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Biomedical subjects

Y Tsunoda

Publications and source records attributed to Y Tsunoda.

At least 91 records · Page 5Linked to original sources
PubMed1995

[Effect of plasma exchange therapy on IgA nephropathy in children--a retrospective study].

Clinical and pathological analyses were performed to evaluate plasma exchange therapy (PEx) in children with severe IgA nephropathy. Values for PEx were obtained in 17 cases (male 13, female 4, 12.2 +/- 4.3 [M +/- SE] years old), whose proteinuria and creatinine clearance (Ccr) were 4.6 +/- 1.8 g/day and 64.4 +/- 31.3 ml/min/1.73 m2, respectively, immediately prior to treatment. Values for proteinuria in children after PEx were significantly higher than those of 151 cases of IgA nephropathy who were not treated by PEx in our unit. Ccr in patients who underwent PEx significantly improved during the first 6 months, whereas serum IgG, IgA and C3 levels returned to pre-PEx levels following a transient reduction at one month. Fourteen out of 17 cases were followed for more than 2 years. Among these patients, 8 (57.1%) progressed to chronic renal failure (CRF, Ccr < 30 ml/min/1.73 m2), and 6 showed improvement in Ccr (non-CRF, Ccr > or = 30 ml/min/1.73 m2). In 4 of these cases, PEx was introduced at an acute clinical phase of glomerulonephritis. Compared to 8 patients with progression (CRF), initial renal histology in these 6 patients revealed a lower percentile of glomerular sclerosis index (GSI) and had a significantly higher percentile of cellular crescents. These results suggest that: 1) PEx is not an adequate method of treatment of IgA nephropathy with advanced glomerulosclerosis, 2) PEx is effective in the acute stage of IgA nephropathy.

Acute Disease↗
PubMed1994

A newly cloned phospholipase A2-activating protein elicits Ca2+ oscillations and pancreatic amylase secretion via mediation of G protein beta/phospholipase A2/arachidonic acid cascades.

Recently we have demonstrated that in rat pancreatic acini the high affinity cholecystokinin receptors are coupled to the phospholipase A2 (PLA2)/arachidonic acid (AA) cascades to mediate Ca2+ oscillations and amylase secretion. This intracellular signal transduction system is associated with an unidentified G protein(s) which is neither Gi/Go nor Gq-alpha. Using a newly cloned PLA2-activating protein (PLAP), we further examined the mechanisms by which PLA2 activates Ca2+ oscillation and pancreatic enzyme secretion. In intact acini, 0.1-1 microM PLAP evoked Ca2+ oscillations in a dose-dependent manner (delta [Ca2+]i: 18-121 nM and frequency: 2.3-5.5 cycles/10 min). PLAP elicited a 3-fold increase in monophasic amylase secretion with an EC50 of 0.1 microM. PLAP dose-dependently caused an increase in the AA metabolite 15-HETE. The PLA2 inhibitor, but not inhibitors of lipoxygenase, cytochrome P-450 and cyclooxygenase, inhibited the action of PLAP, suggesting that AA, but not AA metabolites, functions as a signal messenger. In permeabilized acini, a monoclonal antibody of G protein beta subunits inhibited the action of PLAP. Because of the structural similarity between PLAP and Gbeta protein we hypothesize that the PLA2 coupled G protein is Gbeta and it elicits Ca2+ oscillations and monophasic amylase secretion via the AA pathway.

Aminobenzoates↗
PubMed1994

Clinical assessment of a continuous intraarterial blood gas monitoring system.

We evaluated the clinical performance of a continuous intraarterial blood gas monitoring (CIABG) system which includes a fluorometric intravascular sensor. Seventeen patients undergoing elective surgery were monitored perioperatively with the CIABG system (PB3300; Puritan Bennett, Carlsbad, CA). Conventional laboratory blood gas analyses (BGA) were performed simultaneously whenever indicated, and the values were compared with those obtained from the CIABG system. Monitoring time ranged from 24 to 72 hr. The biases (average error between PB3300 and BGA) of pH, PCO2 and PO2 were 0.003 pH unit, -2.8 mmHg, and 0.9 mmHg in the operating room (OR), and 0.005 pH unit, 3.9 mmHg, and 8.5 mmHg in the intensive care unit (ICU), respectively. The precision (standard deviation of the bias) of pH, PCO2 and PO2 were 0.030 pH unit, 2.1 mmHg, and 29.9 mmHg in the OR and 0.035 pH unit, 3.8 mmHg, and 14.7 mmHg in the ICU, respectively. Although the PB3300 system was clinically useful as a trend monitor, the system's precision and reliability were unacceptable for estimation of true blood gas values.

