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Biomedical subjects

M Tahara

Publications and source records attributed to M Tahara.

At least 55 records · Page 3Linked to original sources

Serum levels of cardiac troponin I and troponin T in estimating myocardial infarct size soon after reperfusion.

BACKGROUND: Cardiac troponin I (TnI) and troponin T (TnT) are highly specific myocardial markers. OBJECTIVE: To determine whether their serum levels can be used to estimate myocardial infarct size soon after reperfusion. METHODS: We measured the serum levels of TnI, TnT, and creatine kinase every 3 h, and the serum cardiac myosin light chain I (MLCI) every 24 h, in 42 patients with acute myocardial infarction in whom reperfusion therapy had successfully been performed. We calculated the severity of regional hypokinesis by analyzing the follow-up ventriculograms with the centerline method. RESULTS: The time from reperfusion to the peak level for TnI was 6.1 +/- 3.5 h, significantly shorter than those for creatine kinase (7.5 +/- 4.1 h) and MLCI (55 +/- 28 h). The time to peak level for TnT (6.8 +/- 4.0 h) differed significantly from that for MLCI but not from that for creatine kinase. There was a significant correlation between the peak levels of TnI and TnT (r = 0.86). The peak TnI and TnT levels were correlated well to the peak creatine kinase level (r = 0.67 and 0.69, respectively), total creatine kinase release (r = 0.66 and 0.66), and the peak MLCI level (r = 0.71 and 0.80). We observed excellent correlations between the peak levels of TnI and TnT, and regional hypokinesis (r = -0.84 and -0.85, respectively). These were comparable to the correlations between regional hypokinesis and the peak creatine kinase level (r = 0.75), total creatine kinase release (r = -0.72), and the peak MLCI level (r = -0.76). CONCLUSIONS: These results suggest that the peak serum levels of TnI and TnT in patients with successful reperfusion are accurate and early indices of infarct size.

Angioplasty, Balloon, Coronary↗

[The risk of palliative operation for bone metastasis].

Palliative operations for various bone metastases are being performed more frequently than before with the improvement of surgical technique and the development of new instruments. However, anesthesia in advanced cancer patients who are under palliative care accompanies inherent risks which are uncommon in general orthopaedic populations. Thus, we made a retrospective analysis of the medical records of 59 patients scheduled for palliative operation against metastatic bone lesions during the last 4 years. The survey revealed 5 cases of perioperative lethal events. Two of them died preoperatively from the hepatic failure and unexpected cerebral tumor embolism. An intraoperative cardiac arrest secondary to pulmonary embolism occurred in a patient during intramedullary nailing. There was a patient who developed disseminated intravascular coagulation and acute renal failure after posterior fixation of the lumbar vertebrae. The remaining one patient with superior vena cava syndrome developed life-threatening airway obstruction during general anesthesia with endotracheal intubation. We conclude that the exact evaluation of the patient's condition and the careful management of vital organ functions are mandatory during the perioperative period. In this regard, the anesthesiologists should be involved not only in the intraoperative anesthetic management but also in the perioperative care of the patients with bone metastasis.

Adult↗

Increase in the delta ST/delta heart rate (HR) index: a new predictor of restenosis after successful percutaneous transluminal coronary angioplasty.

With the goal of improving the prediction of restenosis after percutaneous transluminal coronary angioplasty (PTCA), we evaluated the usefulness of the delta ST/delta heart rate (HR) index derived from serial exercise treadmill tests. Exercise treadmill tests were performed by 125 patients with single-vessel coronary artery disease before and several days after PTCA, and just before follow-up angiography 3 to 12 months later. Simple HR-adjusted indexes of ST-segment depression during exercise (delta ST/delta HR index) were derived. We compared the usefulness of the increase in delta ST/delta HR index at follow-up over the value obtained several days after PTCA for prediction of restenosis with that of a positive exercise treadmill test and a positive thallium scintigram at follow-up. At follow-up, 47 of the 125 patients showed restenosis. The delta ST/delta HR index increased in 43 of 47 patients in the restenosis group and in 18 of 78 patients without restenosis (p < 0.0001). Separate analysis of each criterion revealed the following respective values for sensitivity, specificity, and positive and negative predictive values for prediction of restenosis; increased delta ST/delta HR index of follow-up: 91%, 77%, 70%, and 94%; positive exercise treadmill test: 83%, 65%, 59%, and 86%; and positive thallium scintigram: 79%, 78%, 69%, and 86%. The increased delta ST/delta HR index had a significantly (p < 0.05) higher sensitivity than the positive thallium scintigram and a significantly (p < 0.01) higher specificity than the positive exercise treadmill test. An increased delta ST/delta HR index at follow-up identifies subgroups of patients who are at high risk for restenosis after PTCA.

