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Biomedical subjects

Y Kitamura

Publications and source records attributed to Y Kitamura.

At least 343 records · Page 19Linked to original sources
PubMed1996

Lung granulomatous response induced by infection with the intestinal nematode Nippostrongylus brasiliensis is suppressed in mast cell-deficient Ws/Ws rats.

Certain nematode infections induce eosinophil infiltration and granulomatous responses in the lungs. To examine the role of mast cells in the development of lung lesions, normal +/+ and genetically mast cell-deficient Ws/Ws rats were infected with the nematode Nippostrongylus brasiliensis. In +/+ rats, numbers of eosinophils in bronchoalveolar lavage fluid (BALF) increased significantly 3-7 days after infection, and granulomatous responses composed of histiocytes/ macrophages and multinucleate giant cells were triggered in the lungs 3-14 days after infection. Challenge infection, which was carried out on day 28 after primary infection, induced much higher levels of granulomatous response than after primary infection, suggesting that the response is mediated at least in part by an immunological mechanism. In Ws/Ws rats, both the eosinophil percentage in BALF and the size of the granulomas in the lungs were significantly smaller than in +/+ rats after primary as well as after challenge infection. The amount of rat mast cell protease (RMCP) II in +/+ rat BALF was increased 1 day after primary infection and more significantly after challenge infection, suggesting that lung mucosal mast cells were activated more markedly after the challenge infection. In Ws/Ws rats, RMCP II was undetectable throughout the observation period. The time course of nematode migration in the lungs did not differ in +/+ and Ws/Ws rats. These results suggest that mast cell activation might be relevant to eosinophil infiltration and granulomatous response in the lungs, although the responses do not affect lung migration of the nematode.

Animals↗
PubMed1996

Significance of the cant of the posterior occlusal plane in class II division 1 malocclusions.

In studying a group of fifty adult females with Class II division 1 malocclusion, it was evident that the skeletal problems of this malocclusion involved small, retruded mandibles accompanied by backward rotation. This skeletal pattern was considered to be influenced by the vertical dimension of the upper dentition in the buccal segment for mandibular function. The anterior and the posterior occlusal planes were examined to gain a detailed assessment of the relationship between the dental and the skeletal patterns. The findings indicated that the steep cant of the posterior occlusal plane was strongly correlated with the following: 1. Small, retruded mandible with backward rotation as the skeletal pattern. 2. Short vertical height of the upper second molars and distal inclination of the upper molars as the dental pattern. The increased vertical height of the lower second premolars was found to be related to backward rotation of mandible. In treating skeletal Class II malocclusions, this study indicated that control of the vertical dimension of the posterior teeth is extremely important.

Adolescent↗
PubMed1996

Increase in hepatic tissue blood flow by teprenone.

The major objective of the present study was to evaluate mechanisms by which teprenone, a gastric mucosal protecting agent, increases hepatic mucosal blood flow using male Sprague-Dawley rats. Hepatic and gastric blood flow was measured using a laser blood flow meter after administration of teprenone, dissolved in Tween 80, into the inferior vena cava. Teprenone itself increased hepatic and gastric blood flow. It also increased hepatic and gastric blood flow in rats with acute hepatic disorders due to carbon tetrachloride (CCL4) and improved histological changes, such as inflammatory cell infiltration and fatty changes in the liver. The fact that blood endothelin (ET) concentrations increased after administration of teprenone suggest that teprenone has great affinity for ET beta receptors and shows ET beta-receptor antagonist-like effects. Hepatic blood flow decreased after administration of N-nitro-L-arginine methyl ester, a nitric oxide (NO) synthetase inhibitor, suggesting that teprenone increase NO activity. Teprenone was thought to increase hepatic and gastric blood flow by different mechanisms, because it increased gastric mucosal prostaglandin E2 concentrations.

Animals↗
PubMed1996

Identification of the cell type origin of odontoma-like cell masses in microphthalmic (mi/mi) mice by in situ hybridization.

