Biomedical subjects

T Usui

Publications and source records attributed to T Usui.

At least 253 records · Page 14Linked to original sources

PubMed1994

Metastatic renal cell carcinoma arising in a native kidney of a renal transplant recipient.

We report a case of metastatic renal cell carcinoma arising in the native kidney of a renal transplant recipient. A 39-year-old man, who had undergone living renal transplantation from his mother at age 32, presented with complaints of paraplegia of the leg caused by a pathological fracture of the 3rd lumbar vertebra. The bone tumor was extirpated and pathological examination revealed metastatic adenocarcinoma. Abdominal computerized tomography showed a tumor in the right native kidney. Right nephrectomy and resection of the right 7th rib tumor were performed. Pathological evaluation demonstrated renal cell carcinoma of the right native kidney (pT2bpN0pV0M1, mixed cell type, grade 2). Postoperatively, cyclosporine was discontinued and natural interferon-alpha was given. The remaining bone metastasis had completely resolved with no significant sign of rejection 1 year after surgery.

Adult↗

PubMed1994

Functional analysis of the cell-specific enhancer in the human proopiomelanocortin gene by beta-galactosidase histochemical staining.

Nucleotide sequences responsible for the cell-specific expression of the human proopiomelanocortin (POMC) gene were analyzed by histochemical staining of beta-galactosidase in culture cells transfected with chimeric genes containing the 5'-flanking regions of the human POMC gene fused to the Escherichia coli lacZ gene. The chimeric genes were stably introduced into various culture cells, including AtT-20 cells, which express the endogenous mouse POMC gene. Whereas the control gene containing the cytomegalovirus enhancer was expressed in all cell lines tested, only AtT-20 cells supported the efficient transcription of the gene containing 2.9 kb of the human POMC 5'-flanking region. These results indicate that the stable transfection-expression system utilizing the histochemical detection of the gene expression is a useful method for the analysis of cell-specific gene expression. These results have also confirmed that the trans-acting factors in mouse AtT-20 cells interact with the human POMC gene promoter region and activate the transcription of the gene. Deletion analysis has demonstrated that the profiles of the transcriptional activity of the various human POMC-lacZ fusion genes are similar to those of the rat POMC gene described previously. Comparison of the human and the rat 5'-flanking sequences revealed close homology in several regions, which might be involved in the efficient transcription of the POMC gene in AtT-20 cells.

Animals↗

PubMed1994

In-vitro and in-vivo activity of a new quinolone AM-1155 against Mycoplasma pneumoniae.

We investigated the in-vitro and in-vivo activity of a new quinolone AM-1155 against Mycoplasma pneumoniae, and compared it with ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin, erythromycin and minocycline. AM-1155 was the most potent agent in vitro of the quinolones tested. Its pre-treatment minimal inhibitory concentrations for 90% of the 41 strains (MIC90) was 0.06 mg/L. In contrast, pre-treatment MIC90 values for ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin, erythromycin, and minocycline were 1, 1, 2, 0.5, 0.0156, and 0.5 mg/L, respectively. Post-treatments MIC90s, which may reflect mycoplasmacidal potency, of AM-1155, ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin, erythromycin and minocycline were 0.125, 1, 2, 4, 0.5, 0.125 and 4 mg/L, respectively. In-vitro activities of antimicrobial agents were assessed in an experimental pulmonary infection model in Syrian golden hamsters. AM-1155 was the most effective agent among five antimicrobial agents (AM-1155, ofloxacin, tosufloxacin, erythromycin, minocycline) tested in terms of reduction in viable M. pneumoniae cells and in reducing macroscopic lung lesions. These results suggest that AM-1155 will be a useful antimicrobial agent for the treatment of M. pneumoniae infections.

Animals↗

PubMed1994

A case of testicular teratoma located in the opposite side of the upper abdominal wall.

We report a case of a testicular teratoma located in the opposite side of the upper abdominal wall. A 2-year-old boy presented with a non-palpable right testis and underwent right inguinal exploration for right cryptorchidism. During surgery, the tumor was found in the opposite side of the upper abdominal wall across the midline. Histological investigation of the tumor revealed a mature teratoma occurring in the intra-abdominal testis. No such case has been previously reported.

Child, Preschool↗

PubMed1994

M-VEC (methotrexate, vinblastine, 4'-epirubicin and cisplatin) combined with glycosylated recombinant human granulocyte colony-stimulating factor (rhG-CSF) for the treatment of transitional cell carcinoma of urothelium: reduction in toxicity produced by rhG-CSF.

