Biomedical subjects

S Ohno

Publications and source records attributed to S Ohno.

At least 307 records · Page 17Linked to original sources

PubMed1998

Analysis of ictal EEGs of epilepsy associated with tuberous sclerosis.

PURPOSE: To investigate the significance of cortical pathology of tonic spasms in patients with tuberous sclerosis. METHODS: The subjects were 38 patients with epilepsy associated with tuberous sclerosis. We analyzed ictal EEGs of tonic spasms and partial seizures by means of video-EEG monitoring for a total of 763 tonic spasms in 20 patients and 107 partial seizures in 15 patients. We also investigated the relation between partial seizures and magnetic resonance imaging (MRI) findings of these patients. RESULTS: Ictal EEG patterns of tonic spasms were divided into generalized and focal patterns. Thirteen patients had only generalized patterns, whereas seven had both patterns. In five patients who had focal ictal patterns of tonic spasms and partial seizures, the location of focal patterns corresponded with the location of onset of partial seizures. Focal discharges were seen immediately before, after, and in the middle of tonic spasms in series in 13 patients. The location of focal discharges also corresponded with the location of the onset of partial seizures in 10 of the 13 patients. Regarding partial seizures, four patients had multiple active epileptogenic foci during the same period, and two others had shifting epileptogenic foci with increasing age. CONCLUSIONS: These findings indicate that cortical pathology plays an important role in the occurrence not only of partial seizures but also of tonic spasms in patients with tuberous sclerosis.

Adult↗

PubMed1998

Requirement of atypical protein kinase clambda for insulin stimulation of glucose uptake but not for Akt activation in 3T3-L1 adipocytes.

Phosphoinositide (PI) 3-kinase contributes to a wide variety of biological actions, including insulin stimulation of glucose transport in adipocytes. Both Akt (protein kinase B), a serine-threonine kinase with a pleckstrin homology domain, and atypical isoforms of protein kinase C (PKCzeta and PKClambda) have been implicated as downstream effectors of PI 3-kinase. Endogenous or transfected PKClambda in 3T3-L1 adipocytes or CHO cells has now been shown to be activated by insulin in a manner sensitive to inhibitors of PI 3-kinase (wortmannin and a dominant negative mutant of PI 3-kinase). Overexpression of kinase-deficient mutants of PKClambda (lambdaKD or lambdaDeltaNKD), achieved with the use of adenovirus-mediated gene transfer, resulted in inhibition of insulin activation of PKClambda, indicating that these mutants exert dominant negative effects. Insulin-stimulated glucose uptake and translocation of the glucose transporter GLUT4 to the plasma membrane, but not growth hormone- or hyperosmolarity-induced glucose uptake, were inhibited by lambdaKD or lambdaDeltaNKD in a dose-dependent manner. The maximal inhibition of insulin-induced glucose uptake achieved by the dominant negative mutants of PKClambda was approximately 50 to 60%. These mutants did not inhibit insulin-induced activation of Akt. A PKClambda mutant that lacks the pseudosubstrate domain (lambdaDeltaPD) exhibited markedly increased kinase activity relative to that of the wild-type enzyme, and expression of lambdaDeltaPD in quiescent 3T3-L1 adipocytes resulted in the stimulation of glucose uptake and translocation of GLUT4 but not in the activation of Akt. Furthermore, overexpression of an Akt mutant in which the phosphorylation sites targeted by growth factors are replaced by alanine resulted in inhibition of insulin-induced activation of Akt but not of PKClambda. These results suggest that insulin-elicited signals that pass through PI 3-kinase subsequently diverge into at least two independent pathways, an Akt pathway and a PKClambda pathway, and that the latter pathway contributes, at least in part, to insulin stimulation of glucose uptake in 3T3-L1 adipocytes.

3T3 Cells↗

PubMed1998

Systemic and local immunological features of atopic dermatitis patients with ocular complications.

