Biomedical subjects

H Harada

Publications and source records attributed to H Harada.

At least 109 records · Page 6Linked to original sources

PubMed2001

Cyclin D1 overexpression and p53 inactivation immortalize primary oral keratinocytes by a telomerase-independent mechanism.

The immortalization of human cells is a critical step in multistep carcinogenesis. Oral-esophageal carcinomas, a model system to investigate molecular mechanisms underlying squamous carcinogenesis, frequently involve cyclin D1 overexpression and inactivation of the p53 tumor suppressor. Therefore, our goal was to establish the functional role of cyclin D1 overexpression and p53 inactivation in the immortalization of primary human oral squamous epithelial cells (keratinocytes) as an important step toward malignant transformation. Cyclin D1 overexpression alone was found to induce extension of the replicative life span of normal oral keratinocytes, whereas the combination of cyclin D1 overexpression and p53 inactivation led to their immortalization. This study also demonstrates that immortalization of oral keratinocytes can be independent of telomerase activation, involving an alternative pathway of telomere maintenance (ALT).

Carcinoma, Squamous Cell↗

PubMed2001

Immunohistochemical analysis of small cell carcinoma of the head and neck: a report of four patients and a review of sixteen patients in the literature with ectopic hormone production.

Small cell carcinoma (SCC) occurs mostly in the lung, and in some patients is accompanied by production of ectopic hormones. Small cell carcinoma of the head and neck is very rare. We report 4 patients with SCC of the head and neck (larynx, tonsil, maxillary sinus, and parotid gland). The patient with SCC of the maxillary sinus demonstrated a high level of plasma serotonin and overexpression of parathyroid hormone; however, he did not show any related symptoms. The patient with SCC of the tonsil showed the syndrome of inappropriate secretion of antidiuretic hormone associated with antidiuretic hormone hyperproduction at the terminal stage. In the literature, 16 patients with SCC of the head and neck with ectopic hormone production have been reported. Antidiuretic hormone and adrenocorticotropic hormone were the hormones that caused clinical symptoms (paraneoplastic syndromes). We believe that the evaluation of hormonal syndromes is valuable for diagnosis and treatment.

Aged↗

PubMed2001

Synthesis and structure-activity relationships in a series of ethenesulfonamide derivatives, a novel class of endothelin receptor antagonists.

In the previous paper, we described a series of the 2-arylethenesulfonamide derivatives, a novel class of ETA-selective endothelin (ET) receptor antagonists, including the compounds 1a, b. Compound 1a showed excellent oral antagonistic activities and pharmacokinetic profiles, and the monopotassium salt of 1 (YM-598 monopotassium) is in clinical trials. In this paper, we wish to report the investigation of the further details of structure-activity relationships (SARs) of the 2-phenylethenesulfonamide region in 1a. It was found that methyl substitutions at the 2-, 4- and 6-positions of the phenyl group in 1a led to the discovery of the ET(A)/ET(B) mixed antagonist (6s) with an IC50 of 2.2 nM for the ET(A) receptor. We also found that introduction of an ethyl group to the 1-position of the ethenyl group in 1a gave the ET(A) selective antagonist (6u) with an oral endothelin antagonistic activity in rats.

Animals↗

PubMed2001

Ethenesulfonamide derivatives, a novel class of orally active endothelin-A receptor antagonists.

In the present article we wish to report the discovery of a novel class of ET(A)-selective endothelin (ET) receptor antagonists through the modification of the ET(A)/ET(B) non-selective antagonist, Ro47-0203 (Bosentan, 1). Replacement of the benzenesulfonamide group of 1 with a 2-phenylethenesulfonamide group gave compound 5a and resulted in improvement in ET(A)-selectivity. Optimization of the alkoxy side chain attached to the core pyrimidine ring yielded the 2-fluoroethoxy derivative (5n) with further improvement of ET(A)-selectivity. [IC50=2.1 nM for ET(A) receptor, ET(B)/ET(A) ratio=1200]. After oral administration, compound 5n inhibited the big ET-1 induced pressor response in pithed rats with a DR2 value of 2.6 mg/kg and also exhibited a potent antagonistic activity in conscious rats.

