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Biomedical subjects

K Kondo

Publications and source records attributed to K Kondo.

At least 343 records · Page 19Linked to original sources
PubMed1996

Orally active, nonpeptide vasopressin V2 receptor antagonists: a novel series of 1-[4-(benzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepines and related compounds.

This paper describes a novel series of nonpeptide vasopressin V2 receptor antagonists. It has been demonstrated that the 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-benzazepines and 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-1,5-benzodiazepines show a high affinity for V2 (and V1a) receptors. Among the 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-benzazepine series, compounds with an alkylamino group on the benzazepine ring have been shown to have oral activity. A lipophilic group at the ortho position on the terminal benzoyl ring is important for both high V2 receptor affinity and oral activity. On the basis of these favorable properties, clinical testing of 31b has begun for use as an oral and iv aquaretic agent.

Administration, Oral↗
PubMed1996

hch-1, a gene required for normal hatching and normal migration of a neuroblast in C. elegans, encodes a protein related to TOLLOID and BMP-1.

Proteins of the tolloid/bone morphogenetic protein (BMP)-1 family play important roles in the differentiation of cell fates. Among those proteins are BMP-1, which plays a role in cartilage and bone formation in mammals, the TOLLOID protein, which is required for the establishment of the dorsoventral axis of Drosophila embryos and BP10/SpAN, which are thought to act in the morphogenesis of sea urchins. These proteins have some properties in common. First, they contain the astacin metalloprotease domain, the CUB domain and the epidermal growth factor-like domain. Second, they are expressed in embryos at stages expected for their role in cell differentiation. Third, at least BMP-1 and TOLLOID are thought to interact with proteins of the transforming growth factor-beta family. We report that the hch-1 gene of the nematode Caenorhabditis elegans encodes a tolloid/BMP-1 family protein. The protein has the characteristic domains common to the tolloid/ BMP-1 family. Like other members of the family, it is expressed in embryos. However, the phenotype of hch-1 mutants shows that it is required for normal hatching and normal migration of a post-embryonic neuroblast. Furthermore, in spite of its expression in embryogenesis, it is not required for the viability of embryos. These results show new functions of the tolloid/BMP-1 family proteins and give insight into their evolution.

Amino Acid Sequence↗
PubMed1996

The Drosophila tamou gene, a component of the activating pathway of extramacrochaetae expression, encodes a protein homologous to mammalian cell-cell junction-associated protein ZO-1.

In Drosophila sensory organ development, the balance of activities between proneural genes and repressor genes defines a proneural cluster as a population of competent cells for neural development. In this study, we report the isolation and analysis of the tamou (tam) gene that encodes a cell-cell junction-associated protein, which is homologous to mammalian ZO-1, a member of the membrane-associated guanylate kinase homolog family. The tam mutation reduces the transcription of a repressor gene, extramacrochaetae, and causes enlargement of a proneural cluster where supernumerary precursor cells emerge, resulting in extra mechanosensory organs in the fly. These results suggest that the membrane-associated Tam protein is involved in the signaling pathway that activates emc expression.

Amino Acid Sequence↗
PubMed1996

Novel selective PDE IV inhibitors as antiasthmatic agents. Synthesis and biological activities of a series of 1-aryl-2,3-bis(hydroxymethyl)naphthalene lignans.

A series of 1-aryl-2,3-bis(hydroxymethyl)naphthalene lignans have been synthesized and evaluated for their ability to selectively inhibit PDE IV isolated from guinea pig. Replacement of the 1-phenyl ring by a pyridone ring led to marked improvement of their selectivity for PDE IV over PDE III. The compounds that were most potent and selective involved those bearing an N-alkylpyridone ring at C-1. These compounds also showed potent antispasmogenic activity without causing significant changes in heart rate in the guinea pig. The most potent compound was 6,7-diethoxy-2, 3-bis(hydroxymethyl)-1-[1-(2-methoxyethyl)-2-oxo-pyrid-4-yl]nap hth alene (17f), ED50 values of histamine-induced and antigen-induced bronchoconstriction in the guinea pig being 0.08 and 2.3 mg/kg iv, respectively. This compound was chosen as a candidate for further pharmacological evaluation.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Suppressive effect of N-(benzyloxycarbonyl)-L-phenylalanyl-L-tyrosinal on bone resorption in vitro and in vivo.

