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Biomedical subjects

T Nakata

Publications and source records attributed to T Nakata.

At least 163 records · Page 9Linked to original sources
PubMed1995

Role of baroreflex and central alpha2-adrenergic receptor systems in the diurnal variation of blood pressure and heart rate in normotensive and hypertensive rats.

1. To elucidate whether baroreflex could contribute to manifest the diurnal blood pressure variations (DBPV) in normotension and hypertension, DBPV were recorded continuously via a femoral artery in awake normotensive (NT) rats and spontaneously hypertensive rats (SHR) with and without sinoaortic denervation (SAD). To determine the role of central alpha2-adrenergic receptor system in DBPV in hypertension, guanabentz (0.5-1.0 mu g/kg per min) was infused in SHR. 2. There were no differences in mean arterial pressure (MAP) variability (SD) of MAP of 24 h (MAP -- SD/MAP) and SD of 24 h heart rate (HR -- SD/HR) between SHR and NT. SAD did not elevate MAP and HR in both SHR and NT. 3. However, in SAD rats, MAP -- SD/MAP was significantly greater than those in sham-operated rats in both SHR and NT, while MAP -- SD/MAP and HR -- SD/HR did not show any difference between the two groups even after SAD. On the other hand, SAD did not augment HR -- SD/HR in either strain. 4. During guanabentz infusion, MAP was significantly lowered in sham-operated and SAD -- SHR. Moreover, MAP -- SD/MAP was significantly reduced in sham-operated, but it was not in SAD -- SHR. 5. These findings suggest that baroreflex could suppress tonically the diurnal change of blood pressure in NT and SHR. The regulation of diurnal blood pressure by baroreflex via a central alpha-adrenergic receptor system may be altered in SHR.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1995

Role of basic and acidic fragments in delicious peptides (Lys-Gly-Asp-Glu-Glu-Ser-Leu-Ala) and the taste behavior of sodium and potassium salts in acidic oligopeptides.

The role of the acidic fragment (Asp-Glu-Glu) in delicious peptides was investigated in detail by using the Na+ or K+ salts of acidic oligopeptides so that amount of Na+ or K+ intake of peptides composed of acidic amino acids could be varied by changing their sequences. The taste of these peptides was confirmed to vary with Na+ or K+ intake. Additionally, in order to study the role of basic (Lys-Gly) and acidic (Asp-Glu-Glu) fragments in delicious peptides for producing the taste, five delicious peptide analogs, Ser-Leu-Ala-Lys-Gly-Asp-Glu-Glu, Ser-Leu-Ala-Asp-Glu-Glu-Lys-Gly, Lys-Gly-Ser-Leu-Ala-Asp-Glu-Glu, Lys-Gly-Asp-Glu-Glu, and Glu-Glu-Asp-Gly-Lys, were synthesized. The intensity of the umami and/or salty taste of these peptides and their Na salts was almost the same, despite their chemical structures being different. These results indicate that the acidic fragment as well as the basic fragment plays an important role in the taste production and intensity of delicious peptides, and that an umami or salty taste can be produced by the localization of the cation of the basic fragment and the anion of the acidic fragment.

Amino Acid Sequence↗
PubMed1995

[Prediction of left ventricular functional recovery in patients with acute myocardial infarction using single photon emission computed tomography with thallium-201 and iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid].

The relationships between myocardial perfusion, fatty acid metabolism, and cardiac function were investigated using dual single photon emission computed tomography (SPECT) with thallium and iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid (123I-BMIPP) during the acute (10 +/- 1 days) and recovery (60 +/- 14 days) phases in 29 patients with acute myocardial infarction. There were 18 patients who underwent successful primary coronary angioplasty (PTCA group) and 11 patients who received conservative therapy (non PTCA group). Thallium and BMIPP uptakes were scored visually by a 4-point system and left ventricular ejection fraction (LVEF) was calculated by radionuclide ventriculography. Although significant positive correlations between thallium and 123I-BMIPP scores were observed during both phases, BMIPP scores were significantly lower than thallium scores in both acute and recovery phases in the PTCA group. No significant difference in thallium and 123I-BMIPP scores was observed at the recovery phase in the non PTCA group. LVEF significantly correlated with thallium and 123I-BMIPP scores in both phases in the PTCA group. Furthermore, the difference between thallium and 123I-BMIPP scores during the acute phase significantly correlated with the improvement of LVEF during the follow-up period in the PTCA group (y = 0.92x-0.77, r = 0.65, p < 0.005). These findings suggest that mismatch of perfusion and metabolism in infarcted myocardium assessed by thallium and 123I-BMIPP SPECT is increased by reperfusion therapy and persists at least until the recovery phase of myocardial infarction. The recovery of left ventricular function depends on the extent of the mismatched uptake, indicating a predictor for functional recovery following acute myocardial infarction.

