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M Ogihara

Publications and source records attributed to M Ogihara.

At least 19 recordsLinked to original sources

Glycyrrhizin and some analogues induce growth of primary cultured adult rat hepatocytes via epidermal growth factor receptors.

We investigated the effects of glycyrrhizin (GL-1) and some analogues on DNA synthesis and proliferation in serum-free primary cultures of adult rat hepatocytes. The hepatocytes underwent DNA synthesis and proliferation in response to GL-1 and some analogues. The effects of these agents occurred in a time- and dose-dependent manner. The proliferative potency as judged by half-maximal effective concentrations was in the following order: 18-beta-H-glycyrrhetinic acid (GL-3; 4.5 x 10(-9) M)<18-beta-H-glycyrrhizin (GL-1; 4.4 x 10(-8) M)<18-alpha-H-glycyrrhetinic acid (GL-6; 6.0 x 10(-8) M). The analogue 18-alpha-H-glycyrrhetinic acid 3-O-beta-D-monoglucuronide (GL-5; 1.0 x 10(-7) M) weakly stimulated hepatocyte DNA synthesis and proliferation, whereas 18-alpha-H-glycyrrhizin (GL-4) and 18-beta-H-glycyrrhetinic acid 3-O-beta-D-monoglucuronide (GL-2) did not. The growth-promoting effects of GL-1, GL-3 and GL-6 were significantly inhibited at higher initial plating densities (7.0 x 10(4) and 10 x 10(4) cells/cm(2)). A monoclonal antibody against epidermal growth factor (EGF) receptor (1-100 ng/ml), but not that against EGF (1-100 ng/ml), dose-dependently inhibited glycyrrhizin- and analogue-induced hepatocyte DNA synthesis and proliferation. Specific inhibitors of growth-related signal transducers, such as genistein, PD98059 (2'-amino-3'-methoxyflavone) and rapamycin, completely blocked glycyrrhizin- and analogue-induced hepatocyte DNA synthesis and proliferation. Treatment of hepatocytes with GL-1, GL-3 and GL-6 rapidly stimulated tyrosine phosphorylation of the EGF receptor and p42 MAP kinase, which were inhibited by genistein and PD98059, respectively. These results suggest that glycyrrhizin and some analogues are primary hepatocyte mitogens that bind to EGF receptors and subsequently stimulate the receptor tyrosine kinase/mitogen-activated protein kinase pathway to induce hepatocyte DNA synthesis and proliferation.

Adenylyl Cyclase Inhibitors↗

Prostaglandin E(2) (EP(1)) receptor agonist-induced DNA synthesis and proliferation in primary cultures of adult rat hepatocytes: the involvement of TGF-alpha.

We investigated the effects of prostaglandin (EP) receptor subtype agonists on DNA synthesis and proliferation in primary cultures of adult rat hepatocytes to elucidate their mechanisms of action. Maintained in short-term cultures (i.e. 3.5 h) in a serum-free, defined medium, hepatocyte parenchymal cells underwent DNA synthesis and proliferation in the presence of sulprostone (10(-6) M), PGE(2) (10(-6) M), and 17-phenyl-trinor-PGE(2) (10(-9) M) in a time- and dose-dependent manner. PGE(2) was less potent than 17-phenyl-trinor-PGE(2) in stimulating hepatocyte mitogenesis. Sulprostone (10(-6) M) and 11-deoxy-PGE(1) (10(-6) M) showed weak and insignificant stimulation, respectively, for hepatocyte mitogenesis. These effects of PGE(2), 17-phenyl-trinor-PGE(2), and sulprostone were abolished by treatment with a specific EP(1) receptor antagonist, SC-51322, or the PLC inhibitor U-73122. The effects of these EP(1) receptor agonists were potentiated by ionomycin and blocked by verapamil. Hepatocyte mitogenesis was almost completely blocked by specific inhibitors of growth-related signal transducers, such as genistein, wortmannin, PD98059, and rapamycin. A monoclonal antibody against TGF-alpha dose-dependently inhibited PGE(2)- and 17-phenyl-trinor-PGE(2)-induced hepatocyte mitogenesis. Treatment with the EP(1) receptor agonists significantly increased the secretion of TGF-alpha, reaching a maximum within 5 min. The increase in TGF-alpha secretion was blocked by SC-51322, U-73122, somatostatin, and verapamil and potentiated by ionomycin. These results indicate that the proliferative mechanisms of action of EP(1) receptor agonists are mediated through an increase in the autocrine secretion of TGF-alpha, which is dependent on the EP(1) receptor/G-protein involved in PLC regulation/PLC/Ca(2+) system. The locally secreted TGF-alpha, in turn, acts as a complete mitogen that stimulates the tyrosine kinase/MAPK pathway in these cells.

