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Biomedical subjects

A Ito

Publications and source records attributed to A Ito.

At least 19 recordsLinked to original sources
PubMed1996

Tumor necrosis factor alpha (TNFalpha) induces pro-matrix metalloproteinase 9 production in human uterine cervical fibroblasts but interleukin 1alpha antagonizes the inductive effect of TNFalpha.

We have examined the regulation of precursor of matrix metalloproteinase 9 (proMMP-9)/progelatinase B production by tumor necrosis factor alpha (TNFalpha) and interleukin 1alpha (IL-1alpha) using human uterine cervical fibroblasts. TNFalpha, but not IL-1alpha, induces the production of proMMP-9 in the cervical cells. IL-alpha, however, suppresses the TNFalpha-induced proMMP-9 production. 12-0-tetradecanoylphorbol 13-acetate (TPA) also stimulates the cervical cells to produce proMMP-9, and IL-1alpha synergistically enhances its production. TNFalpha-induced proMMP-9 production is not mediated by protein kinase C (PKC), whereas the effect of IL-1alpha is through PKC. By contrast, proMMP-3/prostromelysin 1 is up-regulated by TNFalpha or TPA in the presence of IL-1alpha, whose modulation is PKC-dependent. The suppressive effect of IL-1alpha on the TNFalpha-induced proMMP-9 production is a new biological effect of IL-1 on MMP production.

Alkaloids↗
PubMed1996

Conformational change in DNA induced by cationic bilayer membranes.

The effect of synthetic cationic lipids on the structure of DNA was studied. The fluorescence enhancement of ethidium bromide on intercalation into DNA was suppressed by the addition of bilayer-forming lipids, but not by micellar ones. Results on the fluorescence depolarization index suggest that ethidium bromide is not released from DNA by lipids intercalated into DNA. CD spectra of the DNA-lipid complexes revealed that the structure of DNA was changed only by bilayer-forming lipids at temperatures lower than their Tc values. Thus, the conformation of DNA is forced to change by cationic lipids forming the rigid bilayer membrane so that ethidium bromide fluorescence might be reduced, and the conformation can be controlled by selection of the appropriate lipid and temperature.

Cations↗
PubMed1996

Coronary artery spasm does not depend on the intracellular calcium store but is substantially mediated by the protein kinase C-mediated pathway in a swine model with interleukin-1 beta in vivo.

BACKGROUND: The intracellular mechanism for coronary artery spasm is still unknown. Since the protein kinase C (PKC)-mediated pathway and Ca2+ release from sarcoplasmic reticulum (SR) are important intracellular mechanisms of vascular smooth muscle contraction, we examined the possible role of these two mechanisms in the pathogenesis of coronary spasm in our swine model in vivo. METHODS AND RESULTS: In 25 pigs, interleukin-1 beta (IL-1 beta) was applied chronically to the coronary arteries from the adventitia to induce an inflammatory/proliferative lesion. Two weeks after the operation, either intracoronary serotonin or histamine repeatedly induced coronary spasm at the IL-1 beta-treated site. At those spastic sites, phorbol-12, 13-dibutyrate, a PKC-activating phorbol ester, also induced coronary spasm, which was blocked by pretreatment with the PKC inhibitors staurosporine and sphingosine. Serotonin- and histamine-induced coronary spasm was also significantly inhibited by pretreatment with staurosporine, sphingosine, or nifedipine (an L-type Ca2+ channel antagonist) but not by ryanodine (an inhibitor of Ca(2+)-induced Ca2+ release from SR) or thapsigargin (an inhibitor of Ca(2+)-ATPase of SR). Bay K 8644 (an L-type Ca2+ channel agonist) also induced coronary spasm at the IL-1 beta-treated site, which was significantly inhibited by pretreatment with staurosporine, sphingosine, and nifedipine. In contrast, coronary vasoconstriction induced by prostaglandin F2 alpha was not affected by pretreatment with staurosporine or sphingosine but was significantly inhibited by pretreatment with ryanodine, thapsigargin, or nifedipine. CONCLUSIONS: These results suggest that (1) PKC activation largely accounts for the serotonin- and histamine-induced coronary spasm; (2) at the spastic site, the calcium influx through L-type Ca2+ channels may be augmented via the PKC-mediated pathway; and (3) the Ca2+ release from the SR into the cytosol may not play a primary role in coronary spasm.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1996

Degradation of interleukin 1beta by matrix metalloproteinases.

