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Biomedical subjects

Y Fukuda

Publications and source records attributed to Y Fukuda.

At least 649 records · Page 36Linked to original sources

Immunohistochemical study on tissue inhibitors of metalloproteinases in normal and pathological human livers.

The localization of tissue inhibitor of metalloproteinases (TIMP) in normal and pathological livers was examined by immunohistochemistry using monoclonal antibodies at the light microscopic level. In normal liver, immunoreactive TIMP was detected in smooth muscle cells and endothelial cells of blood vessels, fibroblasts, bile duct cells and Kupffer cells, indicating that TIMP is likely to be a general element of the liver. Immunoreactivity was observed in newly-formed blood vessels, proliferating bile ductules, and fibroblasts in the expanded portal area and fibrous septa of chronic active hepatitis and cirrhosis. TIMP was strongly stained in the capsule of hepatocellular carcinoma. The intensity of the immunoreaction in the capsule was generally greater than that in cirrhotic liver apart from the tumor mass. In three of five cases with hepatocellular carcinoma, endothelial walls in contact with tumor cells were positive.

Antibodies, Monoclonal↗

Histochemical properties of vascular and sinusoidal endothelial cells in liver diseases.

Liver biopsy specimens with or without liver diseases were examined immunohistochemically to determine the distribution of endothelial cell markers, factor VIII-related antigen (FVIII-RAg). Ulex europaeus agglutinin I (UEA-I) lectin and PAL-E. We also investigated the localization of laminin, a component of the basement membrane. In normal livers, FVIII-RAg, UEA-I and laminin were negative in sinusoidal endothelial cells, but positive in blood vascular endothelia of the portal area. The antigen detected by PAL-E was distributed in venous endothelial cells. PAL-E did not label endothelial cells of the artery. In the lobule, immunoreactivity with PAL-E was weakly detected only in some sinusoids of the periportal area. In chronic active hepatitis and liver cirrhosis, FVIII-RAg and UEA-I stained endothelial cells of neovasculatures in the enlarged portal areas of the fibrous septum surrounding pseudolobules. Some sinusoidal endothelial cells in cirrhotic livers were reactive to UEA-I and FVIII-RAg, whereas PAL-E-positive cells were found rarely in the pseudolobules. In carcinomatous sinusoidal endothelial cells, FVIII-RAg, UEA-I and PAL-E were strongly stained. Laminin underlay these carcinomatous sinusoids. These suggest capillarization of sinusoids in hepatocellular carcinoma. The histochemical approach using endothelial cell markers could be a practical tool in the diagnosis of hepatocellular carcinoma.

Antibodies, Monoclonal↗

Vasculo-Behçet's disease: a pathologic study of eight cases.

Behçet's disease associated with large vascular lesions is called vasculo-Behçet's disease. The pathologic features of eight autopsy cases of vasculo-Behçet's disease were studied. The patients' ages ranged from 31 to 56 years; there were five men and three women. Of these patients, large vascular lesions were as follows: aneurysm (three cases), aneurysm and arterial occlusion (one case), aneurysm with arterial and venous occlusion (one case), and venous occlusion (two cases). Aneurysms were of the saccular or dissecting type. The aneurysm formation most commonly occurred in the aorta (two cases). Histologically, aortitis was seen in six patients. Aortitis was divided into active and scar stages. In one case with active stage aortitis, granulomatous aortitis similar to Takayasu's arteritis was seen. In conclusion, we believe that the large arterial lesion in vasculo-Behçet's disease represents inflammation occurring in the media and adventitia. In the affected arteries, active arteritis occurs initially, followed by destruction of the media and fibrosis. Saccular aneurysms are probably produced by severe destruction of the media by intense active inflammation. The large venous lesions represent thrombophlebitis.

Adult↗

Mechanism of protein folding. III. Disulfide bonding.

It was shown in lysozyme and phospholipase, and generally in proteins with disulfide bonds, that after the formation of secondary structures the hydrophobic interactions between the key pairs responsible for folding tertiary structures bring several cysteine residues close together. Among the possible combination of cysteine residues some definite pairs are realized in the tertiary structure. In the Appendix to this paper an algebraic relation is given which must be satisfied for two cysteine residues to make a disulfide bond. This relation is too strict to be applied to real problems, where the two cysteines come close together, but the distance is still too great to yield a disulfide bond. In this case the two residues can attract each other by disulfide formation potential. A geometrical graphic representation is given for the locus of the H atom of the SH group in the cysteine residue. This looks like a lampshade and provides us with a guide to select the correct choice among cysteine pairs. This method is applied to lysozyme and phospholipase to supplement the discussion of the preceding paper (T. Yoshimura, H. Noguchi, T. Inoue and N. Saitô, Biophys. Chem. 40 (1991) 277).

