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Biomedical subjects

M Matsuda

Publications and source records attributed to M Matsuda.

At least 361 records · Page 20Linked to original sources

Bordetella bronchiseptica dermonecrotizing toxin, which activates a small GTP-binding protein rho, induces membrane organelle proliferation and caveolae formation.

We recently demonstrated that Bordetella bronchiseptica dermonecrotizing toxin (DNT) modifies a small GTP-binding protein rho and causes assembly of actin stress fibers and focal adhesions in MC3T3-E1 cells, indicating that DNT activates the function of rho protein (Horiguchi et al., 1995, J. Cell Sci. 108, 3243-3251). In this study, we examined by electron microscopy ultrastructural changes in DNT-treated MC3T3-E1 cells under conditions in which DNT elicited the above morphological changes. We found that DNT induced proliferation of cytoplasmic membrane organelles, such as Golgi apparatus, smooth and rough endoplasmic reticulum, and mitochondria, and formation of plasmalemmal caveolae. Therefore we examined also the effect of Clostridium botulinum C3 exoenzyme (C3), which has been known to ADP-ribosylate and inactivate rho protein, and found that C3 exoenzyme inhibited the development of membrane organelles in the MC3T3-E1 cells. These findings show that proliferation of membrane organelles and caveolae formation are controlled by the function of rho, which is the target of DNT action.

3T3 Cells↗

In vitro and in vivo suppression of gluconeogenesis by inhibition of pyruvate carboxylase.

The mechanism of inhibition of gluconeogenesis by phenylalkanoic acids was studied in vitro and in vivo. In vitro production of 14CO2 from labeled glucose or palmitate was not inhibited at 4 mM, a concentration of phenylacetic acid that inhibited gluconeogenesis from lactate/pyruvate. In vitro studies with isolated mitochondria showed that the CoA ester of phenylacetic acid was formed. The parent phenylalkanoic acid had no effect on purified pyruvate carboxylase activity, but phenylacetyl CoA ester decreased pyruvate carboxylation in a concentration-dependent manner. Phenylacetic acid inhibited gluconeogenesis in isolated rat liver cells from 10 mM lactate/1 mM pyruvate (decreased 39%, P < 0.05), but not 10 mM L-glutamine or [14C]aspartate, showing that the inhibition of gluconeogenesis occurred at the level of pyruvate carboxylase. A 20 mg bolus with infusion of 1 mg/min of phenylpropionic acid decreased blood glucose levels of normal [110 +/- 12 to 66 +/- 11 mg/dL, N = 7, P < 0.05 (unpaired Student's t-test vs control)] and streptozocin diabetic rats [295 +/- 14 to 225 +/- 12 mg/dL, N = 7, P < 0.01 (paired t-test vs basal)]. Hepatic glucose production in control and diabetic rats was suppressed under conditions where liver glycogen was depleted, indicating that gluconeogenesis had been inhibited in vivo. The results suggest the possibility that the inappropriate overproduction of glucose can be controlled by inhibitors of pyruvate carboxylase. This class of inhibitors may be useful in the treatment of non-insulin-dependent diabetes mellitus.

Animals↗

Abscesses caused by "dropped" stones after laparoscopic cholecystectomy for cholelithiasis: a report of three cases.

While laparoscopic cholecystectomy is a standard therapeutic option for gallbladder stones, it is associated with a significant risk of injury to the gallbladder wall, which may result in the dispersion of free stones within the peritoneal cavity. However, the incidence and consequences of these dropped stones remains unclear. We report herein the cases of three patients in whom abdominal abscesses developed as a result of dropped stones during this procedure. Of particular interest was the relatively long interval from the procedure to the onset of symptoms and the unusual progression of the inflammation. These case reports strongly reinforce the risk of dropped stones during laparoscopic cholecystectomy.

Abdominal Abscess↗

Studies on the mass action effect of glucose in NIDDM and IDDM: evidence for glucose resistance.

