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Biomedical subjects

M Hirata

Publications and source records attributed to M Hirata.

At least 307 records · Page 17Linked to original sources
PubMed1994

Contraction and depolarization induced by fetal bovine serum in airway smooth muscle.

We investigated the effects of fetal bovine serum (FBS) on the resting membrane potential and muscle tone of canine airway smooth muscles using tension recording and microelectrode methods. At concentrations > 0.1%, FBS induced a sustained increase in muscle tone. At concentrations > 1%, FBS depolarized the resting membrane potential of dog trachea in a dose-dependent manner. When FBS was dialyzed, it failed to induce a sustained increase in muscle tone or to depolarize the membrane, indicating that FBS contained factor(s) that induced contraction of dog airway smooth muscles. When FBS was dialyzed against distilled water, the outer solution which was freeze dried and then reconstituted (> 1% in original vol) induced a sustained increase in muscle tone, indicating that FBS contained dialyzable factor(s) that increased muscle tone and depolarized the resting membrane potential of dog airway smooth muscles. Methysergide (10(-6) M) or cyproheptadine (10(-6) M), nonspecific antagonists to serotonin receptors, 5-hydroxytryptamines (5-HT1 and 5-HT2), markedly reduced the FBS-induced increase in the muscle tone to approximately 20% of the original value but did not abolish the response. On the other hand, methysergide (10(-6) M) completely suppressed the increase in the muscle tone evoked by peak fractions obtained by application of the dialysate of FBS or 5-HT to a C18 reverse-phase column, indicating the peak fractions contained only 5-HT. These observations indicate that FBS contained 5-HT and an unknown factor(s) responsible for increase in the muscle tone of the airway smooth muscle induced by FBS.

Animals↗
PubMed1994

Effects of epithelial cell supernatant on membrane potential and contraction of dog airway smooth muscles.

We investigated the effects of cultured epithelial cells and supernatants on resting membrane potential and excitatory neuroeffector transmission in smooth muscle cells of dog trachea and bronchioles. The mean resting membrane potential of the mucosa-free tracheal smooth muscle cells was -59.5 +/- 1.5 mV (+/- SD). Application of cultured epithelial cells (> 2.5 x 10(5) cells/ml) hyperpolarized the membrane, resulting in a potential of -64.5 +/- 1.7 mV. The supernatant of the cultured epithelial cells also increased the resting membrane potential of the mucosa-free tracheal smooth muscle cells by 4 to 9 mV. These hyperpolarizing actions were not modified by indomethacin (10(-5) M), l-NG-nitroarginine (10(-5) M), or oxyhemoglobin (10(-5) M), but were inhibited by glibenclamide (10(-6) M). The supernatants of the cultured epithelial cells completely or partially suppressed the contractile response of epithelium-denuded bronchioles to electrical field stimulations and suppressed the amplitude of excitatory junction potentials of the trachealis evoked by electrical field stimulations. Indomethacin prevented the inhibitory effect of supernatants on the amplitude of twitch contractions and excitatory junction potentials and markedly suppressed supernatant-associated inhibition of the excitatory neuroeffector transmission. Furthermore, indomethacin with AA861, a lipoxygenase inhibitor, completely suppressed this effect. Our findings suggest that cultured airway epithelial cells spontaneously release at least two factors. One factor selectively modulates the resting membrane potential, and the other inhibits the excitatory neuroeffector transmission.

Animals↗
PubMed1994

Granulocyte-macrophage colony stimulating factor suppresses lipopolysaccharide-induced osteoclast-like cell formation in mouse bone marrow cultures.

Lipopolysaccharide (LPS) is a potent bone resorbing factor. We investigated the effect of LPS on osteoclast formation in three types of cultures. LPS inhibited osteoclast formation induced by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], in a dose-dependent manner, in cultures of whole bone marrow cells without dexamethasone. LPS increased the amount of granulocyte-macrophage colony stimulating factor (GM-CSF) in the culture supernatant, and anti-GM-CSF antiserum almost abolished the inhibition of osteoclast formation by LPS, thereby indicating that GM-CSF generated by treatment with LPS may be responsible for the inhibition of osteoclast formation. In cultures with dexamethasone, the amount of GM-CSF was decreased to one-third of that with 1,25(OH)2D3 alone and was not changed by treatment with LPS. In this culture system, LPS enhanced osteoclast formation. In the coculture system of nonadherent bone marrow cells and a stromal cell line in the presence of 1,25(OH)2D3 and dexamethasone, where no detectable GM-CSF was present in the supernatant, LPS markedly enhanced osteoclast formation, whereas exogenously added GM-CSF (100 pg/ml) almost completely inhibited osteoclast formation. LPS stimulated pit formation on dentin slices by the osteoclast-like cells formed by in vitro culture system.

