 records · Page 16Linked to original sources

Visual evoked cortical magnetic fields to pattern reversal stimulation.

We studied visual evoked magnetic fields to pattern reversal stimulation in six healthy subjects. Similar to the N75-P100-N145 components in visual evoked potentials, triphasic deflections, N75m-P100m-N145m, were clearly observed around the midoccipital position. A very small component, P50m, was occasionally observed preceding the N75m. Equivalent current dipoles (ECDs) of the main deflection, P100m, to quadrant-field stimulation were estimated near or around the calcarine fissure contralateral to the stimulation. The vertical ECD location of the P100m to the upper quadrant-field stimulation was estimated significantly lower (0.81 +/- 0.45 cm) than those to lower stimulation. These results were compatible with the retinotopic organization of the visual cortex (cruciform model) and suggested that the P100m originated in the striate cortex. The small P50m, although only a small number of ECDs could be estimated reliably, was located in the contralateral visual cortex. ECDs of the N75m were estimated mainly near or around the contralateral calcarine fissure. ECDs of the N145m were estimated also retinotopically, but with a greater vertical distance (2.90 +/- 1.09 cm) between upper and lower quadrant-field stimulation. MR-overlaid ECDs of the N145m suggested that these originated in the extrastriate cortex. No ECD was estimated when a probe was placed at the midfrontal position.

Adult↗

Relationship of alcohol use, physical activity and dietary habits with serum carotenoids, retinol and alpha-tocopherol among male Japanese smokers.

BACKGROUND: Despite considerable interest in the anticarcinogenic and anti-atherosclerotic effects of carotenoids and alpha-tocopherol, little is known about determinants of these serum micronutrients. METHODS: The association of lifestyle factors including alcohol use, physical activity and dietary habits with serum levels of carotenoids (lycopene, lutein, cryptoxanthin and beta-carotene), retinol and alpha-tocopherol were studied in 194 healthy men aged 24-60 years who smoked > 15 cigarettes/day. A self-administered questionnaire ascertained consumption frequency of 12 food items, alcohol consumption, levels of physical activity and the number of cigarettes smoked per day. RESULTS: Of the dietary items studied, total vegetable intake was significantly, positively associated with beta-carotene levels, as was fruit intake with serum levels of each carotenoid. Tofu intake was unexpectedly, but strongly related to decreased levels of cryptoxanthin and beta-carotene. None of the food items was materially related to serum levels of retinol and alpha-tocopherol. Alcohol consumption was most strongly and inversely associated with levels of all the carotenoids except lutein, whereas was positively associated with retinol level but not with alpha-tocopherol level. Frequency of participation in sports was significantly and positively associated with both retinol and alpha-tocopherol levels. The amount of cigarettes smoked per day was unrelated to each micronutrient level in this study of moderate or heavy smokers. CONCLUSIONS: The consumption of vegetables and fruits is an important determinant of serum carotenoid levels even in smokers. Alcohol consumption is inversely associated with carotenoid levels, although the mechanism for this is not clear. Tofu and physical activity influence serum levels of antioxidative micronutrients, and these relationships need further studies.

Adult↗

Stimulatory roles of muscarinic acetylcholine receptors on T cell antigen receptor/CD3 complex-mediated interleukin-2 production in human peripheral blood lymphocytes.

It is known that there are some bidirectional interactions between the nervous and the immune systems via neurotransmitters and cytokines. To clarify whether any neurotransmitters modulate lymphocyte functions, we examined the effects of oxotremorine-M (Oxo-M) on interleukin-2 (IL-2) production in human peripheral blood lymphocytes by using enzyme-linked immunosorbent assays, Northern blot analyses, reverse transcriptase-polymerase chain reaction, and fluorescence-activated cell sorter. Pretreatment of cells with Oxo-M (10 nM to 10 microM) for 4-24 hr enhanced phytohemagglutinin (PHA)-induced IL-2 mRNA expression and markedly increased IL-2 production compared with those induced by PHA alone. Oxo-M alone did not affect IL-2 mRNA expression and IL-2 production. In CD3-positive T cells, pretreatment with Oxo-M for 24 hr enhanced PHA-induced IL-2 production. Furthermore, pretreatment with Oxo-M enhanced PHA-induced mRNA expression of the alpha and beta subunits of IL-2 receptors and DNA synthesis. Cytometric analysis showed Oxo-M treatment did not up-regulate expression of cell surface molecules such as CD3, CD2, CD4, CD8, and IL-2 receptors. These results suggest that activation of muscarinic receptors enhances T cell antigen receptor/CD3-induced IL-2 production.