Disulfides↗

Presence of two transcribed malate synthase genes in an n-alkane-utilizing yeast, Candida tropicalis.

The presence of two genomic DNA regions encoding malate synthase (MS) was shown by Southern blot analysis of the genomic DNA from an n-alkane-assimilating yeast, Candida tropicalis, using a partial MS cDNA probe, in accordance with the fact that two types of partial MS cDNAs have previously been isolated. This was also confirmed by the restriction mapping of the two genes screened from the yeast lambda EMBL library. Nucleotide sequence analysis of the respective genomic DNAs, named MS-1 gene and MS-2 gene, revealed that both regions encoding MS had the same length of 1,653 base pairs, corresponding to 551 amino acids (molecular mass of MS-1, 62,448 Da; MS-2, 62,421 Da). Although 29 nucleotide pairs differed in the sequences of the coding regions, the number of amino acid replacements was only one: 159Asn (MS-1)----159Ser (MS-2). In the 5'-flanking regions, there were replacements of four nucleotide pairs, deletion of one pair, and insertion of four pairs. In spite of the fact that two genomic genes were present and transcribed, RNA blot analysis demonstrated that only one band (about 2 kb) was observable even when the carbon sources in the cultivation medium were changed. A comparison of the amino acid sequences was made with MSs of rape (Brassica napus L.), cucumber seed, pumpkin seed, Escherichia coli, and Hansenula polymorpha. A high homology was observed among these enzymes, the results indicating that the protein structure was relatively well conserved through the evolution of the molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkanes↗

A comparison of a new solution combining histidine and lactobionate with UW solution and eurocollins for rat liver preservation.

Forty-six rat liver transplants were performed to investigate the effectiveness of a simplified lactobionate solution containing histidine as a buffer (histidine-lactobionate solution) and to compare it with University of Wisconsin solution. This new solution is isoosmotic (320 mOsm/L) and has a higher sodium content and a lower potassium content (Na: 90 mEq/L, K: 45 mEq/L) than standard UW solution. Buffering capacity is increased by adding histidine (90 mM/L) together with KH2PO4 (20 mM/L) and is greater than that of Eurocollins solution or UW solution. Adenosine, insulin, hydroxyethyl starch, and dexamethasone that are included in UW solution are not included in the new solution. The 1-week survival rate of rats transplanted with livers preserved in this solutions at 4 degrees C was 85% (11/13) following 24-hr preservation and 33% (2/6) after 30-hr preservation. By contrast, UW solution gave only a 29% (5/17) survival rate after 24-hr preservation and 0% (0/6) survival after 30-hr preservation, demonstrating that this simplified UW solution with histidine is superior to UW solution in rat liver preservation. No rats (0/4) receiving livers preserved for 24 hr in Eurocollins solution survived. These findings show that the inclusion of histidine as a buffer dramatically improves the effectiveness of lactobionate-based preservation solutions and justify application in a large-animal model and subsequently in clinical liver transplantation.

Adenosine↗

Changes in extracellular matrix materials in the uterine myometrium of rats during pregnancy and postparturition.

Morphological changes in extracellular matrix materials in the uterine myometrium of rats during pregnancy and postparturition were studied by light and electron microscopy together with immunofluorescence microscopy for type III and IV collagens, fibronectin and laminin. The main components present in late pregnancy were 1) various-sized collagen fibrils, 2) thick elastic fibers adjacent to smooth muscle cells, and 3) continuous and thick basement membranes of hypertrophic smooth muscle cells. These findings are considered to indicate degradation of collagen fibrils and development of elastic fibers and basement membranes of smooth muscle cells. This change in extracellular matrix materials in the late stage of pregnancy may be important in the process of uterine enlargement associated with elasticity and preparation for labor. In the postpartum stage, myofibroblastic interstitial cells were seen to phagocytize collagen fibrils, and elastic fibers accumulated mainly around the bundles of smooth muscle cells. These changes in the postpartum stage are thought to be important for the process in which the uterus returns to the nonpregnant condition. It is suggested that smooth muscle cells participate in regulating the development of their basement membranes and elastic fibers, and that myofibroblastic interstitial cells function by clearing degraded collagen fibrils from the uterine myometrium.

