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Biomedical subjects

K Irie

Publications and source records attributed to K Irie.

At least 199 records · Page 11Linked to original sources
PubMed1992

A thromboxane A2 synthetase inhibitor retards hypertensive rat diabetic nephropathy.

Spontaneously hypertensive rats (SHR) were injected with streptozotocin (STZ-SHR) to induce diabetes. The effect of DP-1904, a thromboxane A2 synthetase inhibitor, on diabetic nephropathy was then studied by administering it for 5 months (1 or 10 mg/kg). DP-1904 did not affect renal 6-keto prostaglandin (PG)F1 alpha production in STZ-SHR, but markedly inhibited renal thromboxane (TX) B2 production, so that the 6-keto PGF1 alpha/TXB2 ratio was significantly increased (P less than 0.05). STZ-SHR showed significant uraemia and proteinuria, plus increases in urinary gamma-glutamyl-transpeptidase and urinary N-acetyl-beta-glucosaminidase. DP-1904 significantly decreased (P less than 0.01) the urinary changes. STZ-SHR also showed an increase in mesangial periodic acid-Schiff-positive substance and in relative renal weight, both of which were significantly inhibited by DP-1904 (P less than 0.05). Thus, DP-1904 inhibited both TXB2 production and the progression of renal damage in STZ-SHR.

Acetylglucosaminidase↗
PubMed1992

Histological and biochemical analysis of the fibrous tissue induced by implantation of synthetic ligament (Dacron): an experimental study in a rat model.

We conducted a comparative study to evaluate the quality and true nature of the fibrous tissue formed around synthetic grafts when used in ligament replacement. In one group of Lewis rats, a patellar ligament was replaced with a Dacron prosthesis; the comparison group received a tail tendon isograft. Two-, 4-, 8-, 12-, and 24-week comparisons showed histological and biochemical changes in the Dacron group alone that were consistent with foreign-body reaction. Specifically, the Dacron group showed infiltration by large numbers of macrophages and foreign-body, multinucleated giant cells. In addition, the capsule of fibrous tissue that developed around the Dacron ligaments was characterized by lower collagen solubility, a higher content of noncollagenous protein, and a higher proportion of type III collagen than that comprising the isografted tendons. The results of this study call into question the suitability of synthetics for ligament replacement.

Animals↗
PubMed1992

Histochemical and fine structural study of bone of ipriflavone-treated rats.

Bone labeling, histochemical, and fine structural studies were performed in order to clarify the effects of ipriflavone (IP) on rat bone tissue in vivo and in vitro. Labeling experiments showed a slight increase in bone formation during 3 days' administration. It was also noted that many osteoclasts detached from the bone surface at 1, 2, and 6 hours after administration in vivo. In addition, irregular localization of tartrate-resistant acid phosphatase (TRACPase) activity was observed in osteoclasts. Fine structurally, IP-treated osteoclasts exhibited irregularity in their ruffled borders, as reported in calcitonin administration, and many enlarged rough endoplasmic reticuli and vacuoles were observed. However, osteoclasts at 12 hours after administration, as well as the control, indicated recovery features from the effect of IP. Osteoblast proliferation and differentiation led to increasing alkaline phosphatase activity (ALPase) with time as well as the development of rough endoplasmic reticuli and Golgi apparatus with well-developed fine structure. These findings imply active synthesis of bone matrix. In our in vitro experiment, osteoclasts and osteoblasts displayed histochemical and fine structural characteristics similar to those observed in our in vivo experiment. Moreover, fewer TRACP-positive mononuclear cells were observed after 24-hour culture with IP than with the control. These results suggest that IP inhibits directly and/or indirectly differentiation and activity of osteoclasts and also promotes differentiation of osteoblast-lineage cells and their bone-forming activity.

Acid Phosphatase↗
PubMed1992

Dentigerous cyst associated with a deciduous tooth. A case report.