Tooth abnormalities occur in microphthalmic (mi/mi) mice. The elongated odontogenic epithelium is interrupted by unresorbed bone at the basal end of the mi/mi incisor, with the epithelium gathered into cell clusters. These clusters develop to odontoma-like masses. To identify the origin of the cell types of these odontoma-like masses, the localization of osteonectin (Osn), osteocalcin (Osc), osteopontin (Osp), matrix Gla protein (MGP) and amelogenin (Am) mRNA in the process of tooth development in mi/mi and +/+ mice was investigated by means of in situ hybridization. Decalcified mandibles of neonatal, 5-, 10-, 14-day-old mice were examined. Osn and Osc mRNA, which localized in osteoblasts and odontoblasts, were also detected in the cells of odontoma-like masses in mi/mi mice. The cells expressing these mRNA were short, columnar and odontoblast-like. Am mRNA was detected in ameloblasts. In mi/mi mice, Am mRNA was also detected in ameloblastic cell clusters, which were formed by the tall columnar cells in the odontoma-like masses. No apparent Osp mRNA expression was detected in the masses. These results indicated that even in odontogenic abnormal cells resulting from physical obstruction in mi/mi mice, the genes that are involved in normal tooth development were still expressed.

Animals↗
PubMed1996

Human endogenous retrovirus K10 encodes a functional integrase.

We cloned a human endogenous retrovirus K1O DNA fragment encoding integrase and expressed it as a fusion protein with Escherichia coli maltose-binding protein. Integrase activities were measured in vitro by using a double-stranded oligonucleotide as a substrate mimicking viral long terminal repeats (LTR). The fusion protein was highly active for both terminal cleavage and strand transfer in the presence of Mn2+ on the K1O LTR substrate. It was also active on both Rous sarcoma virus and human immunodeficiency virus type 1 LTR substrates, whereas Rous sarcoma virus and human immunodeficiency virus type 1 integrases were active only on their corresponding LTR substrates. The results strongly suggest that K1O encodes a functional integrase with relaxed substrate specificity.

Amino Acid Sequence↗
PubMed1996

The recessive phenotype displayed by a dominant negative microphthalmia-associated transcription factor mutant is a result of impaired nucleation potential.

In the DNA binding domain of microphthalmia-associated transcription factor (MITF), four mutations are reported: mi, Mi wh, mi ew, and mi or. MITFs encoded by the mi, Mi wh, mi ew, and Mi or mutant alleles (mi-MITF, Mi wh-MITF, Mi ew-MITF, and Mi or-MITF, respectively) interfered with the DNA binding of wild-type MITF, TFE3, and another basic helix-loop-helix leucine zipper protein in vitro. Polyclonal antibody against MITF was produced and used for investigating the subcellular localization of mutant MITFs. Immunocytochemistry and immunoblotting revealed that more than 99% of wild-type MITF and Mi wh-MITF located in nuclei of transfected NIH 3T3 and 293T cells. In contrast, mi-MITF predominantly located in the cytoplasm of cells transfected with the corresponding plasmid. When the immunoglobulin G (IgG)-conjugated peptides representing a part of the DNA binding domain containing mi and Mi wh mutations were microinjected into the cytoplasm of NRK49F cells, wild-type peptide and Mi wh-type peptide-IgG conjugate localized in nuclei but mi-type peptide-IgG conjugate was detectable only in the cytoplasm. It was also demonstrated that the nuclear translocation potential of Mi or-MITF was normal but that Mi ew-MITF was impaired as well as mi-MITF. In cotransfection assay, a strong dominant negative effect of Mi wh-MITF against wild-type MITF-dependent transactivation system on tyrosinase promoter was observed, but mi-MITF had a small effect. However, by the conjugation of simian virus 40 large-T-antigen-derived nuclear localization signal to mi-MITF, the dominant negative effect was enhanced. Furthermore, we demonstrated that the interaction between wild-type MITF and mi-MITF occurred in the cytoplasm and that mi-MITF had an inhibitory effect on nuclear localization potential of wild-type MITF.

3T3 Cells↗
PubMed1996

Diagnosis of lymphoma in paraffin wax sections by nested PCR and immunohistochemistry.

AIMS: To investigate whether nested polymerase chain reaction (PCR) and immunohistochemistry can be used to diagnose malignant lymphoma. METHODS: Paraffin wax embedded tissue sections from 31 patients with malignant lymphoma were analysed by nested PCR and immunohistochemistry using standard protocols. RESULTS: Nested PCR amplification of 1 pg DNA confirmed monoclonality in B cell lymphoma; PCR amplification of 10 pg DNA confirmed monoclonality in T cell lymphoma. Twenty seven (87%) samples were diagnosed as malignant lymphoma by nested PCR, and 24 (77%) by immunohistochemistry. Seven samples were diagnosed as malignant lymphoma by nested PCR, but not by immunohistochemistry, whereas the use of both procedures gave a diagnosis of malignant lymphoma in all 31 samples. CONCLUSIONS: A combination of immunohistochemistry and nested PCR can be used to diagnose malignant lymphoma in routine paraffin wax embedded sections.