AIMS: Clinical factors and data from recent cases of atopic dermatitis (AD) (with or without ocular complications) and non-AD cases were examined to evaluate the mechanism of atopic ocular complications. METHODS: IgE-RAST for eight allergens including rice, egg, and mite and serum total IgE were measured in 216 patients with AD (70 ocular type, 146 non-ocular type) and 69 non-AD individuals. Tear histamine and leukotriene B4 (LTB4) levels were also measured. RESULTS: The serum levels of IgE were significantly increased in AD patients with ocular complications compared with those without ocular complications. The positive rates of IgE-RAST for rice and wheat were significantly higher in ocular type AD than in non-ocular type AD. In ocular type AD, serum IgE was significantly increased in patients with cataract compared with that in those without cataract. Tear histamine and LTB4 levels in AD patients with ocular complications showed significant elevations compared with those in patients with pure AD and controls. CONCLUSIONS: These results suggest that ocular type AD belongs to the most severe end of the spectrum of AD, and that some food antigens may contribute to the pathogenesis of severe AD resulting in ocular complications.

Adolescent↗

PubMed1998

Effects of inhalation of nitroglycerin on hypoxic pulmonary vasoconstriction.

Recent studies suggest that nitric oxide (NO) may play an important role in the pathophysiology of pulmonary hypertension. Nitroglycerin is metabolized to NO, which is a potent vascular smooth muscle relaxant. The aim of the present study was to compare the effects of inhaled and infused nitroglycerin on pulmonary hemodynamics and gas exchange in anesthetized, artificially ventilated dogs. Nitroglycerin was administrated either by inhalation or by infusion. Systemic blood pressure (SBP), pulmonary arterial pressure (PAP), and pulmonary capillary wedge pressure (PCWP) were measured, and cardiac output was estimated by an electromagnetic flowmeter. Blood gas measurements were performed during hypoxic gas exposure (FiO2; 0.1) with a continuous inhalation or infusion of nitroglycerin (1, 2.5 micrograms/kg/min). Inhaled (n = 4) and infused (n = 4) nitroglycerin (1 microgram/kg/min) did not produce any detectable effects on the hemodynamics. Inhaled nitroglycerin (2.5 micrograms/kg/min) reduced SBP, PAP and calculated pulmonary vascular resistance (PVR) in all dogs. Cardiac output did not change. In addition, inhaled nitroglycerin increased PaO2. In contrast, the continuous infusion of nitroglycerin (2.5 micrograms/kg/min) did not change in PAP, whereas infused nitroglycerin decreased the mean SBP. Infused nitroglycerin did not alter cardiac output and calculated PVR. A decreased PaO2 was noted in 2 dogs on nitroglycerin infusion. These findings indicate that inhaled nitroglycerin effects the pulmonary circulation relatively more than infused nitroglycerin, which tends to have more of a general effect on the systemic circulation. The effects of inhaled nitroglycerin may thus be comparable to the effects of NO inhalation.

Administration, Inhalation↗

PubMed1998

Ultrastructural study of anionic sites in glomerular basement membranes at different perfusion pressures by quick-freezing and deep-etching method.

The ultrastructures of anionic sites in rat glomerular basement membranes (GBM) were studied at different perfusion pressures of 100, 150, 200 or 250 cm H2O by a quick-freezing and deep-etching (QF-DE) method, in addition to conventional fixation methods, using polyethyleneimine (PEI) as a cationic tracer. By the QF-DE method, three-dimensional ultrastructures at each pressure were observed more clearly than those seen on conventional ultrathin sections. When the perfusion pressures were changed from low levels to higher ones, the total thickness of GBM with anionic sites became gradually thinner. Many PEI particles were observed around filaments, not only in the laminae lucidae, but also in the lamina densa. These findings indicated the existence of anionic sites in both laminae lucidae and lamina densa of GBM. The numbers of PEI particles in the lamina rara externa were counted on conventional ultrathin sections for morphometric analyses. The numbers per unit length of GBM were significantly decreased at higher perfusion pressures (200 and 250 cm H2O) than those seen at both normal (150 cm H2O) and lower (100 cm H2O) pressures. It is concluded that the ultrastructures of anionic sites in the GBM may be changed in vivo, depending on the hemodynamics in the glomerular capillary.

