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Biomedical subjects

T Nomoto

Publications and source records attributed to T Nomoto.

At least 37 records · Page 2Linked to original sources
PubMed2000

Predisposition to lung tumorigenesis.

Mouse inbred strains with inherited predisposition and resistance to lung cancer provide an essential tool for the dissection of the genetics of this complex disease. We have previously mapped a major locus (Pulmonary adenoma susceptibility 1, Pas1) affecting inherited predisposition to lung cancer in mice on chromosome 6, near Kras2. Appropriate crosses that include susceptible mice (Pas1(s)) provide a model system for identifying loci that can modify the lung cancer predisposition phenotype caused by Pas1. Using this approach we have mapped the Pulmonary adenoma resistance 1 (Par1) locus that behaves like a modifier locus of Pas1. More recently, we mapped additional lung tumor resistance loci (Par2, and Par4), and a locus specifically involved with lung tumor progression (Papg1). The mapping of Pas1 in mice stimulated us to test the possible association of genetic markers located in the homologous human region (12p12) with risk and prognosis of lung adenocarcinomas in man. In the Italian population, we carried out an association study by genotyping lung adenocarcinoma patients and healthy controls for genetic markers located in the putative region of interest. Homozygosity of the A2 allele at a Kras2/RsaI polymorphism, and allele 2 at a VNTR polymorphism in the PTHLH gene showed borderline statistically significant associations with lung cancer risk. Furthermore, the same alleles were significantly associated with tumor prognosis. Studies on association were then performed in the Japanese and in European populations. In the Japanese population, the KRAS2/RsaI marker was significantly associated with prognosis of lung adenocarcinoma, whereas the European study did not confirm this association. Our results may provide evidence for the existence of the human PAS1 locus, suggesting that the mouse model of inherited predisposition to lung tumorigenesis is predictive of a human genetic mechanism of susceptibility to lung cancer.

Adenocarcinoma↗
PubMed2000

Chromosomal mapping of genes controlling development, histological grade, depth of invasion, and size of rat stomach carcinomas.

Rat stomach cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) are widely used as a model of differentiated-type human stomach cancers. ACI/N (ACT) rats are susceptible and BUF/Nac (BUF) rats are resistant to MNNG-induced stomach carcinogenesis, and the presence of an autosomal gene with a dominant BUF allele has been suggested. In this study, we performed a carcinogenicity test by giving MNNG in drinking water to 117 male ACI x (ACIxBUF)F1 backcross rats. Each of 100 effective rats was diagnosed for its "carcinoma development" and when it was bearing stomach carcinoma(s), for histological grade, depth of invasion, and size and number of tumors. Carcinoma development was diagnosed based both on the age of the rat and on the presence of stomach carcinoma(s). Linkage analysis was performed with the genotypes of 161 loci, covering 1637 cM of the rat genome. Contrary to our original expectations, the most influential gene was the one on chromosome (chr.) 15, Gastric cancer susceptibility gene 1 (Gcs1), which confers susceptibility to stomach carcinogenesis (LOD, 3.8) with a dominant BUF allele by promoting conversion from adenomas to carcinomas. Two resistance genes on chr. 4 and chr. 3, Gastric cancer resistance gene 1 (Gcr1) and Gcr2, were shown to confer dominant resistance (LOD, 2.7 and 2.6, respectively). Gcs1, Gcr1, and Gcr2 exerted additive effects on the development of stomach carcinomas. A gene on chr. 16, Gcr3, was indicated to reduce the depth of invasion (LOD, 2.2) and sizes of tumors (LOD, 1.9). No linkage was obtained using the number of tumors. These findings show that the coordinate effect of a susceptibility gene, Gcs1, and two resistance genes, Gcr1 and Gcr2, is responsible for the development of MNNG-induced stomach carcinomas and that Gcr3 is responsible for the growth of a stomach carcinoma, reflected in the depth of invasion and in the tumor size.

Animals↗
PubMed2000

Two different techniques of retrograde cerebral perfusion for thoracic aortic surgery through a left thoracotomy.

