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Biomedical subjects

T Nomoto

Publications and source records attributed to T Nomoto.

At least 19 recordsLinked to original sources
PubMed1997

Identification of cis-acting DNA elements of the human gamma-glutamylcysteine synthetase heavy subunit gene.

Transcriptional activity of the 5'-flanking sequence of the human gamma-glutamylcysteine synthetase heavy subunit (gamma-GCSh) gene was investigated in COS7 cells transfected with hGH reporter constructs having successively deleted 5'-flanking sequence of the gamma-GCSh gene. Transcriptional activity was determined by the amounts of hGH secreted from the reporter constructs. Deletion of the sequence from -1,413 to -664 or -315 base pairs (bp) increased transcriptional activity from 100 to 138 or 136%. Further deletion from -315 to -241 bp, which contained an AP1 site, decreased transcriptional activity to 87%. Mutations introduced into the AP1 decreased transcriptional activity from 136 to 105%. These findings suggested that the AP1 increased transcriptional activity. When the sequence from -241 to -192 bp was deleted, transcriptional activity was restored from 87 to 128%. When this sequence was linked to the thymidine kinase promoter, it also decreased transcriptional activity by 38%. Deletion from -192 to -149, -116, or -108 bp did not significantly alter transcriptional activity. Further deletion of the GC-rich sequences from -108 to -70 and -28 bp dramatically decreased transcriptional activity from 135 to 87 and 34%, respectively. These findings indicate that multiple DNA elements, especially those in the proximal GC-rich sequences, are involved in the regulation of transcriptional activity of the gamma-GCSh gene.

Base Composition↗
PubMed1997

A phase II study of carboplatin-cisplatin-etoposide combination chemotherapy in advanced non-small-cell lung cancer.

It is reported that the combination of cisplatin (CDDP) and carboplatin (CBDCA) is synergistic in vitro. The objective of this study was to evaluate the therapeutic effect and safety of the two platinum compounds in combination with etoposide in the treatment of non-small-cell lung cancer (NSLC). Forty patients were registered. Based on the results of a phase I study, patients were treated with CDDP (80 mg/m2 i.v. on day 1), CBDCA (280 mg/m2 i.v. on day 1), and etoposide (80 mg/m2 i.v. on days 1-3). Of the 40 patients, 30 were men and 10 women. Histology revealed adenocarcinoma(AC) (n = 20), squamous cell carcinoma(SCC) (n = 18), and large cell carcinoma(LCC) (n = 2). Staging: IIIA (n = 3); IIIB (n = 17); and IV (n = 20). A 32.5% overall response rate [13 of 40; 95% confidence interval (CI) 18-47%] was achieved. The response rates in patients with SCC and AC were 55.6 and 10.0% (p < 0.005), respectively. The median duration of response was 47.1 weeks and the overall median survival time was 57.1 weeks. Leukopenia and thrombocytopenia--World Health Organization (WHO) grade IV--occurred in nine and 11 patients, respectively. Nonhematological toxicities were mainly nausea, vomiting, and alopecia. In conclusion, further investigations of this regimen are warranted in the treatment of NSLC.

Adult↗
PubMed1997

Effect of glutathione depletion on cisplatin resistance in cancer cells transfected with the gamma-glutamylcysteine synthetase gene.

Overexpression of the human gamma-glutamylcysteine (gamma-GCS) gene resulted in cisplatin resistance with an increased glutathione (GSH) content, increased ATP-dependent glutathione S-conjugate export pump (GS-X pump) activity and decreased platinum accumulation in human lung cancer cells transfected with a gamma-GCS cDNA expression vector, as we previously reported. In this study, we examined the effects of buthionine sulfoximine (BSO), a specific inhibitor of gamma-GCS, to determine whether GSH depletion alters cisplatin resistance in a gamma-GCS-transfected cell line, SBC-3/GCS. In the presence of 10 microM BSO for 4 days, SBC-3/GCS still showed resistance to cisplatin, although it was partially reversed. Under these conditions, GS-X pump activity remained up-regulated in spite of low GSH content, and the platinum content was decreased. These data suggest that the GS-X pump itself influences cisplatin resistance, as well as cellular GSH content.

Aminoacyltransferases↗
PubMed1997

Interferon-gamma-inducing factor gene transfection into Lewis lung carcinoma cells reduces tumorigenicity in vivo.