Animals↗

PubMed1998

Beta-dystroglycan localization in the photoreceptor and Müller cells in the rat retina revealed by immunoelectron microscopy.

beta-Dystroglycan (beta-DG) is a dystrophin-associated glycoprotein that is expressed in skeletal muscle and other tissues. In the retina, dystrophin is present in the outer plexiform layer (OPL), where it is enriched under the photoreceptor cell membrane. In this study we determined the immunocytochemical localization of beta-DG at both light and electron microscopic levels. beta-DG immunoreactivity was detected at the inner limiting membrane, OPL, and around blood vessels. Immunoelectron microscopy detected beta-DG immunoreactive products under the photoreceptor cell membrane, which are the same regions of dystrophin localization. In addition, beta-DG was detected under the Müller cell membrane that is attached to the paravitreous or perivascular basement membrane. Our results suggest that beta-DG may interact with dystrophin in photoreceptor membranes. However, beta-DG-related interactions between Müller cells and basement membranes appear to be independent of dystrophin and raise the possibility that beta-DG interacts with other molecules. We speculate that beta-DG plays a role in maintaining the structural relationship between photoreceptor and bipolar cells or between Müller cells and basement membranes.

Amino Acid Sequence↗

PubMed1998

Atypical protein kinase C cooperates with PAR-3 to establish embryonic polarity in Caenorhabditis elegans.

Asymmetric cell divisions, critically important to specify cell types in the development of multicellular organisms, require polarized distribution of cytoplasmic components and the proper alignment of the mitotic apparatus. In Caenorhabditis elegans, the maternally expressed protein, PAR-3, is localized to one pole of asymmetrically dividing blastomeres and is required for these asymmetric divisions. In this paper, we report that an atypical protein kinase C (PKC-3) is essential for proper asymmetric cell divisions and co-localizes with PAR-3. Embryos depleted of PKC-3 by RNA interference die showing Par-like phenotypes including defects in early asymmetric divisions and mislocalized germline-specific granules (P granules). The defective phenotypes of PKC-3-depleted embryos are similar to those exhibited by mutants for par-3 and another par gene, par-6. Direct interaction of PKC-3 with PAR-3 is shown by in vitro binding analysis. This result is reinforced by the observation that PKC-3 and PAR-3 co-localize in vivo. Furthermore, PKC-3 and PAR-3 show mutual dependence on each other and on three of the other par genes for their localization. We conclude that PKC-3 plays an indispensable role in establishing embryonic polarity through interaction with PAR-3.

Animals↗

PubMed1998

Quantitative detection of anionic sites in rat femoral cartilage using cationic colloidal gold at low pH levels.

Quantitative analyses of anionic sites in the rat cartilage were performed by using post-embedding LR-Gold method with cationic colloidal gold (CCG) at different pH levels. Alteration of the pH levels affected the CCG staining patterns. The CCG particles were more observed at low pH levels, 1.0 and 2.5, than those at high pH 7.4. So, we quantitatively examined the superficial, intermediate and deep layers at pH 1.0. Morphometric analyses showed that CCG particles were increased from the superficial layer to the deep layer in both pericellular matrix (PM) and interterritorial matrix (IM). Moreover, they were more observed in PM than in IM. After chondroitinase ABC digestion, the CCG labeling was reduced in all matrices of the superficial and intermediate layers, though many CCG particles were still observed in PM of the deep layer. After hyaluronidase digestion, the CCG labeling was markedly reduced in the PM of the deep layer. These findings suggest that anionic sites in the cartilage matrix are detected by using the CCG only at low pH levels. In addition, the PM in the deep layer may consist of different components from those of the other two layers.

Animals↗

PubMed1998

Morphological studies of glomeruli in obstructive kidneys by confocal laser scanning microscopy and quick-freezing replica method.