Animals↗

Necrotizing sialometaplasia in the mouth floor secondary to reconstructive surgery for tongue carcinoma.

Necrotizing sialometaplasia is a benign inflammatory process, which histologically can mimic squamous cell carcinoma. A 63-year-old man underwent left hemiglossectomy involving transplantation of a myocutaneous flap for squamous cell carcinoma of the tongue. One month after the operation, necrotizing sialometaplasia occurred in the minor salivary gland tissue of the mouth floor, compressed by the necrotic flap. This case is very unusual because of the occurrence of necrotizing sialometaplasia in the floor of the mouth. The etiology of the lesion was considered to be ischemia secondary to compression by the necrotic myocutaneous flap.

Biopsy↗

Gentamicin inhibition of Na+,K(+)-ATPase in rat kidney cells.

Na,K(+)-ATPase activity is decreased in homogenized renal tissue from GM-treated rats. This study examines whether the site of the active effect of GM on Na,K(+)-ATPase activity in the kidney can be localized to the proximal convoluted tubules (PCT) where the drug is taken up and where it will produce necrosis. In rats treated with gentamicin (50 micrograms.kg-1.day-1 i.m.) for 7 days, PCT Na,K(+)-ATPase activity was reduced as compared to vehicle-treated rats but returned to control levels 7 days after treatment withdrawal. In another nephron segment, the medullary thick ascending limb of Henle (mTAL), where GM induced lesions are uncommon, Na,K(+)-ATPase activity was the same in GM- and vehicle-treated rats treatment. To study the in vitro effect of GM, dissected PCT and mTAL segments from untreated rats were preincubated for 30 min with GM 10(-3) M, a dose similar to the tissue concentration in chronically treated rats. In tubule segments that were permeabilized to allow the drug to enter the cells, GM 10(-3) M significantly inhibited Na,K(+)-ATPase activity both in PCT and mTAL. In non-permeabilized mTAL segments GM did not inhibit Na,K(+)-ATPase activity. GM inhibition of Na,K(+)-ATPase activity in permeabilized PCT segments persisted after the tubules were rinsed in GM free medium. GM does not inhibit Na,K(+)-ATPase partly purified from the renal cortex. Conclusion. Gentamicin inhibits Na,K(+)-ATPase activity in renal tubule cells when it has access to the cytoplasm. Treatment with GM will therefore cause a selective inhibition of Na,K(+)-ATPase in the proximal tubule cells.

Animals↗

Changes in portal blood flow consequent to partial hepatectomy: Doppler estimation.

Hemodynamic changes in portal blood flow were investigated in 56 patients with hepatic tumors who underwent partial hepatectomy. Portal flow was measured with a Doppler ultrasound system before, during, and after surgery. The portal flow of patients who underwent massive hepatectomy decreased intraoperatively. The portal flow per unit of cardiac output decreased in patients who underwent massive or major hepatectomy, patients with a cirrhotic liver, and patients who had a satisfactory postoperative course. Postoperatively, the portal flow in patients with a poor clinical outcome (multiple organ failure, hepatic failure, and cardiorespiratory failure) decreased significantly. Monitoring portal hemodynamic values appears to be useful in providing an index of "hepatic functional reserve." Adequate portal flow is essential for postoperative hepatic regeneration; changes in portal hemodynamic values may be directly related to the patient's ability to survive surgery and to regain or maintain normal liver function.

Adult↗

Differential respiratory effects of HCO3- and CO2 applied on ventral medullary surface of rats.

