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Biomedical subjects

H Kato

Publications and source records attributed to H Kato.

At least 577 records · Page 32Linked to original sources

Cytotoxicity and pharmacokinetics of 1-beta-D-arabinofuranosyl-2-thiocytosine, a 2-sulphur substituted derivative of cytarabine.

1-(beta-D-Arabinofuranosyl)-2-thiocytosine (araSC), a 2-substituted derivative of cytarabine (araC), has been investigated for its cytotoxicity, enzymatic stability, plasma concentration-time profile in mice, and cytokinetics. This derivative showed strong cytotoxicity in several mammalian cell lines, although activity (IC50s) was weaker than araC. Greater stability to mouse cytidine deaminase was observed; the half-life in the presence of the enzyme was about 4-times longer than that of araC. The plasma concentration-time profile in mice in vivo showed prolonged retention of araSC when compared with araC. Cytokinetic study using flow cytometry indicated a non-S-phase specific effect of this compound.

Animals↗

A rabbit model for evaluation of chlorpromazine-induced orthostatic hypotension.

The present study was conducted to develop an experimental model for evaluation of chlorpromazine-induced orthostatic hypotension in rabbits. In addition, the alpha-adrenoceptor blocking effect of chlorpromazine was investigated in isolated rabbit aorta and saphenous vein in comparison with prazosin. Chlorpromazine (0.1 and 1 mg/kg, i.v.) potentiated significantly a decrease in mean blood pressure at 1 min after the onset of head-up tilt in rabbits anesthetized with urethane alone, urethane+alpha-chloralose or nitrous oxide alone, but not in conscious and morphine+urethane+alpha-chloralose-anesthetized rabbits. There was a negative correlation (r=-0.986, p<0.01) between the extent of chlorpromazine-induced orthostatic hypotension and the amplitude of tilt-induced reflex tachycardia before chlorpromazine treatment. Both prazosin and pentolinium elicited orthostatic hypotension under all four anesthetic conditions. The pA2 value for chlorpromazine to antagonize norepinephrine-induced contraction in aorta was significantly larger than that in saphenous vein, whereas prazosin blocked aortic and venous contractions to a similar extent. These results suggest that a rabbit under an anesthesia which impairs tilt-induced reflex tachycardia may be useful for evaluation of orthostatic hypotension by chlorpromazine. The relatively low potential of chlorpromazine to produce orthostatic hypotension may be partly due to its weak venodilating action.

Adrenergic alpha-Antagonists↗

Coil occlusion of aortopulmonary collateral arteries in an infant with scimitar syndrome.

Scimitar syndrome in infancy is a rare condition, presenting with severe congestive heart failure and pulmonary hypertension. The presence of large systemic-pulmonary collateral arteries may play a role in the cause of heart failure and pulmonary hypertension. A 4-month-old infant underwent coil occlusion of large anomalous systemic arteries supplying the right lower pulmonary lobe. Symptoms of severe congestive heart failure and pulmonary hypertension improved dramatically with coil occlusion, and surgical correction was performed 3 months later without any complications. Coil occlusion of anomalous systemic arteries can improve symptoms of heart failure and pulmonary hypertension in infants and may bring about a good surgical result for this disease.

Collateral Circulation↗

The effect of tulobuterol tape on histamine-induced bronchoconstriction in conscious guinea pigs: long duration of action.

The objective of the present study was to determine the action duration of tulobuterol tape within a 24-hr period in conscious guinea pigs. The bronchoconstriction induced by histamine-inhalation was significantly inhibited by tulobuterol tape in comparison with its placebo tape 8 and 12 hr after binding, and the inhibitory rate was 50+/-11% and 35+/-13%, respectively. Twenty-four hours after binding, the inhibitory effect of tulobuterol tape gradually diminished, but the inhibitory rate was maintained at 30+/-14%. These results suggest that tulobuterol tape has a long lasting bronchodilatory action.

Administration, Cutaneous↗

Repeated 131I treatment of a residual ovarian teratoma containing malignant thyroid tissue.