Antigens, CD↗

Possible participation of Fas-mediated apoptosis in the mechanism of atherosclerosis.

Apoptosis is a programmed cell death that plays a major role during development, homeostasis, and in many diseases. Recent evidence has demonstrated the death of vascular smooth muscle cells (VSMCs) within advanced human atheroma. In the rat balloon-injury model, apoptotic cells were specifically identified in the neointima. The presence of apoptotic cells was demonstrated by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). To clarify the mechanisms that trigger apoptosis in atherosclerotic lesions, we examined whether cytokines released from macrophages can modulate Fas, a death signal, in cultured human VSMCs. Simultaneous treatment with interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) but not with each cytokine alone induced upregulation of Fas in VSMCs. However, coincubation with NG-monomethyl-L-arginine, an inhibitor of nitric oxide (NO) synthesis, inhibited the upregulation of Fas induced by IL-1 and TNF-alpha. Incubation with sodium nitroprusside, a NO donor, also induced upregulation of Fas in VSMCs. Furthermore, fluorescent nuclear staining with Hoechst 33258 revealed that monoclonal antibody to human Fas significantly enhanced NO-induced apoptotis in VSMCs. These findings suggest that macrophage-derived cytokines can induce upregulation of Fas through a NO-dependent mechanism in VSMCs. Thus, Fas-mediated apoptosis may regulate apoptotic death of VSMCs during atherogenesis.

Animals↗

Regulation of vascular type 1 angiotensin receptors by cytokines.

Although various cytokines are known to be expressed in atherosclerotic lesions, it is not known how these cytokines affect receptors for the peptide hormone angiotensin II (Ang II). We therefore examined the effects of interleukin-1 alpha (220 U/mL [10 ng/mL]), tumor necrosis factor-alpha (280 U/mL [100 ng/mL]), and interferon gamma (100 U/mL) on Ang II type 1 (AT1) receptors expressed in rat vascular smooth muscle cells. Treatment with interleukin-1 alpha caused a 1.4- to 1.7-fold increase in AT1 binding after 24 hours (P<.01) and a 2.3-fold increase in AT1 mRNA (P<.05). Tumor necrosis factor-alpha and interferon gamma did not cause a significant change in AT1 binding when administered alone but caused a 30% reduction in binding when administered together (P<.05). The maximal decrease in AT1 binding (60%, P<.01) was seen with the combination of interleukin-1 alpha with tumor necrosis factor-alpha and interferon gamma. Although the upregulation of AT1 by interleukin-1 alpha was unaffected by pretreatment of cells with N-monomethyl-L-arginine or indomethacin, downregulation of AT1 by interleukin-1 alpha combined with tumor necrosis factor-alpha/interferon gamma was inhibited by N-monomethyl-L-arginine (P<.01). Interleukin-1 alpha treatment enhanced Ang II-induced [3H]uridine incorporation, whereas treatment with interleukin-1 alpha combined with tumor necrosis factor-alpha/interferon gamma attenuated Ang II-induced [3H]uridine and [3H]leucine incorporation. These results demonstrate that interleukin-1 alpha upregulates AT1 receptors and enhances Ang II-stimulated hypertrophic responses. However, a combination of interleukin-1 alpha with tumor necrosis factor-alpha and interferon gamma downregulates AT1 receptors by a nitric oxide-dependent mechanism and reduces Ang II-stimulated trophic responses in vascular smooth muscle cells.

Angiotensin II↗

Inhibitory effects of talipexole and pramipexole on MPTP-induced dopamine reduction in the striatum of C57BL/6N mice.

We have investigated the effects of two novel antiparkinsonian drugs, talipexole (Domin) and pramipexole, on MPTP-induced dopamine (DA) reduction in the striatum of C57BL/6N mice in comparison with those of bromocriptine. Fifteen days after MPTP treatment (25 mg/kg, i.p., given daily for 5 days), the DA content in the striatum was decreased to 40-60% of the control value. Among the three dopamine receptor agonists, talipexole and pramipexole (1 mg/kg, i.p., once a day for 20 days) more significantly suppressed the MPTP-induced DA reduction in the striatum than bromocriptine (10 mg/kg, i.p., once a day for 20 days). Talipexole did not influence [3H]MPP+ uptake into striatal synaptosomes. These results suggest that talipexole and pramipexole have a protective effect against MPTP-induced DA reduction in the striatum of C57BL/6N mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Possible involvement of rapamycin-sensitive pathway in Bcl-2 expression in human neuroblastoma SH-SY5Y cells.