Morphological changes of glomeruli in obstructive kidneys were studied by using confocal laser scanning microscopy (CLSM), and quick-freezing and deep-etching (QF-DE) method. Twenty-one rabbits were divided into three groups, consisting of control, 6-hr bilateral ureteral obstruction (BUO) and 24-hr BUO. In the experimental groups, the attenuation of cell bodies, the lengthening and stretching of major processes, the cystic formation in the cytoplasm and the fusion of foot processes were observed on conventional ultrathin sections. These changes in the 24-hr BUO group were more clearly observed than those in the 6-hr BUO group. By the CLSM, cell bodies and foot processes of podocytes in the experimental groups were more intensely immunostained with anti-alpha-tubulin antibody and phalloidin-FITC. By the QF-DE method, cytoskeletons in the podocyte cell bodies and major processes were composed of numerous intermediate filaments, but distinct changes of actin filaments and microtubules were not observed in the control and experimental groups. Considering the physiological changes in BUO, the mechanical stress appeared to be brought about by hemodynamic factors rather than the change of intratubular pressure, resembling the morphological changes in experimental animals with hyperfiltration and the homeostatic adaptation of podocytes under the BUO condition.

Animals↗

PubMed1998

Evaluation of bronchoscopic findings in patients with metastatic pulmonary tumor.

To clarify the bronchoscopic findings in metastatic spread to the bronchi, we analyzed the records of 65 cases of metastatic pulmonary disease in which fiberoptic bronchoscopy had been done. Forty-five patients (69.2%) had abnormal bronchoscopic findings. These patients could be divided into three groups, according to bronchoscopic findings and route of metastatic spread to the bronchi: endobronchial metastasis (n=15), bronchial involvement (that is, direct extension to the bronchi from adjacent metastatic foci, n=15), and lymphangitis carcinomatosa (n=15). Breast cancer and colon cancer were common in cases of endobronchial metastasis, and the bronchial tumor often presented as a polypoid or nodular lesion covered with necrotic material. Submucosal swelling with an irregular margin and narrowing of the bronchial lumen were seen in cases of bronchial involvement. In conclusion, each type of primary extrapulmonary tumor is associated with characteristic endobronchial findings of pulmonary metastases such as endobronchial metastasis and bronchial involvement, which should be discriminated if possible, because of their different metastatic process.

Biopsy↗

PubMed1998

Episcleritis associated with pigmentary retinal degeneration in an HTLV-I carrier.

Human T-cell lymphotropic virus type I (HTLV-I) has been reported as the cause of a kind of endogenous uveitis (HTLV-I associated uveitis; HAU). We observed a case of episcleritis in a HTLV-I carrier with pigmentary retinal degeneration. HTLV-I infection might be associated with the development of episcleritis and pigmentary retinal degeneration. Patients with episcleritis or pigmentary retinal degeneration should be examined for HTLV-I infection.

Carrier State↗

PubMed1998

MICA gene polymorphisms and HLA-B27 subtypes in Japanese patients with HLA-B27-associated acute anterior uveitis.

PURPOSE: HLA-B27-associated acute anterior uveitis (HLA-B27 AAU) seems to be triggered by external factors in persons with a particular genetic background. It is still uncertain whether HLA-B27 or other gene(s) near the HLA-B region predisposes to uveitis in a linkage disequilibrium with B27. The authors investigated microsatellite polymorphism within the transmembrane region of the MICA gene, located 47 kb centromeric of the HLA-B gene, and HLA-B27 subtypes. METHODS: Seventeen HLA-B27-positive Japanese patients with HLA-B27 AAU, 51 Japanese controls, and 20 B27-positive Japanese controls were examined for MICA gene polymorphism within the transmembrane region using polymerase chain reaction (PCR) and subsequent automated fragment detection by fluorescent-based technology. Furthermore, B27-positive patients with HLA-B27 AAU and B27-positive controls were examined for HLA-B27 subtypes by the PCR-sequence-specific primer method. RESULTS: The microsatellite allele in the MICA gene, consisting of four repetitions of GCT/AGC (designated A4 allele), was present at a significantly higher phenotype frequency in the patient group (64.7%) than in the control group (25.5%) (chi 2 = 6.95, Pc = 0.042). Furthermore, the frequency of the A4 allele was significantly higher, even when compared with 20% in the B27-positive control group (chi 2 = 5.88, Pc = 0.042). The frequency of HLA-B27 subtypes was not significantly different between B27-positive patients with HLA-B27 AAU and B27-positive controls. CONCLUSIONS: These results suggest that the MICA gene itself, or other nearby gene(s), linked to the MICA A4 allele may be involved in the development of HLA-B27 AAU and that HLA-B27 subtypes are not important in the development of HLA-B27 AAU in a Japanese population.