Adult↗
PubMed1994

Effects of the reduction of cytoplasm of mouse 2-cell embryos on blastocele formation timing and developmental ability in vitro and in vivo.

Experiments were conducted to test the hypothesis that the nucleo/cytoplasmic ratio of mouse embryos determines the time of blastocele formation. Half the volume of 2-cell stage embryos was removed from each blastomere by micropipette to alter the nucleo/cytoplasmic ratio. Reduced embryos whose nucleo/cytoplasmic ratio increased and non-treated control embryos were cultured in vitro to compare the timing of division to the 4-cell stage and blastocele formation. Reduced 2-cell embryos formed blastoceles significantly earlier than the controls (49.0 +/-2.9 vs 52.2 +/-6 h) and with fewer cells, although division into the 4-cell stage was significantly delayed (11.4 +/-4.4 vs 9.0+/-2.4 h). The cell number of blastocysts 70 h after treatment and developmental ability of blastocysts after transfer to pseudopregnant recipients were the same for the reduced and control groups. The present study indicates that the nucleo/cytoplasmic ratio of embryos may possibly be an important factor that determines the time of blastocele formation.

Journal Article↗
PubMed1994

Effects of the culture density of mouse zygotes on the development in vitro and in vivo.

Different numbers of CD-1 mouse zygotes(1, 5, 10, 20, 40 and 60) were cultured in 10 mul M16 medium, in M16 medium+EDTA, in M16 dedium+SOD+thioredoxin, and in CZB medium, respectively. When the zygotes, regardless of the number, were cultured with M16, no blastocysts could be obtained. The suitable ratio of embryos to 1 mul of M16 medium+EDTA or M16 medium+SOD+thioredoxin was 1:1 or 2:1. Medium volume from 1 to 10 mul did not affect blastocyst development when the embryo density was 1:1. However, blastocysts obtained from zygotes cultured singly had fewer cell numbers and showed inferior development to live fetuses after transfer to recipients. When CZB medium was used, suitable embryo density was not clear. The ratio of embryos to volume of culture medium was shown to be an important factor for in vitro culture of mouse zygotes.

Journal Article↗
PubMed1994

[A case of Borrmann type 4 gastric cancer responding to sequential methotrexate and 5-fluorouracil combined with CDDP].

A case of Borrmann type 4 gastric cancer responding to sequential methotrexate and 5-fluorouracil combined with cis-diamminedichloroplatinum (CDDP) is reported. A 57-year-old woman was admitted to our hospital complaining of abdominal fullness. Upper gastrointestinal series and gastrofiberscopy revealed almost the entire stomach was involved with Borrmann type 4 cancer. Gastrectomy could not be performed because of peritoneal dissemination. However, the patient responded to sequential methotrexate and 5-fluorouracil therapy and CDDP administration. She enjoyed more than one year of hospital-free survival period and survived for almost two years.

Adenocarcinoma↗
PubMed1993

Receptor-operated Ca2+ signaling and crosstalk in stimulus secretion coupling.

In the cells of higher eukaryotic organisms, there are several messenger pathways of intracellular signal transduction, such as the inositol 1,4,5-trisphosphate/Ca2+ signal, voltage-dependent and -independent Ca2+ channels, adenylate cyclase/cyclic adenosine 3',5'-monophosphate, guanylate cyclase/cyclic guanosine 3',5'-monophosphate, diacylglycerol/protein kinase C, and growth factors/tyrosine kinase/tyrosine phosphatase. These pathways are present in different cell types and impinge on each other for the modulation of the cell function. Ca2+ is one of the most ubiquitous intracellular messengers mediating transcellular communication in a wide variety of cell types. Over the last decades it has become clear that the activation of many types of cells is accompanied by an increase in cytosolic free Ca2+ concentration ([Ca2+]i) that is thought to play an important part in the sequence of events occurring during cell activation. The Ca2+ signal can be divided into two categories: receptor- and voltage-operated Ca2+ signal. This review describes and integrates some recent views of receptor-operated Ca2+ signaling and crosstalk in the context of stimulus-secretion coupling.

Animals↗
PubMed1993

Inhibition of acid secretion in gastric parietal cells by the Ca2+/calmodulin-dependent protein kinase II inhibitor KN-93.

