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Biomedical subjects

T Nishimura

Publications and source records attributed to T Nishimura.

At least 757 records · Page 42Linked to original sources
PubMed1993

[Evaluation of the safety and clinical usefulness of a new myocardial imaging agent, 99mTc-PPN1011--multicenter phase II clinical trial report].

A new myocardial perfusion imaging agent, 99mTc-1,2-bis[bis(2-ethoxyethyl phosphino]ethane (99mTc-PPN1011) was administered to 52 patients with various heart diseases each at rest and peak exercise on different days (Method A) and on the same day (Method B). The safety, optimal dosage, imaging procedures and the clinical usefulness were evaluated. No drug related adverse reactions were found. Image quality was considered adequate for diagnosis with as little as 185 MBq per injection, though the optimal dose range was 370-740 MBq. SPECT images were obtainable as early as 10 min, also until 3 hours after injection. There were no significant differences in clinical efficacy between method A and B, as well as sequential tests at rest and exercise. 99mTc-PPN1011 and 201T1 images in the same patient were compared segment by segment. Image quality of 99mTc-PPN1011 was significantly superior to that of 201T1. Analysis of images indicated that both agent were similar in diagnostic efficacy. It was concluded that 99mTc-PPN1011 is useful for myocardial perfusion imaging.

Adult↗
PubMed1993

[Extension of functional limitation for surgery of lung cancer by unilateral pulmonary arterial occlusion test].

We performed unilateral pulmonary arterial occlusion test to determine the indication for lung resection functionally, and investigated 32 cases whose total pulmonary vascular resistance was over 700 dyne.sec.cm-5/M2. Thirteen out of 32 cases underwent surgery. There was no difference in lung function tests between surgical and non-surgical cases. Nine out of 12 cases whose pulmonary vascular resistance was less than 800 dyne by unilateral pulmonary arterial occlusion test underwent surgery, and none of these cases died within 3 months after surgery. In non-surgical cases, two were aged patients and one had chronic renal failure. Four out of 20 cases whose total pulmonary vascular resistance was over 800 dyne underwent surgery. Two cases that underwent surgery died within 3 months after surgery. These results suggest that the functional limitation of lung resection can be extended from 700 dyne.sec.cm-5/M2 to 800 dyne.sec.cm-5/M2 total pulmonary vascular resistance by application of unilateral pulmonary arterial occlusion test.

Aged↗
PubMed1993

[Evaluation of the clinical usefulness of a new myocardial imaging agent, 99mTc-Tetrofosmin (PPN1011)--a report of multicenter phase III clinical trials].

The clinical usefulness of a new myocardial perfusion imaging agent, 99mTc-1,2-bis[bis(2-ethoxyethyl)phosphino]ethane (99mTc-Tetrofosmin, (PPN1011) was evaluated in 355 patients with various heart diseases. Both 1 and 2 day protocols resulted in images that were significantly clearer than those of 201Tl. The absence of significant drug related adverse reaction supported the safety of the agent for clinical use. Regional abnormalities detected by CAG agreed with 99mTc-Tetrofosmin SPECT findings in 74% and with 201Tl SPECT in 78% of this study. Eighty-four percent of an abnormalities were detected with 99mTc-Tetrofosmin SPECT, as compared with those detected with 201Tl SPECT (88.4%). The complete concordance ratio between 99mTc-Tetrofosmin and 201Tl images in segmental analysis was 87-89% at rest and stress. Since 99mTc-Tetrofosmin SPECT was judged clinically useful in 93.2% (331/355) of the patients studied, it is concluded that 99mTc-Tetrofosmin is a promising agent for myocardial perfusion imaging. The simple labeling procedure without heating and cooling is suitable for emergency administration. Reconditioning of myocardial perfusion could be evaluated with 99mTc-Tetrofosmin injection before and after interventional therapy. These are additional features of the agent for clinical use.

Adult↗
PubMed1993

Variant von Willebrand disease with defective binding to factor VIII: the first case from Japan.