Animals↗

PubMed2001

Studies on new platelet aggregation inhibitors 1. Synthesis of 7-nitro-3,4-dihydroquinoline-2(1H)-one derivatives.

A series of 6-cyclic aliphatic amino-7-nitro-3,4-dihydroquinoline-2(1H)-ones were prepared and tested for platelet aggregation inhibitory effect, cardiotonic activity and chronotropic activity. These compounds appeared to show selective inhibitory activity against platelet aggregation. Among them, 6-(4-ethoxycarbonylpiperidino)-7-nitro-3,4-dihydroquinoline-2(1H)-one (22f) showed the most potent inhibitory activity and high selectivity. A divergent synthetic route to 6-cyclic aliphatic amino-7-nitro-3,4-dihydroquinoline-2(1H)-one derivatives has also been investigated.

Acetylation↗

PubMed2001

Transfer of soy isoflavone into the egg yolk of chickens.

A diet containing a high concentration of soy isoflavone was administered to laying hens and the contents of the isoflavones transferred to the plasma and egg yolk were measured. A method for quantitatively measuring the concentration of isoflavone in the yolk was first established, before a high concentration of soy isoflavone was administered to the laying hens over an 18-day period. The concentrations of isoflavone in the plasma and egg yolk reached their highest on the 12th day of the feeding period, the values being 3,167 nmol/l and 65.29 microg/100 g, respectively. The concentration of cholesterol in the yolk was slightly affected during the early stages of the feeding period. These findings clearly demonstrate that soy isoflavone was transferred into the yolk from the feed and that the cholesterol concentration in the yolk was affected by administering the soy isoflavone-enriched feed.

Animal Feed↗

PubMed2001

Xanthogranulomatous cholecystitis mimicking gallbladder cancer: report of a case.

A 61-year-old woman was admitted to our hospital with abnormal findings of abdominal computed tomography. Whereas she had neither fever nor abdominal pain, a cholecystitis was suspected. Ultrasonography showed a mass in the gallbladder with several stones, and an unclear border between the gallbladder and liver. Computed tomography showed a large-mass in the gallbladder with findings that seemed to indicate hepatic invasion and para-aortic lymph node metastasis. On the basis of these findings, we made a diagnosis of gallbladder cancer associated with hepatic invasion and lymph node metastasis. We treated this gallbladder tumor by hepatic arterial infusion chemotherapy via catheter with cisplatin and 5-fluorouracil. Four weeks after administration of the anti-cancer drugs, the tumorous lesion of the gallbladder could not be detected by abdominal imagings, and the gallbladder wall revealed no irregular findings. During laparotomy, the gallbladder showed signs of chronic cholecystitis, and a cholecystectomy was performed. Findings of the resected specimens showed severe inflammation, fibrosis, and bleeding in the gallbladder wall with infiltration by many foamy cells. Histopathological diagnosis was xanthogranulomatous cholecystitis. We report here a case of xanthogranulomatous cholecystitis mimicking gallbladder cancer and review the literature.

Cholecystitis↗

PubMed2001

Polymorphism and allelic loss at the AS3 locus on 13q12-13 in esophageal squamous cell carcinoma.

Our previous studies of esophageal squamous cell carcinoma (ESC) revealed that frequent loss of heterozygosity (LOH) on 13q12-13 was associated with lymph node metastasis. These results suggest that 13q12-13 may harbor a tumor suppressor gene which regulates lymph node metastasis. Recently, a new tumor suppressor candidate, AS3, was identified in this region. We therefore examined AS3 alterations by PCR-SSCP and RT-PCR. Although polymorphisms were found in exon 10 and introns 21, 23, 25 and 29, a possible tumor specific mutation in exon 6 was identified in only one of 31 ESC-derived cell lines, indicating that the remaining allele of AS3 was rarely inactivated by mutational events. Interestingly, ESC patients with rare alleles frequently exhibited lymph node metastasis. These results suggest that polymorphic variation and LOH at the AS3 locus might be associated with lymph node involvement in ESC.