Aged↗

Binding and labeling of omega-conotoxin GVIA in crude membranes from subfractionated fractions and various areas of chick brain.

Specific binding and specific labeling of 125I-omega-CgTX were investigated in crude membranes from both subfractionated fractions and various brain areas in chick whole brain. The specific activities of the marker enzymes 2',3'-cyclic nucleotide 3'-phosphorylase, Na/K ATPase and succinic dehydrogenase in the subfractionated fractions were three- to five-fold higher than those in the P2 fraction. However, the amount of specific [125I] omega-CgTX binding in the fractions of synaptosomes and synaptic plasma membranes was only about 1.2-times higher than that in the P2 fraction. The characteristics of specific 125I-omega-CgTX labeling with disuccinimidyl suberate to the 135-kDa band were generally comparable to those of specific [125I] omega-CgTX binding sites. These results suggest that the specific binding sites of [125I] omega-CgTX were not localized the synaptosomes and synaptic plasma membranes fractions, although each fraction was well isolated from the others from which were decided by the strength of specific activity for marker enzymes.

Animals↗

Involvement of Rabphilin-3A in cortical granule exocytosis in mouse eggs.

Rabphilin-3A is a putative target protein for Rab3A, a member of the small GTP-binding protein superfamily that has been suggested to play a role in regulated exocytosis in presynapses. In this study we determined the expression and the function of Rabphilin-3A in mouse eggs at fertilization. Rabphilin-3A mRNA and protein were detected by reverse transcriptase-PCR and immunoblot analysis, respectively, in metaphase II mouse eggs. Immunofluorescence analysis showed that Rabphilin-3A protein was distributed in the cortical region in eggs. Sperm induces cortical granule (CG) exocytosis via an increase in cytosolic Ca2+ at fertilization. We microinjected the NH2- or COOH-terminal fragment of recombinant Rabphilin-3A into metaphase II eggs. Neither treatments altered the sperm-induced cytosolic Ca2+ increase, but both inhibited CG exocytosis in a dose-dependent manner. The NH2-terminal fragment was more effective than the COOH-terminal fragment. Full-length Rabphilin-3A did not affect CG exocytosis, but it attenuated the inhibition of CG exocytosis by the NH2-terminal fragment. These results show that Rabphilin-3A is involved in Ca(2+)-dependent CG exocytosis at fertilization in mouse eggs.

Adaptor Proteins, Signal Transducing↗

Reactive oxygen species block sperm-egg fusion via oxidation of sperm sulfhydryl proteins in mice.

The effects of reactive oxygen species (ROS) on mouse sperm-egg fusion were determined. Sperm were treated with superoxide and hydrogen peroxide generated by addition of xanthine oxidase (XO: 10-200 mlU/ml) to hypoxanthine (HX: 1 mM). While XO at concentrations higher than 100 mlU/ml decreased the motility and lipid peroxidation of sperm, XO at less than 50 mlU/ml had no such effect. However, 20-50 mlU/ml XO significantly suppressed sperm fusion with zona-free eggs. Two ROS scavengers, superoxide dismutase and catalase, attenuated the inhibition of sperm-egg fusion by HX-XO. The sulfhydryl (SH) reductant, dithiothreitol, also reversed the inhibition. The sperm SH-rich fusion-related proteins were highly sensitive to ROS. These results suggest that ROS at low concentrations may inhibit sperm-egg fusion via oxidation of the SH-proteins in the sperm membrane, without causing loss of motility.

Animals↗

Dynamics of cortical granule exocytosis at fertilization in living mouse eggs.

