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Biomedical subjects

Y Tsunoda

Publications and source records attributed to Y Tsunoda.

At least 55 records · Page 3Linked to original sources
PubMed1998

Thrombopoietin in patients with hepatoblastoma.

Marked thrombocytosis (over 50 x 10(4)/microl) is frequently seen in patients with hepatoblastoma. Thrombopoietin (TPO), c-mpl ligand, has recently been purified as the major physiological regulator of the thrombopoiesis and is mainly produced in the liver. Since it is possible that TPO participates in thrombocytosis and the tumor growth of this particular hepatic tumor, serum TPO levels in addition to interleukin 1beta (IL-1beta) and IL-6 levels were assessed in seven untreated patients by using a sandwich enzyme-linked immunosorbent assay. High serum TPO levels were observed in all of the examined patients. The level ranged from 3.15 to 11.02 (mean +/- standard deviation; 6.08+/-1.25) fmol/ml. IL-6 levels were also somewhat higher than normal. Platelet counts, however, appeared to correlate more with serum TPO levels (p = 0.1) than with IL-1beta (p = 0.5) and IL-6 (p = 0.2) levels. Furthermore, using the reverse transcriptase polymerase chain reaction method, the expression of c-mpl mRNA was found in five of eight hepatoblastoma tissues as well as TPO mRNA in all eight tissues. These observations suggest that thrombocytosis in hepatoblastoma patients results from the production of cytokine members, including TPO, within tumor tissues. Additionally, it is possible that TPO might act as a type of autocrine and/or paracrine system for cellular growth in this tumor.

Child, Preschool↗
PubMed1998

Production of monozygotic twins after freezing and thawing of bisected mouse embryos.

We examined the viability of mouse bisected embryos after freezing and thawing and produced monozygotic twin mice from these embryos. Two-cell embryos were collected from superovulated mature agouti, F1 hybrid (C57BL/6 x CBA) female mice. For bisection, one blastomere of the embryo was aspirated with a micropipette and injected into an empty zona pellucida. After culture for 24 to 28 h to the compacted 4- to 8-cell stage or 48 to 52 h to the late morula to blastocyst stage, the embryos were slowly frozen (-0.5 to -1.0 degrees C/min), thawed (30 degrees C/min), cultured for 24 h, and then transferred to recipient females. The bisected embryos without zonae pellucidae had developmental ability in vitro similar to those with zonae pellucidae (88% vs 89%). However, after freezing and thawing at the compacted 4- to 8-cell stage, bisected embryos with zonae pellucidae had higher viability than those without (60% vs 15%). Zona enclosed, bisected embryos frozen at the compacted 4- to 8-cell stage were more resistnat to freezing and thawing than those at the late morula to blastocyte stage (60% vs 23%). After transfer to recipients 26% of the zona enclosed bisected embryos frozen-thawed at the 4- to 8-cell stage developed to living fetuses a day 17.5 to 18.0 of pregnancy, which was slightly but not significantly lower than that of fresh bisected embryos (48%). On the other hand, only 5% of bisected embryos frozen-thawed at the late morula to blastocyst stage developed to young. The transfer of 15 sets of twin blastocysts as pairs that had been frozen and thawed at the compacted 4- to 8-cell stage yielded 2 (13%) sets of monozygotic twins.

Animals↗
PubMed1998

Effects of the antihypertensive agent, cicletanine, on noradrenaline release and vasoconstriction in perfused mesenteric artery of SHR.

