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Biomedical subjects

Y Homma

Publications and source records attributed to Y Homma.

At least 289 records · Page 16Linked to original sources
PubMed1986

Effects of formalin-induced injuries on urinary bladder carcinogenesis.

In multistage carcinogenesis, promotion is a long-term or repeated growth stimulation of initiated cells. Possible effects of regenerative hyperplasia induced by repeated intravesical instillation of 0.3% formalin solution on urinary bladder carcinogenesis were examined using heterotopically transplanted rat urinary bladders (HTBs) initiated by N-methyl-N-nitrosourea. The HTB system was chosen because in this system, transient generalized hyperplasia lasting less than a week can be induced readily and repeatedly by intravesical instillation of the formalin solution. No statistically significant tumor enhancement was observed after 15 formalin treatments administered in 30 weeks. It appears that regenerative cytotoxic stimuli, even multiple, may have no significant tumor-promoting activity. Discussed is the possibility that mild and, more importantly, persistent non-cytotoxic stimuli may be more effective as tumor promoters.

Animals↗
PubMed1986

Transient and persistent hyperplasia in heterotopically transplanted rat urinary bladders induced by formalin and foreign bodies.

The effects of formalin instillation or teflon bead insertion on heterotopically transplanted rat urinary bladders (HTBs) were investigated. A single instillation of 0.3 per cent formalin dissolved in 0.9 per cent NaCl into HTBs induced multifocal superficial ulcers which were quickly repaired by lateral spreading of regenerating cells migrating from the adjacent mucosa. This was associated with a sharp increase in labeling index (10-30 per cent) on days 1 and 2, followed by focal mild (up to five cell layers) simple hyperplasia (SH) on days 4 and 7. Repeated weekly instillation of formalin for 30 weeks induced only focal mild epithelial hyperplasia. Six weekly instillations of urine one day after formalin administration slightly enhanced the formalin-induced rise in labeling index. Insertion of teflon beads caused extensive diffuse remarkable changes, especially in the presence of urine: multifocal to diffuse SH (four to eight cell layers) and multifocal papillary or nodular hyperplasia was observed by six weeks. The results indicate that responses to formalin instillation are acute and transient, while reactions to bead insertion are persistent. In both cases, presence of urine appeared to enhance hyperplastic changes. These models of bladder injury, by inducing two different types of reactions in the bladder, may be useful in examining the role of trauma in bladder carcinogenesis.

Animals↗
PubMed1986

Translocation of protein kinase C in human leukemia cells susceptible or resistant to differentiation induced by phorbol 12-myristate 13-acetate.

We investigated the possible relationship between the susceptibility of cells to differentiation induced by phorbol 12-myristate 13-acetate (PMA) and the subcellular translocation of calcium- and phospholipid-dependent protein kinase (protein kinase C) activity from the cytosol to the membrane. These two events were analyzed in a number of human leukemia cell lines, including four cell variants of the promyelocytic cell line HL-60 that exhibit different degrees of susceptibility to PMA-induced differentiation. The phenotype of the differentiated cells was characterized by increased reactivity with monoclonal antibodies against maturation-specific cell surface antigens, increased nonspecific esterase activity, and acquisition of morphological cell maturation. Analysis of the subcellular distribution of protein kinase C activity in each of these cell types revealed that 90% of the kinase activity was present in the cytosolic fraction, with the remaining activity in the membrane fraction. Treatment of the differentiation-susceptible cells with 160 nM PMA resulted, within 5 min after treatment, in a greater than 60% decrease in protein kinase C activity in the cytosolic fraction and a greater than 1500% increase in the activity in the membrane fraction. No such subcellular redistribution of protein kinase C activity was found after treatment of the differentiation-resistant cells. On the basis of these findings, we suggest that the process of subcellular translocation of protein kinase C activity, initiated after the binding of PMA to this kinase, is required for the induction of cell differentiation by this phorbol diester.

Cell Compartmentation↗
PubMed1986

Production mechanism of crackles in excised normal canine lungs.

