Biomedical subjects

M Osawa

Publications and source records attributed to M Osawa.

At least 73 records · Page 4Linked to original sources

PubMed2000

Molecular cloning of murine STAP-1, the stem-cell-specific adaptor protein containing PH and SH2 domains.

To identify the novel substrate of c-kit which is important for hematopoietic stem cell self-renewal or differentiation, CD34-low/negative, Sca-1-positive, c-kit-positive, and lineage marker-negative (CD34(low/-)Sca-1(+)c-kit(+)Lin(-)) cells were sorted by a fluorescence-activated cell sorter from mouse bone marrow cells and a yeast two-hybrid cDNA library was constructed. By screening with c-kit as bait, we cloned a novel cDNA, designed STAP-1, encoding an adaptor protein with a Pleckstrin homology domain, the Src homology 2 (SH2) domain, and a number of tyrosine phosphorylation sites. RT-PCR analysis revealed that STAP-1 expression is restricted in the bone marrow cell fraction expressing c-kit. The highest expression was observed in the CD34(low/-)Sca-1(+)c-kit(+)Lin(-) stem cell-enriched fraction. The murine myeloid cell line, M1, expressed a high level of STAP-1. However, the expression was strongly repressed in response to leukemia inhibitory factor (LIF) which induced monocytic differentiation of M1 cells, suggesting that STAP-1 is associated with the undifferentiated cell type. A two-hybrid assay indicated that STAP-1 bound not only to c-kit but also to c-fms but not to JAK2 or Pyk2. In 293 cells, STAP-1 was tyrosine-phosphorylated by activated c-kit. An in vitro binding assay suggested that the STAP-1 SH2 domain interacted with several tyrosine-phosphorylated proteins including c-kit and STAT5. These suggest that STAP-1 functions as an adaptor molecule downstream of c-kit in hematopoietic stem cells.

Amino Acid Sequence↗

PubMed2000

Upregulation of brain somatostatin and neuropeptide Y following lidocaine-induced kindling in the rat.

Male Sprague-Dawley rats received a daily injection of 60 mg/kg of lidocaine (> 30 days). Twenty percent of rats developed convulsions (kindled rats) and remaining rats did not show convulsions (non-kindled rats). The level of immunoreactive somatostatin (IR-SRIF) in kindled rats was significantly increased in amygdala than that in non-kindled rats and control rats. Immunoreactive neuropeptide Y (IR-NPY) contents in kindled rats were significantly increased in amygdala, hippocampus, cortex and striatum compared to non-kindled and control rats. The expression of SRIF mRNA in kindled rats produced a significant increase in amygdala, while NPY mRNA in kindled rats showed an elevated expression in both amygdala and hippocampus. These results coincide with the previous findings with the elevated expression of SRIF and NPY mRNA in electrically and pharmacologically kindled models, suggesting the important role of these peptides in the kindling phenomenon.

Amygdala↗

PubMed2000

A role for pref-1 and HES-1 in thymocyte development.

T lymphocyte development requires a series of interactions between developing thymocytes and thymic epithelial (TE) cells. In this paper we show that TE cells in the developing thymus express Pref-1, a Delta-like cell-surface molecule. In fetal thymus organ cultures (FTOC), thymocyte cellularity was increased by the exogenous dimeric Pref-1 fusion protein, but was reduced by the soluble Pref-1 monomer or anti-Pref-1 Ab. Dimeric Pref-1 in FTOC also increased thymocyte expression of the HES-1 transcription factor. Thymocyte cellularity was increased in FTOC repopulated with immature thymocytes overexpressing HES-1, whereas FTOC from HES-1-deficient mice were hypocellular and unresponsive to the Pref-1 dimer. We detected no effects of either Pref-1 or HES-1 on developmental choice among thymocyte lineages. These results indicate that Pref-1 expressed by TE cells and HES-1 expressed by thymocytes are critically involved in supporting thymocyte cellularity.

Animals↗

PubMed2000

Characterization of the mouse interleukin-13 receptor alpha1 gene.

