Biomedical subjects

N Sato

Publications and source records attributed to N Sato.

At least 595 records · Page 33Linked to original sources

PubMed1997

Androgenic induction of prostate-specific antigen gene is repressed by protein-protein interaction between the androgen receptor and AP-1/c-Jun in the human prostate cancer cell line LNCaP.

In exploring the possible mechanisms of androgen independence of prostate-specific antigen (PSA) gene expression, we investigated the effect of elevating AP-1 by both 12-O-tetradecanoylphorbol 13-acetate (TPA) treatment and transfection of the c-Jun expression vector in LNCaP cells. Transcription of PSA is initiated when ligand-activated androgen receptor (AR) binds to a region in the PSA promoter that contains an androgen-responsive element (ARE). It was found that TPA inhibited androgen-induced PSA gene expression by a mechanism that did not alter nuclear levels of AR protein. Overexpression of AP-1 (jun and fos proteins) also inhibited androgen-induced PSA promoter activity. These observations were apparently related to the disruption of AR.ARE complexes as demonstrated by the results of electrophoretic mobility shift assays. Specifically, c-Jun inhibited the formation of AR.ARE complexes and conversely that AR-glutathione S-transferase proteins inhibited the formation of c-Jun.TPA-responsive element (TRE) complexes. Consistent with the inhibitory effect of both proteins, anti-c-Jun antibody blocked the inhibition of AR.ARE complex formation by c-Jun. A similar, but less marked, effect was obtained when anti-AR antibody was used to prevent AR inhibition of c-Jun.TRE complex formation. These findings together with results obtained from co-immunoprecipitation experiments strongly suggest that mutual repression of DNA binding activity is due to direct interaction between the two proteins and that the degree of repression may be determined by the ratio of AR to c-Jun. The mechanism of repression studied in mutant analysis experiments yielded evidence of an interaction between the DNA- and ligand-binding domains of AR and the leucine zipper region of c-Jun. Thus, the AR is similar to other nuclear receptors in its ability to interact with AP-1. This association provides a link between AP-1 and AR signal transduction pathways and may play a role in the regulation of the androgen-responsive PSA gene.

Androgens↗

PubMed1997

The role of phorbol ester-sensitive protein kinase C isoforms in lymphokine-activated killer cell-mediated cytotoxicity: dissociation between perforin-dependent and Fas-dependent cytotoxicity.

Treatment of lymphokine-activated killer (LAK) cells with phorbol ester (PMA) caused the downmodulation of LAK activity concomitantly with the inhibition of serine esterase (SE) release, which has been shown as a marker for perforin-dependent cell-mediated cytotoxicity. The reduction of perforin-dependent LAK activity by PMA-treatment appeared to be due to the disappearance of PMA-sensitive protein kinase C (PKC) isoforms such as PKC alpha, gamma, epsilon, theta. In contrast, Fas-mediated LAK activity was refractory against PMA-induced downregulation. Treatment of LAK cells with PMA caused a disappearance of cytotoxicity against Fas L5178Y tumor cells, while cytotoxicity against Fas+ transfectants was not affected by PMA treatment. Moreover, Fas-mediated LAK activity of perforin-knockout mice was not inhibited by PMA treatment. These results clearly demonstrated that Fas-mediated cytotoxicity could be dissociated from perforin-mediated cytotoxicity by their different requirement of PMA-sensitive PKC isoforms.

Animals↗

PubMed1997

Involvement of IL-4-producing Vbeta8.2+ CD4+ CD62L- CD45RB- T cells in non-MHC gene-controlled predisposition toward skewing into T helper type-2 immunity in BALB/c mice.

