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Biomedical subjects

Y Mizunoe

Publications and source records attributed to Y Mizunoe.

At least 37 records · Page 2Linked to original sources
PubMed1996

Inhibition of chemiluminescence response of human polymorphonuclear leukocytes by three different stimulations in hyperosmotic condition comparable to the renal medulla.

Hyperosmolality in renal medulla inhibits functions of polymorphonuclear leukocyte (PMN) such as phagocytosis, intracellular killing, and superoxide generation. The main factors of hyperosmolality in the renal medulla are thought to be urea and NaCl. We studied the luminol-dependent chemiluminescence (CL) response of PMNs to three different stimulators: phorbol myristate acetate (PMA), formyl-methionyl-leucyl-phenylalanine (FMLP), and opsonized zymosan (OZ). When PMNs were incubated or preincubated with hyperosmotic urea or NaCl solutions, CL responses were significantly reduced following stimulation by each of PMA, FMLP, or OZ. Reduction of CL response was concentration and osmolality dependent in hyperosmotic urea and NaCl solution. These results suggest that respiratory burst and production of active oxygen species of PMNs through three different signal transduction pathways are inhibited in hyperosomotic conditions comparable to the renal medulla.

Cells, Cultured↗
PubMed1995

Preventive effect of ulinastatin on renal scarring in rat model of pyelonephritis induced by direct or ascending infection with Serratia marcescens or Escherichia coli.

Renal scarring is considered to be a characteristic of reflux nephropathy. The effects of ulinastatin, a strong inhibitor of polymorphonuclear leukocyte elastase, on renal scarring following direct parenchymal or intravesical ascending infection by Serratia marcescens or Escherichia coli were determined. Four days of treatment with ulinastatin initiated 2 or 5 days after infection prevented renal scarring. Doses of 1,000-4,000 units/kg inhibited renal scar formation, but 8,000 units/kg did not. These results suggest that it may be possible to limit renal scar formation in pyelonephritis by the use of an appropriate pharmacologic agent.

Animals↗
PubMed1995

[Murine "sympathetic orchitis" induced by unilateral testicular injury and autoimmune response].

BACKGROUND: Experimental autoimmune orchitis (EAO) has been studied as an animal model for human male immunological infertility. Most EAO models have been induced by immunization with testis antigens in artificial adjuvants. In this paper, we report a more clinical EAO model. METHODS: Ten to 20 needle punctures were made to the unilateral testis of mice and it was crushed by a needle-holder. RESULTS: Contralateral EAO (so-called "sympathetic orchitis") was gradually induced starting on Day 28. Delayed type hypersensitivity (DTH), one of the cell-mediated immunities, to autologous testicular cells (TC) as well as anti-TC antibodies, humoral immunity, were both detected in those mice. Repeated crush(es) of the ipsilateral testis two weeks later (and four weeks later) as a booster did not enhance the contralateral lesion or autoimmune responses. CONCLUSION: Our present injury model mimics clinical testicular trauma; therefore, this testicular injury model can be very useful in studying the immunological mechanism of EAO and of human immunological male infertility.

Animals↗
PubMed1995

Effect of pili of Serratia marcescens on superoxide production and phagocytosis of human polymorphonuclear leukocytes.

PURPOSE: To determine the role played by superoxide in renal scar formation following renal infection. MATERIALS AND METHODS: The piliation of bacteria was assessed for its capacity to interact with human polymorphonuclear leukocytes (PMNs). Two recombinant strains having either MS or MR pili of Serratia marcescens were constructed. RESULTS: The MS-piliated strain stimulated superoxide production of PMNs twice as much as the MR- or nonpiliated strains did. The MS-piliated strain was more susceptible to phagocytosis than was the MR- or nonpiliated strain. CONCLUSION: These data suggest that the MS-piliated strain stimulates superoxide production of PMNs associated with phagocytosis, which leads to tissue damage in infected organs.

Drug Resistance, Microbial↗
PubMed1995

Testicular injury induces cell-mediated autoimmune response to testis.