Animals↗
PubMed1994

Dexamethasone stimulates osteoclast-like cell formation by inhibiting granulocyte-macrophage colony-stimulating factor production in mouse bone marrow cultures.

We investigated the effect of glucocorticoid on the generation of osteoclasts. In mouse bone marrow culture systems, dexamethasone, a synthetic glucocorticoid analog, enhanced osteoclast-like cell formation induced by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in a dose-dependent manner. Conversely, dexamethasone inhibited the endogenous production of granulocyte-macrophage colony-stimulating factor (GM-CSF) in bone marrow cultures. GM-CSF, when added exogenously, suppressed not only the osteoclast-like cell formation induced by 1,25-(OH)2D3, but also the stimulatory effect of dexamethasone, and addition of anti-GM-CSF neutralizing antibody to the cultures significantly increased the osteoclast-like cell formation induced by 1,25-(OH)2D3. These observations suggest that dexamethasone directly affects bone marrow cells and enhances osteoclast generation by inhibiting the endogenous production of GM-CSF, which may function as a negative regulator of osteoclast formation.

Acid Phosphatase↗
PubMed1994

Anti-inflammatory effect of 22-oxa-1 alpha,25-dihydroxyvitamin D3 on carrageenin-induced inflammation in rats.

The anti-inflammatory effect of 22-oxa-1 alpha,25-dihydroxyvitamin D3 [22-oxa-1 alpha,25(OH)2D3], an analogue of the active form of vitamin D3, was studied regarding carrageenin-induced inflammation in rats. In the early phase of the inflammation, the formation of granulation tissue and the weight of exudate were significantly suppressed by both oral and local administrations of 22-oxa-1 alpha,25(OH)2D3 daily for 4 d (day 0-3) after carrageenin injection, though the local injection of 22-oxa-1 alpha,25(OH)2D3 (7 and 10 micrograms/kg) into the carrageenin-air-pouch was much more effective than the oral administration of the compound (20 micrograms/kg). Similarly, oral and local administrations of 22-oxa-1 alpha,25(OH)2D3 from day 4 to 7 significantly suppressed the increase in exudate and the proliferation of granulation tissue in the late phase of carrageenin-induced inflammation in rats. The results suggest that 22-oxa-1 alpha,25(OH)2D3 has an anti-inflammatory activity on both the acute and proliferative phases of inflammation in rats.

Animals↗
PubMed1994

Digestion of endothelin-1 on cultured vascular smooth muscle cells.

The degradation of 125I-endothelin-1 (125I-ET-1) was examined on cultured porcine aortic endothelial cell (EC) and rat vascular smooth muscle cell (SMC) by HPLC analysis. The degradation of ET-1 was observed on SMC and was slightly observed on EC. Membrane fractions of SMC had a strong potency for the degradation of ET-1 and retained activity even in plasma. This activity was inhibited with some of the noble inhibitors which were known as enkephalinase inhibitors. These results suggest that endothelin degradation enzyme on SMC is related to enkephalinase and that this enzyme plays a significant role in the degradation of ET-1 in vivo.

Animals↗
PubMed1994

Purification and characterization of endothelin-1 degradation activity from porcine kidney.

In order to identify the membrane-bound peptidase that is responsible for the degradation of endothelin (ET), an endothelin-1 (ET-1) degradation enzyme was solubilized from membrane fractions of porcine kidney with 1% Triton X-100, and subsequently purified by column chromatographies, i.e., diethylamino-Sepharose ion exchange, gel permeation, Con A Sepharose and hydroxyapatite chromatography. On DEAE-Toyopearl ion exchange column chromatography, the ET degradation enzyme and aminopeptidase were separated, but ET degradation enkephalinase activities were not separable. In order to separate ET degradation enzyme and enkephalinase, the active fractions were loaded on each of the column chromatographies: sephacryl S-200, Con A Sepharose or hydroxyapatite. The ET degradation activities were co-migrated with enkephalinase activities on all of the three chromatographies. In addition, the ET degradation activities were inhibited by thiorphan, phosphoramidon and EDTA, which are known to inhibit enkephalinase. These results suggest that ET degradation activity in the membrane fractions of the kidney is related to enkephalinase and may be involved in the degradation of ET-1 in vivo.

