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Biomedical subjects

I Tanaka

Publications and source records attributed to I Tanaka.

At least 217 records · Page 12Linked to original sources
PubMed1996

Pump neurons of the nucleus of the solitary tract project widely to the medulla.

Axonal projections of pump neurons (P-cells) of the nucleus of the solitary tract were studied in Nembutal-anesthetized, paralyzed, and artificially ventilated cats. Extracellular recordings were made from single P-cells which were monosynaptically activated by electrical stimulation of the ipsilateral vagal afferents and distributed in close proximity to the solitary tract. Antidromic stimulation of the medulla showed that all P-cells examined projected their axons to the ipsilateral ventrolateral medulla. Axonal arborizations were found in respiration-related areas and their vicinity between the level of the retrofacial nucleus and the level a few millimeters caudal to the obex. Some of these P-cells sent axon collaterals to the contralateral nucleus of the solitary tract (NTS) as well. This study is the first to show wide spread medullary projections of P-cell axons.

Afferent Pathways↗
PubMed1996

Measurement of anti-factor IX IgG subclasses in haemophilia B patients who developed inhibitors with episodes of allergic reactions to factor IX concentrates.

We have established a simple enzyme-linked immunosorbent assay (ELISA) for the detection of anti-factor IX IgG subclasses in haemophilia B patients with inhibitors. The assay was performed using immobilized purified factor IX. Specific IgG subclasses were detected by peroxidase-conjugated anti-human IgG1,2,3 and 4. Ten plasma samples from 6 haemophilia B patients with inhibitors ranging from 1.0 to 253 Bethesda Units/ml were analyzed. All samples were positive for IgG4. Six out of 10 samples were positive only for IgG4. Three samples were positive for IgG2. Five of the 6 patients had previously had allergic reactions to factor IX concentrates. Three patients had allergic episodes within the past month. Three samples from these latter patients taken on the day when the allergy had occurred showed positive also for IgG1. In later samples, however, taken at 4 days and 4 weeks respectively from two of these same patients. IgG1 was not detected. In two of the five patients in whom allergic reactions had occurred more than one month previously IgG1 was not detected. The results suggested that allergic reactions in patients with haemophilia B treated with factor IX concentrates were associated with the development of the specific IgG1 subclass of antibody to factor IX.

Adolescent↗
PubMed1996

Crystal structure of macrophage migration inhibitory factor from human lymphocyte at 2.1 A resolution.

The three-dimensional structure of the macrophage migration inhibitory factor (MIF) from human lymphocytes has been determined by X-ray crystallography at 2.1 A resolution. The structure was solved by a molecular replacement technique using the coordinates of rat MIF. The molecule forms a trimer structure similar to the rat MIF. However, unlike the rat MIF whose C-terminal tail (residues 104-114) is disordered in the crystal, human MIF has a definite main-chain conformation up to the C-terminal end. These eleven residues create two more beta-strands and join to the inter-subunit beta-sheet, which contribute to forming a trimer structure. Thus, the trimer structure consists of three seven-stranded beta-sheets surrounded by six alpha-helices. Each beta-sheet is comprised of beta-strands from each of the three monomers. This architecture is almost identical to 5-carboxymethyl-2-hydroxymuconate isomerase (CHMI) and is related to the E. coli signal transducing protein PII.

Amino Acid Sequence↗
PubMed1996

Chemotactic and chemokinetic activities of stem cell factor on murine hematopoietic progenitor cells.

We investigated the effects of stem cell factor (SCF) on the migration of murine bone marrow hematopoietic progenitor cells (HPC) in vitro using a modification of the checkerboard assay. Chemotactic and chemokinetic activities of SCF on HPC were evaluated by the numbers of HPC migrated on positive and negative gradients of SCF, respectively. On both positive and negative gradients of SCF, HPC began to migrate after 4 hours incubation, and their numbers then increased time-dependently. These results indicated that SCF functions as a chemotactic and chemokinetic agent for HPC. Analysis of types of colonies derived from the migrated HPC showed that SCF had chemotactic and chemokinetic effects on all types of HPC. When migrating activities of other cytokines were examined, interleukin (IL)-3 and IL-11 also affected the migration of HPC, but the degrees of each effect were lower than that of SCF. The results of the present study demonstrated that SCF is one of the most potent chemotactic and chemokinetic factors for HPC and suggest that SCF may play an important role in the flow of HPC into bone marrow where stromal cells constitutively produce SCF.