To estimate whether H+ is the unique stimulus of the medullary chemosensor, ventilatory effects of HCO3- and/or CO2 applied on the ventral medullary surface using an improved superfusion technique and of CO2 inhalation were compared in halothane-anesthetized spontaneously breathing rats. Superfusion with low [HCO3-]-acid mock cerebrospinal fluid (CSF) (normal Pco2) induced a significant increase in ventilation, with an accompanying reduction in endtidal Pco2 (PETco2). High [HCO3-]-alkaline CSF depressed ventilation. Changes in Pco2 of superfusing CSF, on the other hand, had no significant effect despite the similar changes in pH. Simultaneous decrease in [HCO3-] and Pco2 of mock CSF with normal pH also maintained stimulated respiration. CO2 inhalation during superfusion with various [HCO3-] solutions caused further increase in ventilation as PETco2 increased. The results suggest that the surface area of the rat ventral medulla contains HCO3- (or H+)-sensitive respiratory neural substrates which are, however, little affected by CO2 in the subarachnoid fluid. A CO2 (or CO2-induced H+)-sensitive chemosensor responsible for the increase in ventilation during CO2 inhalation may exist elsewhere functionally apart from the HCO3- (or H+)-sensitive sensor in the examined surface area.

Animals↗

Respiratory stimulation by female hormones in awake male rats.

The respiratory effect of progestin differs among various animal species and humans. The rat does not hyperventilate in response to exogenous progestin. The present study was conducted to determine whether administration of combined progestin and estrogen prompts ventilatory stimulation in the male rat. Ventilation, blood gases, and metabolic rates (O2 consumption and CO2 production) were measured in the awake and unrestrained male Wistar rat. The combined administration of a synthetic potent progestin (TZP4238) and estradiol for 5 days significantly increased tidal volume and minute expiratory ventilation (VE), reduced arterial PCO2, and enhanced the ventilatory response to CO2 inhalation (delta VE/delta PCO2). On the other hand, respiratory frequency, O2 consumption, CO2 production, and body temperature were not affected. The arterial pH increased slightly, with a concomitant decrease in plasma [HCO3-]. Administration of either TZP4238 or estradiol alone or vehicle (Tween 80) had no effect on respiration, blood gases, and ventilatory response to CO2. The results indicated that respiratory stimulation following combined progestin plus estradiol treatment in the male rat involves activation of process(es) that regulate tidal volume and its augmentation during CO2 stimulus.

Animals↗

Ontogeny of the regulation of Na+,K(+)-ATPase activity in the renal proximal tubule cell.

This study examines the ontogeny of the regulation of Na+,K(+)-ATPase activity in the proximal tubule (PT) by a first messenger, dopamine (DA), and by direct stimulation of a third messenger, protein kinase C (PKC). PT segments dissected from 10- (PT10), 15-(PT15), 20- (PT20), and 40- (PT40) d-old rats were preincubated with DA 10(-5) M, diacylglycerol (DAG) 10(-5) M (an endogenous activator of PKC), or phorbol 12,13-dibutyrate (PDBu) 10(-6) M (an exogenous activator of PKC). DA inhibited Na+,K(+)-ATPase activity in PT40. In PT20, DA also inhibited Na+,K(+)-ATPase activity, but the inhibitory effect in PT20 was less pronounced than in PT40. In PT15, DA had no effect on Na+,K(+)-ATPase activity. DAG significantly inhibited Na+,K(+)-ATPase activity in PT40. DAG also inhibited Na+,K(+)-ATPase activity in PT20, but the inhibition was slightly less pronounced than in PT40. DAG had no effect on Na+,K(+)-ATPase activity in PT15. Na+,K(+)-ATPase activity in PT40 and PT20 preincubated with PDBu was significantly lower than with vehicle. The inhibitory effect in PT20 was less pronounced than in PT40. When PT40 and PT20 were preincubated with both PDBu and 5 x 10(-5) M sphingosine, an inhibitor of PKC activation, the inhibitory effect of PDBu was abolished. In both PT40 and PT20 incubated with 4-alpha-12,13 phorbol didecanoate 10(-7) M, a phorbol ester that will not activate PKC, Na+,K(+)-ATPase activity was not different from the control. In PT10, Na+,K(+)-ATPase activity was the same after PDBu incubation and after vehicle incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

A pathologic study on the inhibitory effects of a herbal medicine against the glomerular lesion induced by Agkistrodon venom in mice.