Studies on testis autoimmunity are needed for a better understanding of immunological male infertility. Evidence has accumulated that the delayed type hypersensitivity (DTH) response plays a key role in the induction and/or maintenance of experimental autoimmune orchitis (EAO), an animal model for human immunological male infertility or aspermatogenesis. We report here that an antigen-specific DTH response to autologous testicular cells (TC) could be induced by bilateral testicular injury (trauma) in mice. Pretreatment of traumatized mice with a high dose of cyclophosphamide (CY) enhances the DTH response in a dose-dependent manner. The DTH response induced by testicular injury reaches its peak on the ninth day. We have shown that the local passive transfer of the footpad reaction to normal recipients by T cells further defines the DTH reaction. These characteristics resemble those of the previously reported DTH response to syngeneic TC induced by subcutaneous immunization with viable syngeneic crude TC. Our present injury model mimics clinical testicular trauma; therefore, this testicular injury model can be very useful in studying the immunological mechanism of EAO and of human immunological male infertility.

Animals↗
PubMed1994

Renal scarring.

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Bibliography, Descriptive↗
PubMed1993

Direct inactivation of human polymorphonuclear leukocyte by hyperosmotic urea comparable to the renal medulla.

Hyperosmolarity in the renal medulla inhibits host defenses against bacterial pyelonephritis. Urea and NaCl contribute most to high osmolarity in the renal medulla. We therefore examined the inhibitory mechanism of urea on superoxide generation by human polymorphonuclear leukocytes. Superoxide production was inhibited by high concentration of urea. This inhibition was found to be direct and immediate. In addition, direct inactivation of NADPH oxidase, the key enzyme complex of superoxide generation, was shown by an NADPH oxidase activity assay using cell lysates of polymorphonuclear leukocytes stimulated by phorbol myristate acetate. The inhibitory effect of urea on NADPH oxidase was reversed by washing urea out of the assay system of cell lysates. Kinetic analysis of the inhibition of NADPH oxidase activity by urea showed decreased Vmax and Km, suggesting uncompetitive inhibition. These findings suggested that urea inactivated polymorphonuclear leukocyte superoxide production through a direct and uncompetitive inhibition of NADPH oxidase.

Dose-Response Relationship, Drug↗
PubMed1993

Renal scarring is enhanced by phorbol myristate acetate following infection with bacteria with mannose-sensitive pili.

Renal scarring is considered to develop in the later stages of chronic pyelonephritis. In our experimental model of pyelonephritis, bacteria with mannose-sensitive (MS) pili on their surface promoted renal scarring following inoculation into the renal parenchyma. The administration of cyclophosphamide to induce leukopenia and of superoxide dismutase to inactivate superoxide released from polymorphonuclear leukocytes (PMN) at the infection site suppressed any renal scarring following the infection. Conversely, the administration of phorbol myristate acetate at an early stage of infection significantly enhanced the renal scarring. These findings suggest that the PMNs which infiltrate the infection site and the superoxide they release play an important role in any renal scarring following infection with MS-piliated bacteria.

Animals↗
PubMed1993

Suppression of chemotactic activity of neutrophils in hyperosmotic conditions comparable to the renal medulla: partial preservation by phosphoenolpyruvate.

Chemotaxis is one of the most important functions of the polymorphonuclear leukocyte (PMN). In the host defense against pyelonephritis, the renal medulla is a site of interaction between bacteria and PMNs. At this site the osmotic pressure is elevated due to a high concentration of NaCl and urea. We evaluated the in vitro chemotactic activity of PMNs under the hyperosmolar conditions created by high concentrations of NaCl and urea. This activity was suppressed by the stimulation of opsonized zymosan and formyl-methionyl-leucyl-phenylalanine. The inhibition of chemotaxis was partially preserved by phosphoenolpyruvic acid (PEP), a precursor of adenosine triphosphate (ATP), in hyperosmolar NaCl but not in urea. The intracellular content of ATP was increased by supplementing the hyperosmolar NaCl with PEP. These observations suggest that inhibition of the chemotactic activity of PMNs is due to differing mechanisms for each NaCl and urea, and that PEP may protect the PMNs against hyperosmolar NaCl by maintaining ATP content.