Adult↗
PubMed1996

Canine retinal arterial and arteriolar dilatation induced by nipradilol, a possible glaucoma therapeutic.

The effects of nipradilol, an ocular hypotensive drug, on isolated canine retinal central arteries and on retinal arterioles in vivo were investigated. Nipradilol (10(-9) to 10(-5) mol/l) produced a dose-related relaxation of the arterial strips contracted with prostaglandin F2 alpha which was not influenced by timolol or indometacin. The median effective concentration of this drug was five times that of glycerol trinitrate (GTN). The nipradilol-induced relaxation in the endothelium-intact strips was not influenced by NG-nitro-L-arginine, a nitric oxide synthase inhibitor, but was abolished by oxyhemoglobin and methylene blue. Treatment with high concentrations of sodium nitroprusside abolished the response to nipradilol, as observed with that to GTN. Retinal arterial strips responded to isoproterenol with a slight relaxation which was depressed by nipradilol. In anesthetized dogs, intra-arterial injections of nipradilol dilated the retinal arterioles in the ocular fundus; the dilator potency was approximately one fifth that of GTN. It is concluded that nipradilol dilates canine retinal arteries in vitro and arterioles in vivo, possibly due to activation of soluble guanylate cyclase and increased production of cyclic guanosine monophosphate that are associated with nitric oxide liberated from the molecule itself in the tissue but not derived from the endothelium and perivascular nerve. Beta adrenoceptor blocking action was determined in the retinal artery.

Animals↗
PubMed1996

Inhibition of histamine synthesis by glycyrrhetinic acid in mast cells cocultured with Swiss 3T3 fibroblasts.

The effect of glycyrrhetinic acid (18-O-beta-glycyrrhetinic acid, GA) on histamine metabolism was investigated in cultured mast cells (CMCs) cocultured with Swiss 3T3 fibroblasts. GA strongly inhibited histamine synthesis in the cocultured CMCs. Since 50 microM GA inhibited about 80% of histidine decarboxylase (HDC) activity, the inhibitory activity of GA for histamine synthesis was considered to be derived from the inhibition of HDC activity. The number of berberine-sulfate-positive cells also decreased in the presence of GA, which indicated that maturation of CMCs was inhibited by GA. Furthermore, we examined the effect of GA on the mRNA expression of novel protein kinase C delta (nPKC delta), a major isoform of CMCs, by northern blot analysis. The expression of nPKC delta mRNA in the presence of GA was significantly lower than in the absence of GA. These results suggest the possibility that the inhibition of histamine synthesis by GA is regulated by nPKC delta.

3T3 Cells↗
PubMed1996

Expression of oxytocin receptor in human pregnant myometrium.

Around the onset of labor, uterine sensitivity to oxytocin (OT) increases tremendously. Although this is considered to reflect OT receptor (OTR) augmentation in myometrium, neither spatial expression of OTR nor the level of the receptor message during the course of pregnancy have been investigated at the molecular level. We examined the localization and expression of the OTR in human myometrium by means of in situ hybridization, immunohistochemistry, and Northern and Western blotting. In the term pregnant myometrium, OTR expressing smooth muscle cells are observed diffusely and heterogeneously. Some of the smooth muscle cells were expressed high levels of the receptor at the messenger RNA and protein level, and they were surrounded with cells weakly positive for the OTR or negative. The level of OTR transcripts increased according to the course of pregnancy. The receptor messenger RNA level reached over 300-fold at parturition compared with the nonpregnant myometrium. In the myometrium at 32 weeks of gestation and not in labor, a relatively large amount (about 100-fold) of the receptor message was expressed. In the nonpregnant myometrium, significant amount of the receptor protein was revealed by Western blotting. We also found that the receptor protein was augmented at term and after the onset of labor. These findings indicated that the expression of OTR changes dynamically at the transcription and protein level during pregnancy and that its expression is heterogeneous in the term myometrium.

Amino Acid Sequence↗
PubMed1996

Hyperglycemia decreases dehydroepiandrosterone in Japanese male with impaired glucose tolerance and low insulin response.

