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Biomedical subjects

J Kato

Publications and source records attributed to J Kato.

At least 163 records · Page 9Linked to original sources
PubMed1998

A Case of Sclerosing Lymphocytic Lobulitis of the Breast Associated with Diabetes Mellitus.

BACKGROUND: The benign breast disease sclerosing lymphocytic lobulitis is thought to result from autoimmune diseases causing insulin-dependent diabetes mellitus (IDDM) due to insulinitis. In cases of sclerosing lymphocytic lobulitis accompanied by IDDM, the clinical term gdiabetic fibrous breast disease hhas been proposed. METHODS: A case of sclerosing lymphocytic lobulitis of the breast is described RESULTS: The patient was a 43-year-old woman diagnosed with non insulin-dependent diabetes mellitus (NIDDM) 8 years previously. Insulin therapy was thought to be necessary because treatment with glibenclamide was not effective. She visited our facility complaining of a lump in her right breast that was 5 cm in diameter, painless, rock-hard, discrete, and irregularly outlined. Biopsy was performed because breast cancer was strongly suggested by its hardness and its irregular internal echo on ultrasonography. Histopathological findings demonstrated marked stromal sclerosis and lymphocyte infiltration in the perivascular and perilobular areas. Sclerosing lymphocytic lobulitis was diagnosed. CONCLUSION: Referring physicians should avoid performing unnecessary repeated biopsies by recognizing this disease entity, which often occurs bilaterally.

Journal Article↗
PubMed1998

Bloom's and Werner's syndrome genes suppress hyperrecombination in yeast sgs1 mutant: implication for genomic instability in human diseases.

Bloom's syndrome (BS) and Werner's syndrome (WS) are genetic disorders in which an increased rate of chromosomal aberration is detected. The genes responsible for these diseases, BLM and WRN, have been found to be homologs of Escherichia coli recQ and Saccharomyces cerevisiae SGS1 genes. Here we show that yeast Sgs1 helicase acts as a suppressor of illegitimate recombination through homologous recombination and that human BLM and WRN helicases can suppress the increased homologous and illegitimate recombinations in the S. cerevisiae sgs1 mutant. The results imply a role of BLM and WRN helicases to control genomic stability in human cells. Similar to Sgs1 helicase, BLM helicase suppressed the cell growth in the top3 sgs1 mutation background and restored the increased sensitivity of the sgs1 mutant to hydroxyurea, but the WRN helicase did not. We discussed differential roles of BLM and WRN helicases in human cells. BLM- and WRN-bearing yeasts provide new useful models to investigate human BS and WS diseases.

Base Sequence↗
PubMed1998

Concentrations of thrombopoietin in bone marrow in normal subjects and in patients with idiopathic thrombocytopenic purpura, aplastic anemia, and essential thrombocythemia correlate with its mRNA expression of bone marrow stromal cells.

The function of bone marrow (BM) stromal thrombopoietin (TPO) in megakaryopoiesis remains unknown. In the present study we attempted to clarify the pathophysiological implications of stromal TPO in normal subjects (NS) and in patients with idiopathic thrombocytopenic purpura (ITP), aplastic anemia (AA), and essential thrombocythemia (ET) by measuring TPO concentrations in BM and peripheral blood (PB) and by estimating the levels of stromal TPO mRNA with TaqMan fluorescence-based post-reverse transcription-polymerase chain reaction product detection system. The results showed that TPO concentrations in PB were significantly elevated in patients with ITP (34.9 +/- 11.7 pg/mL) and AA (364.1 +/- 153.5 pg/mL) but within normal range in patients with ET (each 20.0 and 22.1; NS, 22.1 +/- 8.2 pg/mL). In all subjects, the TPO concentrations in BM correlated well with the PB levels, and the former were consistently higher than the latter. The concentrations of TPO in BM also correlated with the levels of TPO mRNA in stromal cells. Furthermore, expression levels of TPO mRNA clearly correlated with megakaryocyte counts in NS and patients with ITP, indicating that stromal TPO actually enhances megakaryopoiesis. Thus, our results in the present study indicate that TPO from BM stromal cells is considered to play an essential role for megakaryopoiesis under various patho-physiological conditions.

