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Biomedical subjects

M Sawada

Publications and source records attributed to M Sawada.

At least 91 records · Page 5Linked to original sources
PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 3). Effects of repeated doses of ethinylestradiol for 2 and 4 weeks on the male reproductive organs.

Male Sprague-Dawley rats were subcutaneously administered 0.3 and 3.0 mg/kg/day of ethinylestradiol for 2 and 4 weeks. Two weeks treatment decreased body weight gain, food consumption, absolute weights of testis, epididymis, prostate and seminal vesicle, and relative weights of epididymis, prostate and seminal vesicle. On the other hand, it increased absolute and relative weights of pituitary and adrenal glands, and induced atrophy of Leydig cells, degeneration/necrosis of pachytene spermatocytes, vacuolar degeneration of Sertoli cells, and retention of spermatids. In addition to the changes found after 2 weeks treatment, 4 weeks treatment induced exfoliation of germinal cells, decreases in spermatid and multinucleated giant cell formation and relative weights of testis. These results suggest that examination of prostate and seminal vesicle weights and histopathological changes in the testis are important for evaluation of male reproductive toxicity of ethinylestradiol and 2 weeks treatment is sufficient to detect toxicity on male reproductive organs.

Adrenal Glands↗
PubMed2000

Acute intermittent porphyria associated with transient elevation of transaminases during an acute attack.

A 44-year-old woman with acute intermittent porphyria (AIP) was admitted to Kudanzaka Hospital because of abdominal pain. A cholecystectomy was performed in another hospital without improvement. On admission, her transaminases were elevated to greater than 1,000 mU/ml. After an intravenous drip of mainly glucose, her transaminases returned to normal. Her acute attacks occurred during stress, and she died of respiratory failure after repetitive acute episodes. AIP should be included in a list of the differential diagnosis of gastrointestinal diseases, neurosis, and hysteria. This is the first case of AIP accompanied by transient marked elevation of transaminases during an acute attack.

Adult↗
PubMed2000

Detection of acute promyelocytic leukemia (APL) cells intermediately differentiated by all-trans retinoic acid in the cerebrospinal fluid: central nervous system involvement in APL.

We report a patient with acute promyelocytic leukemia (APL) involving the central nervous system. A 55-year-old male was admitted to our hospital with dysarthria and incomplete right hemiplegia. A CT scan of the brain revealed a low density area in the left cerebrum. APL was diagnosed by bone marrow aspiration and chromosomal analysis. The patient received all-trans retinoic acid (ATRA) in combination with chemotherapy. Complete hematological remission (CR) was obtained, and the patient's neurological symptoms improved. However, a cytospin smear of the cerebrospinal fluid after CR showed immature myelocytes ("intermediate cells") that had possibly been derived from leukemic promyelocytes. Comprehensive intrathecal treatment as well as cranial irradiation, caused a further reduction in dysarthria and a complete disappearance of hemiplegia with no atypical cells in the cerebrospinal fluid. The patient has undergone maintenance chemotherapy as an out-patient.

Brain Neoplasms↗
PubMed2000

Management of severe neutropenia with cyclosporin during initial treatment of Epstein-Barr virus-related hemophagocytic lymphohistiocytosis.

Severe neutropenia (absolute neutrophil count <500/gl) is probably due to the combined effects of dysregulated cytokine production and chemotherapeutic agents, and is one of the risk factors in the initial treatment of patients with Epstein-Barr virus-related hemophagocytic lymphohistiocytosis (EBV-HLH). We report here 9 cases of neutropenic HLH, of which 8 were treated with cyclosporin (CSA, 2-6 mg/kg/day; continuous infusion, or 6 mg/kg/day; per os, for periods ranging from 9 days to >8 weeks) in the initial neutropenic phase during induction treatment using corticosteroids and etoposide. Five of the 6 cases, in which CSA treatment was started early (before the second week of induction), survived the critical period with recovery of neutrophil counts within a week. The remaining 3 cases, in which CSA was introduced later or not at all, died of infection. Based on these results, we recommend a prompt short-term CSA infusion during neutropenic episodes in the most common treatment regimen of etoposide and corticosteroids in patients with HLH. Improved neutrophil recovery as a result of CSA treatment makes it possible to continue immunochemotherapy safely and obtain improved patient outcomes.

Adolescent↗
PubMed2000

[Two cases of orbital non-Hodgkin's lymphoma presenting with hemophagocytic syndrome].

