Biomedical subjects

K Kondo

Publications and source records attributed to K Kondo.

At least 217 records · Page 12Linked to original sources

PubMed1998

Analysis of human herpesvirus 6 U3 gene, which is a positional homolog of human cytomegalovirus UL 24 gene.

The US22 gene family was first discovered in human cytomegalovirus (HCMV) and contains several conserved amino acid motifs. Human herpesvirus 6 (HHV-6) also encodes several genes belonging to the US22 family, including the U3 gene (a positional homolog of HCMV UL24). Because the gene products of the US22 gene family function as gene regulators in general, we analyzed the HHV-6A U3 gene. Six transcripts with different molecular weights of 7.5-1.8 kb were detected by Northern blot analysis using a U3-specific probe. Sequence analyses of the respective cDNA clones and primer extension experiments revealed that the U3 gene encoded the 2.0- and 3.5-kb transcripts and had no splicing within the U3 gene region. By immunofluorescence testing using antibodies raised to a fusion protein of MBP (maltose-binding protein) and U3, the U3 viral antigen was detected as early as 24 h p.i. in HHV-6A-infected U373 cells. The antigens were found in cytoplasmic granules, preferentially in the endoplasmic reticulum. Moreover, cotransfection assay using a luciferase gene expression system revealed that the U3 gene product was capable of activating the human immunodeficiency virus long terminal repeat promoter in CV1 cells.

Cytomegalovirus↗

PubMed1998

Hydroxyl radical generation after the third hour following ischemia contributes to brain damage.

The purpose of the present study was to determine after what time period hydroxyl radical formation contributes most to ischemic brain damage in focal ischemia, using a hydroxyl radical scavenger, EPC-K1, L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyl-tridecyl)-2H-1-be nzopyran-6yl-hydrogen phosphate] potassium salt. Focal ischemia was produced by thrombotic occlusion of the left middle cerebral artery in rats. After evaluation of the pharmacokinetics of EPC-K in the brain tissue and plasma following 10 mg/kg intravenous bolus treatment of conscious rats, we investigated the neuroprotective effect of EPC-K1 in the middle cerebral artery occlusion model. A single intravenous bolus of EPC-K1 was given immediately, 3 or 6 h after ischemia, and cerebral brain damage was measured 24 h after ischemia. When EPC-K1 was injected 3 h after ischemia, a significant (P < 0.01) reduction of cerebral brain damage was observed. EPC-K1 delivered by intravenous infusion that started immediately after ischemia and lasted for 24 h, also significantly (P < 0.05) reduced brain damage, but the efficacy of the neuroprotective effect was the same as that of the 3 h after ischemia bolus treatment. These results may indicate that the period of hydroxyl radical formation most critical for ischemic brain damage is a few hours after the third hour following ischemia in this model.

Animals↗

PubMed1998

Glial cell line-derived neurotrophic factor/neurturin-induced differentiation and its enhancement by retinoic acid in primary human neuroblastomas expressing c-Ret, GFR alpha-1, and GFR alpha-2.

Neuroblastomas often undergo spontaneous differentiation and/or regression in vivo, which is at least partly regulated by the signals through neurotrophins and their receptors. Recently, glial cell line-derived neurotrophic factor (GDNF) and a second family member, neurturin (NTN), have been found to mediate their signals by binding to a heterotetrameric complex of c-Ret tyrosine kinase receptors and glycosylphosphatidylinositol-linked proteins, GFR alpha-1 (GDNFR-alpha) or GFR alpha-2 (TrnR2/GDNFR-beta/NTNR-alpha/RETL2). Here, we studied the effect of GDNF and NTN on human neuroblastomas in the short-term primary culture system, as well as the expression of c-Ret, GFR alpha-1, GFR alpha-2, GDNF, and NTN. GDNF (1-100 ng/ml) induced morphological differentiation in 34 of 38 primary neuroblastomas and an accompanying increase in c-Fos induction. These effects were markedly enhanced by treatment with 5 microM all-trans-retinoic acid. Although GDNF alone induced a rather weak differentiation independent of the disease stages, the enhancement of neurite outgrowth induced by treatment with both GDNF and all-trans-retinoic acid was significantly correlated with younger age (less than 1 year; P = 0.0039), non-stage 4 diseases (P = 0.0023), a single copy of N-myc (P = 0.027), and high levels of TRK-A expression (P = 0.0062). To examine the expression levels of GFR alpha-1, we cloned a short form of the human GFR alpha-1 gene with a 15-bp deletion by screening a human adult substantia nigra cDNA library. Many primary neuroblastomas expressed c-Ret, GFR alpha-1, and GFR alpha-2 as well as their ligands, GDNF and NTN, suggesting the presence of a paracrine or autocrine signaling system within the tumor tissue. The effect of NTN on primary culture cells of neuroblastoma was similar to that of GDNF. These imply that the GDNF(NTN)/c-Ret/GFR alpha-1(GFR alpha-2) signaling may have an important role in regulating the growth, differentiation, and cell death of neuroblastomas.