Anemia, Aplastic↗
PubMed1998

Affinity maturation in Lyn kinase-deficient mice with defective germinal center formation.

Lyn kinase-deficient (lyn-/-) mice show several abnormalities such as reduced numbers of circulating B cells, hyper-IgM, and low proliferative responses induced by CD40 ligand. Lyn-/- mice also develop splenomegaly, produce autoreactive Abs with age, and finally develop glomerulonephritis. Another abnormality observed in lyn-/- mice is that their disability to form germinal centers (GCs). It has been considered that GCs play an important role in affinity maturation and differentiation to B cell memory upon immunization with thymus-dependent Ag. Since Lyn kinase has been thought to be downstream of the signals from the B cell Ag receptor as well as CD40, we studied whether or not lyn-/- mice could exhibit normal Ag-specific class switching and affinity maturation following somatic hypermutation. The mice were immunized with (4-hydroxy-3-nitrophenyl)acetyl-chicken gamma-globulin (NP-CG). Production of NP-specific IgG1 Abs was slightly reduced but clearly detectable. The affinity of Abs produced was comparable to that in wild-type mice. Furthermore, somatic hypermutation occurred in the heavy-chain variable region at the same level as that in wild-type mice. Therefore, we conclude that isotype switching and affinity maturation occur normally in lyn-/- mice without the formation of GCs. The results lead to a speculation that Lyn may not play a role in induction of isotype switching or affinity maturation, despite being downstream of the signals from the B cell Ag receptor complex and CD40, and that GC architecture may not be absolutely essential for affinity maturation.

Amino Acid Sequence↗
PubMed1998

A proof of glutathione S-transferase-pi-related multidrug resistance by transfer of antisense gene to cancer cells and sense gene to bone marrow stem cell.

In order to directly prove the involvement of GST-pi in drug resistance, it's antisense gene was transduced into human colorectal cancer cell line which has been shown to express high level of GST-pi and the sensitivity of this cell line to anticancer drugs were assessed. The transfectant showed higher sensitivity to adriamycin (3.3-fold), Cisplatnum (2.3-fold), Melphalan (2.2-fold), Etoposode (2.2-fold) than the parental cell, while the sensitivity to vincristine, mitomicin C, 5-fluorouracil was unchanged by transfection. When the transfectant and parental cells were innoculated in nude mice and treated with adriamycin, a significant suppression of tumor growth was observed with the transfectant as compared to the parental cell. On the basis of this observation, we then transduced sense GST-pi gene into human bone marrow stem cells (CD34+ cells) to protect them from toxicity of anticancer drug. The gene transduced CD34+ cells formed more CFU-GM than nontransduced CD34+ cell in the presence of adriamycin (30 ng/ml). Thus, the autotransplantation of GST-pi gene transduced cell into cancer patients to protect the bone marrow from subsequent highdose chemotherapy is considered to be a new strategy for cancer gene therapy.

Animals↗
PubMed1998

Efficient conditional transgene expression in hepatitis C virus cDNA transgenic mice mediated by the Cre/loxP system.

Conditional gene expression has greatly facilitated the examination of the functions of particular gene products. Using the Cre/loxP system, we developed efficient conditional transgene activation of hepatitis C virus (HCV) cDNA (nucleotides 294-3435) in transgenic mice. Efficient recombination was observed in transgenic mouse liver upon intravenous administration of adenovirus that expresses Cre DNA recombinase. After transgene activation, most hepatocytes were stained with anti-core polyclonal antibody, and 21-, 37-, and 64-kDa proteins were detected by Western blot analysis in liver lysates using anti-core, E1, and E2 monoclonal antibodies, respectively. Serum core protein was detected in transgenic mice 7 days after transgene activation with concurrent increases in serum alanine aminotransferase levels. Subsequently, an anti-core antibody response was detected 14 days after infection. Furthermore, a CD4 and CD8 positive cell depletion assay normalized both the serum alanine aminotransferase increases and pathological changes in the liver. These results suggest that HCV proteins are not directly cytopathic and that the host immune response plays a pivotal role in HCV infection. Thus, this HCV cDNA transgenic mouse provides a powerful tool with which to investigate the immune responses and pathogenesis of HCV infection.