To investigate the immunoregulatory effect of murine interferon-gamma-inducing factor (mIGIF), we transfected Lewis lung carcinoma (LLC) cells with a mammalian expression vector containing the mIGIF complementary DNA. The culture medium of the transfectant cells stimulated interferon-gamma (IFN-gamma) production by spleen cells in vitro in the presence of anti-CD3 antibody and markedly potentiated the effect of interleukin-12 (IL-12) on IFN-gamma production by spleen cells. mIGIF transfectant cells showed reduction of tumorigenicity and induction of an in vivo immuno-protective effect against the parental LLC cells. To examine the combined effect of systemic administration of recombinant IL-12 (rIL-12) and local mIGIF on the tumorigenicity, mice were challenged with LLC or transfectant cells on day 0, and the tumor-bearing mice were injected with 50 ng of rIL-12 intraperitoneally from day 7 to 11. Systemic rIL-12 showed an anti-tumor effect. However, mIGIF gene expression did not potentiate this effect of systemic rIL-12 in vivo.

Animals↗
PubMed1997

Cavernous angioma with olivary hypertrophy and contralateral cerebellar diaschisis.

We describe a 66-year-old man with a 20-year history of ataxic gait who suddenly developed diplopia on rightward gaze. Neurologic examination revealed right hemi-ataxia and hemi-hypesthesia, and left internuclear ophthalmoplegia. MRI showed a cavernous angioma in the left tectum, mild right cerebellar atrophy, and left interior olivary hypertrophy. Single photon emission computed tomography (SPECT) imaging demonstrated contralateral cerebellar diaschisis. We discuss the findings and review the literature concerning contralateral cerebellar diaschisis.

Aged↗
PubMed1997

[Cushing's syndrome due to small cell lung cancer with ectopic production of adrenocorticotropic and parathyroid hormone].

A 72-year-old man was admitted to our hospital because of a tumor-like shadow on a chest X-ray film. At the initial examination, he had clinical signs of Cushing's syndrome: moon face, central obesity, and hypertension. A computed tomographic scan of chest showed an abnormal shadow in the lung (5 x 6 cm) with involvement of the right paratracheal and anterior tracheal lymph nodes, and a right-sided pleural effusion. Small cell lung cancer (extended disease; T2N2M6 stage IV) was diagnosed after a transbronchial biopsy. The concentrations of adrenocorticotropic hormone, cortisol, and parathyroid hormone in plasma were markedly elevated, and there was no circadian rhythm (336 pg/ml. more than 60.1 micrograms ml. and 805 pg/ml, respectively). Fluid obtained by thoracentasis had malignant cells, and the levels of adrenocorticotropic hormone and parathyroid hormone in the effusion (1120 pg/ml and 1810 pg/ml, respectively) were higher than those in serum, which indicates that these hormones were produced by the tumor cells. The patient received chemotherapy and responded well, but he died of respiratory failure 26 months later. The response rate to chemotherapy in elderly patients with lung cancer is said to be comparable to that in younger patients, but treatment may be difficult because of poor performance status and diminished physical capacity. Although patients with lung cancer complicated by Cushing's syndrome have a poor prognosis, this patient survived for more than 2 years after the disease was diagnosed.

Adrenal Cortex Hormones↗
PubMed1997

[A pilot study of mass screening program for prostatic cancer by means of prostate specific antigen (PSA) filter paper method].

BACKGROUND: Mass screening program for prostatic cancer (PC) using prostate specific antigen (PSA) filter paper method was performed in an urban area of Kyoto in 1995. METHODS: In the primary study, males more than the age of 55 years were examined by PSA (Delfia PSA kit) with blood samples on a filter paper. The cut-off values were set at 4 and 10 ng/ ml. Subjects whose PSA level ranged from 4.1 to 10.0 ng/ml (gray zone) were examined by digital rectal examination (DRE), transrectal sonography (TRS) and PSA density (PSAD; more than 0.15) in the secondary study, then the suspected subjects of PC underwent 6 sextant biopsies under interventional ultrasound. Subjects whose PSA level were more than 10.1 ng/ml were biopsied directly. RESULTS: Of 3,749 males who took the annual health checkup system organized by the government, 2,387 males wished to submit this screening. Among them, 2,217 (92.9%) showed a negative PSA, 107 belonged to the gray zone and 43 had a PSA more than 10.1 ng/ml. Of these, 102 subjects underwent biopsy. PC was finally detected in 28 (1.2%). The positive predictive value for positive PSA and gray zone PSA was 46.3% and 8.4%, respectively. In the detected cancers, 17 cases (60.7%) belonged to Stage B, 5 (17.9%) to Stage C and 6 (21.4%) to Stage D. CONCLUSION: The results suggested that this system of mass screening program for PC combined with the annual health checkup was suitable for the future "national-level" screening.