Lung crackles may be produced by the opening of small airways or by the sudden expansion of alveoli. We studied the generation of crackles in excised canine lobes ventilated in an airtight box. Total airflow, transairway pressure (Pta), transpulmonary pressure (Ptp), and crackles were recorded simultaneously. Crackles were produced only during inflation and had high-peak frequencies (738 +/- 194 Hz, mean +/- SD). During inflation, crackles were produced from 111 +/- 83 ms (mean +/- SD) prior to the negative peak of Pta, presumably when small airways began to open. When end-expiratory Ptp was set constant between 15 and 20 cmH2O and end-expiratory Ptp was gradually reduced from 5 cmH2O to -15 or -20 cmH2O in a breath-by-breath manner, crackles were produced in the cycles in which end-expiratory Ptp fell below -1 to 1 cmH2O. This pressure was consistent with previously known airway closing pressures. When end-expiratory Ptp was set constant at -10 cmH2O and end inspiratory Ptp was gradually increased from -5 to 15 or 20 cmH2O, crackles were produced in inspiratory phase in which end-inspiratory Ptp exceeded 4-6 cmH2O. This pressure was consistent with previously known airway opening pressures. These results indicate that crackles in excised normal dog lungs are produced by opening of peripheral airways and are not generated by the sudden inflation of groups of alveoli.

Animals↗
PubMed1986

Incidence of serum-precipitating antibodies to farmer's lung antigens in Hokkaido.

The prevalence of serum-precipitating antibodies to Micropolyspora faeni and Thermoactinomyces vulgaris was studied by immunoelectrophoresis in 442 dairy farmers living in Hokkaido, the northernmost district of Japan. The prevalence rates of antibodies to M. faeni and T. vulgaris were 24.2 and 11.6%, respectively. The rate of antibodies to M. faeni was higher among females than males. This difference may be due to the large number of nonsmokers among females. Prevalence of antibodies to M. faeni or M. faeni and T. vulgaris was associated with a higher hay acreage and longer working hours per day in the cowshed, and not to the size of the dairy herd. These results were partly different from those reported from other countries.

Adolescent↗
PubMed1986

Dissociation of protective immunity against tuberculosis and tuberculin hypersensitivity at a level of lymphokines.

On the basis of present knowledge on the purification and the action mechanisms of macrophage regulating lymphokines, as summarized in Table VIII, tuberculosis immunity and tuberculin delayed type hypersensitivity may be dissociated at a level of responsible lymphokines. Table VIII. Dissociation of TB-IMM and DTH at a level of lymphokine 1. Purification of mediators resulted in separation of MIF/MAF and MCF 2. Anti-MIF antibody has no suppression of MCF reaction 3. Lipid metabolisms of macrophages stimulated with MIF/MAF and MCF are different 4. MIF/MAF suppresses MCF-reaction through monokines.

Animals↗
PubMed1986

Prevention of inhibitory effects of alpha-difluoromethylornithine on rat urinary bladder carcinogenesis by exogenous putrescine.

We previously demonstrated that repeated instillation of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), inhibits (or retards) urinary bladder carcinogenesis in rats. Since ODC catalyzes the first step in polyamine synthesis, the inhibition of polyamine formation may be responsible for tumor inhibition by DFMO. The present experiment was conducted using male Fischer rats with a heterotopically transplanted urinary bladder (HTB) to determine whether the effects of DFMO are prevented by exogeneous Pu. HTBs were treated with 0.25 mg of N-methyl-N-nitrosourea (MNU) once a week for 3 weeks and the animals were then arbitrarily divided into 6 groups. Beginning one week following the last MNU treatment, all rats received twice a week instillation (0.5 ml each) as follows: Group 1 rats, normal rat urine; Group 2, 2% DFMO in urine; Group 3, 250 microM Pu and 2% DFMO in urine; Group 4, 250 microM Pu in urine; Group 5, urine for 10 weeks followed by 2% DFMO in urine; and Group 6, urine for 10 weeks followed by 250 microM Pu and 2% DFMO in urine. At 10 weeks following the last MNU instillation 5 rats from each of Groups 1 through 4 were killed for determination of urothelial polyamine levels. An additional 4 rats of Group 1 were killed at 10 weeks for histological examination. All remaining rats were killed 20 weeks after the last MNU instillation. Polyamine levels showed no significant difference among the 4 groups. The incidence of carcinoma was significantly lower in the group treated with DFMO (p less than 0.001, Group 1 vs Group 2), confirming our previous observation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Evidence for differential activation of arachidonic acid metabolism in formylpeptide- and macrophage-activation-factor-stimulated guinea-pig macrophages.