Forty-six patients with urothelial cancer were treated with a systemic chemotherapeutic regimen consisting of methotrexate, vinblastine, 4'-epirubicin and cisplatin (M-VEC) in conjunction with glycosylated recombinant human granulocyte colony stimulating factor (rhG-CSF); then 33 were evaluated for response. Complete response was observed in 7 patients (21%) and partial response in 13 (39%). As far as the toxic effects of this treatment are concerned, mucositis of a minimum grade and leukopenia greater than grade 3 occurred in 5% and 10% of the patients, respectively; there were no cases of nadir sepsis and drug-related death. Minor toxicity such as nausea vomiting occurred in 81% of patients, and no patient required either dose-reduction or a delay of more than 5 d before starting of the second cycle. Thus, it may be concluded that M-VEC chemotherapy combined with rhG-CSF is useful in the treatment of urothelial cancer, especially when used as a neoadjuvant.

Adult↗

PubMed1994

Association between patient characteristics and treatment history, and toxicity associated with methotrexate, vinblastine, adriamycin and cisplatin (M-VAC) for advanced urothelial cancer.

OBJECTIVE: To determine whether patient characteristics and treatment history are associated with an increased risk of adverse side-effects resulting from combination chemotherapy. PATIENTS AND METHODS: A study was made on 71 patients with advanced urothelial cancer who underwent combination chemotherapy consisting of methotrexate, vinblastine, adriamycin, and cisplatin (M-VAC). Both the laboratory data and the toxic symptoms were evaluated from cycle 1 to cycle 3. RESULTS: A total of 168 cycles of treatment were performed. The mean value of the nadirs of the white blood cell counts showed a significantly lower level in cycle 1 than cycle 2 (P < 0.05). There were three deaths due to disseminated intravascular coagulation or sepsis resulting from severe myelosuppression. Factors related to the occurrence of myelosuppression were gender (female), poor performance status and previous treatment by radiotherapy. CONCLUSION: Special consideration should be given to the patient's background prior to application of this regimen.

Adult↗

PubMed1994

Critical PQ interval for the appearance of diastolic mitral regurgitation and optimal PQ interval in patients implanted with DDD pacemakers.

Diastolic mitral regurgitation (MR) may be induced by prolonging atrioventricular (AV) delay, and a significant negative correlation has been described between the critical PQ interval for the appearance of diastolic MR and pulmonary capillary wedge pressure (PCWP) in patients with DDD pacemakers. We report the relationship between the critical PQ interval for the appearance of diastolic MR and the optimal PQ interval in 11 patients (69.1 +/- 12.6 years). Cardiac output (CO) and PCWP were measured by Swan-Ganz catheter and transmitral blood flow was recorded by pulsed-Doppler echocardiography. AV delay was prolonged stepwise by 0.025 seconds starting from 0.065 seconds. The pacing rate was fixed at 70 beats/min. CO was highest when the PQ interval was 0.18 +/- 0.04 seconds. There was a significant positive correlation between the critical PQ interval for the appearance of diastolic MR and the PQ interval at which CO was the highest (r = 0.91, P < 0.01). The PQ interval at which CO was the highest was 0.02 +/- 0.02 seconds shorter than the critical PQ interval for the appearance of diastolic MR (P < 0.05). When the PQ interval was increased by 0.025 seconds from the critical PQ interval for the appearance of diastolic MR, CO decreased from 4.3 +/- 0.6 L/min to 4.1 +/- 0.6 L/min and PCWP increased from 7.5 +/- 6.4 mmHg to 8.5 +/- 7.3 mmHg (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Pharmacokinetics and cardiovascular effects of YM-21095, a novel renin inhibitor, in dogs and monkeys.

The pharmacokinetics and cardiovascular effects of YM-21095 ((2RS), (3S)-3-[N alpha-[1,4-dioxo-4-morpholino-2-(1-naphthylmethyl)- butyl]-L-histidylamino]-4-cyclohexyl-1-[(1-methyl-5-tetrazolyl)thi o]-2-butanol), a potent renin inhibitor, have been studied in beagle dogs and squirrel monkeys. Plasma levels of YM-21095 after 3 mg kg-1 intravenous dosing to dogs declined biphasically and fitted a two-compartment model. Kinetics were as follows: t1/2 alpha = 4.9 +/- 0.2 min, t1/2 beta = 2.76 +/- 0.79 h, Vdss = 3.86 +/- 1.04 L kg-1, plasma clearance = 2.22 +/- 0.39 L kg-1, and AUC = 1445 +/- 266 ng h mL-1. After 30 mg kg-1 oral dose, maximum plasma concentration, tmax and AUC of YM-21095 were 28.8 +/- 9.6 ng mL-1, 0.25 h and 23.6 +/- 7.7 ng h mL-1, respectively. Systemic bioavailability as determined on the basis of the ratio of AUC after intravenous and oral dose was 0.16 +/- 0.04%. In conscious, sodium-depleted monkeys, YM-21095 at an oral dose of 30 mg kg-1 lowered systolic blood pressure and inhibited plasma renin activity without affecting heart rate and plasma aldosterone concentration. Maximum plasma concentration of YM-21095 after 30 mg kg-1 oral dose to monkeys was 71.8 +/- 41.5 ng mL-1, which was reached 0.5 h after the dose. At equihypotensive doses, captopril and nicardipine increased plasma renin activity markedly and slightly, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