Aged↗
PubMed1997

Mid-term results of mitral valve replacement combined with chordae tendineae replacement in patients with mitral stenosis.

BACKGROUND AND AIMS OF THE STUDY: Although many studies have found that preservation of the continuity between the mitral annulus and the papillary muscles during mitral valve replacement improves postoperative left ventricular performance in patients with mitral regurgitation, much less research has been done in this respect in patients with mitral stenosis. We reviewed our experience with mitral valve replacement combined with chordae tendineae replacement in 29 patients with mitral disease, 26 of whom had mitral stenosis. METHODS: During mitral valve replacement, continuity between the papillary muscle and annulus was restored with expanded polytetrafluoroethylene (ePTFE) mattress sutures, which were threaded into the compact portion of each papillary muscle and placed at the 2, 4, 8 and 10 o'clock positions in the mitral annulus. Postoperatively, the patients were followed by echocardiographic assessment and exercise (stress) radionuclide angiography testing. The stress test results were compared with those in patients who had undergone traditional mitral valve replacement, and also those in normal people. RESULTS: There were no hospital deaths, complications, or cardiac deaths or events during a median follow up of two-and-a-half years. Echocardiography showed no postoperative cardiac dilatation. The stress tests found no significant differences between the ejection fraction in mitral stenosis patients who underwent conventional mitral valve replacement and in those who had valve replacement combined with ePTFE chordae tendineae replacement. CONCLUSIONS: A direct advantage of chordae-preserving mitral valve replacement over conventional replacement with respect to postoperative global left ventricular performance in patients with mitral valve stenosis has not been demonstrated. However, postoperative regional left ventricular contraction in patients with mitral stenosis has been observed to be better among those who have undergone the chordae-preserving procedure. Additional investigations are needed to elucidate the effects of this procedure in mitral stenosis, but we believe that the technique improves left ventricular performance and may decrease the risk of left ventricular rupture.

Adult↗
PubMed1997

[A case of paratesticular rhabdomyosarcoma with a paraaortic lymph node metastasis].

A case of paratesticular rhabdomyosarcoma in a 22-year-old male is reported. Radiological examination revealed a gross metastatic mass in the paraaortic lymph node. Right high orchiectomy was followed by chemotherapy consisting of cisplatin, vincristine, cyclophosphamide and adriamycin (IRS-III regimen 35). A complete response was seen 4 months after start of therapy. However, recurrent disease developed in the same paraaortic lymph node 25 months postoperatively. The patient died of tumor progression 11 months later.

Adult↗
PubMed1997

[A case of renal cell carcinoma associated with ossification].

A 40-year-old woman presented with left lumbar pain. A plain abdominal roentgenogram showed patchy calcifications dispersed in a diameter of 7.5 cm at the lower pole of the left kidney. Computed tomography and angiography revealed a hypovascular tumor 10 cm in diameter. A left radical nephrectomy was performed. Histopathological diagnosis was renal cell carcinoma, clear cell subtype, pT2N0M0, accompanied with marked stromal calcification. The patient remains free of recurrence 42 months postoperatively. This is the 26th case reported in the Japanese literature.

Calcinosis↗
PubMed1997

[Mass screening for prostatic cancer].

Two mass screening programs for prostatic cancer (PC) have been conducted at our institution. The first program, based on transrectal ultrasonography (TRUS), was performed between 1975 and 1995 in a total of 16,313 men over 55 years of age. Those showing abnormal findings on TRUS were referred to the secondary urological examination including needle biopsy of the prostate. PC was detected in 93 men (0.6%) and 43 of them were in the early stage. In 1995, a new mass screening program for PC was performed in an urban area of Kyoto. Of 3,749 men over 55 years of age who took the annual health checkup organized by the government, 2,387 wished to receive this screening. The primary examination consisted of Delfia prostate specific antigen (PSA) assay of dried blood samples on a filter paper. Men with PSA levels > 4.0 and < or = 10.0 ng/ml showing abnormal findings on TRUS and/or digital rectal examination, or PSA density > 0.15, underwent 6 sextant biopsies under transrectal ultrasonography, as well as men with PSA levels > 10.0 ng/ml. PSA levels were < or = 4.0 in 2,217 men, > 4.0 and < or = 10.0 in 107, and > 10.0 in 43. Prostatic biopsy was performed in 102 men. PC was detected in 28 men (1.2%) and 17 of them were in the early stage. These findings suggest that the PSA-based mass screening program for PC combined with the annual health checkup is suitable for future "national-level" screening.

