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T Homma

Publications and source records attributed to T Homma.

At least 109 records · Page 6Linked to original sources
PubMed1993

Hepatocyte growth factor stimulates phosphoinositide hydrolysis and mitogenesis in cultured renal epithelial cells.

Hepatocyte growth factor (HGF), a novel heparin-binding peptide growth factor of MW 97-kDa, is a potent mitogen for parenchymal hepatocytes. HGF is present in normal serum and increases following liver injury or partial hepatectomy. In addition to liver, HGF mRNA has been detected in kidney. In cultured rabbit proximal tubule cells, recombinant human HGF (10(-10) M) increased DNA synthesis, measured as [3H] thymidine incorporation, from 1345 +/- 213 to 2931 +/- 636 cpm/10(6) cells; n = 9; p < 0.005). HGF was found to exert mitogenic effects at lower concentrations than epidermal growth factor (EGF), with half maximal effects seen at 6 x 10(-11) M compared to 7 x 10(-10) M for EGF. HGF was additive with EGF in stimulating [3H] thymidine incorporation. In addition to rabbit proximal tubule cells, HGF increased proliferation in a cultured mouse proximal tubule cell line, MCT, and in rat glomerular epithelial cells. In contrast, HGF did not stimulate proliferation of either rat mesangial cells or a rat aortic smooth muscle cell line, A7r5. The HGF receptor is the product of the c-met proto-oncogene. C-met mRNA was detected in total kidney and in cultured proximal tubule cells but was not detected in cultured mesangial cells. In contrast, HGF mRNA was detected in mesangial cells but not in cultured proximal tubule cells. Preincubation of rabbit proximal tubule cells with the tyrosine kinase inhibitor, genistein (50 microM), prevented HGF-stimulation of [3H] thymidine incorporation. In LiCl pretreated rabbit proximal tubule cells loaded with [3H] myoinositol, HGF increased total inositol phosphate release, measured by anion exchange chromatography (control: 2181 +/- 414 vs HGF: 2609 +/- 478 cpm/10(6) cells; n = 6; p < 0.05). Although genistein did not affect baseline phosphoinositide hydrolysis, it inhibited the HGF stimulation. Thus, HGF is mitogenic for cultured proximal tubule cells as well as glomerular epithelial cells. Inhibition of proliferation and PI turnover by genistein suggests that HGF's actions are mediated in part by tyrosine kinase activity. In mammalian kidney, HGF released from mesangial cells may serve as a paracrine activator of the adjacent epithelial cells.

Animals↗
PubMed1993

Volume and agonist-induced regulation of myosin light-chain phosphorylation in glomerular mesangial cells.

We investigated whether cell volume decrease per se can activate intracellular mechanisms leading to mesangial cell contraction. For this purpose, we applied hyperosmotic stress to cultured glomerular mesangial cells and examined the effects on phosphorylation of myosin light chain (MLCP). Compared with control cells, hyperosmotic stress (390 mosmol/kg) attained by either NaCl or raffinose significantly increased MLCP to 140.7 +/- 7.0% (n = 5) and 134.8 +/- 7.7% (n = 4), respectively, in parallel with a decrease in the cell volume. This increase was comparable to that achieved by the following agonists: arginine vasopressin (AVP, 100 nM; n = 5) and endothelin-1 (ET, 10 nM; n = 5). By using two-dimensional tryptic phosphopeptide mapping, contribution of myosin light-chain kinase (MLCK) and protein kinase C (PKC) to the observed phosphorylation was examined by identifying phosphorylation at serine-19 (by MLCK) and at serine-1 or serine-2 (by PKC). Under resting conditions, relative distribution of phosphorylation between MLCK and PKC sites was 60.1 +/- 8.4 and 39.9 +/- 8.4%. The relative contribution by these enzymes remained similar during hyperosmotic stress or agonist stimulation. Since cytosolic Ca2+ concentration ([Ca2+]i) is an important determinant of MLCP, we also examined [Ca2+]i in these settings. While AVP and ET-induced a characteristic transient spike in [Ca2+]i, hyperosmotic stress caused a gradual and modest increase in [Ca2+]i. These studies show that, in mesangial cells, reduction in cell volume induces MLCP through mechanisms distinct from those involved in agonist-induced events.

