Biomedical subjects

M Kitamura

Publications and source records attributed to M Kitamura.

At least 127 records · Page 7Linked to original sources

PubMed1999

Fractional myocardial flow reserve (FFRmyo) after coronary intervention as a predictor of chronic restenosis.

The angiographic assessment of coronary stenosis has many limitations, especially after coronary intervention. To determine the physiologic significance of such lesions, we measured the mean translesional pressure gradients at rest (P1), those during hyperemia induced by intracoronary administration of papaverine (12 mg in the left and 8 mg in the right coronary artery) (P2), and fractional myocardial flow reserve (FFRmyo) which is derived from the ratio of the mean distal coronary pressure and aortic pressure during hyperemia. Our objective was to determine the relations among P1, P2, and FFRmyo and restenosis as potential predictors of chronic restenosis. The grouped study consisted of 32 patients with ischemic heart disease scheduled to undergo intervention. The distal coronary pressure was measured using a 0.014 inch pressure monitoring wire (Pressure Guide, Radi Medical Systems, Uppsala, Sweden). The guidewire was advanced through the lesional segment. The mean percent diameter stenosis (%DS) was 67.9 +/- 13.3% before intervention and 22.9 +/- 15.3% after intervention. The mean P2 (9.9 +/- 5.3 mmHg) was significantly higher than the mean P1 (4.5 +/- 3.6 mmHg; p < 0.0001). There was no correlation of P1, P2 or FFRmyo with the %DS after intervention. Follow-up angiography (after 6 months) performed on all patients revealed restenosis (%DS > or =50%) in four patients (12.5%). There was no correlation between P1 and the %DS at the follow-up angiography, but the relation between P2, FFRmyo and the %DS at the follow-up angiography was significant (r = 0.599, p < 0.01; r = 0.703, p < 0.0001, respectively). As a measurement of P2, FFRmyo is useful for the determination of the endpoint of intervention in consideration of prevention of restenosis. A new endpoint may be established after further evaluation in a greater number of patients.

Aged↗

PubMed1998

Transgenic knockout mice exclusively expressing human hemoglobin S after transfer of a 240-kb betas-globin yeast artificial chromosome: A mouse model of sickle cell anemia.

Sickle cell anemia (SCA) and thalassemia are among the most common genetic diseases worldwide. Current approaches to the development of murine models of SCA involve the elimination of functional murine alpha- and beta-globin genes and substitution with human alpha and betas transgenes. Recently, two groups have produced mice that exclusively express human HbS. The transgenic lines used in these studies were produced by coinjection of human alpha-, gamma-, and beta-globin constructs. Thus, all of the transgenes are integrated at a single chromosomal site. Studies in transgenic mice have demonstrated that the normal gene order and spatial organization of the members of the human beta-globin gene family are required for appropriate developmental and stage-restricted expression of the genes. As the cis-acting sequences that participate in activation and silencing of the gamma- and beta-globin genes are not fully defined, murine models that preserve the normal structure of the locus are likely to have significant advantages for validating future therapies for SCA. To produce a model of SCA that recapitulates not only the phenotype, but also the genotype of patients with SCA, we have generated mice that exclusively express HbS after transfer of a 240-kb betas yeast artificial chromosome. These mice have hemolytic anemia, 10% irreversibly sickled cells in their peripheral blood, reticulocytosis, and other phenotypic features of SCA.

Anemia, Sickle Cell↗

PubMed1998

Telomerase activity in gastrointestinal stromal tumors.

BACKGROUND: Telomerase activity has been observed in 80-90% of carcinomas derived from various organs. However, to the authors' knowledge this report is the first assessment of telomerase activity in gastrointestinal stromal tumors (GISTs). METHODS: Telomerase activity was analyzed by the telomerase repeat amplification protocol assay in 29 tumors from 26 patients (23 primary tumors from 22 patients, 1 pair of primary and metastatic tumors from 1 patient, and 4 metastatic tumors from 3 patients). Phenotypes, tumor cell proliferation, and overexpression of p53 protein were evaluated immunohistochemically. RESULTS: Seven of 24 primary tumors (29%) and 5 of 5 metastatic tumors (100%) showed telomerase activity. Telomerase activity positive (+) GISTs were significantly larger (P < 0.05) and showed a significantly higher rate of proliferation than telomerase activity negative (-) tumors (P < 0.0001). All telomerase activity (+) GISTs were classified histologically as high risk tumors. Conversely, 15 of the 17 telomerase (-) GISTs were classified histologically as low risk tumors (P < 0.0001). With regard to p53 immunoreactivity, two and seven telomerase activity (+) tumors showed diffuse and sporadic positivity, respectively, whereas only five telomerase activity (-) tumors showed only focal or sporadic positivity. Telomerase activity was correlated significantly with poor prognosis (P < 0.05) in the patients in whom the primary GISTs were evaluated (n = 23). CONCLUSIONS: Telomerase activity may be a useful marker for evaluating the malignant potential of GIST. A distinct subgroup of GISTs is a target for therapy with a telomerase inhibitor.