It was found that freshly isolated BALB/c CD4+ T cells produced high levels of IL-4 and IL-10 in response to immobilized anti-CD3 mAb, while C57BL/6 CD4+ T cells produced low amounts of IL-4 and IL-10. The high IL-4-producing ability of BALB/c mice was demonstrated to be genetically dominant and it was controlled by non-MHC gene (or genes). The cells responsible for IL-4 production in BALB/c mice were defined as TCRVbeta8.2+ CD4+ CD62L- CD45RB- memory-type T cells, which were distinct from NK1.1+ CD4+ NKT cells. Although these memory-type T cells were also detected in C57BL/6 mouse spleen at the same frequency, they showed a functionally different property from BALB/c CD4+ CD62L- CD45RB- T cells in terms of IL-4 production. The fact that germfree BALB/c mouse spleen cells also produced high levels of IL-4 suggested that the IL-4 producer in BALB/c mice might be developed under the influence of unknown factors other than environmental Ags. The CD4+ CD62L- CD45RB- T cells obtained from BALB/c mice accelerated the development of IL-4-producing memory-type CD4+ T cells from CD4+ CD62L+ CD45RB+ naive T cells prepared from OVA-specific TCR-transgenic mice. Therefore, IL-4-producing CD4+ CD62L- CD45RB- T cells might play an important role in the preferential induction of Th2-dominant immunity in BALB/c mouse strain.

Animals↗

PubMed1997

FR167653, a dual inhibitor of interleukin-1 and tumor necrosis factor-alpha, ameliorates endotoxin-induced shock.

Increased production of interleukin-1 and tumor necrosis factor-alpha (TNF-alpha) have been implicated in the pathophysiology of a variety of diseases including circulatory shock. The present study evaluated the efficacy of FR167653 (1-[7-(4-fluorophenyl)-1,2,3,4-tetrahydro-8-pyridylpyrazolo[5,1-c] [1,2,4]triazin-2-yl]-2-phenylethanedione sulfate monohydrate), a dual inhibitor of interleukin-1 and TNF-alpha production, to protect rabbits from the shock and lethality induced by lipopolysaccharide. In this sepsis model, FR167653 at a dose of 0.32 mg/kg per h ameliorated the 7-day mortality from 93% in the placebo group to 47% in the FR167653-treated group and, at doses of 0.10-0.32 mg/kg per h, attenuated the hypotensive response to lipopolysaccharide challenge and returned mean arterial blood pressure to almost normal levels. The increases in plasma interleukin-1 and TNF-alpha levels evoked by lipopolysaccharide administration were also inhibited by treatment with FR167653, which was efficacious at doses of 0.1-0.32 mg/kg per h. In addition, FR167653 treatment attenuated the increases in plasma creatinine concentrations consistent with renal damage in a dose-dependent manner. These findings suggested that FR 167653 has a beneficial potential as a drug for septic shock or multiple organ dysfunction syndrome.

Animals↗

PubMed1997

T/G polymorphism at intron 9 of presenilin 1 gene is associated with, but not responsible for sporadic late-onset Alzheimer's disease in Japanese population.

To investigate whether presenilin 1 (PS1) gene, a major causative gene of familial early-onset Alzheimer's disease (AD), also contributes to the etiology of sporadic AD, we evaluated associations between Japanese AD and polymorphisms located at 14q24.3. While the D14S43 and FOS loci showed no association with either early- or late-onset AD, late-onset AD carrying no APOE-epsilon4 allele was associated with the G allele of the T/G polymorphism located at intron 9 of the PS1 gene (P = 0.016). Considering another study showing a positive association between AD and the T allele, this polymorphism is associated with, but not responsible for sporadic late-onset Alzheimer's disease.

Age of Onset↗

PubMed1997

Effects of cardiac denervation on development of heart failure and catecholamine desensitization.