A 49-year-old woman with ovarian teratoma received 131I treatment three times for an unresectable mass containing malignant thyroid tissue after surgery. Repeated 131I treatment effectively reduced serum thyroglobulin (Tg) level and tumour uptake of 131I, despite absence of any change in size of the treated tumour. Treatment did not inhibit the increase of serum CA-125 and tumour 201Tl uptake, associated with progression of a radioresistant intratumoral hyper-perfused tissue component, detected by colour Doppler ultrasound. Serum CA-125 level and tumour 201Tl uptake were not significantly changed despite temporary increases in serum Tg level after each 131I treatment. These observations indicate the importance of diagnostic measures using combined functional imaging and tumour markers in managing this rare tumour.

Biomarkers, Tumor↗

Changes in interleukin-1beta mRNA expression in the rat ovary during the estrous cycle in response to lipopolysaccharide.

The changes in interleukin-1 (IL-1) beta mRNA expression and the number of macrophages were studied in the ovary during the estrous cycle in rats and after intraperitoneal injection of lipopolysaccharide (LPS, 2 mg/body) 2 hours before autopsy. IL-1beta mRNA expression was very low in the ovary, and there was no statistically significant change during the estrous cycle. Hybridization signals of IL-1beta mRNA were localized intensely in the thecal layer, moderately in the corpora lutea, and slightly in granulosa cells of the ovary during the cycle. The number of macrophages seen mainly in the hilum and interstitium significantly increased on proestrus compared with other estrous days. LPS significantly increased IL-1beta mRNA expression on each day with the highest response to LPS at 1500 h on proestrus, and caused an increase in the number of macrophages in the ovary within 2 hours. These results indicate that IL-1beta mRNA expressions are low during the estrous cycle in rats, and proestrus is the day of maximal IL-1beta synthesis in response to LPS. The increase in IL-1beta synthesis caused by LPS might be due to at least the influx of macrophages into the ovary.

Animals↗

Changes in nitric oxide synthase activity in the ovary of gonadotropin treated rats: the role of nitric oxide during ovulation.

Immature rats receiving equine chorionic gonadotropin (eCG) and human CG (hCG) were used to study the time course changes in nitric oxide synthase (NOS) activity in the ovary during ovulation. To study the role of NO in ovulation, the effects of intrabursal injection of L-N(G)-monomethylarginine (L-NMMA, 125 microg/20 microl/bursa), a NOS inhibitor, on the number of ova shed were also examined. Rats were sacrificed at -48, 0, 3, 6, 9, 12, and 24 h after hCG injection, and the ovaries were collected for the NOS activity assay, Western blotting, NADPH-diaphorase histochemistry and immunohistochemistry. Total NOS and constitutive NOS activities in the ovary increased significantly at 9 h after hCG injection and the values remained high thereafter. Inducible NOS (iNOS) activity was detectable as a small peak at 3 and 6 h after hCG injection. Endothelial NOS (eNOS) protein production increased after hCG injection with a peak at 12 h, whereas iNOS protein production decreased at 12 and 24 h after hCG injection. NADPH-diaphorase positive cells increased at the thecae of growing follicles after hCG injection, appeared at mural granulosa cells before ovulation, and were detected in newly formed corpora lutea, which coincided with the results in eNOS positive cells by immunohistochemistry. L-NMMA given to rats at 5 or 7 h after hCG was most effective in reducing the number of ova shed. These results indicate that the NOS activity and NOS positive cells increased after hCG injection, and that eNOS was likely the main NOS increasing in the ovary during ovulation. It is concluded that NO produced between 5 and 9 h after hCG might play a supportive role in ovulation.

Animals↗

Therapeutic efficacy of transcranial magnetic stimulation for hereditary spinocerebellar degeneration.