1. The mechanism by which cicletanine (CIC) exerts its antihypertensive effects has not been fully elucidated. The present study was undertaken to examine the effects of in vivo and in vitro treatment with CIC on the pressor response and noradrenaline (NA) overflow during periarterial nerve stimulation (PNS) in perfused mesenteric arterial beds isolated from spontaneously hypertensive rats (SHR). 2. CIC at a dose of 50 mg kg(-1) day(-1) was administered orally to both SHR and normotensive Wistar-Kyoto rats (WKY) from the 6th to 10th week of age. At the 10th week, the isolated mesenteric arterial bed was perfused with Krebs-Henseleit buffer and changes in perfusion pressure and NA overflow during PNS were measured. 3. Chronic treatment with CIC suppressed the age-related elevation of systemic blood pressure in SHR but not in WKY. 4. The PNS (20 Hz)-induced mesenteric vasoconstrictor response and NA overflow were greater in SHR than in WKY. In the vasculature of SHR chronic treatment with CIC resulted in a significant attenuation of the vasoconstriction and the NA overflow during PNS, whereas it did not alter vasoconstrictor responses to bolus injections of KCl and phenylephrine. 5. Treatment with 30 microM CIC in vitro diminished the PNS-induced vasoconstriction and NA overflow but not the NA- and KCl-induced vasoconstriction in the vasculature of untreated SHR. 6. In the vasculature of SHR PNS-induced NA overflow was attenuated by prostaglandin E2 (0.05 microM), whereas it was augmented by the cyclo-oxygenase inhibitor diclofenac-Na (30 microM). In the presence of diclofenac, in vitro treatment with CIC did not attenuate the NA overflow during PNS. 7. The results suggest that the antihypertensive effect of CIC in SHR is partially due to the presynaptic inhibition of NA release during sympathetic nerve activation. Transjunctional inhibition of NA release by prostaglandins may contribute to the inhibitory action of CIC on NA release in the vasculature of SHR.

Animals↗
PubMed1998

Pathologic role of endothelin-1 in septic shock.

To elucidate the pathologic role of endothelin-1 (ET-1) in septic shock, we measured plasma ET-1 concentrations after bacterial lipopolysaccharide (LPS) administration in dogs and determined systemic, pulmonary, and renal hemodynamics and blood gas parameters with or without the nonselective ET receptor antagonist TAK-044. Plasma ET-1 concentrations increased significantly after LPS administration, which correlated positively with mean arterial pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, and central venous pressure. LPS infusion induced hypotension, metabolic acidosis, hypoxemia, and renal dysfunction. TAK-044 prevented LPS-induced metabolic acidosis, hypoxemia, and renal dysfunction, but not hypotension. These findings suggest that increased circulating ET-1 plays a compensatory role in the reversal of systemic vasodilatation in septic shock, but exerts deleterious effects on renal and pulmonary circulation.

Animals↗
PubMed1998

Mammalian bombesin receptors are coupled to multiple signal transduction pathways in pancreatic acini.

We investigated the structural requirements for bombesin (BB)-like peptides to stimulate amylase secretion in rat pancreatic acini and examined the responsible intracellular signal transduction pathways. The tetradecapeptide BB-(1-14) was a full agonist, whereas the heptapeptide BB-(8-14) did not evoke amylase secretion. The mammalian BB analog neuromedin C decapeptide [NMC-(5-14)] was as potent as BB-(1-14) in stimulating amylase secretion, suggesting that Gly5-Asn6-His7 (or Gln7) of the COOH-terminal decapeptide are essential amino acids for full biological activity. BB and NMC equipotently stimulated D-myo-inositol 1,4,5-trisphosphate production, which was inhibited by the phospholipase C (PLC) inhibitor U-73122. BB and NMC also stimulated protein tyrosine kinase (PTK) activities. The half-maximal effective concentration (EC50) for NMC-activated PTK was 2 log units less than the EC50 for BB-activated PTK. NMC was 10-34 times more potent than BB in increasing leukotriene C4 (an index of arachidonic acid production). The production of leukotriene C4 was inhibited by the phospholipase A2 (PLA2) inhibitor ONO-RS-082. NMC is structurally homologous to BB-(5-14) except that Gln7 in BB is replaced by His7 in NMC. Therefore, substitution of Gln7 for His7 may alter the signal transduction systems to include the PTK and PLA2 pathways. U-73122 inhibited Ca2+ spiking and amylase secretion induced by NMC and BB. However, the PTK inhibitor genistein and the PLA2 inhibitor ONO-RS-082 inhibited secretion induced by NMC but not that induced by BB. In contrast to nonmammalian BB receptors, which primarily use the PLC pathway, the rat BB receptor is linked to three different signal transduction systems: PLC, PTK, and PLA2 pathways.

