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Biomedical subjects

S Shimada

Publications and source records attributed to S Shimada.

At least 217 records · Page 12Linked to original sources

Home mechanical ventilation in the aftermath of the Hanshin-Awaji earthquake disaster.

Children who were dependent upon home mechanical ventilation (HMV), suffered in various ways from the disastrous Hanshin-Awaji earthquake disaster. The earthquake abruptly cut the supplies of water, gas and electricity, causing intense anxiety for those families. Through loss of the respirator function, some of them experienced an unexpected catastrophe. In the disaster area, there were children who were dependent upon HMV (19 cases) and children who were preparing for HMV in hospitals (nine cases). Information was gathered from questionnaires about the disaster, communication and correspondence with families. None of the 28 cases died or were injured. Nineteen cases had a variety of problems. In eight cases, respiratory support problems were acute. Nevertheless, all of them survived the crisis successfully even in the midst of such a catastrophic situation. An organization of HMV children's families, called the Baku-Baku Club, helped families with HMV problems by supplying water, food, oxygen and compressed air cylinders among other things. Additional outside batteries for portable respirators are essential equipment for HMV, especially for emergencies. A manual for clarifying the system for support in the Baku-Baku Club and a registration system for public medical service should be established in preparation for such a crisis.

Child↗

Expression of endotoxic activities by synthetic monosaccharide lipid A analogs with alkyl-branched acyl substituents.

Synthetic monosaccharide lipid A analogs with alkyl-branched acyl substituents instead of the usual ester-branched acyl substituents were investigated for their biological activities. The activities were compared with those of a representative synthetic monosaccharide lipid A analog with an ester branch (GLA-60) and synthetic complete lipid A (506) to estimate the role of the attaching mode of the branched side chains for expression of endotoxic activities. Among the analogs with alkyl branches, GLA-146 and GLA-147, which have C12 and C14 alkyl side chains, respectively, showed strong endotoxic activities. These analogs exhibited comparable or stronger activities than those of GLA-60 in murine macrophage activation activities to induce mediators such as tumor necrosis factors, interleukin 6, and nitric oxide and in mitogenic activity towards murine spleen cells; however, these activities were weaker than the respective activities of 506. With respect to lethal toxicity to galactosamine-sensitized mice, the analogs showed stronger activity than that of GLA-60 and activity closer to that of 506. With respect to adjuvant activity, no significant activity was observed in the analogs, while the activities of GLA-60 and 506 were strong. When lipopolysaccharide-resistant C3H/HeJ mice were used, the activities described above were not observed either for the analogs under investigation nor for GLA-60 and 506. These findings indicate that the ester type of branch in lipid A and its analogs does not play an indispensable role in the expression of various endotoxic activities. However, it may play some role in the expression of adjuvant activity and in lowering the level of toxicity.

Adjuvants, Immunologic↗

Primary cutaneous CD30(Ki-1)-positive lymphoma of non-T, non-B origin.

A 71-year-old Japanese woman had two dome-shaped tumors on her right buttock with several surrounding papules. Histological examination revealed that large anaplastic cells and atypical lymphoid cells densely infiltrated the entire dermis. On immunohistochemical examination, Ki-1, HLA-DR, CD25 (IL-2 receptor alpha), CD122 (IL-2 receptor beta), CD4, CD11c and CD68 were all positive in the tumor cells, whereas CD1a, CD3, CD5, CD8 and CD19 were negative. Neither rearrangement of the T-cell receptor beta, T-cell receptor gamma nor the immunoglobulin heavy-chain was seen. Ultrastructurally, most of the tumor cells contained thick bundles of intermediate filaments in the perinuclear cytoplasm. Thus, this patient was diagnosed as having Ki-1-positive lymphoma of non-T, non-B origin. No recurrence or metastasis of the tumor has been observed in the last 2 years, although surgical resection was required 3 times before control was achieved.