BACKGROUND: Two signatures of heart failure are activation of the sympathetic nervous system and catecholamine desensitization. However, whether or not the elimination of cardiac nerves affects either the progression of heart failure or catecholamine desensitization is not clear. METHODS AND RESULTS: We studied 8 dogs with selective ventricular denervation (VD) (surgical technique) and 10 intact dogs, chronically instrumented for measurement of left ventricular (LV) and arterial pressures, LV dP/dt, LV internal diameter, and wall thickness before and after heart failure was induced by rapid pacing (240 bpm) for 3 to 4 weeks. VD was confirmed by the absence of reflex effects induced by intracardiac veratrine and depletion of tissue norepinephrine and by supersensitive responses to norepinephrine. During the development of heart failure, LV end-systolic and end-diastolic stresses and heart rate increased, while myocardial contractility, as reflected by LV dP/dt and mean velocity of circumferential fiber shortening corrected for heart rate (Vcf(c)), decreased in both intact and VD dogs. However, the increases in LV end-diastolic stress and decreases in LV dP/dt as well as the relationship between LV systolic stress and Vcf(c) in heart failure were less (P<.05) in VD dogs. The responses of LV dP/dt and heart rate to both isoproterenol and norepinephrine in intact dogs were reduced in heart failure. The physiological desensitization to the inotropic effects of isoproterenol and norepinephrine was less in dogs with VD (P<.05), but chronotropic responses were similar because atrial innervation remained intact. Plasma norepinephrine levels were not different in VD dogs (592+/-79 pg/mL) compared with intact dogs (576+/-81 pg/mL) in heart failure. CONCLUSIONS: Dogs with selective VD tolerated the development of heart failure better than intact dogs and demonstrated significantly less catecholamine desensitization. The latter indicates that intact ventricular innervation is required for physiological expression of catecholamine desensitization despite comparable elevation of plasma catecholamines during the development of heart failure.

Adrenergic alpha-Agonists↗

PubMed1997

A metastatic and androgen-sensitive human prostate cancer model using intraprostatic inoculation of LNCaP cells in SCID mice.

Several metastasizing murine and human animal models for prostate cancer are available. However, these models are androgen-independent and lack differentiated features such as androgen receptor and androgen-regulated gene expression like prostate-specific antigen (PSA). The objective of this study was to develop a metastasizing prostate cancer model with differentiated features using the human LNCaP cell line. Athymic and SCID mice were injected either s.c. or intraprostatically with 1 x 10(6) LNCaP cells. Changes in serum and tumor PSA mRNA levels were determined before and after castration to assess time to androgen-independent progression. Local tumor and metastatic growth was assessed at sacrifice after 12 weeks. Reverse transcription-PCR (RT-PCR) was used to detect circulating LNCaP cells. LNCaP tumor incidence after s.c. injection was 100% (65 of 65) in SCID mice and 80% in athymic mice. No lymph node or distant metastases were observed with s.c. tumors, and RT-PCR for PSA transcripts was negative. Primary tumor incidence after intraprostatic injection was 89% (39 of 44) in SCID mice and 60% in athymic mice. In 10 SCID mice with primary tumors followed for 12 weeks, retroperitoneal or mediastinal lymph node metastases were found in 100%, and microscopic pulmonary metastases were identified in 40%. RT-PCR for PSA transcripts was positive in 3 of 10 mice tested. Serum PSA levels in mice with s.c. and intraprostatic tumors decreased by 65% to nadir levels at 7 and 4 days after castration, respectively. Serum PSA and LNCaP tumor PSA mRNA levels increased to precastration levels earlier in SCID mice with intraprostatic tumors compared to those with s.c. tumors. Intraprostatic injection of LNCaP cells in SCID mice provides a useful animal model to investigate mechanisms of metastasis and to evaluate therapies targeted toward inhibiting the metastatic cascade.

Animals↗

PubMed1997

Adult T cell leukemia (ATL)-derived factor/human thioredoxin prevents apoptosis of lymphoid cells induced by L-cystine and glutathione depletion: possible involvement of thiol-mediated redox regulation in apoptosis caused by pro-oxidant state.