A case of a dentigerous cyst associated with a deciduous tooth in a 2-year-old boy is presented. Radiologic examination revealed a well-defined radiolucency in the right maxilla associated with the crown of a maxillary second deciduous molar. The cyst cavity was lined with nonkeratinized squamous epithelium, and odontogenic epithelial islands were seen in subepithelial connective tissue.

Child, Preschool↗
PubMed1992

Electrophysiological study of four patients with Fisher syndrome: a mechanism of areflexia.

Electrophysiological studies were performed on four patients with the Fisher syndrome (two 4-year-old boys, a 5-year-old boy and a 9-year-old girl). Motor nerve conduction velocity (MNCV), nerve action potential, F wave, H reflex and T reflex were measured at the stage when areflexia was present but ataxia and ophthalmoplegia had recovered. MNCV and SNCV by compound mixed nerve potential were normal in all our patients. The amplitude of the muscle responses (M-responses) and compound mixed nerve action potentials were also within normal limits. The latencies of the F waves and F wave conduction velocities were normal. However, H-reflexes and T-reflexes were absent in all four cases. Our results suggested that areflexia in the Fisher syndrome is attributed to the desynchronization of the impulses or the partial conduction block of GIa fibers.

Ataxia↗
PubMed1992

Effects of a human antiflagellar monoclonal antibody in combination with antibiotics on Pseudomonas aeruginosa infection.

The in vivo activity of human immunoglobulin M monoclonal antibody IN-2A8, which is specific for flagellum type b of Pseudomonas aeruginosa, was evaluated in comparison to anti-O antigen (serotype B) MAb KO-2F2 and in combination with antibiotics. IN-2A8 showed stronger activity than KO-2F2 against subcutaneous infection in burned mice, while it was much less active against intraperitoneal infection in normal mice. In a burn infection model, IN-2A8 inhibited the increase of bacteria in skin lesions weakly and that in blood significantly, suggesting that it strongly suppressed bacterial spread to blood. The activity of IN-2A8 in combination with 10 antipseudomonal antibiotics against intraperitoneal infection was examined. Clear additive effect was observed with a combination of either carbapenem or aminoglycoside antibiotics in terms of mouse survival. The administration of an antibiotic, imipenem-cilastatin, simultaneously with or before that of IN-2A8 gave a combined effect, but the reverse order did not. The combination of IN-2A8 with imipenem-cilastatin decreased numbers of viable bacteria in the peritoneal cavity and blood and kept them low for a longer time than did either treatment alone. These results suggest that an antiflagellar monoclonal antibody would be effective against systemic infection in combination with some kinds of antibiotics.

Animals↗
PubMed1992

[Studies on biological characteristics of undifferentiated carcinoma of the esophagus].

To study the biological characteristics of undifferentiated carcinoma of the esophagus, the nuclear DNA content, the growth fraction using monoclonal antibody Ki-67 (Ki-67), immunohistochemical expression of epidermal growth factor receptor (EGFR) and the grade of Leu-7 positive cells infiltrating at the marginal area of the cancerous tissue were measured in 5 cases of undifferentiated carcinoma and 131 cases of squamous cell carcinoma. The following results were obtained. 1) DNA aneuploid was found in 60% of undifferentiated carcinoma, 47% of squamous cell carcinoma. 2) The Ki-67 labeling rates of undifferentiated carcinoma were higher than those of squamous cell carcinoma, and a variable proportion of Ki-67 labeling rates of undifferentiated carcinoma was ranging from 12% to 34%. It was demonstrated that undifferentiated carcinoma had high proliferative potential. 3) The expression of the EGFR was stained in the basal cell and parabasal layers of normal epithelia. In squamous cell carcinoma, EGFR was located on the cancer cell membrane and was observed 79%, while in all cases of undifferentiated carcinoma, it was not detected. 4) The grade of Leu-7 positive cells was related to pathological stage and prognosis in squamous cell carcinoma. The patients with low grade of Leu-7 positive cells frequently had early recurrences of the carcinoma after esophagectomy, and their prognosis was poorer than those with higher grade of Leu-7 positive cells. The patients of undifferentiated carcinoma, independently of pathological stage, were observed low grade of Leu-7 positive cells and had poor prognosis except only one case. Therefore undifferentiated carcinoma seems to be escaped from defensive mechanism of host immune response.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