Adult↗
PubMed1995

Cardiac sympathetic denervation in transthyretin-related familial amyloidotic polyneuropathy: detection with iodine-123-MIBG.

In familial amyloidotic polyneuropathy (FAP), the peripheral nervous system is predominantly impaired. Cardiac sympathetic function has not been directly assessed. A 65-yr-old man with severe peripheral neuropathy due to primary systemic amyloidosis was studied. Echocardiograms and scintigraphic examinations with 20Tl and 99mTc-pyrophosphate demonstrated highly thickened but normally perfused left ventricular walls with intense diffuse amyloid deposits. No definite myocardial activity of [123I]metaiodobenzylguanidine (MIBG) was detected in any cardiac region, indicating lack of sympathetic nerve endings. Despite maintained cardiac contractility, left ventricular diastolic performance and heart rate variability assessed by power spectral analysis were markedly depressed. Thus, the myocardial defect of MIBG activity may provide direct evidence of impaired cardiac sympathetic nerve endings due to amyloid deposits in FAP.

3-Iodobenzylguanidine↗
PubMed1995

[Quantitative assessment of myocardial viability by thallium-201 reinjection with SPECT: comparative studies with resting image in myocardial infarction].

Exercise-stress thallium (Tl) scintigraphy is a reliable diagnostic tool for evaluating the reversibility of injury to the myocardium; however, overestimation of infarcted volume has been considered as a clinical limitation, both in recent and in old myocardial infarctions. To reveal the clinical efficacy of reinjection modification, infarcted and ischemic myocardium were quantitatively evaluated by stress, reinjection, and resting image with 201Tl SPECT in 43 patients with myocardial infarction. A quite significant correlation was found in severity scores from reinjection and resting images (87 +/- 12 vs. 81 +/- 10, r = 0.85, p < 0.001), these were significantly lower than the scores from post-exercise (124 +/- 13) and 4-hour delayed (103 +/- 11) images. The fractions of reversible ischemic myocardium predicted by reinjection and resting images also correlated with each other (r = 0.55, p < 0.05) and were significantly larger than those from 4-hour delayed images. Furthermore, the degree of redistribution of myocardial perfusion observed in reinjection image showed a significant positive linear correlation with improved myocardial perfusion after coronary revascularization (r = 0.80, p < 0.001), while that from the 4-hour delayed image did not. These results suggest that the severity score of thallium reinjection method is useful for quantifying both labile and non-labile myocardium after myocardial infarction and contributes to predicting the effect of coronary revascularization therapy.

Adult↗
PubMed1995

[Clinical implications of mismatched uptakes of beta-methyl fatty acid analogue and thallium in infarcted myocardium: correlations with coronary stenosis and regional wall motion abnormality].

Myocardial perfusion and fatty acid metabolism were assessed by using myocardial single-photon emission computed tomography with thallium and beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) during acute and/or late stages of myocardial infarction in 157 infarcted segments of 100 patients. The incidence of reduced thallium perfusion relative to BMIPP uptake ("T-type" mismatch) was significantly (p < 0.05) lower (9%) compared to that of reduced BMIPP uptake relative to thallium perfusion ("B-type" mismatch) (59%) or non-mismatched segment (32%). In an anteroseptal region, B-type dissociation had a significantly higher incidence compared to no or T-type mismatch; 68% vs. 27% vs. 5%, respectively, whereas the incidence of T-type uptake was relatively high in inferior and posterolateral regions; 13%, 11%, respectively. Severe coronary stenosis was observed in 76% of B-type segments and 72% of non-mismatched segments but in only 43% of T-type segments. The incidence of regional wall motion abnormality was significantly lower (46%) in the T-type mismatch segments when compared to the B-type (91%) or non-mismatched segments (96%). In conclusion, myocardial fatty acid metabolism was more markedly impaired compared to an involved coronary perfusion, resulting in the mismatch of perfusion and fatty acid metabolism. Coronary stenosis and regional wall motion abnormality are more closely related to "B-type" mismatch but not necessarily to "T-type" dissociation, probably because of attenuation artifacts in inferior and posterolateral regions in thallium scan.

