Biomedical subjects

S Nagata

Publications and source records attributed to S Nagata.

At least 361 records · Page 20Linked to original sources

PubMed1995

A missense mutation in the beta-myosin heavy chain gene in a Japanese patient with hypertrophic cardiomyopathy.

A 55-year-old man had been previously admitted at the age of 44 because of chest pain on effort. He was diagnosed as hypertrophic obstructive cardiomyopathy with a left ventricular outflow pressure gradient of 65 mmHg. We analyzed the cardiac beta-myosin heavy chain gene in this patient using polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP analysis). PCR-SSCP analysis revealed a sequence variation within exon 16. A G-to-A transversion with replacement of Val by Met at codon 606 was confirmed by sequencing analysis. Previously, a 606Val-->Met mutation has been reported to give a benign prognosis because of the neutral charge substitution. However, there have been some premature deaths in this patient's kindred. Thus, despite the absence of a change in charge, this mutation may be malignant in some kindreds.

Cardiomyopathy, Hypertrophic↗

PubMed1995

Pathways of tumour cell killing by activated macrophages: both tumour cell membrane and nucleus can be the primary target.

Plasma membrane and nucleus can be primary targets of tumour cell killing by activated macrophages (AMø). Necrotic-type cytotoxicity with loss of membrane integrity and cytoplasmic swelling was expressed by AMø from normal and from perforin-deficient mice, indicating that perforin was not involved. Incubation with AMø consistently triggered the release of thymidine from prelabelled targets, whereas chromatin condensation and small DNA fragments were only occasionally detected. It is shown by means of Pulsed-Field Gel Electrophoresis that DNA degradation in target cells is a slowly progressing process that may stop at any time, indicating that nuclear-type killing doesnot necessarily lead to the formation of low molecular weight fragments. Neither Fas nor the p55 tumour necrosis factor receptor appear to be involved in signalling nuclear-type killing. Accordingly, AMø do mediate membrane- and nuclear-type killing but the mechanisms differ from those identified in T cell cytotoxicity.

Journal Article↗

PubMed1995

Lethal effect of carbonyl cyanide m-chlorophenylhydrazone on Escherichia coli and a halotolerant Brevibacterium species.

An attempt was made to examine quantitatively the survival of Escherichia coli and the halotolerant Brevibacterium species, as a function of the exposure time to carbonyl cyanide m-chlorophenylhydrazone (CCCP), a proton conductor. Growth rates, viability, and protein concentrations of E. coli grown in the absence of glucose were unaffected by the addition of 100 microM CCCP. In the presence of glucose the viability was reduced after 24 h incubation with CCCP. Such a high efficiency of CCCP lethality for E. coli cells in the presence of glucose was attributed to not only the growth phase but also the acidic pH of the culture due to metabolites from glucose, mainly lactic acid. The culture of E. coli appeared to be in a syncopic state hovering between life and death when it was exposed to CCCP in the presence of more than 30 mM glucose. In contrast, growth rates of Brevibacterium were reduced in proportion to the exposure time to CCCP. The lethal effect of CCCP to Brevibacterium was slightly enhanced by the addition of glucose into the culture.

Anti-Bacterial Agents↗

PubMed1995

Antihypertensive properties of a new long-acting angiotensin converting enzyme inhibitor in renin-dependent and independent hypertensive models.

The antihypertensive properties of a new long-acting, angiotensin-I-converting enzyme (ACE) inhibiting agent, (2S,3aS,7aS)-1-(N2-nicotinoyl-L-lysyl-gamma-D-glutamyl) octahydro-1H-indole-2-carboxylic acid (CAS 116662-73-8, DU-1777), were investigated orally in various experimental models of hypertension in comparison to a standard ACE inhibitor, lisinopril. The hypotensive potency of DU-1777 was not as marked as that of lisinopril in renin-dependent hypertensive models, i.e., two-kidney one-clip renal hypertensive rats (2K-1C RHR) (ED-20mmHg: 3.1 versus 1.0 mg/kg) or two-kidney two-clip renal hypertensive dogs (2K-2C RHD) (ED-20 mmHg: 2.5 versus 1.0 mg/kg), though the actions of the two drugs were both long-lasting and dose-related. When spontaneously hypertensive rats (SHR) were used, however, DU-1777 was as active as lisinopril (ED-20 mmHg: 17.9 versus 13.6 mg/kg). The most distinguishing results with DU-1777 were its hypotensive effects in renin-independent hypertensive models. In contrast to lisinopril, the drug produced a sustained and dose-related hypotensive effect in DOCA salt hypertensive rats (DOCA-HR) and one-kidney one-clip renal hypertensive rats (1K-1C RHR). There exists an inconsistency between the long duration of the agent's hypotensive action in all tested hypertensive models and its short duration of ACE inhibiting activity as demonstrated both in vivo and ex vivo. The sustained antihypertensive action of DU-1777 cannot be reasoned solely with respect to ACE inhibition, suggesting some additional mechanisms of action yet to be defined.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1995