Matrix metalloproteinases (MMPs) and interleukin 1 (IL-1) are implicated in inflammation and tissue destruction, where IL-1 is a potent stimulator of connective tissue cells to produce the extracellular matrix-degrading MMPs. Here, we report that IL-1beta, but not IL-1alpha, is degraded by MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin 1), and MMP-9 (gelatinase B). This degradation was effectively blocked by tissue inhibitor of metalloproteinases (TIMP)-1. When IL-1beta was treated with MMPs it lost the ability to enhance the synthesis of prostaglandin E2 and pro-MMP-3 in human fibroblasts. The primary cleavage site of IL-1beta by MMP-2 was identified at the Glu25-Leu26 bond. These results suggest that IL-1beta stimulates connective tissue cells to produce MMPs, but activated MMPs in turn negatively regulate the activity of IL-1beta.

Amino Acid Sequence↗
PubMed1996

Disialosyl galactosylgloboside as an adhesion molecule expressed on renal cell carcinoma and its relationship to metastatic potential.

Aberrant glycosylation expressed in specific types of human cancer may define stage, direction, and fate of tumor progression. Well-studied examples are expression of sialosyl-Lewis(x) or sialosyl-Lewis(a) in colorectal carcinoma and histo-blood group A and H/Le(y) in lung cancer. In renal cell carcinoma (RCC), expression of sialosyl-Lewis(x) has no correlation with metastatic potential. Clinicopathological studies have revealed that the degree of expression of disialosyl galactosylgloboside (DSGG) and monosialosyl galactosylgloboside is correlated with metastatic potential (to lung and lymph nodes) of RCC and inversely correlated with patient survival. In the present study, we compared the adhesion of RCC lines to sections of various tissues measured by Stamper-Woodruff assay and other similar assays under dynamic flow conditions. Of the eight RCC lines tested, only TOS-1 (which expresses DSGG) bound strongly to lung tissue sections. TOS-1 did not bind to sections of liver, kidney, or lymph nodes. In the same eight RCC lines, we also compared expression of DSGG and monosialosyl galactosylgloboside (reflected by reactivity with RM1 and RM2), overall ganglioside patterns, and correlation with lung tissue-binding ability. Under both static and dynamic flow conditions, the binding of TOS-1 cells to lung alveolar tissue was correlated with their DSGG expression, i.e., the binding was inhibited by RM2 but not by RM1. This binding was also inhibited by sialidase but not by EDTA (i.e., it was CA 2+ independent). The other seven cell lines (TOS-2, TOS-M, SMKT-R1, -R2, -R3, and -R4, and ACHN), which do not express DSGG, showed much weaker adhesion to lung tissue. None of the eight cell lines showed E- or P-selectin-dependent adhesion. These results suggest the existence of a yet-uncharacterized sialoadhesive receptor++ that specifically recognizes DSGG. This receptor could be the binding target in RCC metastasis to lung.

Carbohydrate Conformation↗
PubMed1996

Translational augmentation of pro-matrix metalloproteinase 3 (prostromelysin 1) and tissue inhibitor of metalloproteinases (TIMP)-1 mRNAs induced by epidermal growth factor in human uterine cervical fibroblasts.

The mechanisms by which epidermal growth factor (EGF) enhances the production of pro-matrix metalloproteinase 3 (proMMP-3/prostromelysin 1) and tissue inhibitor of metalloproteinases (TIMP)-1 were investigated using human uterine cervical fibroblasts. The treatment of the cells with EGF for 24 h resulted in about 5-6-fold increase in the production of proMMP-3 and TIMP-1 compared with the untreated control cells. This increase was accompanied by an increase of proMMP-3 and TIMP-1 mRNAs. However, an about 3- and 2-fold increase in the production of proMMP-3 and TIMP-1, respectively, was observed as early as 1 h after the treatment of the cells with EGF, and it was not accompanied by any apparent increase in proMMP-3 and TIMP-1 mRNAs. This early effect of EGF on the enhanced production of proMMP-3 and TIMP-1 was not inhibited by actinomycin D, even though actinomycin D inhibited the synthesis of the total RNA in both the EGF-treated and untreated cells. These results indicate that EGF enhances the apparent production of proMMP-3 and TIMP-1 by two mechanisms: one by the accelerated translation of their mRNAs; and the other by the enhanced transcription of their genes. The former event takes place much earlier than the latter.

Cells, Cultured↗
PubMed1996

Chronic treatment with interleukin-1 beta induces coronary intimal lesions and vasospastic responses in pigs in vivo. The role of platelet-derived growth factor.