Aminopeptidases↗
PubMed1994

Effect of P-450 inducers on glutathione (GSH) depletion by bromobenzene in primary cultures of dog hepatocytes.

Primary cultures of dog hepatocytes sensitivity responded to various inducers of cytochrome P-450; phenobarbital (PB) significantly elevated the activity of 7-ethoxycoumarin O-deethylase (ECOD) and progesterone 6 beta-hydroxylase (6 beta-OHP). beta-Naphthoflavone (beta-NF) and rifampicin (Rif) elevated the levels of 7-ethoxyresorufin O-deethylase (EROD) and 6 beta-OHP, respectively. When primary cultures of dog hepatocytes were incubated with bromobenzene, cellular reduced glutathione (GSH) levels decreased time- and dose-dependently. Pretreatment of the cultures with PB enhanced GSH depletion by bromobenzene, while beta-NF and Rif had little effect, suggesting that the 2B type cytochrome P-450 is responsible for the primary oxidation of bromobenzene to GSH-reactive metabolite(s). Bromobenzene-dependent GSH depletion was completely prevented by 10 microM SKF-525A both in the control and PB-treated primary cultures. Treatment of dog primary cultures with PB analogues also elevated the level of drug-metabolizing activity leading the cells to be more susceptible to GSH depletion by bromobenzene.

Animals↗
PubMed1994

Pheophorbide a, a potent endothelin receptor antagonist for both ETA and ETB subtypes.

Many crude drugs were screened for their capacity to inhibit the binding of endothelin-1 (ET-1) to ET receptors; several crude drugs showed significant binding inhibitory activity. Pheophorbide a (1), a potent non-peptide ET receptor antagonist, was isolated from Altemisiae capillaris Flos ("Inchinko" in Japanese), which has been utilized as a remedy for hepatitis in Oriental medicine. In receptor binding experiments, compound 1 inhibited ET-1 binding specifically to both the ETA receptor (ETAR) and ETB receptor (ETBR), with IC50 values of 8.0 x 10(-8) and 2.1 x 10(-7) M, respectively. Thus, compound 1 is an ET-1 binding inhibitor; however, it exhibited no affinity for the other receptors of angiotensin II and atrial natriuretic peptide. We also evaluated the inhibitory activity of porphyrin compounds, and found that some exhibited moderate activity.

Animals↗
PubMed1994

[Antioxidative effect of mammalian liver hydrolyzate on lipid peroxidation].

The antioxidative effect of the mammalian liver hydrolyzate preparation (LH) was investigated mainly in the mouse liver homogenates. At lower concentrations, LH stimulated lipid peroxidation induced by Fe2+ and ascorbic acid in the homogenates, but inhibited completely the oxidation at higher concentrations. LH also inhibited the peroxidation of linolenic acid and linoleic acid. LH reduced 1,1-diphenyl-2-picrylhydrazyl, a free radical model, in a concentration-dependent manner, suggesting that the radical scavenging property of LH is involved in its antioxidative action. Fe2+ and glutathione, contained in LH, seem to act as a stimulator and an inhibitor of peroxidation, respectively.

Animals↗
PubMed1994

Increased lactic dehydrogenase (LDH)-linked immunoglobulin associated with interferon-alpha therapy in a case of chronic hepatitis C.

A 47-year-old man diagnosed as having chronic hepatitis C was admitted to our hospital where he was treated with interferon (IFN)-alpha. After initiation of this treatment, his serum LDH became elevated, and when the drug was stopped, it decreased gradually to within the normal range. The histopathological findings and the liver function were not aggravated. The administration of IFN-alpha showed a correlation to LDH-linked immunoglobulin, a complex of LDH and immunoglobulin, often causing high levels of LDH. In patients on IFN therapy with elevated LDH, LDH-linked immunoglobulin should be tested.

Antigen-Antibody Complex↗
PubMed1994

Pediatric renal transplantation.