Thiol compounds, such as L-cysteine and glutathione (GSH), play crucial roles in the regulation of lymphocyte proliferation. In this study, we analyzed the effect of L-cystine and GSH depletion on lymphocyte survival and investigated the regulatory roles of adult T cell leukemia (ATL)-derived factor (ADF)/human thioredoxin (hTRX) in relation to these low m.w. thiols. MT-1, MT-2, and Jurkat cells underwent apoptosis when cultured in the L-cystine- and GSH-free medium within 18 to 24 h. Dichlorofluorescin oxidation assay indicated that the apoptosis in MT-1 and MT-2 cells was preceded by an increase in the level of intracellular hydrogen peroxide (H2O2). The addition of catalase and recombinant ADF/hTRX (rADF) partially blocked the apoptosis in a dose-dependent manner. rADF has been also shown to enhance the internalization of L-cystine into MT-2 cells in a dose-dependent manner, whereas oxidized rADF or mutated rADF that has no insulin-reducing activity failed to do so. Furthermore, culture in the L-cystine- and GSH-free medium lowered the cellular GSH content of PHA blasts, which was restored dose-dependently by rADF. These data suggest that the inability to neutralize oxidative stress results in the apoptosis of lymphoid cells under L-cystine- and GSH-depleted conditions. The protective effects of rADF may be explained by direct scavenging action on H2O2 (catalase-like activity) or by indirect neutralizing effects on the pro-oxidant status through enhancing the L-cystine internalization and elevating the intracellular GSH content.

Apoptosis↗

PubMed1997

Elevated amyloid beta protein(1-40) level induces CREB phosphorylation at serine-133 via p44/42 MAP kinase (Erk1/2)-dependent pathway in rat pheochromocytoma PC12 cells.

The deposition of amyloid beta protein (A beta) in the cerebral cortex is the pathological characteristic of Alzheimer's disease (AD), and patients with AD suffer from progressive memory loss. Transgenic experiments have revealed that long-term memory is dependent on cyclic AMP-response element binding protein, CREB. CREB phosphorylation at serine-133 is essential for its transcriptional activity. Here we demonstrated that A beta(1-40), at a concentration more than 1 microM, induced CREB phosphorylation at serine-133 in rat pheochromocytoma PC12 cells. A beta(1-40) induced phosphorylation of p44 and p42 MAP kinases (Erk1 and Erk2) at tyrosine-204, and PD98059, a MEK1 inhibitor, inhibited A beta(1-40)-induced CREB phosphorylation at serine-133. We conclude that elevated A beta(1-40) level induces CREB phosphorylation at serine-133 via p44/42 MAP kinase-dependent pathway.

Amyloid beta-Peptides↗

PubMed1997

Microbial system for polysaccharide depolymerization: enzymatic route for gellan depolymerization by Bacillus sp. GL1.

A bacterium-producing polysaccharide lyase (gellan lyase) was isolated from soil samples and identified to be Bacillus sp. The lyase was purified from the culture fluid of the bacterium (designated Bacillus sp. GL1) grown in the presence of gellan as a carbon source. The purified gellan lyase depolymerized deacetylated gellan and gave a single oligosaccharide product with a molecular weight of 646, which was determined by fast atom bombardment mass spectrometry. The structure of the product was determined by the combination of mass spectrometry, HPLC analysis, and high-resolution proton nuclear magnetic resonance spectroscopy to be a tetrasaccharide of glucuronyl-glucosyl-rhamnosyl-glucose with unsaturated glucuronic acid at the nonreducing terminal. When incubated in cell extracts of Bacillus sp. GL1, the tetrasaccharide was first converted to trisaccharide without unsaturated glucuronyl residue, and the trisaccharide was then converted to hydrolyzed monosaccharides glucose and rhamnose. These results show that, in the bacterium Bacillus sp. GL1, gellan is first depolymerized to give a tetrasaccharide, a repeating unit in gellan molecule, by an extracellular gellan lyase and then the tetrasaccharide is hydrolyzed to monosaccharides by successive actions of intracellular exoglycosidases.

