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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

[Thallium-201 scintigraphy after dipyridamole infusion in patients with ischemic heart disease--comparison with maximal exercise].

Myocardial images after dipyridamole infusion (DIP-Tl) were compared with maximal thallium-201 images (Ex-Tl) to determine the utility for detecting coronary artery disease and the ischemic level in ischemic regions. Ex-Tl was performed in 36 patients of angina pectoris (Group 1), and DIP-Tl was performed in 22 patients of angina pectoris (Group 2), who were divided into two groups (Group 2a: 15 patients with low level exercise, Group 2b: 7 patients without low level exercise). Each group had normal controls (41, 27 and 31 people). The detectability of coronary artery by DIP-Tl was almost same with Ex-Tl (sensitivity 85% vs. 86%, specificity 80% vs. 95%). In the case of normal controls, the mean washout rate of group 2b was 44.4%, which was less than other two groups (50.6% for group 1, 48.8% for group 2a). And the mean myocardial/background (M/B) ratio of group 2b was 4.3 less than other two groups (4.7 for group 1, 4.9 for group 2a). In the case of the patients of angina pectoris, washout rate, M/B ratio, initial % uptake and delayed % uptake in the ischemic region were almost same among the 3 groups. This study demonstrates that DIP-Tl is as effective as Ex-Tl, and the ischemic level in the ischemic region is almost same among the 3 groups. But the thallium accumulation in the background of the group 2b is slightly higher than other two groups in the normal controls, so it is suggested that the image after only dipyridamole infusion becomes slightly unclear.

Coronary Disease

[Phase 2 study of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid, a myocardial imaging agent for evaluating myocardial fatty acid metabolism].

A phase 2 study of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid (123I-BMIPP), a myocardial imaging agent developed for evaluating myocardial fatty acid metabolism, was performed in 197 patients with various heart diseases. The myocardial distribution of 123I-BMIPP did not change from early to late images in 88% of 91 patients with ischemic heart disease (IHD), while washout and/or fill-in were observed in 45% of 55 patients with hypertrophic cardiomyopathy (HCM). In comparison with 201Tl in 165 patients with various heart diseases, the decrease in uptake was more profound with BMIPP in 56% and with 201Tl in only 4%. 123I-BMIPP showed more severely decreased uptake in 83% of the patients with subacute myocardial infarction (15 to 30 days after the onset) and in 73% of the patients with HCM. High-quality SPECT images were obtained with 123I-BMIPP in 93% of 194 patients analyzed. However, the image quality in cardiomyopathy was inferior to that in IHD. The optimal injection dose range and standard dose of 123I-BMIPP were considered to be 74-148 MBq and 111 MBq, respectively. These findings suggest that 123I-BMIPP myocardial imaging is safe and useful for evaluating myocardial fatty acid metabolism in various heart diseases.

Adolescent

[Diagnostic utility of myocardial imaging using 123I-labeled beta-methyl-iodophenyl pentadecanoic acid in ischemic heart disease].

We evaluated the myocardial metabolism in the acute and subacute phases of myocardial infarction or unstable angina using 123I-labeled beta-methyl-iodophenyl pentadecanoic acid (BMIPP). We then compared those findings with (1) myocardial perfusion images obtained with 201TlCl and (2) the regional and global left ventricular function determined by left ventriculography. Thirty-one patients were examined, consisting of 16 with acute myocardial infarction (6.8 +/- 2.6 days after onset), 8 with subacute myocardial infarction (35 +/- 3.0 days after onset) and 7 with unstable angina. The BMIPP images showed a larger uptake-defect than 201TlCl images in the patients in the acute or subacute phase of myocardial infarction. This finding was especially remarkable in the acute phase after successful coronary revascularization therapy. Moreover, in such cases, the myocardial BMIPP uptake improved to the same degree as 201TlCl one month later. The decrease in myocardial uptake of BMIPP agreed well with the decrease in regional wall motion in the acute and subacute phases of myocardial infarction. In contrast, the myocardial perfusion of 201TlCl did not always agree with the regional wall motion in stunned or hibernating myocardium, where BMIPP showed an uptake-defect in the acute phase but improved in the subacute phase. Thus, BMIPP is surmised to be able to depict fatty acid metabolism in in vivo myocardial imaging.