1. Approximately half of the pediatric patients received grafts from their parents and half from cadaver donors. Pediatric recipients accounted for only 5% of cadaver-donor transplants. 2. Pediatric patients differed from adults in the incidence of primary disease, principally in the occurrence of diabetes (almost no juvenile diabetics had progressed to renal failure compared with 30% among adults). Obstructive uropathy and dysplasia were the primary diseases for about 37% of pediatric patients compared with 3% in adults. 3. Pediatric patients under the age of one had a markedly lower graft survival with cadaver donors. Such patients had much higher survival rates with parental donor kidneys. 4. Pediatric retransplants from parents had a graft survival comparable to adult grafts. Regraft survival in children given cadaveric kidneys were significantly lower than adult grafts. 5. Patients under the age of 18 with no diuresis on the first day or who required dialysis in the first week had a markedly lower graft survival rate compared with that of adults with comparable early dysfunction. 6. Kidneys from donors under 2 years old yielded a 67% one-year graft survival rate in infants, but an 87% survival in patients 16-18 years of age at 6 selected individual centers. These centers, that had performed more than 20 infant-donor renal transplants, achieved results comparable to those of transplants using grafts from older donors in recipients aged over 11 years. 7. Pediatric patients who received grafts mismatched for 5- and 6-HLA antigens had a significantly lower graft survival rate than those with better matches. 8. Black patients ages 11-18 years old had a lower graft survival rate than White patients in the same age group.

Adolescent↗
PubMed1994

Renal retransplantation.

1. In 1984, second graft survival rates were 10% lower than first grafts, but in 1992, the survival difference was reduced to 1%. Multiple grafts in 1984 were 23% lower than first grafts, but showed only a 7% difference in 1992. In 1992, 12% of kidney grafts were performed into second graft recipients and 3% into multiple graft recipients. 2. If first grafts survived one to 12 months posttransplant, the second graft survival was less than if they had survived longer than 12 months, as seen in many previous analyses. Here we showed that patients with a first graft duration of one to 12 months had a higher incidence of sensitization than patients with a first graft duration of more than 12 months. This may indicate that immunization was the cause of failure more frequently among those patients who rejected earlier than later. 3. Since 1989, the interval between first graft rejection and second graft transplantation was not a factor in second graft survival. A strong correlation was noted between high PRA and interval to regrafting. This probably reflects the increasing difficulty in finding negative-crossmatch donors as PRA increases. 4. Repeat mismatches for HLA-DR were deleterious to second grafts, although repeat mismatches for HLA-A,B were not, confirming earlier studies (1,5). HLA-A,B,DR mismatches correlated well with second and multiple transplant outcomes. 5. Patients receiving second cadaver-donor transplants had the same graft survival regardless of whether the first graft was another cadaver donor or a living-related one. On the other hand, second living-related donor transplants had a higher graft survival rate if the first graft had also been from a living-related rather than a cadaver donor (p < 0.05). This suggests that it would be advantageous if the first graft came from a living-related donor with a cadaver donor as the second graft, rather than the reverse situation. 6. Urine production on the first postoperative day was a very strong indicator of subsequent graft survival, particularly for second and multigraft patients. Failure to diurese on the first day resulted in a second graft survival of 60% at one year compared with 80% for those that diuresed on the first day. 7. Similarly, dialysis requirements were a major factor in predicting subsequent graft survival. For second graft patients who required dialysis, one-year graft survival was 63%, compared with 84% if no dialysis was needed. 8. The fraction of patients who had insulin dependent diabetes for first grafts was 27%, 15% for second grafts, and 9% for multiple grafts.(ABSTRACT TRUNCATED AT 400 WORDS)

Graft Survival↗
PubMed1994

Rabbit CAP18 derived peptides inhibit gram negative and gram positive bacteria.

CAP18 (cationic antimicrobial protein of 18 kDa) was originally isolated from rabbit granulocytes using as an assay the agglutination of Re-lipopolysaccharide coated erythrocytes. The C-terminal 37 amino acids of CAP18 comprise the LPS-binding domain called RNIP, reactive nitrogen inhibitory peptide. Synthetic RNIP has broad antimicrobial activity versus both gram positive [IC50 = 130-200 nM] and gram negative bacteria [IC50 = 20-100 nM). Susceptible strains include Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Streptococcus pyogenes. Antimicrobial activity is highly dependent upon peptide structure. Although a 32 amino peptide resulting from truncation of five amino acids from the C terminus of RNIP is highly active, other fragments of RNIP including truncation of its N-terminus do not exhibit antimicrobial activity. Unlike previously characterized antimicrobial peptides derived from granulocyte proteins RNIP is active in serum. RNIP or a derivative peptide may have therapeutic potential for bacterial sepsis.