Antineoplastic Agents↗

PubMed1998

Decreased MUC1 expression induces E-cadherin-mediated cell adhesion of breast cancer cell lines.

Two breast cancer cell lines, YMB-S and ZR-75-1S, were established in our laboratory. They proliferated in suspension culture without aggregation in a complete liquid medium. We found that sodium butyrate (NaB) arrested the cells in the G0-G1 phase of the cell cycle, inhibited their proliferation, and induced cell-cell and cell-surface adhesion. In this study, we explored the mechanism of this adhesion. Adhesion was inhibited by an anti-E-cadherin antibody, suggesting a role for E-cadherin. However, there were no changes in the expression of E-cadherin, alpha-catenin, and beta-catenin. Northern blot analysis and cytofluorometry revealed that NaB-treated cells showed a lower expression of MUC1 than did untreated cells. To examine the possibility that the adhesion of these cells might be induced by decreased MUC1 expression, the level of MUCI expression was directly reduced using an antisense oligonucleotide. The MUC1 antisense oligonucleotide induced cell-cell and cell-surface adhesion of these breast cancer cells, just as NaB did. Our observations indicate that E-cadherin can be functionally suppressed by overexpression of MUC1 but resumes its activity after suppression of MUC1 expression. Thus, regulation of MUC1 might be a new strategy for cancer therapy.

Blotting, Northern↗

PubMed1998

Potent growth-suppressive activity of a serine protease inhibitor, ONO-3403, toward malignant human neuroblastoma cell lines.

FOY-305 is a synthetic serine protease inhibitor and ONO-3403 and FO-349 are its derivatives. The effects of these compounds on the proliferation of 13 human neuroblastoma cell lines were investigated in vitro by MTT colorimetric assay. The half maximum inhibition concentrations of ONO-3403 varied between 22 and 90 microg/ml while those of FOY-305 and FO-349 were higher than 100 microg/ml. ONO-3403 showed higher growth-inhibitory activity for N-myc-amplified neuroblastomas as compared with that for non-amplified cells. Since N-myc amplification in neuroblastomas is well correlated with a poor prognosis, ONO-3403 could be an effective anticancer drug for malignant neuroblastomas.

Allylglycine↗

PubMed1998

Genomic organization of the flt-1 gene encoding for vascular endothelial growth factor (VEGF) receptor-1 suggests an intimate evolutionary relationship between the 7-Ig and the 5-Ig tyrosine kinase receptors.

The flt-1 tyrosine kinase gene encodes a high affinity receptor for Vascular Endothelial Growth Factor, and belongs to the so-called '7-Ig' or flt gene family which has characteristics of 7-Immunoglobulin (Ig)-like domains in the extracellular region. This is structurally distantly related to 5-Ig domain-containing receptors such as Fms/Kit/PDGF-R. However, the whole genomic organization for any 7-Ig receptor gene has not been determined yet. To examine the genomic structure of flt-1 and the evolutionary relationship between genes of the 7-Ig and 5-Ig receptor families, we isolated the mouse genomic DNAs carrying all exons of the flt-1 gene. The mouse flt-1 gene consisted of 30 exons, whose exon-intron boundaries were highly related to those in the 5-Ig receptor genes, except for the amino terminal region. The sequences corresponding to the first and second Ig-domains in the flt-1 gene were encoded by four exons, whereas this region was encoded by only two exons in the 5-Ig receptor genes. These results raise the interesting possibility that deletion or insertion mutations of introns in one of these receptor genes took place in the evolutionary generation of the other receptor genes.

Amino Acid Sequence↗

PubMed1998

Accumulation, Metabolism, and Depuration of Organotin Compounds in the Marine Mussels Mytilus graynus and Mytilus edulis under Natural Conditions.