[Combination therapy of doxifluridine (5'-DFUR) + cyclophosphamide (CPA) + tamoxifen (TAM) for advanced or recurrent breast cancer. Joint Research Group in the Osaka Area for Combination Therapy of 5'-DFUR with Other Drugs].

Outpatients with advanced and recurrent breast cancer were treated by a combination therapy of the following drugs: doxifluridine (5'-DFUR) orally administered at a dose of 1200 mg/day; cyclophosphamide (CPA) orally given at dose of 100 mg/day; and tamoxifen (TAM) orally given at dose of 20 mg daily. 5'-DFUR and CPA were administered on consecutive days 1-14, then discontinued for 14 days. The response rate was 44.8% including five CR and eight PR out of 29 complete cases. As for response cases in terms of the subject lesions, corresponding cases were chiefly found in soft tissue and the lung. As for the response rate with or without pretreatment, cases previously treated showed a higher response rate such as 42.9% indicating that the present therapy was effective in pretreatment cases. The main side effect was leukopenia, but not so severe. Few cases with diarrhea were found. Based on the above findings, the present treatment is conceivably a highly useful therapy, on an outpatient basis, for advanced and recurrent breast cancer, especially metastatic lesions of soft tissue and the lung.

Administration, Oral↗
PubMed1991

A new protein kinase, SSP31, modulating the SMP3 gene-product involved in plasmid maintenance in Saccharomyces cerevisiae.

The pleiotropic smp3 mutation on the Saccharomyces cerevisiae chromosome confers three phenotypes, (i) stable maintenance of a heterologous plasmid pSR1 isolated from Zygosaccharomyces rouxii, (ii) slow cell growth, and (iii) temperature-sensitive growth. The SSP31 gene of S. cerevisiae was isolated as a chromosomal DNA fragment suppressing the thermosensitive cell growth of the smp3 mutant when it was ligated into the low-copy vector, YCp50. However, it did not suppress the phenotypes of stable maintenance of pSR1 and slow cell growth of the smp3 mutant, even when ligated into the multicopy vector, YEp24. The nucleotide sequence of SSP31 suggested that it encodes a protein of 148 kDa containing all the conserved domains of protein kinases. The putative SSP31 protein also has a hybrid structure of serine/threonine and tyrosine kinases in the diagnostic subdomains for target specificity of protein kinases. Disruption of SSP31 was not lethal, but resulted in slow cell growth. The SSP31 was mapped between the ilv3 and ura2 loci on chromosome X.

Amino Acid Sequence↗
PubMed1991

L-NG-nitro-arginine inhibits nicotine-induced relaxation of isolated rat duodenum.

We studied the effects of L-NG-nitro-arginine (L-NOARG), which inhibits nitric oxide (NO) biosynthesis from L-arginine, on the non-adrenergic, non-cholinergic (NANC)-mediated relaxation induced by nicotine in isolated rat duodenum. L-NOARG reduced nicotine-induced relaxation, and L-arginine prevented the inhibitory effect of L-NOARG. However, L-NOARG did not inhibit the tetrodotoxin-insensitive relaxation induced by adenosine 5'-triphosphate, alpha, beta-methyleneadenosine 5'-triphosphate, thyrotropin-releasing hormone or the calcitonin gene-related peptide. Endogenous NO thus could possibly be involved in the NANC-mediated relaxation of rat duodenum induced by nicotine.

Adenine Nucleotides↗
PubMed1991

SGV1 encodes a CDC28/cdc2-related kinase required for a G alpha subunit-mediated adaptive response to pheromone in S. cerevisiae.