The inhibitory effects of a prescription of herbal medicine, tentatively named P-3, were studied pathologically in an experimental model of the glomerular lesion induced by purified snake Agkistrodon acutus venom proteinase (Ac1-P) in mice. Ac1-P was intravenously inoculated at a single LD50 dose. In the treated group, mice were intraperitoneally injected with an extract of P-3 at a designated time once every two days from 2 days before to 1 week after Ac1-P inoculation. The control group mice were injected with saline instead of P-3. In the control group, the main pathologic changes within 48 hrs after inoculation were pulmonary and gastrointestinal tract hemorrhage and renal petechiae with hematuria. The kidney microscopically showed cystic transformation of the glomerular capillary tufts. followed by occlusive thrombosis. One week after inoculation, the glomerular lesions were mostly replaced by proliferative or proliferative-sclerosing changes with occasional crescent formation. Early signs of tubular atrophy accompanying the glomerular changes were observed. In the P-3 treated mice surviving 48 hrs and 1 week, the changes observed in the controls were markedly inhibited, although P-3 treated mice dying earlier than 30 hrs exhibited hemorrhagic changes similar to controls. This indicated that the herbal medicine had efficacy against the tissue injuries induced by Ac1-P as a proteolytic enzyme.

Angiography↗

[New experimental rabbit model with PTFE grafts interpositioned in infrarenal abdominal aorta--influence of hyperlipidemia in prosthetic grafts].

The major obstacle to clinical application of artificial blood vessel grafts with inside diameter of less than 4 mm is neogenic intimal hypertrophy at anastomotic sites. With the aim of preventing this artificial blood vessel graft anatomotic intimal hypertrophy, attempts have been made to improve surgical techniques and develop new materials for sutures and the grafts themselves. In the assessment of the preventive effects of various measures on anastomotic intimal hypertrophy, it is desirable to minimize variation in preoperative arteriosclerotic changes and uniform hemodynamics after vessel replacement surgery among the subjects. The present authors succeeded in creating an infrarenal abdominal aorta replacement model that meets these requirements using rabbits, and conducted experiments using this model to assess the effects of hyperlipidemia on anastomotic intimal hypertrophy. The anastomotic intimal hypertrophy lesion in the present rabbit infrarenal abdominal aorta replacement model is both morphologically and histologically similar to that found in human artificial blood vessel graft anastomotic sites. In addition, this model permits the easy obtain of animals showing the same hemodynamic status after vascular surgery. For these reasons, the present model is expected to serve well as an experimental model of artificial blood vessel graft anastomotic intimal hypertrophy.

Animals↗

Hypoxic inhibition of respiratory neural regulation in anesthetized rats.

To determine the neural mechanism of hypoxic respiratory inhibition, discharge patterns of efferent phrenic (Phr), vagal superior laryngeal (Xsl), and vagal pharyngeal (Xphar) nerves were analyzed during systemic hypoxia in the urethane-anesthetized, vagotomized and artificially ventilated rat. In the carotid sinus nerve (CSN) intact rat, moderate hypoxia (end-tidal Po2, 40-50 mmHg) caused an initial increase in respiratory activity which was followed by inhibition due to reduction in respiratory frequency (f). The decrease in f was associated with prolongation of decremental Xphar expiratory (E) activity and retardation of the onset of inspiratory (I) activity. Integrated peak Phr or Xs1 I and Xphar E activities remained augmented during respiratory inhibition. After bilateral CSN section, moderate hypoxia produced an extreme reduction in f due to delayed onset of I activity and a strong reduction in the Xphar E activity. Phr and Xs1 I activities were little affected, and changes in inspiratory time were small. These results suggest that hypoxia centrally inhibits the process of initiating the onset of rhythmic I activity and the activity of decremental Xphar E motoneurons. Carotid chemoreceptor stimulation was inadequate to offset the central inhibitory effect of hypoxia on the onset of I activity.

Anesthesia↗

Effects of felodipine on vascular smooth muscle in comparison with nifedipine.

Felodipine (ethylmethyl 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl- 3,5-pyridine dicarboxylate, CAS 72509-76-3), a vasoselective calcium antagonist, has a slow onset inhibitory effect on high K(+)-induced contractions in vascular smooth muscle and a longer duration than that of nifedipine. In addition it non-competitively inhibits Ca(++)-induced contraction in the depolarized aorta or femoral artery in the rat. Felodipine's inhibitory effect on caffeine or norepinephrine-induced contraction was observed at a micromolar range. This result suggests that felodipine may inhibity Ca++ release from intracellular Ca++ stores through a mechanism of Ca++ or inositol 1,4,5-triphosphate induced Ca++ release in addition to a blockade of Ca++ influx through the sarcolemma.

Animals↗