Acute Disease↗

PubMed1998

Establishment, characterization, and chromosomal analysis of new leukemic cell lines derived from MT/p210bcr/abl transgenic mice.

The p210bcr/abl chimeric protein is implicated in the pathogenesis of Philadelphia chromosome-positive human leukemias. Previously, we generated transgenic mice expressing p210bcr/abl by the metallothionein enhancer/promoter (MT/p210bcr/abl) and observed that these mice reproducibly developed T cell leukemia. In this report, we describe the establishment, characterization, and chromosomal analysis of two novel leukemic cell lines derived from MT/p210bcr/abl leukemic mice. Both cell lines carried the transgene and showed the same gene rearrangement patterns as observed in the parental leukemic cells. Expression, tyrosine-phosphorylation, and enhanced kinase activity of the p210bcr/abl were also detected. RT-PCR/SSCP for p53 transcript revealed that one of the cell lines carried a mutation, in contrast to the normal pattern shown by the parental leukemic cells. In addition, the other cell line showed a karyotype of trisomy 15. These results suggest that the p53 mutation and chromosomal abnormality may confer a proliferative ability on leukemic cells in vitro. These new cell lines are considered to be a valuable model not only for examining the biologic properties of p210bcr/abl but also for investigating the malignant process that promotes the proliferation of the leukemic cells expressing p210bcr/abl. Furthermore, these cell lines could be used in therapeutic studies, including adoptive immunotherapy.

Animals↗

PubMed1998

Ultrastructural changes and immunocytochemical localization of microtubule-associated protein 1 in guinea pig optic nerves after acute increase in intraocular pressure.

PURPOSE: To investigate ultrastructural changes and localization of microtubule-associated protein 1 (MAP 1) in optic nerves of guinea pigs in conditions of acute increase in intraocular pressure (IOP). METHODS: Intraocular pressure was increased acutely in 40 guinea pig eyes, and 40 eyes were examined in 20 normal control animals. Analytic methods included quick-freezing and deep-etching (QF-DE) and conventional fixation. Microtubule-associated protein 1 immunocytochemistry was performed. RESULTS: In conventional ultrathin sections, an alteration of the axoplasmic ultrastructure was seen only at the level of the lamina cribrosa sclerae. The number of microtubules was significantly decreased in the axoplasm that exhibited accumulations of membranous organelles. Cross-bridged filaments on microtubules were significantly reduced in number when determined by the QF-DE method. The immunostaining of tubulin or MAP 1 was less positive than in other samples with normal IOP, revealed by light microscopic immunocytochemistry. Immunoelectron microscopy demonstrated that MAP 1 was significantly decreased in the axoplasm that showed accumulations of membranous organelles. CONCLUSIONS: The acute alteration of axoplasmic ultrastructures in some parts of the optic nerves at the level of the lamina cribrosa involves a decrease in the amount of MAP 1 and a decrease in the number of axonal cross-bridges on microtubules in a condition of acutely increased IOP, which could be related to microtubule instability and abnormal organelle transport in the axoplasm.

Acute Disease↗

PubMed1998

Increased frequencies of interleukin-2- and interferon-gamma-producing T cells in patients with active Behçet's disease.

PURPOSE: To elucidate the profile of cytokine-producing T cells in patients with active or inactive Behçet's disease (BD), the frequencies of type 1 (Interleukin- [IL] 2, interferon-gamma [IFN-gamma]) and type 2 (IL-4) cytokine-producing CD4+ and CD8+ cells in peripheral blood were investigated, and the effect of immunosuppressive drugs on the profile of cytokine-producing cells was evaluated. METHODS: Fifty-two patients with BD (32 with active and 20 with inactive BD) and 33 healthy control subjects were the subjects in this study. Patients were or were not treated with immunosuppressive drugs. Peripheral blood mononuclear cells were fixed, permeabilized, and stained for intracellular cytokines in combination with cell surface markers CD4 and CD8 for flow cytometric analysis. RESULTS: In nontreated patients with BD, the frequencies of IL-2- and IFN-gamma-producing CD4 and CD8+ cells in active patients were significantly higher than those in inactive patients. Conversely, the frequencies of IL-4 producing CD4+ and CD8+ cells in nontreated patients with active BD were comparable with those in patients with inactive disease and in control subjects. Patients with inactive BD who were treated with immunosuppressive drugs showed significantly lower frequencies of IL-2- and IFN-gamma-producing CD4+ and CD8+ cells than did treated patients with active BD. CONCLUSIONS: The frequencies of type 1 cytokine-producing CD4+ and CD8+ cells increased in patients with active BD. Effective immunosuppressive treatments decreased the population of type 1 cytokine-producing CD4+ and CD8+ cells. These results suggest that type 1 cytokine-producing cells play an important role in the immunopathogenesis of the inflammation in BD.