Animals↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1999). I. Susceptibility distribution].

The bacterial strains isolated from patients diagnosed as having urinary tract infections (UTIs) in 9 institutions in Japan were supplied between the period of August 1999 to July 2000. Then, the susceptibilities of them to many kinds of antimicrobial agents were investigated. The number of them were 499 strains. The breakdown of these strains was Gram-positive bacteria as 31.3% and Gram-negative bacteria as 68.7%. Susceptibilities of these bacteria to antimicrobial agents were as follows; vancomycin (VCM), ampicillin (ABPC) and imipenem (IPM) showed strong activities against Enterococcus faecalis. The increase of low-susceptible strains which was noticed in the former year showed a slight recovery in this year. VCM showed a strong activity against MRSA preventing growth of all strains with 1 microgram/ml. In addition, the activity of arbekacin (ABK) was also strong with the MIC90 of 2 micrograms/ml against MRSA. However, MSSA and MRSA showing low susceptibilities were detected in one strain each (MIC: 16 micrograms/ml and 32 micrograms/ml, respectively). Carbapenems showed high activities against Citrobacter freundii and Escherichia coli. Meropenem (MEPM) prevented growth of all strains within 0.125 microgram/ml. Quinolone resistant E. coli decreased in this year compared with those in the last year, that percentage was less than 5%. Almost all drugs showed strong activities against Klebsiella pneumoniae and Proteus mirabilis. MEPM and carumonam (CRMN) prevented growth of all strains within 0.125 microgram/ml. On the other hand, one strain of K. pneumoniae showing resistance to cefaclor (CCL) and one strain of P. mirabilis showing low susceptibility to most of cephems were detected. Against Pseudomonas aeruginosa, almost drugs were not so active. The MIC90s of carbapenems were 8 micrograms/ml and those of all other drugs were more than 16 micrograms/ml.

Anti-Bacterial Agents↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1999). II. Background of patients].

Five-hundred forty four bacterial strains isolated from 412 patients diagnosed as having urinary tract infections (UTIs) in 9 institutions in Japan were supplied between the period of August 1999 to July 2000. Then, the clinical background of patients were investigated such as sex, age and type of infections, infections and kind of bacteria, frequency of isolation of bacteria by age and infections, bacteria and infections by timing of administration of antibiotics, and bacteria and infections by surgical procedures. About the relationship between age and sex of patients and type of infections, the number of male patients aged less than 50 years was few, and complicated UTIs without indwelling catheter was the most frequent. In females, the number of patients aged less than 20 years was few. Complicated UTIs without indwelling catheter was the most frequent among female patients aged between 40 to 59 years, in other age groups, uncomplicated UTIs was most frequent. As for type of infections and kind of bacteria, Escherichia coli decreased when the infections became complicated, and Pseudomonas aeruginosa and Enterococcus faecalis increased when the infection became complicated. Considering this result by age of patients, isolation frequency of E. coli was gradually decreased with aging in patients aged more than 20 years with uncomplicated UTIs or complicated UTIs without indwelling catheter. The isolation frequencies of E. faecalis and Staphylococcus aureus were gradually increased with aging in complicated UTIs without indwelling catheter. In patients with complicated UTIs with indwelling catheter, there was no difference between age group, and P. aeruginosa and E. faecalis were frequently isolated. As for type of causative organisms in UTIs before and after the administration of antibiotics, the isolation of bacteria was remarkably decreased after administration in patients with uncomplicated UTIs and complicated UTIs without indwelling catheter. E. coli decreased after administration of antibiotics, and P. aeruginosa and E. faecalis increased after administration in patients with all infections. As for type of causative organisms in UTIs and surgical procedures, E. coli were more frequently isolated in patients with uncomplicated UTIs when surgical procedures were experienced. Also, Klebsiella spp. and E. faecalis were more frequently isolated in patients with surgical procedures. However, in complicated UTIs, type of causative organisms had no relationship with surgical procedures.