Adult

[Usefulness of 201Tl myocardial scintigraphy after dipyridamole infusion in patients with atherosclerotic vascular disease].

To determine the utility for detecting ischemic heart disease (IHD), Dipyridamole thallium myocardial images (DIP-Tl) have been performed in the 103 patients with atherosclerotic vascular disease who can't exercise fully. Of 103 patients, there were 36 patients with arteriosclerosis obliterans (ASO), 31 patients with aneurysm of the abdominal aorta (AAA), 24 patients with aneurysm of the thoracic aorta (TAA) and 12 patients with dissecting aortic aneurysm (DAA). Clinical evidence of IHD was found in 20 patients with ASO, 10 with AAA, 7 with TAA and 4 with DAA respectively. Positive evidence of DIP-Tl was identified in 66% of 41 patients who had clinical evidence of IHD, and particularly in the patients with AAA (80%) and ASO (65%). On the other hand, in the patients without clinical evidence of IHD, positive evidence of DIP-Tl was identified in 19% of 62 patients and particularly in the patients with AAA (39%). In all patients, the percentage of the positive DIP-Tl ratio was 38%. And, when the 38% patients of the positive DIP-Tl were added to the patients of the negative DIP-Tl who had clinical evidence of IHD, almost half patients (51%) were considered to be complicated with IHD. This study suggests that the atherosclerotic vascular disease is highly complicated with IHD and DIP-Tl is useful to detect IHD.

Aged

Glial fibrillary acidic protein stimulates proliferation and immunoglobulin synthesis of lymphocytes from Alzheimer's disease patients.

The level of anti-GFAP (glial fibrillary acidic protein) IgG antibody titer was assayed in sera of patients with Alzheimer's disease, multi-infarct dementia, and the age-matched control subjects. Significantly higher level of anti-CFAP titer was found in sera of Alzheimer's disease patients. The in vitro lymphocyte response was studied by stimulation with GFAP and interleukin 2 (IL-2). The lymphocytes of Alzheimer's disease patients showed higher proliferative response than those of the control by GFAP and IL-2 stimulation. The IgG secretion by lymphocytes from Alzheimer's disease patients was also stimulated by GFAP as well as by GFAP plus IL-2. The results demonstrate that the lymphocytes of Alzheimer's disease patients are more responsive to GFAP than those of the control subjects.

Aged

[Phase 3 study of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid, a myocardial imaging agent for evaluating fatty acid metabolism--a multi-center trial].

A multi-center trial of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid (123I-BMIPP) was performed to assess its clinical usefulness in the evaluation of myocardial fatty acid metabolism in 587 patients with various heart diseases. 123I-BMIPP showed relatively decreased uptake compared with 201Tl in the myocardial lesions of 62% of patients with ischemic heart disease (IHD), 39% of those with cardiomyopathy and 32% of those with other heart diseases. In case of myocardial infarction, less uptake of 123I-BMIPP (Type B) than 201Tl was more frequently seen in patients with successful recanalization than in those without recanalization. The patients with matched distribution of the two tracers (Type E) increased in the direct proportion to the interval between the onset of myocardial infarction and the radionuclide studies. The uptake of 123I-BMIPP correlated well with myocardial viability evaluated by 201Tl exercise-redistribution studies. Type B was frequently seen in the areas with 201Tl redistribution, while Type E was seen in the fixed defect areas. In the other heart diseases studied, Type E was observed in approximately 60% of patients with dilated or secondary cardiomyopathies. Type B was seen in about 45% of patients with valvular heart diseases and myocarditis. Various types of mismatch between the two tracers were demonstrated in hypertrophic cardiomyopathy and hypertensive heart disease. It is concluded that 123I-BMIPP is a safe and useful agent for the diagnosis of various heart diseases, since it reflects myocardial fatty acid metabolism.