The authors used profound hypothermic circulatory arrest and continuous retrograde cerebral perfusion for aortic surgery that involved the distal arch through a left thoracotomy. For the first seven patients, oxygenated blood from cardiopulmonary bypass was perfused retrogradely through a venous cannula positioned into the right atrium. In the last 11 cases, venous blood, provided by a perfusion from the lower body, was circulated passively in the brain with the descending aorta clamped. The period of profound hypothermic circulatory arrest was 34.6 +/- 11.1 min, and continuous retrograde cerebral perfusion was 31.3 +/- 11.1 min. Seventeen patients survived, but there was one early death. Two patients with a severely atherosclerotic aneurysm developed permanent neurological dysfunction. The combination of profound hypothermic circulatory arrest, continuous retrograde cerebral perfusion and open aortic anastomosis through a left thoracotomy protects the brain adequately, and facilitates evacuation of debris and air in the aortic arch. It produces satisfactory results for aortic surgery that involves the distal arch.

Aged↗
PubMed2000

A phase II study of combined chemoradiotherapy for limited disease-small-cell lung cancer.

A study to evaluate the efficacy of cisplatin, doxorubicin, and etoposide chemotherapy with combined radiotherapy was undertaken in 26 patients with limited disease-small-cell lung cancer. Patients were treated with cisplatin (80 mg/m2) intravenously (i.v.) on day 1, doxorubicin (30 mg/m2) i.v. on day 1, and etoposide (80 mg/m2) i.v. on days 1, 3, and 5, every 4 weeks for four cycles. Thoracic irradiation of 40 Gy in 20 fractions was delivered during 4 weeks to the primary site starting on day 8 of the second cycle of chemotherapy. The objective response rate was 100%. A complete response was observed in 10 patients (38%). The median survival time was 23 months, and the 3-year survival rate was 42%. Seven patients (27%) continued to survive at least 8 years and remain free from disease. Grade III/IV leukopenia was observed in 25 patients (96%). Grade III/IV thrombocytopenia developed in 19 patients (73%). Grade III/IV esophagitis was not seen. Interstitial pneumonitis occurred in two patients. This regimen is effective and has acceptable toxicity for use in the treatment of limited disease-small-cell lung cancer.

Aged↗
PubMed2000

[Salvage chemotherapy in refractory testicular cancer].

A treatment strategy for patients with refractory testicular cancer who failed in the initial therapy has not been established. Patients with metastatic testicular cancer are treated with BEP (BLM, etoposide, CDDP) therapy, which is recognized as the standard first line chemotherapy regimen. About 80% of patients attain complete remission (CR) with BEP therapy and following salvage surgery. The patients who fail to achieve CR or have recurrences during the period of follow-up will be candidates for salvage chemotherapy. Salvage chemotherapies include VIP (ETP, ifosfamide, CDDP) therapy or high dose chemotherapy with peripheral blood stem cell auto-transplantation (PBSCT); however, the effectiveness of these therapies is limited. Those who fail in these salvage therapies are treated with irinotecan hydrochloride (CPT-11) in Japan. Clinical trials with paclitaxel and gemcitabine have recently been started in the United States and Europe. Further investigations are necessary to develop more useful regimens with these novel anticancer agents for refractory testicular cancer.

Germinoma↗
PubMed2000

[Surgical results of the Senning operation and arterial switch operation for complete transposition of the great arteries].

From March 1980 to August 1997, 42 patients with complete transposition of the great arteries (TGA) type I and II underwent arterial switch procedure (n = 20) or Senning (n = 22) procedure in our institution. In arterial switch procedure group, there were two operative death. No late death occurred, and one patient underwent reoperation and one underwent balloon pulmonary angioplasty for right sided obstruction. The freedom from the intervention rate for right sided obstruction was 83.0% at 5 years, subsequently. In Senning procedure group, operative death occurred in two patients with TGA type II, and one patient with TGA type II and two patients with type I died because of cardiac events in the late stage. In this group, two patients died from accident. The survival rate excluding accidental deaths was 77.7% and 77.7% at 5 and 10 years, respectively. However, those patients who died in the late stage had severe pre-operative and post-operative complication. In conclusion, mid-term results of arterial switch procedure is satisfactory, however, reintervention rate was not so low. Long term results of Senning procedure without preoperative or postoperative complication was satisfactory.

