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Biomedical subjects

T Nishimura

Publications and source records attributed to T Nishimura.

At least 73 records · Page 4Linked to original sources

Implication of the common gamma chain of the IL-7 receptor in intrathymic development of pro-T cells.

The effects of IL-7 on the growth and differentiation of thymocytes were analyzed using murine fetal thymus organ cultures (FTOC) in the presence of mAbs specific for the conventional IL-7 receptor (IL-7R) and for the common gamma (gamma c) chain. In FTOC, the development of CD4-CD8- double-negative thymocytes to CD4+CD8+ double-positive (DP) and CD4+ or CD8+ single-positive (SP) cells was not completely blocked by adding these mAbs, although cell growth was reduced by the treatment. To define a developing stage sensitive to the mAbs, most immature thymocytes, Pgp-1+ c-kit+ cells, were cultured in 2-deoxyguanosine treated fetal thymus. In the presence of both mAbs in the culture, neither DP nor SP thymocytes developed whereas either of the mAbs partially blocked their development. These results indicate that the gamma c chain is involved in early T cell development as an indispensable subunit of the functional IL-7 receptor complex.

Animals

Clinical application of spontaneous red blood cell labeling with Tc-99m sodium pertechnetate.

Red blood cells (RBC) may be labeled with Tc-99m after Tc-99m sodium pertechnetate is injected in the presence of a reducing agent, such as stannous chloride. Thus, spontaneous RBC labeling with Tc-99m is expected to be seen in patients with a high plasma concentration of tin. Spontaneous RBC labeling with Tc-99m was obtained in a 73-year-old woman who was clinically diagnosed with tin intoxication and proved to have a high concentration of plasma tin. The RBC labeling rate was calculated as 96% with blood sampling. Spontaneous RBC labeling with Tc-99m is a very simple method for proving a high plasma tin concentration and is adaptable to clinical diagnosis.

Aged

Ultrastructure of the intramuscular connective tissue in bovine skeletal muscle. A demonstration using the cell-maceration/scanning electron microscope method.

The three-dimensional arrangement of intramuscular connective tissues in bovine semitendinosus muscle was investigated using the cell-maceration method for scanning electron microscopy, by which cellular elements were eliminated and collagen fibrils and fibers were exposed. The 60-100 microns diameter honeycomb structures of the endomysium housing individual muscle fibers were clearly observed. The sheath of endomysium was membranous and consisted of tightly arranged collagen fibrils 30-70 nm in diameter. The perimysium was composed of several layers of 100-200 microns-thick sheets surrounding the sheaths of the endomysium. The sheets of the perimysium were wavy and consisted of collagen fibers made up of tightly bundled fibrils. The epimysium was composed of two distinct layers of thick sheets. The inner layer consisted of thousands of collagen fibers lying in an extremely regular wavy pattern parallel to the axis of the muscle fiber. The outer layer of epimysium was composed of several wavy sheets of collagen fibers which ran transversely to the axis of the muscle fiber. In a region of the epimysium, there was a thick wall of about 1 mm thickness, where fiber bundles of 200-300 microns in diameter ran longitudinally parallel to the axis of muscle fiber.

Animals

Successful percutaneous transluminal angioplasty of the intracranial vertebral artery 1 month after total occlusion--case report.

A 51-year-old male suffering from recurrent cerebral ischemia due to total occlusion of the bilateral intracranial vertebral arteries more than 1 month old was successfully treated by percutaneous transluminal angioplasty (PTA). The totally occluded portion from the right intracranial vertebral artery to the basilar artery was adequately dilated. Follow-up angiography approximately 3 months after angioplasty demonstrated no evidence of restenosis. His symptoms have not recurred. PTA is potentially a much less invasive and safer reconstruction than bypass surgery for total occlusions of the intracranial vertebral arteries less than 3 months old.

Angioplasty, Balloon

Nuclear export of recombinant baculovirus nucleocapsids through small pore or nuclear-pore-like structure in Sf9 cells.

Translocation of baculovirus nucleocapsids (45 nm in diameter, approximate length of 280-300 nm) from nucleoplasm to cytoplasm was studied morphologically using cryofixation and gold labeled wheat germ agglutinin (WGA-gold) during recombinant Autographa californica nuclear polyhedrosis virus infection in Sf9 cells. Nucleocapsids formed in the nucleoplasm migrated into protrusions of the nuclear envelope, but not into nuclear pore complexes. We found cross-like membranous structures. Small pores seemed to be in the protruding nuclear double membranes. The middle piece of a nucleocapsid was located within the small pore whereas the upper part was in the cytoplasm. Other nucleocapsids were situated within pores without colocalization of WGA-gold in the nuclear envelope. These results suggest that baculovirus nucleocapsids use small pores in the nuclear-derived membranes or incomplete nuclear pores in the nuclear envelope to migrate from the nucleoplasm to the cytoplasm, but not complete nuclear pore complexes proper.