We report 2 cases of orbital non-Hodgkin's lymphoma (NHL) with hemophagocytic syndrome (HPS). Patient 1 was a 64-year-old man with a diagnosis of peripheral T-cell lymphoma originating in the right orbita (clinical stage: IV B). Epstein-Barr virus DNA was demonstrated in tissue specimens by polymerase chain reaction. Laboratory findings on admission were WBC: 4,700/microliter, Hb: 12.1 g/dl, Plt: 14.6 x 10(4)/microliter, LDH: 951 IU/l, sIL-2R: 2,553 IU/ml, and ferritin: 5998.1 ng/ml. Patient 2 was a 73-year-old man with a diagnosis of diffuse large B-cell lymphoma originating in the right orbita (Clinical stage: IV B). Laboratory findings on admission were WBC: 9,100/microliter, Hb: 7.7 g/dl, Plt: 15.4 x 10(4)/microliter, LDH: 1,043 IU/l, sIL-2R: 10,090 IU/ml, and ferritin: 2079.3 ng/ml. Both patients had high-grade fever and extremely high serum cytokine levels. Bone marrow aspiration disclosed many histiocytes with hemophagocytosis. In both cases, combined chemotherapy was transiently effective, but patient 1 died of relapse of HPS and patient 2 of cerebral bleeding. Orbital non-Hodgkin's lymphoma with HPS is rare. These cases were interesting in terms of the relationship between HPS and the primary site of lymphoma.

Aged↗
PubMed2000

Abstinence from drink ameliorated cerebral blood flow and vasoreactivity in patients with chronic alcoholism.

High dose ethanol consumption is a risk factor for both ishemic and hemorrhagic cerebrovasucular disease. This link between heavy drinkers and the risk factor of stroke has been considered as hypertension, liver dysfunction, abnormality of platelet function or other unknown mechanisms. Recently some of the experimental study suggest that direct action of ethanol on the inhibition of the synthesis/release of nitric oxide from endothelium and neurons may contribute to this link. Few studies in this field, however, were performed clinically. We examined cerebral blood flow (CBF) and vaso-reactivity in the patients with chronic alcoholism on abstinence from drink. CBF of nine male patients were measured by use of stable Xe-CT method before and after acetazolamide load. Regional CBF increased in second measurement after abstinence, but there were no significant changed statistically. However, %vaso-reactivity in right ACA and MCA significantly improved. We considered that large brain vessels dilated then small vessels could response to acetazolamide.

Acetazolamide↗
PubMed2000

A specific thrombin inhibitor (argatroban) ameliorated cerebral blood flow in the patients with acute cerebral infarction.

Argatroban, one of the arginine derivatives, has been reported to have a safe and potent antithrombin action. This compound is active in several animal models of thrombosis and also has been shown to improve general neurological symptomatology, general subjective symptomatology and general daily behavior in the patients with acute thrombosis. This was considered to reflect remarkable improvement of microcirculation. No published clinical data, however, exist on the effect of argatroban on cerebral blood flow (CBF) change during acute stroke. Three patients with acute cerebral infarction were subjected to this study. Intravenous argatroban injection (2.5 mg/hr) was continued in 48 hours. Regional CBF (rCBF) was measured before and after injection of argatroban using Xe-CT method. Argatroban increased CBF not only in the injured side hemisphere or penumbra, but also contralateral side of lesion in the patients with acute cerebral infarction.

Aged↗
PubMed2000

Refractory facial cellulitis following cosmetic rhinoplasty after cord-blood stem cell transplantation.

We report a case of a 38-year-old female patient who developed facial cellulitis after cord-blood stem cell transplantation (CBT). The cellulitis was refractory to treatment with antibiotics and antifungal agents. Because facial cellulitis is rare after transplantation, its mechanism could not be determined exactly. On day 40 after CBT, a nurse with expertise in cosmetic surgery attended our rounds and correctly assumed that the patient had received cosmetic rhinoplasty. Although conventional x-rays of the head were normal, a computed tomographic (CT) scan of the brain disclosed the presence of a foreign body over the nasal dorsum. As a result, the patient's symptoms were diagnosed as facial cellulitis associated with foreign material that had been implanted at the time of cosmetic surgery. At a pretransplantation interview, the patient did not mention her history of rhinoplasty. Even after she was shown the head CT scans that revealed the presence of nasal implants, she denied that she had received rhinoplasty before CBT. Unless we realize that patients may have received cosmetic surgery before transplantation, it is difficult to make a diagnosis of infection associated with foreign implants. To our knowledge this is the first report after transplantation of infection associated with cosmetic surgery. Such infections should be included on the list of complications after bone marrow transplantation.