Aged↗

Localization and rapid regulation of Na+/myo-inositol cotransporter in rat kidney.

myo-inositol, a major compatible osmolyte in renal medulla, is accumulated in several kinds of cells under hypertonic conditions via Na+/myo-inositol cotransporter (SMIT). To investigate the physiological role of the SMIT, we sought to determine its localization by in situ hybridization and its acute regulation by NaCl and furosemide administration. Northern analysis demonstrated that SMIT is strongly expressed in the medulla and at low levels in the cortex of kidney. Intraperitoneal injection of NaCl rapidly induced SMIT mRNA in both the cortex and medulla, and furosemide completely abolished this induction. In situ hybridization revealed that SMIT it predominantly present in the medullary and cortical thick ascending limbs of Henle's loop (TALH) and macula densa cells. Less intense signals were seen in the inner medullary collecting ducts (IMCD). NaCl loading increased the signals throughout the TALH, and furosemide reduced the signals. SMIT in the IMCD is less sensitive to these kinds of acute regulation. Thus, the distribution pattern of SMIT does not correspond to the corticomedullary osmotic gradient, and SMIT in the TALH and macula densa cells is regulated very rapidly. These results suggest that SMIT expression in TALH may be regulated by intracellular and/or peritubular tonicity close to the basolateral membrane, which is supposed to be proportional to the magnitude of NaCl reabsorption.

Animals↗

Atrial natriuretic peptide and antihypertensive action due to beta-blockade in essential hypertensive patients.

The effects of beta-blocker treatment on hemodynamics were studied in relation to plasma atrial natriuretic peptide (ANP) levels in 17 outpatients with essential hypertension. Administration of propranolol for twelve weeks to untreated subjects resulted in a significant (P < 0.001) rise in plasma ANP levels (from 37.9 +/- 21.2 to 66.7 +/- 46.2 pg/mL, mean +/- SD). Systolic and diastolic blood pressures were significantly decreased (P < 0.05 and P < 0.01, respectively). Heart rate was also significantly decreased (P < 0.001). On the other hand, a significant reduction of cardiac index was detected (from 4.12 +/- 1.34 to 2.96 +/- 0.75 L/min/m2, P < 0.01) with chronic administration of propranolol, suggesting a reflection of decreased cardiac function. A significant negative correlation was observed between %changes in systolic blood pressure and %changes in plasma ANP (r = -0.594, P < 0.05). These results suggest that the increased plasma ANP levels may contribute to the antihypertensive effect with propranolol.

Adrenergic beta-Antagonists↗

Inactivation of (1-->3)-beta-D-glucan in mice.

Intraperitoneally or intravenously administered (1-->3)-beta-D-glucan remained in the liver and spleen, for a long time without major structural changes, but the priming activity to lipopolysaccharide (LPS)-triggered tumor necrosis factor-alpha (TNF-alpha) production was reduced more quickly. The relationship between the deposited glucan contents and the antitumor activity was examined by comparing kinetics of the activity using solid form Sarcoma 180 tumor in ICR mice. We used three kinds of soluble glucans, sonifilan (SPG), grifolan (GRN), and SSG, and a particulate glucan, zymosan (ZYM). These were administered 5 weeks before (-5W) the tumor inoculation and the tumor weight was compared 5 weeks after the inoculation. Compared with the activity of those administered at the optimum timing, all of the glucans reduced the activity about 5 fold, although significant activity still remained, especially in the case of SPG. Five weeks after intraperitoneal (SPG, GRN, SSG) or intravenous (ZYM) administration of the glucans, all were found in the liver and spleen in significant quantities. These facts strongly suggested that the activity of the glucan was reduced not only because of chemical/physical degradation but also a certain physiological inactivation mechanism.

Animals↗

Gene structure and glial expression of the glycine transporter GlyT1 in embryonic and adult rodents.

Na+/Cl(-)-dependent glycine transporters are crucial for the termination of neurotransmission at glycinergic synapses. Two different glycine transporter genes, GlyT1 and GlyT2, have been described. Several isoforms differing in their 5' ends originate from the GlyT1 gene. We have determined the genomic structure of the murine GlyT1 gene to elucidate the genetic basis underlying the different isoforms. Analysis of cDNA 5'-ends revealed that the GlyT1a and 1b/1c mRNAs are transcribed from two different promoters. During murine embryonic development GlyT1 mRNAs were detectable by RNase protection assays as early as embryonic day E9 and reached maximal levels between E13 and E15. In situ hybridization revealed GlyT1 expression in the developing spinal cord mainly in the ventral part of the ventricular zone at E12. At later stages (E15) transcripts were also found in the lateral half of the basal and intermediate gray matter. In contrast, the second glycine transporter gene GlyT2 displayed a completely different expression pattern. At E11 it is expressed in the mantle zone, and at later stages throughout the ventral horns. In the adult rat brain and spinal cord, GlyT1 hybridization signals were found exclusively in glial cells. Our data indicate that GlyT1 is an early marker of neural development and encodes glia-specific transporter proteins.