Animals↗
PubMed1996

Local Control and Cosmetic Outcome after Sector Resection with or without Radiation Therapy for Early Breast Cancer.

Breast conserving surgery and radiation therapy (RT) can achieve a more favorable cosmetic outcome than mastectomy in patients with early breast cancer. However, it is widely recognized that RT is an impediment to improving the cosmetic outcome. Between 1985 and 1993, 113 patients were enrolled in a prospective randomized study to examine whether or not RT could be avoided following sector resection in patients with Stage I and II (UICC) invasive breast cancer. There was no significant difference in the 8 year local recurrence free survival rate between the RT and non-RT groups (92.3% versus 89.8% respectively). The characteristics of suitable patients would be negative nodes and microscopically negative resection margins. In conclusion, sector resection without RT is a reasonable option for some patients with early breast cancer.

Journal Article↗
PubMed1996

Glycine-15 in the bend between two alpha-helices can explain the thermostability of DNA binding protein HU from Bacillus stearothermophilus.

On the basis of sequence comparison of thermophilic and mesophilic DNA binding protein HUs, Bacillus stearothermophilus DNA binding protein HU (BstHU) seems to gain thermostability with a change in amino acid residues present on the molecular surface. To evaluate the contribution of exchange of each amino acid to the thermostability of BstHU, we constructed three mutants, BstHU-T13A (Thr13 to Ala), BstHU-G15E (Gly15 to Glu), and BstHU-T33L (Thr33 to Leu), in which the amino acids in BstHU were changed to the corresponding ones in Bacillus subtilis DNA binding protein HU (BsuHU). Stability of the mutant proteins was determined from thermal-denaturation curves. Replacement of Gly15 located in the turn region between alpha 1 and alpha 2 helices (HTH motif), with Glu (BstHU-G15E), resulted in a decrease in thermostability, and the Tm value was 54.0 degrees C compared to the Tm value of 63.9 degrees C for BstHU. The mutants, BstHU-T13A and BstHU-T33L, were, by contrast, slightly more stable (Tm values of 67.0 and 65.6 degrees C for BstHU-T13A and BstHU-T33L, respectively) than the wild type. We then generated the BsuHU mutant protein BsuHU-E15G, where Glu15 in BsuHU was in turn replaced by Gly, and we analyzed the thermostability. This substitution clearly enhanced the melting temperature by 11.8 degrees C (Tm value: 60.4 degrees C for BsuHU-E15G) compared to the value for BsuHU (Tm: 48.6 degrees C). Thus, Gly15 in the HTH motif of BstHU has an important role in the thermostability of BstHU. Characterization of the structure of the BstHU-G15E by 1H-NMR analysis showed that solvent accessibility of amide proton of Ala21 in the mutant was significantly increased compared with that of wild type, which means that the structure of the HTH motif in the N-terminal region in the mutant was changed to a more open conformation, thereby avoiding the interaction of Ala21 with either Ser17 by hydrogen bond or Ala11 by hydrophobic interaction.

Bacterial Proteins↗
PubMed1996

Gene expression of the human prostaglandin E receptor EP4 subtype: differential regulation in monocytoid and lymphoid lineage cells by phorbol ester.