Sperm-egg fusion induces an intracellular free calcium concentration ([Ca2+]i) increase and exocytosis of cortical granules (CGs). Recently we used an impermeable fluorescent membrane probe, 1-[4-(trimethylammonio)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH), to develop a method to evaluate the kinetics of exocytosis in single living cells. In this study we used digital imaging and confocal laser scanning microscopy to evaluate CG exocytosis in living mouse eggs with TMA-DPH. Time-related changes of CG exocytosis were estimated as the percent increase of TMA-DPH fluorescence. The increase of fluorescence in the egg started after sperm attachment, continued at an almost uniform rate, and ceased at 45-60 min. Whereas the [Ca2+]i increase at fertilization was transient or oscillatory, exocytosis was not always induced concomitantly with each [Ca2+]i peak. Next we used this method to determine some intracellular mediators of exocytosis in the egg. An intracellular calcium chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester, and a microfilament inhibitor, cytochalasin B, blocked sperm-induced exocytosis. A guanosine 5'-triphosphate-binding protein activator, AlF4-, induced exocytosis. These results suggest that [Ca2+]i, microfilament, and guanosine 5'-triphosphate-binding proteins may be involved in CG exocytosis. In conclusion, this method has significant advantages for studying exocytosis in living eggs.

Animals↗

[Trial of bladder sparing for patients with invasive bladder cancer by transurethral resection and intra-arterial chemotherapy].

BACKGROUND: We reviewed our experience with bladder conservative treatment for invasive bladder cancer in 20 patients to investigate which type of tumor was suitable for organ conservation. METHODS: We performed radical transurethral resection with dissection to deep layer of the muscle plus intra-arterial chemoinfusion of the cis-platinum at a dose of 80-100 mg/body twice at least, and the recurrent tumor was treated by the same procedure. There were 13 cases of stage T2 and 7 cases of stage T3a. All patients were pathologically diagnosed transitional cell carcinoma with 9 cases of grade 2 and 11 cases of grade 3. RESULTS: With a follow-up of 36 months (range 18 to 82), 15 (75%) of 20 patients were survived and 10 (50%) of 20 patients were free of tumor. Of 5 patients with residual or recurrent tumor, 2 patient underwent cystectomy and the others were required transurethral resection. Of 5 patients died, 4 patients died of cancer all with distant metastasis (lung meta: 2 cases, liver meta: 2 cases). In reference to tumor characteristics, all 4 patients had over 3 cm diameter tumors with non-papillary surface and 3 of 4 patients had invasive tumors extended to bladder neck and prostatic urethra. Of 15 patients alive, 7 (47%) patients had non-papillary tumors, 9 (60%) had grade 3 tumors, 5 (33%) had T3a tumors, but invasion of the prostate urethra was recognized in only 3 patients (20%). CONCLUSION: We had possibility of doing organ prevention therapy for the patients with invasive bladder cancer, even though it was non-papillary or grade 3 tumor. On the other hand, it was thought that a conservative approach should not be considered in patients with large non-papillary tumors that extended to bladder neck and prostatic urethra.

Adult↗

[In vitro direct antiproliferative activity and in vivo antitumor activity of bropirimine against bladder cancer].

Bropirimine is an antitumor agent currently used in clinical trials on bladder cancer. It is known to induce IFN, to activate NK cells and to inhibit the growth of tumor cells. In this study, we examined the in vitro and in vivo efficacy of bropirimine on human and murine bladder cancer. Bropirimine showed in vitro antiproliferative activity on the human bladder cancer cell lines, T 24 and KoTCC-1. This activity was not: affected by the neutralizing antibodies against IFN-alpha, TNF-alpha or IL-1 beta, indicating it is the direct activity of bropirimine without involvement of cytokine production by tumor cells. Bropirimine was active at the concentrations comparable to those in serum or urine attained in clinical trials, which suggests that this direct antiproliferative activity is one of the important antitumor mechanisms of bropirimine. In in vivo experiments, bropirimine reduced the growth of transplanted murine MBT-2 and human KoTCC-1 bladder cancers by oral administration every 4 days starting on day 1, but did not show efficacy when the drug treatment was started on day 8. The antitumor activity of bropirimine was dependent on the timing for drug treatment initiation.

Animals↗

An atypical variant of Fabry's disease in men with left ventricular hypertrophy.

