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Biomedical subjects

T Nomoto

Publications and source records attributed to T Nomoto.

At least 91 records · Page 5Linked to original sources

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↗

[Surgical treatment of infective endocarditis].

From 1981 to 1996, 48 consecutive patients, aged range 1 to 72 years, underwent surgical treatment for infective endocarditis. The infection was in the aortic valve in 10 patients, the mitral valve in 17, the aortic and mitral valves in 7, mixed aortic, mitral and tricuspid valves in one, the tricuspid valve in 9, the pulmonary valve in 3, and the other in 2, thirty-seven patients had native valve endocarditis (NVE) of which 22 cases were in the active stage. Seven cases had active prosthetic valve endocarditis (PVE) and 4 had VSD patch infection. The overall hospital mortality rate was 14.6% (7/48). The hospital mortality rate of NVE was 2.7% (1/37) and that of active NVE was 4.5% (1/22). That of PVE was 71.4% (5/7) and one of 4 cases with VSD patch infection was lost, so the mortality rate of the prosthetic material infection was 54.5% (6/11). Only 1 patient required reoperation for persistent infection. There were 2 late deaths caused by noncardiac disease. Thirty-nine of the total IE patients are now survived. These data demonstrate excellent results in patient with NVE undergoing the surgical treatment at the early phase, and support the premise that patients with active PVE should have also early surgical intervention.

Adolescent↗

Phorbol ester and okadaic acid-resistant cells: the crossroads of signal transduction and drug resistance.

Many factors are involved in the development of drug resistance for anticancer drugs. The drugs should pharmacokinetically attain the appropriate concentration. They should be metabolized to the active forms. Tumor cells should have sensitivity to them. Several molecular and biochemical mechanisms that may explain cellular drug resistance have been identified. The contribution of protein phosphorylation and dephosphorylation for drug resistance is demonstrated in phorbol ester and okadaic-acid-resistant cells. The modulation of drug resistance by substances that affect the signal transduction pathway is an important issue in the development of an effective method for overcoming drug resistance.

Antineoplastic Agents↗

[Cell cycle regulation by anticancer agent].

Some anticancer agents induce cell cycle arrest. We analyzed the effect of anticancer agents on cell-cycle regulators, such as CDK. Our data suggested that arresting cells in the G2-phase of the cell cycle by cisplatin might be regulated by dephosphorylation of cdc2 kinase. Butyrolactone I inhibits both cdc2 and CDK2 kinase in the cell-free system. The cytotoxic effect of paclitaxel shows mainly in the M-phase of the cell cycle. Suramin inhibits cdc2 kinase. UCN-01, a protein kinase-C inhibitor, also inhibits both cdc2 and CDK2 kinase. Some anticancer agents induce apoptosis.

Antineoplastic Agents↗

[Primary lung cancer in young patients].

We studied the clinical characteristics and prognosis of patients, 40 years old or younger, in whom primary lung cancer was diagnosed and treated at National Nishigunma Hospital between 1982 and 1993, and compared them with those of 978 patients more than 40 years old. Younger patients numbered 30 (3.0%). Females accounted for 16 of the 30 cases (53.3%), a proportion higher than the female: male ratio for the older patients (27.8%). There were more smokers among the older patients (72.8%) than among the younger patients (53.3%) (p < 0.01). Adenocarcinoma was significantly more common (19/30, 63.3% vs 43.8%, p < 0.05) and squamous cell carcinoma was less common (3.30, 10.0% vs 34.3%, p < 0.05) in the younger patients than in the older patients. Median survival time in younger patients was 30.0 months, and in older patients it was 14.6 months, but we found no significant difference in survival between younger and older patients. In the younger group, all the cases of stage I or II disease were discovered during mass screening.

Adenocarcinoma↗

[Evaluation of surgical treatment for bone metastatic lesion in renal cell carcinoma].

Ten renal cell carcinoma (RCC) patients with bone metastatic lesions were treated in the Kyoto Prefectural University of Medicine between January, 1977, and December, 1992. Surgical treatment for the metastatic lesion was performed on 4 patients, while conservative treatment was performed on the other 6 patients. Surgical treatment made the patients painless consecutively, resulting in higher activities of daily life. However, recurrence of RCC developed in all the cases between 2 and 7 years later. Surgical treatment for the metastatic lesion was considered to be only a palliative therapy for RCC with bone metastasis and the indication should be limited to patients expected to have a good prognosis.

Adult↗

[Benign hemorrhagic renal cyst diagnosed by endoscopic biopsy: a case report].

A case of benign renal hemorrhagic cyst in a 73-year-old man is reported. Ultrasonography, computed tomography and magnetic resonance imaging revealed a solid mass in the left renal cyst. Percutaneous puncture of left renal cyst was carried out followed by endoscopic biopsy of the intracystic masses. Specimens showed no malignancy. As we could not rule out malignancy, left partial nephrectomy was performed. The surgical specimen was free from malignancy by pathological examination. Thus endoscopic biopsy of intracystic tumor indicated the correct diagnosis.