A novel Ca2+/calmodulin-dependent protein kinase II (CaM Kinase II) inhibitor, KN-93 potently inhibits gastric acid secretion from parietal cells. As previously reported (1), treatment of parietal cells with a selective inhibitor of CaM kinase II, KN-62 resulted in the inhibition of cholinergic-stimulated rabbit parietal cell secretion, whereas it failed to inhibit the histamine and forskolin response. In contrast effects of carbachol, histamine and forskolin were significantly inhibited by KN-93 with an IC50 of 0.15, 0.3 and 1 microM, respectively; these effects occurred without any changes in intracellular cyclic AMP and Ca2+ levels. In the present study we investigated the mechanism by which KN-93 acts upon the acid-secreting machinery of gastric parietal cells. Neither redistribution of the proton pump activity nor the morphological transformation were affected by KN-93. The drug only weakly inhibited the H+, K(+)-ATPase activity but strongly dissipated the proton gradient formed in the gastric membrane vesicles and reduced the volume of luminal space. Thus KN-93 acts at pH gradient formation whereas KN-62 acts only at CaM Kinase II.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Differential involvement of phospholipase A2/arachidonic acid and phospholipase C/phosphoinositol pathways during cholecystokinin receptor activated Ca2+ oscillations in pancreatic acini.

In pancreatic acini, administration of the phospholipase C inhibitor, U-73122, abolished Ca2+ oscillations and amylase secretion induced by CCK but had much less effect on the action of CCK analog JMV-180. In contrast, the phospholipase A2 inhibitor, ONO-RS-082, inhibited both Ca2+ spikes and amylase secretion induced by JMV-180, but it had little effect on the action of CCK-8. Both arachidonic acid (AA) and a cytochrome P-450 inhibitor, SKF-96365, generated Ca2+ spikes from the agonist-sensitive pool. AA was capable of releasing Ca2+ from the endoplasmic reticulum (ER), suggesting the direct Ca2+ releasing pathway. There is no evidence of Ca(2+)-induced Ca2+ release (CICR) since neither caffeine, a CICR potentiator, nor ryanodine, a CICR inhibitor, modulated agonist-induced Ca2+ oscillations and Ca2+ release from the ER. On the contrary, increasing concentrations of caffeine abolished agonist-induced Ca2+ spikes. Therefore we have demonstrated that depending on the agonists used, CCK receptor activation may result in the differential involvement of the phosphoinositol and arachidonic acid pathways to mediate calcium oscillation and amylase secretion.

Aminobenzoates↗
PubMed1993

Transforming growth factor-alpha (TGF alpha) inhibition of parietal cell secretion: structural requirements for activity.

Parietal cells of the gastric fundus produce transforming growth factor-alpha (TGF alpha) which functions as a potent inhibitor of acid secretion. We have previously demonstrated that TGF alpha can inhibit aminopyrine uptake in isolated rabbit parietal cells. In this study, we have evaluated the components of TGF alpha structure which determine its ability to inhibit parietal cell function. Both human and rat TGF alpha inhibited histamine stimulation by increasing the EC50 for agonist stimulation. Three fragments containing the third loop domain of TGF alpha (rat TGF alpha 34-43, human TGF alpha 34-43 and human TGF alpha 34-50) all inhibited histamine stimulation with IC50 values 20, 33 and 4-fold higher, respectively, than that of the native molecule. Rat TGF alpha inhibited carbachol stimulation throughout an agonist dose response. Human TGF alpha was only effective in inhibiting carbachol if incubations were performed in the presence of air rather than 100% O2. In air incubation, all three of the TGF alpha fragments inhibited carbachol stimulation but, in contrast to the effects on histamine, the peptides all were virtually equipotent with the native molecule. The human sequence fragments, like the native human TGF alpha, elicited no inhibition when incubations were performed in the presence of 100% O2. The results suggest that there are pharmacological differences in the response of isolated parietal cells to TGF alpha-mediated inhibition of histamine and carbachol. In addition, in contrast with previous investigations on the mitogenic action of TGF alpha, third loop fragments of TGF alpha retain the capacity to inhibit aminopyrine accumulation.

Amino Acid Sequence↗
PubMed1993

Effect of aging of recipient oocytes on the development of bovine nuclear transfer embryos in vitro.