Bacillus↗

PubMed1997

Modeling the Exchanges of Energy, Water, and Carbon Between Continents and the Atmosphere

Atmospheric general circulation models used for climate simulation and weather forecasting require the fluxes of radiation, heat, water vapor, and momentum across the land-atmosphere interface to be specified. These fluxes are calculated by submodels called land surface parameterizations. Over the last 20 years, these parameterizations have evolved from simple, unrealistic schemes into credible representations of the global soil-vegetation-atmosphere transfer system as advances in plant physiological and hydrological research, advances in satellite data interpretation, and the results of large-scale field experiments have been exploited. Some modern schemes incorporate biogeochemical and ecological knowledge and, when coupled with advanced climate and ocean models, will be capable of modeling the biological and physical responses of the Earth system to global change, for example, increasing atmospheric carbon dioxide.

Journal Article↗

PubMed1997

alpha 1-Antichymotrypsin as a risk modifier for late-onset Alzheimer's disease in Japanese apolipoprotein E epsilon 4 allele carriers.

In the Japanese population, sporadic late-onset Alzheimer's disease (LOAD) cases had significantly higher frequencies of the A allele of alpha 1-antichymotrypsin (ACT) gene as well as the epsilon 4 allele of apolipoprotein E (APOE) gene than controls. The odds ratio for LOAD in APOE4 carriers with the ACT-A allele was more than six times that in APOE4 carriers without the ACT-A allele (21.1 vs 3.2). These results indicate that the ACT-A allele is a risk modifier for LOAD in APOE4 carriers.

Age of Onset↗

PubMed1997

Effect of albendazole on recurrent and residual alveolar echinococcosis of the liver after surgery.

Patients with alveolar echinococcosis of the liver (AEL) can be cured by complete excision of the lesions; however, it is not always completely resectable in advanced cases. Recently, benzimidazole-type drugs have been reported to be effective in nonresectable AEL. One hundred fifty-two patients with AEL have been surgically treated in our institution since 1937. Our clinical trial with albendazole, one of the benzimidazole carbamates, has included 26 cases of AE since September 1988, each of whom had undergone an operation. Complete resection was performed in only six cases. Evaluation of response to the treatment was possible in 20 cases. A favorable response to albendazole, such as decreases in the size of the lesions, changes in cyst morphology, and amelioration in clinical symptoms or signs, was achieved in 11 (55%) cases. These favorable responses were also seen in cases of noncurative resection and palliative operation. The cumulative survival rate of the patients was 87%, 15 years after the operation. A complete response was achieved in one case; the residual lesion in the liver completely disappeared on the computed tomography image 3.5 years after noncurative surgery. Palliative or mass reduction surgery combined with albendazole therapy may be a strategy for advanced disease, especially when complete resection might result in significant morbidity or mortality.

Adult↗

PubMed1997

Fibronectin facilitates corneal epithelial wound healing in diabetic rats.

To determine whether the effect of fibronectin on corneal epithelial healing occurs in eyes affected by diabetes, the effect of fibronectin on the rates at which corneal epithelial wounds healed was compared in diabetic and normal rats. Streptozotocin was used to induce diabetes in rats. Two weeks after treatment, the whole corneal epithelium of diabetic and untreated rats was debrided. Fibronectin eye drops, at concentrations ranging from 0-01 to 1 mg ml-1, were given six times a day for three days, starting immediately after debridement. The area of the corneal epithelial wound was measured every 12 hr. Although the healing process was similar in normal and diabetic rats, the healing rate in diabetic rats was slower than that in normal controls after the 12 hr immediately following debridement. In both diabetic and normal rats, fibronectin eye drops reduced the wound area in a dose-dependent manner. The fibronectin dose of 1 mg ml-1 reduced the wound area significantly, compared with control eyes treated with phosphate-buffered saline. These results demonstrated that fibronectin facilitates corneal epithelial wound healing in diabetic rats.