Alterations of phospholipid and arachidonic acid metabolism were studied by treatment of guinea-pig peritoneal-exudate macrophages with chemotactic peptide, formylmethionyl-leucylphenylalanine (fMet-Leu-Phe) and macrophage activation factor (MAF). The chemotactic peptide caused a rapid rearrangement in inositol phospholipids, including a breakdown of polyphosphoinositides within 30s, followed by a resultant formation of phosphatidylinositol (PI), diacylglycerol, phosphatidic acid and non-esterified arachidonic acid within 5 min. In addition to these sequential alterations, arachidonic acid was released mainly from PI. On the other hand, MAF induced a slow liberation of arachidonic acid, mainly from phosphatidylethanolamine (PE) and phosphatidylcholine (PC) by phospholipase A2 after the incubation period of 30 min, but not any rapid changes in phospholipids. Treatment of macrophages for 15 min with fMet-Leu-Phe produced the leukotrienes (LTs) B4, C4 and D4, prostaglandins (PG) E2 and F2 alpha and thromboxane (TX) B2. In contrast, MAF could not stimulate the production of arachidonic acid metabolites during the incubation period of 15 min, but could enhance that of PGE2, PGF2 alpha, TXB2 and hydroxyeicosatetraenoic acids at 6 h. However, the stimulated formation of LTs was not detected at any time. These results indicate that the effects of fMet-Leu-Phe on both phospholipid and arachidonic acid metabolism are very different from those mediated by MAF.

Animals↗
PubMed1985

Epidermal growth factor stimulates diacylglycerol kinase in isolated plasma membrane vesicles from A431 cells.

We have examined the effect of epidermal growth factor(EGF) on three kinds of kinases activities, phosphatidylinositol(PI) kinase, phosphatidylinositol 4-phosphate[PI(4)P] kinase and diacylglycerol(DG) kinase that make important roles in the regulation of inositol phospholipids metabolism. When isolated plasma membrane vesicles from A431 cells were incubated at 30 degrees C with [gamma-32P]ATP and exogenously added DG, EGF enhanced the activity of DG kinase approximately 2-fold. This stimulation is found to be dose-dependent with a half maximal activation at 1 nM. In this case, EGF increased Vmax without changing Km Value for ATP or DG. Although this activation was observed in the absence of detergent, it was more evident when membrane vesicles were treated with 1 mM deoxycholate. Interestingly, the effect of EGF was only detected in magnesium containing medium. The use of manganese instead of magnesium diminished the stimulatory effect in either condition, presence or absence of deoxycholate. On the other hand, the stimulation of PI kinase or PI(4)P kinase activity was not caused by EGF. These results suggest that DG kinase activation by EGF makes important roles in cellular responses leading to cell growth.

Cell Membrane↗
PubMed1985

Role of enhanced inositol phospholipid metabolism in neutrophil activation.

When guinea pig neutrophils were stimulated with chemotactic peptide [formylmethionyl-leucyl-phenylalanine (fMLP)], a marked release of lysosomal enzyme and production of superoxide anion were detected. The breakdown of phosphatidylinositol 4,5-bisphosphate (TPI) and the subsequent formation of diacylglycerol, phosphatidic acid and free arachidonic acid also occurred during the processes. Ca2+ ionophore A23187 caused an evident secretion of lysosomal enzyme but no superoxide anion production. Ca2+ ionophore also caused TPI breakdown to diacylglycerol although this breakdown was not as significant as that detected by fMLP. The tumor promotor tetradecanoylphorbol acetate (TPA), which is a strong activator of superoxide anion production but not a good stimulator of lysosomal enzyme secretion, did not cause a significant decrease of TPI or arachidonic acid release. Since TPA is known not to increase the intracellular Ca2+ level, these results suggest that lysosomal enzyme secretion is correlated closely with enhanced inositol phospholipid metabolism and Ca2+-dependent processes. On the other hand, superoxide anion production seemed to be caused mainly by Ca2+-independent processes, perhaps by protein kinase-C activation through newly formed diacylglycerol, when neutrophils were activated by chemotactic peptide.