Studies in vitro have suggested that inflammatory cytokines may play an important role in the pathogenesis of atherosclerosis. However, little is known about their effects in vivo. Thus, the present study was designed to determine in vivo what histological and functional changes may be induced by chronic treatment with IL-1 beta, one of the major inflammatory cytokines, and also to clarify what mechanisms are involved in those changes. Under aseptic conditions, proximal segments of the left porcine coronary arteries were gently wrapped with cotton mesh absorbing Sepharose beads either with or without recombinant human IL-1 beta. From 1 to 4 wk after the operation, coronary vasospastic responses to intracoronary serotonin or histamine were noted at the IL-1 beta-treated site but not at the control site. Histologically, intimal thickening was greater at the IL-1 beta-treated site than at the control site. Those functional and histological changes induced by the chronic treatment with IL-1 beta were significantly inhibited by the simultaneous treatment with a neutralizing antibody to either IL-1 beta or PDGF. These results indicate that chronic treatment with Il-1 beta induces coronary intimal lesions and vasospastic responses in porcine coronary arteries in vivo and also suggest that these changes are substantially mediated by PDGF.

Animals↗
PubMed1996

Molecular typing of Helicobacter pylori: differences in pathogenicity among diverse strains.

Helicobacter pylori appears to be a species with strain diversity, according to studies carried out using various molecular biological techniques. Differences in pathogenicity caused by the strain diversity of H. pylori were therefore investigated. Two hundred and thirty strains were divided into four types by polymerase chain reaction-restriction fragment length polymorphism, and their relationship to endoscopic diagnosis, ammonia concentration of gastric juice, and urease activity were assessed. With regard to incidence by type, patients infected with type 1, type 2, and type 3 exhibited the highest incidences of gastric ulcer, duodenal ulcer, and gastritis, respectively. The urease activity of type 2 was significantly lower than that of types 1 and 3 (P < 0.05). These observations suggest differences in pathogenicity due to the strain diversity of H. pylori. However, the diversity of diseases related to H. pylori is also presumed to be caused by both the diversity of H. pylori strains and differences in the host immunological reaction. Future studies should be directed toward clarifying the entire pathogenic mechanism of H. pylori infection.

Bacterial Typing Techniques↗
PubMed1996

Long-term neuroleptic treatments counteract dopamine D2 agonist inhibition of adenylate cyclase but do not affect pertussis toxin ADP-ribosylation in the rat brain.

We have investigated the response of adenylate cyclase to GTP and to dopamine (DA) in striatal membranes of rats treated for 3 weeks with chlorpromazine or haloperidol, and further measured the level of Gi (an inhibitory GTP-binding protein) or Go (a similar GTP-binding protein of unknown function) in 3 areas (cerebral cortex, striatum and hippocampus) utilizing pertussis toxin-catalyzed ADP ribosylation. In saline-treated control membranes, GTP exerted a biphasic effect on basal and DA-stimulated enzyme activity--peak levels of stimulation by DA plus GTP were observed at 1 microM GTP. Conversely, dopaminergic inhibitory effects at 10-100 microM GTP were completely attenuated in chlorpromazine or haloperidol-treated membranes. D2 inhibition of adenylate cyclase by the selective D2 agonist PPHT was also attenuated due to these neuroleptic treatments, while an increase in D2 receptor binding was observed. The pertussis toxin ADP-ribosylation of G-proteins (Gi/Go) did not differ significantly in any area. This indicates that long-term neuroleptic treatments increased D2 receptor binding, but attenuated D2 inhibition of adenylate cyclase, and exercised no influence on pertussis toxin ADP-ribosylation.

Adenosine Diphosphate Ribose↗
PubMed1996

Measurement of soft X-ray absorption spectra and elemental analysis in local regions of mammalian cells using an electronic zooming tube.

Direct measurement of absorption spectra for minute areas (2 microns x 2 microns) in a dried mammalian cell was attempted using X-ray contact images of a whole cell. The wavelength region used ranged from 1.5 to 10nm covering the absorption edges of the major cellular elements. The measurements were achieved taking advantage of synchrotron radiation as a tuneable light source and an electronic zooming tube as an X-ray detector with a high spatial resolution. The spectra in every intracellular area exhibited marked absorption changes at the absorption edges of carbon, nitrogen and oxygen, while minor but significant changes for iron and calcium were observed, particularly in the cytoplasmic areas. These results reveal the different spatial distributions of the constituent elements in a cell.

Animals↗
PubMed1996

Regulation of Bcl-2 protein expression in human neuroblastoma SH-SY5Y cells: positive and negative effects of protein kinases C and A, respectively.