The accumulation, transformation, and depuration of tri-n-butyltin (TBT) were studied over periods of approximately 60-70 days using marine mussels, Mytilus graynus and Mytilus edulis, under natural conditions. M. graynus collected at a lightly polluted site were transplanted to a highly polluted site and M. edulis collected at a highly polluted site were transplanted to a lightly polluted site. TBT taken up in M. graynus showed a bioconcentration factor of 10 500 in the accumulation phase. Di-n-butyl(3-oxobutyl)tin, which is a main metabolite of TBT in M. edulis, showed a longer half-life (8.13 days) than that of the parent compound (4.82 days) in the depuration phase. On the other hand, another metabolite, di-n-butyl(3-hydroxybutyl)tin, showed a shorter half-life (3.98 days) than that of the parent compound. The different half-lives among TBT and its metabolites are responsible for the different metabolic patterns in blue mussels at each sampling time.

Journal Article↗

PubMed1998

High frequency expressions of CD44 standard and variant forms in non-small cell lung cancers, but not in small cell lung cancers.

BACKGROUND AND OBJECTIVES: Organ specificity has been demonstrated in the mode of CD44 expression among several cancers. METHODS: We examined the expressions of CD44 standard (CD44s) and CD44 variants (CD44v) in 14 cell lines (small cell lung cancer (SCLC): 5, non-small cell lung cancer (NSCLC): 9 and 20 surgically resected samples (SCLC: 7, NSCLC: 13) of lung cancer using reverse transcription polymerase chain reaction and immunohistochemistry. RESULTS: Although both NSCLC and SCLC expressed CD44s, the frequency and intensity of CD44s expression in NSCLC were different from those in SCLC: cell lines, 89% vs. 40%; tumor samples, 100% (diffusely stained) vs. 57% (focally stained). CD44s expression was partially or completely repressed in SCLC. However, NSCLC frequently expressed CD44v, but SCLC expressed infrequently: cell lines, 67% vs. 20%; tumor samples, 69% vs. 0%. The N-417 line, which only expressed some CD44v in SCLC, falls SCLC and NSCLC both in biomarkers and in growth patterns. CONCLUSIONS: CD44 expression was repressed in SCLC but was enhanced in NSCLC.

Adenocarcinoma↗

PubMed1998

Preoperative embolization therapy for esophageal operation.

BACKGROUND AND OBJECTIVES: Since 1993, we have performed preoperative embolization therapy (PET) in an attempt to augment the blood flow of the gastric tube and prevent anastomotic leakage after esophageal resection. The clinical effects and complications associated with PET are reported. METHODS: The femoral artery was punctured and the left gastric artery, right gastric artery, and splenic artery underwent embolization, leaving the right gastroepiploic artery as the only patent feeding artery for the stomach. PET was performed in 54 patients, and data concerning blood flow of the stomach before and after the construction of the gastric tube were available in 51 patients. Of the 25 patients who were operated in the same period without undergoing PET, similar data were available in 20 patients. RESULTS: In the group of patients who underwent PET, the blood flow of the gastric tube after its construction was 67% of the value measured at the upper part of the stomach just after opening the abdominal cavity. For those who were not pretreated by PET, it declined to 33%. CONCLUSIONS: PET for esophageal cancer is a safe procedure that contributes to the decrease in the frequency of anastomotic dehiscence after esophageal operation, owing to the augmented tissue blood flow of the upper portion of the stomach following the construction of gastric tubes.

Anastomosis, Surgical↗

PubMed1998

Idiopathic renal arteriovenous fistula demonstrating a huge aneurysm with a high risk of rupture: report of a case.

This paper reports a case of an idiopathic renal arteriovenous fistula demonstrating a huge guitar-shaped aneurysm, which required a total nephrectomy. Although the patient insisted on having been asymptomatic, echocardiography and cardiac catheterization clearly revealed that the influence on hemodynamics was unexpectedly significant. Interestingly, the aneurysm was also considered to have a high risk of rupture, which was preoperatively suggested by an aneurysm wall projection discernible on both computerized tomograms and angiograms, and this suspicion was also convincingly supported by the perioperative and histopathological findings.

Aneurysm↗

PubMed1998

[Removal of the endocardial pacemaker leads--experience with 16 leads in 10 patients].