[Growing skull fracture: a case report].

An 18-day-old male baby who had fallen from his mothers arms and hit his head on the floor was admitted to our hospital. On admission, the patient was crying, but no weakness was noted in the extremities. A small fluctuant protrusion was visible in the right parietal region. The plain skull X-ray film revealed a wide linear fracture in the parietal bone. Computed tomography (CT) showed swelling of the right hemisphere and a traumatic subarachnoid hemorrhage. At 41 days old, the subcutaneous fluid collection had increased in volume and the width of the linear skull fracture was also enlarged as shown on the X-ray film. CT and magnetic resonance imaging (MRI) revealed a large cyst herniating through the wide parietal bone defect. There was also an enlarged right lateral ventricle and a torn dural margin in the brain. The cranioplasty with dural plasty was performed on the 43rd day of ago under the diagnosis of growing skull fracture of the right parietal bone. The postoperative course was uneventful, without seizure or weakness. In order to diagnose growing skull fracture, especially to show the relationship between the fracture, torn dura matter, the ventricle and the contused brain, MRI was very helpful combined with CT and plain skull X-rays. Cranioplasty with dural repair was considered the essential procedure for the treatment of such growing skull fractures.

Craniotomy↗

PubMed1995

Hepatic fibrosis produced in guinea pigs by chronic ethanol administration and immunization with acetaldehyde adducts.

Experimental hepatic fibrosis was produced in the guinea pig. We produced hepatic necrosis associated with inflammatory cell infiltration in guinea pigs immunized with acetaldehyde adducts and fed ethanol for 40 days. Extending the period of these treatments to 90 days resulted in producing hepatic fibrosis developing around individual hepatocytes in the terminal hepatic venule areas and portal areas, accompanied by an increase in hepatic hydroxyproline content. In contrast, no fibrosis was observed in the livers of the control groups that had been exposed to nothing, ethanol alone, or a combination of ethanol and immunization with unmodified human hemoglobin. Minimal fibrotic changes were observed in animals immunized with human hemoglobin acetaldehyde adducts but not fed ethanol. These results indicate that the formation of acetaldehyde adducts and the acquisition of immunity against them can produce hepatic fibrosis. Immune mechanisms against acetaldehyde adducts may, in part, be involved in the pathogenesis of hepatic fibrosis seen in alcoholics.

Acetaldehyde↗

PubMed1995

Electron microscopic lectin histochemistry of the trabecular meshworks in human eyes.

Ten normal human trabecular meshworks were examined by electron microscopy using avidin-biotin complex in order to investigate the localization of binding sites of eight lectins. The tissue specimens were fixed in paraformaldehyde and glutaraldehyde mixture and embedded in Lowicryl K4M at low temperature. The ultrathin sections were stained with biotin labelled lectins and colloidal gold labelled streptoavidin and were observed with the conventional transmission electron microscope. Some lectins such as ABA, ConA and DSA were localized on fine fibrils underneath the endothelium of the trabecular wall of the Schlemm's canal, electron-dense cores of elastic fibers, fine granular like materials, basement membranes, collagen fibers and the long-spacing fibers. However, the other lectins such as DBA, SBA, Lotus, UEA-I and RCA60 were not specifically localized in these tissues. From the results it was demonstrated that the differential ultrastructural localization of glycoconjugate residues in the human trabecular meshworks can be revealed using this lectin staining.