Adenoviridae↗
PubMed1998

The intermediate form of glycine-extended adrenomedullin is the major circulating molecular form in human plasma.

Adrenomedullin (AM), a potent vasodilator peptide, is processed from its AM precursor as glycine-extended AM (AM-gly), an intermediate form of AM. Subsequently, mature AM is converted from AM-gly by enzymatic amidation. Using two kinds of radioimmunoassay which recognize the entire AM molecule (E-AM-RIA) and C-terminal amide structure (C-AM-RIA), human plasma AM immunoreactivity was chromatographically characterized. In analyses of gel filtration and reverse phase high-performance liquid chromatography, most of the AM immunoreactivity measured by E-AM-RIA was eluted at a position identical to where mature AM and AM-gly emerged and was not recognized by C-AM-RIA. These data show that immunoreactive AM measured by E-AM-RIA is not amidated. When amidated by peptidylglycine alpha-amidating enzyme, the immunoreactive AM was converted to a form that can be detected by C-AM-RIA. These results indicate that most of the total AM immunoreactivity measured by E-AM-RIA represents immunoreactivity of AM-gly and that the concentration of immunoreactive mature AM in plasma is much lower than that of AM-gly. In practice, plasma concentration of AM-gly and mature AM in healthy volunteers was 2.7 +/- 0.18 fmol/ml and 0.48 +/- 0.05 fmol/ml, respectively. Furthermore, plasma concentration of AM-gly and total AM was significantly elevated in patients with hypertension compared to normotensive control. The present data indicate that most of circulating plasma AM immunoreactivity is occupied by AM-gly, an intermediate form of AM, which may reflect the process of production of AM in tissues.

Adrenomedullin↗
PubMed1998

Analysis of patients with congenital diaphragmatic hernia requiring pre-operative extracorporeal membrane oxygenation (ECMO).

The purpose of this report was to analyze the patients requiring preoperative extracorporeal membrane oxygenation (ECMO) as the most critical group of patients with congenital diaphragmatic hernia (CDH) and to identify any special features. Over the past 11 years, out of 72 neonates with CDH admitted before 24 h of age, 40 (56%) could be managed with conventional therapies while the other 32 (44%) required ECMO. Seventeen infants requiring preoperative ECMO were classified as group 1, and the 15 with postoperative ECMO as group 2 (controls). The records of patients in both groups were analyzed. Patients in group 1 were not only severely hypoxic, but also significantly hypercapneic on admission, and in 14 (82%) the diaphragmatic defect was so large or totally agenetic that a prosthetic patch was necessary. The average age at onset of ECMO in group 1 was 13.1 h, and the average duration was 159 h. Major hemorrhagic complications including intracranial hemorrhage occurred with a significantly higher frequency in group 1. The survival rate in group 1 was 41%, compared with 73% in group 2 and 85% in non-ECMO patients. Four infants in group 1 with extremely hypoplastic lungs could not be weaned from ECMO, and died without undergoing an operation. Moreover, 4 of the 7 survivors in group 1 required prolonged (105-658 days) ventilator care with a tracheostomy after weaning from ECMO, and were frequently hospitalized thereafter. The pulmonary function of these patients remained severely underdeveloped for a long time; indeed, the average pulmonary perfusion ratio of the affected side remained at only 40% of the contralateral side in group 1, although the volume ratio reached 85%. These findings may suggest that the main pathology of the patients requiring preoperative ECMO was a high degree of pulmonary hypoplasia, and that there will be limitations to management using ECMO.

Extracorporeal Membrane Oxygenation↗
PubMed1998

Distribution and origin of nerve fibers in the rat temporomandibular joint capsule.