BACKGROUND: Fabry's disease is considered very rare. Left ventricular hypertrophy is one of the common manifestations in adults with classic hemizygous disease. Recently, several cases of an atypical variant of hemizygous Fabry's disease, with manifestations limited to the heart, have been reported. Therefore, we assessed the incidence of hemizygosity for Fabry's disease among male patients with left ventricular hypertrophy. METHODS: We measured plasma alpha-galactosidase activity in 230 consecutive male patients with left ventricular hypertrophy. Clinical manifestations were assessed, endomyocardial biopsies were performed, and the patients were screened for mutations in the alpha-galactosidase gene. RESULTS: Seven of the 230 patients with left ventricular hypertrophy (3 percent) had low plasma alpha-galactosidase activity (0.4 to 1.2 nmol per hour per milliliter; 4 to 14 percent of the mean value in normal controls). These seven unrelated patients, ranging in age from 55 to 72 years, did not have angiokeratoma, acroparesthesias, hypohidrosis, or corneal opacities, which are typical manifestations of Fabry's disease. Endomyocardial biopsy was performed in five patients and revealed marked sarcoplasmic vacuolization in all five. Samples from four patients were examined by electron microscopy and revealed typical lysosomal inclusions with a concentric lamellar configuration in all four. Two patients had novel missense mutations in exon 1 (Ala20Pro) and exon 6 (Met296lle). The remaining five had no mutations in the coding region of the alpha-galactosidase gene, but the amounts of the alpha-galactosidase messenger RNA were markedly lower than normal. CONCLUSIONS: Seven unrelated patients with atypical variants of hemizygous Fabry's disease were found among 230 men with left ventricular hypertrophy (3 percent). Fabry's disease should be considered as a cause of unexplained left ventricular hypertrophy.

Adolescent↗

Characteristics of specific 125I-omega-conotoxin GVIA binding and 125I-omega-conotoxin GVIA labeling using bifunctional crosslinkers in crude membranes from chick whole brain.

Characteristics of specific 125I-omega-conotoxin GVIA (125I-omega-CgTX) binding and 125I-omega-CgTX labeling using bifunctional crosslinkers were systematically investigated in crude membranes from chick whole brain. Aminoglycosides and dynorphine A (1-13) inhibited the specific binding of 125I-omega-CgTX, but not that of the L-type calcium ion channel antagonist [3H](+)PN200-110. It seems likely that the inhibitory effect of dynorphine A (1-13) does not involve kappa-opiate receptors, based on results with the opiate receptor antagonist naloxone and the kappa-opiate receptor agonist U50488H. Spider venom, Cd2+ and La3+ inhibited the specific binding of 125I-omega-CgTX, as well as that of [3H](+)PN200-110. Various L-type Ca2+ channel antagonists did not affect the specific binding of 125I-omega-CgTX. 125I-omega-CgTX specifically labeled 135 kDa and 215 kDa bands in crude membranes under reduced and non-reduced conditions, respectively. The crosslinker disuccinimidyl suberate (DSS) yielded better 125I-omega-CgTX labeling than the other two crosslinkers tested. We investigated the effect of various Ca2+ channel antagonists on 125I-omega-CgTX labeling with DSS in detail, and found that there is a strong correlation between the effects of Ca2+ channel antagonists on 125I-omega-CgTX labeling of the 135 kDa band and specific 125I-omega-CgTX binding. These results suggest that aminoglycosides and dynorphine A (1-13) are specific inhibitors of specific 125I-omega-CgTX binding, and that labeling of the 135 kDa band with 125I-omega-CgTX using DSS involves the specific binding sites of 125I-omega-CgTX, perhaps including one of the neuronal N-type Ca2+ channel subunits in the crude membranes.

Affinity Labels↗

Changes in serum myosin light chain I following aortocoronary bypass operations.