Adult↗

PubMed1995

[Feasibility of the left ventricular volume measurement by acoustic quantification method: comparison with ultrafast computed tomography].

Acoustic quantification (AQ: the real-time automated boundary detection system) allows instantaneous measurement of cardiac chamber volumes. The feasibility of this method was evaluated by comparing the left ventricular (LV) volumes obtained with AQ to those derived from ultrafast computed tomography (UFCT), which enables accurate measurements of LV volumes even in the presence of LV asynergy, in 23 patients (8 with ischemic heart disease, 5 with cardiomyopathy, 3 with valvular heart disease). Both LV end-diastolic and end-systolic volumes obtained with the AQ method were in good agreement with those obtained with UFCT (y = 1.04 x - 16.9, r = 0.95; y = 0.87x + 15.7, r = 0.91; respectively). AQ was reliable even in the presence of LV asynergy. Interobserver variability for the AQ measurement was 10.2%. AQ provides a new, clinically useful method for real-time accurate estimation of the left ventricular volume.

Feasibility Studies↗

PubMed1995

[Prediction of ineffective outcome of surgical treatment for constrictive pericarditis].

The preoperative factors predicting the outcome of surgical treatment for constrictive pericarditis were investigated in 22 patients with constrictive pericarditis who underwent pericardiectomy. The NYHA functional class was improved in nine patients after surgery (improved group), but not in the other 13 patients (unimproved group). Preoperative right and left heart catheterization data and echocardiograms were compared between these two groups. Right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) were significantly higher in the unimproved group. The left atrial diameter (LAD) measured by echocardiography was significantly greater in the unimproved group. These results indicate that pericardiectomy will cause a worsened immediate outcome in patients with severe pericardial constriction. LAD was the most useful parameter in predicting the ineffectiveness of the pericardiectomy. If the borderline value of LAD is taken as 40 mm, the sensitivity and specificity predicting ineffective surgery were 92% and 89%, respectively. RAP and PCWP could not separate the two groups satisfactorily. Pericardiectomy should be performed before the pericardial constriction progresses, and before LAD reaches 40 mm.

Adult↗

PubMed1995

[Evaluation of surgical procedures based on the types of hypertrophied obstructive cardiomyopathy].

The surgical procedures were reviewed based on the types of hypertrophied obstructive cardiomyopathy in 20 patients. The patients were classified in three groups: (1) Asymmetric septal hypertrophy (ASH), (2) Atypical or diffuse concentric hypertrophy (DIF), (3) Mid ventricular obstructive hypertrophy (MID). Among 11 patients with ASH, the ventricular septal myotomy (My) or the myotomy-myectomy (Mye) were performed in 9 patients and MVR was performed in 2 patients. Among 6 patients with DIF, My or Mye were performed in 4 and MVR was performed in 2. All three patients with MID were treated with MVR. The intraventricular systolic pressure gradient greater than 40 mmHg was still existent postoperatively in one ASH patient on whom Mye was performed and in 3 DIF patients on whom My or Mye were performed. The four patients had III degree mitral regurgitation preoperatively and were successfully treated. The postoperative NYHA functional class became II or less in all patients. For ASH, the My was effective in 9 patients except one earlier patient. For DIF, further consideration of surgical procedure might be required. For MID, a MVR is recommended.

Adult↗

PubMed1995

Total auricular reconstruction with a three-dimensional costal cartilage framework.

Microtia (hypoplasia of the auricle) is known to result from incomplete development of the auricle during embryonic development so that the size and shape of the deformity vary from case to case. Total auricular reconstruction for microtia is dependent on the degree of hypoplasia in comparison to that of the normal auricle on which the specific reconstruction method is based. I have classified microtia into 3 major types: 1) The lobule type. 2) The concha type, and 3) The small concha type which has been previously described [32]. Regardless of the size and shape of the deformity, the ultimate goal of total reconstruction of the auricle consists of construction of an auricle with an appearance as close as possible to that of a normal auricle. With this objective in mind, total reconstruction of the article is a science and not just a form of art as frequently considered. If it is only an art, the constructed auricle is greatly influenced by the artist's individuality and by the observer's. Thus, as a reconstructive plastic surgeon, the final outcome or result of total reconstruction of the auricle is that the constructed auricle should resemble as closely as possible the normal auricle, regardless of the observer and without any personal influence of the surgeon. I therefore consider total reconstruction of the auricle to be a field of science attained by numerous refinements and modifications in the procedures and techniques [33-36] and not just a simple form of art. The auricle constitutes only a small portion of the total body surface area, but it is probably one of the most complicated and/or sophisticated morphological structures of the body. It is necessary to fully understand the three-dimensional (3-D) morphological properties of the auricle and to pursue the ultimate goal of reconstructing an everlasting auricle as to the normal auricle. In other words, the constructed close as possible auricle must not be a sculptured object or structure, but is a living structure. A healthy constructed auricle is lasting and alive. Follow-up studies must be performed with strict standards and evaluation criteria in order to determine whether or not a reconstructed auricle is healthy.