Adenosine Triphosphate↗
PubMed1993

Effect of recombinant human granulocyte-colony-stimulating factor on renal scarring following infection with MS-piliated bacteria.

Renal scars have been thought to occur only in later stages of chronic pyelonephritis. In our experimental pyelonephritis model, bacteria with mannose-sensitive (MS) pili on its surface promoted renal scarring when inoculated into renal parenchyma. Pretreatment with recombinant human granulocyte-colony-stimulating factor (rhGCSF) inhibited the renal scarring which followed inoculation with MS-piliated bacteria, whereas posttreatment at an early stage of infection had no effect on renal scarring. These findings suggest that rhGCSF may be useful for the prevention of infection without increasing the tissue damage to the renal parenchyma which leads to the renal scarring. Even when rhGCSF is used for treatment of kidney infection, it does not promote increased renal scarring through the increased invasion of leukocytes at the inflammatory site.

Animals↗
PubMed1993

Effect of prednisolone on renal scarring in rats following infection with Serratia marcescens.

Renal scarring is considered a criterion of reflux nephropathy and the end stage of pyelonephritis. Prednisolone, a strong anti-inflammatory drug, at doses of 1 or 2 mg/kg prevented renal scarring in rats following infection with Serratia marcescens. Four or 8 mg/kg of prednisolone, however, did not inhibit renal scar formation. In a time course experiment, renal scarring was prevented when 4-day treatment with prednisolone was initiated 2, 5, or 13 days after infection. These results show that prednisolone is effective in preventing such scarring and suggest the clinical use of this drug for preventing renal scar formation after pyelonephritis and reflux nephropathy.

Animals↗
PubMed1991

Significance of urinary endotoxin concentration in patients with urinary tract infection.

Endotoxin is a component of the outer membrane of gram-negative rods (GNR). Since GNR are responsible for the majority of urinary tract infection (UTI), we measured the concentration of endotoxin in urine using chromogenic endotoxin-specific assay and examined its diagnostic utility in patients with suspected UTI. In all 18 urine samples with an endotoxin concentration exceeding 350 pg/ml and 2 samples with 10-350 pg/ml of endotoxin concentration, GNR were detected at a count of 10(4) cfu/ml. Negative for endotoxin were 3 samples of culture positive for gram-positive cocci (GPC), 2 samples containing various bacterial contaminants and all 37 samples with no growth on culture. Two urine samples collected 5 h after antibiotic dosage showed negative culture for GNR but a significant concentration of endotoxin. In an in vitro experiment, a residual concentration of antibiotic in urine inhibited bacterial growth, leading to a false-negative culture. These results suggest that chromogenic endotoxin assay is a reliable method for diagnosing UTI caused by GNR and detecting false-negative culture of GNR.

Adult↗
PubMed1991

Role of superoxide in renal scarring following infection by mannose-sensitive piliated bacteria.

The role of superoxide in scar formation following renal infection caused by mannose-sensitive (MS) piliated strains of bacteria was studied in the experimental pyelonephritis model using female Sprague-Dawley rats. The MS piliated strain stimulated renal scarring to a significantly greater extent than either the non-piliated or MR-piliated strain. Modulation of leukocytes by administering cyclophosphamide to induce neutropenia and colchicine to inhibit leukocyte migration was effective in preventing renal scarring. Treatment with superoxide dismutase during the early stage of infection was also effective in preventing scar formation. Finally, the production of superoxide by rat leukocytes was significantly larger following stimulation by MS piliated than either the non-piliated or MR piliated strains. These observations suggest that superoxide released from leukocytes plays a critical role in the development of renal scarring following a bacterial infection, especially by MS piliated strains.