Interleukin (IL)-13 is a pleiotropic immune regulatory cytokine that shares structural and biological characteristics with IL-4. The receptor for IL-13 is comprised of the IL-4 receptor alpha (IL-4Ralpha) subunit and a low-affinity IL-13-binding subunit, IL-13Ralpha1. An additional receptor, IL-13Ralpha2, binds to IL-13 with high affinity, but lacks the cytoplasmic domain for signaling. In this study, we isolated the mouse IL-13Ralpha1 gene (Il13ra1) of approximately 56 kb that spans the entire coding region. The mouse Il13ra1 gene is composed of 11 exons, and shows striking similarity in genomic structure to the previously reported class I cytokine receptor genes. Motifs characteristic of the cytokine receptor family are similarly organized on the genome, including conserved cysteines, a WSxWS motif, and Box1, indicating closely related genetic evolution of the cytokine receptor superfamily. Alternative mRNA splicings were demonstrated to generate variant transcripts that encode soluble IL-13Ralpha1. The mouse Ill13ra1 gene was mapped to the proximal region of the mouse X chromosome, and was closely linked to the DXPas3 locus by interspecific backcross analysis. Il13ra1 mRNA was co-expressed with I14ra mRNA in mouse myeloid and natural killer cells on which IL-13 has been known to act, whereas the Il13ra2 mRNA was not detected in these cells, indicating that IL-13Ralpha1 is the major component of the IL-13 receptor complex in lymphohematopoietic cells.

Alternative Splicing↗

PubMed2000

A case of fatal methemoglobinemia of unknown origin but presumably due to ingestion of nitrate.

A case of fatal methemoglobinemia (MetHb-emia) which was presumably due to ingestion of nitrate is presented. An unidentified man was taken to a local emergency hospital suffering from deep cyanosis and 7 h later he was found dead in the hospital bed. The post-mortem examination of the blood revealed a methemoglobin (MetHb) concentration of 78% and the concentrations of nitrate and nitrite were 1.50 and 0.76 microg/mL, respectively. Capillary gas chromatography coupled to mass spectrometry (GC-MS) and capillary gas chromatography with a nitrogen-phosphorus detector (NPD) were used to detect nitrates and nitrites in the blood.

Aged↗

PubMed2000

Pyloromyotomy versus atropine sulfate for infantile hypertrophic pyloric stenosis.

PURPOSE: Atropine sulfate (atropine) and pyloromyotomy were compared for managing infantile hypertrophic pyloric stenosis (IHPS). METHODS: From 1996 to 1998, cases of IHPS treated surgically (pyloromyotomy; n = 20) or medically (atropine; n = 14) at separate institutions were compared retrospectively with regard to status on presentation, physical symptoms and signs, progress, and costs. Atropine was given orally, then intravenously if ineffective. Refractory cases were referred for pyloromyotomy. RESULTS: All subjects were matched for clinical and physiological status on admission. Oral atropine alone was effective in 11 cases, was converted to intravenous atropine in 2 cases, and was terminated in 1 case because of hematemesis. Two cases were referred for pyloromyotomy. All pyloromyotomies were successful. Atropine took on average, 2.6 days to take effect. The difference in time taken for normalization of pyloric muscle thickness between the 2 groups was not significant. Average time to return to full feeding was longer in the atropine group (P<.01). Costs were lower in the atropine group (P<.01). There were 2 wound infections in the pyloromyotomy group, but no adverse effects of atropine. There were no recurrences in either group. CONCLUSION: This study provides reasonable evidence to support a trial of atropine in IHPS.

Adult↗

PubMed2000

Risks of surgery for patients with unruptured intracranial aneurysms.

BACKGROUND: With the widespread use of less invasive imaging tools, such as magnetic resonance angiography and computed tomographic angiography, unruptured cerebral aneurysms are found much more often than in the past. This retrospective study was undertaken to determine the risk factors for surgical intervention in a patient with an unruptured intracranial aneurysm. METHODS: Over a 5-year period, 1,558 patients with intracranial aneurysms underwent surgery at our center. Of these, 310 patients (20%) with unruptured aneurysms were included in this study. RESULTS: Out of 310 patients with unruptured aneurysms, 292 (95%) had a favorable outcome, and only one patient (0.3%) with a giant vertebral artery aneurysm died. Aneurysm size larger than 15 mm and location of the aneurysm in the posterior circulation were independent risk factors associated with less favorable outcomes. Patients with a single aneurysm had a better outcome than did patients with multiple aneurysms. CONCLUSION: Our results support the contention that surgical treatment of unruptured intracranial aneurysms carries a low risk of morbidity and mortality and may improve the outcome in patients harboring cerebral aneurysms by preventing the devastating effects of subarachnoid hemorrhage. Aneurysm size, location, and number were risk predictors for surgical morbidity in patients with unruptured aneurysms.