Alleles↗

PubMed2001

Three aberrant splicing variants of the HMGIC gene transcribed in uterine leiomyomas.

Cytogenetic aberrations involving chromosome region 12q13-15 occur frequently among benign mesenchymal tumors in humans, e.g., pleomorphic adenomas of the parotid gland, pulmonary chondroid hamartomas, lipomas, or uterine leiomyomas. HMGIC, a gene encoding a protein of the high-mobility group, has been identified as a target of those events. Using the 3' rapid amplification of cDNA ends (RACE) technique, we identified six different fusion transcripts of the HMGIC gene among 13 uterine leiomyomas; three of these variants had not been described before. Radiation-hybrid mapping located all three of the novel fusion transcripts in the same chromosomal region as the HMGIC gene. Cloning of the entire HMGIC gene in a genomic contig of P1-derived artificial chromosomes and cosmids revealed that the 3' portion of each novel fusion transcript contained cryptic exonic sequences (designated a, b, and c) present in intron 3 of the HMGIC gene. Thus, aberrant alternative splicing was responsible for abnormal HMGIC isoforms in those myomas. Identification of these novel variants suggested that aberrant splicing can join chromosomal translocation and inversion as a mechanism for producing abnormal HMGIC transcripts, and that separation of the DNA binding domains of HMGIC from its acidic carboxyl-terminal regulatory domain can lead to development of benign mesenchymal tumors.

Alternative Splicing↗

PubMed2001

A case of a chronic traumatic thoracic aneurysm 11 years after injury.

A 28-year-old male, who was involved in an automobile accident 11 years previously, was diagnosed as having a chronic traumatic thoracic aneurysm. An enhanced computed tomographic scanning (CT) and three-dimensional CT demonstrated that a thoracic aortic aneurysm of 50 mm in the maximal axis was located at the aortic isthmus and dilated posteriorly. He underwent thoracic aorta graft replacement using Femoro-femoral partial bypass. The surgery was successful and the postoperative course was uneventful.

Accidents, Traffic↗

PubMed2001

Surgical treatment of an aneurysm of the aberrant right subclavian artery involving an aortic arch aneurysm and coronary artery disease.

A 55-year-old man presented with clinical signs of an aortic arch aneurysm. Angiography, MRI and CT demonstrated an aortic arch aneurysm and an aneurysm of the aberrant right subclavian artery. Coronary angiography revealed 95% stenosis in the right coronary artery. Right common carotid artery-right subclavian artery bypass, arch graft replacement and coronary artery bypass grafting were performed successfully. The use of internal shunt tube, hypothermic circulatory arrest and selective cerebral perfusion were useful methods in prevention of cerebral ischemia during surgical reconstruction of the aortic arch. To our knowledge, this is the first report in the literature of a successfully managed case with an aneurysm of an aberrant right subclavian artery involving an aortic arch aneurysm and coronary artery disease.

Aneurysm↗

PubMed2001

Population dynamics of anaerobic microbial consortia in thermophilic granular sludge in response to feed composition change.

A thermophilic UASB reactor was operated at 55 degrees C for greater than 470 days in order to investigate the effects of feed composition on the changes in microbial community structure where thermophilic granular sludge was used as the inoculum source. The feed compositions were changed with cultivation days; phase 1 (1-70 days), alcohol distillery wastewater; phase 2 (71-281 days), artificial acetate wastewater; phase 3 (282-474 days), artificial sucrose wastewater. During the first one month of each phase, the methanogenic activity and cell density of methanogens quantified by fluorescence in situ hybridization (FISH) drastically changed as a result of shift in feed composition. When artificial acetate wastewater was used as feed, retained granular sludge was partially disintegrated due to a decrease in the number of symbiotic bacterial community members: acetogens (acidogens) and hydrogenotrophic methanogens. In contrast, when the feed was shifted to sucrose (phase 3), granulation of biomass was promoted by a remarkable proliferation of the symbiotic community. The presence of hydrogen-utilizing methanogens and acetogens (acidogens) are shown to be effective for the enhancement of thermophilic granulation. The cell density of methanogens determined by FISH was strongly correlated with the methane-producing potential of the retained thermophilic granular sludge.