Cardiac Surgical Procedures↗
PubMed1999

Early and mid-term outcomes of cardiac and thoracic aortic surgery in over-75-year-olds with postoperative quality of life assessment.

The early and mid-term outcomes of cardiac and thoracic aortic surgery were reviewed in seventy-two consecutive patients aged 75 years and older, together with assessment of postoperative quality of life. Twenty-six patients had ischemic heart disease, twenty had valvular heart disease, one had congenital heart disease, and twenty-five had thoracic aortic aneurysm. Twenty-five (34.7%) required an emergency operation. There were 6 early deaths (8.3%) and 11 late deaths (17.2%), of which the emergency cases had higher mortality of 5 early deaths (20.0%) and 3 late deaths (15.0%). In particular, most cases with a ruptured thoracic aortic aneurysm died eventually from various complications including neurological dysfunction. The others with a non-ruptured aneurysm also had atherosclerotic aortic or arterial lesions which caused a lethal cerebrovascular accident or ischemic heart disease. The quality of life of 51 of 53 survivors was assessed using the Rosser and Watts index being based on disability and distress scores. The response was satisfactory--the disability score was 2.6 +/- 1.9 and the distress score was 1.4 +/- 0.4. The patients with a thoracic aortic aneurysm had worse quality of life scores than those of the ischemic heart disease or valvular heart disease patient-groups because of various perioperative complications. Our experiences demonstrate that the results including the postoperative quality of life following cardiac and aortic surgery in the elderly is satisfactory except for emergency cases. The results would prompt us to operate, if possible, electively in their stable conditions, even on elderly over-75-year-olds.

Age Factors↗
PubMed1999

Oral administration of the dopamine prodrug docarpamine shortens need for drip infusion of dopamine in patients with low cardiac output syndrome after cardiac surgery.

BACKGROUND: Docarpamine (DOC) is a dopamine prodrug which can be orally administered. It has been found that oral docarpamine transforms into dopamine in vivo, and increases cardiac output and renal blood flow as effectively as intravenous dopamine. METHODS: We reviewed the records of 26 patients who had developed low cardiac output syndrome (LOS) after cardiac surgery and received docarpamine during the early postoperative course. Five patients discontinued docarpamine within 2 days due to arrhythmia. There were 3 hospital deaths. The remaining 18 patients were divided into two groups according to the timing of docarpamine administration. In group A docarpamine was administered during and after weaning from intravenous catecholamines, in group B only on demand after weaning from intravenous catecholamines. RESULTS: There were 12 patients in group A and 6 in group B, and the severity of LOS was relatively milder in group B than in group A. Stable hemodynamics and sufficient daily urinary output were maintained by oral administration of DOC in both groups just as well as by drip infusion of catecholamines. CONCLUSION: Sinse continuous drip infusion of catecholamine commonly slows recovery in LOS patients, it is considered that switching from drip infusion of catecholamines to oral DOC administration is safe and useful for earlier recovery in LOS patients after cardiac surgery.

Administration, Oral↗
PubMed1999

Enhancement of cisplatin sensitivity in high mobility group 2 cDNA-transfected human lung cancer cells.