Adult↗

PubMed1998

Oxidant stress incites spreading of macrophages via extracellular signal-regulated kinases and p38 mitogen-activated protein kinase.

Cultured macrophages exhibit spreading in response to external stimuli. It is relevant to in vivo morphologic changes of macrophages during extravasation, migration, and differentiation. The present study was performed to elucidate molecular mechanisms that regulate spreading of macrophages. Redox is a crucial factor that modulates a wide range of cell function. We found that macrophages undergo spreading in response to oxidant stress caused by hydrogen peroxide or an oxidant generating agent menadione. To identify signaling pathways involved, a role of mitogen-activated protein (MAP) kinases was investigated. Western blot analysis showed that treatment of macrophages with menadione rapidly induced phosphorylation of extracellular signal-regulated kinases (ERK1, ERK2) and p38 MAP kinase, but not c-Jun N-terminal kinase (JNK). Pharmacologic inhibition of either ERK or p38 activation blunted the macrophage spreading. Similarly, transfection with dominant-negative mutants of ERKs or a mutant p38 significantly suppressed the oxidant-triggered spreading. ERKs and p38 are known to activate serum response element (SRE) via phosphorylation of the ternary complex factor Elk-1. To further identify downstream events, we focused on a role of SRE. Stimulation of macrophages with menadione induced activation of SRE. Intervention in the SRE activation by a dominant-negative mutant of Elk-1 inhibited the menadione-induced spreading. These results suggest that oxygen radical metabolites, the well-known mediators for tissue injury, incite spreading of macrophages via the MAP kinase-SRE signaling pathways.

Animals↗

PubMed1998

Bcl-2 is located predominantly in the inner membrane and crista of mitochondria in rat liver.

Bcl-2 is now recognized as a potent inhibitor of apoptotic cell death. It has been reported that Bcl-2 is located in the mitochondria, endoplasmic reticulum, and nuclear membrane in some cell lines, and it is not expressed in normal human and rat liver. An earlier study showed that Bcl-2 is an inner mitochondrial membrane protein. On the contrary, the following investigations using immunoelectron microscopy demonstrated that Bcl-2 resides predominantly in the mitochondrial outer membrane. In this study, using a cryo-sectioning immunogold labeling technique and immunoblotting, we carefully determined the subcellular localization of Bcl-2. Here we report that Bcl-2 is expressed in normal rat liver, and it is located predominantly in the inner membrane and crista rather than in the outer membrane of mitochondria.

Animals↗

PubMed1998

Endothelial myosin light chain kinase regulates neutrophil migration across human umbilical vein endothelial cell monolayer.

Although extravasation of neutrophils is a critical step in acute inflammation, the role of the endothelial cytoskeleton in neutrophil transmigration has not been fully investigated. We used an in vitro model of neutrophil transmigration across a monolayer of HUVEC cultured on amniotic membrane. Human neutrophils were allowed to migrate across the HUVEC monolayer in response to a gradient leukotriene B4 and then the number of migrated neutrophils were counted microscopically. We also followed endothelial F-actin and myosin filament formation using rhodamine-phalloidin and anti-myosin Ab staining. Myosin light chain (MLC) phosphorylation in endothelial cells was determined by immunoprecipitation of 32P-labeled HUVEC with anti-myosin polyclonal Ab. Normally, neutrophil migration induced F-actin formation, myosin filament formation, and MLC phosphorylation in HUVEC. When HUVEC was pretreated with the myosin light chain kinase (MLCK) inhibitor, ML-9, neutrophil migration was diminished and F-actin formation, myosin filament formation, and MLC phosphorylation were inhibited. Pretreatments of HUVEC with the intracellular calcium ion chelator, bis-(O-aminophenoxyl)ethane-N, N, N', N'-tetraacetic acid acetoxymethyl ester (BAPTA/AM), and the calmodulin antagonist, trifluoperazine, had similar effects. These results indicate that a calcium/ calmodulin-dependent MLCK in endothelial cells regulates neutrophil transendothelial migration.