Amino Acid Sequence↗
PubMed1998

Src kinase and PI 3-kinase as a transduction pathway in ceramide-induced contraction of colonic smooth muscle.

Ceramide mediates sustained contraction of smooth muscle cells. C2 ceramide induced a rapid increase in Src kinase activity within 15 s, peaked at 1 min, and was sustained up to 8 min. Contraction and Src kinase activity were inhibited in cells incubated in Ca2+-free medium containing 2 mM EGTA and in cells preincubated with herbimycin A, a Src kinase inhibitor. Immunoblotting using a phosphospecific anti-Src (416Y) antibody showed a ceramide-induced increase in pp60(src) tyrosine phosphorylation. Immunoprecipitation using an anti-phosphotyrosine antibody followed by Western immunoblotting using a monoclonal IgG anti-phosphoinositide 3-kinase NH2 terminal-SH2 domain antibody showed a ceramide-induced increase in phosphoinositide 3-kinase (PI 3-kinase) tyrosine phosphorylation at a protein mass corresponding to 85 kDa, the regulatory subunit of PI 3-kinase, which contains the Src kinase binding site. PI 3-kinase phosphorylation was inhibited by herbimycin A and by the PI 3-kinase inhibitors wortmannin and LY-294002. Preincubation of cells with herbimycin A or PI 3-kinase inhibitors also resulted in an inhibition of mitogen-activated protein (MAP) kinase p42 and p44 activities as seen on Western blots. In summary, we found that 1) the maintenance of sustained contraction is dependent on extracellular Ca2+; 2) ceramide activates a nonreceptor tyrosine kinase pathway through activation of pp60(src) and PI 3-kinase; and 3) the converging signals are probably through activation of MAP kinase.

Amino Acid Sequence↗
PubMed1998

Beneficial effect of atrial natriuretic peptide on pulmonary gas exchange in patients with acute lung injury.

STUDY OBJECTIVES: The purpose of this study was to investigate the effect of i.v. infusion of atrial natriuretic peptide (ANP) on hemodynamics, pulmonary gas exchange, and urine volume during mechanical ventilation with positive end-expiratory pressure (PEEP) in patients with acute lung injury. DESIGN: Prospective, randomized, comparable study. SETTING: ICU of a university hospital. PATIENTS: Forty patients with moderate acute lung injury (lung injury score > or = 2.0) who required mechanical ventilation with PEEP were studied. INTERVENTIONS: The patients were randomly divided into two groups: ANP group (n=20) and control group (n=20). The ANP group received genetic recombination alpha-human ANP (carperitide) at the rate of 0.1 microg/kg/min for 24 h. The control group did not receive ANP. MEASUREMENTS AND RESULTS: Hemodynamic and blood gas parameters, and urine volume were measured at baseline, 3 h, and 24 h after initiating the ANP infusion. Plasma ANP concentrations markedly (p<0.01) increased from 112.0+/-27.0 to 1,868.3+/-385.3 pg/mL after 24 h in the ANP group, whereas they remained unchanged in the control group. In the ANP group, hemodynamic parameters did not change, but PaO2/FIO2 (fraction of inspired oxygen) and thoracic compliance significantly (p<0.01) increased at 24 h after initiating the ANP infusion, associated with significant (p<0.01) decreases in lung injury score and shunt. Urine volume significantly (p<0.01) increased during 0 to 3 h after initiating the ANP infusion. In the control group, hemodynamics, pulmonary gas exchange, and urine volume did not significantly change during the study period. There were significant differences in PaO2/FIO2 (24 h), thoracic compliance (24 h), lung injury score (24 h), and urine volume (3 h) between the two groups. CONCLUSION: The results suggest that ANP infusion induces diuresis and improves pulmonary gas exchange in patients with acute lung injury during mechanical ventilation with PEEP.