To elucidate the role of high mobility group 2 protein (HMG2) in cis-diamminedichloroplatinum (II) (cisplatin, CDDP) sensitivity, we constructed a human HMG2-transfected human non-small cell lung cancer cell line, PC-14/HMG2. The HMG2 mRNA expression level was approximately twice those of parental PC-14 and mock-transfected PC-14/CMV. Gel mobility shift assay revealed a CDDP-treated DNA-protein complex in the nuclear extract of PC-14/HMG2, which was not found in the extracts of PC-14 and PC-14/CMV. This complex formation was subject to competition by CDDP-treated non-specific salmon sperm DNA, indicating that ectopic HMG2 recognizes CDDP-damaged DNA. PC-14/HMG2 showed more than 3-fold higher sensitivity to CDDP than PC-14 and PC-14/CMV. The intracellular platinum content of PC-14/HMG2 after exposure to 300 microM CDDP was 1.1 and 1.5 times that of PC-14 and PC-14/CMV, respectively. Cellular glutathione levels were not different in these cell lines. Repair of DNA interstrand cross-links determined by alkaline elution assay was decreased in PC-14/HMG2. These results suggest that HMG2 may enhance the CDDP sensitivity of cells by inhibiting repair of the DNA lesion induced by CDDP.

Carboplatin↗
PubMed1999

Aortic valve replacement for aortic regurgitation in a patient with primary antiphospholipid syndrome.

A 42-year-old woman with the diagnosis of aortic regurgitation was admitted to hospital for surgical treatment. Ten years ago, primary antiphospholipid syndrome had been diagnosed, and she had a history of recurrent spontaneous abortions and deep vein thrombosis. She was suffering from moderate exertional dyspnea and chest pain. Catheter investigation revealed progressive dilatation of the left ventricle and a deterioration of the ejection fraction. The aortic valve was excised and replaced with a mechanical valve. A specimen of the aortic valve showed localized thickening and shrinkage of the midportion and base of each cusp, with vegetation on the surface. These localized, specific findings suggest that another mechanism may be involved in the cardiac valve pathology in patients with primary antiphospholipid syndrome. No hemostatic or thromboembolic problems were encountered after the surgery, and her postoperative course was uneventful.

Adult↗
PubMed1999

[Prognostic factors in a patients with renal cell carcinoma].

PURPOSE: The purpose of this study is to evaluate prognostic factors of renal cell carcinoma using univariate statistics. MATERIALS AND METHODS: Materials are 182 patients treated from 1976 to 1992. Kaplan-Meier method and generalized wilcoxon test were used for statistical analysis. RESULTS: Seventy cases were found incidentally without any symptoms. The overall 5- and 10-year survival rates by Kaplan-Meier method were 73.8% and 66.2%, respectively. In the univariate analysis, sex, chief complaints, tumor sizes, T-Stages, venous invasions and grades were statistically significant prognostic factors. The prognosis of males more than 60 years of age was significantly poor. The prognosis of patients with incidentalomas was far better than that of symptomatic patients. CONCLUSION: Sex and chief complaints were pointed out as significant prognostic factors for renal cell carcinoma.

Adult↗
PubMed1999

[The investigation of age-specific PSA reference range as the cut-off values in the mass screening for prostatic cancer].

BACKGROUND: The objective of this study is to determine age-specific PSA reference ranges in Japanese healthy men and investigate the effectiveness of these ranges as the cut-off values in the mas screening for prostatic cancer. METHODS: The study included a total of 5,206 male aged from 55 to 89 years old who wished to submit the mass screening for prostatic cancer in an urban area of Kyoto in 1995-1997, but had no evident prostatic cancer. We measured serum PSA levels by the filter paper method (Delfia PSA kit). RESULTS: We found the increase in serum PSA levels with the advancing age. With the 95th percentile for serum PSA as the upper limit, the age-specific PSA reference ranges were determined to be 2.1 ng/ml for patients aged 55 to 59 years old, 3.2 ng/ml for 60 to 69 years old, 4.4 ng/ml for 70 to 79 years old, 6.5 ng/ml for 80 to 89 years old. If we used these ranges as the cut-off values in the mass screening this time, five cases from 76 to 89 years old of prostatic cancer were overlooked. CONCLUSIONS: We found the increase in serum PSA levels with advancing age. But the positive proof of using this range to a mass screening for prostatic cancer was not certified, because time incidence of prostatic cancer in the examinees was uncertain and there is a possibility of overlooking some cases.

Age Factors↗
PubMed1999

Single-stage surgery for distal aortic arch aneurysm and infrarenal abdominal aortic aneurysm through anterolateral approach.