Age Factors↗

PubMed2000

Dominant expansion of human T cells in non-obese diabetic/severe combined immunodeficiency mice implanted with human bone fragments.

OBJECTIVE: To establish an in vivo animal model in which human T cells develop and function normally, a step toward developing new vaccines or chemical compounds that modulate immune functions and toward understanding T-cell immunity in humans. MATERIALS AND METHODS: Human bone fragments were implanted into non-obese diabetes/severe combined immunodeficiency (NOD/SCID) mice. The presence of human blood cells in the peripheral blood of these mice was monitored periodically by immunostaining and fluorescence-activated cell sorting. RESULTS: After implantation of bone fragments, dominant expansion of human T lymphocytes, rather than myeloid and B cells, was observed over a 3-month period. In some cases, the proportion of human T cells rose to 40% of the peripheral blood mononuclear cells. These T cells showed CD4/CD8 ratios similar to those observed in human peripheral blood lymphocytes and had a broad repertoire of rearranged T-cell receptor genes. Graft-versus-host reaction was not noted in any organ analyzed. To assess the suitability of NOD/SCID mice implanted with human bone fragments (hu-bone-NOD/SCID mice) as an in vivo model for HIV infection, the mice were infected with a T-lymphotropic strain of HIV-1 (NL4-3) at 7 weeks posttransplant. Serum p24 gag was detected at 2 weeks after inoculation, after which total CD4-positive cell numbers declined, as seen clinically in patients infected with HIV. CONCLUSION: Although the precise mechanism is yet to be determined by which predominant expansion of human T cells occurs in hu-bone-NOD/SCID mice, such mice appear likely to serve as a useful and versatile model for studies involving human T-cell immunity.

Animals↗

PubMed2000

Visual evoked potentials in cerebral white matter hyperintensity on MRI.

OBJECTIVES: To investigate the correlation of the cerebral white matter hyperintensities (WMH) on MRI, and latency and amplitude of visual evoked potentials (VEPs) in elderly subjects. PATIENTS AND METHODS: Pattern VEP (PVEP) and flash VEP (FVEP) were recorded in 25 patients with WMH consisting of 12 patients with frontal dominant WMH (FMH) and 13 patients with occipital dominant WMH (OMH) and 25 patients with basal ganglionic hyperintensities (BGH). RESULTS: In WMHs, there were significantly larger P100 and P2 amplitudes than in BGHs and controls. Regarding the distribution of WMH, OMH showed significantly larger P100 amplitudes than FMH. In OMH in males, there was significantly prolonged P100 latency compared with females, and in females, there were significantly larger P100 and P2 amplitudes compared with males. CONCLUSION: Appropriate clinical values in VEP should take into consideration WMH in addition to gender and age-related changes.

Aged↗

PubMed2000

Fc alpha/mu receptor mediates endocytosis of IgM-coated microbes.

IgM is the first antibody to be produced in a humoral immune response and plays an important role in the primary stages of immunity. Here we describe a mouse Fc receptor, designated Fc alpha/microR, and its human homolog, that bind both IgM and IgA with intermediate or high affinity. Fc alpha/microR is constitutively expressed on the majority of B lymphocytes and macrophages. Cross-linking Fc alpha/microR expressed on a pro-B cell line Ba/F3 transfectant with soluble IgM or IgM-coated microparticles induced internalization of the receptor. Fc alpha/microR also mediated primary B lymphocyte endocytosis of IgM-coated Staphylococcus aureus. Thus, Fc alpha/microR is involved in the primary stages of the immune response to microbes.

Amino Acid Sequence↗

PubMed2000

Deficiency of the macrophage migration inhibitory factor gene has no significant effect on endotoxaemia.

By targeted disruption of the MIF gene, we have established a mouse strain deficient in macrophage (Mphi) migration inhibitory factor (MIF). Despite previous reports indicating an essential role of MIF in endotoxaemia, an injection of lipopolysaccharide (LPS) into the MIF-deficient mice (maintained under specific pathogen-free conditions) caused shock. No significant difference was detected between the MIF-deficient mutant and normal mice in susceptibility to LPS for endotoxaemia or tumour necrosis factor-alpha (TNF-alpha) formation upon LPS injection. Peritoneal Mphi from the two strains produced TNF-alpha in response to LPS with similar dose responses. Dexamethasone suppressed the LPS-induced TNF-alpha response of Mphi, but no difference was detected between the Mphi from the two strains. These results suggest that endogenous MIF has no significant effect on the LPS-induced TNF-alpha production and no effect on suppression of the response by glucocorticoids. Thus, MIF is not crucial for LPS-induced immune responses leading to shock.