In human neuroblastoma SH-SY5Y cells, treatment with immunosuppressants such as FK506, cyclosporin A or rapamycin for 4 days induced the enhancement of the 27-kDa Bcl-2alpha protein level. Among immunosuppressants, rapamycin has most potency. Treatment with herbimycin A or wortmannin also enhanced Bcl-2 expression, but the BB type of platelet-derived growth factor decreased the level. These results suggest that Bcl-2 expression is probably regulated by the cascade of tyrosine kinase, phosphatidylinositol 3-kinase and rapamycin-sensitive p70 S6-kinase in human neuroblastoma SH-SY5Y cells.

Gene Expression↗

Three modes of ossification during distraction osteogenesis in the rat.

We developed a rat model of limb lengthening to study the basic mechanism of distraction osteogenesis, using a small monolateral external fixator. In 11-week-old male rats we performed a subperiosteal osteotomy in the midshaft of the femur with distraction at 0.25 mm every 12 hours from seven days after operation. Radiological and histological examinations showed a growth zone of constant thickness in the middle of the lengthened segment, with formation of new bone at its proximal and distal ends. Osteogenic cells were arranged longitudinally along the tension vector showing the origin and the fate of individual cells in a single section. Typical endochondral bone formation was prominent in the early stage of distraction, but intramembraneous bone formation became the predominant mechanism of ossification at later stages. We also showed a third mechanism of ossification, 'transchondroid bone formation'. Chondroid bone, a tissue intermediate between bone and cartilage, was formed directly by chondrocyte-like cells, with transition from fibrous tissue to bone occurring gradually and consecutively without capillary invasion. In situ hybridisation using digoxigenin-11-UTP-labelled complementary RNAs showed that the chondroid bone cells temporarily expressed type-II collagen mRNA. They did not show the classical morphological characteristics of chondrocytes, but were assumed to be young chondrocytes undergoing further differentiation into bone-forming cells. We found at least three different modes of ossification during bone lengthening by distraction osteogenesis. We believe that this is the first report of such a rat model, and have shown the validity of in situ hybridisation techniques for the study of the cellular and molecular mechanisms involved in distraction osteogenesis.

Animals↗

Normal and abnormal development of the human intrahepatic biliary system: a review.

Morphology and immunohistochemical features of the developmental process of the human intrahepatic biliary system (IBS) are reviewed. Human IBS arises from the ductal plate, a double-layered cylindrical structure located at the interface between portal mesenchyme and primitive hepatocytes. The ductal plate first appears from primitive hepatocytes (hepatoblasts) around 8 gestational weeks (GW), and its formation proceeds from the hepatic hilum to the periphery. The ductal plate gradually undergoes remodeling from 12 GW; some parts of the ductal plate disappear and other parts migrate into the portal mesenchyme. Around 20 GW, the migrated duct cells transform into immature bile ducts and peribiliary glands. Some immature peribiliary glands transform into pancreatic acinar cells around postnatal 3 months. The immature biliary elements express cytokeratins no. 7, 8, 18 and 19. Several growth factors (TGF-alpha, HGF) and their receptors (EGFR, MET, ERBB2) were expressed in the primitive IBS cells. Some extracellular matrix proteins including type IV collagen, laminin and tenascin are expressed in the mesenchyme around the primitive IBS. During IBS remodeling, apoptosis and cell proliferation occur with appropriate expression of apoptosis-related proteins (bcl-2, Fas, c-myc, Lewis(y)). Some pancreatic digestive enzymes (alpha-amylase, trypsinogen, lipase), cathepsin B, and matrix metalloproteinases (MMP-1, 2, 3, 9) and their inhibitors (TIMP-1, 2) are expressed in the remodeling IBS cells. Glycoconjugate residues of glycoproteins gradually appear during IBS development. The appropriate expression of these immunophenotypes may play an important role in the normal development of IBS.

Animals↗

[Thoracoscopic surgery for pneumothorax with bullous emphysema in an elderly patient: a case report].