UNLABELLED: The ability of hyperglycaemia to enhance glucose uptake was evaluated in 9 non-insulin-dependent (NIDDM), 7 insulin-dependent (IDDM) diabetic subjects, and in 6 young and 9 older normal volunteers. Following overnight insulin-induced euglycaemia, a sequential three-step hyperglycaemic clamp (+ 2.8 + 5.6, and + 11.2 mmol/l above baseline) was performed with somatostatin plus replacing doses of basal insulin and glucagon, 3-3H-glucose infusion and indirect calorimetry. In the control subjects as a whole, glucose disposal increased at each hyperglycaemic step (13.1 +/- 0.6, 15.7 +/- 0.7, and 26.3 +/- 1.1 mumol/kg.min). In NIDDM (10.5 +/- 0.2, 12.1 +/- 1.0, and 17.5 +/- 1.1 mumol/kg.min), and IDDM (11.2 +/- 0.8, 12.9 +/- 1.0, and 15.6 +/- 1.1 mumol/kg.min) glucose disposal was lower during all three steps (p < 0.05-0.005). Hepatic glucose production declined proportionally to plasma glucose concentration to a similar extent in all four groups of patients. In control subjects, hyperglycaemia stimulated glucose oxidation (+4.4 +/- 0.7 mumol/kg.min) only at +11.2 mmol/l (p < 0.05), while non-oxidative glucose metabolism increased at each hyperglycaemic step (+3.1 +/- 0.7; +3.5 +/- 0.9, and +10.8 +/- 1.7 mumol/kg.min; all p < 0.05). In diabetic patients, no increment in glucose oxidation was elicited even at the highest hyperglycaemic plateau (IDDM = +0.5 +/- 1.5; NIDDM = +0.2 +/- 0.6 mumol/kg.min) and non-oxidative glucose metabolism was hampered (IDDM = +1.8 +/- 1.5, +3.1 +/- 1.7, and +4.3 +/- 1.8; NIDDM = +0.7 +/- 0.6, 2.1 +/- 0.9, and +7.0 +/- 0.8 mumol/kg.min; p < 0.05-0.005). Blood lactate concentration increased and plasma non-esterified fatty acid (NEFA) fell in control (p < 0.05) but not in diabetic subjects. The increments in blood lactate were correlated with the increase in non-oxidative glucose disposal and with the decrease in plasma NEFA. IN CONCLUSION: 1) the ability of hyperglycaemia to promote glucose disposal is impaired in NIDDM and IDDM; 2) stimulation of glucose oxidation and non-oxidative glucose metabolism accounts for glucose disposal; 3) both pathways of glucose metabolism are impaired in diabetic patients; 4) impaired ability of hyperglycaemia to suppress plasma NEFA is present in these patients. These results suggest that glucose resistance, that is the ability of glucose itself to promote glucose utilization, is impaired in both IDDM and NIDDM patients.

Adult↗

Successful treatment of a rectal anastomotic stenosis by transanal endoscopic microsurgery (TEM) using the contact Nd:YAG laser.

We report the advantage of employing transanal endoscopic microsurgery (TEM) using the contact Nd:YAG laser for the treatment of a rectal anastomotic stenosis. A 72-year-old woman was admitted to our hospital with a postoperative rectal anastomotic stenosis. Twenty months prior to admission, the patient underwent a low anterior resection for the treatment of the rectal cancer using an EEA stapling device. A barium enema and colonoscopy revealed a rectal stenosis, 0.8-cm diameter. This stenosis was at the anastomotic site, approximately 4.0 from the dental line. An endoscopic treatment was performed transanally using the contact Nd:YAG laser. The stenotic rectal wall was fulgurated or vaporized completely. There were no intraoperative or postoperative complications. We concluded that TEM appears to be a safe and minimally invasive procedure. Furthermore, the contact Nd:YAG laser is very effective in treating the gastrointestinal stenotic area. To our knowledge, this is the first successful report of this novel procedure.

Aged↗

Increased expression of prolactin receptor mRNA in adenomyotic uterus in mice.