Aged↗
PubMed1998

Not only inner cell mass cell nuclei but also trophectoderm nuclei of mouse blastocysts have a developmental totipotency.

The nuclei of mouse trophectoderm cells were found to have developmental totipotency like inner cell mass cells after serial nuclear transfer. Single inner cell mass or trophectoderm cells from expanded blastocysts synchronized with the cell cycle by treatment with nocodazole and aphidicolin to the G1 stage were injected into the perivitelline space of enucleated metaphase II oocytes together with Sendai virus. All oocytes were given three electrical pulses to induce fusion and activation (first nuclear transfer). Aphidicolin was present in all media used until fusion. When reconstituted oocytes developed to the two-cell stage, the nuclei of the reconstituted eggs were fused with the enucleated blastomeres of fertilized two-cell embryos by inactivated Sendai virus (second nuclear transfer). The reconstituted embryos were cultured in vitro and transferred to recipients. After the second nuclear transfer, 23-64% (for inner cell mass cells) and 32-62% (for trophectoderm cells) developed to morula or blastocyst stage. Better development of second nuclear transfer embryos was observed when oocytes fused with trophectoderm nuclei did not extrude a polar body after the first nuclear transfer. After transfer of morulae and blastocysts to recipients, four males were obtained, two from inner cell mass and two from trophectoderm nuclei. These findings indicate that the nucleus of inner cell mass and trophectoderm cells of mouse blastocysts can be reprogrammed within the cytoplasm of unfertilized oocytes and then in fertilized embryos.

Animals↗
PubMed1998

Eosinophilic fasciitis complicated with peripheral polyneuropathy.

Peripheral polyneuropathy and the complication of eosinophilic fasciitis (EF) is rare; only 2 such cases have been described previously. A 40-year-old woman suffered from swelling of the extremities after strenuous exercise and complained of bilateral paresthesia on the soles of her feet. The diagnosis was EF according to clinical symptoms, peripheral eosinophilia, and histological examination of the fascia. Nerve conduction tests also revealed sensory disturbance as mononeuritis multiplex. After administration of prednisolone, the swelling and tenderness of the extremities improved immediately but the neuropathy lasted for 6 months.

Adult↗
PubMed1997

A comparative investigation on the potency of cells from the inner cell mass and trophectoderm of mouse blastocysts to produce chimeras.

The ability of trophectoderm (TE) cells to produce chimeric mice (pluripotency) was compared with that of inner cell mass (ICM) cells. TE and ICM cells of blastocysts and hatching or hatched blastocysts derived from albino mice (CD-1, Gpi-1a/a) were aggregated with zona cut 8- to 16-cell stage embryos or injected into the blastocoele from non-albino mice (C57BL/6 x C3H/He, Gpi-1b/b). After transfer to pseudopregnant female mice, the contribution of the donor cells was examined by glucose phosphate isomerase (GPI) analysis of embryos, membrane and placenta at mid-gestation (Day 10.5 and 12.5) or by the coat color of newborn mice. In contrast to ICM cells, there was no contribution of TE cells in the conceptuses and no coat color chimeric young were obtained. After pre-labeling of TE cells with fluorescent latex microparticles, they were aggregated with embryos and the allocation of TE cells at the compacted morula and blastocyst stages was observed under a fluorescent microscope. Although the TE cells were observed attached onto the surface of the embryos at morula and blastocyst stages, unlike the ICM cells, they were not positively incorporated into the embryos. Thus, the pluripotency of TE cells from mouse blastocysts was not induced by the aggregation and injection methods.

Journal Article↗
PubMed1997

Full-term development after transfer of nuclei from 4-cell and compacted morula stage embryos to enucleated oocytes in the mouse.