PubMed1994

In vitro and in vivo activities of sparfloxacin against Mycoplasma pneumoniae.

The in vitro and in vivo activities of sparfloxacin against Mycoplasma pneumoniae were compared with those of erythromycin, levofloxacin, ofloxacin, and minocycline. The MICs of sparfloxacin, erythromycin, levofloxacin, ofloxacin, and minocycline for 90% of the 43 M. pneumoniae strains tested were 0.063, 0.016, 0.5, 1, and 0.5 microgram/ml, respectively. In the experimental pulmonary M. pneumoniae infection model in Syrian golden hamsters, sparfloxacin was as effective as erythromycin when orally administered at 15 mg/kg twice daily for 5 days and more effective than erythromycin when orally administered at 10 mg/kg once daily for 5 days. Sparfloxacin was more effective than levofloxacin and ofloxacin in both dosing regimens. The peak concentrations of sparfloxacin in hamster sera after administration of single oral doses of 15 mg/kg were almost the same as those in human sera after administration of single oral doses of 200 mg (the usual clinical dose), and the half-life of sparfloxacin in hamster serum was shorter than that in human serum after administration of a single oral dose of 200 mg. These results suggest that sparfloxacin may be clinically useful for the treatment of M. pneumoniae infections.

Animals↗

PubMed1994

In vitro and in vivo activities of macrolides against Mycoplasma pneumoniae.

We investigated the in vitro and in vivo activities of macrolides against Mycoplasma pneumoniae. In vitro MICs of azithromycin, erythromycin, clarithromycin, and roxithromycin were determined. Azithromycin was the most potent antimicrobial agent tested in vitro. Its MIC for 90% of the strains was 0.00024 micrograms/ml. MICs for 90% of the strains of erythromycin, clarithromycin, and roxithromycin were 0.0156, 0.0078, and 0.03125 micrograms/ml, respectively. In vivo activities were assessed in a pulmonary infection model with Syrian golden hamsters. We evaluated the in vivo effects on reduction of viable M. pneumoniae cell counts and on reduction of microscopic and macroscopic histopathologies for azithromycin, erythromycin, and clarithromycin given at 10 mg/kg once daily for 1 and 3 days and given at 15 mg/kg twice daily for 2.5 and 5 days. Azithromycin was significantly more effective than erythromycin or clarithromycin in the same regimens. Especially at 10 mg/kg once daily for 1 day, only azithromycin was significantly effective in the reduction of viable M. pneumoniae cells and histopathologies. These results show that azithromycin is more efficacious than the other drugs tested against M. pneumoniae pneumonia in hamsters. These data suggest that clinical studies of macrolides in human patients are warranted.

Animals↗

PubMed1994

Study of estramustine binding protein: its relationship to androgen dependency and histological differentiation in human prostatic carcinoma tissue.

For the purpose of elucidating the clinical significance of estramustine binding protein (EMBP), EMBP concentration in human prostatic carcinoma (PC) tissue was measured by radioimmunoassay (RIA) using an antibody raised against rat EMBP and was compared with dihydrotestosterone (DHT) level and histological differentiation in the same tissue. The mean concentrations of EMBP in 20 untreated and 6 hormonally refractory PC were 112.6 +/- 120.7 and 218.0 +/- 102.3 ng/g tissue, respectively. In the 20 untreated PC, the EMBP concentration was not significantly different between the high and low tissue DHT groups. On the other hand, the EMBP concentration was significantly higher in moderately and poorly differentiated PCs as compared with well-differentiated PC, whereas the DHT level was highest in well-differentiated and lowest in poorly differentiated PC. Furthermore, in the 6 hormonally refractory PC, the EMBP concentration was higher in spite of a lower tissue DHT level in comparison with untreated PC. These results suggest that the EMBP concentration does not reflect androgen status in PC tissue but might reflect the malignant potential of the tumor.