Animals↗

PubMed2000

Successful trial of amantadine hydrochloride for two patients with alternating hemiplegia of childhood.

We report here the efficacy of amantadine hydrochloride for two patients with alternating hemiplegia of childhood (AHC) that did not respond to flunarizine. Amantadine was administered to one patient at age one year and seven months and to the other at age 25 years. The frequencies and duration of the hemiplegic attacks significantly improved in both patients. However, the attacks gradually returned to the previous level after a significant reduction in seizures for three years in the younger patient with ongoing AHC. Our therapeutic results further support the hypothesis that glutamate and NMDA receptors are involved in inducing alternating hemiplegic attacks, because amantadine as well as its derivative, memantine, are clinically available non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, with neuroprotective effects. Amantadine is worth trying when treating patients with AHC as a first trial or a substitute for flunarizine once the latter agent looses effect.

Adult↗

PubMed2000

Surgical indication for refractory childhood epilepsy.

Recent progress in surgical intervention for medically refractory epilepsy has helped to shed light on more complex epileptogenic problems in children and infants. Surgical treatment increasingly is being used in pediatric patients, but the indications for surgery in this age group have not been well defined. The developing child with a seizure disorder has several problems that are different from adults, such as neural plasticity, deleterious effects of seizures on developmental status, and spontaneous resolution of epilepsy. The critical age for irreversible brain dysfunction and the timing of surgery are the main issues for the treatment of children. Thus, earlier surgical intervention is generally recommended to prevent further detrimental seizure effects, but we still do not know the optimal age. Until the establishment of guidelines for pediatric epilepsy surgery, surgical indications should be determined by the prognosis and the presence of a resectable epileptogenic focus, which in turn are based on the localization of the epileptic focus, seizure frequency, severity, and cognitive function of each case, rather than just the patient's age.

Age Factors↗

PubMed2000

[Chest radiograph of atypical pneumonia: comparison among Chlamydia pneumoniae. Pneumonia, ornithosis, and Mycoplasma pneumoniae pneumonia].

No report has been found comparing Chlamydia pneumoniae (C. pneumoniae) pneumonia radiographically with other atypical pneumonias, Chlamydia psittaci (C. psittaci) pneumonia and Mycoplasma pneumoniae (M. pneumoniae) pneumonia. We described the chest radiographs of three kinds of pneumonia cases: 46 cases of C. pneumoniae pneumonia, 39 cases of C. psittaci pneumonia, and 131 cases of M. pneumoniae pneumonia. Radiographic shadows were categorized into main shadows and sub-shadows. The main shadows are classified from the viewpoint of the characteristics; air space consolidation(AS), ground-glass opacity(GG), reticular shadow(RS), bronchopneumonia(BP), and small nodular shadows (SN). The size, the site, and the number of the main shadows were also analyzed. In comparison among the three pneumonias, BP was the most frequent in M. pneumoniae pneumonia (0.40/case). AS predominated in C. pneumoniae pneumonia (0.67/case), and GG in C. psittaci pneumonia (0.62/case). The number of main shadows was equal, about 1.4/case in three pneumonias. Large shadows were less frequent in M. pneumoniae pneumonia than C. pneumoniae pneumonia (p = 0.02) and C. psittaci pneumonia (p = 0.01). Main shadows were more frequent in the outer zone in M. pneumoniae pneumonia than C. psittaci pneumonia (p = 0.01), and in the middle zone in C. psittaci pneumonia than in M. pneumoniae pneumonia (p = 0.02). Cases with bilateral main shadows were less common in M. pneumoniae pneumonia (9%) than C. pneumoniae pneumonia(33%, p = 0.001) and C. psittaci pneumonia(30%, p = 0.005). Thickening of bronchovascular bundles as a sub-shadow was most frequently noted in M. pneumoniae pneumonia. Some differences among the three atypical pneumonias were seen in the chest radiograph. However, no specific findings of C. pneumoniae pneumonia were shown radiographically in this study.

Aged↗

PubMed2000

Topographic mapping of P300 and frontal cognitive function in Parkinson's disease.