We applied transcranial magnetic stimulation (TMS) as a therapeutic approach for patients with spinocerebellar degeneration (SCD). The subjects were four familial SCD patients (three men and one woman) aged from 27 to 76 years old. They were genetically analysed as two spinocerebellar ataxia type 6 (SCA 6), one SCA 1, and one SCA 7. The durations of their illness ranged from 1 to 7 years. Ten consecutive magnetic pulses were delivered over the scalp corresponding to the right cerebellar hemisphere, the middle of the cerebellum and the left cerebellar hemisphere, respectively, every day for 21 days. In all patients, the time and the number of steps required for a 10 m walk examination were significantly decreased after TMS trial compared with those before TMS. The number of feasible steps in tandem gait test increased. The total length of tracing body balance for 30 seconds measured by gravinometer was significantly decreased. However, nystagmus, dysarthria or incoordination of the upper limbs did not change after TMS trial. It is of interest that the blood flow of the cerebellar hemisphere, putamen and pons were significantly increased during the TMS trial. Although we do not know the exact mechanism by which TMS improved the ataxic gait, we speculate the increase of blood flow in the cerebellum, putamen and pons takes part in the improvement. These findings suggest that TMS over the cerebellum may be an effective therapy for patients with SCD.

Adult↗

A quantitative comparison of induction and challenge concentrations inducing a 50% positive response in three skin sensitization tests; the guinea pig maximization test, adjuvant and patch test and Buehler test.

The sensitivities of three skin sensitization tests such as the Guinea pig maximization test (GPMT), Adjuvant and patch test (APT) and Buehler test (BT), were quantitatively compared with reference to induction and challenge concentrations. Four chemical which had different physico-chemical properties (octanol-water partition coefficient (logP) and reactivity with NH2-group) were used in order to clarify the effect of the physico-chemical properties of chemicals on the sensitivity of the different methods. The induction concentrations inducing a 50% positive response (IC50) demonstrated extreme variation with the three methods. For example, the BT/GPMT ratio of IC50 values for 2,4-dinitrochlorobenzene was 33, whereas that for maleic anhydride was 300,000. The results were thought to be caused by difference properties such as the logP and reactivity of chemicals. This correlation was confirmed by using 2-dodecen-1-yl succinic anhydride, which had the same reactivity but higher logP than that of maleic anhydride. On the other hand, the challenge concentrations inducing 50% positive responses (CC50) were less affected by the methods and the BT/GPMT ratios for CC50 values were all within a 10-fold range. These results suggest that the sensitivity might be strongly different with reference to induction concentration, but not challenge concentration among the three methods.

Adjuvants, Immunologic↗

Effects of indomethacin and hyperventilation on cerebral hemodynamics and oxygenation in newborn piglets.

We investigated the effect of indomethacin (INDO) and hyperventilation (HV) on cerebral hemodynamics and oxygenation in newborn piglets using near-infrared spectroscopy (NIRS). A total of 10 piglets aged 7-10 days were divided into 2 groups. INDO (Experimental group; 0.2 mg/kg i.v.) or saline (Control group) was administered after steady state, then each group was hyperventilated (pCO2; 20 mm Hg). Cerebral oxyhemoglobin concentrations (HbO2) significantly decreased immediately after INDO administration compared to controls (p < 0.01). This decrease continued for 15 min. During HV, HbO2 remained low compared to the steady state (p < 0.05) in the experimental group. Total hemoglobin concentrations (HbT) decreased simultaneously with HbO2. In the control group, no changes in HbO2 or HbT were observed after saline administration, and only a slight decrease in HbO2 was observed during the 5 minutes' HV compared to the steady state. No changes in cytochrome aa3 (Cytaa3) were observed in either group during 100% O2 inhalation. We conclude that INDO decreased HbO2 and HbT by vasoconstriction, but that HV did not further aggravate this tendency. Great care should be taken when using INDO for newborn neonates.

Animals↗

Aspergillus osteomyelitis in a child who has p67-phox-deficient chronic granulomatous disease.