This is the first case of variant von Willebrand disease (vWD) with defective binding of von Willebrand factor (vWF) to factor VIII (F.VIII) to be diagnosed in Japan. An 8-year-old Japanese girl, who had had recurrent episodes of subcutaneous hematomas, showed a prolonged A-PTT, low F.VIII (F.VIII:C 4 U/dl, FVIII:Ag 4 U/dl), and normal level of vWF (RCof 80 U/dl, vWF:Ag 60 U/dl). The patient's vWF-multimeric structure on SDS agarose gel electrophoresis was similar to that in normal subjects. A F.VIII binding assay was performed, as described by Nishino et al. (1989). F.VIII binding (y) of vWF was expressed as a function of the amount of immobilized vWF (x) on the wells of a polystyrene plate. Regression lines from normal subjects and the patient had a high correlation coefficient. F.VIII binding capacity was estimated by the slope of the regression lines. The slope for normal subjects showed y = 0.002 + 0.653x, while, in contrast, the slope for the patient showed y = 0.005 + 0.009x, indicating that the capacity of vWF from the patient to bind F.VIII was markedly decreased. Exons 18-20 of the vWF gene, covering the first 132 amino acids of mature vWF subunit from the patient, were sequenced, using the PCR amplification method. A point mutation C-->T at codon 816 in exon 19, predicting a substitution of Trp for Arg(53), was characterized; this was inherited by the patient from her mother.

Base Sequence↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

[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↗
PubMed1992

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↗
PubMed1992

[Raise up 99mTc-HMPAO brain SPECT for detecting the changes in cerebral perfusion pressure].

99mTc-HMPAO crossed the blood brain barrier instantly in proportional to cerebral blood flow. Raise up stress and supine resting 99mTc-HMPAO with brain SPECT was devised for detecting abnormal response in the changes of cerebral perfusion pressure. Asymmetric ratio in the middle cerebral artery area in patients with internal carotid artery occlusion (n = 5) was changed significantly from 0.82 +/- 0.06 to 0.90 +/- 0.06 and that of normal (n = 5) was not changed from 0.94 +/- 0.03 to 0.95 +/- 0.01. Raise up 99mTc-HMPAO brain SPECT enhanced the detectability in abnormality of regional cerebral blood flow and visualized the dys-autoregulated area during blood pressure falls.

Blood Pressure↗
PubMed1992

Dimethyl sulfoxide (DMSO) blocks GABA-induced current in rat dorsal root ganglion neurons.

The effects of dimethyl sulfoxide (DMSO) on gamma-aminobutyric acid (GABA)-induced Cl- currents of rat dorsal root ganglion neurons in primary culture were studied by the whole-cell patch-clamp technique. Bath application of 5 microM GABA evoked sustained inward and outward currents at membrane potentials of -60 mV and +30 mV, respectively, when the external and internal solutions both contained 142 mM Cl-. DMSO at concentrations of 0.3-3% (v/v) caused a dose-dependent inhibition of the inward current induced by 5 microM GABA at -60 mV. DMSO at 3% inhibited the GABA-induced inward and outward currents at -60 mV and +30 mV to similar extents (54% and 53% of the control, respectively), but the time-course of inhibition of the outward current at +30 mV was much faster than that of the inward current at -60 mV. These results suggest that DMSO suppressed the currents by interacting with GABA receptor-Cl- channel complex protein rather than by affecting the lipid-bilayer of the cell membrane.

Animals↗
PubMed1992

Human c-erbB-2 proto-oncogene product as a target for bispecific-antibody-directed adoptive tumor immunotherapy.