Animals↗
PubMed1993

Leukotriene B4 induces lung injury in the rabbit: role of neutrophils and effect of indomethacin.

The effects of exogenous leukotriene B4 (LTB4) on the pulmonary microvascular permeability and the roles of polymorphonuclear (PMN) leukocytes and the cyclooxygenase products of arachidonic acid in the microvascular response to LTB4 in the isolated non-blood-perfused rabbit lungs were studied. Microvascular permeability and lung edema were evaluated by use of the fluid filtration coefficient (Kf) and the wet-to-dry lung weight ratio (W/D ratio), respectively. Pulmonary capillary pressure was estimated by the double occlusion technique. We studied five groups of lungs: lungs were given 1) both PMN leukocytes and a bolus injection of LTB4 (5 micrograms, n = 6), 2) LTB4 alone (n = 5), 3) PMN leukocytes alone (n = 5), 4) control vehicles (n = 5), or 5) indomethacin (40 micrograms/ml) before PMN leukocytes and LTB4 (n = 6). We observed that LTB4 increased Kf and W/D ratio in the presence of PMN leukocytes in the perfusate without affecting the pulmonary arterial and capillary pressures. Neither LTB4 alone nor PMN leukocytes alone produced changes in Kf and W/D ratio. Indomethacin failed to inhibit the LTB4-induced increases in Kf and W/D ratio. These results suggest that LTB4 produces lung injury that is dependent on PMN leukocytes but not on the cyclooxygenase pathway of arachidonic acid metabolism.

Animals↗
PubMed1993

Effect of platelet on protein degradation in rat skeletal muscle.

The effects of activated platelet (Plt) on muscle degradation were investigated, employing the in vivo disseminated intravascular coagulation (DIC) model induced by thrombin injection and the in vitro tissue culture system of skeletal muscles in rats. Both the release of tyrosine and leucine into the culture medium during 2 h incubation from the muscles harvested 30 min after thrombin injection increased by about 50% compared with control muscles. The addition of thrombin-activated platelet supernatant (TAPS) significantly increased the release of leucine into the incubation medium of the soleus muscles dissected from normally fed rats by 31% in comparison with the respective controls. No significant effect was observed in terms of the release of tyrosine or leucine from the incubated muscles by aspirin treatment before obtaining TAPS, or by the addition of thrombin itself up to the concentration of 0.67 micron/ml which was contained in the incubation medium of TAPS. These data suggest that protein catabolism is accelerated in the muscle from the thrombin-treated rats exhibiting DIC. The supernatant of activated Plt might contain a factor which modulates protein metabolism. That factor is different from prostaglandins or thrombin. Thus, active consumption of Plt may contribute to an increase of muscle breakdown in various catabolic states.

Animals↗
PubMed1993

Expression of glycoconjugates in pancreatic, gastric, and colonic tissue by Bauhinia purpurea, Vicia villosa, and peanut lectins.

We have earlier prepared a pancreatic cancer-associated mucin, whose altered carbohydrate structure was recognized by Vicia villosa (VVA), Bauhinia purpurea (BPA), and peanut (PNA) lectins and which was found preferentially in the sera of patients with pancreatic or gastric cancer. Cancer-associated structures of the sugar chain on serum antigen may reflect those occurring in malignant tissues. Accordingly, we investigated the tissue distribution of carbohydrate structures reactive to these lectins by using lectin histochemistry in pancreatic cancer, gastric cancer, and colonic cancer tissue specimens and in their normal counterparts. VVA showed a higher affinity for pancreatic cancer (77.5%), gastric cancer (89%), and colonic cancer (87%) cells than for the cells of their normal counterparts, whose affinity was 0%, 41.7%, and 36.4%, respectively. PNA showed a higher affinity for pancreatic (70%) and colonic cancer cells (86.5%). BPA failed to show significant binding differences between neoplastic and normal cells in any of the pancreatic, gastric, or colonic tissue specimens. It did, however, bind to intraductal contents in most of the pancreatic cancer tissues but bound to intraductal contents in only a few chronic pancreatitis and normal pancreatic tissues. VVA and PNA did not bind to intraductal contents in any of the normal, chronic pancreatitis, or pancreatic cancer tissues. These results imply that, among the lectins used so far, VVA has the highest affinity for neoplastic cells, and it may provide a supplement for use in the pathologic diagnosis of malignant diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1993

[Pathogenesis of development of lung cancer in idiopathic interstitial pneumonia--growth factors in bronchoalveolar lavage fluid].