Here we describe Aspergillus osteomyelitis of the tibia in a 9-year-old boy who has an autosomal recessive form of chronic granulomatous disease (CGD). The patient showed a p67-phagocyte oxidase (phox) deficiency, which is rare type of CGD in Japan. The initial treatment which consisted of surgical debridement and antibiotic therapy with amphotericin B (AMPH), did not control the infection. Aspergillus fumigatus (A. fumigatus) pure isolated from drainage fluid and necrotic bone tissue demonstrated less susceptible to antifungal agents, including AMPH, fluconazole and flucytosine. Recombinant interferon gamma was then administrated, and it was effective in controlling the course of severe invasive aspergillosis. This report indicates the use of interferon gamma might be helpful in control for Aspergillus osteomyelitis of the tibia in a child with CGD demonstrated p67-phox deficiency refractory to conventional therapy with AMPH.

Amphotericin B↗

Mutation and transcription analyses of the p63 gene in cervical carcinoma.

Genetic mutation of p53, which monitors DNA damage and operates cellular checkpoints, is a major factor in the development of human malignancies. A novel gene p63/p73L/p51, encoding a protein with significant homology to p53 and p73, was recently identified at 3q27-9. To investigate the penetration of p63 in cervical carcinogenesis, mutation and transcription analyses of p63 were performed in cervical carcinoma. A certain isotype of p63 called TAp63gamma encodes the acidic N-terminus and possesses a short C-terminus. Using reverse transcriptase-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) analysis for TAp63gamma, one mutation was found in the cervical carcinoma cell line SKG-I. However, no mutations causing amino acid substitutions or frameshifts were found in 54 cases examined for TAp63gamma, which is thought to be a tumor suppressor gene. While cervical carcinomas tended to yield a positive signal in the RT-PCR reaction designed to amplify transcripts encoding the acidic N-terminus, normal cervix and cervical intraepithelial neoplasia (CIN) did not express this transcript. These data suggest that the p63 gene does not play an essential role as a tumor suppressor gene, but expression of TAp63gamma may be speculatively associated with tumor growth in cervical carcinogenesis.

Adenocarcinoma↗

[Endothelial-derived nitric oxide mediates the peripheral vasodilatory effects of amrinone in humans].

Amrinone, which is used for the treatment of acute congestive heart failure, has vasodilatory and positive inotropic effects through the increment of intracellular cyclic adenosine monophosphate. Recent in vitro investigations have shown that amrinone has an endothelium-dependent vasodilatory effect. The present study examined whether amrinone shows this endothelium-dependent vasodilatory effect in human peripheral vessels. Forearm blood flow during intra-arterial infusion of graded doses (12.5, 25, 50, 100, 200 micrograms/min) of amrinone was measured using plethysmography in 10 healthy subjects without organic vascular disease before and after nitric oxide synthase blocking with NG-monomethyl-L-arginine (L-NMMA, 400 mumol). The graded dose of amrinone produced progressive increases in amrinone plasma concentrations, and a dose over 100 micrograms/min caused amrinone plasma concentrations of more than 1.0 microgram/ml. The increase in forearm blood flow in response to amrinone was significantly depressed after L-NMMA doses of less than 100 micrograms/min, but the increase in forearm blood flow during infusion of higher doses (100, 200 micrograms/min) was not affected by L-NMMA. These results suggest that endothelial-derived nitric oxide may partially contribute to amrinone-induced vasodilation in humans. Thus, the vasodilatory effect of amrinone might be impaired in patients with endothelial dysfunction.

Adult↗

Assisted reproduction technology for patients with congenital bilateral absence of vas deferens.

PURPOSE: We investigate the frequency of cystic fibrosis transmembrane conductance regulator gene mutations in Japanese patients with congenital bilateral absence of the vas deferens, and assess treatment outcomes of assisted reproduction interventions. MATERIALS AND METHODS: In 10 Japanese patients with bilateral congenital absence of the vas deferens genetic analysis was performed for known frequent mutations of the cystic fibrosis transmembrane conductance regulator gene using polymerase chain reaction amplification followed by dot-blot hybridization with the allele-specific oligonucleotide probes and direct sequencing. Intracytoplasmic sperm injection using spermatozoa retrieved from the testes was performed in 7 of the couples. RESULTS: No known mutations of the gene were detected in the patients. However, analysis of the polythymidine tract polymorphism in intron 8 revealed 30% allele frequency of 5T. Pregnancy was achieved in 7 cycles of intracytoplasmic sperm injection using spermatozoa retrieved from the testes. CONCLUSION: The 5T variant in intron 8 polythymidine tract was identified with high allelic frequency in Japanese patients with congenital bilateral absence of the vas deferens, suggesting that the disease in Japan is also partially caused by this particular mutation of the cystic fibrosis transmembrane conductance regulator gene. Modern assisted reproduction technology offers an important option for patients with congenital bilateral absence of the vas deferens.