Animals↗

PubMed1997

Hyaluronan facilitates corneal epithelial wound healing in diabetic rats.

We investigated the effect of hyaluronan on corneal epithelial wound healing in rats affected by diabetes. Furthermore, because hyaluronan is thought to affect corneal epithelial wound healing through the mechanism of binding of hyaluronan to provisional fibronectin in the wounded area, we compared the localization of fibronectin immunohistochemically during corneal epithelial wound healing in diabetic and non-diabetic rats. Streptozotocin was used to induce diabetes in half the rats. Two weeks after treatment, the whole corneal epithelium of diabetic and untreated rats was debrided. The rats were divided into groups (seven or eight rats per group), and hyaluronan eye drops at concentrations of 0.03, 0.1, or 0.3%, chondroitin sulfate (3%), or phosphate buffered saline (PBS) was given in eye drops 6 times a day for 4 days, starting immediately after debridement. The area of the corneal epithelial wound was measured immediately after debridement and at 12, 18, 24, 30, 48, 72, and 96 hours afterwards. Although the healing process was similar in non-diabetic and diabetic rats, the healing rate in diabetic rats was slower than that in normal controls. In both diabetic and non-diabetic rats, hyaluronan increased the healing rate in a dose-dependent manner; the difference was significant compared with the PBS-treated group, at hyaluronan doses of 0.1% and 0.3%. However, chondroitin sulfate did not affect corneal epithelial wound closure, regardless of whether the rats were diabetic or not; the healing rates were identical to those of PBS-treated diabetic and non-diabetic controls. In both diabetic and non-diabetic corneas, fibronectin was localized in the corneal subepithelial region, and in streaks between collagen fibers of the stroma. One day after debridement, a layer of fibronectin immunofluorescence was clearly visible on the surface of the denuded stroma. As healing progressed staining of fibronectin diminished at the interface between the new epithelium and the stroma. These changes in localization of fibronectin during corneal epithelial wound healing were similar in both diabetic and non-diabetic rats. Our results demonstrate that hyaluronan facilitates corneal epithelial wound healing in diabetic rats, and suggest that one possible mechanism of its stimulatory effect lies in its binding to a provisional fibronectin matrix, in both diabetic and non-diabetic rats.

Animals↗

PubMed1997

Induction of human thioredoxin in cultured human retinal pigment epithelial cells through cyclic AMP-dependent pathway; involvement in the cytoprotective activity of prostaglandin E1.

Human thioredoxin is one of the oxidative stress-inducible proteins and has a protective function against oxidant-induced injury. To evaluate the possible involvement of thioredoxin in the cytoprotective function of prostaglandin E1, we analysed the effect of prostaglandin E1 on cellular injury by hydrogen peroxide and intracellular thioredoxin induction. Cellular survival of human retinal pigment epithelial cell line, established from normal retinal pigment epithelial cells, following exposure to hydrogen peroxide was markedly improved by pretreatment of 1 microm prostaglandin E1. Thioredoxin expression was augmented in a dose-dependent manner when retinal pigment epithelial cells were pretreated with 10 nm-1 microm prostaglandin E1 1 hr before the exposure to hydrogen peroxide. Intracellular cyclic AMP level was elevated by Prostaglandin E1 when the cells were simultaneously exposed to hydrogen peroxide. Forskolin, an activator of adenylate cyclase, and dibutylyl cAMP, a cyclic AMP analog, could also induce thioredoxin and extend survival of retinal pigment epithelial cells. On the other hand, thioredoxin induction and cellular protection by prostaglandin E1 was blocked by Rp diastereoisomer of cyclic adenosine 3', 5', monophosphorothioate, a competitive inhibitor of cyclic AMP dependent protein kinase. Thioredoxin induction was augmented significantly by pretreatment with prostaglandin I2, a stimulator of cyclic AMP dependent signal pathway, while treatment with prostaglandin F2alpha, a stimulator of inositol phosphate-dependent signal pathway, failed to enhance thioredoxin. These findings indicate that prostaglandin E1 has a cytoprotective activity against oxidative injury, partly through thioredoxin induction via cyclic AMP dependent pathway.