Recent advances in pacemaker leads have contributed to the improvement of their stability at the anchored sites. However, we sometimes have difficulty in removing them. We have experienced the removal of 16 leads in 10 patients (male: 7, female: 3) in the last 5 years. The age of patients ranged from 48 to 87 years, and the average was 60. The reasons for the removal were as follows; pocket infection in 6 cases, sepsis in 1 case, ischemic skin erosion in 1 case, retained fractured ventricular lead in 1 case, fracture of Accufix atrial lead in 1 case. The methods of removal consisted of using the removal kit, the snare or the basket snare transvenously, direct surgical approach or a combination of them. We used the removal kit alone in 12 electrodes (6 atrial, 6 ventricular), and removal of 5 atrial and 3 ventricular leads were successfully by this method only. The removal of 4 leads by kits alone failed, so that 2 ventricular leads were removed transvenously, one atrial and one ventricular lead were removed surgically, and 1 ventricular lead was left untreated. Finally, we were able to remove 15 of 16 leads (93.3%) successfully. This experience indicates that these interventions should be performed as less invasively as possible, yet we should give an explanation to the patients as to the options we may employ when we have failed in the intended procedure.

Aged↗

PubMed1998

[Coronary artery bypass graft surgery in dialysis patient].

To determine the operative outcome of coronary artery bypass graft surgery (CABG) for severe coronary artery disease in long-term hemodialysis patients, we analyzed a group of 16 patients who underwent CABG over a ten-year period in our institution. Hospital mortality was 12.5% (2 of 16 patients). These two patients died of ischemic colitis and perioperative myocardial infarction, respectively. There were five late deaths: one patient died from myocardial infarction, one from uremia, one from gastro-intestinal bleeding, one from gastric cancer and one from unknown cause. There were four significant postoperative complications (morbidity 25%), consisted of one pulmonary tuberculosis, one sternal dehiscence secondary to mediastinitis, one mediastinal hematoma secondary to late bleeding from the LITA dissection area and one A-V shunt trouble. Graft patency rate within the first two months was 93% (30 to 42 in 13 patients). Hospital survivors experienced complete relief from angina. Actuarial survival was 68.8% at 3 years, 57.3% at 5 years and 28.6% at 7 years. This rate is not significantly different from the survival of all dialysis patients, but seems to be better than that of dialysis patients with not operated coronary artery disease. We concluded that CABG in dialysis patients can be accomplished with acceptable morbidity and mortality and effective relief of symptoms.

Cause of Death↗

PubMed1998

[A case of recurrent esophageal cavernous hemangioma increasing rapidly after surgery].

A 40-year-old female was referred to our hospital for dysphagia. A hemangioma measuring 5 x 2.5 x 2.5 cm was revealed as a round defect by esophagography and was partially cystic on CT and MRI. Through a neck incision, the esophageal wall on the tumor side was initially opened. The tumor partially adhered to the esophageal wall, but was dissected from the esophageal wall and then resected easily. Microscopic examination of tumor revealed cavernous hemagioma. Thirty days after the initial surgery, the recurrent tumor was detected in the pharynx and increased rapidly. Then a second operation was performed. The tumor was completely resected by mucosectomy including normal esophageal mucosa. Recurrence was caused by residual cystic wall of the hemangioma adhering to the esophageal mucosa after the first procedure.

Adult↗

PubMed1998

[Metastatic lung tumor developing 15 years after resection of invasive thymoma].

A 57-year-old man with myasthenia gravis had undergone extended thymothymomectomy for invasive thymoma and postoperative irradiation 15 years ago. At present, an abnormal shadow on his left lung field on chest X-ray and an elevated SCC-Ag level led us to suspect primary lung cancer (squamous cell lung cancer). He underwent left lower lobectomy and partial resection of the upper lobe. After the operation, this tumor was identified pathologically as a thymoma. Comparing this tumor with the previous invasive thymoma, we concluded that the present lesion was a metastasis of the former thymoma. This case suggests that a metastatic lung tumor should be suspected when an abnormal shadow is detected on chest X-ray following extended thymothymomectomy for invasive thymoma.

Humans↗

PubMed1998

Infrequent genetic alterations of the PTEN gene in Japanese patients with sporadic prostate cancer.

Prostate cancer is a major cause of cancer death among elderly men in America, Europe, and Japan. However, the molecular mechanism of carcinogenesis is not yet well characterized. Frequent loss of heterozygosity (LOH) on chromosome 10q was reported in prostate cancer, and a candidate tumor suppressor gene, PTEN, was isolated on chromosome band 10q23.3. To investigate the genetic alterations of PTEN, we examined 45 primary prostate cancer specimens. LOH at the PTEN locus was observed in two (11.1%) of 18 tumors. However, no mutations were observed in any of the primary prostate cancers. These data suggest that mutation of the PTEN gene does not play a major role in prostate carcinogenesis of Japanese patients.

Aged↗

PubMed1998

In vivo karyotypic evolution with altered biological characteristics in a case of neuroblastoma.