The suppressive effect of N-(benzyloxycarbonyl)-L-phenylalanyl-L-tyrosinal on bone resorption was examined in vitro and in vivo. This synthetic peptidyl aldehyde was found to be a potent and selective cathepsin L inhibitor in our screening for cysteine protease inhibitors. In the pit formation assay with unfractionated rat bone cells, 1.5 nM of this compound markedly inhibited parathyroid hormone-stimulated osteoclastic bone resorption. In addition, intraperitoneal administration of this peptidyl aldehyde (2.5-10 mg/kg) for 4 weeks suppressed bone weight loss dose dependently in the ovariectomized mouse, experimental model of osteoporosis. Hydroxyproline measurement of the decalcified femurs from these ovariectomized mice suggested that this compound acts as a bone resorption suppressor through the inhibition of collagen degradation.

Animals↗
PubMed1996

Resuscitation of Vibrio cholerae O1 strain TSI-4 from a viable but nonculturable state by heat shock.

Vibrio cholerae strain TSI-4 was incubated in an M9 salt solution at 15 degrees C for more than 100 days. The plate counts showed no viable cells on day 30, but a broth culture from that day showed the growth of bacteria. However, after 35 days the bacteria entered the nonculturable state, based on the assessment of both the plate counts and broth culture. A portion of the culture was heated at 45 degrees C for 1 min in a water bath and subsequently plated onto a nutrient agar plate. More than 1000 colonies were recovered after this heat-shock treatment. The recovered cells showed the same chromosomal DNA pattern in the restriction map and the same outer membrane protein pattern in SDS-PAGE. Recovery of viable cells by heat-shock was achieved in cultures grown on M9 salt but not from cultures grown in phosphate-buffered saline. This suggests that the presence of NH4Cl in the M9 salt solution may support the growth of the bacteria in a low nutrient medium, while also playing an important role in resuscitation.

Bacterial Proteins↗
PubMed1996

Expression pattern of messenger RNAs for prostanoid receptors in glial cell cultures.

Expression level of messenger RNAs (mRNAs) for prostanoid EP3, FP, and TP receptors was investigated in cultured rat astrocytes, oligodendrocytes, and microglia, as well as in meningeal fibroblasts, rat glioma C6 cells, rat pheochromocytoma PC12 cells, whole brain, and several peripheral tissues by reverse transcriptase-polymerase chain reaction. Cultured astrocytes and oligodendrocytes expressed mRNAs for 3 prostanoid receptors examined. In contrast, cultured microglia and pheochromocytoma PC12 cells expressed EP3 and TP receptor mRNAs, but not FP receptor mRNA. Glioma C6 cells expressed only TP receptor mRNA among 3 prostanoid receptors with the same expression level as that in astrocytes. Cultured meningeal fibroblasts expressed 3 receptor transcripts, and their expression levels were lower than those in astrocytes. Expression level of mRNA for each prostanoid receptor in cultured glial cells was higher than that in whole brain. These observations suggest that each prostanoid has its specific roles in each glial cell type of the brain.

Animals↗
PubMed1996

Tranilast suppresses intimal hyperplasia after photochemically induced endothelial injury in the rat.

Intimal thickening in the femoral artery of spontaneously hypertensive rats (SHR) was initiated by endothelial damage induced by the photochemical reaction between green light and systemic rose bengal. This model represents a non-mechanical method of producing vessel wall denudation. Neointima formation was assessed by calculating the cross-sectional area of intima, media and lumen, using computer analysis. Tranilast (30, 100 and 300 mg/kg, p.o.), administered 2 days prior to endothelial injury, reduced intimal area by 29, 62 and 87%, respectively, compared to that of vehicle-treated controls. In cultured SHR-derived vascular smooth muscle cells, tranilast produced concentration-dependent inhibition of mitogenesis, whether stimulated by platelet-derived growth factor, basic fibroblast growth factor, insulin-like growth factor or fetal bovine serum. These results suggest that tranilast may be effective in preventing coronary restenosis.