It has been generally accepted that lung fibrosis as in idiopathic interstitial pneumonia (IIP) is frequently associated with the development of lung cancer. This observation implies that the mechanism involved in carcinogenesis and/or enhanced proliferation of cancer cells is common to the fibrosing process. However, there are few studies reported on the pathogenesis of associated lung cancer except for several studies assessed from the point of view of surgical pathology. This study was undertaken to learn whether BAL fluid, which reflects the local milieu of the fibrosing process, enhances the proliferation of human lung cancer cell line Lu-99, Lu-65 and rat lung fibroblasts as assessed by 3H-thymidine incorporation. BAL fluid was obtained from patients with IIP (n = 8) and normal volunteers (n = 8). BAL fluids from patients with IIP enhanced the mean incorporation of 3H-thymidine of Lu-99 up to 3.6 times (p < 0.01) compared to that of normal volunteers. Furthermore, the mean incorporation of Lu-65 was increased up to 1.8 times (p < 0.05) by BAL fluids from patients with IIP. In contrast, BAL fluids from patients caused no significant increase of the mean incorporation of rat lung fibroblasts as compared to normal BAL fluids. The enhancing activities on the growth of cancer cell line Lu-99, Lu-65 were eluted in several fractions by high performance liquid chromatography using Superose 12. These observations indicate that the BAL fluid of IIP patients contains factors enhancing the growth of cancer cells.

Aged↗
PubMed1993

The intrarenal renin-angiotensin system.

In this article, we have discussed the localization of components of the renal renin-angiotensin system, as well as the existing information on the regulation of this axis and the effects of Ang II on renal function. All the components of the renin-angiotensin system are present in both fetal and adult kidney. In the adult kidney, renin is principally localized to jg cells of the distal afferent arteriole, where release is stimulated by increases in intracellular cAMP and inhibited by increases in cytosolic calcium. Four distinct stimuli mediating renin release are (1) NaCl sensed at the macula densa, (2) the sympathetic nervous system, (3) humoral factors, with Ang II, vasopressin, endothelin, and adenosine inhibiting renin release, and (4) changes in intrarenal blood pressure. Alterations in renal renin gene expression have been reported in pathophysiological states, such as salt depletion, diabetes mellitus, ureteral obstruction, Bartter's syndrome, and with high protein feeding. The highest renal concentrations of mRNA for the renin substrate angiotensinogen are found in the PT, where the protein is localized to subapical granules. Both salt depletion and androgens upregulate renal angiotensinogen mRNA. Of interest, renal angiotensinogen mRNA levels are lower in SHR than in normotensive WKY rats. As with angiotensinogen, renal ACE is mainly localized to the PT, with highest concentration on the brush border. The mechanisms of regulation of both renal angiotensinogen and ACE require further study. Using recently developed specific nonpeptide Ang II receptor antagonists, it appears that adult renal Ang II receptors are principally of the AT1 class, whereas fetal kidney Ang II receptors are of the AT2 subtype. By binding to AT1 receptors, Ang II exerts constrictive effects on both afferent and efferent arterioles, with increased effect reported on efferent arterioles. Glomerular Ang II receptors are localized to mesangial cells, mediating contractile responses resulting in changes in glomerular surface area and Kf, and potentially regulating mesangial sieving and phagocytosis. These receptors are reduced with salt restriction or in experimental diabetes. The highest concentrations of tubular Ang II receptors are found in PT, on both brush border and basolateral membranes.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiotensinogen↗
PubMed1992

Schedule-dependent inhibition of thymidylate synthase by 5-fluorouracil in gastric cancer.