The GPA1 gene of S. cerevisiae encodes a G alpha subunit that plays a positive role in the transduction of signals stimulating recovery from pheromone-induced cell cycle arrest. The GPA1Val50 mutation, in which Gly-50 is replaced by valine, causes hyperadaptation to pheromone. However, GPA1Val50 cells do not recover from division arrest in the absence of both CLN1 and CLN3, which encode G1 cyclins, indicating that the recovery-promoting activity of GPA1Val50 requires the function of G1 cyclins. An sgv1 mutation suppresses the hyperadaptive response caused by GPA1Val50 and also confers cold- and temperature-sensitive growth. The SGV1 gene encodes an apparent protein kinase homologous to CDC28/cdc2 kinase: SGV1 is 42% identical to CDC28. The activated mutation, CLN3-2, partially suppresses the growth defect of sgv1, suggesting that the SGV1 and CLN3 proteins may act in the same growth control pathway.

Amino Acid Sequence↗
PubMed1991

A thromboxane A2 synthase inhibitor, DP-1904, prevents rat renal injury.

The effects of DP-1904, a thromboxane (TX) A2 synthase inhibitor, on renal function were investigated by analysis of prostanoid metabolism in hydronephrotic and ischemic rat kidney models, and in isolated perfused normal and hydronephrotic rat kidneys. The increase in production of TXB2 in hydronephrotic or ischemic kidneys was significantly suppressed by intraperitoneal DP-1904 (10 mg/kg), with the 6-keto-prostaglandin F1 alpha to TXB2 ratio being significant increased. Urine volume, glomerular filtration rate and renal plasma flow were all improved. DP-1904 (0.3 micrograms/min) blocked the effects of infused arachidonic acid on isolated perfused normal rat kidneys thus reducing TXB2 levels and perfusion pressure but the pressor response to norepinephrine or angiotensin II remained unchanged. In isolated perfused hydronephrotic rat kidneys, DP-1904 suppressed the increase in perfusion pressure and TXB2 production caused by platelet-activating factor. These findings suggested that DP-1904 improved renal failure by specifically inhibiting TXA2 production.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Mutations in a Saccharomyces cerevisiae host showing increased holding stability of the heterologous plasmid pSR1.

We have isolated Saccharomyces cerevisiae mutants, smp, showing stable maintenance of plasmid pSR1, a Zygosaccharomyces rouxii plasmid. The smp mutants were recessive and were classified into at least three different complementation groups. The three mutants also showed increased stability of YRp plasmids and the mutations are additive for plasmid stability. One mutation, smp1, confers a respiration-deficient (rho0) phenotype and several Rho- mutants independently isolated by ethidium bromide treatment of the same yeast strain also showed increased stabilities of pSR1 and YRp plasmids. The wild-type S. cerevisiae cells showed a strongly biased distribution of pSR1 molecules as well as YRp plasmids to the mother cells at mitosis, while the smp1 mutant did not show this bias. Another mutation, smp3, at a locus linked to ade2 on chromosome XV, confers temperature-sensitive growth. The SMP3 gene encodes a 59.9 kDa hydrophobic protein and disruption of the gene is lethal.

Amino Acid Sequence↗
PubMed1991

Synthesis of biologically active adenovirus preterminal protein in insect cells using a baculovirus vector.