Recent advances in optical and endoscopic operating instruments have made thoracoscopic surgery easier. The authors report the case of an 83-year-old patient who was referred to our hospital for right spontaneous pneumothorax associated with severe bullous emphysema. Chest X-ray films showed 40% collapse of right lung and the right spontaneous pneumothorax was treated by chest tube drainage for 3 weeks. However air leak was not decreased and subcutaneous emphysema appeared. Chest computerized tomography revealed multiple bullae. Thoracoscopic surgery was performed because of preservation of the respiratory function. The ruptured bulla was resected by using ENDO GIA and the other multiple bullae were resected similarly in order to improve the pulmonary function. A surgical drain was removed on the 14th postoperative day because of a little air leak continuing. His postoperative course was uneventful after removal of the chest drain. He was discharged on 27th postoperative day and had no shortness of breath in daily life. From our experience, thoracoscopic surgery appears to be much better than thoracotomy for spontaneous pneumothorax because of much less postoperative disability and preservation of respiratory function.

Aged↗

Expression of mast-cell-specific proteases in tissues of mice studied by in situ hybridization.

The protease mRNA expression phenotype of individual mast cells was studied by in situ hybridization. Mouse mast cell protease (MMCP)-2 mRNA was expressed by mast cells located in the mucosa of the stomach of WB(-)+/+ and (WB x C57BL/6)F1(-)+/+ (hereafter WBB6F1(-)+/+) mice but not by mast cells in the same tissue of C57BL/ 6(-)+/+ mice. Even in the stomach of WBB6F1(-)+/+ mice, mast cells located in the muscularis propria did not express MMCP-2 mRNA. The mRNAs of MMCP-4 and mouse mast cell carboxypeptidase A were not expressed by mast cells in the stomach mucosa of untreated WBB6F1(-)+/+ mice but were expressed after the infection of Strongyloides venezuelensis. We examined whether MMCP-2 mRNA expression varied by changing environments of mast cells. Cultured mast cells of WBB6F1(-)+/+ mice that expressed MMCP-2 mRNA were transplanted into the stomach wall of genetically mast-cell-deficient WBB6F1(-)W/Wv mice. Mast cells that appeared in the mucosa expressed the MMCP-2 mRNA, but mast cells that appeared in the muscularis propria did not, indicating the adaptation of cultured mast cells into a new environment. In contrast to cultured mast cells, peritoneal mast cells of WBB6F1(-)+/+ mice that expressed MMCP-2 mRNA as well did not adapt to the muscularis propria of WBB6F(1)-W/Wv mice. The MMCP-2 mRNA remained to be expressed after the settlement in either the mucosa or the muscularis propria. Furthermore, the peritoneal mast cells did not change the MMCP-4 and MMCP-6 mRNA expression phenotype after the settlement in either the mucosa or the muscularis propria of WBB6F(1)-W/Wv mice. The present result indicated that both intracellular factors such as strain specificity and source of mast cells and extracellular factors such as tissue specificity and helminth infection influenced the protease expression phenotypes.

Animals↗

Mechanisms of constitutive activation of c-kit receptor tyrosine kinase.

We investigated the mechanism of constitutive activation of c-kit receptor tyrosine kinase (KIT) found in the FMA3 murine mastocytoma cell line, and compared it with the mechanisms observed in other tumor mast cell lines (the HMC-1 human mast cell leukemia cell line, the RBL-2H3 rat mast cell leukemia cell line, and the P-815 murine mastocytoma cell line). The c-kit gene obtained from FMA3 cells was found to have 21-base deletion at the juxtamembrane domain of KIT, thereby leading to the constitutive activation of KIT. The deletion at the juxtamembrane domain resulted in constitutive dimerization of c-kit proteins, whereas the point mutation that were detected at the kinase domain of KIT in HMC-1, RBL-2H3, and P-815 cells caused constitutive activation of KIT without dimerization. These constitutively activating mutations of c-kit may play a role in development of mast cell tumors.

Animals↗

Cellular localization of thrombopoietin mRNA in the liver by in situ hybridization.

The expression of thrombopoietin (TPO) mRNA is observed in several tissues, including liver, kidney, brain, skeletal muscle, intestine, spleen, and bone marrow. Among these organs, the highest expression of TPO mRNA is detected in the liver. We identified cells producing TPO by means of in situ hybridization of adult rat liver using digoxigenin-11-UTP-labeled cRNA probes. We found that the cells expressing TPO mRNA also expressed serum albumin mRNA. TPO mRNA was detected in parenchymal cells (hepatocytes) but not in non-parenchymal cells (including endothelial cells, epithelial cells, and so forth). To determine the location of TPO expression in embryogenesis, sections of fetal mice were further analyzed by in situ hybridization. TPO mRNA was detected only in hepatocytes of fetal liver, which was also the major site of hematopoiesis. The expression of TPO mRNA in fetal liver was observed from 12.5 days postcoitus. Northern blot analysis showed that mouse liver transcribed the same size of TPO mRNA in the fetus and in the adult. These results clearly demonstrate that hepatocytes are the primary site of TPO production in the liver from fetus to adult.