The distribution and origin of nerve fibers containing neuropeptides and NOS projecting to the temporomandibular joint capsule (TMJ) of the rat were studied by retrograde tracing in combination with immunocytochemistry. Numerous nerve fibers were seen in the TMJ as revealed by the neuronal marker protein gene product 9.5. Nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide (PACAP), substance P (SP), calcitonin gene-related peptide (CGRP), and nitric oxide synthase (NOS) were seen in the synovial membrane, the joint capsule and entering the articular disc. Injection of the retrograde tracer True Blue (TB) into the TMJ resulted in the appearance of numerous labeled nerve cell bodies in the trigeminal and superior cervical ganglia, and moderate numbers in the nodose, the otic, the sphenopalatine, the stellate and the dorsal root ganglia at levels C2-C5. Most of the TB-labeled cell bodies in the superior cervical and stellate ganglia contained NPY. In the trigeminal ganglion, numerous TB labeled cell bodies contained CGRP and a minor population stored SP, a few cell bodies were seen to store NOS or PACAP. In the sphenopalatine and otic ganglia, TB labeled cell bodies contained NOS or VIP. In the nodose ganglion, labeled cell bodies contained CGRP; other labeled cell bodies harbored NOS. In the cervical dorsal root ganglia, the majority of the labeled cell bodies stored CGRP and smaller populations stored SP and PACAP. Thus, the innervation of the TMJ is complex and many different ganglia are involved.

Animals↗
PubMed1998

The RHC21 gene of budding yeast, a homologue of the fission yeast rad21+ gene, is essential for chromosome segregation.

The Saccharomyces cerevisiae gene RHC21 is a homologue of the fission yeast rad21+ gene, which affects the sensitivity of cells to gamma-irradiation and is essential for cell growth in S. pombe. Disruption of the RHC21 gene showed that it is also essential in S. cerevisiae. To examine its function in cell growth further, we have isolated temperature-sensitive mutants for the RHC21 gene and characterized one of them, termed rhc21-sk16. When this mutant was incubated at 36 degrees C, the percentage of large-budded cells was increased. Most of the large-budded cells had aberrant nuclear structures, such as unequally extended nuclear DNA with incompletely elongated spindles across the mother-daughter neck or only in a mother cell. Furthermore, a circular minichromosome is more unstable in the mutant than in the wild-type, even at 25 degrees C. Flow cytometry showed that the bulk of DNA replication takes place normally at the restrictive temperature in the mutant. These results indicated that the RHC21 gene is required for proper segregation of the chromosomes. In addition, we found that the mutant is sensitive not only to UV radiation and gamma-rays but also to the antimicrotubule agent nocodazole at 25 degrees C. This suggests that the RHC21 gene is involved in the microtubule function. We discuss how the RHC21 gene product may be involved in chromosome segregation and microtubule function.

Cell Cycle Proteins↗
PubMed1998

Suppressive effect of ethanol on the expression of hepatic asialoglycoprotein receptors augmented by interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha.

Blood levels of inflammatory-related cytokines, including interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha, are elevated in patients with alcoholic liver diseases. We investigated the effects of these cytokines and ethanol on the expression of hepatic asialoglycoprotein receptors (AGPRs) in a human hepatoblastoma cell line, HepG2. An [125I]-asialo-orosomucoid binding assay showed significant increases in surface AGPR numbers in HepG2 cells by treatment with IL-1beta, IL-6, and TNF-alpha, to levels which were approximately 130% of the values in untreated control cells. However, the enhanced AGPR numbers induced by treatment with these cytokines were markedly suppressed, to 70%-80% of the number in the untreated cells, by treatment with ethanol. Immunological detection of AGPR with a specific antibody demonstrated that the modulation of surface AGPR numbers was correlated with the cellular expression levels of AGPR. These results suggest that, although IL-1beta, IL-6, and TNF-alpha stimulate the synthesis of hepatic AGPR, ethanol suppresses the expression of AGPR augmented by these cytokines. This leads to an increase in serum asialo-orosomucoid levels caused by the disordered catabolism mediated by AGPR in patients with alcoholic liver disease.

Asialoglycoprotein Receptor↗
PubMed1998

Localization of neuropeptide Y Y1 receptor mRNA in human tooth pulp.

With immunocytochemistry numerous nerve fibres containing neuropeptide Y (NPY) were found in human molar pulp tissue, often around small blood vessels. Reverse transcriptase-polymerase chain reaction, using specific primers, detected mRNA of the human NPY Y1 receptor in the human pulp tissue. Thus, both NPY-containing nerve fibres and NPY Y1 receptor mRNA are present in human tooth pulp, possibly regulating vascular tone and pain perception.