We isolated a cDNA clone encoding the human prostaglandin (PG) E receptor EP4 subtype and examined the gene expression in human blood cells. Northern blot analysis revealed that the EP4 gene is expressed at a high level in peripheral blood mononuclear cells, and at lower levels in cultured human blood cell lines, THP-1 and U937 (monocytoid cell lines), MOLT-4 and Jurkat (T-cell lines), and Raji (B-cell line). To examine regulation of the EP4 gene expression in the immune system, we studied the effects of phorbol 12-myristate 13-acetate (PMA) on these cell lines. Gene expression was upregulated in THP-1, U937, and Raji cells by PMA, and was downregulated in MOLT-4 and Jurkat cells. In THP-1 cells the effects of PMA were further analyzed, and the upregulation of the EP4 gene was shown to be followed by an increase in PGE2 binding sites and in PGE2-induced cAMP accumulation. In the striking contrast, other PGE receptor subtypes (EP1, EP2 and EP3) and other prostanoid receptors (IP and DP) were shown not to be upregulated by PMA. Therefore, this is the first demonstration of a highly specific upregulation of the EP4 subtype in THP-1 cells treated with PMA, suggesting the importance of the EP4 subtype in the immune system. In the present study we also clarified that EP4 gene expression is regulated differently among human monocytoid and lymphoid lineage cells, thus leading to the better understanding of the regulatory mechanisms for the human EP4 gene expression in the immune system.

Burkitt Lymphoma↗
PubMed1996

Spontaneous antibody-secreting cells in the stomach of gastric cancer patients.

The gastric mucosa has been regarded as an active site of humoral immunity since the discovery of Helicobacter pylori. The present study was conducted to determine the in vivo activity of gastric B cells in 53 gastric cancer patients. B-cell activity was measured by protein-A plaque assay, in which IgA-, IgM-, and IgG-plaque-forming cells (PFC) were counted. The number of PFC was associated with the stage of cancer, but the response of lymphocytes in a non-tumorous area (NML) and tumor-infiltrating lymphocytes (TIL) differed. PFC in both sites were decreased compared to n0 cancer in n1 lymph node metastasis-positive cancer, while only NML showed raised PFC in n2 + (P < 0.05, vs TIL). Cancer cells penetrating the submucosa caused the PFC of TIL (but not of NML) to decrease. Invasion of the intratumor capillary (V) or lymphatic (Ly) vessels also caused PFC to change, showing differences of Ig class; there was a decrease of PFC in V2 (IgG- and IgM-PFC) and in Ly2 (all Ig-PFC). IgA-PFC in Ly1 differed in TIL (decrease of PFC) and NML (increase). PFC also differed in TIL and NML in cancer cells, as follows: TIL < NML in tubular and poorly differentiated adenocarcinoma and TIL > NML in papillary and signet ring cell adenocarcinoma. Changes in lymph node (LNL) and blood lymphocytes were similar to those in gastric PFC whose IgA value was 10 times as much as that of LNL. The 5-year survival rate was significantly better in patients with lower rather than higher PFC such as 89% vs 68%. Gastric B cells thus appear to be active and to reflect gastric mucosal immunity.

Adult↗
PubMed1996

Crystal structure of the macrophage migration inhibitory factor from rat liver.

The tertiary structure of the macrophage migration inhibitory factor (MIF) from rat liver (12,300 Mr) is presented at 2.2 A resolution. Each monomer consists of two beta/alpha/beta motifs aligned in quasi two-fold symmetry, comprising a domain consisting of a four-stranded mixed beta-sheet and two antiparallel alpha-helices. The protein exists as a trimer in the crystal. An extra beta-strand that is almost perpendicular to the other beta-strands joins to the beta-sheet of the neighbouring monomer in the trimer. Unexpected similarities were detected between MIF and two kinds of isomerase.

Amino Acid Sequence↗
PubMed1996

Myeloid antigen, CD13, CD14, and/or CD33 expression is restricted to certain lymphoid neoplasms.