Amino Acid Sequence↗

Early detection of pancreatic glucagonoma.

Glucagonoma is a rare islet cell tumor of pancreas. Only 122 proven cases have been reported in the English literature so far. Diagnosis of glucagonoma has usually been delayed. The average size of clinically detected glucagonomas was 5.8 cm, and 54.7% of them exhibited metastasis. We describe the case of a 0.7-cm asymptomatic pancreatic glucagonoma. A 45-yr-old female was demonstrated to have a demarcated, small, low echoic mass in the pancreatic head by routine ultrasonography. Table incremental dynamic computed tomography showed a small well-enhanced mass recognized only in an early phase. A 0.7 x 0.7 cm firm nodule on the pancreatic head was excised at operation. Immunohistochemical and ultrastructural studies revealed that this tumor was a glucagon-producing adenoma. This may be the smallest glucagonoma detected by image diagnostics that has been reported in the English literature. Possible early detection of glucagonoma was discussed in this report.

Female↗

[The pharmacokinetics of the glycyrrhizin and glycyrrhetic acid after intravenous administration of glycyrrhizin for the patients with chronic liver disease caused by type C hepatitis virus].

Glycyrrhizin had been used widely for the patients with chronic liver disease. We examined the pharmacokinetics of the glycyrrhizin and glycyrrhetic acid in the blood stream after intra-venous administration of glycyrrhizin. The stream concentration of glycyrrhizin in the patients of liver cirrhosis tend to be kept higher than that of chronic hepatitis but there were no significant difference between them except for after a half hour from the administration. There was negative correlation between ICG R15 and the speed of excretion of glycyrrhizin from the serum. On the other hand, the concentration of the glycyrrhetic acid was kept higher in the patients with liver cirrhosis than that of chronic hepatitis, but there were no significant difference between them except for after a half hour from the administration. These findings suggested that the accumulation of glycyrrhizin and glycyrrhetic acid in the patients of liver cirrhosis can be seen by long term administration.

Aged↗

Molecular cloning and characterization of the complementary DNA of an M(r) 110,000 antigen expressed by human gastric carcinoma cells and upregulated by gamma-interferon.

An M(r) 110,000 antigen was initially described in human gastric carcinoma cells by its cross-reactivity with anti-carcinoembryonic antigen (CEA) monoclonal antibodies, as well as the ability of gamma-interferon to increase its level of expression. We describe the molecular cloning and sequence analyses of overlapping clones that constitute a full-length complementary DNA that encodes for the entire M(r) 110,000 molecule. The 1.5-kilobase message encodes for a 407-amino acid polypeptide whose structural analysis was consistent with an integral membrane glycoprotein. In particular, the extracellular domain was rich in serine and threonine residues at which carbohydrate substitution is likely through O- and N-linked glycosylation. This would explain the higher molecular weight of the antigen whose polypeptide backbone is approximately M(r) 42,000. Further computer-aided sequence analyses revealed no significant homology with any member of the CEA gene family. The cross-reactivity with anti-CEA monoclonal antibodies may be explained by the presence of CEA and normal cross-reacting antigen homologous sites proximal to the transmembrane region. No sequence homology was found with any known protein. Thus, the M(r) 110,000 molecule represents a potentially novel cell membrane glycoprotein whose possible role in human cancer and/or as a gamma-interferon-inducible gene product warrants further investigation.

Amino Acid Sequence↗

Genes for members of the GATA-binding protein family (GATA-GT1 and GATA-GT2) together with H+/K(+)-ATPase are specifically transcribed in gastric parietal cells.

mRNAs for novel DNA-binding proteins (GATA-GT1 and GATA-GT2) recognizing the (G/C)PuPu(G/C)NGAT(A/T)PuPy sequence and H+/K(+)-ATPase (proton pump) alpha subunit were detected in parietal cells of the rat gastric body mucosa by in situ hybridization. These results suggest that GATA-GT1 and GATA-GT2 together with H+/K(+)-ATPase are transcribed specifically in gastric parietal cells and that the two DNA-binding proteins may have important roles in cell specific gene regulation. Furthermore, we could detect parietal cells in different states of gene expression.