To investigate changes in uterine prolactin receptor (PRLR) expression in advanced uterine adenomyosis induced by ectopic pituitary isograft, the amount of PRLR mRNA was measured, by a quantitative competitive PCR, in both normal uteri and uteri with adenomyosis in mice at 20 days or 4, 5 and 6 months after pituitary grafting. There was no difference in the amount of PRLR mRNA between the normal uteri and uteri with pituitary grafts, at 20 days after grafting. At 4-6 months after the operation, however, uteri with adenomyosis contained 2-10 times more PRLR mRNA than did in intact uteri, and the increased amount accompanied the advance of the pathological disorder. The ratio of the short to the long form of PRLR mRNA was little affected by the progress of adenomyosis. These findings suggest that increases in the amount of functional PRLR are in fact a result of the progress of adenomyotic changes, rather than simply a result of elevated circulating prolactin levels.

Animals↗

Differences in the change in the time course of plasma endothelin-1 and endothelin-3 levels after exercise in humans. The response to exercise of endothelin-3 is more rapid than that of endothelin-1.

Several studies have indicated that endothelin-1 (ET-1) and endothelin-3 (ET-3) are produced by different cells. Although ET-1 is produced by vascular endothelial cells, these cells do not produce ET-3. The presence of ET-3 in the brain of several species suggests that ET-3 is a novel neuropeptide. It is unclear whether there are differences in the release of ET-1 and ET-3 under various physiological conditions in humans. In the present study, we measured the plasma concentrations of both ET-1 and ET-3 before and after endurance exercise on a cycle ergometer. Male athletes exercised on a cycle ergometer for 30 min at intensity of 130% of their individual ventilatory threshold (VT), which is intense exercise. Plasma ET-1 and ET-3 were greatly elevated by exercise, but there was a marked difference in the time-course of the change in plasma concentration between the two peptides. The level of ET-1 peaked 30 min after exercise, whereas that of ET-3 peaked immediately after exercise. Thus, plasma ET-3 increased faster than plasma ET-1 after exercise. The exercise-induced change in the time course in plasma ET-3, but not in ET-1, is similar to that in plasma norepinephrine which is a neurotransmitter, suggesting that the rapid elevation in plasma ET-3 is partly attributable to the neuronal response to exercise. The observed difference in the change in the time course of plasma ET-1 and ET-3 levels suggests that the mechanisms by which exercise alters the release and/or synthesis of these two peptides differ.

Adolescent↗

Botulinolysin, a thiol-activated hemolysin produced by Clostridium botulinum, inhibits endothelium-dependent relaxation of rat aortic ring.

The effects of botulinolysin (Blyn), a thiol-activated hemolysin produced by Clostridium botulinum, on contractility of rat aortic ring were studied in order to clarify an underlying mechanism of vasoconstriction by the toxin observed previously as an increase in perfusion pressure in isolated rat organs. Blyn (30 hemolytic units/ml; HU/ml) itself did not elicit any apparent change in resting tension of the ring. Contractile tension elicited by a high concentration of phenylephrine in endothelium-intact rings increased significantly after treatment with Blyn (30 HU/ml), while phenylephrine-induced contraction of endothelium-denuded rings was not influenced by toxin treatment. In rings with intact endothelium, acetylcholine (ACh)-induced relaxation was significantly inhibited after treatment with Blyn (30, 10, 1 HU/ml). In contrast, relaxation of denuded rings by sodium nitroprusside was not affected by toxin treatment (30 HU/ml). Arginine (10(-4) M) partly reversed the inhibition of ACh-induced relaxation by the toxin (1 HU/ml). Endothelium-dependent relaxation by histamine or adenosine triphosphate was also inhibited by Blyn (1 HU/ml), but the relaxation elicited by calcium ionophore A23187 was not influenced by the toxin. The results indicate that Blyn acts on endothelium and inhibits agonist-induced endothelium-dependent relaxation of blood vessels.

Acetylcholine↗

Organochlorine pesticides, polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins and dibenzofurans in human adipose tissue from western Kyungnam, Korea.

Hexachlorocyclohexanes (HCHs), dichlorodiphenyl trichloroethane and its metabolites (DDTs), hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/DFs) were determined in human adipose tissue samples collected from western Kyungnam, Korea. The residue levels of organochlorine compounds were in the order of DDTs followed by PCBs > HCHs > HCB > PCDDs/DFs. The mean concentrations of 2,3,7,8-TeCDD in male and female tissues were 2.8 and 1.7 pg.g-1 on lipid weight basis, respectively. No significant difference was found in the residue levels of PCDDs/DFs between sexes. In contrast, PCBs and DDTs showed a significant difference between sexes. Unlike the age trend observed for HCHs, PCBs and DDTs, PCDDs/DFs revealed a constant or rather decreasing pattern with increasing age. This is the first report on PCDDs/DFs contamination in human adipose tissue from Korea. Organochlorine concentrations in human adipose tissues from western Kyungnam were generally much lower than those of other countries.