Animals↗
PubMed1985

Phonopneumograph possible for real-time tracing.

We constructed a new phonopneumograph that provides real-time tracing of lung sounds at a high speed without the steps of memory and playback by use of a thermal printer system. Accuracy of the recorded wave form was considered adequate even at the maximum speed of 750 mm/sec for detailed wave form analysis. The device is easily connected to a recording system for respiratory flow rate or volume. To test the clinical usefulness of this portable instrument, the difference in the interpretation of four types of basic adventitious lung sounds by different listeners was examined. The "trained" group who had experience in using this instrument interpreted adventitious lung sounds more accurately than did the "untrained" group. Even in the "trained" group, however, the accuracy of identifying certain sounds was sometimes low. These results suggest that this device is useful for bedside interpretation of adventitious lung sounds or for training of auscultation ability.

Analog-Digital Conversion↗
PubMed1985

Gamma glutamyl transpeptidase activity in rat urothelium treated with bladder carcinogens.

Gamma glutamyl transpeptidase (GGT) activity during urothelial carcinogenesis was examined histochemically in rats treated with N-methyl-N-nitrosourea (MNU) or N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN). GGT-positive cells developed with a high frequency in foci of nodulopapillary hyperplasia and carcinoma. GGT-positive cells, both individually and in nests, were also frequent in foci of simple hyperplasia and interlesion normal urothelium of carcinogen-treated bladders. The results suggest that development of GGT-positive cells in interlesion normal urothelium is specific to carcinogen treatment.

Animals↗
PubMed1985

alpha-Difluoromethylornithine inhibits cell growth stimulated by a tumor-promoting rat urinary fraction.

The growth stimulating activity of a tumor-promoting rat urinary fraction (Fraction I), and its inhibition by alpha-difluoromethylornithine (DFMO) were examined in vitro using a rat bladder carcinoma cell line, 804G cells. Cell growth was markedly stimulated by Fraction I when added to the basic medium containing 0.2% fetal calf serum (FCS). The increased proliferative activity was associated with an increase in ornithine decarboxylase (ODC) activity and intracellular polyamine content. DFMO effectively inhibited the growth of 804G cells stimulated by Fraction I or by 10% FCS, and the inhibition was associated with suppression of ODC activity and partial depletion of intracellular putrescine and spermidine. Growth inhibition was reversed by exogenous putrescine. These results show that (i) urinary Fraction I, both a tumor promoter in bladder carcinogenesis and an ODC inducer in 804G cells, has potent mitogenicity in 804G cells, and (ii) the mitogenicity is inhibited by DMFO, an irreversible inhibitor of ODC.

Animals↗
PubMed1985

Agglutination by concanavalin A of urothelial cells of heterotropically transplanted rat urinary bladders: effect of bladder carcinogens and urine.

N-butyl-N-(3-carboxypropyl)nitrosamine (BCPN) has been considered to be a carcinogenic urinary metabolite of N-butyl-N-(4-hydroxybutyl)nitrosamine. No tumor developed, however, in the heterotropically transplanted rat urinary bladders (HTBs) following repeated instillation of BCPN dissolved in physiological saline. In the present study, the possibility that BCPN dissolved in urine may induce tumors was explored using a short-term screening assay. When tested with the concanavalin A agglutination assay with which a close correlation between increase in cell agglutinability and carcinogenicity of test compounds has been well demonstrated, no significant increase in agglutinability attributable solely to BCPN was observed in HTB cells whether it was dissolved in saline or urine. Based on the current findings together with other available data, it is suggested that urothelial cells have a very limited capability to activate BCPN to the ultimate carcinogen, and require continuous contact with the carcinogen to respond with tumor formation.

Agglutination↗