The developmental ability of enucleated mouse oocytes reconstituted between the nucleus from 4-cell mouse embryos at different cell stages and recipient cytoplasms at different conditions, and the developmental ability of oocytes receiving nuclei from compacted morulae were examined. The highest development was observed with the nucleus at the G1 stage fused with cytoplasm at the M stage. Although the enucleated oocytes receiving a nucleus from 4-cell embryos did not develop after transfer to a recipient female, young were obtained after renuclear transfer to enucleated fertilized eggs. Live mice were also obtained from the nucleus of compacted morula.

Animals↗
PubMed1997

Effect of uncoupling NO/cGMP pathways on carbachol- and CCK-stimulated Ca2+ entry and amylase secretion from the rat pancreas.

Nitric oxide (NO) production reportedly regulates guanosine 3', 5'-cyclic monophosphate (cGMP) formation and Ca2+ influx in pancreatic acini. We have investigated the functional roles of the NO/cGMP messenger system in rat pancreatic acini. In dispersed acini, the levels of amylase secretion, cytosolic [Ca2+]([Ca2+]i), NO synthase, and cGMP were measured. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 0.01-100 microM) had no effect on amylase secretion induced by various concentrations of carbachol, cholecystokinin octapeptide (CCK-8) or the high affinity CCK agonist, JMV-180. Similarly, L-NAME up to 100 microM did not affect the changes in Ca2+ spiking evoked by these secretagogues; nor was Ca2+ entry, refilling or oscillation altered by L-NAME. Sub- and supramaximal concentrations of these secretagogues did not change NO synthase activities compared with basal levels. While sodium nitroprusside (SNP), a NO donor, caused a 9.4-fold increase in cGMP levels compared with basal levels, carbachol, CCK-8 and JMV-180 had no effect. In addition, the guanylate cyclase inhibitor LY 83583 (10 nM to 10 microM) altered neither amylase secretion nor Ca2+ signaling induced by these secretagogues. These findings indicate that the stimulatory action of carbachol or CCK-8 is not mediated by NO or cGMP. To investigate whether cGMP stimulates pancreatic secretion we showed that both SNP and a cell-permeant cGMP analog at 0.1-1 mM stimulated amylase secretion and Ca2+ transients to a level equal to 10-15% and 13-24%, respectively, of those observed with maximal concentrations of secretagogues. The guanylate cyclase activator guanylin (1-10 microM), which increased cGMP levels 2.4-fold compared with basal levels, elicited a small amount of amylase secretion and a small Ca2+ transient. In conclusion, exogenous NO is capable of increasing endogenous cGMP, which results in a modest increase in the [Ca2+]i transient and pancreatic amylase secretion. However, the NO/cGMP system does not appear to be involved significantly in the mediation of Ca2+ signaling and amylase secretion stimulated by carbachol and CCK-8.

Amylases↗
PubMed1997

Down-regulation of manganese-superoxide dismutase gene expression in idiopathic nephrotic syndrome.

An oxidant stress has been shown to prevail in experimental and clinical nephrotic syndrome. Such oxidant stress may be induced by a reduced activity of antioxidant systems. We examined the altered expression of manganese-superoxide dismutase (Mn-SOD), an antioxidant enzyme, in patients with idiopathic nephrotic syndrome, in whom an increased oxidant stress had been demonstrated. The Mn-SOD activities in peripheral blood mononuclear cells obtained from 12 patients with active nephrotic syndrome (6.0 +/- 1.1 years of age, mean +/- SE) and hypoproteinemia were 42% lower (p < 0.05) than in 12 control subjects (5.5 +/- 0.5 years of age) with normal serum total protein concentrations. Reverse-transcriptase polymerase chain reaction also demonstrated that Mn-SOD messenger RNA expression in the patients with nephrotic syndrome was, on average, 59% lower than in control subjects. Because expressions of some genes are sensitive to serum, the serum dependency of Mn-SOD gene transcription was studied in glomerular endothelial cells transfected with a luciferase reporter gene fused with a rat Mn-SOD DNA fragment of -806 to +22 bp of the transcription initiation site (-806:+22). When these cells were exposed to different concentrations of fetal bovine serum (0.5% to 15%), the transcriptional activities determined by luciferase activities were proportional to serum concentrations. This serum-dependent transcriptional activation was also demonstrated by the fragment (-220:+22) but not by the fragment (-220:-20). When glomerular endothelial cells transfected with the fragment (-220:+22) were treated with 5% serum from patients with active nephrotic syndrome, transcriptional activation was more than 80% less than that by 5% serum from control subjects without nephrosis. These results indicate that Mn-SOD gene transcription is regulated at least in part by serum, and that the serum-dependent transcription of the gene is diminished in patients with idiopathic nephrotic syndrome. The regulatory region of serum-dependent gene transcription resides within its early promoter region. Our findings suggest that down-regulation of antioxidant enzyme transcription may contribute increased oxidant stress in idiopathic nephrotic syndrome.