Actins↗

PubMed1998

Activity differentially regulates the surface expression of synaptic AMPA and NMDA glutamate receptors.

Distinct subtypes of glutamate receptors often are colocalized at individual excitatory synapses in the mammalian brain yet appear to subserve distinct functions. To address whether neuronal activity may differentially regulate the surface expression at synapses of two specific subtypes of ionotropic glutamate receptors we epitope-tagged an AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor subunit (GluR1) and an NMDA (N-methyl-D-aspartate) receptor subunit (NR1) on their extracellular termini and expressed these proteins in cultured hippocampal neurons using recombinant adenoviruses. Both receptor subtypes were appropriately targeted to the synaptic plasma membrane as defined by colocalization with the synaptic vesicle protein synaptophysin. Increasing activity in the network of cultured cells by prolonged blockade of inhibitory synapses with the gamma-aminobutyric acid type A receptor antagonist picrotoxin caused an activity-dependent and NMDA receptor-dependent decrease in surface expression of GluR1, but not NR1, at synapses. Consistent with this observation identical treatment of noninfected cultures decreased the contribution of endogenous AMPA receptors to synaptic currents relative to endogenous NMDA receptors. These results indicate that neuronal activity can differentially regulate the surface expression of AMPA and NMDA receptors at individual synapses.

Adenoviridae↗

PubMed1998

TGF-beta1 as an endogenous defender against macrophage-triggered stromelysin gene expression in the glomerulus.

Recent investigation has indicated that TGF-beta1, the macrophage (Mphi) deactivator, may attenuate Mphi-mediated acute glomerular injury. Using stromelysin as an indicator, this study investigated whether and how endogenous TGF-beta1 modulates the glomerular cell activation triggered by Mphi. Rat mesangial cells were stably transfected with a cDNA encoding the active form of TGF-beta1 and a cDNA coding for a dominant-negative mutant of the TGF-betaR type II. Compared with mock-transfected cells, TGF-beta1 transfectants exhibited blunted expression of stromelysin in response to the Mphi-derived, inflammatory cytokine IL-1beta. In contrast, mesangial cells expressing the dominant-interfering TGF-betaR showed enhanced expression of stromelysin in response to IL-1beta, suggesting that endogenous TGF-beta functions as an autocrine inhibitor of the IL-1 response. In isolated, normal rat glomeruli, externally added TGF-beta1 suppressed the induction of stromelysin by mediators that were elaborated by activated Mphi. Similarly, when isolated, nephritic glomeruli producing the active form of TGF-beta1 were stimulated by IL-1beta or Mphi-conditioned medium, the induction of stromelysin was dramatically suppressed as compared with normal glomeruli. To investigate whether endogenous TGF-beta1 affects the glomerular cell activation triggered by Mphi, a technique for adoptive Mphi transfer was used. LPS-stimulated reporter Mphi were transferred into either normal rat glomeruli or nephritic glomeruli expressing active TGF-beta1. In the normal glomeruli, stromelysin expression was markedly induced in resident cells after the transfer of activated Mphi. This induction was substantially repressed in those glomeruli producing active TGF-beta1. These results reinforce the idea that TGF-beta1 is an endogenous defender that attenuates certain actions of infiltrating Mphi in the glomerulus.

Animals↗

PubMed1998

Unexpected suppression of alpha-smooth muscle actin, the activation marker of mesangial cells, by pp60v-src tyrosine kinase.