The changes in myosin light chain I (MLC I) following aortocoronary bypass were studied in 31 patients and the curves of these changes were classified into three different patterns. A peak level of 14.7 +/- 1.54 ng/ml was seen in seven patients on postoperative day (POD) 2 which decreased suddenly to less than twice the normal value by POD 7 (group 1). Another 19 patients showed a peak level of 20.7 +/- 16.5 ng/ml on POD 5, which decreased slowly and was still high even by POD 7 (group 2). The remaining five patients developed only a slight increase in the MLC I level after the operation, with a peak value of 5.5 +/- 0.8 ng/ml (group 3). Creatine kinase myocardial band and glutamic oxaloacetic transaminase also remained low in this group. No correlation existed between the peak value of MLC I and the aortic cross-clamping time, or between the peak value of MLC I and the cardiopulmonary bypass time. Furthermore, the difference in cardiac output before and after the operation did not significantly differ among the three groups. These findings indicate that the measurement of MLC I is useful for diagnosing perioperative myocardial damage and may also be useful in the study of myocardial protection.

Adult↗

Characteristics of [125I]omega-conotoxin labeling using bifunctional cross linker DSP in crude membranes from chick brain.

Characteristic of [125I]omega-conotoxin (omega-CgTX) labeling using bifunctional cross linker (dithio bis[succinimidyl propionate]:DSP) was systematically investigated in crude membranes from chick whole brain. [125I]omega-CgTX specifically labeled 216 kDa as a main and 236 kDa as a minor bands in the crude membranes under non-reduced condition, but not labeled under reduced condition. We investigated the effect of various Ca channel antagonists on [125I]omega-CgTX labeling with DSP in detail, and found that there is a strong correlation between the effects of Ca channel antagonists on [125I]omega-CgTX labeling of the 216 kDa band and specific [125I]omega-CgTX binding. These results suggest that labeling of the 216 kDa band under non-reduced condition with [125I]omega-CgTX using DSP involves the specific binding sites of [125I]omega-CgTX, perhaps including one of the neuronal N-type Ca channel subunits in the crude membranes.

Animals↗

Expression of messenger ribonucleic acid for epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha), and EGF receptor in human amnion cells: possible role of TGF alpha in prostaglandin E2 synthesis and cell proliferation.

The amnion plays important structural and functional roles in the maintenance of pregnancy and the initiation of parturition. Recently, we reported that epidermal growth factor (EGF) activates prostaglandin (PG) production and cell growth in cultured amnion cells. In this study, we showed the expression of EGF, transforming growth factor-alpha (TGF alpha), and EGF receptor protein and messenger ribonucleic acid in amnion cells, using an immunofluorescence technique and the reverse transcription-polymerase chain reaction. Next, we studied the effect of TGF alpha on intracellular Ca2+ mobilization and PGE2 production in amnion cells. TGF alpha induced an increase in the intracellular Ca2+ concentration in amnion cells, and this increase was significantly reduced when the cells were incubated with cobalt chloride (a Ca2+ channel blocker; 2.5 mmol/L) or EGTA (a Ca2+ chelator; 5 mmol/L). TGF alpha enhanced PGE2 production, and this increase was significantly inhibited when the cells were incubated with indomethacin (a cyclooxygenase inhibitor; 10 mumol/L), cobalt chloride (2.5 mmol/L), or EGTA (5 mmol/L). We also investigated the effect of TGF alpha on the growth of cultured human amnion cells by using flow cytometric analysis of the DNA content. TGF alpha induced DNA synthesis by human amnion cells, and indomethacin inhibited the TGF alpha-induced DNA synthesis. These results suggest that 1) EGF/TGF alpha are expressed and produced in amnion cells; 2) these endogenous factors may regulate the proliferation of amnion cells in an autocrine or paracrine manner; and 3) these growth factors may exert their effects via intracellular Ca2+ mobilization and PGE2 production.

Amnion↗

Scanning electron microscope assessment of exocytotic changes in purified gonadotropes.

These studies were undertaken to characterize the exocytotic changes in purified gonadotropes by three-dimensional imaging using scanning electron microscopy. Rat gonadotropes were purified using a fluorescence-activated cell sorter and an argon laser treatment system. The purified gonadotropes were stimulated with GnRH under various conditions and fixed for scanning electron microscopy. After the GnRH stimulation, many 'hole' structures (diameter 0.1-0.5 micron) were observed on the cell surface, and notably the population of cells with 10 or more holes was clearly increased. The pattern of the time-course of the changes in this population was perfectly consistent with the LH secretory profile of pituitary cells, and their formation of the cells with 10 or more holes was completely inhibited by pretreatment with a GnRH antagonist. Our data suggest that the hole structure represents an exocytotic opening site and that regulated exocytosis in purified gonadotropes can be evaluated by scanning electron microscopy. This method may be widely applicable to other endocrine cells.