Adolescent↗

PubMed1995

Quantitative comparison of human computer interaction for direct prescription entry systems.

An objective and quantitative method is described for evaluating human-computer interaction (interface) in a direct prescription entry system. This method is based on a GOMS model and represented by a tree structure. Three different interfaces at university hospitals were compared by this evaluation method, and the differences among them were measured.

Clinical Pharmacy Information Systems↗

PubMed1995

Long-lasting antagonistic effects of monatepil on Ca2+ current in guinea-pig ventricular cells.

Monatepil maleate (CAS 103377-41-9, AJ-2615), a new derivative of dihydrodibenzothiepins, showed dose-dependent inhibition of Ca2+ current (ICa) in single cardiac cells isolated from guinea-pig ventricle. ICa was elicited by depolarization from -40 mV to +10 mV at 0.2 Hz. IC50 value of monatepil for the peak ICa at +10 mV was 18.7 nmol/l. The ICa inhibition was still sustained 30 min after washout, indicating that monatepil had long lasting activity in the mammalian single muscle cell.

Animals↗

PubMed1994

Defective T cells from gld mice play a pivotal role in development of Thy-1.2+B220+ cells and autoimmunity.

The gld mouse represents a fascinating animal model of autoimmune disease, which is characterized by massive development of Thy-1.2+B220+ CD4-CD8- cells. These cells thus have double positive markers for T and B cells, but are double negative for CD4 and CD8 markers and are thus designated DN cells in the present context. An additional important feature in gld mice is a defect in expression of Fas ligand. To investigate the regulatory role of bone marrow-derived cells for the development of these DN cells and of gld autoimmunity, we constructed chimeric mice transplanted with fetal liver cells or fetal thymus from gld mice into nonirradiated severe combined immunodeficient (SCID) mice. These chimeric mice regenerated, developed both these DN cells and the gld autoimmune syndrome and also generalized lymphoproliferative disorders. However, when fetal liver cells from both gld and non-gld mice (C57BL/10 Thy-1.1 mice) were co-transplanted into SCID mice, the development of DN cells was apparently inhibited. Further, this inhibition was also seen in SCID mice that had been grafted with both gld and non-gld fetal thymus revealing the pivotal role played by T cells in development of DN cells. When B cells purified from non-gld (C3H+/+) mice were transplanted into SCID mice grafted with gld fetal thymus, the development of DN cells was not inhibited. Taken together, these findings indicate that T cells from non-gld mice inhibit the expression of gld features, e.g., lymphoproliferation, immune-based nephritic disease, and autoantibody production. These findings also suggest that the Fas ligand is selectively expressed on T cells.

Animals↗

PubMed1994

Characterization of the regulatory elements in the promoter of the human elongation factor-1 alpha gene.

Most eukaryotic cells abundantly express polypeptide chain elongation factor-1 alpha (EF-1 alpha), an enzyme which catalyzes the GTP-dependent binding of aminoacyl-tRNA to ribosomes. In this study, a series of deletion and scanning mutations was introduced in the promoter region of human EF-1 alpha chromosomal gene. Mutated promoters were fused to the bacterial chloramphenicol acetyltransferase gene, and their promoter activity was determined in human HeLa cells. These analyses indicated that both the 5'-flanking region and the first intron of the EF-1 alpha gene are essential for its promoter activity. The region responsible in the intron contains several Sp1 and Ap1 elements which seem to have additive effects on its promoter activity. In the 5'-flanking region, two cis-elements (EFP1 and EFP2) which work interdependently were identified. Gel shift assay with EFP1 and EFP2 elements indicated that several nuclear factors bind to EFP1 and EFP2, and one of the three retarded bands with EFP2 could be super-shifted with the anti-Sp1 antibody. These results indicate that Sp1 or its related factor cooperatively enhances the expression of the EF-1 alpha gene in the 5' flanking region.