BACKGROUND: An optimal treatment schedule of 5-fluorouracil (5-FU) remains to be clarified. METHODS: A randomized study was conducted to investigate schedule-dependent thymidylate synthase (TS) inhibition by 5-FU in 16 patients with gastric cancer who underwent surgical resection. Surgical specimens of tumor, normal gastric mucosa, and regional lymph nodes were obtained 12 hours after administration of 5-FU either as a continuous infusion (1000 mg/m2 for 48 hours) or as a bolus injection (500 mg/m2 x 2 in 48 hours). RESULTS: The total TS activity (567.8 +/- 294 fmol/mg protein) and the rate of TS inhibition (74.7 +/- 23.1%) in cancer tissues were significantly higher in the continuous-infusion group than in the bolus-injection group (228.5 +/- 104.6 fmol/mg protein and 48.8 +/- 12%, respectively). Likewise, the total TS activity (807.4 +/- 440.3 fmol/mg protein) and the rates of TS inhibition in lymph nodes (72.3 +/- 17.1%) and in normal gastric mucosa (85.1 +/- 12.2%) were significantly higher in the continuous-infusion group than those in the bolus-injection group (232.4 +/- 142.3 fmol/mg protein and 53.6 +/- 17.0% in lymph nodes and 46.5 +/- 14.3% in normal gastric mucosa, respectively). There was a significant correlation between the total TS activity and TS inhibition. CONCLUSIONS: Continuous infusion of 5-FU provides a superior antimetabolic effect in the treatment of gastric cancer, which may lead to a superior antitumor effect.

Aged↗
PubMed1992

Activation of S6 kinase by repeated cycles of stretching and relaxation in rat glomerular mesangial cells. Evidence for involvement of protein kinase C.

Quiescent rat glomerular mesangial cells were exposed to repeated cycles of stretching and relaxation, and the effects on the rate of collagen production, proliferation, and S6 kinase activity were investigated. Stretch/relaxation induced increases in production of both collagen and non-collagenous proteins. Proliferation of mesangial cells was stimulated by stretch/relaxation and epidermal growth factor, but not by angiotensin II; however, administration of angiotensin II augmented stretch/relaxation-induced cell proliferation. Cytosolic S6 kinase activity was stimulated by stretch/relaxation, angiotensin II, epidermal growth factor, or phorbol 12-myristate 13-acetate. The increased S6 kinase activity was detectable within 30 min after initiation of stretch/relaxation and was blocked by either inhibitors of protein kinase C or prior down-regulation of protein kinase C following prolonged incubation with phorbol 12-myristate 13-acetate. Both translocation of protein kinase C from the cytosolic to the membrane fraction and phosphorylation of an endogenous 80-kDa protein were observed within 5 min of initiation of stretch/relaxation. These results demonstrate that in mesangial cells, mechanical factors alone can induce increases in production of collagen and non-collagenous proteins and in cell proliferation. The observation that stretch/relaxation induced stimulation of S6 kinase activity through protein kinase C-dependent mechanisms suggests that activation of protein kinase C may be a key event in initiating adaptive responses of mesangial cells to increased workload.

Adenosine Triphosphate↗
PubMed1992

Effects of the S2-serotonergic receptor antagonist, ketanserin, on cerulein-induced pancreatitis in the rat.

We investigated the effects of ketanserin, a S 2 (5-hydroxytryptamine 2; 5-HT 2)-serotonergic receptor antagonist, on cerulein-induced pancreatitis in the rat. Large pharmacological doses of cerulein induced acute pancreatitis in the rat. Ketanserin reduced the cerulein-induced increase in serum amylase concentration in a dose-dependent manner. Treatment with 10 mg/kg of ketanserin per os markedly improved cerulein-induced pancreatitis and was associated with a significant reduction of the increase in serum amylase concentration. In addition, a very specific serotonin S 2 antagonist, ritanserin which has no antihypertensive effect, also reduced the cerulein-induced increase in the serum amylase concentration. These results suggest that S 2 (5-HT 2) may play a role in pathophysiology of cerulein-induced pancreatitis in the rat.

Acute Disease↗
PubMed1992

Establishment of a multi-dose study of chondroitin sulfate iron colloid for evaluation of the reticuloendothelial system function.