Aged↗

Developmental changes in the response of rat isolated duodenum to nicotine.

Developmental changes in the response to ganglionic stimulants, nicotine and dimethylphenylpiperazinium, were investigated in rat isolated duodenum by recording isotonic mechanical activity. The duodenal response to nicotine/dimethylphenylpiperazinium (3 x 10(-7) to 10(-3) M) in neonatal rats was contraction, which was blocked by hexamethonium, tetrodotoxin and hyoscine. The response to nicotine/dimethylphenylpiperazinium (10(-6) to 10(-4) M) in the adult duodenum was relaxation, which was blocked by tetrodotoxin and hexamethonium, but by neither guanethidine nor hyoscine. The transition of the response to nicotine/dimethylphenylpiperazinium from contraction to relaxation occurred at around the 3rd postnatal week. Nicotine-induced relaxation of adult duodenum was significantly inhibited by preincubation with alpha-chymotrypsin, a proteolytic enzyme, and a combination of nucleotide pyrophosphatase and 8-phenyltheophylline, a P1 purinoceptor antagonist. Nicotine-induced relaxation was desensitized by alpha, beta-methylene ATP, a stable P2x purinoceptor agonist. These results suggest that the contractile response of isolated duodenum to nicotine is mediated through cholinergic transmission in neonatal rats and the relaxant response is mediated through non-adrenergic, non-cholinergic transmission, which involves both peptidergic and purinergic transmission, in adult rats.

Adenosine Triphosphate↗

Possible involvement of L-arginine-nitric oxide pathway in modulating regional blood flow to brown adipose tissue of rats.

To evaluate whether the L-arginine-nitric oxide (NO) pathway is involved in the regulation of regional blood flow to brown adipose tissue (BAT), the effects of two specific NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA), on the blood flow to interscapular brown adipose tissue (IBAT) were studied in urethane-anesthetized rats. Regional blood flow in IBAT was measured with laser-Doppler flowmetry. An intravenous injection of L-NAME and L-NMMA, but not of either D-enantiomer, caused a transient and dose-dependent increase in IBAT blood flow. Dose-response curves for these NO synthase inhibitors showed that L-NAME was more potent than L-NMMA in increasing IBAT blood flow. We also observed a concomitant pressor effect accompanied by a slight decrease in heart rate following intravenous injection of L-NAME and L-NMMA. An elevation of IBAT blood flow and blood pressure induced by both L-NAME and L-NMMA was reversed by L-arginine in an enantiomerically specific manner. The increase in IBAT blood flow induced by NO synthase inhibitors was of shorter duration and less sensitive to L-arginine than the increase in blood pressure. Our results show that the IBAT blood flow is increased by inhibition of NO synthase and that the response of IBAT vasculature to NO synthase inhibitors is different from that of the resistance vessels which regulate blood pressure. The involvement of L-arginine-NO pathways in modulating microcirculation in IBAT is suggested.

Adipose Tissue, Brown↗

Membrane-bound cytochrome c is an alternative electron donor for cytochrome aa3 in Nitrobacter winogradskyi.

We purified membrane-bound cytochrome c-550 [cytochrome c-550(m)] to an electrophoretically homogeneous state from Nitrobacter winogradskyi. The cytochrome showed peaks at 409 and 525 nm in the oxidized form and peaks at 416, 521, and 550 nm in the reduced form. The molecular weight of the cytochrome was estimated to be 18,400 on the basis of protein and heme c contents and 18,600 by gel filtration. The N-terminal amino acid sequence of cytochrome c-550(m) was determined to be A-P-T-S-A-A-D-A-E-S-F-N-K-A-L-A-S-A-?-A-E-?-G-A-?-L-V-K-P. We previously purified soluble cytochrome c-550 cytochrome c-550(s)] from N. winogradskyi and determined its complete amino acid sequence (Y. Tanaka, Y. Fukumori, and T. Y. Yamanaka, Biochim. Biophys. Acta 707:14-20, 1982). Although the sequence of cytochrome c-550(m) was completely different from that of cytochrome c-550(s), ferrocytochrome c-550(m) was rapidly oxidized by the cytochrome c oxidase of the bacterium. Furthermore, the liposomes into which nitrite cytochrome c oxidoreductase, cytochrome c oxidase, and nitrite were incorporated showed nitrite oxidase activity in the presence of cytochrome c-550(m). These results suggest that cytochrome c-550(m) may be an alternative electron mediator between nitrite cytochrome c oxidoreductase and cytochrome c oxidase.

Amino Acid Sequence↗

[A clinical study of 17 cases of penile cancer].