Adolescent↗

PubMed1998

Histochemical study on rat tear film and ocular surface epithelial cells.

PURPOSE: To investigate the histochemistry of the tear film, conjunctival goblet cells and corneal superficial epithelial cells by an in vivo cryofixation with the freeze-substitution method. METHODS: Following rapid freezing of the eyeballs by an isopentane-propane mixture cooled by liquid nitrogen directly, the specimens were freeze-substituted and then embedded in Lowicryl K4M resin at low temperature, or in epoxy resin for histochemical study, using light and transmission electron microscopy. RESULTS: The tear film was weakly positive with periodic acid-Schiff staining, but negative with alcian blue at pH 2.5 or pH 1.0 and high iron diamine staining. Conjunctival goblet cells were positively stained by all these techniques. There was a gradually weakening staining intensity of mucus from the goblet cells to the conjunctival surface. With the periodic acid-thiocarbohydrazide-silver protein method the tear film was weakly stained, while glycocalices, vesicles, glycogen in epithelial cytoplasm and the mucus secretory granules of goblet cells were all intensely stained. CONCLUSIONS: The tear film consists mainly of dilute mucus and contains either neutral or acid glycoproteins.

Acrylic Resins↗

PubMed1998

Transaxillary approach for the endoscopic extirpation of benign breast tumors.

Cosmetic factors in the treatment of breast disease have long been neglected despite the fact that patients are highly concerned about the length and extent of the incision. Recent developments in both endoscopy and endoscopic devices have now made it possible to reach breast mass(es) from small incisions in the axilla. We describe the successful extirpation of a giant fibroadenoma of the breast in a 20-year-old woman, using a 3-mm or 10-mm endoscope and a 3-mm or 5-mm endoscopic device with a transaxillary approach. A scar-free breast with an excellent cosmetic result was achieved by use of this technique and these devices. Benign tumors (both single large tumors and multiple masses) are therefore considered to be ideal candidates for this type of minimally invasive endoscopic surgery.

Adult↗

PubMed1998

Tumor angiogenesis and micrometastasis in bone marrow of patients with early gastric cancer.

In a subset of patients with early gastric cancer, there were recurrences of the disease after a curative resection had been done. Direct evidence of tumor seeding in distant organs at the time of surgery for gastric cancer is not available. An immunocytochemical assay for epithelial cytokeratin protein may fill this gap because it is a feature of epithelial cells that would not normally be present in bone marrow. From 1994-1997, the bone marrow of 45 patients with early gastric cancer was examined for tumor cells, using immunocytochemical techniques and an antibody reacting with cytokeratin, a component of the intracytoplasmic network of intermediate filaments. Intratumoral microvessels were stained with anti-CD31 monoclonal antibody. Clinicopathological characteristics were determined for subjects with cytokeratin-positive cells in the bone marrow. Of these 45 patients, 9 (20.0%) had cytokeratin-positive cells in the bone marrow at the time of primary surgery. These positive findings were not related to tumor advance-related factors of lymph node metastasis and distinct lymphatic and vascular invasion. Microvessel density in the primary tumor exceeded 2-fold in cytokeratin-positive cells, compared with findings in negative cells (P < 0.05). Tumor cells in bone marrow are indicative of the general disseminative metastasis in patients with early gastric cancer, and the metastatic potential was closely related to angiogenesis in the primary tumor.

Aged↗