Adolescent

Application of artificial neural network to computer-aided diagnosis of coronary artery disease in myocardial SPECT bull's-eye images.

We have developed a computerized system that can aid in the radiologist's diagnosis in the detection and classification of coronary artery diseases. The technique employs a neural network to analyze 201Tl myocardial SPECT bull's-eye images. This multi-layer feed-forward neural network with a backpropagation algorithm has 256 input units (pattern: compressed 16 x 16-matrix images), 5-140 units in a single hidden layer, and eight output units (diagnosis: one normal and seven different types of abnormalities). The neural network was taught using pairs of training (learning) input data (bull's-eye "EXTENT" image) and desired output data ("correct" diagnosis). The effects of the numbers of hidden units and learning iterations in the network on the recognition performance were examined. In our initial stage, the results show that the recognition performance of the neural network is better than that of the radiology resident but worse than that of the experienced radiologist. Our study also demonstrates that the result produced in the neural network depends on the variety of the training examples used. The preliminary study suggests that the neural network approach is useful for the computer-aided diagnosis of coronary artery diseases in myocardial SPECT bull's-eye images.

Coronary Disease

Diagnostic value of technetium-99m radionuclide angiography for detecting thrombosis in left atrial appendage.

In mitral valve disease, it is important to know whether thrombi are present in the left atrium when deciding upon a course of treatment. The left atrial thrombus usually locates in the left atrial appendage. In most cases of mitral valve disease, the left atrial appendage is clearly demonstrated by radionuclide angiography using 99mTc-labeled red blood cells and it can be speculated that the cases in which left atrial appendage are not demonstrated by RNA have left atrial thrombi. On the basis of this hypothesis, the diagnostic accuracy of radionuclide angiography to detect left atrial thrombi was evaluated retrospectively in 60 patients with mitral valve disease who had undergone surgery. The sensitivity of first-pass and equilibrium radionuclide angiography to detect left atrial thrombi was 83% and 67%, the specificity 79% and 54%, and the accuracy 80% and 57%, respectively. Although there were two false-negative cases in which the left atrial thrombi did not locate in the appendage and 10 false-positive cases in which left atrial appendages were not dilated, the negative predictive value was so high that a clearly demonstrated left atrial appendage can be translated into the absence of left atrial thrombi.

Adult

Effect of bright light in the morning on diurnal variations of pineal indoles in NZBWF1 mice.

Exposure to bright light (2000 lx) for 2 h at the beginning of a 12 h light period (10 lx) resulted in about 1 h advances in the onset and termination of N-acetylserotonin (NAc5HT) synthesis in the pineal gland of NZBWF1 strain mice compared with those in mice not exposed to bright light. These effects are in contrast with the effect of exposure to bright light throughout the light period, which delayed the onset of pineal NAc5HT synthesis in NZB mice. The possible relationship of these effects with the mechanism of action of phototherapy of human affective disorder is discussed.

Animals

Monoclonal antibody against actin cross-reacts with the Thy-1 molecule and inhibits lymphocyte function-associated antigen-1 dependent cell-cell interaction of T cells.

To assess the molecular mechanisms involved in cell-cell interactions of T cells, we produced a mAb that could block PMA-induced homotypic T cell aggregation. The established mAb (TN14 mAb) showed an inhibitory effect on T cell aggregation as large as that of mAb against lymphocyte function-associated Ag-1. TN14 mAb showed a strong reactivity with cell surface molecules on T cells, whereas it did not react with any cell surface Ag on macrophages, B cells, bone marrow cells, or WEHI 164 cells, which were used for immunization. However, all cell lysates could react with TN14 mAb in Western blotting analysis, indicating that TN14 mAb recognized some cytoplasmic protein. From biochemical analysis, TN14 mAb was demonstrated to react with the 43-kDa cytoskeletal protein actin. Moreover, from an immunoprecipitation study, TN14 mAb was demonstrated to cross-react with the Thy-1 molecule on T cells. The binding activity of TN14 mAb with the Thy-1 molecule on T cells was strongly blocked by the addition of purified actin, indicating that TN14 mAb recognized an actin-related epitope of the Thy-1 molecule. TN14 mAb blocked not only T cell aggregation but also cell-mediated cytotoxicity by CTL. These results strongly support the hypothesis that the Thy-1 molecule, a member of the Ig superfamily, may play an important role in cell-cell interactions of T cells.