Adult↗
PubMed1999

Exogenous microglia enter the brain and migrate into ischaemic hippocampal lesions.

We compared migration of systemically injected microglia into normal brain vs. ischaemic brain using a model of ischaemic hippocampal lesion. Microglia were labeled by a fluorescent dye using our standard phagocytosis procedure of microscopic particles and then injected intra-arterially into Mongolian gerbils subjected to ischaemia reperfusion neuronal injury. Delayed death of pyramidal neurons was confirmed by conventional histological analysis and dUTP nick end labeling (TUNEL) method. Clusters of dye-tagged cells migrating into the hippocampal ischaemic lesions were confirmed histochemically to be microglia. Since peripherally injected microglia exhibit specific affinity for ischaemic brain lesions and does not exacerbate ischaemic neuronal injury in the present model, we suggest that microglia may have a potential to be used as a piggy-back ride to deliver therapeutic genes and/or drugs for CNS repair following transitory global ischaemic insult.

Animals↗
PubMed1999

Migration of exogenous immature hematopoietic cells into adult mouse brain parenchyma under GFP-expressing bone marrow chimera.

Bone marrow transplantation with GFP-expressing cells from GFP-transgenic mice resulted in migration of GFP-positive cells into peripheral tissues and brain parenchyma. Most of these cells were observed as colony-like clusters. GFP-positive clusters in the brain were stained by antibody for ER-MP12, but those in the peripheral tissues were not. Since ER-MP12 antigen has been reported as a marker for murine early-stage myeloid precursor, this might suggest that some parts of phagocytic cells in the brain parenchyma such as microglia are derived from undifferentiated pluripotent hematopoietic cells.

Animals↗
PubMed1999

Enhanced Fos expression in the hippocampus of El mice after short-term vestibular stimulation.

The El mouse is an animal model for human epilepsy. The mouse manifest seizures in response to periodically repeated vestibular stimuli such as being tossing-up. Although this technique has been traditionally employed to accelerate this disease in the mouse, its meaning remained obscure. The present study was conducted to estimate the effects of tossing-up stimuli on expression of c-fos, a well-known marker of neuronal activation. Expression of c-fos was significantly increased even after single tossing-up specimen. It was blocked by pretreatment of the mouse with MK-801, a NMDA receptor antagonist. A marked expression of the oncoprotein was observed in the granule cell layer of dentate gyrus and CA1-3 pyramidal cell layer in the hippocampus of the mouse. These results suggest that the El mice are genetically hyper-sensitive to the vestibular stimuli.

Animals↗
PubMed1999

Ibudilast suppresses TNFalpha production by glial cells functioning mainly as type III phosphodiesterase inhibitor in the CNS.

Tumor necrosis factor alpha (TNFalpha) is considered to play a critical role in the development of various pathological processes in the central nervous system (CNS), such as neuronal degeneration, demyelination and HIV-related pathology. In order to search for the agents which suppress TNFalpha production in the CNS for future treatment of these pathological conditions, we examined the effects of ibudilast on TNFalpha production by murine microglia and astrocytes. Some actions of ibudilast are reportedly mediated by inhibition of type IV phosphodiesterase (PDE). Type IV PDE inhibitor has been shown to be the most effective for experimental autoimmune inflammatory demyelination. Therefore, we also determined the subtype of PDE inhibited by ibudilast. Ibudilast significantly and selectively suppressed TNFalpha production by microglia in a dose-dependent manner, without affecting their viability. The inhibition assay indicated that ibudilast is a rather selective inhibitor for type III PDE purified from brain, heart and kidney with moderate inhibitory activity against types I, II and IV PDEs from various tissues. Although it required 10 microM or higher concentrations to effectively suppress TNFalpha production in vitro, the combination of ibudilast with other subtypes of PDE inhibitors synergistically suppressed TNFalpha and nitric oxide production by microglia at 1 microM, a similar concentration that could be obtained in vivo at usual therapeutic dose. Thus, ibudilast, when used in a combination with other PDE inhibitors, will be useful for future strategies to treat intractable neurological diseases in which TNFalpha may play a causative role.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1999

Regulation of phosphorylation level and distribution of PTP36, a putative protein tyrosine phosphatase, by cell-substrate adhesion.