Animals↗

Preferential usage of the Fc receptor gamma chain in the T cell antigen receptor complex by gamma/delta T cells localized in epithelia.

zeta and eta chains of the T cell antigen receptor (TCR) complex and the gamma chain of Fc receptors (FcR gamma) constitute a family of proteins important for the expression of, and signal transduction through, these receptors in hematopoietic cells. In zeta-deficient mice, TCR expression was reduced in most T cells. By contrast, CD8 alpha alpha + TCR-gamma/delta + intestinal intraepithelial lymphocytes in these mice expressed a normal level of TCR. Biochemical analysis of the TCR complex in these cells from zeta-deficient as well as normal mice revealed the predominant usage of FcR gamma. Furthermore, gamma/delta + T cells in epithelia of the skin and female reproductive organs from zeta-deficient mice also showed relatively high TCR expression, indicating the usage of FcR gamma. These observations demonstrate the preferential usage of FcR gamma by gamma/delta + T cells localized in epithelia of normal mice.

Animals↗

Marked increase in glutamate-aspartate transporter (GLAST/GluT-1) mRNA following transient retinal ischemia.

We have demonstrated the cellular localization of glutamate-aspartate transporter (GLAST/GluT-1) mRNA in the rat retina and its induction after ischemia by in situ hybridization. GLAST mRNA was expressed in the inner two-thirds of the inner nuclear layer (INL) and in sparse small cells in the inner portion of the ganglion cell layer (GCL) of the adult rat retina. GLAST mRNA was also found in about 90% of cells in the optic nerve head where more than 90% of cells express glial fibrillary acidic protein (GFAP) mRNA. Moreover, experimental occlusion of the central retinal artery followed by reperfusion for 48 h resulted in degeneration of neurons and a marked increase in GLAST mRNA expression in the INL. These findings suggest that GLAST may be expressed in Müller cells and astrocytes in the retina, and may play an important role in regulation of extracellular glutamate concentration especially under ischemic conditions.

Amino Acid Transport System X-AG↗

Distribution of cocaine recognition sites in rat brain: in vitro and ex vivo autoradiography with [125I]RTI-55.

The distribution of binding sites of [125I]RTI-55 (3 beta-(4-iodophenyl)tropan-2 beta-carboxylic acid methyl ester), a phenyl tropane analog of cocaine, and the selective labeling of the dopamine transporter (DAT) were studied by in vitro and ex vivo autoradiography in the rat whole brain. Recent evidence has shown that RTI-55 binds to not only DAT but also serotonin transporter (5HTT). In the present study, in vitro autoradiography revealed that [125I]RTI-55 bound to the olfactory tubercle, the caudate putamen, the accumbens nucleus, the midline and lateral geniculate nuclei of the thalamus, the hypothalamic nuclei, the substantia nigra compact part, the subthalamic nucleus, the ventral tegmental area, the superior colliculus, the dorsal raphe nucleus, and the facial nucleus. Further, in the presence of clomipramine, a selective ligand for 5HTT, [125I]RTI-55 binding was remarkably inhibited in the midline and lateral geniculate nuclei of the thalamus, the hypothalamic nuclei, the superior colliculus, the dorsal raphe nucleus, and the facial nucleus, while [125I]RTI-55 binding remained in the olfactory tubercle, the caudate putamen, the accumbens nucleus, the substantia nigra compact part, the subthalamic nucleus, and the ventral tegmental area. These findings suggest that [125I]RTI-55 binds to 5HTT in the former areas and to DAT in the latter areas. It is therefore concluded that RTI-55 is a suitable ligand for studying the action of cocaine in whole brain regions, including the thalamus, the hypothalamus and the dorsal raphe nucleus, regions in which cocaine is thought to act evoking several neurological effects, e.g., analgesia and elevation of adrenocorticotropic hormone. DAT was also labelled selectively both in vitro and in vivo using [125I]RTI-55 combined with clomipramine. Therefore, radiolabelled RTI-55, combined with unlabelled clomipramine, which displaces its binding to 5HTT, also appears to be suitable for the selective imaging of DAT in vivo.

Animals↗

Effects of patent ductus arteriosus on left ventricular output and organ blood flows in preterm infants with respiratory distress syndrome treated with surfactant.