Base Sequence↗

PubMed1994

Clonal expansion but lack of subsequent clonal deletion of bacterial superantigen-reactive T cells in murine retroviral infection.

Several studies have suggested that activation-induced apoptosis of Ag-specific CD4+ T cells leads to depletion of this subset during HIV infection. The bacterial superantigen, staphylococcal enterotoxin A (SEA), is known to induce activation-induced apoptosis in the TCR V beta-bearing CD4+ T cells in the periphery after clonal expansion of these cells. The murine retroviral model of AIDS (MAIDS), which is induced by LP-BM5 murine leukemia virus, shares many common features with HIV infection in humans, except that CD4+ T cells increase progressively in susceptible strains. In this study, we challenged SEA to MAIDS mice and examined whether this retrovirus affects the fate of the SEA-reactive CD4+ T cells in vivo. At 4 wk post-infection with LP-BM5 murine leukemia virus, clonal expression and subsequent deletion of SEA-reactive CD4+V beta 3+ T cells occurred normally after SEA administration, whereas in vitro proliferative responses were severely impaired. At 8 wk postinfection, the in vivo expansion of CD4+V beta 3+ T cells was evident, but not followed by clonal deletion, as late as 14 days after SEA administration. This expanding subset in the infected mice expressed the Fas Ag in the same amount as the same subset in uninfected controls. These findings suggest that activation-induced apoptosis of superantigen-reactive CD4+ T cells is interfered with in vivo during the course of MAIDS, which is not attributable to underexpression of the Fas Ag by the CD4+ T cells.

Animals↗

PubMed1994

No requirement of reactive oxygen intermediates in Fas-mediated apoptosis.

Fas is a cell surface molecule that mediates apoptosis, but the intracellular mechanisms leading to apoptosis are not well understood. It is known that diethylmaleate (DEM)-induced cell death can be blocked by substances with antioxidant activity. Here we have studied whether antioxidants have any effect on Fas-mediated apoptosis and show that they are not able to block Fas-mediated apoptosis. Therefore, it seems that reactive oxygen intermediate (ROI)-dependent and -independent mechanisms which lead to apoptosis do exist. Fas-mediated apoptosis probably proceeds via a ROI-independent pathway.

Animals↗

PubMed1994

Ligand binding domain of granulocyte colony-stimulating factor receptor.

The amino-terminal domain of the cytokine receptor homologous region (BN domain; roughly 100 amino acid residues) in the receptor for murine granulocyte colony-stimulating factor (G-CSF) was secreted as a maltose-binding protein fusion into the Escherichia coli periplasm. The murine BN domain (mBN) was prepared from the fusion protein by restriction protease Factor Xa digestion and purified to homogeneity. The purified BN domain specifically and stoichiometrically bound G-CSF, with an apparent dissociation constant (Kd) of 3-8 x 10(-8) M. The CD spectrum of the mBN domain was similar to that of the extracellular region of the human growth hormone (GH) receptor, which is composed of turns and beta-sheets held together by disulfide bonds. Tertiary folding and the beta-sheet of this small domain was confirmed by NMR spectroscopy. Disulfide bonds determined by peptide mapping were in the following locations: Cys107-Cys118, Cys153-Cys162, and Cys143-Cys194. Among them, the first and the second produce small loops (roughly 10 amino acid residues) as found in the human GH receptor. These results suggested that the mBN domain of the G-CSF receptor expressed by E. coli has a GH receptor-like structure. However, the third disulfide bond varied considerably between the G-CSF and GH receptors. Disruption of these disulfide bonds in the BN domain of the G-CSF receptor suggested that all of them are critical for maintaining a stably folded protein. Our results will facilitate understanding of the biophysical and structural properties of this receptor.

Amino Acid Sequence↗