To develop an efficient strategy for the targeting of anti-tumor effector cells, we prepared bispecific antibody (BsAb) containing anti-CD3 and an anti-c-erbB-2 proto-oncogene product. The prepared BsAb specifically reacts with both c-erbB-2-positive tumor cells and CD3+ CTL. Human CD4+ helper/killer T cells, induced from peripheral-blood mononuclear cells by activation with immobilized anti-CD3 monoclonal antibody (MAb) plus IL-2, showed no significant cytotoxicity against tumor cells. However, treatment of human CD4+ helper/killer cells with the BsAb caused the induction of specific cytotoxicity against c-erbB-2-positive tumor cells. CD4+ helper/killer cells also produced significant amounts of IL-2 during co-culture with c-erbB-2-positive tumor cells in the presence of the BsAb. Moreover, by combination with the BsAb, CD4+ helper/killer cells showed a strong in vivo anti-tumor effect against c-erbB-2 transfectant or human colon-cancer cells implanted in nude mice. Our results strongly suggest that the c-erbB-2 proto-oncogene product on human tumor cells may be a good target for BsAb-directed adoptive tumor immunotherapy.

Antibodies, Monoclonal↗
PubMed1992

Amyloid beta-protein precursor deposition in rat hippocampus lesioned by ibotenic acid injection.

Ibotenic acid was injected into 3 parts of the lateral rat hippocampus. The animals were sacrificed 100 days after treatment, and studied immunohistochemically. The lesioned side of the hippocampus was highly atrophic with extensive neuronal loss and gliosis. Although silver staining revealed no particular structures such as neurofibrillary tangles or senile plaques, globular and granular depositions of amyloid beta-protein precursor (APP) immunoreactivity was observed by immunostaining in the lesion with the monoclonal antibody (clone 22C11). Increased immunoreactivities of glial fibrillary acidic protein (GFAP) and ubiquitin were found in the lesioned area, while the immunoreactivities of microtubule-associated protein 2 (MAP2) and 200 kDa neurofilament subunit protein (NF-H) were diminished. The results indicate that APP deposition is formed in the lesioned area where neuronal degeneration is produced by ibotenic acid in rat hippocampus.

Amyloid beta-Protein Precursor↗
PubMed1992

Generation propagation, and targeting of human CD4+ helper/killer T cells induced by anti-CD3 monoclonal antibody plus recombinant IL-2. An efficient strategy for adoptive tumor immunotherapy.

We developed a culture system for the rapid generation of CD4+ T cells that have both helper and killer functions. CD4+ T cells isolated from human PBL did not proliferate or develop significant cytotoxicity when treated with rIL-2 because of the lack of p75 IL-2R expression. However, culture of isolated CD4+ T cells with immobilized anti-CD3 mAb plus rIL-2 resulted in a marked proliferation (500-fold increase in 14 days) of CD4+ T cells. The proliferating CD4+ T cells produced IL-2 (92 U/ml) and showed strong cytotoxicity against OKT3 hybridoma cells and Daudi, K562, and U937 tumor cells in an anti-CD3 mAb-dependent manner. The CD4+ T cells contained significant amounts of cytolytic granule-related proteins such as serine esterase and perforin. Activated CD4+ helper/killer cells can be generated from both healthy donors and tumor patients and can be propagated in vitro for 14 to 35 days by biweekly restimulation with immobilized anti-CD3 mAb plus rIL-2. This culture yielded about 20,000-fold increase in cell number after a 21-day culture. Bispecific antibody containing anti-CD3 and anti-glioma Fab components enhanced the cytotoxicity of activated CD4+ helper/killer cells against IMR32 glioma cells. Moreover, the activated CD4+ helper/killer cells showed both helper and antitumor activity in vivo and prevented growth of anti-CD3 hybridoma cells in nude mice whether or not IL-2 was administered. These results indicate that anti-CD3 mAb plus IL-2-activated CD4+ helper/killer cells may provide an effective strategy for adoptive tumor immunotherapy of cancer.

Antibodies, Monoclonal↗
PubMed1992

Mouse rRNA gene transcription factor mUBF requires both HMG-box1 and an acidic tail for nucleolar accumulation: molecular analysis of the nucleolar targeting mechanism.