Actins

An immunohistochemical study of MAP2 and clathrin in gerbil hippocampus after cerebral ischemia.

Changes in MAP2 and clathrin immunoreactivity were studied in gerbil hippocampus after transient cerebral ischemia. MAP2 immunoreactivity decreased significantly by 1 h in the subiculum-CA1 and CA2 areas which correspond to reactive change, while no decrease was observed in CA1 until day 4. Before the initiation of delayed neuronal death, MAP2 immunoreactivity was not changed in CA1. On the other hand clathrin immunoreactivity increased in the pyramidal cell layer of CA1 by 3 h after ischemia and remained high for 2 days. Clathrin immunoreactivity in the pyramidal cell layer of CA1 diminished after delayed neuronal death. The transient change of clathrin was noted especially in CA1 in the period prior to delayed neuronal death. These results imply an abnormal change in clathrin turnover after ischemia, which may participate in the pathogenesis of delayed neuronal death.

Animals

Abnormal distribution of cathepsins in the brain of patients with Alzheimer's disease.

Formalin-fixed paraffin-embedded hippocampal sections of brains with early-onset and late-onset Alzheimer's disease were studied immunohistochemically with antisera against cathepsin D and cathepsin B. In addition to the staining of neuronal perikarya, some of the senile plaques visualized by Bielshowsky silver staining and some of reactive astrocytes were positively stained with the antisera against cathepsin D and cathepsin B in brains with Alzheimer's disease. Abnormal localization of cathepsin D and cathepsin B immunoreactivity in neuronal perikarya was observed in brains with early-onset Alzheimer's disease. These findings demonstrate that the distribution of lysosomal proteases was altered in brains with Alzheimer's disease, suggesting the primary and/or secondary involvement of the lysosomal proteases in the pathological process of Alzheimer's disease.

Alzheimer Disease

Cloning and structural analysis of cDNA and the gene for mouse transcription factor UBF.

The gene and protein structure of the mouse UBF (mUBF), a transcription factor for mouse ribosomal RNA gene, have been determined by cDNA and genomic clones. The unique mUBF gene consists of 21 exons spanning over 13 kb. Two mRNAs coding for mUBF1 and mUBF2 having 765 a.a. and 728 a.a., respectively, are produced by an alternative splicing of exon 8. It specifies 37 amino acids constituting a part of the regions homologous to high mobility group proteins (HMG box 2). A human UBF (hUBF) cDNA obtained by polymerase chain reaction also indicates the presence of two kinds of mRNAs, the shorter form lacking the same region as mUBF2. Comparison of the cDNAs from hUBF and mUBF revealed an unusual conservation of nucleotide sequence in the 3'-terminal non-coding region. We examined the relative amounts of expression of mUBF1 and mUBF2. The eight tissues studied contained both molecular species, although mUBF2 was the predominant form of UBF. The mRNA of mUBF1 was expressed one half of the mUBF2 in quiescent mouse fibroblasts but reached the same amount in growing state.

Amino Acid Sequence

Binding of calpain fragments to calpastatin.