Amino Acid Sequence↗
PubMed1994

Endotoxin-binding synthetic peptides with endotoxin-neutralizing, antibacterial and anticoagulant activities.

Endotoxin(lipopolysaccharide = LPS), cell wall component of gram-negative bacteria, activates monocytes and macrophages to release cytokines, reactive nitrogen intermediates (RNI), and to generate tissue factor(TF) which initiate coagulation. We have purified 7kDa and 18kDa cationic antibacterial proteins (CAP-7 and CAP-18) with LPS-binding and LPS-neutralizing activities from rabbit granulocytes using as an assay the agglutination of erythrocytes coated with Re-LPS. From protein sequencing, CAP-7 was identified as the C-terminal 37 amino acid fragment of CAP-18. Synthetic peptide #197 (identical sequence to CAP-7, Gly1-Try37) and #36-1 (a truncation of CAP consisting of 32 amino acid residues, Gly1-Ala32) showed LPS-binding activity. Each peptide inhibited LPS-induced tissue factor(TF) generation by murine peritoneal macrophages, even added 1-3 hours after stimulation of cells with LPS. C57BL/6 mice treated with #197 were significantly protected from lethal LPS challenge. Peptide #36 also blocked the LPS-induced lethality. These peptides had antibacterial activity to gram-negative bacteria, such as E.coli, S.typhimurium, K.pneumonia, Ps.aeruginosa and also to gram-positive S.aureus (Methicillin sensitive and resistant strains). Both peptides inhibited TF- and Xa-induced plasma clotting. Using synthetic chromotogenic substrates, both CAP7 peptides blocked the coagulation cascade at two sites, activation of factor X to Xa and conversion of Factor II (prothrombin) to factor IIa (thrombin). In vivo treatment of peptide #197 prevented acute lethality in mice injected with tissue factor (rabbit brain thromboplastin). Two other peptides, #32(Gly1-Phe9) and #50(Ile13-Typ37) failed to demonstrate LPS-binding, LPS-neutralizing, antibacterial and anticoagulant activities. The active peptides but not the inactive peptide maintain a putative heparin binding domain at their N-termini. This heparin binding domain is participate in the LPS-binding, LPS neutralizing, antibacterial and anticoagulant activities of CAP7. These active peptides may have a therapeutic potential for treatment for DIC due to sepsis and endotoxin shock.

Amino Acid Sequence↗
PubMed1994

Mechanically assisted intraoperative peritoneal lavage for generalized peritonitis as a result of perforation of the upper part of the gastrointestinal tract.

BACKGROUND: The efficiency of intraoperative peritoneal lavage (IOPL) and peritoneal drainage in patients with generalized peritonitis remains controversial. The benefit of large volume IOPL, using a newly designed device, and of peritoneal drainage were evaluated in 101 patients with generalized peritonitis. STUDY DESIGN: Patients were divided into two groups, one treated by mechanically assisted IOPL (group 1), and the other treated by manual IOPL (group 2). They were further divided into two groups, one undergoing drainage (DR group) and the other undergoing no drainage (ND group). Based on data in the progress notes, patients in these groups were compared with each other with respect to disease process, volume of IOPL fluid, incidence of infectious complications, and other prognostic factors. RESULTS: In group 1, the incidence of infectious complications was significantly lower than in group 2 (10.8 versus 62.9 percent, p < 0.01). Patients who underwent operative treatment 12 hours or more after onset of peritonitis had a lower incidence of infection following high volume IOPL (greater than or equal to 30 L) compared with those patients who underwent low volume IOPL. The incidence of infectious complications was significantly higher in the DR group (32.8 versus 12.9 percent). CONCLUSIONS: A large volume of saline (greater than or equal to 30 L) was needed for IOPL. The new device for IOPL proved to be very successful and efficient. When IOPL was successful, it seemed that peritoneal drainage did not provide any additional benefits to the treatment of generalized peritonitis.

Adolescent↗