Animals

[Bacteriological and clinical studies on cefozopran in pediatric field].

We carried out clinical studies on cefozopran (CZOP, SCE-2787). The results are summarized as follows. Treatment with CZOP was made in 17 cases of pediatric bacterial infections including 2 cases of purulent tonsillitis, 11 cases of acute pneumonia and 2 cases each of urinary tract infections and enteritis. Results obtained were excellent in 12 cases, good in 2 cases, fair in 2 cases and poor in 1 case. All of 9 isolated bacteria were eradicated by the treatment. As side effects and laboratory test results, rash was observed in one case and transient increase of platelets in one case, slight increase of eosinophil in 2 cases and transient elevation of GPT and GOT.GPT in one case.

Bacteria

[Low serum TSH levels in patients with emergent conditions due to ischemic heart disease or congestive heart failure].

We investigated the pathophysiological and clinical significance of thyroid stimulating hormone (TSH) levels in patients within 4 days after onset of ischemic heart disease (IHD) or aggravation of congestive heart failure (CHF) due to myocardial infarction. We classified patients into 3 groups: 1) angina pectoris (AP) group [n = 66, 62 years (Mean)], 2) acute myocardial infarction (AMI) group (n = 58, 65 years) and 3) CHF group (n = 16, 68 years). Soon after admission, blood samples were obtained to measure TSH by the IRMA method. Blood samples for creatine phosphokinase (CPK) were obtained every 3 hours. All patients showed TSH levels that were normal or below normal. Those in whom TSH levels were below normal, were defined as "low TSH" patients. The incidence of low TSH patients in the CHF group (31.3%) was significantly higher (p < 0.05) than that in the AP group (4.5%). In the AMI group, plasma CPK activity of 5037 +/- 1102 U/l (Mean +/- SEM) in low TSH patients were significantly higher (p < 0.05) than that of 1931 +/- 255 U/l in patients with normal TSH levels. These results indicate that in patients with extensive myocardial cell damage, "low TSH" frequently develops during emergency.

Aged

[An efficient methods for the induction of human antitumor effector CD4+ and CD8+ T cells: their application to tumor immunotherapy].

It is an important issues to investigate an efficient methods to induce antitumor effector T cells from peripheral blood lymphocytes of tumor patients for the development of a novel tumor immunotherapy. We established a large scale culture system of human CD4+ helper/killer T cells which have both helper and killer functions. Targeting of CD4+ helper/killer T cells to tumor using anti-CD3 x anti-c-erbB-2 mAb caused the lysis of tumor and triggering of IL-2 production. It was also demonstrated that culture of human CD4+ T cells with staphylococcal enterotoxin A (SEA) or IL-12 caused a selective induction of Th1 type of CD4+ helper/killer T cells. IL-12 also revealed a novel effect on CD8+CTL functions. Culture of CD8+ T cells with IL-12 resulted in the augmentation of IFN-gamma production and cytotoxicity. Moreover, culture of tumor-infiltrating lymphocytes with IL-12 caused a marked enhancement of CD8+CTL against autologous tumor cells. These findings suggest that IL-12 will become a useful cytokine for the tumor immunotherapy. In this paper, we will discuss the key role of CD4+ T cells for the induction of antitumor immunity in tumor-bearing host.

CD4-Positive T-Lymphocytes

Activation of two angiotensin-generating systems in the balloon-injured artery.

Participation of angiotensin II in the myointimal proliferation following a vascular injury was postulated. This study assessed the potential involvement of the local angiotensin II-forming enzymes in injured arteries of dogs. The potential angiotensin II-forming enzymes are angiotensin-converting enzyme (ACE) and chymostatin-sensitive angiotensin II-generating enzyme (CAGE) which is highly homologous to or could be identical to the mast cell chymase. Both ACE and CAGE catalyze the conversion of angiotensin I to angiotensin II. We found that the enzymatic activities of ACE and CAGE, and the mRNA levels of ACE and chymase were increased in the injury-induced hypertrophied vessels. The results suggest that ACE and CAGE participate in the hypertrophy through the production of angiotensin II which is a growth promoter for vascular smooth muscle cells.