Aged↗
PubMed1995

[123I-metaiodobenzylguanidine myocardial scintigraphy in a case of pheochromocytoma before and after resection of it].

A 55-year-old man with pheochromocytoma was examined by 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy before and after resection of the tumor. MIBG images showed decreased uptake in infero-posterior wall before operation. The heart to upper mediastinum uptake ratio was low at the delayed anterior planar image, and mean MIBG clearance from the left ventricle was increased. These abnormal scintigraphic findings improved after resection of the tumor. We thought that these abnormal MIBG findings were not due to abnormal cardiac sympathetic nerve function, because ECG, chest X-ray, UCG and 201Tl myocardial scintigram did not reveal any abnormality. It may be presumed that these abnormal MIBG findings were caused by high plasma catecholamines concentration. The mechanism of abnormal MIBG findings of the heart remains uncertain in various heart diseases. MIBG findings in this case with pheochromocytoma before and after resection may contribute to interpretation of the kinetics of MIBG in heart.

3-Iodobenzylguanidine↗
PubMed1995

[Induction and release of manganese superoxide dismutase caused by tumor necrosis factor-alpha from mitochondria in human umbilical vein endothelial cells].

The effects of tumor necrosis factor-alpha (TNF-alpha) on cultured human umbilical vein endothelial cells (EC) and five cancer cell lines, A549, ME180, A2780, KURAMOCHI, and Hela, were compared. While A549, A2780, KURAMOCHI, and Hela cells were fairly resistant to the cytolytic effects of TNF-alpha, ME180 cells were sensitive. EC were also less sensitive to TNF-alpha than ME180 cells as judged by the viability of individual cells and by the release of lactate dehydrogenase (LDH) into the medium. Manganese superoxide dismutase (Mn-SOD) was markedly induced by these cytokines in EC and in A549 cells but not in ME180 cells. The levels of Mn-SOD in the conditioned medium of EC were dramatically increased after stimulation with cytokines, whereas those in ME180 and A549 cells were relatively low. The amount of Mn-SOD released appears to be comparable to that from cells lysed by other means. Immunoblot analysis of Mn-SOD in the medium showed that the molecular mass of the immunoreactive protein was the same as mitochondrial Mn-SOD, indicating that no proteolysis had occurred. These data suggest that in vivo the TNF-alpha produced by cancer cells may induce Mn-SOD in vascular endothelial cells, resulting in release of a relatively large amount of this protein into the serum.

Biomarkers, Tumor↗
PubMed1994

A complex of GRB2-dynamin binds to tyrosine-phosphorylated insulin receptor substrate-1 after insulin treatment.

Insulin drives the formation of a complex between tyrosine-phosphorylated IRS-1 and SH2-containing proteins. The SH2-containing protein Grb2 also possesses adjacent SH3 domains, which bind the Ras guanine nucleotide exchange factor Sos. In this report, we examined the involvement of another SH3 binding protein, dynamin, in insulin signal transduction. SH3 domains of Grb2 as GST fusion proteins bound dynamin from lysates of CHO cells expressing wild-type insulin receptor (IR) (CHO-IR cells) in a cell-free system (in vitro). Immunoprecipitation studies using specific antibodies against Grb2 revealed that Grb2 was co-immunoprecipitated with dynamin from unstimulated CHO-IR cells. After insulin treatment of CHO-IR cells, anti-dynamin antibodies co-immunoprecipitated the IR beta-subunit and IRS-1, as tyrosine-phosphorylated proteins and PI 3-kinase activity. However, purified rat brain dynamin did not bind directly to either the IR, IRS-1 or the p85 subunit of PI 3-kinase in vitro. Together, these results suggest that in CHO-IR cells, insulin stimulates the binding of dynamin to tyrosine-phosphorylated IRS-1 via Grb2 and that IRS-1 also associates with PI 3-kinase in response to insulin. This complex formation was reconstituted in vitro using recombinant baculovirus-expressed IRS-1, GST-Grb2 fusion proteins and dynamin peptides containing proline-rich sequences. Furthermore, dynamin GTPase activity was found to be stimulated when an IRS-1-derived phosphopeptide, containing the Grb2 binding site, was added to the dynamin-Grb2 complex in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptor Proteins, Signal Transducing↗
PubMed1994

Induction of manganese superoxide dismutase mRNA by okadaic acid and protein synthesis inhibitors.