The present study was undertaken to examine the effect of the length of in vitro maturation of oocytes on the efficiency of enucleation, parthenogenetic activation and blastomere fusion by electric stimulus. In vitro development of reconstituted oocytes receiving a blastomere from 8 to 16-cell bovine embryos fertilized in vitro was investigated to assess the effect of aging of the oocytes. The proportion of oocytes with a first polar body at 22 to 24 hours after maturation was high (80%) compared with those obtained at 16 to 18, 28 to 30 or 42 to 44 hours (50 to 75%). The success rate of enucleation significantly decreased with aging (88, 85, 74 and 55%). The activation rate significantly increased with the length of maturation in vitro (P<0.01) (1 to 4, 24 to 41, 57 to 70 and 80 to 87%). The proportion of oocytes fused with a blastomere from 8- to 16-cell embryos was not dependent on the age of the oocytes (54 approximately 59%). The ability of the reconstituted oocytes to develop to the 2-cell and the 8- to 16-cell stage increased with the length of maturation of recipient oocytes. When oocytes enucleated and a blastomere at 22 to 24 hours were incubated further for 22 to 23 hours until electrofusion. The proportions of oocytes which developed to the 2-cell and the 8- to 16-cell stages (74 and 17%) were similar to those obtained at 42 to 44 hours after maturation. However, only 1 to 6% of reconstituted eggs receiving a blastomere from 8- to 16-cell embryos fertilized in vitro developed into a blastocyst in vitro.

Journal Article↗
PubMed1993

Tyrosine kinase activities in the modulation of stimulated parietal cell acid secretion.

The effects of protein tyrosine kinase (PTK) activities on the modulation of secretion were investigated in isolated rabbit parietal cells. Two classes of inhibitors, genistein (an inhibitor of both soluble and membrane-associated PTK activities) and an erbstatin analogue (an inhibitor of membrane-associated PTK activities), were tested against both secretagogue stimulation as well as transforming growth factor-alpha (TGF-alpha) inhibition. Pretreatment of rabbit parietal cells with 10(-7) M rat TGF-alpha resulted in inhibition of both histamine- and carbachol-stimulated [14C]-aminopyrine (AP) accumulation. TGF-alpha inhibition was totally reversed by simultaneous pretreatment of cells with 50 microM genistein or an erbstatin analogue, indicating that a receptor-associated PTK activity is likely involved in the inhibition of parietal cell secretion. Furthermore, genistein, but not the erbstatin analogue, potentiated histamine-stimulated AP accumulation with a change in EC50 from 1.9 to 0.5 microM. Similarly, genistein, but not the erbstatin analogue, potentiated the response to forskolin with a change in EC50 from 1.5 to 0.1 microM. Genistein had no effect on stimulation of AP uptake by either dibutyryladenosine 3',5'-cyclic monophosphate or carbachol. In addition, genistein failed to increase histamine or forskolin stimulation beyond the maximal level and had no significant effect on either cellular adenosine 3',5'-cyclic monophosphate production or intracellular Ca2+ concentration. These results suggest that a PTK-protein phosphotyrosine phosphatase system may be involved in the potentiation of the histamine signal by a mechanism independent of adenylate cyclase activation.

Animals↗
PubMed1993

Circulating endothelin-1 concentrations in acute respiratory failure.

To elucidate the pathophysiologic role of endogenous endothelin (ET)-1 in acute respiratory failure, we measured plasma immunoreactive ET-1 levels in 13 patients with acute respiratory failure, and compared those with hemodynamic and respiratory parameters. The mean plasma ET-1 levels (10.7 +/- 5.0 pg/ml) in 13 patients with acute respiratory failure at the time of hospital admission were about sevenfold greater than those of healthy subjects (1.5 +/- 0.5 pg/ml, n = 16). Plasma ET-1 levels positively correlated with right atrial pressure (r = 0.626), systolic pulmonary arterial pressure (r = 0.726), mean pulmonary arterial pressure (r = 0.591), and the resistance ratio (pulmonary vascular resistance/systemic vascular resistance) (r = 0.658). They also showed correlations with peak airway pressure (r = 0.588), mean airway pressure (r = 0.607), and airway resistance (r = 0.756). Stepwise multiple regression analysis confirmed the significance of these observations. Our data suggest that raised circulating ET-1 levels may partly contribute to the development of pulmonary vasoconstriction and bronchoconstriction associated with acute respiratory failure.

Acute Disease↗
PubMed1993

Nuclear transplantation of embryonic stem cells in mice.

The developmental ability of enucleated mouse eggs that had received embryonic stem cells was examined. In a preliminary study, none of the reconstituted eggs formed a nucleus using inactivated Sendai virus (HVJ) after activation with ethanol. DC pulses were applied at 100 or 140 V mm-1 in addition to this treatment. After electrofusion, 29-40% of reconstituted eggs formed nuclei and 41-60%, 25-44%, 12-24% and 12-18% developed to two-cell and four-cell and morulae and blastocysts, respectively. The ability of reconstituted eggs to form blastocysts did not depend on the age of recipient eggs, except in cases of very young and very old eggs. Although implantation sites were observed, no live fetuses were obtained after the transfer of reconstituted eggs to the recipients.

Animals↗