Recent studies indicate that experimentally induced hyperinsulinemia may reduce serum dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEA-S). Serum DHEA and DHEA-S decrease in diabetic patients, but the mechanism by which hyperglycemia decreases DHEA and DHEA-S is unknown. In this study, we investigated the effect of hyperglycemia on DHEA and DHEA-S in impaired glucose tolerance (IGT) by means of the 75g-oral glucose tolerance test (OGTT). We selected 30 male IGT patients receiving diet therapy only, whose insulinogenic Index was under 0.3. Oral glucose challenge significantly reduced DHEA (P = 0.0001) and DHEA-S (P < 0.05) at 60 and 120 min after OGTT. Setting the value of DHEA and DHEA-S at time zero as 100%, we calculated the DHEA and DHEA-S values at 60 and 120 min after OGTT as %DHEA(-S) 60 min and %DHEA(-S) 120 min, respectively. DHEA and DHEA-S at time zero showed no correlation with BMI, HbA1c, the sum of insulin values (sigma IRI) or the area under the curve of plasma glucose (AUC). We found decreases in %DHEA 60 min (r = -0.411, P < 0.05), %DHEA-S 60 min (r = -0.508, P < 0.01) and %DHEA-S 120 min (r = -0.393, P < 0.05) as AUC increased, but sigma IRI showed no correlation with %DHEA(-S) 60 min or %DHEA(-S)120 min. We conclude that the depression of DHEA and DHEA-S after OGTT is attributable to hyperglycemia in male Japanese IGT with low insulin response.

Dehydroepiandrosterone↗
PubMed1996

Antibodies to the 37,000-Mr tryptic fragment of islet antigen were detected in Japanese insulin-dependent diabetes mellitus patients.

Sera from 30 Japanese insulin-dependent diabetes mellitus (IDDM) patients of short duration were examined to determine whether they had antibodies to proteolytic fragments of islet antigen, the molecular weights of which were 37,000 and/or 40,000 Mr (37KAb). The median age and disease duration of the patients were 13 (range 6-22) years old and 12 (range; 0-24) months, respectively. Twelve out of the 30 IDDM patients (40%) had 37KAb, while none of the 16 control subjects was positive for 37KAb. The frequency of the 37KAb was not correlated with disease duration tested. We further investigated the antibodies to ICA512, by radioligand binding assay, which has been proposed to be a target antigen for the 37 KAb. Twenty-two (73.3%) patients had antibodies to ICA512 (ICA512AA), but none of the control subjects did. The levels of ICA512AA, which were described as indexes using standard sera, were significantly higher in the patients than in the control subjects (1.436 +/- 2.674 and 0.001 +/- 0.002, respectively, P < 0.05). The frequency of antibodies to glutamic acid decarboxylase 65 (GAD65Ab) was also higher in the patients than in the control subjects (70% and 0%, respectively), but 7 out of 9 GAD65Ab-negative patients had ICA512AA and/or 37KAb. Since 93% of the IDDM patients had at least one of these antibodies, combined analysis with 37KAb, ICA512AA, and GAD65Ab facilitates diagnosis of Japanese IDDM.

Adolescent↗
PubMed1996

Depression of dehydroepiandrosterone in Japanese diabetic men--comparison between non-insulin-dependent diabetes mellitus and impaired glucose tolerance.

Hyperglycemia is known to reduce dehydroepiandrosterone (DHEA) circulating levels; however, the mechanism by which hyperglycemia decreases DHEA is not elucidated. In this study, serum DHEA and DHEA sulfate (DHEA-S) levels were compared in 50 men with non-insulin-dependent diabetes mellitus (NIDDM) and 50 age-matched men with impaired glucose tolerance (IGT) receiving only diet therapy. Serum concentrations of DHEA and DHEA-S in the NIDDM group were significantly lower than in the IGT group (7.8 and 9.7 nmol/l vs 3.4 and 4.9 mumol/l, respectively; p < 0.01) but there was no significant difference in immunoreactive insulin between the two groups. When the results from both groups were combined, HbA1C was significantly inversely related to DHEA (r = -0.243, p < 0.01) and DHEA-S (r = -0.305, p < 0.01). Immunoreactive insulin showed no correlation with DHEA and DHEA-S. Multiple regression analysis showed that HbA1C was independently negatively related to both DHEA and DHEA-S. We conclude that hyperglycemia may decrease serum DHEA and DHEA-S in Japanese men with NIDDM, but the depression of DHEA(-S) is independent of serum insulin level.

Dehydroepiandrosterone↗
PubMed1996

[A case of the "shrinking lung syndrome" in SLE--improvement with corticosteroid therapy].