Adolescent↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1999). III. Secular changes in susceptibility].

The bacteria (Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as having urinary tract infections (UTIs) in 9 institutions in Japan were supplied between the period of August 1999 to July 2000. Then, the susceptibilities of these bacteria to various antimicrobial agents were examined and the results were compared with those obtained between 1991 and 1998. Comparison was made by classifying strains isolated from patients into those with uncomplicated UTIs and those with complicated UTIs (including with or without indwelling catheter). About E. faecalis, increase of low sensitive strains noted in the former year showed a decreasing tendency, however, one strain each with MIC of 4 micrograms/ml to vancomycin (VCM) was detected in patients with both uncomplicated and complicated UTIs. As for S. aureus, many sensitive strains to cephems, imipenem (IPM) and VCM were noted, and each MIC50 was better than that in the former years. S. aureus strains showing low susceptibility to arbekacin (ABK) were detected in patients with complicated UTIs in this year as well as in the former year, and one strain each with MIC of 16 micrograms/ml and 32 micrograms/ml was detected. Susceptibilities of E. coli were effective to all drugs except for penicillins and minocycline (MINO). Decrease of low sensitive strains was also noted in all drugs except for quinolones. Each MIC90 of ciprofloxacin (CPFX) and sparfloxacin (SPFX) in patients with complicated UTIs against E. coli was 3 degrees classes lower than that in patients with uncomplicated UTIs. As for Klebsiella pneumoniae, decrease of low sensitive strains to cephems was noted in patients with uncomplicated UTIs in 1998. In 1999, low sensitive strains decreased also in patients with complicated UTIs, and few were detected. Susceptibilities of K. pneumoniae to quinolones were effective as compared with those in the former years with the MIC80s of 0.125 microgram/ml or below without detection of low sensitive strains. One low sensitive strain of K. pneumoniae with MIC of 8 micrograms/ml was detected for gentamicin (GM). Susceptibilities of P. aeruginosa to carbapenems were notable. The MIC90 of meropenem (MEPM) and IPM was 4 micrograms/ml each which was 2 degrees better than that in 1998. Resistant P. aeruginosa strains to other drugs except for monobactams decreased in 1999.

Anti-Bacterial Agents↗

[A case of 7q distal trisomy syndrome associated with West syndrome].

We report a five-year-old girl with 7q distal trisomy syndrome. At the age of five months, West syndrome was diagnosed based on electroencephalogram (EEG) findings. Her EEG showed occipital dominant spikes and diffuse multiple spike-wave complexes which continued almost continuously (modified hypsarrhythmia). Brief generalized tonic seizures were observed in series fashion, lasting for 5-10 minutes. She has some dysmorphic features including hypertelorism, bifid uvula, long philtrum, and dysplastic ears. Chromosome analysis by the spectral karyotyping method revealed that her karyotype was 46,XX,der(20)t(7;20) (q32.3;q13.33) de novo. To our knowledge, there are 23 reported cases of 7q distal trisomy syndrome with a breakpoint on q32, among which two sibling cases had epileptic seizures. Our case is the first case complicated by West syndrome.

Child, Preschool↗

Stimulation of DNA synthesis and proliferation by prostaglandins in primary cultures of adult rat hepatocytes.