We have reported that the phorbol ester phorbol 12-myristate 13-acetate (PMA) enhances the expression of manganese superoxide dismutase (Mn-SOD) mRNA [Fujii and Taniguchi (1991) J. Biol. Chem. 266, 23,142-23,146]. Okadaic acid, an inhibitor of type I and type IIa phosphatases, was also found to induce Mn-SOD mRNA at submicromolar concentrations in HeLa cells. Addition of cycloheximide resulted in superinduction of PMA- or tumour necrosis factor-stimulated expression of the mRNA, but not of okadaic acid-stimulated expression. When the effect of cycloheximide on the decay of Mn-SOD mRNA was examined by inhibiting mRNA synthesis with actinomycin D, cycloheximide had virtually no effect on mRNA stability, suggesting that accumulation of the mRNA was caused by activation by this reagent of transcription of the gene. PMA pretreatment of HeLa cells markedly enhanced cycloheximide-dependent superinduction of Mn-SOD mRNA. These data suggest that phosphorylation of several proteins is implicated in the regulation of Mn-SOD gene expression.

Animals↗
PubMed1994

Association of Ash/Grb-2 with dynamin through the Src homology 3 domain.

Ash/Grb-2 is an adaptor protein composed only of Src homology (SH) 2 and SH3 domains that is considered to be essential for Ras activation. To clarify the downstream of Ash signaling, we investigated Ash-bound proteins. Ash-glutathione S-transferase (GST) fusion proteins were used to affinity-purify proteins bound to Ash. We found 180-, 150-, 100-, and 70-kDa proteins bound to GST-Ash, among which the 100 kDa protein was found to be dynamin by amino acid sequencing and Western blot with anti-dynamin antibody. Next, the in vitro and in vivo associations between Ash and dynamin were examined using PC12 cells. Dynamin in PC12 cell lysates bound to GST-Ash independent of NGF treatment. Also, Ash and dynamin co-precipitated when cell lysates of PC12 were immunoprecipitated with anti-Ash antibody or anti-dynamin antibody. Using various GST-Ash constructs, we studied the importance of the individual domains in binding and found that the SH3 domain is necessary for binding. This binding was inhibited by a synthetic peptide (GPPQVPSRPNRC, amino acids 827-838 in dynamin). These data show that Ash SH3 domains bind to the proline-rich region of dynamin. Considering the function of dynamin in membrane trafficking, Ash may regulate endocytosis in addition to Ras activation.

Adaptor Proteins, Signal Transducing↗
PubMed1994

SV40 large T antigen reinduces the cell cycle in terminally differentiated myotubes through inducing Cdk2, Cdc2, and their partner cyclins.

Terminally differentiated skeletal muscle myotubes are arrested in G0 phase of the cell cycle and are unable to be released from this arrest by stimulation with mitogens including serum and growth factors. To inspect a possibility of reversing the quiescence at the G0 phase, we have exploited the mouse skeletal muscle cell line C2SVTts11, which is a clone of C2 cells transfected with the SV40 T antigen gene (encoding thermolabile large T and wild-type small t) fused to an inducible promoter. When the large T is induced in the myotubes, the terminally differentiated cells reenter the cell cycle and proceed to S and M phases. To elucidate how large T forces the myotubes to traverse each phase of the cell cycle, we examined the expression and activity of Cdk2 and Cdc2, which in complex with cyclin A and cyclin B are essential for S and M phases, respectively in undifferentiated cells. The levels of their mRNAs and proteins and histone H1 kinase activity, which was ascribed to Cdc2-cyclin B, were high in the proliferating myoblasts but gradually decreased during terminal differentiation. In contrast, they were reinduced in the myotubes reentering the cell cycle. Stimulation of the myotubes with serum failed to evoke these factors. These results indicate that large T, but not mitogens, is able to drive terminally differentiated myotubes to pass each phase of the cell cycle through eliciting these factors as do mitogens on proliferating undifferentiated cells. Since large T is a nuclear protein, signals generated by the protein in the nucleus are likely to be sufficient to induce each phase of the cell cycle in the terminally differentiated cells.