RNA polymerase I requires at least two nucleolar transcription factors, UBF and SL-1, for ribosomal RNA gene (rDNA) transcription. UBF requires SL-1 for the formation of a stable initiation complex on the rDNA promoter region. We have determined the region of mouse UBF (mUBF) required for nucleolar targeting. Although mUBF has a nuclear localization sequence, this sequence alone is not sufficient for mUBF to accumulate in the nucleolus. Deletion analyses show that mUBF requires a wide region except for the N-terminal 101 amino acids for nucleolar targeting. Deletion of either the HMG-box1, a region crucial for rDNA binding, or the acidic tail, a region that may interact with SL-1, results in the loss of nucleolar targeting. We show by DNA affinity analysis that the HMG-box1 is absolutely necessary for mUBF to bind to the upstream control element of the rDNA. We also show that mUBFs with various internal deletions retain both nucleolar targeting and DNA binding ability. A clear correlation was demonstrated between the DNA binding and nucleolar targeting ability. These results suggest that UBF is transferred to the nucleus by its NLS and is sequestered in the nucleolus by its specific and stable binding to the rDNA promoter via HMG-boxes and the acidic tail.

Animals↗
PubMed1992

Visualization of posture-dependent cerebral blood flow in a patient with Takayasu's disease by means of 99mTc-HMPAO brain single photon emission tomography.

A case of Takayasu's disease in a 22-year-old woman who complained of severe fainting attacks is presented. Bilateral obstruction of the cervical arteries was confirmed by digital subtraction angiography. Preoperative technetium-99m hexamethylpropylene amine oxime brain SPET in the sitting position showed bilateral hypoactivity in the temporoparietal areas. Subtraction brain SPET showed slightly increased activity in the lying position. The patient has had no fainting attacks since bypass surgery. Postoperative 99mTc-HMPAO brain SPET in the sitting position showed normal activity except in the right temporoparietal area. This area was filled in the lying position. 99mTc-HMPAO brain SPET is the only technique that can visualize the cerebral blood flow in any position, this capability deriving on the fact that the distribution of 99mTc-HMPAO in the brain is fixed in the first 2-3 min following injection. The use of both sitting and lying 99mTc-HMPAO brain SPET is very useful for detecting an abnormality (i.e. an inhomogeneous response due to the fall in perfusion pressure) that could not be seen if the cerebral blood flow were to be assessed only in the lying position.

Adult↗
PubMed1992

Serial assessment of denervated but viable myocardium following acute myocardial infarction in dogs using iodine-123 metaiodobenzylguanidine and thallium-201 chloride myocardial single photon emission tomography.

Iodine-123 metaiodobenzylguanidine (mIBG) is taken up by sympathetic nerve endings, allowing scintigraphic imaging of myocardial sympathetic innervation. We investigated the denervated but viable canine myocardium after acute myocardial infarction by serial mIBG and thallium-201 chloride (201TlCl) single photon emission tomography (SPET). In 12 dogs, acute myocardial infarction was produced by ligation of the left circumflex coronary artery. Images of mIBG and thallium SPET were obtained 6 h, 1, 4 and 6 weeks later. The defect size was calculated in percentage points from short axial views, and the 123I-mIBG/201TlCl ratio was determined. The uptake ratio was high at 1 week but gradually decreased. Three dogs were killed at each time point, and tissue samples were obtained from infarcted (both 201TlCl and 123I-mIBG defects), peri-infarcted (123I-mIBG defect and 201TlCl normal) and normal myocardium (both mIBG and 201TlCl normal). The changes in tissue content of noradrenaline in these lesions were measured. Noradrenaline tissue content gradually recovered in the peri-infarcted area. However, no recovery was noted in the infarcted area at 6 weeks. We conclude that sympathetic denervation and re-innervation occur following acute myocardial infarction, and the denervated but viable myocardium could be detected non-invasively by combined mIBG and thallium SPET.

3-Iodobenzylguanidine↗