The assay system of chondroitin sulfate iron colloid (CSFe) was established to evaluate the reticuloendothelial system (RES) function in individual rabbits. In the multi-dose study of CSFe, CSFe was repeatedly administered to each individual rabbit with increasing doses (0.6, 1.2, 2.4, 6.0 mg/kg) at set intervals. Blood samples were serially collected after injection of CSFe and the concentration of CSFe in serum was directly measured as an iron concentration by modifying the previously described assay method [1] to minimize the sample volume. The clearance rate of CSFe at each injected dose was computed by the least-squares method and the double-reciprocal plotting of the doses against the phagocytic velocities by the Lineweaver-Burk method was obtained in each rabbit. The maximum phagocytic velocity (Vmax) and the CSFe concentration producing 1/2 Vmax (Kp) obtained in ten rabbits were 0.129 +/- 0.025 mg/kg per min and 0.417 +/- 0.121 mg/kg (mean +/- S.D.), respectively. The results obtained from this multi-dose study were comparable to our previous results obtained from the mean values of five groups given different doses [1]. The clearance rates of CSFe (0.6, 1.2, 6 mg/kg) decreased after the co-injection of 80 mg/kg of carbon colloid. The calculated Vmax and Kp in 29 rabbits were 0.125 mg/kg per min and 1.167 mg/kg. The Kp was apparently greater than that of the control (Vmax = 0.128 mg/kg per min, Kp = 0.421 mg/kg). Carbon colloid (80 mg/kg) was injected to six rabbits after the completion of the first multi-dose study of CSFe and then the second multi-dose study of CSFe was repeated after 24 h. No differences were found in Vmax and Kp between the two studies as were in the control group (10 rabbits) where saline was injected instead of carbon colloid. These results indicated that carbon colloid (80 mg/kg) gives a competitive and reversible inhibition on the RES. This multi-dose study of CSFe may be applicable for a bed-side analysis of the RES function in a patient.

Animals↗
PubMed1992

Endothelin-1 receptor antagonist: effects on endothelin- and cyclosporine-treated mesangial cells.

Endothelin-1 (Et) has profound effects on glomerular microcirculation and mesangial cell contraction. A parameter of mesangial cell contraction was examined by measuring myosin light chain phosphorylation (MLCP) in glomerular mesangial cells in the presence and absence of a newly developed endothelin-1 receptor antagonist (EtA). Addition of Et alone (10 nM) caused a marked increase in MLCP, which, on average, rose by 53 +/- 6% above the level in cells exposed to vehicle (P less than 0.0005). This effect was shown to continue for at least one hour; MLCP at 60 minutes was 64 +/- 12% higher than controls, (P less than 0.025), constituting a unique observation of an in vitro parameter which parallels the characteristic in vivo effect of Et. Treatment of cells with EtA virtually abolished this Et-induced increase in MLCP, which rose by only 2 +/- 3% and -1 +/- 4% for doses of EtA of 44 nM and 66 nM, respectively. Examination of the intracellular calcium concentration, [Ca2+]i, revealed that EtA almost completely abolished the transient increase in [Ca2+]i evoked by Et and also suppressed the early portions of the sustained increase in [Ca2+]i. EtA was ineffective in abolishing [Ca2+]i increase in response to arginine vasopressin. Finally, to evaluate EtA's efficacy in a pathophysiologic setting, we also studied mesangial cells exposed to cyclosporine (Cs). Exposure of mesangial cells to Cs (10(-5) M) for 60 minutes caused a significant increase in MLCP, on average, by 38 +/- 6% above control (P less than 0.0005), while cells exposed to Cs in the presence of EtA increased MLCP significantly less, by only 15 +/- 9%. These data provide further evidence for Et's long-lasting cellular actions, and demonstrate inhibitory effects of an Et receptor antagonist after direct cellular exposure to Et and also after Cs exposure, a pathophysiologic setting which likely involves Et.