The regulatory mechanism of Bcl-2 protein expression was investigated in SH-SY5Y cells, the human neuroblastoma cell line that expresses natively Bcl-2 proteins. WHen the cells were treated with 12-O-tetradecanoylphorbol 13-acetate (TPA) or retinoic acid, the level of Bcl-2 protein was increased compared with the control. These effects were inhibited by pretreatment with a protein kinase C (PKC) inhibitor, staurosporine or calphostin C. The level of Bcl-2 protein was also increased by treatment with carbachol, a muscarinic acetylcholine receptor (mAChR) agonist, and the effect were also inhibited by pretreatment with staurosporine or calphostin C. An addition, a carbachol-induced increase in Bcl-2 protein levels and a transient elevation of [Ca2+]i were inhibited by pretreatment with 4-DAMP (4-diphenylacetoxy-N-methylpiperidine), an m3 mAChR antagonist. In contrast, the level of Bcl-2 protein was decreased by treatment with dibutyryl cAMP (diBu-cAMP), forskolin, or cholera toxin, and the effects of diBu-cAMP were inhibited by pretreatment with a protein kinase A (PKA) inhibitor, H-89. From these results, we suggest that the expression of Bcl-2 proteins is regulated by PKC and PKA in positive and negative manners, respectively, in SH-SY5Y cells. Furthermore, the nucleosomal DNA fragmentation induced by serum depletion for 4 h was observed in SH-SY5Y cells when the level of Bcl-2 protein was down-regulated by treatment with 1 mM diBu-cAMP for 3 days, although the DNA fragmentation by serum depletion for 4 h was not observed in nontreatment cells, indicating that Bcl-2 proteins whose expression is regulated by PKC and PKA play important roles in serum depletion-induced apoptosis.

Apoptosis↗
PubMed1996

Changes in serum fibrogenesis markers during interferon therapy for chronic hepatitis type C.

We serially measured the levels of serum N-terminal peptide of type III procollagen (PIIINP), the 7S domain of type IV collagen (IV-7S), and hyaluronate (HA) before (0 month), at the end (6 months), and 24 weeks after the end of interferon therapy (12 months) in patients with chronic hepatitis type C to estimate the effects of interferon alfa (IFN-alpha) on serum levels of hepatic fibrogenesis markers. One hundred twenty-one patients with chronic hepatitis type C received intramuscular injection of 6 million U of natural IFN-alpha for 24 weeks. Patients were divided into three groups: sustained complete response (CR-S), complete response with rebound (CR-R), and nonresponse (NR). Serum PIIINP, IV-7S, and HA levels were significantly decreased and reached normal levels at 12 months in CR-S; only IV-7S levels were significantly decreased at 12 months in CR-R, whereas these levels remained abnormally high in the NR. These results suggest that IFN-alpha therapy could lower the levels of serum hepatic fibrogenesis markers along with improvements in hepatic inflammation.

Adult↗
PubMed1996

Influence of paternal (252) Cf neutron exposure on abnormal sperm, embryonal lethality, and liver tumorigenesis in the F(1) offspring of mice.

Experiments were conducted to determine whether neutron-induced genetic damage in parental germline cells can lead to development of cancer in the offspring. Seven-week-old C3H male mice were irradiated with (252) Cf neutrons at a dose of 0, 50, 100, or 200 cGy. Two weeks or three months after irradiation, the male mice were mated with virgin 9-week-old C57BL females. Two weeks after irradiation, the irradiated male mice showed an increased incidence of sperm abnormalities, which led to embryo lethalities in a dose-dependent manner when they were mated with unirradiated female mice. Furthermore, liver tumors in male offspring of male mice in the 50 cGy group were significantly increased in 19 of 44 (43.2%) animals, in clear contrast to the unirradiated group (1 of 31; 3.2%) (P < 0.01). In the 100 cGy group, 6 of 39 (15%) mice had lesions. At 3 months after irradiation abnormal sperm and embryonal lethality were not significantly increased. The incidences of liver tumors in male offspring from the 50 cGy, 100 and 200 cGy groups were 6 of 20 (30%), 5 of 22 (23%) and 1 of 19 (5%), respectively, which are not significantly increased compared with the control. It is concluded that increased hepatic tumor risk in the F(1) generation may be caused by genetic transmission of hepatoma-associated trait(s) induced by (252) Cf neutron irradiation.

Animals↗
PubMed1996

Gastric tumorigenicity of 1,2-dimethylhydrazine on the background of gastric intestinal metaplasia induced by X-irradiation in CD (SD) rats.