Angiotensin II

Neuropathologic changes in the gerbil brain after chronic hypoperfusion.

BACKGROUND AND PURPOSE: An animal model has been developed to elucidate the pathological changes in brain cytoskeletal proteins during chronic hypoperfusion. METHODS: Newly designed coiled clips were placed around both carotid arteries of Mongolian gerbils (n = 10) to cause stenosis without occlusion. Those gerbils showing impaired learning ability by the passive avoidance paradigm were killed for neuropathologic study after 12 weeks. RESULTS: The brains showed ventricular dilatation, cortical atrophy, and rarefaction of the white matter. Immunoreactivity to anti-microtubule-associated protein 2 antibody in the cerebral cortex and the hippocampus was diminished, indicating dendritic changes of neurons. In the thalamic axonal regions, staining with anti-neurofilament 200K protein antibody was increased, suggesting increased amounts of neurofilament proteins or increased phosphorylation of the protein. Increased immunoreactivity to anti-glial fibrillary acidic protein antibody was observed in a wedge-shaped configuration, corresponding to the border zone of perfusion by small vessels. CONCLUSIONS: These findings suggest that changes in the cytoskeletal proteins in dendrites, axons, and glial cells may cause neuronal death under conditions of chronic cerebral hypoperfusion.

Animals

Perfusion lung scintigraphy in primary pulmonary hypertension.

15 cases of primary pulmonary hypertension were classified into two groups by patterns of perfusion lung scintigraphy. Perfusion scintigrams showed multiple, small, ill-defined defects (mottled + ve) pattern in eight cases, and the remaining seven cases had a normal (mottled - ve) pattern. The mean pulmonary arterial pressure in patients with a mottled pattern (54 +/- 10 mmHg) was higher than in those with a normal pattern (42 +/- 9 mmHg, p < 0.05). There were no significant differences between the two groups in right ventricular ejection fraction, partial pressures of oxygen in the arterial blood or alveolo-arterial oxygen difference. All the patients with a mottled pattern died within 2 years following the lung scintigraphy. There was a significant difference in the survival curves between the two groups. Although our statistical analysis must be evaluated with caution because of small numbers of patients it is suggested that perfusion lung scintigraphy is useful in assessing the prognosis in primary pulmonary hypertension.

Adult

New mutation of the myelin P0 gene in a pedigree of Charcot-Marie-Tooth neuropathy 1.

P0, the major structural protein of peripheral myelin, is a homophilic adhesion molecule with a single immunoglobulin (Ig) domain, which contains a single N-linked glycosylation site and two cysteines. We have previously reported four different mutations of the myelin P0 gene in four families of Charcot-Marie-Tooth neuropathy type 1 (CMT1). In this study we found a new mutation of the myelin P0 gene in a small family of CMT1. The affected persons had an A - to - G substitution of nucleotide 245 of the myelin P0 gene in one allele, leading to a cysteine substitution for tyrosine82 in the extracellular Ig-domain. An additional cysteine in the extracellular domain may form a disulfide bond and cause an inappropriate change in the tertiary structure of the functional Ig-domain of P0.

Adolescent

[A case of amylase producing lung cancer].

The patient was a 72-year-old man, who was admitted to our hospital because of cough. Chest X-rays showed a mass shadow in the right lower lung field. Amylase activities in serum and urine were extremely high. Amylase isozyme pattern identified salivary type amylase. Cytological examination of the sputum suggested adenocarcinoma. Amylase activities in serum and urine gradually decreased with the administration of chemotherapy. Afterwards, pleural effusion increased, and the amylase activity in pleural fluid was also extremely high. Pleural fluid also showed adenocarcinoma. Enzyme-labeled antibody method (PAP) on this specimen from pleural fluid proved that tumor cells were producing amylase ectopically.

Adenocarcinoma

Assembly regulatory domain of glial fibrillary acidic protein. A single phosphorylation diminishes its assembly-accelerating property.

Phosphorylation of glial fibrillary acidic protein (GFAP) induces disassembly of the filaments. An amino-terminal fragment of bovine GFAP (G-Hf) was produced by lysylendopeptidase digestion. G-Hf formed ribbon-like filaments in the presence of GFAP even in low ionic strength, whereas the fragment itself did not form any structures. Only one (PK3) of the five V8 protease fragments of G-Hf accelerated GFAP assembly to the same degree as G-Hf did, whereas the other fragments did not. When PK3 was cleaved into two fragments, it lost the assembly-accelerating property. The sequence of PK3 was determined as RRRVTSATRRSYVSSSE, which corresponded to residues 3-19 of porcine GFAP. It was concluded that PK3 contains a sequence indispensable for GFAP assembly and that neither PK1 (RRRVTS) nor PK2 (ATRRSYVSSSE) included all of the sequence. A single phosphorylation of PK3 by cyclic AMP-dependent protein kinase diminished its assembly-accelerating property. The phosphorylation site was determined as Ser-12 of porcine GFAP. It was shown that single phosphorylation of the amino-terminal head domain, which contains an indispensable sequence for GFAP assembly, might be sufficient for GFAP disassembly.