We studied the effects of several prostaglandins on DNA synthesis and proliferation in serum-free primary cultures of adult rat hepatocytes. Maintained in short-term cultures (i.e., 3.5 h), the hepatocyte parenchymal cells synthesized DNA and proliferated in the presence of various prostaglandins in a dose-dependent manner. The half-maximal effective concentrations (ED(50)) of prostaglandin F(2alpha), prostaglandin E(1), prostaglandin E(2) and prostaglandin I(2) for proliferation were estimated to be 1.7 x 10(-9), 2.3 x 10(-8), 2.7 x 10(-8) and 3.3 x 10(-9) M, respectively. Prostaglandin E(2) and prostaglandin I(2) produced greater maximal responses than did either prostaglandin E(1) or prostaglandin F(2alpha). The cells responded only weakly to prostaglandin D(2). The stimulatory effects of 10(-6) M prostaglandin E(1) and 10(-6) M prostaglandin E(2) on hepatocyte DNA synthesis and proliferation were inhibited by a specific antagonist of the EP(1) receptor, 8-chlorodibenz[b, f][1, 4]oxazepine-10(11H)carboxylic acid, 2-[3-[(2-furanylmethyl)-thio]-1-oxopropyl]hydrazide (SC-51322; 10(-6) M). Specific inhibitors of signal transducing elements (e.g., 1-[6-[17beta-3-methoxyestra-1, 3, 5(10)-trien-17-yl]amino] hexyl]-1H-pyrrol-2,5-dione (U-73122); 10(-6) M), 10(-6) M verapamil, 5 x 10(-6) M genistein) almost completely blocked the growth-promoting effects of the prostaglandins. These results suggest that prostaglandins stimulate hepatocyte DNA synthesis and proliferation by their own receptors and exert their effects through both phospholipase C/Ca(2+) and receptor tyrosine kinase pathways.

Animals↗

Potentiation of effects of anticancer agents by local electric pulses in murine bladder cancer.

Electrochemotherapy is a novel cancer treatment in which electric pulses (EP) are used as a means of delivering anticancer agents to the cytoplasm of cancer cells (electroporation). The present study evaluates whether electrochemotherapy has in vitro and in vivo anticancer effects in murine bladder cancer. Using mouse bladder tumor cells (MBT-2 cells), in vitro electrochemotherapy was performed by applying EP to the cell suspension immediately after the addition of anticancer agents. The cytotoxicity of adriamycin (ADM), bleomycin (BLM) and cis-diamminedichloroplatinum(II) (CDDP) was determined by measuring succinate dehydrogenase (SD) activity in both electroporated and non-electroporated cells. In addition, intracellular concentrations of these anticancer agents were also measured. In the in vivo study, tumor-bearing C3H/He mice were treated with an intraperitoneal injection of anticancer agents followed by a local delivery of EP at the tumor site. Then, tumor growth rate (TGR) was determined and compared to that in the sham-treated control group, the EP-only group and the drug-only group. The in vitro study showed that, with electroporation, the cytotoxicity of BLM in electroporated cells was increased by as much as 95.7-fold compared to that of non-electroporated MBT-2 cells; CDDP showed only an increase of 1.8-fold and ADM showed no increase. After electroporation, the intracellular concentration of BLM, CDDP and ADM showed an increase of 120-, 1.7- and 0.8-fold, respectively. In electrochemotherapy for in vivo growing tumors, the potentiation of the antitumor effect was most prominent when combined with BLM, only slightly with CDDP, and totally absent with ADM. It is clear from in vitro and in vivo studies that, in a murine bladder tumor, the anticancer effect of BLM can be considerably potentiated by applying EP. Thus, BLM seems to be the most suitable anticancer agent for electrochemotherapy of bladder cancer.

Animals↗

Psoas abscess complicating Crohn's disease: report of a case.