Adult↗

Carrier-mediated lung distribution of HSR-903, a new quinolone antibacterial agent.

HSR-903 [(S)-(-)-5-amino-7-(7-amino-5-azaspiro[2. 4]hept-5-yl)-1-cyclopropyl-6-fluoro-1, 4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid methanesulfonate] is a newly synthesized quinolone with a potent antibacterial activity and a low toxicity. The lung concentration of unchanged HSR-903 was about nine times higher than that in plasma after oral administration (5 mg/kg) in rats. In comparative studies, HSR-903 was accumulated more efficiently than levofloxacin, ciprofloxacin, and lomefloxacin in rat lung. To clarify the mechanism of the specific distribution of HSR-903 into the lung, the uptake of [14C]HSR-903 was studied using isolated rat lung cells and an isolated rat lung perfusion technique. Initial uptake of HSR-903 by isolated lung cells was temperature dependent, saturable, stereospecific, and Na+ and Cl- dependent. The Hill coefficients (1. 90 for Na+ and 1.13 for Cl-) suggest that two Na+ and one Cl- are associated with the transport of one HSR-903 molecule. The uptake of HSR-903 was inhibited by other quinolone antibacterial agents, grepafloxacin, and sparfloxacin. The extraction ratio of HSR-903 in isolated lung perfusion was temperature dependent and saturable. These findings suggest that HSR-903 is taken up by the lung cells via a carrier-mediated transport mechanism, resulting in a concentrative distribution into the lung.

Algorithms↗

[Management of mycobacteriosis in general hospital without isolation ward for tuberculosis patients. 5. The management of the patients excreting tubercle bacilli in a university hospital without isolation ward for tuberculosis].

The Japanese low ruled that the patients excreting tubercle bacilli should be treated in the isolated ward for tuberculosis. However, it is often difficult to transfer a patient with serious illness to the isolated ward with insufficient medical facilities. We investigated retrospectively the manner of the management of patients excreting tubercle bacilli in the Aichi Medical University Hospital without the isolation ward for tuberculosis. Materials were 166 patients (0.17%) out of 97,275 in-patients during 11 years since 1986 to 1996. Respiratory symptoms were observed in 114 patients (68.7% of 166 patients) on admission. The initial bacteriological examination was ordered by the attendant doctor within a week in 93 patients (81.6%) of 114 patients with respiratory symptoms. On the other hand, a half of the 52 patients without respiratory symptoms on admission were not examined for sputum bacteriology beyond a week. Anti-tuberculous treatment was started within a week after positive bacteriological results in 129 patients (77.7% of the whole 166 patients), while the treatment was not carried out or delayed in 21 patients (12.6%) because of the communication failure of the bacteriological report to the physicians. Some complications were observed in 101 patients: 21 diabetes mellitus, 20 cancers, 15 hematological disorders, 9 collagen diseases, 6 renal failures on dialysis. Serious illnesses were observed in 33 patients (20.6% of the 166 patients). Twenty-four patients (73% of the seriously ill patients) were died of renal failure, pancytopenia, cancer or respiratory failure. We considered that an isolated room for infectious tuberculosis with independent air conditioning system in a general hospital or a educational hospital was very convenient not only to the treatment of the patients with serious complications, but also to the education and training on tuberculosis for the medical student or medical stuffs.

Adult↗

[Hepatitis B].

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Diagnosis, Differential↗