A 56-year-old Japanese woman had a 8-year history of systemic lupus erythematosus (SLE) with recurrent flares. When she was 48 years old, she was diagnosed as having SLE on the basis of fever, polyarthritis, oral ulcers, leukopenia, and positive anti-DNA antibody. Three years later she developed pericarditis and pleuritis, that were improved with treatment with 30 mg of prednisone a day. With tapering of prednisone dose to 9 mg a day in January 1993, she was admitted due to shortness of breath on exertion. Chest radiograph revealed bilateral elevated diaphragms and sluggish movement with clear lung field. Pulmonary function tests showed restrictive defect with a vital capacity 38% of predicted value. A diagnosis of "shrinking lung syndrome" was made. Simultaneously, blood test revealed leukopenia, elevated red cell sedimentation rate, and elevated anti-DNA antibody titer. Therefore, we suspected this pulmonary involvement was related to lupus flare-up. Treatment with 20 mg of prednisone a day resulted in resolution of the patient's dyspnea and in improvement of her vital capacity. Corticosteroid therapy for acute "shrinking lung syndrome" in active SLE can improve symptoms and pulmonary function.

Acute Disease↗
PubMed1996

Differentiation of receptive fields in the sensory cortex following stimulation of various nerves of the lower limb in humans: a magnetoencephalographic study.

The authors investigated magnetoencephalography following stimulation of the posterior tibial (PT) and sural (SU) nerves at the ankle, the peroneal nerve (PE) at the knee, and the femoral nerve (FE) overlying the inguinal ligament in seven normal subjects (14 limbs) and confirmed its usefulness in clarifying the detailed differentiation of the receptive fields in the lower limb area of the primary sensory cortex in humans. The results were summarized as follows: 1) the equivalent current dipoles (ECDs) estimated by the magnetic fields following stimulation of the PT and SU were located very close to each other, along the interhemispheric fissure in all 14 limbs. They were directed horizontally to the hemisphere ipsilateral to the stimulated nerve. 2) The ECD following stimulation of the FE was clearly different from that seen in the other nerves, in terms of the location and/or direction, in all 14 limbs. The ECDs of 14 limbs were classified into two types according to the distance of ECD location between PT and FE; Type 1 (> 1 cm, nine limbs) and Type 2 (< 1 cm, five limbs). The ECD following FE stimulation was located on the crown of the postcentral gyrus or at the edge of the interhemispheric fissure in Type 1 and was close to the ECDs following PT and SU stimulation along the interhemispheric fissure in Type 2. 3) The ECD following PE stimulation was located along the interhemispheric fissure in all 14 limbs as for PT and SU. Its location was slightly but significantly higher than that of PT and SU in Type 1 and was close to ECDs following PT and SU stimulation in Type 2. The present findings indicated that approximately 65% (nine of 14) of the limbs showed the particular receptive fields compatible with the homunculus. Large inter- and the intraindividual (left-right) differences found in the present study indicated a significant anatomical variation in the area of the lower limb in the sensory cortex of humans.

Adult↗
PubMed1996

Transforming and differentiation-inducing potential of constitutively activated c-kit mutant genes in the IC-2 murine interleukin-3-dependent mast cell line.

Two mutations of c-kit receptor tyrosine kinase (KIT), valine-559 to glycine (G559) and aspartic acid-814 to valine (V814), resulted in its constitutive activation. To examine the transforming and differentiation-inducing potential of the mutant KIT, we used the murine interleukin-3-dependent IC-2 mast cell line as a transfectant. The IC-2 cells contained few basophilic granules and did not express KIT on the surface. The KITG559 or KITV814 gene was introduced into IC-2 cells using a retroviral vector. KITG559 and KITV814 expressed in IC-2 cells were constitutively phosphorylated on tyrosine and demonstrated kinase activity in the absence of stem cell factor, which is a ligand for KIT. IC-2 cells expressing either KITG559 or KITV814 (IC-2G559 or IC-2V814 cells) showed factor-independent growth in suspension culture and produced tumors in nude athymic mice. In addition, IC-2G559 and IC-2V814 cells showed a more mature phenotype compared with the phenotype of the original IC-2 cells, especially after transplantation into nude mice. The number of basophilic granules and the content of histamine increased remarkably. KITG559 and KITV814 also influenced the transcriptional phenotype of mouse mast cell proteases (MMCP) in IC-2 cells. The expression of MMCP-2, MMCP-4, and MMCP-6 was much greater in IC-2G559 and IC-2V814 cells than in the original IC-2 cells. The results indicated that constitutively activated KIT had not only oncogenic activity but also differentiation-inducing activity in mast cells.

Animals↗