We describe herein the case of a psoas abscess complicating Crohn's disease, and present a review of the literature on this unusual disease entity. A 22-year-old Japanese man with a 5-year history of Crohn's ileocolitis presented with right lower abdominal and hip pain, and a diagnosis of right psoas abscess was subsequently made by abdominal computed tomography (CT). Following the administration of antibiotics and CT-guided percutaneous drainage of the abscess, the patient's symptoms temporarily improved; however, 2 weeks later, the abscess cavity was found to have extended around the periarticular tissue of the right hip joint. To prevent the development of septic arthritis of the hip joint, surgical drainage of the abscess cavity and ileocecal resection were immediately performed, after which the patient's condition greatly improved. The resected specimen showed Crohn's ileocolitis with an external fistula in the terminal ileum which was considered to have caused the psoas abscess. Since psoas abscess in Crohn's disease can result in serious complications such as septic arthritis of the hip joint if left untreated, aggressive treatment should be initiated without delay.

Adult↗

[A case of cadaveric kidney transplantation from a heart-beating donor].

We experienced a case of cadaveric kidney transplantation from a heart-beating donor, a 23-year-old man who became brain dead after a traffic accident. The recipient, a 39-year-old man, had been receiving regular hemodialysis since 1990, was admitted to our hospital on June 14, 1999. The number of human lymphocyte antigen mismatches was 3. The left kidney of the donor was transplanted to the right iliac fossa of the recipient 6 hours 28 minutes after the start of in situ cooling of the kidney. For the purpose of immunosuppressive induction, tacrolimus, azathioprine, antilymphocyte globulin, methylpredonisolone and deoxyspergualin were administered. Immediate function was obtained, moreover, the serum creatinine level of the recipient was normalized without hemodialysis. The histopathological examination of the transplant kidney biopsied 1 hour after transplantation revealed little damage of renal tubules. Since no rejection episode was recognized, the patient was discharged on the 48th day after transplantation. This is the third case of cadaveric kidney transplantation from a heart-beating donor after enforcement of the law concerning organ transplantations in Japan.

Adult↗

[Significance of interferon alpha therapy for advanced renal cell carcinoma. Fukushima Renal Cancer Study Group].

We ranked prognostic factors to retrospectively evaluate the clinical significance of interferon alpha (IFN-alpha) therapy in patients with Robson stage IVB renal cell carcinoma. A total of 44 Robson stage IVB renal cancer patients were divided into 2 groups, one with more than 6 months administration of IFN-alpha (3-7 times a week: group A) and another without any IFN-alpha administration. The distribution of these 2 groups was not randomized. In addition to IFN-alpha therapy, survival was analyzed with respect to performance status (PS), mass reductive nephrectomy, concomitant use of other cytotoxic therapies, the number of metastatic organs, growth type, site of metastasis and the period of diagnosis, using a multivariate method with Cox proportional hazards regression. The multivariate analysis showed administration of IFN-alpha to be the most significant factor influencing a good prognosis. Improved survival was also significantly correlated with slow growing type and good PS. Among group A, a significant favorable prognosis was obtained in patients with the responses of no change (NC), partial response (PR) and complete remission (CR) 6 months after initiating administration of IFN-alpha, as well as with good PS and a slow growing type carcinoma. We conclude that IFN-alpha therapy might improve the prognosis of patients with Robson stage IVB renal cell carcinoma, especially, in cases when a greater than NC response is obtained after 6 months administration of IFN-alpha.

Aged↗

Transforming growth factor-beta1 inhibits the growth of primary adult rat hepatocyte cultures by increasing cAMP levels.

We investigated the mechanisms of transforming growth factor-beta1 (TGF-beta1) inhibition on transforming growth factor-alpha (TGF-alpha)-induced DNA synthesis and proliferation in primary cultures of adult rat hepatocytes. TGF-alpha (1.0 ng/ml) produced a 4.2-fold elevation of DNA synthesis during 3 h of culture and a 1. 2-fold increase in nucleus number (proliferation) during 4 h of culture. TGF-beta1 dose dependently inhibited the TGF-alpha-induced hepatocyte DNA synthesis and proliferation: half-maximal inhibition occurred at a TGF-beta1 concentration of 0.08 ng/ml. The inhibitory effects of 1.0 ng/ml TGF-beta1 were almost completely reversed by adenylate cyclase inhibitors, 2,4-dideoxyadenosine (10(-6) M), and somatostatin (3 x 10(-7) M), or by a specific inhibitor of protein kinase A, H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10(-7) M). In addition, while TGF-alpha did not affect the basal cellular adenosine 3',5'-monophosphate (cAMP) levels, TGF-beta1 was found to produce dose-dependent increases in cellular cAMP levels. The cAMP-elevating effects of TGF-beta1 were also reversed by 2,4-dideoxyadenosine (10(-6) M), and somatostatin (3 x 10(-7) M), but not by H-89 (10(-7) M). The present results suggest that the specific mechanisms involved in the growth inhibitory effect of TGF-beta1 on TGF-alpha-induced hepatocyte DNA synthesis and proliferation are via stimulation of adenylate cyclase, which increases intracellular cAMP and subsequently activates protein kinase A.