Adipose Tissue↗

Soluble intercellular adhesion molecule-1 levels of patients with acute myeloid leukemia after allogeneic bone marrow transplantation.

Concentrations of serum-soluble intercellular adhesion molecule-1 (ICAM-1) were measured for 10 patients with or without chronic graft versus host disease after allogeneic bone marrow transplantation. Levels of soluble ICAM-1 were higher among patients with chronic graft versus host disease than among those without it, a statistically significant difference. The results indicated that measurement of serum-soluble ICAM-1 is useful for prediction of chronic graft versus host disease.

Acute Disease↗

Determination of a novel anti-psychotic agent AD-5423 and its metabolites in plasma by high-performance liquid chromatography with fluorescence detection.

AD-5423, 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocy cloocta [b]pyridine, is a novel anti-psychotic agent. In order to investigate the pharmacokinetics of AD-5423, a simple and sensitive high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of AD-5423 and its two N-oxidized metabolites (N-desethyl AD-5423 and AD-5423 N-oxide) in plasma. After pretreatment of a plasma sample by solid-phase extraction, AD-5423 and its metabolites were analyzed on a HPLC with fluorescence detection (335/410 nm). Chromatography was performed on two C18 reversed-phase columns connected by a switching system, with a mobile phase of acetonitrile-methanol-25 mM sodium phosphate buffer (pH 2.5) containing 25 mM sodium 1-heptanesulfonate (36:26:38 v/v/v). The method gives satisfactory accuracy and precision for the determination of AD-5423 and its metabolites. In human plasma, accurate determination are possible over the concentration ranges of 0.04-5 ng ml-1 for AD-5423 and 0.1-5 ng ml-1 for N-oxidized metabolites. The intra- and inter-day assay precision (R.S.D.) of AD-5423 (0.5 ng ml-1) were 3.6 and 7.2%, respectively. In plasma of experimental animals, the validated quantitative range are 0.1-100 ng ml-1 for both AD-5423 and its metabolites.

Adult↗

Defects at center P underlie diabetes-associated mitochondrial dysfunction.

Detailed respiration studies on isolated liver mitochondria from streptozotocin-induced diabetic Sprague-Dawley rats revealed a disease-associated decrease in the ADP/O ratio, a marker for mitochondrial ability to couple the consumption of oxygen to the phosphorylation of ADP. This decrease was observed following induction of respiration with glutamate/malate, succinate, or duroquinol, which enter the electron transport chain selectively at complexes I (NADH dehydrogenase), II (succinate dehydrogenase), or III (cytochrome bc1 complex), respectively. These data, coupled with studies using respiratory inhibitors (most importantly antimycin A and myxothiazol), localize at least a portion of this defect to a single site within the electron transport chain (center P in the Q-cycle portion of complex III). These results suggest that liver mitochondria from diabetic animals may generate increased levels of reactive oxygen species at the portion of the electron transport chain already established as the major site of mitochondrial free radical generation. The reduction in the ADP/O ratio occurred in mitochondria that do not have overt defects in the respiratory control ratio or in State 3 and State 4 respiration. The data in this paper suggest that defects in center P of the electron transport chain likely increase mitochondrial exposure to oxidants in the diabetic. This data may partially explain the evidence of altered exposure and/or response to reactive species in mitochondria from diabetics. This work thus provides further clues to the interaction between oxidative stress and diabetes-associated mitochondrial dysfunction.

Adenosine Diphosphate↗

Profiles of fragments after pulsed-field gel electrophoresis of cleaved genomic DNA from strains of Taylorella equigenitalis isolated from horses in Norway.