Animals↗
PubMed1991

Inhibition of chemiluminescent response of human polymorphonuclear leukocytes by hyperosmolality comparable to renal medulla and preservation by ofloxacin.

Hyperosmolality of the urine and renal medulla inhibits polymorphonuclear leukocyte (PMN) functions such as phagocytosis, intracellular killing and superoxide generation. The main factors of hyperosmolality in the urinary tract are urea and NaCl. We studied the chemiluminescent (CL) functions of PMNs in hypersomotic urea and NaCl solutions and the effects of ofloxacin, a new quinolone antimicrobial, for inhibiting the functions of PMNs subjected to hyperosmolality. When PMNs were incubated with hypersomotic urea and NaCl solutions, the CL response was significantly reduced. The reduced CL response was significantly preserved by supplementation with ofloxacin (OFLX). The CL response of PMNs may thus also be reduced in the urinary tract and OFLX may exert strong antimicrobial and preservative effects on PMN.

Culture Media↗
PubMed1990

Increased renal scarring by bacteria with mannose-sensitive pili.

Renal scars are thought to be the end stage of chronic pyelonephritis and one of the most important causes of renal insufficiency and renal hypertension. The role of bacterial pili was examined in scar formation after an infection of newly constructed bacterial strains using the recombinant DNA technique, which possessed either mannose resistant (MR) or mannose sensitive (MS) pili of Serratia marcescens. Strains that differed in only a single virulence factor, namely, MR or MS pili, were used in a rat model of chronic pyelonephritis. In this model, MS-piliated bacteria stimulated renal scarring more severely than non-piliated or MR-piliated bacteria.

Animals↗
PubMed1990

Suitability of colchicine and superoxide dismutase for the suppression of renal scarring following an infection with bacteria showing mannose-sensitive pili.

Two new strains of Serratia marcescens were constructed by the gene manipulation method from the clinical isolate US 46, which has two kinds of pili--mannose-sensitive (MS) and mannose-resistant (MR) ones--on the cell surface. After cloning the genes of the MS and MR pili, either the MS or the MR gene was transferred to the nonpiliated Escherichia coli, and MS- or MR-piliated strains were obtained. In the experimental pyelonephritis model of rats, MS- or MR-piliated bacteria were inoculated directly to the renal parenchyma, and the following results were obtained. MS-piliated rather than MR-piliated strains stimulated severe scarring of the kidney, and this scarring was suppressed by treatment with colchicine or superoxide dismutase (SOD) during an early stage of the infection. These findings suggest that MS-piliated bacteria stimulated polymorphonuclear leukocytes, which released large amounts of superoxide resulting in renal scarring. SOD was hoped to be a drug capable of preventing renal scarring, and such a result was successfully obtained.

Animals↗
PubMed1989

A cryptic fimbrial gene in Serratia marcescens.

The gene coding for the mannose-sensitive hemagglutinating fimbriae in Serratia marcescens US5 was cloned into Escherichia coli K4 with a cosmid vector system. One of the transformants, US5-1, expressed two morphologically distinct fimbriae, one that was 5-nm wide and one that was 3-nm wide. The latter fimbria was morphologically and serologically indistinguishable from that of strain US5. Genetic analysis of transformant US5-1 showed that the gene responsible for the 5-nm-wide fimbriae was located more than 10 kilobases away from the gene responsible for the 3-nm-wide fimbriae. The molecular sizes of the subunits of these two fimbriae, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were 19 kilodaltons for the 3-nm-wide fimbriae and 20 kilodaltons for the 5-nm-wide fimbriae. Serologically, the 5-nm-wide fimbriae did not cross-react with monoclonal or polyclonal antibodies raised against the mannose-sensitive hemagglutinating fimbriae of strain US5. Strain EL101, which expressed only the 5-nm-wide fimbriae, did not agglutinate chicken or human erythrocytes. These experimental results suggest that the gene for the 5-nm-wide fimbriae is cryptic in strain US5 and is expressed in E. coli K4 only after it is moved by transformation.

Amino Acid Sequence↗