Recently we have cloned a putative protein tyrosine phosphatase, PTP36/PTPD2/pez, which possesses a domain homologous to the N-terminal half of band 4.1 protein. In mouse fibroblasts adhered to substrates, PTP36 was phosphorylated on serine residues. PTP36 was found to make complexes with serine/threonine kinase(s), which phosphorylated PTP36 in vitro. PTP36 was dephosphorylated rapidly when the cell-substrate adhesion was disrupted and it was phosphorylated again along with the reattachment of the cells to fibronectin. Rephosphorylation of PTP36 seemed to depend on actin polymerization since it was inhibited by cytochalasin D. The cell detachment also induced the translocation of PTP36 into the membrane-associated cytoskeletal fraction. Staurosporine and ML-9, which inhibited the phosphorylation of PTP36 in vivo, induced the translocation of PTP36 too. On the contrary, when the dephosphorylation of PTP36 was inhibited by okadaic acid, no translocation of PTP36 was induced by the cell detachment. These results demonstrate that the cell-substrate adhesion and cell spreading regulates the intracellular localization of PTP36 most likely through its phosphorylation and therefore, PTP36 may play important roles in the signal transduction pathway of cell-adhesion.

Animals↗
PubMed1999

Potentiation of GABA(A) receptor-mediated Cl-current by urotensin peptides in identified Aplysia neurons.

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the vertebrate and invertebrate central nervous systems, including those of molluscs. The effects of extracellularly applied urotensin peptides (urotensin I (UI) and urotensin II (UII)) on the GABA-induced Cl- current recorded from identified neurons (R9 and R12) of Aplysia kurodai were investigated using voltage-clamp and pressure ejection techniques. Focal application of 100 nM UI and UII potentiated the GABA-induced Cl- current without affecting the resting membrane conductance and holding current. The increase was completely reversible. The GABA-induced Cl- current also was potentiated by bath-applied UI and UII (5-10 nM). The potentiating effects of UI and UII on the GABA-induced Cl- current were concentration-dependent and completely reversible. These results suggest that neurotensin peptides may decrease neuronal excitability by potentiating the GABA(A) receptor-mediated Cl- current in the neurons of mammalian and invertebrate central nervous systems.

Animals↗
PubMed1999

Molecular cloning and characterization of a plasma membrane-associated sialidase specific for gangliosides.

Gangliosides are plasma membrane components thought to play important roles in cell surface interactions, cell differentiation, and transmembrane signaling. A mammalian sialidase located in plasma membranes is unique in specifically hydrolyzing gangliosides, suggesting crucial roles in regulation of cell surface functions. Here we describe the cloning and expression of a cDNA for the ganglioside sialidase, isolated from a bovine brain cDNA library based on the amino acid sequence of the purified enzyme from bovine brain. This cDNA encodes a 428-amino acid protein containing a putative transmembrane domain and the three Asp boxes characteristic of sialidases and sharing 19-38% sequence identity with other sialidases. Northern blot and polymerase chain reaction analyses revealed a general distribution of the gene in mammalian species, including man, and the mouse. In COS-7 cells transiently expressing the sialidase, the activity was found to be 40-fold that of the control level with ganglioside substrates in the presence of Triton X-100, and the hydrolysis was almost specific to gangliosides other than GM1 and GM2, both alpha2-->3 and alpha2-->8 sialyl linkages being susceptible. The major subcellular localization of the expressed sialidase was assessed to be plasma membrane by Percoll density gradient centrifugation of cell homogenates and by immunofluorescence staining of the transfected COS-7 cells. Analysis of the membrane topology by protease protection assay suggested that this sialidase has a type I membrane orientation with its amino terminus facing to the extracytoplasmic side and lacking a signal sequence.

Amino Acid Sequence↗
PubMed1999

Serial analysis of gene expression in a microglial cell line.

We used the serial analysis of gene expression (SAGE) method to systematically analyze transcripts present in a microglial cell line. Over 10,000 SAGE tags were sequenced, and shown to represent 6,013 unique transcripts. Among the diverse transcripts that had not been previously detected in microglia were those for cytokines such as endothelial monocyte-activating polypeptide I (EMAP I), and for cell surface antigens, including adhesion molecules such as CD9, CD53, CD107a, CD147, CD162 and mast cell high affinity IgE receptor. In addition, we detected transcripts that were characteristic of hematopoietic cells or mesodermal structures, such as E3 protein, A1, EN-7, B94, and ufo. Furthermore, the profile contained a transcript, Hn1, that is important in hematopoietic cells and neurological development (Tang et al. Mamm Genome 8:695-696, 1997), suggesting the probable neural differentiation of microglia from the hematopoietic system in development. Messenger RNA expression of these genes was confirmed by RT-PCR in primary cultures of microglia. Significantly, this is the first systematic profiling of the genes expressed in a microglial cell line. The identification and further characterization of the genes described here should provide potential new targets for the study of microglial biology.

Animals↗