Adult↗
PubMed1998

Venovenous extracorporeal membrane oxygenation in newborn infants using the umbilical vein as a reinfusion route.

PURPOSE: The authors report on four neonates treated with venovenous (VV) extracorporeal membrane oxygenation (ECMO) using the umbilical vein as a reinfusion route. METHODS: From 1994 to 1997, 26 instances VV-ECMO in neonates have been carried out at our neonatal center for the treatment of severe respiratory and cardiac failure. Among them, 22 patients could be treated with VV-ECMO mainly using 15F double-lumen catheter (DLC), adding the cephalic drainage using another catheter. In the remaining four cases, however, attempts to insert the DLC into the right internal jugular vein failed because the vein was too small or technical problems. For such instances, two catheters were cannulated into the right atrium and the cephalic portion of the right internal jugular vein, respectively. These two venous catheters were connected to the drainage route of ECMO circuit with a "Y" connector. Then, the umbilical vein was cannulated with 10F or 8F catheter, which was connected to the reinfusion route of ECMO to return the oxygenated blood to the infant. RESULTS: The median age at which ECMO was initiated was 18 hours, and the median ECMO course was 72 hours. The liver function tests were slightly and transiently worsened in two patients during VV perfusion, (in one patient serum glutamic-oxaloacetic transaminase [SGOT] elevated to 76 IU/L and serum glutamic-pyruvic transaminase [SGPT] to 49 IU/L, and in another patient SGOT elevated to 56 IU/L and SGPT remained in normal range). Preumbilical cannula pressures were measured in two patients. In a patient who used 10F umbilical cannula, the preumbilical maximum pressure was 43 mm Hg at 250 mL/min of ECMO flow. In another with an 8F catheter, it was 72 mm Hg at 180 mL/min of ECMO flow. All of the patients survived without any neurological complications. CONCLUSIONS: If the right internal jugular vein would not accommodate the DLC, VV-ECMO using the umbilical vein as a infusion route could be selected.

Catheterization, Peripheral↗
PubMed1998

Isolated cavernous hemangioma of the stomach in a neonate.

This is a report of an extremely rare case of isolated cavernous hemangioma of the stomach found in a neonate. Hematemesis developed in a 7-day-old baby boy weighing 2.8 kg at birth. This was followed by melena. Endoscopic examination findings showed a large hemorrhagic mass on the lesser curvature of the stomach. During laparotomy, a large vascular tumor was identified and subtotal gastrectomy was carried out. On section, the tumor extended through the submucosa to the serosal surface. Histological diagnosis was cavernous hemangioma. The authors could collect only 10 cases of hemangioma of the stomach diagnosed in childhood from the world literature.

Gastrectomy↗
PubMed1998

The multiple untranslated first exons and promoters system of the oestrogen receptor gene in the brain and peripheral tissues of the rat and monkey and the developing rat cerebral cortex.