Animals↗
PubMed1996

A dose-response relationship between the frequency of p53 mutations and tobacco consumption in lung cancer patients.

Mutations of the p53 tumor suppressor gene are frequent in lung cancers. It is suggested that p53 mutations are associated with smoking-induced lung carcinogenesis. We examined p53 mutations in 53 lung cancers by analyzing reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) to ascertain the association between p53 mutations and smoking. Twenty-five (47%) of 53 lung cancers carried p53 mutations. A discriminant analysis showed that the Brinkman index (0.156) and gender (0.140) significantly influenced p53 mutations. Furthermore, there was a dose-response relationship between the quantity of cigarettes consumed and the frequency of p53 mutations in lung cancer patients (P < 0.001). In patients with adenocarcinoma, the frequency of p53 mutations correlated with the amount of the tobacco smoked (P < 0.05). We suggest that the p53 gene is a target of particular carcinogen in tobacco smoke.

Adenocarcinoma↗
PubMed1996

Expression of MRP and mdr1 in human gastrointestinal cancer cell lines: a correlation with resistance against doxorubicin.

The mRNA expression of mdr1 and MRP, each of which codes for a transport protein belonging to ATP-binding cassette superfamily and are reported to be responsible for multidrug resistance phenotype, were semi-quantified by RT-PCR in a panel of gastrointestinal cancer cell lines. Although the expression of MRP was predominant in esophageal cancer cell lines, expression of either or both of the genes was detected in all the cell lines tested. Expression of these two genes added together correlated significantly with chemosensitivity against doxorubicin, implicating that expression of both genes should be evaluated in the future analysis of multidrug resistance phenotype. The ID50 values for pirarubicin, although generally lower than the values for doxorubicin, correlated well with the latter, suggesting that the similar phenotype as that for doxorubicin might be responsible for drug resistance against this semisynthetic anthracycline glycoside.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Von Hippel-Lindau tumour suppressor gene. Localization of expression by in situ hybridization.

Inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene is responsible not only for VHL disease, but also for sporadic renal cell carcinoma and cerebellar haemangioblastoma. The distribution of VHL gene expression in the mouse embryo was recently studied by in situ hybridization, along with human VHL in 14-week-old fetal kidney: there was widely distributed expression in the former and expression in the tubules and blastema in the latter. Adult human tissue and other fetal organs were not examined. The present paper describes an in situ hybridization study to assess the function of the VHL gene in adult human tissues and in tissues of human fetus at 28 weeks of gestation. The expression of the VHL gene was limited to the adult and fetal brain and kidney, and the adult prostate. Nerve cells in adult and fetal brain were positive, including the cerebellar Purkinje cells. In adult and fetal kidney, the proximal tubular epithelium, the putative origin of the common type of renal cell carcinoma, showed intense signal, whereas the distal nephron, glomeruli, and nephrogenic blastema showed no significant signal. The prostate showed significant signal in the basal epithelium. The adrenal, pancreas, and epidydimis showed no significant signal, in spite of the frequent occurrence at these sites of neoplastic or hamartomatous lesions in VHL disease.

Animals↗
PubMed1996

Malignant lymphoma of the gastric stump developing 25 years after a distal gastrectomy for benign gastric disease: report of a case.

We report herein the case of a 57-year-old man in whom malignant lymphoma originating in the gastric remnant was confirmed 25 years after a subtotal gastrectomy with Billroth II reconstruction had been performed for gastric ptosis. Gastroscopy revealed an ulcerated tumor on the fornix, and histologic examination of the endoscopic biopsy specimens demonstrated malignant lymphoma. Thus, total gastrectomy with splenectomy, pancreatectomy, and resection of the previously anastomosed jejunal stoma were performed. Histologic examination of the stomach remnant confirmed a diagnosis of B-cell lymphoma of the large-cell type. Although we were unable to study the surgical specimen from the initial operation, the possible relationship between pseudolymphoma and malignant lymphoma has been presented in the literature, which is reviewed following this case report.