Amino Acid Sequence

Cellular and peptide requirements for in vitro clonal deletion of immature thymocytes.

Thymocytes from DO10 T-cell-receptor transgenic mice undergo apoptosis, or programmed cell death, when chicken ovalbumin-(323-339) peptide is administered in vivo. Using DO10 mice thymocytes, we have now developed a simple in vitro model system that recapitulates the in vivo clonal-deletion process. When transgenic thymocytes were cocultured with fibroblasts, B cells, or thymic nurse cell lines (all bearing I-Ad) in the presence of chicken ovalbumin-(323-339), deletion of the transgenic TCR+CD4+CD8+ thymocytes was seen within 8-20 hr. Thymocytes designed to bear I-Ad on their surface could mediate the deletion themselves. Thus, thymocyte clonal deletion entirely depends on the stage at which the thymocytes are vulnerable to the onset of apoptosis, rather than on the nature of the peptide antigen-presenting cells. Furthermore, thymic nurse cell line TNC-R3.1 could cause deletion, strongly suggesting that some thymic epithelial/stromal components are potentially capable of participating in negative selection. In all cases examined, little deletion could be induced at a peptide concentration less than 10 nM, thus defining the minimum amount of peptide antigen required for negative selection. The peptide-dependent in vitro negative-selection system will allow further dissection of the molecular and cellular processes involved in clonal deletion due to apoptosis in the thymus.

Amino Acid Sequence

[Detectability of diagonal branch disease by 201TlCl exercised myocardial scintigraphy].

The detectability of diagonal branch disease in 10 patients (five with angina pectoris, five with myocardial infarction) with isolated diagonal branch lesions (more than 75% luminal stenosis in coronary angiography) was reviewed. In exercised 201TlCl myocardial scintigraphy, chest pain occurred in four of 10 patients, electrocardiographic change indicating myocardial ischemia was seen in four, and diagonal branch lesion was detected in only four patients by planar images. In contrast, diagonal branch lesions were detected in 10 of 10 patients by SPECT (single photon emission computed tomography). In planar images, perfusion defects appeared high in the anterolateral, posterolateral, and anterior walls of the left ventricle. In SPECT images they appeared high in the anterior to anterolateral wall. The extent of diagonal branch lesions could be quantitatively evaluated by coronary territory maps developed from unfolded maps of exercised SPECT. The mean ratio of the extent of diagonal branch lesion to left anterior descending branch territory was 24.7%, and the extent of myocardial infarction was significantly larger than that of angina pectoris (p < 0.05). In conclusion, SPECT is useful for detecting diagonal branch lesions and can quantitatively show the extent of these lesions by coronary territory map.

Aged

Purification and properties of aminopeptidase H from chicken skeletal muscle.

Aminopeptidase H was purified from fresh chicken breast muscle by ammonium sulfate fractionation and successive chromatographies on DEAE-cellulose, Ultrogel AcA 34, activated thiol-Sepharose 4B, phenyl-Sepharose CL-4B and DEAE-cellulose again. The purified enzyme migrated as a single band on SDS/PAGE. Aminopeptidase H exhibits activity against both L-leucine beta-naphthylamide and alpha-N-benzoyl-DL-arginine beta-naphthylamide. The molecular mass of this enzyme was found to be 52 kDa on SDS/PAGE and 400 kDa on Sepharose 6B column chromatography. The optimum pH for the hydrolysis of both substrates was 8.0 and this activity was remarkably enhanced by reducing agents. The enzyme was strongly inhibited by monoiodoacetate and leupeptin, but not affected by EDTA, phenylmethylsulfonyl fluoride, pepstatin, bestatin or puromycin. Aminopeptidase H has been shown to hydrolyze di-, tri- and tetrapeptides in the manner of an aminopeptidase, as well as the beta-naphthylamide derivatives of amino acids. However, the enzyme has not been shown to hydrolyze proteins such as hemoglobin, bovine serum albumin, myofibrillar proteins or sarcoplasmic proteins.

Amino Acid Sequence