Aged↗

PubMed1994

Molecular cloning of human prostacyclin receptor cDNA and its gene expression in the cardiovascular system.

BACKGROUND: Prostacyclin elicits a potent vasodilation and inhibition of platelet aggregation through binding to its membrane receptor. The impairment of prostacyclin receptor activity is implicated in various human cardiovascular diseases. In the present study, we succeeded in the isolation and characterization of human prostacyclin receptor cDNA and elucidated its gene expression in human tissues. METHODS AND RESULTS: We isolated a cDNA clone encoding the human prostacyclin receptor from a human lung cDNA library. The isolated cDNA clone encodes a 386-amino acid protein with seven putative transmembrane domains, which belongs to the G protein-coupled receptor superfamily. [3H]iloprost, a prostacyclin receptor agonist, specifically bound to the receptor transiently expressed in COS-7 cells. The binding was inhibited in the rank order of iloprost = cicaprost, another prostacyclin receptor agonist, > prostaglandin E1 (PGE1) >> PGE2, PGF2 alpha, PGD2, STA2. In addition, iloprost dose-dependently stimulated cAMP generation in these COS-7 cells. These results are consistent with the characteristics of the human prostacyclin receptor. Northern blotting analysis on human tissues revealed that prostacyclin receptor mRNA is abundantly expressed in the aorta, lung, atrium, ventricle, and kidney. CONCLUSIONS: We cloned human prostacyclin receptor cDNA and elucidated its abundant gene expression in the human cardiovascular system. The present study will lead to better understanding of the significance of prostacyclin in humans and further facilitate the clinical application of prostacyclin.

Amino Acid Sequence↗

PubMed1994

Synthesis and aldose reductase inhibitory activity of 2-substituted 6-fluoro-2,3-dihydrospiro[4H-1-benzopyran-4,4'-imidazolidine]-2',5'-dio nes.

Optically active and racemic 2-substituted 6-fluoro-2,3-dihydrospiro[4H-1- benzopyran-4,4'-imidazolidine]-2',5'-diones were synthesized stereoselectively from (+)-, (-)-, and (+/-)-6-fluoro-3, 4-dihydro-4-oxo-2H-1-benzopyran-2-carboxylic acid [(+)-1, (-)-1, and (+/-)-1], respectively, for evaluation as new aldose reductase inhibitors. Among these compounds, the 2S,4S compounds were found to be more potent inhibitors of aldose reductase in vitro and in vivo than the corresponding 2R,4R enantiomers. The chloromethyl compound [(+)-5] showed highly potent activities in inhibiting cataract formation in the lenses and polyol accumulation in the sciatic nerve of rats.

Aldehyde Reductase↗

PubMed1994

The true nature of the adductor brevis dually innervated by the anterior and posterior branches of the obturator nerve in humans.

To clarify the true nature and the mechanism of the human adductor brevis (specific adductor brevis, SAB) innervated dually by the anterior and posterior branches of the obturator nerve, we have carried out gross anatomical examination of 100 body halves of 50 adult Japanese cadavers. The SAB was found in 23 of the 100 thighs (23.0%), and its anterior and posterior surfaces received respectively the twigs from the anterior branch of the obturator nerve and the filament(s) from the posterior branch. The filament(s) was either indirectly derived from the medial stratum of the posterior branch through the formation of a common trunk with the twigs distributed in the obturator externus (14/23 thighs, 60.9%) or directly originating in the medial stratum of the posterior branch of the obturator nerve (9/23 thighs, 39.1%). In the close examination of the intramuscular distribution of the nerve to the SAB, the region innervated by the anterior branch of the obturator nerve could clearly be distinguished from that innervated by the posterior branch. The obturator nerve received fibers from L1234 (2/23 thighs) or from L234 (21/23 thighs), and the posterior branch of the obturator nerve ran through the obturator externus (18/23 thighs, 78.3%) or ran over the obturator externus (5/23 thighs, 21.7%), and finally emerged into the thigh. In view of the mode of origin of the filament(s), the structural element of the filament(s), and the pattern of entry of the filament(s) into the SAB, the fasciculus of the SAB, which is innervated by the posterior branch of the obturator nerve, was considered to originate in the obturator externus. Thus, the true nature of the SAB was concluded to be a complex product which was formed by a mechanism in which the fasciculus, which had separated from the obturator externus during the process of ontogeny, fused secondarily to the posterior surface of the regular adductor brevis. From findings in our series of studies, it was estimated that the maximum frequency of occurrence of the SAB could be 56%. Furthermore, from a statistical point of view, the segmental composition or course of the obturator nerve is not considered to be related to either the formation or the incidence of this muscle.