Adrenergic Agonists↗

Stimulation by transforming growth factor-alpha of DNA synthesis and proliferation of adult rat hepatocytes in primary cultures: modulation by alpha- and beta-adrenoceptor agonists.

We investigated the effects of transforming growth factor alpha (TGF-alpha) on DNA synthesis and proliferation in primary cultures of adult rat hepatocytes and examined the influence of alpha and beta adrenoceptor agonists on the TGF-alpha-induced responses. TGF-alpha (1.0 ng/ml) produced a 4.1-fold elevation of DNA synthesis during 3 h of culture and a 1.2-fold increase in the nucleus number (proliferation) during 4 h of culture at a cell density of 3.3 x 10(4) cells/cm(2). The TGF-alpha-induced hepatocyte DNA synthesis and proliferation were dose-dependent at EC(50) values of 0.36 ng/ml and 0.45 ng/ml, respectively. Hepatocyte DNA synthesis and proliferation induced by 1.0 ng/ml TGF-alpha did not reduce even at higher initial plating densities (5.0 x 10(4) and 1.0 x 10(5) cells/cm(2)). Increasing concentrations of the beta(2) adrenoceptor agonist metaproterenol (10(-7)-10(-6) M) markedly reduced the proliferative effects of TGF-alpha, whereas those of the alpha(2) adrenoceptor agonist 5-bromo-6-[2-imidazolin-2-yl-amino]-quinoxaline (UK-14304; 10(-6)-10(-5) M) and the alpha(1) adrenoceptor agonist phenylephrine (10(-7)-10(-6) M) significantly potentiated the TGF-alpha action. The proliferative effects of TGF-alpha (1.0 ng/ml) were not affected significantly by a monoclonal antiepidermal growth factor receptor antibody (1-100 ng/ml) and were almost completely blocked by specific inhibitors of signal transducers such as genistein (10(-5) M), 1-6[[17beta-3methoxyestra-1,3, 5(10)-trien-17-yl]amino]hexyl]-1H-pyrrol2,5-dione (U-73122; 0(-5) M), wortmannin (5 x 10(-7) M), sphingosine (5 x 10(-6) M), 2'-amino-3'-methoxyflavone (PD98059; 5 x 10(-5) M), and rapamycin (10 ng/ml). These results suggest that among the elements that link signals of cell surface receptor to the nucleus, the proliferative action of TGF-alpha is mediated, at least, by tyrosine kinase, phospholipase C, phosphatidylinositol 3-kinase, protein kinase C, mitogen-activated protein kinase kinase, and ribosomal protein p70 S6 kinase.

Adrenergic Antagonists↗

Effects of insulin-like growth factor I and II on DNA synthesis and proliferation in primary cultures of adult rat hepatocytes.