Acetates↗

PubMed2001

[Usefulness of time-resolved projection MRA on evaluation of hemodynamics in cerebral occlusive diseases].

The usefulness for evaluation of cerebral hemodynamics using time-resolved projection MRA was studied in normal volunteers and patients of cerebrovascular diseases. Six normal volunteers and ten patients with cerebrovascular occlusive diseases including 6 of IC occlusion and 4 of post EC/IC bypass surgery underwent time-resolved projection MRA on a 1.5 T clinical MRI system. Projection angiograms are acquired with 2 D-fast SPGR sequence with a time resolution of approximately one image per second, 40 images being acquired consecutively before and after bolus injection Gd-DTPA. And all images were calculated by complex subtraction from the background mask in a work station. In normal volunteers, the quality of images of time-resolved projection MRA was satisfactory. The arteries from internal carotid artery through M 2 segment of middle cerebral artery and all major venous systems were well portrayed. In 4 cases of IC occlusion who were assessed the collateral flow through the anterior communicating artery and posterior communicating artery, there were delayed to demonstrate the ipsilateral MCA. However, in 2 cases of IC occlusion that were assessed the collateral flow through leptomeningeal anastomosis, ipsilateral MCA and collateral circulation were not demonstrated. In all patients of post EC/IC bypass surgery, the patency of EC/IC bypass could be evaluated as properly with time-resolved projection MRA as 3 D-TOF MRA. Although the temporal and spatial resolutions are insufficient, time-resolved projection MRA was powerful non-invasive method to evaluate the cerebral hemodynamics via the basal communicating arteries in IC occlusion and identify the patency of EC/IC bypass.

Adult↗

PubMed2001

[A case of isolated tricuspid regurgitation caused by a dilated tricuspid annulus treated by ring annuloplasty].

Isolated tricuspid regurgitation is rare. A 64-year-old man was admitted to our hospital with a complaining of shortness of breath and edema of lower extremities. Chest X-ray showed remarkable cardiomegaly (cardiothoracic ratio, 73%). Echocardiogram demonstrated severe tricuspid regurgitation and dilated right atrium. At operation, the tricuspid annulus was severely dilated about 7 cm in diameter, and all leaflets of tricuspid valve were intact. Prosthetic ring annuloplasty with a 32 mm Carpentier-Edwards ring was performed. Postoperative course was uneventful. Four weeks after operation he was discharged from the hospital and he is now leading a normal life. Careful follow up for long time is essential in this case.

Dilatation, Pathologic↗

PubMed2001

Overrepresentation of the EBAG9 gene at 8q23 associated with early-stage breast cancers.

EBAG9, an estrogen-responsive gene located at 8q23 was identified in an effort to clone CpG-binding sites. Its product was later found to be identical to RCAS1, a cancer cell-surface antigen implicated in immune escape. We determined the sequence of the complete cDNA and the genomic structure for EBAG9. EBAG9 gene copy number in 21% (27 of 129) primary breast cancers we examined; EBAG9 mRNA was consistently expressed in cancer cell lines. Detailed physical mapping of the 8q arm, including polymorphic markers for EBAG9 and the CMYC loci, revealed allelic gain of either EBAG9, CMYC, or both, in 45% (58 of 129) of the breast cancers we examined. The EBAG9 gene was increased exclusively in 16 of the 27 tumors showing gain at that locus; the other 11 showed gain of a larger chromosomal region containing both EBAG9 and CMYC. Analysis of subsequent series of 144 primary breast cancers for allelic gain at EBAG9 and CMYC locus showed a similar degree of gain at EBAG9, CMYC, or both. When a total of 273 breast cancers from two series were combined and analyzed for clinicopathological correlation, almost all of the tumors with EBAG9 increased but not those with CMYC. Twenty-eight of 29 were T1/T2 stage carcinomas (<5 cm in diameter), whereas one third (21 of 61) of the tumors in which CMYC was increased but EBAG9 was not, were advanced T3-stage tumors (P = 0.0012). These data suggest that EBAG9 and CMYC gene are independent targets of gain and that overrepresentation of EBAG9 may play a specific role in early stages of breast carcinogenesis.