The purpose of this study was to evaluate the relationship between P300 that is one of the event-related potentials and frontal cognitive functions in Parkinson's disease (PD) without clinically apparent dementia. Subjects were 20 PD cases 48 to 79 years of age, all of whom were within normal limits on the Mini-Mental State examination, and 55 age-matched healthy adults. P300 was elicited with an auditory oddball paradigm and recorded at 15 sites on the scalp. Cognitive functioning of the frontal lobe was evaluated using the New Modified Wisconsin Card Sorting Test (WCST) and the Letter Pick-Out Test (LPOT) which reflects selective attention and semantic categorization. P300 latency was delayed in 30.0% of P300 demonstrated abnormal distribution in 20.0%. the WCST and the LPOT were abnormal in 15.0%, P300 latency significantly correlated with number of subcategories achieved on the WCST. P300 amplitude correlated with scores on the LPOT. These results suggest that cognitive dysfunction which linked partly to the frontal lobe might begin in PD even without clinically apparent dementia.

Journal Article↗

PubMed2000

Evidence for the AT1 subtype of the angiotensin II receptor in the rat submandibular gland.

We have characterized angiotensin II (Ang II) receptor subtypes on rat submandibular gland membranes using a radioligand binding assay. [3H]Ang II binding to the membrane fractions exhibited both high (Kd =0.08 nm, Bmax =2.19 fmol/mg protein) and low (Kd =4.19 nm, Bmax = 13.7 fmol/mg protein) affinity. Ang 11, Ang III and saralasin completely displaced the [3H]Ang II binding, whereas CV-11974, an AT1 receptor antagonist and PD123319, an AT2 receptor antagonist maximally displaced up to approximately 87 and 13% of the total binding, respectively. [3H]DuP753 binding to the membrane fractions exhibited a single population of binding site with a Kd of 4.22 nM and Bmax of 3.77 pmol/mg protein. Ang II, Ang III and CV-11974 completely displaced the [3H]DuP753 binding with slope factors near unity, but PD123319 did not. These findings suggest that rat submandibular gland membranes contain predominantly the AT1 receptor subtype.

Angiotensin Receptor Antagonists↗

PubMed2000

Familial cases of severe measles pneumonia.

We report two cases of severe measles pneumonia. Patient 1, a 17-year-old boy who contracted measles in the acute phase of infectious mononucleosis caused by Epstein-Barr virus (EBV), transmitted the disease to patient 2, his father. Both patients presented severe pneumonia with bilateral diffuse micronodular shadows. Diagnoses were established in both patients by antibody titers for measles and reverse transcriptase-polymerase chain reaction (RT-PCR) of blood and throat swab. Multinucleated giant cells with intranuclear inclusion bodies were revealed in the transbronchial lung biopsy (TBLB) specimen of patient 2. Both patients recovered with pulse steroid therapy.

Adolescent↗

PubMed2000

[Complications of percutaneous endoscopic gastrostomy in the elderly: local skin infection and respiratory infection].

We investigated post-operative management of acute complications of percutaneous endoscopic gastrostomy (PEG) which often caused respiratory infections and local skin infections. The subjects were a total of 341 patients (male 131, female 210, and the mean age was 80.3), they were classified into six groups by method of feeding and use of antibiotics. Patients were divided into three groups based on the time that feeding was started. In Group I, enteral feeding was not started within the first five days. In Group II, sterilized enteral feeding (lactated Ringer's solution for intravenous infusion) using sterilized intravenous infusion kit started within 24 hours after the procedure, and in Group III, feeding of the usual enteral formula started within 24 hours after the procedure. And as for the using of antibiotics, they were also divided into two groups, antibiotics administered[AB (+)] and no antibiotics administered[AB (-)]. Thus, the patients were divided into six groups according to the time of starting nutrition and the use of antibiotics. The rates of incidence of acute respiratory infections and local skin infections in the six groups were compared by the chi-square test and differences in the rates of incidence of complication were also compared between two PEG methods; the Pull/Push method and the Introducer method. The frequency of local skin infection in Group III was significantly higher than in Group I and Group II. As for the PEG methods, the frequency of local skin infection in the Pull/Push method was significantly higher than Introducer methods. Acute respiratory infections occurred significantly less in the AB (+) group than in the AB (-) group. Postoperative administration of antibiotics would seem to be appropriate for prophylaxis of respiratory infection in elderly patients after PEG. On the other hand, local skin infections are not related to administration of antibiotics, and are highly related to the method of feeding. We concluded that nutrition of sterilized enteral feeding immediately after operation using a sterilized intravenous infusion kit and administration of antibiotics are advisable to prevent major complications in elderly patients.

Aged↗