The genomic DNA of eight strains of Taylorella equigenitalis, isolated from seven Norwegian Trotters and a Norwegian pony with contagious equine metritis in Norway, was examined by pulsed-field gel electrophoresis after separate digestions with two restriction enzymes, namely, ApaI and NotI. The respective electrophoretic profiles of the fragments were essentially identical but differed from those of T. equigenitalis NCTC11184T and Kentucky 188. They also exhibited slight differences from profiles obtained from Japanese isolates. These results may possibly suggest a common genotype and a common source of infection for all these eight isolates in Norway.

Animals↗

Predictive value of serum medroxyprogesterone acetate concentration for response in advanced or recurrent breast cancer.

Medroxyprogesterone acetate (MPA) is one of the most commonly prescribed drugs for endocrine therapy of metastatic breast cancer. In this study, the serum MPA concentration was measured by high-performance liquid chromatography (HPLC) and evaluated for its usefulness in predicting the response in 79 cases of advanced or recurrent breast cancers. Overall, 29 patients (37%) achieved an objective response. The response rate correlated significantly with the oestrogen receptor (ER) status (P = 0.03), proliferative activity determined by DNA polymerase alpha (P = 0.04), the disease-free interval (DFI) (P = 0.05) and the serum MPA concentration (P < 0.001). Patients with ER-positive tumours, lower proliferative activity, a longer (DFI) or a higher serum MPA concentration responded more frequently. The mean serum MPA concentration in the responders with ER-positive tumours (P = 0.01) or tumours with a lower proliferative activity (P = 0.008) were significantly lower than in cases with ER-negative tumours or tumours with a higher proliferative activity, respectively. Cases with soft tissue metastases showed responses at significantly lower MPA concentrations (P = 0.003) than those with bone or visceral metastases. Furthermore, there was a dramatic decrease in the MPA concentration when a responder with a high concentration became unresponsive to the therapy. Thus, the serum MPA concentration is a determining factor for the response to treatment.

Adult↗

A fraction unresponsive to growth inhibition by TGF-beta among the high-proliferative potential progenitor cells in bone marrow of p53-deficient mice.

Transforming growth factor-beta (TGF-beta) has been found to block the progression of the cell-cycle by up-regulating a Cdk inhibitor, p15, only in epithelial cells; on the other hand, wild-type p53 was shown to activate transcriptionally the gene for another Cdk inhibitor, p21. The regulatory effects of TGF-beta on hematopoietic tissues is poorly understood. Hence, we investigated the effect of TGF-beta on hematopoietic progenitor cells in p53-deficient mice to determine whether an inhibitory signal from TGF-beta is linked to p53 in hematopoietic regulation. We found that the proliferation of megakaryocyte-progenitors (CFU-Mk) in our wild-type mice was markedly inhibited by TGF-beta. Contrary to an earlier report, an erythroid and a granulocyte-macrophage progenitor, stimulated by IL-3, were not significantly inhibited, whereas TGF-beta also completely inhibited the growth of high-proliferative potential progenitor cells (HPP-CFC) in the marrow of mice with 5-fluorouracil (5FU), as reported. It is interesting that in the p53-deficient mice, the inhibitory action of TGF-beta on the HPP-CFC was incompletely abolished. The response curve we obtained for graded doses of TGF-beta suggests that there is, at least, a subpopulation of HPP-CFC which is less sensitive to the regulation by TGF-beta. In contrast to HPP-CFC, the CFU-Mk, which TGF-beta inhibited only in wild-type mice not treated with 5FU, remained inhibited in the p53-deficient strain. Thus, HPP-CFC might be regulated by TGF-beta through their signal pathways which are linked to p53.

Animals↗

A battery of monoclonal antibodies that induce unique conformations to evolve cryptic but constitutive functions of plasminogen.