The authors examined the expression of myeloid antigens (MyAg): CD11b, CD13, CD14, CD15, and CD33 in 249 adults with lymphoid neoplasms using flow cytometric analysis. In this study, acute leukemia that was myeloperoxidase negative by light microscopy and had at least one lymphoid antigen was defined as acute lymphoblastic leukemia (ALL). The patients were classified as follows: 6 with unclassified ALL, 35 early B precursor ALL, 32 T-ALL, 25 B-cell chronic lymphocytic leukemia (B-CLL) and its variants, 24 B-cell non-Hodgkin's lymphoma (B-NHL), 7 plasma cell disorders, 8 T-CLL, 2 adult T-cell leukemia, and 10 T-NHL. CD11b and CD15 were present in a wide range of lymphoid disorders irrespective of B/T lineage and maturity. Unclassified ALL and phenotypically immature ALL frequently expressed CD13 and CD33, and occasionally expressed CD14. Among early B precursor ALL, CD13, and/or CD33 were significantly associated with the presence of stem cell marker CD34 and the chromosomal abnormality t(9;22). In addition, ALL with deletion of chromosome 7 commonly expressed CD13 and CD33. Taken together, CD13 and/or CD33 positive ALL may originate from a multipotential stem cell. Among mature neoplasms, CD14 was frequently, and CD13 and CD33 were occasionally expressed in B-cell, but not T-cell tumors. These results suggest that CD13, CD14, and CD33 are preferentially expressed in two types of lymphoid neoplasms, namely undifferentiated ALL and mature B-cell lymphoproliferative disorders.

Adolescent↗
PubMed1996

Development of a potassium-specific adsorbent for direct hemoperfusion.

Direct hemoperfusion (DHP) over an exchange resin for sodium is capable of rapidly lowering an elevated serum potassium level but has not been used clinically because of subsequent electrolyte abnormalities. After the completion of detailed in vitro studies, we developed a sodium/calcium/magnesium exchange resin mixture specifically to remove potassium from the blood. The mixture, which consisted of exchange resins for sodium (48%), calcium (48%), and magnesium (4%), gave the most satisfactory results in vitro. DHP through these resin-mixture columns for 2 h reduced elevated plasma potassium levels (6.7 +/- 1.1 to 3.5 +/- 0.6 mEq/L, p < 0.001) in anephric dogs without including any significant change in the levels of sodium, calcium, magnesium, albumin, total protein, or cholesterol. The platelet losses and changes in the plasma free hemoglobin levels observed were similar to those found with activated charcoal hemoperfusion. These results suggest that this resin hemoperfusion may be useful in patients with acute hyperkalemia.

Animals↗
PubMed1996

Comparison of Two Questionnaires on Respiratory Symptoms in a Nicaraguan Population: Value in Diagnosis of Chronic Bronchitis.

Two questionnaires about respiratory symptoms were evaluated for reliability and ability to diagnose chronic bronchitis in a study population of 129 Nicaraguans (110 workers and 19 patients with chronic bronchitis). The first questionnaire (AQ) had symptom questions that were based on British Medical Research Council (MRC) questions, adapted to local Spanish. The second questionnaire (MRCQ) contained MRC symptom questions translated directly into Spanish. The reliability of the questions was measured in a test-retest procedure. The questionnaire-based diagnosis of chronic bronchitis was compared with the diagnosis made by a physician (for workers) or from the hospital records (for patients). The questions concerning symptoms in both questionnaires were of acceptable reliability. For the diagnosis of chronic bronchitis in workers, the AQ showed similar sensitivity, a somewhat higher specificity, and a substantially higher positive predictive value (90%) than the MRCQ (57%). Among the patients, the AQ identified 17 patients as positive (sensitivity 89%), while the MRCQ identified 15 (sensitivity 79%). respiratory questionnaire; reliability; chronic bronchitis; Nicaragua Hanley & Belfus, Inc. Int J Occup Environ Health 1077-3525 2 2 1996 April/June Chronic Exposure to Cigarette Smoke Inhibits the Stimulating Effects of Mineral Fibers on the Production of Tumor Necrosis Factor by Alveolar Macrophages of Rats 95 98 EN Yasuo Morimoto Department of Environmental Health Engineering, University of Occupational and Environmental Health, Japan 1-1, Iseigaoka, Yahatanishiku, Kitakyushu 807, Japan. Ziro Nambu Hajime Hori Tohru Tsuda Hiroshi Yamato Toshiaki Higashi Yasuyuki Yokosaki Masamitsu Kido Isamu Tanaka The objective of this study was to evaluate the chronic combined effects of mineral fibers and cigarette smoke on the production of tumor necrosis factor (TNF) by alveolar macrophages. The authors chronically exposed ten rats to cigarette smoke in vivo and measured the production of TNF by alveolar macrophages in the presence of mineral fibers in vitro. For smoke exposure, rats were divided into two groups. Five rats were exposed daily to a concentration of 10 mg/m(3) of cigarette smoke for six hours a day, five days a week, for four weeks, and five rats (control) were not exposed to smoke. A broncho-alveolar lavage was performed after the smoke exposure, and the recovered alveolar macrophages were incubated with either chrysotile or ceramic fibers on a microplate for 24 hours. TNF activity in the supernatant was determined by the L929 bioassay. When alveolar macrophages were not stimulated by mineral fibers, TNF production tended to be lower in smoke-exposed alveolar macrophages than in unexposed ones, although the difference was not significant statistically. When alveolar macrophages were stimulated in vitro by chrysotile or ceramic fibers, both fibers stimulated TNF production, but TNF production in smoke-exposed alveolar macrophages was lower than that in unexposed macrophages. These results revealed that long-term exposure to cigarette smoke inhibited the stimulating effect of mineral fibers on the production of TNF.