Cultured mesangial cells constitutively express alpha-smooth muscle actin (alpha-SMA), a marker of cellular activation. We unexpectedly found that tyrosine kinase pp60v-src, a known activator for a wide range of signalling cascades, suppressed the alpha-SMA expression in mesangial cells. The present study was conducted to elucidate molecular events involved in this phenomenon. Transfection with a reporter plasmid revealed that the serum response element (SRE), the cis-element required for alpha-SMA expression, was constitutively active in mesangial cells. When mesangial cells were transfected with pp60v-src, activity of both SRE and the alpha-SMA promoter was down-regulated. This was associated with depressed levels of phosphorylated extracellular signal-regulated kinases (ERKs), but not c-Jun N-terminal kinase. Selective inhibition of ERKs by PD098059 abrogated constitutive SRE activity, leading to suppressed alpha-SMA expression. These results uncovered a novel potential of pp60v-src for suppression of alpha-SMA via intervention in the ERK-SRE signalling pathway.

Actins↗

PubMed1998

Molecular cloning of a murine homologue of membrane cofactor protein (CD46): preferential expression in testicular germ cells.

Human membrane cofactor protein (MCP, CD46) has been suggested, although no convincing evidence has been proposed, to be a fertilization-associated protein, in addition to its primary functions as a complement regulator and a measles virus receptor. We have cloned a cDNA encoding the murine homologue of MCP. This cDNA showed 45% identity in deduced protein sequence and 62% identity in nucleotide sequence with human MCP. Its ectodomains were four short consensus repeats and a serine/threonine-rich domain, and it appeared to be a type 1 membrane protein with a 23-amino acid transmembrane domain and a short cytoplasmic tail. The protein expressed on Chinese hamster ovary cell transfectants was 47 kDa on SDS/PAGE immunoblotting, approximately 6 kDa larger than the murine testis MCP. It served as a cofactor for factor I-mediated inactivation of the complement protein C3b in a homologous system and, to a lesser extent, in a human system. Strikingly, the major message of murine MCP was 1.5 kb and was expressed predominantly in the testis. It was not detected in mice defective in spermatogenesis or with immature germ cells (until 23 days old). Thus, murine MCP may be a sperm-dominant protein the message of which is expressed selectively in spermatids during germ-cell differentiation.

Amino Acid Sequence↗

PubMed1998

New system for linear accelerator radiosurgery with a gantry-mounted video camera.

PURPOSE: We developed a positioning method that does not depend on the positioning mechanism originally annexed to the linac and investigated the positioning errors of the system. METHODS AND MATERIALS: A small video camera was placed at a location optically identical to the linac x-ray source. A target pointer comprising a convex lens and bull's eye was attached to the arc of the Leksell stereotactic system so that the lens would form a virtual image of the bull's eye (virtual target) at the position of the center of the arc. The linac gantry and target pointer were placed at the side and top to adjust the arc center to the isocenter by referring the virtual target. Coincidence of the target and the isocenter could be confirmed in any combination of the couch and gantry rotation. In order to evaluate the accuracy of the positioning, a tungsten ball was attached to the stereotactic frame as a simulated target, which was repeatedly localized and repositioned to estimate the magnitude of the error. The center of the circular field defined by the collimator was marked on the film. RESULTS: The differences between the marked centers of the circular field and the centers of the shadow of the simulated target were less than 0.3 mm.

Computer Terminals↗

PubMed1998

Peripheral edema after esophagectomy.

Patients who have undergone major surgery such as esophagectomy may develop peripheral edema in the immediate postoperative period, the cause of which is not fully understood. The purpose of this study was therefore to determine the mechanism of this phenomenon. Finger edema was measured as a marker for peripheral edema before and after esophagectomy in eight patients. Plasma interleukin-6 (IL-6) was also measured by an enzyme-linked immunosorbent assay. Finger edema markedly increased in the immediate postoperative period and remained significantly elevated until after postoperative day (POD) 3 compared to the preoperative value (P < 0.05). Plasma IL-6 also markedly increased in the immediate postoperative period and remained significantly elevated on POD 2 compared to the preoperative value (P < 0.05). The degree of finger edema highly correlated with the level of plasma IL-6 (r = 0.71, P = 0.0001). These findings indicate that peripheral edema after esophagectomy might be caused by a proinflammatory cytokine response.

Body Weight↗

PubMed1998

[Postoperative therapy using human atrial natriuretic peptide in cases of valve replacement].