Adult↗
PubMed1997

[Emergent coronary artery bypass grafting in a patient with mirror-image dextrocardia].

A 49 year-old-man with known situs inversus totalis was admitted to our hospital with a history of angina pectoris of 4 months duration. Coronary arteriography revealed that the left main trunk had a 90% stenosis. After the arteriography, the patient's hemodynamics was deteriorated, and he required a support of intraaortic balloon pumping. He underwent emergent coronary artery bypass grafting with saphenous veins the following day, and recovered uneventfully. Technical problems in this patient from a surgical viewpoint were discussed. As far as we know, this is the first case of coronary bypass grafting on a patient with mirror-image dextrocardia and a stenosis of the left main trunk.

Coronary Artery Bypass↗
PubMed1996

Warm heart operation in a patient with myotonic dystrophy.

Myotonic dystrophy is the most severe form of myotonic disorder. Hypothermia or hyperkalemia may cause generalized muscle contraction during heart operations. We successfully repaired an atrial septal defect and pulmonary stenosis in a patient with myotonic dystrophy using systemic normothermia with continuous normokalemic coronary perfusion. This is the second reported case of a patient with myotonic dystrophy who underwent a cardiac operation.

Adult↗
PubMed1996

Phase I study of a carboplatin-cisplatin-etoposide combination chemotherapy in advanced non-small-cell lung cancer.

Cisplatin (CDDP)-containing chemotherapy has become the mainstay of clinical trials in unresectable non-small-cell lung cancer (NSCLC), but the role of chemotherapy in the routine management of NSCLC remains controversial. We conducted a phase I study with the combination carboplatin (CBDCA), CDDP, and etoposide (Etop) in unresectable NSCLC. CBDCA, at a starting dose of 80 mg/m2, on day 1, was combined with a fixed dose of CDDP (80 mg/m2, day 1) and Etop (80 mg/m2, days 1-3). Escalation was performed after four patients entered at each dose level. If no World Health Organization (WHO) grade 4 toxicity developed after the first cycle in more than half of the patients or WHO grade 3/4 toxicity in more than two thirds, the dose was escalated. The maximum tolerated dose was established at 300 mg/m2 for CBDCA. Thrombocytopenia and leukopenia were the dose-limiting toxicities. No grade 3/4 nonhematologic toxicities were seen. The recommended dose of CBDCA to be combined with CDDP (80 mg/m2, day 1) and Etop (80 mg/m2, days 1-3) is 280 mg/m2. This trial suggests that our combination chemotherapy may be effective in patients with advanced NSCLC. A multicenter phase II study based on these findings is now under way.

Adult↗
PubMed1996

A lipid lowering drug (bezafibrate) has a favorable effect on liver enzymes (Al-P and gamma-GTP).

We administered 400 mg of bezafibrate daily to 27 patients with hyperlipidemia for seven moths. Most biochemical parameters remained unchanged, whereas levels of alkaline phosphatase (Al-P)and gamma-glutamyl transpeptidase (gamma-GTP), which are the hepatobiliary enzymes, were significantly decreased. Blood lipid levels were improved. Al-P levels decreased significantly from the baseline level of 174.5 IU/l to 116.7 IU/l (-26.5%) and gamma-GTP levels also decreased from 64.4 IU/l to 34.4 IU/l (-29.5%) (p < 0.001). When we compared the changes in serum lipid levels with those in Al-P and gamma-GTP levels following bezafibrate therapy, we found a slight degree of correlation between changes in gamma-GTP and triglyceride (T-G) levels, but no correlation at all between the changes of Al-P and total-cholesterol (T-cho), T-G or high density lipoprotein cholesterol (HDL-C). A close correlation was observed between both Al-P and gamma-GTP (r = 0.81, p < 0.001). From these results it was suggested that bezafibrate has not only a lipid lowering effect but has a favorable efficacy on the hepatobiliary enzymes.

Aged↗