Animals↗
PubMed1997

Cloning of bovine embryos by multiple nuclear transfer.

The in vitro development of multiple generation bovine nuclear transferred embryos to blastocysts and their survival ability after freezing and thawing were examined. Parent donor embryos which had 20 to 50 cells were recovered from superovulated cows. Follicular oocytes matured in vitro were used as recipient oocytes. The recipient oocytes enucleated at 22 to 24 h after the onset of maturation were preactivated at 33 h. Enucleated oocytes with a donor blastomere were fused 9 h after activation by an electric stimulus and the fused oocytes were cultured in vitro (first generation). Reconstituted oocytes that had developed to the 8- to 16-cell stage 3 to 4 d after fusion were used as donor embryos for the next generation. Recloning procedures were performed twice (second and third generations). The proportion of recipient oocytes successfully fused with a blastomere increased with the cycle of nuclear transfer. Eighty to 86% of fused oocytes developed to the 2-cell stage and there was no significant difference with the generation. The proportion of reconstituted embryos receiving blastomeres derived from first generation embryos had higher developmental ability in vitro, than those derived from other generations (43 vs 31% for 8 to 16-cell stage, 37 vs 20 and 21% for blastocyst stage). The number of cloned blastocysts increased with repeated nuclear transfer (once: 6.2 +/- 4.3, twice: 19.8 +/- 9.2 and three times: 30.0 +/- 14.7) but varied greatly with each parent donor embryo. The in vitro viability of cloned blastocysts after freezing and thawing (59%) was low but not significantly different from that obtained for in vitro fertilized blastocysts (72%). After transfer of either fresh or frozen-thawed cloned blastocysts to 21 recipients, 10 of them were pregnant on Day 60. Four and 3 offspring were produced from 20 fresh and 14 frozen-thawed blastocysts,respectively.

Journal Article↗
PubMed1997

Increased plasma concentrations of brain natriuretic peptide in patients with acute lung injury.

PURPOSE: This study was performed to elucidate the pathophysiological role of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in acute lung injury. MATERIALS AND METHODS: We sequentially measured plasma concentrations of immunoreactive BNP and ANP in 10 patients (mean age, 63 years (with acute lung injury and compared those with hemodynamic parameters and pulmonary functions. RESULTS: Plasma concentrations of immunoreactive BNP and ANP were markedly elevated at entry into the study. Plasma BNP concentrations during the early course (3 days) showed significant (P < .01) positive correlations with systemic vascular resistance index (r = .708) and pulmonary vascular resistance index (r = .573), but a negative correlation with cardiac index (r = .608). Plasma ANP concentrations showed a significant (P < .05) positive correlation with pulmonary capillary wedge pressure (r = .398). Plasma BNP in 4 patients who died and 1 patient with acute renal failure remained elevated during the entire hospital length of stay (12 days). CONCLUSION: These findings suggest that circulating BNP plays an important role in acute lung injury along with ANP as a compensatory mechanism for cardiac dysfunction accompanied by increased systemic vascular resistance index and pulmonary vascular resistance index. Circulating BNP may be a sensitive humoral marker for the degree of ventricular dysfunction associated with acute lung injury.