The effect of hANP (atrial natriuretic peptide) was investigated clinically in 40 patients who underwent isolated valve replacement. Patients were divided into four groups: aortic regurgitation (AR), aortic stenosis (AS), mitral regurgitation (MR) and mitral stenosis (MS). Each group was divided into two subgroups: one was administered hANP after the operation until leaving ICU, and the other was not administered hANP. We measured the levels of hANP and c-GMP and blood pressure, pulmonary artery pressure, central venous pressure and levels of Na, K of urine and blood prcoperatively, immediately postoperatively and 1, 2, 4, 6 hours after operation. First, to examine the relationship between preoperative level of hANP and cardiac function, the relationship between preoperative level of hANP and history of cardiac failure and pulmonary artery wedge pressure (PAWP) were evaluated. Also, we evaluated the relationship between preoperative level of hANP and each dimension on echocardiography. There was a weak statistical relationship between hANP and PAWP (row = 0.39 (p = 0.04) Pearson correlation method) and there was no statistical relationship between hANP and duration of cardiac failure (row = 0.00445 (p = 0.98) Pearson correlation method). Preoperatively Left atrial diameter (LAD) showed a statistical relationship with level of hANP in every group using Spearman correlation method. Other dimensions such as left ventricular diastolic diameter (LVDd) and left ventricular systolic diameter (LVDs) and also fractional shortening (FS) did not show a strong correlation with preoperative level of hANP. Especially, in AS group there was a strong relationship between every dimension and preoperative level of hANP. Only in MS group LAD and the level of hANP were negatively related. This finding suggests that atrial dilatation results in reduction of secretion of hANP in cases of MS on long term follow up. Finally, hNAP therapy was shown to have a continuous diuretic effect, with stable hemodynamics.

Adult↗

PubMed1998

[An analysis of the mechanism of postoperative hyperbilirubinemia following resection of thoracic esophageal cancer in terms of hepatic venous oxygen saturation and excessive systemic reactions].

Hepatic venous oxygen saturation (ShvO2), parameters of systemic circulation and cytokine (Interleukin 6) (IL-6)) level were measured in 21 patients with thoracic esophageal cancer in order to analyze the mechanism of occurrence of postoperative hyperbilirubinemia (PHB). ShvO2 fell during operation, especially during intrathoracic procedures, and a significant correlation was noted between the total time during which ShvO2 was below 60% and the postoperative peak serum bilirubin level (peak-Bil) (r = 0.595, p = 0.0037). Patients with PHB (group H) had worse systemic circulation and a lower oxygen supply postoperatively than patients without PHB (group N). Body weight and water balance recovered earlier in group N. Postoperatively, numbers of peripheral lymphocytes and platelets changed lower in group H, while CRP and IL-6 changed higher in group H. Furthermore, a significant correlation was noted between the IL-6 level just after operation and peak-Bil (r = 0.669, p = 0.0006). These results suggests PHB results from intraoperative liver hypoxia and poor postoperative systemic circulation. Individual severeness of reactions to the operative stress, excessive or adequate, plays a role in the occurrence of PHB as well.

Aged↗

PubMed1998

Significance of preoperative elevation of serum C-reactive protein as an indicator for prognosis in colorectal cancer.

BACKGROUND: C-reactive protein (CRP) is a product synthesized in hepatocytes and has been reported to be upregulated by such proinflammatory cytokines as interleukin-1, interleukin-6, and tumor necrosis factor. The significance of a preoperative serum elevation in CRP as a predictive indicator for the malignant potential and prognosis in colorectal cancer has not been elucidated. METHOD: One hundred and twenty consecutive patients with colorectal cancer, whose local lesions were resected in our department, were selected. Any patients with inflammatory diseases such as infection or collagen diseases were excluded from the current study. The preoperative serum CRP level was measured, and the relationship between the serum elevation of CRP and both the clinicopathologic factors and prognosis of the patients was investigated. RESULTS: The incidences of liver metastases, peritonitis carcinomatosa, histopathologic lymph nodes metastasis, and intravascular invasion in patients with a preoperatively elevated serum CRP level were significantly more frequent than in those with a negative serum protein level. The survival rates of the patients without a preoperative elevation of the serum CRP proved to be significantly more favorable than that of the patients with such an elevation (P <0.001). CONCLUSIONS: A preoperative serum elevation of CRP was thus found to be an indicator of the malignant potential of the tumor as well as a predictor of the prognosis of patients with colorectal cancer.