Animals↗

[Efficacy of lidocaine tape for venous cannulation in children].

We evaluated whether lidocaine tape (3 X 5 cm, contained 18 mg of lidocaine) could reduce pain caused by venous cannulation in children during anesthetic induction. One hundred and thirty-five children scheduled for elective surgery were randomly assigned to three groups according to the application time of the tape (30 min, 60 min and 120 min). Pain assessment was made by using our pain score (0: no response, 1: slight agitation, 2: strong agitation, at the venous cannulation). The effect of pain reduction (pain score 0 and 1) was found in 81 % of all patients. Especially in the group of 120 min, the effect was remarkable. Only 6.7% of all patients had slight adverse effects including skin redness and itching. In another 25 patients (weighing 3.5-30 kg), plasma concentration of lidocaine were measured 120 min after application of a piece of this tape. Arterial blood was sampled at 30 and 120 min after the tape was removed. Plasma lidocaine levels were always below 0.8 mcg.ml-1 In conclusion, the lidocaine tape may be useful and safely applicable for venous cannulation in children.

Administration, Cutaneous↗

aFGF, endogenous satiety substance, facilitates learning, memory and immune function in aging.

aFGF injection s.c. once a week into SAMP8 was begun at 3 weeks after birth and continued for 10 months. Saline was injected as a control. learning and memory and cellular immunological functions in the aFGF group were enhanced significantly, while those of the saline group deteriorated. 1. The number of cholinergic neurons was decreased by less than 20% and ChAT activity in individual neurons in the medial septum which send monosyonaptic terminals to the hippocampus was significantly decreased in the saline group, but not so much in the aFGF group. 2. The respective densities of muscarinic and aFGF receptors, on the hippocampal neurons were significantly higher in the aFGF group than in the saline group. 3. The LTP in hippocampal slice preparations was significantly facilitated in the aFGF group, but not in the saline group. 4. The DTH, (T cell immune response) measured at the end of the 2nd and 7th months were reduced in the 7th month as compared with the 2nd month in the saline group, but aFGF group protected against this reduction. 5. These results show that aFGF provides protection against impairment of not only learning and memory but also the DTH immunoreactivity in SAMP8.

Aging↗

Involvement of transcription factor encoded by the mouse mi locus (MITF) in apoptosis of cultured mast cells induced by removal of interleukin-3.

Mast cells develop when spleen cells of mice are cultured in the medium containing interleukin (IL)-3. Cultured mast cells (CMCs) show apoptosis when they are incubated in the medium without IL-3. We obtained CMCs from tg/tg mice that did not express the transcription factor encoded by the mi gene (MITF) due to the integration of a transgene at its 5' flanking region. MITF is a member of the basic-helix-loop-helix-leucine zipper (bHLH-Zip) protein family of transcription factors. We investigated the effect of MITF on the apoptosis of CMCs after removal of IL-3. When cDNA encoding normal MITF ((+)-MITF) was introduced into tg/tg CMCs with the retroviral vector, the apoptosis of tg/tg CMCs was significantly accelerated. The mutant mi allele represents a deletion of an arginine at the basic domain of MITF. The apoptosis of tg/tg CMCs was not accelerated by the introduction of cDNA encoding mi-MITF. The overexpression of (+)-MITF was not prerequisite to the acceleration of the apoptosis, as the apoptotic process proceeded faster in +/+ CMCs than in mi/mi CMCs. The Ba/F3 lymphoid cell line is also dependent on IL-3, and Ba/F3 cells show apoptosis after removal of IL-3. The c-myc gene encodes another transcription factor of the bHLH-Zip family, and the overexpression of the c-myc gene accelerated the apoptosis of Ba/F3 cells. However, the overexpression of (+)-MITF did not accelerate the apoptosis of Ba/F3 cells. The (+)-MITF appeared to play some roles for the acceleration of the apoptosis specifically in the mast cell lineage.

Animals↗