Their cDNA-derived amino acid sequences predict that the 80-kDa subunits of the micromolar and millimolar Ca(2+)-requiring forms of the Ca(2+)-dependent proteinase (mu- and m-calpain, respectively) each consist of four domains and that the 28-kDa subunit common to both mu- and m-calpain consists of two domains. The calpains were allowed to autolyze to completion, and the autolysis products were separated and were characterized by using gel permeation chromatography, calpastatin affinity chromatography, and sequence analysis. Three major fragments were obtained after autolysis of either calpain. The largest fragment (34 kDa for mu-calpain, 35 kDa for m-calpain) contains all of domain II, the catalytic domain, plus part of domain I of the 80-kDa subunit of mu- or m-calpain. This fragment does not bind to calpastatin, a competitive inhibitor of the calpains, and has no proteolytic activity in either the absence or presence of Ca2+. The second major fragment (21 kDa for mu-calpain and 22 kDa for m-calpain) contains domain IV, the calmodulin-like domain, plus approximately 50 amino acids from domain III of the 80-kDa subunit of mu- or m-calpain. The third major fragment (18 kDa) contains domain VI, the calmodulin-like domain of the 28-kDa subunit. The second and third major fragments bind to a calpastatin affinity column in the presence of Ca2+ and are eluted with EDTA. The second and third fragments are noncovalently bound, so the 80- and 28-kDa subunits of the intact calpain molecules are noncovalently bound at domains IV and VI. After separation in 1 M NaSCN, the 28-kDa subunit binds completely to calpastatin, approximately 30-40% of the 80-kDa subunit of mu-calpain binds to calpastatin, and the 80-kDa subunit of m-calpain does not bind to calpastatin in the presence of 1 mM Ca2+.

Amino Acid Sequence

Buffy coat from families of Alzheimer's disease patients produces intracytoplasmic neurofilament accumulation in hamster brain.

Buffy coat of three members from a family with Alzheimer's disease was inoculated into hamster brains. Eighteen months after the inoculation, all experimental animals were sacrificed for the neuropathological study. Hematoxylin-eosin staining showed no gross vacuolar degeneration, or neuronal loss in the cortex. The spongiform degeneration was minimum. Immunostaining with antibodies against neurofilament 200 kDa subunit protein revealed massive immuno-positive intracytoplasmic inclusion bodies within neurons of the brainstem nuclei. By electron microscopy, the intracytoplasmic inclusion body was shown to be composed of proliferated 10 nm neurofilaments. The intra-cytoplasmic neurofilament proliferation was observed with the hamsters inoculated with the buffy coat from Alzheimer's disease patients as well as an apparently normal member of the family.

Alzheimer Disease

Low glucose-1, 6-bisphosphate and high fructose-2, 6-bisphosphate concentrations in muscles of patients with glycogenosis types VII and V.

The level of glucose-1, 6-bisphosphate, a potent allosteric activator of phosphofructokinase, was markedly decreased in muscles of patients with glycogenosis type VII (muscle phosphofructokinase deficiency) and type V (muscle phosphorylase deficiency). Glucose-1-phosphate kinase activity in muscle was virtually absent in a patient with glycogenosis type VII, whereas it was normal in a patient with type V glycogenosis. Glucose-1-phosphate level was increased in type VII glycogenosis, whereas it was decreased in type V glycogenosis. Another activator of phosphofructokinase, fructose-2, 6-bisphosphate was increased in muscles of patients with both types of glycogenosis although it was much higher in type VII than in type V. This finding may be partly related to the difference of fructose-6-phosphate concentrations. The results suggest that phosphofructokinase would contribute to the major glucose-1-phosphate kinase activity in normal human muscle and would also form a kind of self-activating system.

Fructosediphosphates

[Hepatic parenchymal changes after intraarterial administration of lipiodol: an animal experiment].

The effect of Lipiodol (LPD) on the hepatic parenchyma bearing VX2 tumor was investigated in 12 rabbits. In these rabbits Adriamycin (ADM) soluble Urografin and LPD were injected through the hepatic artery. As the control another 12 rabbits bearing VX2 tumor which were intraarterially injected with ADM solution in saline were used. Liver function tests revealed significantly higher values of serum transaminases in the LPD group than in the control group. Histologically in the LPD group, hepatocellular degeneration was observed and the severity was at its peak 3 days after injection whereas control animals preserved almost normal structure. The degeneration of the tumor-bearing lobe was more severe than that of the tumor-free lobe. This study showed the histologically and functionally demonstrable adverse effects of LPD.

Animals