Recent studies on the human oestrogen receptor (ER) gene have revealed the complex system with the multiple untranslated first exons and promoters in the ER gene expression. Little information is however available on the system in the ER gene of the rat or nonhuman primate. The rat genomic library was first screened by the rat ER cDNA (0-1) probe. One of the four positive clones (lambda rEgE1) was subcloned and sequenced. The nucleotide sequence was found to contain the exon 0, the intron 0, and the exon 1 with its 3'-ends. The novel untranslated first exons, the exon ON and the exon OS, were further identified. These results indicated the presence of at least four subtypes of the rat ER mRNAs; the messages transcribed from promoter P-0 (ER mRNA (0-1)), putative promoter P-1 (ER mRNA (1-1)), promoter P-ON (ER mRNA (ON-1)) and promoter P-OS (ER mRNA (OS-1)). The P-O- or P-1 driven message (0-1) or (1-1) appeared to be expressed most strongly in major oestrogen central- (anterior pituitary, AP, hypothalamus-preoptic area, HPOA, and amygdala, AMG) and peripheral targets (uterus and ovary). The message (ON-1) was strongly expressed in the liver and kidney, but not in the HPOA, AMG, cerebral cortex, CC, and cerebellum, Ce. The OS-1 message was expressed variably but generally in the tissues examined except for the CC and Ce. Thus, the region- and tissue specific expression of the rat ER gene is likely to be regulated by the multiple untranslated exons and promoters system. Furthermore, when the ER mRNA subtypes were examined in the rat neonatal CC where the ER protein level rose transiently, considered as a model for the development of the ER or progestin receptor A and B isoforms, the expression of the ER mRNAs seemed to be differential postnatally, implicating some stage dependent usage of the promoters in the development. In the monkey, we identified the untranslated first exon OS, the homologue of the rat exon OS. Interestingly, the exon C was found to consist of two different exons, the exon OK and the exon OG. By the alternative usage of the promoters and the alternative splicing, at least six ER mRNA subtypes, that is, ER mRNAs (0-1), (1-1), (OS-1), (OS-OG-1), (OK-1) and (OK-OG-1) were identified in the monkey tissues. These messages were also differentially distributed in the monkey brain and other tissues. It was noteworthy that the P-OK driven messages were expressed almost exclusively in the monkey liver. These results have suggested that the systems of the multiple untranslated first exons and promoters and the alternative splicing are involved in the regulation of the region- and tissue specific expression of the ER gene in the brain and peripheral tissues of the rat and monkey. Stage-related usage of the promoters was also suggested in the ER gene expression in the CC of the postnatal rat in development.

Amino Acid Sequence↗
PubMed1998

Escherichia coli HU protein suppresses DNA-gyrase-mediated illegitimate recombination and SOS induction.

BACKGROUND: The HU protein is an abundant DNA binding protein of bacteria and is a major constituent of the bacterial nucleoid. HU protein is known to be involved in several fundamental biological functions, including DNA supercoiling, DNA replication, site-specific DNA inversion, and transposition. It is generally thought that a functional relationship exists between HU protein and DNA gyrase. RESULTS: We found that an hupA hupB double mutant displays enhanced spontaneous illegitimate recombination during the formation of lambdabio transducing phage in Escherichia coli. Nucleotide sequence analysis of the resulting transducing phages showed that the E. coli bio and lambda recombination sites did not have any homologous sequence. This mutation also enhanced the spontaneous expression of SOS functions. Furthermore, either overproduced GyrA protein or a temperature-sensitive gyrB mutation suppressed the illegitimate recombination enhanced by the defect of HU protein. CONCLUSION: These results show that the defect of HU induces illegitimate recombination and SOS response, which are probably mediated by DNA gyrase, implying that HU protein plays roles in suppression of illegitimate recombination and SOS response through interaction with DNA gyrase.

Bacterial Proteins↗
PubMed1998

Isolation of a Schizosaccharomyces pombe rad21ts mutant that is aberrant in chromosome segregation, microtubule function, DNA repair and sensitive to hydroxyurea: possible involvement of Rad21 in ubiquitin-mediated proteolysis.

The fission yeast DNA repair gene rad21+ is essential for cell growth. To investigate the function essential for cell proliferation, we have isolated a temperature-sensitive mutant of the rad21+ gene. The mutant, rad21-K1, showed abnormal mitosis at the nonpermissive temperature. Some cells contained abnormal nuclear structures, such as condensed chromosomes with short spindles, or chromosomes stretched or unequally separated by elongating spindles. Other cells exhibited the displaced nucleus or a cut-like phenotype. Similar abnormalities were observed when the Rad21 protein was depleted from cells. We therefore concluded that Rad21 is essential for proper segregation of chromosomes. Moreover, the rad21-K1 mutant is sensitive not only to UV and gamma-ray irradiation but to thiabendazole and hydroxyurea, indicating that Rad21 plays important roles in microtubule function, DNA repair, and S phase function. The relation to the microtubule function was further confirmed by the fact that rad21+ genetically interacts with tubulin genes, nda2+ and nda3+. Finally, the growth of the rad21-K1 mutant was inhibited at the permissive temperature by introduction of another mutation in the cut9+ gene, coding for a component of the 20S cyclosome/anaphase promoting complex, which is involved in ubiquitin-mediated proteolysis. The results suggest that these diverse functions of Rad21 may be facilitated through ubiquitin-mediated proteolysis.

Cell Cycle Proteins↗