Animals↗
PubMed1994

KIF3A is a new microtubule-based anterograde motor in the nerve axon.

Neurons are highly polarized cells composed of dendrites, cell bodies, and long axons. Because of the lack of protein synthesis machinery in axons, materials required in axons and synapses have to be transported down the axons after synthesis in the cell body. Fast anterograde transport conveys different kinds of membranous organelles such as mitochondria and precursors of synaptic vesicles and axonal membranes, while organelles such as endosomes and autophagic prelysosomal organelles are conveyed retrogradely. Although kinesin and dynein have been identified as good candidates for microtubule-based anterograde and retrograde transporters, respectively, the existence of other motors for performing these complex axonal transports seems quite likely. Here we characterized a new member of the kinesin super-family, KIF3A (50-nm rod with globular head and tail), and found that it is localized in neurons, associated with membrane organelle fractions, and accumulates with anterogradely moving membrane organelles after ligation of peripheral nerves. Furthermore, native KIF3A (a complex of 80/85 KIF3A heavy chain and a 95-kD polypeptide) revealed microtubule gliding activity and baculovirus-expressed KIF3A heavy chain demonstrated microtubule plus end-directed (anterograde) motility in vitro. These findings strongly suggest that KIF3A is a new motor protein for the anterograde fast axonal transport.

Animals↗
PubMed1994

Direct visualization of the microtubule lattice seam both in vitro and in vivo.

Microtubules are constructed from alpha- and beta-tubulin heterodimers that are arranged into protofilaments. Most commonly there are 13 or 14 protofilaments. A series of structural investigations using both electron microscopy and x-ray diffraction have indicated that there are two potential lattices (A and B) in which the tubulin subunits can be arranged. Electron microscopy has shown that kinesin heads, which bind only to beta-tubulin, follow a helical path with a 12-nm pitch in which subunits repeat every 8-nm axially, implying a primarily B-type lattice. However, these helical symmetry parameters are not consistent with a closed lattice and imply that there must be a discontinuity or "seam" along the microtubule. We have used quick-freeze deep-etch electron microscopy to obtain the first direct evidence for the presence of this seam in microtubules formed either in vivo or in vitro. In addition to a conventional single seam, we have also rarely found microtubules in which there is more than one seam. Overall our data indicates that microtubules have a predominantly B lattice, but that A lattice bonds between tubulin subunits are found at the seam. The cytoplasmic microtubules in mouse nerve cells also have predominantly B lattice structure and A lattice bonds at the seam. These observations have important implications for the interaction of microtubules with MAPs and with motor proteins, and for example, suggest that kinesin motors may follow a single protofilament track.

Animals↗
PubMed1994

Association of blood pressure variability with induction of atherosclerosis in cholesterol-fed rats.

The influence of increased lability of blood pressure on the development of aortic atherosclerosis was examined. Because sinoaortic denervation (SAD) produced increased lability of blood pressure without blood pressure elevation, the development of atheromatous plaque was examined in SAD rats. These rats were fed a high-cholesterol diet and were denuded of endothelium so that development of atherosclerosis was accelerated. Five groups of male Wistar rats were used: A) controls, B) high-cholesterol diet (HC), C) HC+denudation (DN), D) HC+DN+renal artery clipping (2K1C), and E) HC+DN+sinoaortic denervation (SAD). Denudation was accomplished by scraping the aortic lumen with a balloon catheter, and hypertension was induced by clipping the left renal artery. After recording blood pressure and heart rate for 6 weeks, the rats were killed, blood samples were collected, and thoracic aortas were removed for pathologic examination. All the groups of rats fed a high-cholesterol diet developed marked hypercholesterolemia and hypotriglyceridemia. High-cholesterol diet alone could not induce aortic atherosclerosis, whereas aorta of HC+DN rats showed slight intimal thickening with smooth muscle cell proliferation. On the other hand, aorta of HC+DN + 2K1C rats showed marked atheromatous plaque with prominent cellular proliferation, and aorta of SAD rats also showed mild to moderate atheromatous plaque. Accordingly, we concluded that increased variability in circadian blood pressure per se, as well as hypertension, could induce aortic atherosclerosis in the hypercholesterolemic and endothelium-denuded rats.

Animals↗