Anastomosis, Roux-en-Y↗
PubMed1996

Tomographic distribution of acetylated histone H4 in plant chromosomes, nuclei and nucleoli.

Root tip cells of broad bean (Vicia faba L. cv. 'Wase soramame') and barley (Hordeum vulgare L. cv. 'Minorimugi') were immunostained with antibodies specific for acetylated histone H4. With an antiserum that recognizes histone H4 acetylated at lysine-5, the nucleolar organizing region (NOR) in mitotic chromosomes was strongly labeled in both species. The broad bean had two signals in the metaphase and telophase chromosome complements and four signals in the prophase and anaphase chromosome complements, while the barley had four signals in the metaphase and telophase chromosome complements and eight signals in the prophase and anaphase complements. Five different patterns of signals were observed at interphase: in type I only nucleoli were wholly stained; in type II perinucleolar knob-like signals and/or fiber-like signals emanated from the nucleus; in type III aggregate signals appeared in the nucleolus; in type IV many small dot-like signals were distributed throughout the nucleus, except nucleoli; and in type V string-like or some granule-like signals appeared in the nucleoli. Type II was very similar to previous results by in situ hybridization with sense rDNA probes. Type III was similar to the patterns of DNA synthesis recognized as chromatin domains by anti-BrdU antibodies. Type V was very similar to the results of in situ hybridization with pTa71, rDNA probes and the appearance of the dense fibrillar components of the nucleolus.

Acetylation↗
PubMed1996

A case of chromophobe renal cell carcinoma associated with low chromosome number and microsatellite instability.

Cytogenetic study in a case of a human chromophobe renal cell carcinoma revealed a hypodiploid chromosome number of 36 with loss of chromosomes 1, 2, 5, 6, 10, 13, 15, 17, 21, and X. The tumor DNA showed microsatellite instability in dinucleotide repeat microsatellite markers. This is the fourth case that has been fully karyotyped and showed a low chromosome number in a chromophobe renal cell carcinoma. Our data in the present study are consistent with those in the literature. It is suggested that human chromophobe renal cell carcinoma may possibly be characterized by tumor cells with low chromosome number or microsatellite instability.

Adult↗
PubMed1996

Neuropeptide FF reduces food intake in rats.

The effect of neuropeptide FF (NPFF), a mammalian FMRFamide-like peptide with antiopioid activity, on food intake was investigated in food-deprived rat. The ICV administration of NPFF (5 or 10 micrograms/rat) reduced food intake during the first 60 min after administration. ICV injection of naloxone (10 or 100 micrograms/rat), an opioid antagonist, also decreased food intake. However, the combination of NPFF and naloxone showed no additivity in the anorexigenic effect, suggesting that NPFF and naloxone reduced food intake by the common mechanism. These results indicate that NPFF may function as an endogenous anorexigenic peptide with anitiopioid function.

Animals↗
PubMed1996

Esophageal tracheobronchoplasty for diseases of the central airway.

Three infants with congenital tracheal stenosis and three adults with various diseases of the central airway underwent esophageal tracheobronchoplasty to repair long-segment stenoses and defects. The primary operative goal was enlargement of the stenosis (n = 4), repair of the defect (n = 1), or both (n = 1). Cardiopulmonary support was required in two cases. All three infants were operated on for generalized congenital tracheal stenoses. There was one postoperative death on the fifth day. Another infant died of pneumonia 3 months after operation. Tracheal patency was excellent in two infants. One infant is well without symptoms 6 years after the operation, although balloon dilation was required three times during the first postoperative year. In the three adult patients, the primary diseases were congenital tracheal stenosis, iatrogenic injury associated with relapsing polychondritis, and malignant mediastinal tumor involving the trachea. All lesions involved both the trachea and main stem bronchi. Postoperative airway patency was excellent in all three adults, although expandable metallic stents had to be inserted in one patient. Postoperative pulmonary function was improved, particularly forced expiratory volume in 1 second and peak expiratory flow rate. Although the postoperative mortality rate was still high, especially among the infants, and prolonged postoperative ventilatory support was required for five of the six patients, long-term patency and postoperative pulmonary functional improvement are encouraging.

Adult↗