A 58-year-old man with a distal aortic arch aneurysm (DAA) associated with an infrarenal abdominal aortic aneurysm (AAA) successfully underwent a single-stage replacement of the aneurysms. A left anterolateral thoracotomy was used for replacement of the DAA, which was performed using profound hypothermic circulatory arrest and continuous retrograde cerebral perfusion. An extraperitoneal approach in conjunction with a lateral abdominal incision was employed for replacement of the AAA. The combination of an anterolateral thoracotomy and a lateral abdominal incision is useful in combined surgery for DAA and AAA.

Anastomosis, Surgical↗
PubMed1999

[Valve replacement in children].

Between May 1979 and September 1998, 202 children underwent surgical treatment for valvular heart disease. Of these 23, who ranged in age from 25 days to 15 years, underwent valve replacement, including 1 reoperation. The valve replacement consisted of the aortic valve in 5 patients, the mitral valve in 3, the tricuspid valves in 9, including 5 systemic atrioventricular valves for atrioventricular discordance, the pulmonary valve in 6, 5 bioprostheses and 18 mechanical prostheses. There were 4 operative deaths, 1 hospital death and 3 late deaths. At the 10-years follow-up, the actual survival rate was 67.8%, the event free rate was 76.1% and the freedom from reoperation rate was 86.2%. Valve re-replacement was performed in only 1 patient due to a thrombosed tricuspid valve. These results suggest that there is a small risk of major complications and reoperation in children who undergo valve replacement, whether a bioprosthetic valve or a mechanical valve. The long-term results of younger patients should be followed more closely according to their growth.

Adolescent↗
PubMed1999

Purulent pericarditis presenting as an extracardiac mass in a patient with untreated diabetes.

A 50-year-old man with symptoms of bi-ventricular heart failure was transferred to our hospital with a diagnosis of extracardiac tumor. He had a 10 year history of untreated diabetes. Chest computed tomography (CT) revealed an extracardiac mass in the right atrio-ventricular groove. Cardiac catheterization revealed an elevated mean right atrial pressure of 18 mmHg, mean pulmonary wedge pressure of 16 mmHg, and the right ventricular pressure curve demonstrated typical dips and plateaus. At surgery, there was severe adhesion between the pericardium and epicardium, and the pericardium was severely thickened and contained turbid pus. In the left thoracic cavity, there was large amount of pleural effusion and pus. Therefore, the patient was diagnosed with purulent pericarditis caused by left empyema. The thickened pericardium at the anterior portion of the heart was resected, however resection of the remaining portion was abandoned because the adhesion was so tight. After surgery, the patient underwent irrigation of the heart and left thoracic cavity by 1% povidone iodine solution and 0.5 mg/ml of imipenem for 7 days. Bacteriologic culture of the pus from the pericardium revealed anaerobic gram negative bacteria. After 4 months of antibiotics infusion, his C reactive protein became negative and the patient was subsequently discharged from our hospital.

Anti-Infective Agents, Local↗
PubMed1999

[The salvage chemotherapy for refractory testicular cancer with novel anticancer agents].

Despite the generally high cure rate in patients with metastatic testicular cancer, 20% to 30% of treated patients will become candidates for salvage chemotherapy. We reviewed the recent salvage chemotherapy trials of refractory diseases. CPT-11 is a new derivative of camptothecin and has activity in a variety of solid tumors. We evaluated the antitumor effect of combination chemotherapy using CDDP and CPT-11 against refractory testicular cancer. Fourteen patients who failed to achieve complete remission with salvage chemotherapy were treated with combination chemotherapy with CPT-11 and CDDP or 254-S (nedaplatin) as third line chemotherapy. Six patients remain alive and disease-free and 5 patients died of disease. The combination of CPT-11 and either CDDP or nedaplatin was significantly more effective than other salvage therapy regimens such as VIP. Paclitaxel, ifosfamide, etoposide regimens were also effective in patients with refractory testicular tumors. We concluded that these combination regimens demonstrated significant activity against refractory testicular tumor and further investigation is warranted.

Adult↗