Adult↗

PubMed1998

Hydrogen peroxide derived from hepatocytes induces sinusoidal endothelial cell apoptosis in perfused hypoxic rat liver.

BACKGROUND & AIMS: Evidence is accumulating that hypoxic liver injury involves not only necrosis but also apoptosis. Reactive oxygen species can cause apoptosis. This study examined the hypothesis that H2O2 induces apoptosis in hypoxic rat liver. METHODS: Blood-perfused rat livers were made hypoxic by reducing the perfusion flow. H2O2 was detected by both 2',7'-dichlorofluorescein fluoroimaging and cerium electron-microscopic methods. To evaluate the apoptosis, the liver was stained with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method. To further investigate the involvement of H2O2 in hypoxia-induced liver cell apoptosis, small pieces of liver in the cultured media were exposed to 0.5 mmol/L of reagent H2O2 and stained with the TUNEL method. RESULTS: In the hypoxic liver, H2O2 was produced predominantly by hepatocytes, and the number of apoptotic nonparenchymal cells was significantly increased, particularly in the midzone. All the apoptotic cells were positively stained with monoclonal antibody against the hepatic sinusoidal endothelial cells (SECs). In incubated liver pieces, reagent H2O2 induced apoptosis selectively in SECs. CONCLUSIONS: Low-flow hypoxia induces H2O2 production in hepatocytes, and this H2O2 induces apoptosis selectively in SECs in the rat liver.

Animals↗

PubMed1998

Susceptibility to idiopathic azoospermia in Japanese men is linked to HLA class I antigen.

PURPOSE: Approximately 15 to 20% of infertile men have azoospermia. In the Y chromosome a deletion, termed the azoospermic factor, has been found in some cases of idiopathic azoospermia. We investigate the relationship of factors in autosomal chromosomes (HLA class I antigens) to spermatogenesis failure in idiopathic azoospermia. MATERIALS AND METHODS: We evaluated 65 infertile Japanese men with idiopathic azoospermia. The frequency of the HLA allele reported in 1,216 healthy Japanese men was used as a control. HLA class I typing was performed by the National Institutes of Health standard serological method or polymerase chain reaction-sequence specific primer analysis. Allele frequencies were calculated. We determined statistical significance in the frequency of each allele in patients and controls using the chi-square test. The relationship of HLA antigens to idiopathic azoospermia was expressed as relative risk. RESULTS: In Japanese men with idiopathic azoospermia the frequency of HLA-A33, B13 and B44 was significantly increased compared with controls. The relative risk of HLA-B44 was 8.4, an extremely high value compared with that of other diseases and HLA antigens. CONCLUSIONS: We suggest that HLA class I antigens are important genetic markers that represent a risk factor for idiopathic azoospermia.

Alleles↗

PubMed1998

Effects of pituitary adenylate cyclase activating polypeptide-27 on alkaline secretory and mucosal ulcerogenic responses in rat duodenum.

Effects of pituitary adenylate cyclase activating polypeptide (PACAP) on duodenal mucosal HCO3- secretion and ulcerogenic responses induced by mepirizole in anesthetized rats were examined and compared with those of vasoactive intestinal polypeptide (VIP). Animals were given mepirizole (200 mg/kg, s.c.) for induction of duodenal ulcers, and gastric acid and duodenal HCO3- secretions were measured with or without pretreatment of PACAP-27 or VIP. Mepirizole increased acid secretion and induced hemorrhagic lesions in the proximal duodenum within 6 h. Intravenous bolus injection or infusion of PACAP-27 (4 and 8 nmol/kg or 8 nmol/kg/h) increased duodenal HCO3- secretion even in the presence of mepirizole, without effect on acid secretion, and significantly reduced the severity of duodenal lesions caused by mepirizole. In contrast, VIP (8 nmol/kg, i.v.) given by bolus injection significantly decreased acid secretion induced by mepirizole, in addition to stimulation of HCO3- secretion, and prevented duodenal lesions in response to mepirizole. These results suggest that PACAP-27 increases duodenal HCO3- secretion and this action may be important in maintaining the duodenal mucosal integrity against acid, and VIP affords duodenal protection by both increasing duodenal HCO3- secretion and decreasing acid secretion. The reason for the different effects of PACAP and VIP on acid secretion is unknown.

Animals↗