Journal Article↗
PubMed1996

Prostaglandin E receptor subtypes in mouse osteoblastic cell line.

PGE2 is one of the key molecules in the osteoblast. It is the major prostanoid in the bone, and its production is under the control of both systemic and local factors. PGE2 has been reported to have multiple actions in the osteoblast, such as growth promotion and cell differentiation. To better understand the action of PGE2 in the osteoblast, we determined the PGE receptor subtypes in MC3T3-E1, an osteoblastic cell line derived from the normal mouse calvaria. Northern blot analysis revealed that EP1 and EP4 subtypes are expressed in MC3T3-E1. In contrast, EP3 subtype was not detected by either Northern blot analysis or RT-PCR. The contribution of each subtype was evaluated by studying the effects of subtype-specific analogs on osteoblastic function at confluency and 5 days after confluency. An EP1 agonist, 17-phenyl-omega-trinor PGE2, increased DNA synthesis and decreased alkaline phosphatase activity. 11-Deoxy-PGE1, and EP2 and EP4 agonist, decreased DNA synthesis and increased alkaline phosphatase activity at both stages. Butaprost, an EP2-selective agonist, showed effects similar to those of 11-deoxy-PGE1 only at confluency. Another and more differentiated osteoblastic marker, osteocalcin production, was detectable and was stimulated by 11-deoxy-PGE1 only 5 days after confluency. The exposure of these cells to EP1 agonist changed the cell shape to a more fibroblastic appearance. These results indicate that EP1, EP4, and probably EP2 are present in MC3T3-E1 cells; EP1 promotes cell growth, and EP2 and EP4 mediate differentiation of the osteoblast. Furthermore, the decreased response to EP2-specific agonist 5 days after confluency suggests that the expression of PGE receptor subtype is dependent on the stage of osteoblastic differentiation. This is the first report to determine PGE receptor subtypes in the bone.

Alprostadil↗
PubMed1996

Type 2 angiotensin II receptor is expressed in human myometrium and uterine leiomyoma and is down-regulated during pregnancy.