We compared the effects of insulin-like growth factor I (IGF-I) and II (IGF-II) on DNA synthesis and proliferation and investigated various signal transduction mechanisms involved in insulin-like growth factor-induced mitogenesis in primary cultures of adult rat hepatocytes. IGF-I stimulated hepatocyte DNA synthesis and proliferation with an EC50 of 75 ng/ml within 4 h of culture. These effects were sensitive to the IGF-I concentration and cell density. Hepatocyte proliferation induced by IGF-I was potentiated by metaproterenol (10(-6) M) as well as by 8-bromo-cAMP, phorbol 12-myristate 13-acetate (PMA; 10(-8) M) and was inhibited by U-73122 (1-(-[[17beta-3-methoxyestra-1,3,5(10)-triene-17-yl]amino]hexyl]-+ ++1Hpyrrol-2,5-dione)), genistein, wortmannin, PD98059 (2'-amino-3'-methoxyflavone) and rapamycin. The IGF-I effect was independent of pertussis toxin (100 ng/ml). IGF-II also dose dependently stimulated hepatocyte DNA synthesis and proliferation with an EC50 of 0.75 ng/ml within 4 h of culture. However, these effects were not dependent on the initial plating density. The stimulatory effects of IGF-II were potentiated by UK-14304 (5-bromo-6-[2-imidazolin-2-ylamino]-quinoxaline) (10(-5) M) and inhibited by phenylephrine, PMA, metaproterenol, 8-bromo-cAMP, PD98059, rapamycin, and pertussis toxin. The IGF-II effects were not affected by genistein, U-73122, and wortmannin. These results suggest that IGF-I and IGF-II rapidly stimulate the DNA synthesis and proliferation of adult rat hepatocytes by separate mechanisms.

Animals↗

Expression of alpha2- and beta2-adrenergic responses by hepatocyte growth factor and platelet-derived growth factor in primary cultures of adult rat hepatocytes.

We investigated the effects of hepatocyte growth factor (HGF) and platelet-derived growth factor (PDGF) on the expression of alpha2- and beta2-adrenergic responses in primary cultures of adult rat hepatocytes. HGF (1 and 5 ng/ml) rapidly stimulated the expression of beta2-adrenergic responses and significantly increased alpha2-adrenergic responses with a maximal response at 21 h. The stimulatory effects of HGF were reduced dependent on the initial plating density and were completely blocked by cycloheximide (5 microM). On the other hand, PDGF (10 ng/ml) significantly increased the beta2-adrenergic response, but only slightly increased the alpha2-adrenergic responses. Expression of the alpha2- and beta2-adrenergic responses by PDGF was independent of the initial plating density. The expression of these responses was blocked by cycloheximide (5 microM). Northern blot analysis of the hepatocyte mRNA showed increased expression induced by the HGF and PDGF of the both alpha2- and beta2-adrenergic receptor mRNA, and this expression was inhibited by actinomycin D (5 ng/ml). These results indicate that the expression of alpha2- and beta2-adrenergic responses produced by these two growth factors is regulated differently by the cell density of the primary cultures. The results suggest that the expression of alpha2- and beta2-adrenergic responses is mediated through increased synthesis of these receptor proteins.

Adrenergic alpha-2 Receptor Agonists↗

[Inhibitory effects of shimotsu-to, a traditional Chinese herbal prescription, on ultraviolet radiation-induced cell damage and prostaglandin E2 release in cultured Swiss 3T3 cells].

We have investigated the effects of Shimotsu-to, a traditional Chinese herbal prescription (Kampo medicine), on ultraviolet (UV) radiation-induced cell damage and prostaglandin E2 (PGE2) release in cultured Swiss 3T3 cells to examine the anti-inflammatory mechanism of Shimotsu-to. Short-term UV irradiation significantly induced cell damage and stimulated PGE2 release in Swiss 3T3 cells cultured for 4 h. The UV-radiation-induced cell damage and the stimulation of PGE2 release were significantly suppressed by the treatment with Shimotsu-to. Among the single crude drug components of Shimotsu-to, Rehmanniae Radix showed significant protective effects against UV-radiation-induced cell damage and PGE2 release. Other synthetic anti-inflammatory agents, such as dexamethasone, dipotassium glycyrrhizinate and allantoin also protected against UV-induced cell damage and inhibited PGE2 release in cultured Swiss 3T3 cells. These results suggest that the anti-inflammatory mechanism of Shimotsu-to against UV-irradiated erythema (acute skin inflammation) in guinea pigs in vivo may be mediated by the inhibition of PGE2 release from cutaneous target cells.

3T3 Cells↗