A clinical evaluation of 17 patients with penile cancer treated in our hospital from 1965 to 1991 were surveyed. They were between 34 and 74 years old with a mean age of 63.8 years. The average interval between the onset and the first visit was 22.8 months. Fourteen patients (83%) complained of the manifestation of a tumor and 14 patients (83%) were phimotic. The stage classified according to Jackson was Stage I for 6, Stage II for 6, Stage III for 4 and Stage IV for 1 patient. At the first visit, the inguinal lymph nodes were palpated in 8 patients and metastasis was confirmed in 5 (63%) of them. Surgical treatment was given to 15 patients (88%) (radical or partial penectomy was performed in most cases). Chemotherapy was given to 9 patients (60%) (main chemotherapeutic agent was bleomycin) and irradiation to 5 patients (30%). The overall 3-year survival rate was 71%, and 5-year survival rate was 56%. The 5-year survival rate in the low stage group (Stage I, II) was 75%, while that in the high stage group (Stage III, IV) was 0%, showing a significant difference.

Adult↗

[A case of long-term survival in a patient with small cell lung carcinoma with syndrome of inappropriate secretion of anti-diuretic hormone].

A 73-year-old man was admitted on April 1984 because of an abnormal shadow on chest X-ray. He was diagnosed as having small cell lung carcinoma (oat cell type) with inappropriate secretion of antidiuretic hormone (SIADH). Initial chemotherapy with cyclophosphamide, ACNU, vincristine, adriamycin, cis-platinum and etoposide was administered. The mass subsequently disappeared, and the serum sodium level normalized. About 2 years later, the patient developed a relapse of the primary lesion with hyponatremia. The same regimen as the initial chemotherapy was initiated and a complete response was again obtained. Similar episodes were repeated four times, and he died in April 1991. This patient survived for about seven years after the initial treatment without maintenance chemotherapy.

Aged↗

Developmental changes in the effect of atrial natriuretic peptide on tissue cyclic GMP content and particulate guanylate cyclase activity of aorta, kidney and lung of rats.

To investigate possible developmental changes in the physiological effect of atrial natriuretic peptide (ANP) after birth, we studied the effect of ANP on the slice cGMP content and the particulate guanylate cyclase activity of aorta, kidney and lung in neonate, 2-week-old and adult rats of both sexes. Incubation with human ANP(99-126) (hANP) increased significantly the slice cGMP content of aorta, kidney and lung in three ages of rats. The hANP-stimulated fraction of cGMP contents of kidney decreased, that of lung increased with development, whereas that of aorta showed no significant change. Consistently, the hANP-responsive particulate guanylate cyclase activity decreased in kidney, increased in lung during development, without significant developmental change in aorta. These results indicate a differential change in the effect of hANP on the slice cGMP content among tissues during development. The developmental change in the effect of hANP on slice cGMP content is probably caused by the ontogenetic change in activation of ANP receptor-linked guanylate cyclase.

Aging↗

[Changes in arachidonic acid-induced respiratory distress in streptozotocin-diabetic mice].

Using streptozotocin (STZ)-diabetic mice, we examined the respiratory distress induced by arachidonic acid. Male ddY mice were made diabetic by injecting STZ (170 mg/kg, i.p.) 2 weeks prior to the experiment. Control mice received the vehicle (citrate buffer, pH 4.6). The duration of respiratory distress was observed by a slow i.v.-injection of sodium arachidonic acid (AA) into the caudal vein of mice at the dose of 50 mg/kg. Aspirin was i.p.-administered 30 min before AA. OKY-046 (specific thromboxane A2 (TXA2) synthetase inhibitor), OP-41483 (stable prostacyclin analog) and 9, 11 epithia-11, 12-methano-TXA2 (STA2, stable TXA2 analog) were i.v.-administered 30 min before AA. The duration of respiratory distress induced by AA was significantly reduced in STZ-diabetic mice. Aspirin (10-50 mg/kg) and OKY-046 (25-100 mg/kg) enhanced the AA-induced respiratory distress in STZ-diabetic mice. OP-41483 (1-100 micrograms/kg) reduced the AA-induced effect in both control and STZ-diabetic mice. STA2 (10 micrograms/kg) enhanced the AA-induced effect in both control and STZ-diabetic mice. ONO-1078 (1-10 mg/kg) did not affect the AA-induced effect in both control and STZ-diabetic mice. TMK-688 (0.01-1 mg/kg) reduced the AA-induced effect in the control mice, but not in the STZ-diabetic mice. These results suggest an involvement of leukotriene in the respiratory response to AA in diabetic mice, especially when cyclooxygenase and TXA2 synthetase are inhibited.

Animals↗

L-NG-nitro-arginine inhibits nicotine-induced relaxation of isolated rat duodenum.

We studied the effects of L-NG-nitro-arginine (L-NOARG), which inhibits nitric oxide (NO) biosynthesis from L-arginine, on the non-adrenergic, non-cholinergic (NANC)-mediated relaxation induced by nicotine in isolated rat duodenum. L-NOARG reduced nicotine-induced relaxation, and L-arginine prevented the inhibitory effect of L-NOARG. However, L-NOARG did not inhibit the tetrodotoxin-insensitive relaxation induced by adenosine 5'-triphosphate, alpha, beta-methyleneadenosine 5'-triphosphate, thyrotropin-releasing hormone or the calcitonin gene-related peptide. Endogenous NO thus could possibly be involved in the NANC-mediated relaxation of rat duodenum induced by nicotine.

Adenine Nucleotides↗