Humans↗

PubMed1994

Disposition and metabolism of a novel diurea inhibitor of acyl CoA: cholesterol acyltransferase (YM17E) in the rat and dog.

1. We have investigated the disposition and metabolism of YM17E after intravenous and oral administration in the rat and dog. 2. Bioavailability of YM17E was 5-9% at oral doses of 3-30 mg/kg in rat, and 9 and 13% at oral doses of 10 and 30 mg/kg in dog. 3. Five N-demethylated metabolites, which have significant pharmacological activity, were found in rat and dog plasma after oral administration. Plasma concentrations of each of these metabolites were comparable with that of unchanged drug. 4. When 14C-YM17E was administered to rat, AUC of unchanged drug was 7% of that of radioactivity. However, AUC of the combined concentration of unchanged drug and five active metabolites was about 50% of that of radioactivity, indicating that the pharmacological activity of the agent was maintained in spite of its biotransformation. 5. After oral administration of 14C-YM17E at a dose of 10 mg/kg to rat, radioactivity was distributed widely to almost all tissues except the brain. The concentration of radioactivity in the liver, one of the target organs, was 65 times higher than that in plasma at 1 h after administration. 6. A significant amount of radioactivity in the liver was located in the microsomal subfraction, which contains much acyl CoA:cholesterol acyl transferase activity. More than 50% of this microsomal radioactivity was derived from unchanged YM17E and five active metabolites. 7. From excretion data in the bile duct-cannulated rat, the absorption ratio of YM17E from the gastrointestinal tract in this species was estimated to be at least 40%, suggesting that the low bioavailability of the drug is due to extensive first-pass metabolism. 8. Some 95% of the administered radioactivity was excreted in the faeces of rat following iv or po doses of 14C-YM17E.

Animals↗

PubMed1994

[Surgical treatment of renal cell carcinoma with extension into the vena cava].

Between 1985 and 1992, 9 patients (6 men and 3 women), 50-76 years old (mean age 63.6), underwent radical nephrectomy and removal of the tumor thrombus for the treatment of renal cell carcinoma extending into the vena cava at the Department of Urology, Hiroshima University Hospital. Seven tumors were located in the right kidney and two in the left kidney. Three tumor thrombi extended into the vena cava within 2 cm (level 1 according to the Novick's classification), 2 extended into the infrahepatic vena cava (level 2), 2 extended into the suprahepatic vena cava (level 3), and other 2 extended into the right atrium (level 4). Two patients had distant metastases preoperatively. The tumor thrombi at the level 1 were removed by venacavotomy with a short duration of surgery and a small amount of blood loss, while in those at the level of 2 or 3, both the duration of surgery and the amount of blood loss increased because the mobilization of the liver needed to remove the thrombi. For removing tumor thrombi at the level 4, cardiopulmonary bypass and deep hypothermic circulatory arrest were applied, resulting in longer duration of surgery but less amounts of blood loss than those at the level 2 or 3. Postoperatively, 2 patients had a renal insufficiency and another 2 had a liver dysfunction. One operative death occurred in this series because of pulmonary embolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Synthesis of 2''-amino-2''-deoxyarbekacin and its analogs having potent activity against methicillin-resistant Staphylococcus aureus.

Based on our studies on the enzymatic modifications of arbekacin by methicillin-resistant Staphylococcus aureus (MRSA), replacement of the 2''-hydroxyl group by an amino group in arbekacin was designed to synthesize derivatives that would be active against MRSA. 2''-Amino-2''-deoxyarbekacin and five analogs were synthesized starting from dibekacin. Among them, 2''-amino-2''-deoxyarbekacin and the 5-epiamino analog showed excellent antibacterial activities against not only MRSA but also Gram-negative bacteria including Pseudomonas, and lower toxicities than arbekacin.

Carbohydrate Sequence↗

PubMed1994

[Parameters for estimating abnormal reticulocyte specimens from blood cell counts].

In order to estimate reticulocyte levels, low, normal or high, parameters for discrimination are calculated using hematology count data. Multivariate discriminant functions were used for detecting abnormal reticulocyte specimens for computerized laboratories. The method detects 60.2%, 60.3% and 15.7% of low, high and normal reticulocyte specimens respectively. Discrimination method with individual test data are used for uncomputerized laboratories. The tests used for detecting abnormal reticulocyte specimens are white blood cells, red blood cells, mean cell hemoglobin concentration and red blood cell distribution width. Detection efficiencies for low, high and normal reticulocyte specimens are 55.9%, 50.4% and 14.7%.

Blood Cell Count↗