Animals↗

Transforming growth factor-beta 1 post-transcriptionally inhibits mouse growth hormone releasing factor secretion in placenta.

The aim of this study was to investigate whether TGF-beta 1 regulates mouse GHRF secretion by primary cultures of placental cells from day 12 of pregnancy. Ten ng/ml TGF-beta 1 significantly inhibited mouse GHRF secretion by the third day of culture. The lowest concentration of TGF-beta 1 that significantly inhibited mouse GHRF secretion was 1 ng/ml. The inhibitory effect of TGF-beta 1 on mouse GHRF secretion was completely eliminated by addition of an anti-TGF-beta 1 antibody. Steady-state levels of mouse GHRF mRNA as assessed by Northern analysis was not reduced by incubation of placental cells from day 12 of pregnancy with 10 ng/ml TGF-beta 1 for 5 days. Both placenta and decidua expressed TGF-beta 1 mRNA, and the level of TGF-beta 1 mRNA in decidua increased during gestation while the level of TGF-beta 1 mRNA was constant throughout gestation. These findings suggest that TGF-beta 1 is one of the potent regulators of mouse GHRF secretion and that TGF-beta 1 regulates mouse GHRF secretion in an autocrine or paracrine manner in the mouse placenta in vivo.

Animals↗

Characterization of rat pituitary cells by their responses to hypothalamic releasing hormones.

Rat pituitary cells in monolayer culture were characterized by their [Ca2+]i responses to hypothalamic releasing hormones, growth hormone (GHRH), thyrotropin-releasing hormone (TRH), gonadotropin-releasing hormone (GnRH) and corticotropin-releasing hormone (CRH). The percentages of the cell population responding to GHRH, TRH, GnRH, CRH and non-responding cells were 27.3%, 47.6%, 13.8%, 6.2% and 35.3%, respectively. Some of the cells responded to two or more of those hormones. In the GHRH-responding cells, the population of TRH-responding cells was 51.4%, In the TRH-responding cells, the population of GHRH-responding cells was 30.8%. Some of the GHRH-responding cells also responded to CRH and GnRH. In the GnRH-responding cells, the population of TRH-responding cells was 61.8%. In summary, GHRH-responding cells have an especially close relationship with TRH-responding cells, and GnRH-responding cells also have close relationship with TRH-responding cells. There is also some relationship between the populations responding to other pairs of releasing hormones. These findings suggest functional overlapping among each population of pituitary cells.

Animals↗

Increased heparin-releasable platelet factor 4 and D dimer in patients one month after the onset of acute myocardial infarction: persistent activation of platelets and the coagulation/fibrinolytic system.

To evaluate the activity of platelets and the coagulation/fibrinolytic system 1 month after the onset of acute myocardial infarction, we measured the plasma levels of molecular markers, i.e. beta-thromboglobulin, platelet factor 4, thrombin-antithrombin III complex and D dimer, in 16 patients with acute myocardial infarction and in 11 normal subjects. Blood was drawn through a catheter placed in the pulmonary artery before heparin injection. The heparin-releasable platelet factor 4 was calculated by subtracting the level before the injection of 5000 U of heparin, from the level 5 min after injection. The plasma beta-thromboglobulin, thrombin-antithrombin III complex and the D dimer levels in the acute phase of myocardial infarction were 134.9 +/- 121.2, 11.2 +/- 7.1 and 164.4 +/- 115.3 ng/ml, respectively. These values were significantly higher than those in the normal subjects. The plasma levels of beta-thromboglobulin and thrombin-antithrombin III complex, 1 month after the onset (36.6 +/- 16.4 and 4.6 +/- 2.3 ng/ml, respectively) were not significantly different from those of the normal subjects. In contrast, D dimer and heparin-releasable platelet factor 4 were 216.9 +/- 176.9 and 80.5 +/- 29.3 ng/ml, respectively, and significantly higher than in the normal subjects. These findings suggest a latent but persistent activation of the platelets and the coagulation/fibrinolytic system 1 month after the onset of acute myocardial infarction.

Adult↗