Angiotensin II (Ang II) acts on at least two receptor subtypes, type 1 (AT1) and type 2 (AT2). The AT2 receptor is abundant in the fetus and decreases rapidly after birth. The uterus expresses the AT2 receptor abundantly even in adults, suggesting its role in reproduction. To explore the roles and regulation of the AT2 receptor in human uterus and to examine whether its expression is related to the proliferative characteristics of leiomyoma, we studied Ang II receptor gene expressions in nonpregnant and pregnant myometrium and in uterine leiomyomas obtained from patients who underwent gynecological surgery. Receptor binding studies revealed that all samples exhibited high-affinity binding for [Sar1, Ile5]Ang II, most (> 90%) of which was of the AT2 subtype. In nonpregnant myometrium (n = 5), receptor density [maximum binding capacity (Bmax)] and dissociation constant (Kd) for AT2-selective CGP42112A were 287 +/- 46 fmol/mg protein and 0.48 +/- 0.09 nM, respectively. In the myometrium of early (n = 6) and late pregnancy (n = 3), Bmax for the AT2 receptor was significantly decreased (62 +/- 17 and 25 +/- 6 fmol/mg protein, respectively). Furthermore, administration of combined oral contraceptive pills induced a comparable reduction in AT2 Bmax (54 +/- 12 fmol/mg protein, n = 4). AT2 Bmax or Kd values in uterine leiomyomas from nonpregnant women showed no significant differences from those in nonpregnant myometrium. Changes of AT2 Bmax in uterine leiomyomas during pregnancy or with oral contraceptive were similar to those in the myometrium. Northern blots revealed AT1 and AT2 receptor messenger RNA (mRNA) expressions in all samples examined; the former was much lower than the latter. Although the AT1 receptor mRNA expression did not change significantly, the AT2 receptor mRNA level was significantly decreased during pregnancy or with oral contraceptives. These results indicate that AT1 and AT2 receptors are expressed in human myometrium and uterine leiomyoma, in which the AT2 receptor is predominant. AT2 receptor gene expression is down-regulated during pregnancy, possibly mediated by sex steroids.

Adult↗
PubMed1996

Synthetic cationic amphiphile for liposome-mediated DNA transfection with less cytotoxicity.

A cationic peptide amphiphile comprising an L-alanine residue interposed between a charged head group and a double-chain segment, N,N-dihexadecyl-N alpha-[6-(trimethylammonio)- hexanoyl]-L-alaninamide bromide (NC5Ala2C16), was synthesized and used to prepare sonicated liposomes. We examined the efficiency of this liposome in gene transfer according to the transient expression of chloramphenicol acetyltransferase (CAT). This cationic liposome reagent facilitates efficient DNA transfection in COS-7 cells. We determined the optimum conditions for NC5Ala2C16 liposome-mediated transfection. The optimal amounts of the amphiphile and plasmid DNA were determined to be about 100 micrograms and 10 micrograms per 35-mm dish, respectively. The activity of this liposome was greater than that of commercial reagents, lipofectin, and N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethyl-ammonium methylsulfate (DOTAP), and it was less toxic than lipofectin and DOTAP in COS-7 cells.

Animals↗
PubMed1996

Environmental tobacco smoke and policies for its control.

This study evaluated the effect of designated smoking areas in an office and the efficacy of air cleaners in a smoking room. The concentrations of suspended particulates (SP) were measured at 13 points in the office, including the smoking room, corridors around the smoking room, and a non-smoking office. The SP concentrations were between 0.52 to 1.31 mg/m3 in the smoking room, 0.06 to 0.22 mg/m3 in the corridors and 0.03 to 0.05 mg/m3 in the non-smoking office, respectively. The results showed that the area restriction on smoking in this office was successful, although an outflow of tobacco smoke was observed in the corridors. The SP concentration in the smoking room where three electrostatic air cleaners had been installed was monitored over 24 hours. The SP concentration due to tobacco smoke in the smoking room was much greater than the control concentration of SP in air-conditioned buildings in Japan, that is, not more than 0.15 mg/m3. The effectiveness of electrostatic air cleaners in closed smoking rooms is discussed.

Air Pollution, Indoor↗
PubMed1996

Surgical simulation of facial paralysis.

We are developing a prototype of a surgical simulation system for restoring facial expression lost in cases of facial paralysis. Correcting facial paralysis requires careful planning of surgery procedures and accurate prediction of the surgical results. So far techniques to perform this task largely relied on the physician's experience, and there were few quantitative data to refer to. The system we propose is finally aimed at helping the surgeon plan the surgery and predict the results. The 3D model of the face used in our system is generated directly from the CT scan of the patient. The face model consists of skin, skull and selected facial muscles based on anatomy. The mass and spring lattice approach is used to give physical attributes to the face model. The present prototype system lets the user directly manipulate graphical representations of facial expression.

Computer Graphics↗