Adenylyl Cyclases↗

PubMed1997

Beta-adrenergic receptor signalling in stunned myocardium of conscious pigs.

The primary goal of this study was to compare the effects of isoproterenol which stimulates beta-adrenergic receptors and forskolin, and NKH 477, a water soluble derivative of forskolin, which stimulate adenylyl cyclase in stunned myocardium of conscious pigs, previously instrumented for measurements of left ventricular pressure and dP/dt, arterial pressure, and wall thickening. Ten min of coronary artery occlusion induced transmural reductions in blood flow (radioactive microspheres) in subepicardium (-98 +/- 2%) and subendocardium (-99 +/- 1%). Wall thickening (piezoelectric crystals) fell from 2.50 +/- 0.26 mm to -0.26 +/- 0.26 mm and remained depressed at 1.37 +/- 0.19 mm after 20-30 min coronary artery reperfusion, reflecting myocardial stunning. At that time, isoproterenol (0.2 microgram/kg) increased wall thickening in stunned myocardium (+1.40 +/- 0.16 mm, P < 0.05) more than in control (+0.71 +/- 0.22 mm), while forskolin elicited the opposite effects. NKH 477 (30 micrograms/kg), which does not penetrate the blood-brain barrier, increased systolic wall thickening similarly before (+0.95 +/- 0.25 mm) and during (+1.01 +/- 0.24 mm) myocardial stunning. The reflex inotropic responses to inferior vena caval occlusion on wall thickening were diminished, P < 0.05, in the stunned myocardium (+0.53 +/- 0.05 mm) compared with control (+0.95 +/- 0.07 mm). beta-adrenergic receptor density, which was quantitated with 125I-cyanopindolol binding, was increased transmurally in stunned myocardium compared with non-ischemic myocardium (subepicardium: +23 +/- 5%, subendocardium: +34 +/- 13%, P < 0.05). Basal and forskolin-stimulated adenylyl cyclase activities were decreased slightly, but significantly, in the stunned subendocardium but not in the subepicardium, while isoproterenol stimulation of adenylyl cyclase activity showed no differences. In summary, paradoxical responses to beta-adrenergic receptor stimulation were observed in stunned myocardium, with pharmacological stimulation with isoproterenol evoking enhanced responses, and neural stimulation with inferior vena caval occlusion eliciting depressed responses. The diminished responses to forskolin in vivo, in stunned myocardium were out of proportion to the biochemical measurements, and may be attributed to neurally mediated cardiac effects of forskolin, since the responses to direct stimulation of adenylyl cyclase by NKH 477 were preserved.

Adenylyl Cyclases↗

PubMed1997

Effects of epidermal growth factor and insulin on migration and proliferation of primary cultured rabbit gastric epithelial cells.

We assessed the influence of epidermal growth factor (EGF) and insulin on gastric epithelial restoration in vitro. Rabbit gastric epithelial cells were cultured and formed a complete monolayer cell sheet in 2 days. We created a wound (1.8 +/- 0.05 mm2) by denuding an area of cells, and EGF (0.1-30 ng/ml) and/or insulin (1 nM-1 microM) was added. The restoration process, which included cell migration and proliferation, was monitored by measuring the cell-free area every 12 h for 2 days. Proliferating cells were detected by sequential staining with bromodeoxyuridine (BrdU). Control cells showed complete repair in 36-48 h and restoration was accelerated dose-dependently by EGF or insulin. EGF plus insulin further accelerated restoration, which was then completed in 12-24 h. EGF and/or insulin increased the number of BrdU- positive cells. The results indicated that EGF and insulin additively accelerated gastric epithelial wound repair by stimulating both the migration and the proliferation of gastric epithelial cells (particularly the former).

Animals↗