Amino Acid Sequence↗
PubMed1992

Secretion of beta-2-microglobulin from human hepatoblastoma and hepatoma cells on stimulation with interleukin-6.

beta 2-microglobulin (beta 2-M) was secreted in a dose- and time-dependent manner after interleukin-6 (IL-6) treatment of human hepatoblastoma (HuH-6) and hepatoma cells (HuH-7). Pancreatic secretory trypsin inhibitor, which is one of the acute phase proteins secreted in these cells, was also secreted dose- and time-dependently in HuH-6 cells and dose-dependently in HuH-7 cells. It is conceivable that IL-6 induces the production of beta 2-M as an acute phase protein in the liver.

Carcinoma, Hepatocellular↗
PubMed1992

Thenar and hypothenar muscles and their innervation by the ulnar and median nerves in the human hand.

The thenar and hypothenar muscles as well as their supplying nerves were analyzed with an improved dissecting method. Among the four thenar muscles, the m. abductor pollicis brevis (AbPB) has a separate muscle belly, whereas the m. opponens pollicis (OP), the superficial and deep heads of the flexor pollicis brevis (sFPB and dFPB), and the adductor pollicis (AdP) are fused with each other to make a single mass (deep thenar muscle group). These muscles are innervated by branches of the recurrent nerve and the accessory recurrent nerve from the median nerve as well as by terminal branches of the deep branch (ramus profundus) of the ulnar nerve. These three nerves frequently form a loop within the deep thenar muscle group (thenar loop), and a branch to the OP and one to deep parts of the sFPB often make a smaller loop (intrathenar loop), whereas the AbPB receives a separate nerve branch. Among the hypothenar muscle, the m. abductor digiti minimi and the m. flexor digiti minimi brevis are fused with each other, and their supplying nerves frequently form a loop in these muscles (intrahypothenar loop), whereas the m. opponens digiti minimi is separated from the others and receives a separate nerve branch. In the distribution pattern of supplying nerves to the thenar and hypothenar muscles, we find regularities in that they branch off in a regular manner from the ulnar and the median nerve, and that nerve branches to those muscles with fused bellies frequently communicate with each other to make loops.

Hand↗
PubMed1992

Effects of frequency and intensity of sound on cochlear blood flow.

Laser Doppler flowmetry demonstrates that loud sound induces a decrease of blood flow in the cochlea of the guinea pig. In this experiment, we observed the effects of frequency and intensity of sound on cochlear blood flow using 15 guinea pigs. In the first 5 guinea pigs, a Doppler probe was attached to the basal turn of the cochlea and sounds of 6, 7, 8, 9 and 10 kHz were delivered to the ear serially from lower to higher frequency, i.e. from 6 kHz to 10 kHz. In the next 5 guinea pigs, the sound was delivered from higher to lower frequency, i.e. from 10 kHz to 6 kHz. The sound intensity delivered to the ear was changed from lower to higher intensity (80 to 120 dB SPL by 10 dB width) at each frequency. In the last 5 guinea pigs, the blood flow in the basal, second, third, and fourth turns of the cochlea was measured at 120 dB SPL of 10 kHz. No change of blood flow was seen in the cochlear basal turn at 6 and 7 kHz up to 120 dB SPL, but a decrease of blood flow was found at 110 and 120 dB SPL at 8, 9, and 10 kHz. On the other hand, the sound of 120 dB SPL at 10 kHz induced a decrease of blood flow only in the basal turn of the cochlea. Our results suggest that there is a corresponding blood flow area which is sensitive to specific frequency in the cochlea.

Animals↗
PubMed1992

[Diagnosis of respiratory system diseases using radio isotopes].

Common respiratory diagnostic imaging techniques using radioisotopes are ventilation-perfusion, perfusion, aerosol inhalation and tumor scintigraphy. The special features of respiratory imaging diagnostic techniques using radioisotopes are the possibility of early detection of disease and the non-invasiveness of the procedure. Also, no patient effort is required. The kinds of isotopes used are as follows: ventilation-perfusion (133Xe, 13N, 99mTc-pseudogas), perfusion (131I, 99mTc), aerosol inhalation (99mTc), tumor (67Ga, 201Tl). The advantages of these procedures are expected to lead to further developments in respiratory examinations using radio isotopes.

Female↗