Thirty preterm infants (birth weight < 1500 gm) treated with Surfactant TA for the respiratory distress syndrome, who had no complicating clinical problems other than ductal patency, were studied by serial Doppler flow examinations to determine the effects of early left-to-right shunt through the patent ductus arteriosus on the left ventricular output and organ blood flows. Doppler flow variables in 15 infants with a hemodynamically significant patent ductus arteriosus (hsPDA) were compared with those in 15 subjects without hsPDA matched for age, body weight, and gestational age. Infants with hsPDA had significantly higher left ventricular output and significantly lower blood flow volume in the abdominal aorta, and lower temporal mean blood flow velocities, with concomitant increases in the relative vascular resistance in the celiac artery, superior mesenteric artery, and renal artery. Pulsatility indexes of these vessels and the anterior cerebral artery were significantly higher in the hsPDA group, but the temporal mean blood flow velocities in the anterior cerebral artery and its vascular resistance were not significantly different between the two groups. After closure of the patent ductus arterious was achieved with mefenamic acid therapy, alterations in Doppler flow variables in the hsPDA group reverted to the levels seen in the group without hsPDA. These results suggest that despite large left-to-right ductal shunting, the heart of the preterm infant is capable of mounting a compensatory increase of cardiac output sufficient to maintain unchanged cerebral blood flow, but is unable to maintain postductal organ blood flows because of decreased perfusion pressure (ductal steal) and localized increase in vascular resistance.

Blood Flow Velocity↗

Cortical expression of the human angiotensinogen gene in the kidney of transgenic mice.

We have previously generated "Tsukuba hypertensive mice" with elevated blood pressure by cross-mating separate lines of transgenic animals carrying either 15 kb of the human renin gene including its native 3-kb promoter or 14 kb of the human angiotensinogen gene along with its 1.3-kb promoter, the former of which is expressed predominantly in the kidney and the latter of which is also expressed in the kidney to levels comparable to those found in the liver. To investigate whether the integrated human angiotensinogen gene is prominently expressed in the kidney of transgenic mice, we have analyzed a production region of the transgene mRNA by in situ hybridization technique. This analysis clearly demonstrated that human angiotensinogen mRNA is localized specifically to the cortex region of transgenic mouse kidney. The present finding indicates a possible involvement of the renal renin-angiotensin system in the pathogenesis of high blood pressure in transgenic mice.

Angiotensinogen↗

Bilateral periorbital eccrine hidrocystoma.

We saw four patients showing identical features as cystic lesions on the bilateral external canthi. Histological examination showed cystic cavities in the dermis. Histological and enzyme histochemical findings suggest that these cystic tumors are of eccrine origin. Thus we diagnosed these cystic tumors as eccrine hidrocystoma with characteristic clinical feature. The recognition of this feature would help to correctly diagnose these eccrine hidrocystoma.

Adult↗

T cell receptor expression by dendritic epidermal T cells.

Dendritic epidermal T cells (DETC) in murine epidermis express the gamma delta T cell receptor (TCR). The major population of DETC utilize V gamma 5 and V delta 1 without any junctional diversity, corresponding to the earliest fetal thymocytes which express TCR gamma delta. Using PCR, we recently found another population of DETC which express V gamma 1-V delta 6 with junctional diversity in addition to V gamma 5-V delta 1, although they exist in small numbers in normal mice. In athymic nude mice, V gamma 1+ cells also exist. Therefore, this subset of gamma delta T cells is the product of an extrathymic pathway. These V gamma 1+ cells may recognize mycobacterium antigen or heat shock protein (HSP), thus playing an important role in the first defense of the skin. In contrast to normal mice, in nude mice, we could not detect any DETC using anti CD3 epsilon antibody (2C11). In order to solve this puzzle, we examined the components of TCR complex utilizing immunoprecipitation and northern blot analysis. TCR is composed of either alpha beta or gamma delta chains associated with CD3 gamma, delta, epsilon and zeta-zeta chains. By immunoprecipitation of 125I labelled DETC cell lines using anti-CD3 epsilon antibody, we detected gamma delta chains and CD3 gamma and CD3 epsilon chains, but not CD3 delta or CD3 zeta chains. Northern blot analysis showed that these cells express CD3 gamma, epsilon, and zeta chains, but not the CD3 delta chain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