Two groups of anti-plasminogen monoclonal antibodies, whose epitope was either in the kringle 1 + 2 + 3 domain (F3P2, F11P5, F11P6, and F12P18) or the kringle 5 domain (F1P6 and F12P16), were isolated and their effects on the conformation of plasminogen were explored. All antibodies except F1P6 had 3- to 10-fold higher affinity toward Lys-plasminogen than Glu-plasminogen. F1P6 exhibited a comparable affinity to Glu- and Lys-plasminogen. Among these, only F11P5 binding was inhibited by epsilon-amino-nu-caproic acid (EACA) in a concentration-dependent manner, with half maximal inhibition at 3 mM. From a competition assay, we concluded that the epitopes of F11P5, F11P6, and F12P18 should be very close, and located at or near the low affinity lysine binding site on the kringle 2 + 3. These three antibodies dramatically enhanced the binding of Glu-plasminogen to the other antibodies, except to F1P6. Interestingly, F3P2, whose non-overlapping epitope was in the kringle 2 + 3 domain, also augmented the binding of Glu-plasminogen to the other antibodies. In contrast, we did not observe enhanced binding of Lys-plasminogen to one antibody in the presence of the other antibodies, and the binding of Glu-plasminogen to these antibodies did not increase in the presence of 10 mM EACA. In the presence of these antibodies, including F1P6, Glu-plasminogen bound more efficiently to immobilized degraded fibrin, with a binding profile similar to Lys-plasminogen. All antibodies except F1P6 enhanced the conversion rate of plasminogen to plasmin remarkably. Taken together, we propose that these two groups of monoclonal antibodies can dissociate the intramolecular interactions of Glu-plasminogen and induce the conformational transition of Glu-plasminogen to Lys-plasminogen. In addition, the kringle 2 + 3 and kringle 5 structures of Glu-plasminogen liganded with EACA are distinct from the Lys-plasminogen structure.

Animals↗

CD56-positive (nasal-type T/NK cell) lymphoma arising on the skin. Report of two cases and review of the literature.

Several authors have reported cases of patients with malignant lymphoma with unique characteristics, designated nasal-type T/NK cell lymphoma, which expresses the natural killer (NK) cell marker and shows frequent extra-nodal involvement and poor prognosis. We report 2 cases of this type of lymphoma which were CD56-positive and showed a histopathologically angiocentric pattern with cutaneous and subcutaneous tumorous lesions. Patient 1 had extensive invasion of skin, underlying skeletal muscle, spleen and bone marrow, and died of sepsis 34 months after onset. Patient 2 had multiple subcutaneous nodules and invasion to mammary gland, lung, lymph node and spleen at the time of her first visit. She died of a rapid invasion of lymphoma cells to the liver 5 months after onset. Both patients showed similar immunophenotypes of tumor cells (CD2+, CD3-, CD4-, CD8-, CD20-, CD56+) and germ line configuration of the heavy chain of immunoglobulin (JH), T-cell receptor C beta-1 subunit DNA and T-cell receptor J gamma subunit DNA. Epstein-Barr virus early regions RNA was demonstrated in the nuclei of tumor cells of both patients with in situ hybridization. The histopathological examination of the skin lesions of both patients revealed the features of angiocentric lymphoma. The detection of CD56 in the tumor cells of cutaneous lymphomas should be routinely performed for the early diagnosis of this type of lymphoma with extremely poor prognosis.

Antigens, CD↗

Effects of posterior chamber lens implantation on the endothelium of transplanted corneas.

AIMS: The morphological changes of the corneal endothelium after posterior chamber lens implantation in the transplanted corneas were investigated. METHODS: 36 patients underwent extracapsular cataract extraction with posterior chamber lens implantation. Among these, penetrating keratoplasty had been performed in 18 patients before cataract surgery. The indications for penetrating keratoplasty in these cases included keratoconus, herpetic keratitis, and macula cornea. 18 cataract patients with normal corneas were also studied as controls. The central corneal endothelium in each subject was examined with a wide field specular microscope at a few days before and 3 months after cataract surgery. RESULTS: Although the transplanted corneas showed lower endothelial cell densities, marked polymegethism, and pleomorphism in the baseline variables, the endothelial morphological changes in the transplanted corneas after posterior chamber lens implantation were comparable with those in the normal corneas. Also, there was no clinical evidence, especially, of corneal epithelial and/or endothelial rejections and corneal decompensation in all corneas. CONCLUSION: Even though the transplanted corneas have a lower endothelial cell density and marked polymegethism, it is believed that cataract surgery does not induce corneal decompensation in cases where the peripheral recipient endothelium can be considered to have normal morphology.

Adult↗