A DNA fragment encoding the polyhedrin promoter of Autographa californica multiple nuclear polyhedrosis virus (AcMNPV strain) was constructed using overlapping oligodeoxyribonucleotides (oligos), which included the 5'-untranslated leader sequence of the polyhedrin-encoding gene. This DNA fragment was cloned into an intermediate transfer vector (pKX105) providing a unique BamHI site for the insertion of foreign genes. The Escherichia coli lacZ gene was first cloned at the BamHI site of pKX105 and the XhoI-KpnI fragment containing the lacZ gene was transferred to another plasmid vector (pEI) consisting of flanking AcMNPV sequences (pEI-lacZ). The E. coli beta-galactosidase that was produced in the infected insect cells using the recombinant virus constituted about 10% of the total cytoplasmic proteins. The pKX105 plasmid was also modified to give rise to pTT-lacZ which consisted of the lacZ gene under the control of the Rous sarcoma virus long terminal repeat promoter to facilitate rapid screening of the baculoviral recombinants in which the gene of interest was cloned under the control of the polyhedrin promoter. The efficiency of these transfer vectors was verified by obtaining high levels of expression of the adenovirus(Ad)-encoded preterminal protein (pTP) which is involved as a protein primer in the initiation of Ad DNA replication. The baculovirus-produced pTP was immunoprecipitable using rabbit polyclonal antibodies raised against a hydrophilic domain of pTP. The pTP protein was localized in the nucleus of the infected insect cells, and was biologically active in the in vitro Ad type 2 (Ad2) replication initiation assay.

Adenoviruses, Human↗
PubMed1991

Response to opioids of isolated small intestine in the house musk shrew, Suncus murinus.

1. Response to the opioids of isolated small intestine of Suncus murinus, an insectivore, was examined and compared with that of guinea-pig ileum. 2. The mechanical response to morphine and U50,488H, preferential mu- and kappa-agonist respectively, was relaxation which was antagonized by tetrodotoxin and naloxone in the Suncus small intestine. 3. Methionine5-enkephalin and D-alanine2, D-leucine5-enkephalin, both preferential delta-agonists, elicited contraction or relaxation in the Suncus small intestine, while enkephalins elicited sustained contraction in the tetrodotoxin-pretreated intestine. 4. In the guinea-pig ileum, the response to morphine and enkephalins was consistently relaxation which was antagonized by tetrodotoxin and naloxone. 5. Morphine, D-alanine2,D-leucine5-enkephalin and U50,488H inhibited electrically-evoked twitch responses of intestine in a concentration-dependent manner in both animals. 6. The relative potencies calculated from IC50 values of opioids for twitches followed the order, D-alanine2,D-leucine5-enkephalin greater than U50,488H greater than morphine in the Suncus small intestine, whereas U50,488 greater than D-alanine2,D-leucine5-enkephalin greater than morphine in the guinea-pig ileum. 7. Suncus small intestine has unique features such that D-alanine2,D-leucine5-enkephalin was most potent in inhibiting electrically-evoked twitches and that enkephalins induced contraction following tetrodotoxin pretreatment.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

Quantitative structure-activity studies on indole alkaloid tumor promoter indolactam congeners.

Nine indolactam congeners with L-Abu, gamma,delta-delta-Nva, Nva, Phg, tert-Leu, Leu, Ile, allo-Ile, Nle, instead of L-Val in (--)-indolactam-Val, were synthesized by microbial conversion and examined using two biological tests related to tumor promotion. The tests were inhibition of the specific binding of [3H]12-O-tetradecanoylphorbol-13-acetate (TPA) to the mouse epidermal particulate fraction, and stimulation of radioactive inorganic phosphate incorporation into phospholipids of HeLa cells. These two biological activities correlated well for each derivative. (--)-Indolactam-Ile with L-Ile in place of L-Val in (--)-indolactam-Val, which we have recently confirmed to occur naturally, was the most active of the ten indolactam congeners tested, suggesting that (--)-indolactam-Ile is a more potent tumor promoter than (--)-indolactam-Val in vivo. The effects of the substituents at position 12 on the TPA receptor binding were analyzed quantitatively using physicochemical substituent parameters and regression analysis. The results indicated that both hydrophobicity and bulkiness of the substituents at position 12 increased the binding ability to the TPA receptor, supporting the recent hypothesis that the isopropyl group at position 12 of (--)-indolactam-Val is involved in the hydrophobic interaction on the receptor site.

Alkaloids↗