Acute Disease↗
PubMed1997

Cholecystokinin peptides stimulate pancreatic secretion by multiple signal transduction pathways.

In an attempt to examine the structure-activity relationship of the cholecystokinin (CCK) peptide, we examined the structural motif of CCK truncated peptides responsible for rat pancreatic acinar amylase secretion and signal transduction. CCK-6 (Met28-Gly29-Trp30-Met31-Asp32-Phe33 -NH2), CCK-5 [CCK-(29-33)], and CCK-4 [CCK-(30-33)] caused monophasic amylase secretion with EC50 values of 3, 20, and 30 nM, respectively. CCK-7 [Tyr(SO3H)27 plus CCK-(28-33)] evoked biphasic secretion with an EC50 of 0.7 pM, whereas CCK-3 [CCK-(31-33)] had no effect, suggesting the importance of Tyr(SO3H)27 and Trp30. Whereas CCK-7 [Tyr(SO3H)27/ Met28] evoked biphasic amylase secretion, CCK-OPE [Tyr(SO3H)27/Nle28] and CCK-6 (Met28) caused monophasic secretion. Thus Tyr(SO3H)27/Met28 appears to be required for biphasic secretion. CCK-8-OH and CCK-5-OH did not cause amylase secretion and Ca2+ spiking, suggesting the importance of Phe33 amidation. Similar to CCK-8, CCK-6 and CCK-4 caused Ca2+ oscillations at low doses and large Ca2+ transients at high doses. In contrast, similar to JMV-180 and CCK-OPE, CCK-5 elicited Ca2+ oscillations at all concentrations. Phospholipase C (PLC) inhibitor inhibited amylase secretion induced by high doses of CCK-6 and CCK-4 but not by CCK-5. Protein tyrosine kinase (PTK) inhibitor only inhibited the action of high doses of CCK-4. Neither PLC inhibitor nor PTK inhibitor affected amylase secretion evoked by low doses of CCK-6, CCK-5, and CCK-4. In contrast to its actions on JMV-180 and CCK-OPE, phospholipase A2 (PLA2) inhibitor had no effect on the action evoked by all CCK short peptides. CCK-6, CCK-5, and CCK-4 caused a 2.1- to 3.2-fold increase in intracellular inositol 1,4,5-trisphosphate levels over basal. None of these CCK short peptides increased intracellular arachidonic acid levels. CCK-6 and CCK-5 did not stimulate PTK activity, whereas CCK-4 evoked a 3.2- to 5.3-fold increase over basal. We conclude that Tyr(SO3H)27, Trp30, and Phe33-CONH2 of the CCK peptide are key amino acids in evoking amylase secretion. At low doses, CCK-6, CCK-5, and CCK-4 utilize some yet to be identified pathways to evoke Ca2+ oscillations and amylase secretion. At high doses, CCK-6 and CCK-4 utilize PLC but not PLA2 pathways. CCK-4 possesses the minimal essential amino acids to fully activate the PTK pathway.

Aminobenzoates↗
PubMed1997

Implantation on the suture material and efficacy of povidone-iodine solution.

Suture implantation of viable exfoliated tumour cells may be responsible for local recurrence of colorectal cancer. Using a colon cancer cell line, we obtained a suture implantation without intraperitoneal metastasis in about 80% of the control animals, when sacrificed on the 2nd postoperative week. The cytotoxic efficacy of povidone-iodine (PVP-I) was tested in vivo by a rat model with viable intracaecal tumour cells, and in vitro by trypan blue exclusion and the MTT assay. In vivo PVP-I at 5% significantly reduced the incidence of tumour growth, while the product at 2.5% had a significant effect in only the monofilament polypropylene group. In an in vitro toxicity study, PVP-I higher than 0.16% was effective at killing almost all tumour cells. PVP-I had effective cytotoxicity in vivo and in vitro, being less cytotoxic in vivo than in vitro.

Animals↗