Five-week-old male CD (SD) rats were X-irradiated with a total of 20 Gy in 2 equal fractions with a 3-day interval. After the second irradiation, rats were fed normal diet supplemented with 1% sodium chloride, which is known to increase intestinal metaplasia. 1,2-Dimethylhydrazine (DMH) solution was injected i.m. into the back musculature at a dose of 20 mg/kg body weight weekly for 10 weeks, beginning 20 weeks after the final irradiation. Twelve months after the initial carcinogen treatment, gastric tumors in the glandular stomach were observed in 2 (3 lesions) of 30 animals in the X-irradiated and DMH-treated group fed diet supplemented with 1% sodium chloride. No gastric tumors were observed in the group which excluded X-irradiation from the experimental protocol.

1,2-Dimethylhydrazine↗
PubMed1996

[Hansenula anomala fungemia in a patient undergoing IVH-treatment with ascending colon carcinoma].

A case of catheter-related fungemia due to Hansenula anomala is reported. A 61-year-old male was diagnosed as having stage 3 ascending colon carcinoma stenosing the colon severely and was admitted to our hospital to receive an operation of the carcinoma. Just after admission, an intravenous hyperalimentation (IVH) catheter was inserted and IVH was started to prevent development of ileus and to prepare for laparotomy. Nine days later, he developed a fever. On the next day, the IVH catheter was removed and cultures of blood and the catheter revealed the presence of yeast-like organisms that were identified as H. anomala. Laboratory data showed hypogranulocytemia, slight disturbances of liver and kidney, a prolongation of PT, an increase of FDP and positive reaction of candida antigen by CAND-TEC. He improved after the removal of the catheter, and treatment with intravenous infusion of fluconazole 2 days after the removal was thought to be useful for recovery and to prevent the reappearance of infection though susceptibility to fluconazole was not good. Human infections due to H. anomala are rare and this is the 8th case of H. anomala fungemia in Japan. From this report and a review of the literature, risk factors for developing this fungemia include the use and abuse of central venous catheters such as IVH-catheter. It appears that H. anomala has recently emerged as a potential pathogen in the immunocompromised hosts and patients after insertion of central venous catheters and that these organisms should be added to the growing list of unusual fungal pathogens in these patients.

Colonic Neoplasms↗
PubMed1996

[Effects of long-term physical training on body composition, cardiovascular function, and serum lipids in mildly obese middle-aged subjects].

To investigate the effects of long-term physical exercise on humans, body composition, cardiovascular function and serum lipids were measured for a training period of 20 months in 8 men and 8 women, aged 36-67 years who were mildly obese. The subjects participated in physical training for 90 minutes about twice a week for 20 months. The intensity of training was at most 60% VO2max for each subject as calculated by karvonen's formula. The results are summarized as follows: (1) Body weight and estimated body fat weight decreased from baseline after the training in both sexes. The percentage decreases in body weight and estimated body fat weight in men were about threefold those in women. (2) Following the training, heart rate, blood pressure and rate pressure product (RPP) at rest had significantly decreased from initial levels in both sexes. (3) Following the training, the physical work capacity at a heart rate of 150bpm significantly increased, and systolic blood pressure at the heart rate of 150bpm significantly decreased from baseline levels in both sexes. (4) Following the training, the serum HDL-cholesterol and HDL-/total-cholesterol ratio significantly increased from baseline, and serum triglycerides and total cholesterol also significantly decreased from baseline levels in both sexes. These results suggest that long-term physical training with moderate intensity improves body composition, cardiovascular function and serum lipids in mildly obese middle-aged men and women, and reduces the risks for coronary heart disease.

Adult↗
PubMed1996

Intestinal ciliates found in the feces of Japanese native Tokara pony, with the description of a new genus and a new species.

The composition of intestinal ciliates excreted in the feces of 20 Tokara native ponies kept in Iriki farm of Kagoshima University was surveyed. Eleven genera consisting of 18 species were identified based on the description of Strelkow. One new genus including a new species, Wolskana tokarensis n. gen., n. sp., of the family Buetschliidae was recognized and described. The average ciliate density of all horses was 13.8 x 10(3)/ml. Those of stallions (n = 5), mares (n = 11) and foals (n = 4) were 3.9, 16.1 and 43.3 x 10(3)/ml respectively. The value of stallions was significantly lower and that of foals higher than that of mares. Brillouin's diversity index of all horses was 1.554 on average. The index of stallions, 1.470, was significantly lower than those of mares, 1.539, and foals, 1.698. The average number of species per host was 11.7.

Aging↗