Alleles↗

PubMed2001

[Aggressively metastatic neuroendocrine carcinoma in the middle mediastinum].

A 50-year-old male patient with no symptoms was admitted to our hospital for further evaluation of a right superior mediastinal mass shadow found in chest radiographs during a health examination. Computed tomographic (CT) scans demonstrated a middle mediastinal mass of 4 cm in diameter surrounded by the SVC, the ascending aorta and the trachea at the subaortic level. Routine examination disclosed no metastatic or primary lesion elsewhere. A surgical biopsy resulted in a diagnosis of neuroendocrine carcinoma of unknown primary organ. The patient was given 1 course of chemotherapy with CAV-PE, but little effect was seen. However, when a PE regimen combined with thoracic radiation was used, the tumor shrank to half of its size. After the patient subsequently received high-dose treatment with Etoposide, CT imaging and cytologic analysis revealed multiple metastases to the subcutaneous tissue, both adrenal glands and the liver. Lung lesions also spread aggressively, and the patient died of metastasis. Although neuroendocrine carcinomas can arise from the systemic neuroendocrine cells including those in the mediastinum, their appearance in the middle mediastinum is rarely reported.

Adrenal Cortex Neoplasms↗

PubMed2001

[A case of eosinophilic myositis proven by immunohistochemistry using antibodies against eosinophilic granule protein].

A 50-year-old man had been well until three months earlier, when he felt general fatigue, and cutaneous rash with itching. Thereafter a general muscular weakness developed and the patient could not walk for a month. Four weeks before referral to our hospital, he had high fever and could not role over in the bed. On admission, the patient was able to walk. He had no skin rash. Neurologically, he showed mild weakness in proximal muscles. Hematologic examination showed mild eosinophilia and serum creatine kinase was mildly elevated. Needle electromyogram revealed a diffuse myogenic pattern in extremities. Eosinophilic myositis was diagnosed by a biopsy of the left calf muscle showing mild infiltration of eosinophilis which was identified using antibodies against eosinophilic granule protein.

Autoantibodies↗

PubMed2001

[Role of neutrophils in acute lung injury induced by Candida sepsis].

To evaluate the role of inflammatory cells in acute lung injury induced by Candida sepsis, we investigated the time course of cell counts in bronchoalveolar lavage (BAL) fluid, the lung wet-to-dry weight (W/D) ratio and the CFU of Candida after a Candida infection. Male BALB/c mice were injected intravenously with 107 CFU of Candida albicans. They were sacrificed by exsanguination 0, 6, 12, 18, and 24 h after infection. The lung W/D ratio was determined in order to assess the severity of pulmonary edema. BAL was performed 3 times with 0.5 ml of sterile saline. The lung W/D ratio increased significantly 24 h after the injection of Candida, and the neutrophil counts in the BAL fluid increased significantly 12, 18, and 24 h after Candida injection. To assess the effect of neutrophils on Candida-induced acute lung injury, we investigated that of neutrocytosis and neutropenia on cell counts in BAL fluid, of the W/D ratio, and of the CFU of Candida in the lung 24 h after infection. We created neutrocytotic mice using G-CSF, and neutropenic mice with cyclophosphamide. Peripheral neutrophil counts decreased significantly in cyclophosphamide-treated mice, and increased significantly in G-CSF-treated mice. The lung W/D ratio increased significantly in cyclophosphamide-treated mice. Neutrophil counts in BAL fluid increased significantly in G-CSF-treated mice, and decreased significantly in cyclophosphamide-treated mice. The CFU of Candida in the lung decreased significantly in G-CSF-treated mice, and increased significantly in cyclophosphamide-treated mice. We concluded that neutrophils play a protective role in Candida albicans-induced acute lung injury.

Acute Disease↗