Molecular and biological analyses of a neuroblastoma case in which the original tumor contained a nodular region are described. No significant difference was observed between the nodular and the surrounding tumor tissue with respect to histopathologic examination, N-myc amplification, and trkA expression. However, flow cytometric analysis demonstrated that the nodular region consisted of a hypertetraploid clone, whereas the surrounding tissue mostly contained a hyperdiploid clone. Chromosome analysis showed that each clone had a similar chromosome acquisition pattern, suggesting that the hypertetraploid cells of the nodular region arose from the hyperdiploid cells of the surrounding tissue. Moreover, primary culture findings of the tumor cells showed that the responses to nerve growth factor or retinoic acid were different between the two. Collectively, this case suggests the possibility that neuroblastoma acquires novel biological characteristics through karyotypic evolution in vivo.

Abdominal Neoplasms↗

PubMed1998

Age-associated decrease in response of rat aquaporin-2 gene expression to dehydration.

It is well known that urine-concentrating ability decreases with aging and that this decreasing ability results from a reduced sensitivity of the renal collecting duct to arginine vasopressin (AVP). AVP regulates the water channel (aquaporin-2:AQP2) through V2 receptors and increases the water permeability of the collecting duct. To elucidate the mechanism of change with aging in urine-concentrating ability, we investigated the change of V2 receptor and AQP2 mRNA expression in young (8-week-old) and older (7-month-old) rats after dehydration for 2 days. After dehydration, plasma AVP levels in older rats were higher than young rats, and urinary osmolality in older rats was lower than young rats. By Northern blot analysis, there was no significant difference between young and older rats in both V2 receptor and AQP2 mRNA expression before dehydration. After dehydration, V2 receptor mRNA expression in young and older rats decreased in the same degree, suggesting the downregulation of V2 receptors may occur in the mRNA level. Northern blot analysis and in situ hybridization histochemistry showed that AQP2 mRNA expression increased and the increased expression in older rats was less than in young rats. The present study suggests the reduced response of AQP2 mRNA expression to dehydration, observed in 7-month-old rats, might be partially responsible for the decreasing urine-concentrating ability with aging.

Aging↗

PubMed1998

Adenosine 5'-diphosphate as a factor in platelet aggregation induced by human plasma remnant lipoproteins.

The action of lipoprotein lipase on chylomicrons (CM) and very low density lipoproteins (VLDL) produces remnant lipoproteins (RLP) which are rich in triglycerides, cholesterol and apolipoprotein E (apo E). Apo E serves as a ligand for uptake of RLP by macrophages, platelets, endothelial cells and other cells expressing the LDL-receptor or the remnant receptor, thus having a major role in the clearance of plasma cholesterol and triglycerides, but at the same time, uptake of apo E-bearing RLP can profoundly alter the physiology of these cells and promote atherosclerosis. Like RLP, blood platelets also have roles in atherosclerosis and thrombosis, hence it is likely that RLP influence platelet activity as well. RLP derived from normal human plasma VLDL and CM were prepared using two monoclonal antibodies, anti-apo B-100 (JI-H) and anti-apo A-I (H-12) coupled to Sepharose 4B gel to form an immunoaffinity column. Lipoproteins containing apo B-100 including VLDL and LDL adsorb to (JI-H)-gel, while CM and HDL with apo A-I adsorb to (H-12)-gel. The particles in the unbound fraction (RLP) are rich in apo B-48, apo E and apo B-100 containing particles with multiple molecules of apo E. The RLP fraction with a total triglyceride of 14+/-3.2 mg/ml; cholesterol, 0.39+/-0.1 mg/ml and protein, 0.78+/-0.24 mg/ml (n=19) was added to aliquots of blood of man, rabbits, guinea pigs, mice, and rats at protein equivalents of 0.98 to 78 microg/ml blood and agitated gently at 37 degrees C for 40 sec. Platelet aggregation was measured as a fall in single platelet count. RLP induced aggregation of platelets in man (p<0.005) rabbit (p<0.0005), guinea pig (p<0.002) and mouse (p<0.0001), but no RLP induced platelet aggregation was observed in the rat blood. Scanning electron microscopy revealed that in the presence of RLP, platelets had adhered to and formed aggregates on red cells. The platelet response to RLP was inhibited by apyrase known to scavenge ADP, by 5 microM 2-chloroadenosine, a platelet ADP receptor antagonist and by 3.4 microM cilostazol, a phosphodiesterase type III inhibitor known to raise cyclic AMP level in platelets. It is thought that RLP cause leakage of ADP from red cells which then mediates platelet aggregation.

2-Chloroadenosine↗