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Biomedical subjects

M Horiuchi

Publications and source records attributed to M Horiuchi.

At least 271 records · Page 15Linked to original sources

Local control rate of split-course irradiation combined with chemotherapy for head and neck cancer.

Between 1976 and 1984, 99 patients were treated with radical external irradiation (RT) for squamous cell carcinoma of the head and neck excluding the glottis and paranasal cavity. Twenty-six out of 55 patients (47%) on chemotherapy (CT) were treated by split-course (split) RT, mainly because of acute mucositis. Only 8 out of 44 patients (18%) not on CT were treated by split RT. Although the group given split RT alone rested for 14 days and received 35 Gy, the split RT + CT group rested for 16 days and received a lower dose (30.5 Gy). The mean total doses for each treatment modality were 64 Gy in the continuous course (contin.) of RT alone, 63 Gy in contin. RT + CT, 67 Gy in split RT, and 62 Gy in split RT + CT. The observed/predicted (by a Radiation Therapy Oncology Group) control ratios of primary lesions at 2 yrs were 61/80 (0.76), 72/83 (0.87), 75/73 (1.03), and 69/71 (0.97), respectively. Among patients with a predicted rate of over 80%, the observed rates were almost identical (72%, 74%, 4/4, and 75%, respectively). However, for patients with predicted rates of 50-80%, the observed rate was 71% (12/17) in the group given combined therapy against 50% (5/10) in RT alone group. Among patients with predicted rates under 50%, the observed rate was 57% (4/7) in split RT + CR and only 25% (1/4) in contin. RT; there were no cases in contin. RT + CT. Split RT + CT is considered to be favorable for patients with poor prognostic factors.

Aged↗

Change in activity of an adenosine triphosphate-stimulated glucocorticoid receptor translocation promoter in the cytosol and nucleus of rat liver under various physiological conditions.

Rat liver contains an ATP-stimulated translocation promoter (ASTP), which is not a receptor and which enhances nuclear binding of activated receptor-glucocorticoid complex in the presence of ATP. Studies were made on changes in ASTP activity under various conditions to elucidate its physiological role in the action of glucocorticoid hormone. ASTP activity in the cytosol fraction increased markedly after adrenalectomy. Conversely, 30 min after a single injection of dexamethasone it decreased and then gradually increased. The increase in ASTP activity after adrenalectomy was inhibited by actinomycin D or cycloheximide. With decrease in ASTP activity in the cytosol fraction after the administration of glucocorticoids, activity appeared in the nuclear fraction 30 min after injection and then decreased. Thus, after the dexamethasone injection, the changes in ASTP activity in the cytosol and nuclei were similar to but not coincident with those in the glucocorticoid receptor. These results suggest, but do not prove, that ASTP is translocated or binds to nuclei with activated receptor-glucocorticoid complexes. From these results, we consider that ASTP may be an integral part of the regulatory mechanism for the action of steroid hormones and may influence specific gene expression by increasing nuclear binding of the activated complex.

Adenosine Triphosphate↗

Species difference of (2R,4R)-2-(o-hydroxyphenyl)-3-(3-mercaptopropionyl)-4-thiazolidinec arb oxylic acid (SA446) in inhibition of angiotensin converting enzyme.

A marked species difference was observed both in vitro and in vivo in the activity of SA446, an orally active inhibitor of angiotensin converting enzyme (ACE), as compared with that of captopril in five different animal species. The activity of SA446 in vitro in inhibiting plasma ACE correlated with the activity in vivo as determined by inhibition of the pressor response to angiotensin I (AI). SA446 was more potent as an inhibitor of AI response in dogs, cats and rabbits than in guinea pigs and rats. Furthermore, ACE activity in whole blood in vivo was inhibited by SA446, and the activity of SA446 was also more potent in dogs than in rats. The concentration of SA446 in the ultrafiltrate of blood (free form) was significantly higher in dogs than in rats, while no difference was observed in level of SA446 in the whole blood (free and protein-bound form) between these two species after intravenous injection. The binding rate of SA446 to plasma protein of rats in vitro was more than twice as high as that of dogs. These results suggest that the difference in the protein binding rate of SA446 is reflected in ultrafiltrate level and is one of the important components in defining the species difference in SA446 action.

3-Mercaptopropionic Acid↗

Effects of D- and L-thyroxine on the glucocorticoid binding capacity of adult rat liver.

Administration of either D- or L-thyroxine (T4) significantly increased the glucocorticoid binding capacity of cytosol of the livers of adrenalectomized adult rats. Administration of up to 0.5 mg/100 g body wt. of L-T4 was more effective than that of D-T4, but higher doses (0.8-3 mg/100 g body wt.) of D-T4 increased the binding capacity markedly to more than that with L-T4. T4- administration did not alter the apparent dissociation constant of glucocorticoid binding proteins for glucocorticoid binding, or their behavior on DEAE-cellulose chromatography either before or after thermal activation (23 degrees C for 40 min). Thus the increased binding capacity seemed to be due to increase in the level of glucocorticoid receptor in rat liver.

Animals↗

Reconstruction of the defect of the oropharynx using free jejunum.

Reconstruction of oropharyngeal defect using free jejunum was carried out in two patients with selected situation. One patient had problem of donor site, which was developed breast. Another patient had problem of recipient site, which required the flap with thin subcutaneous tissue. Reconstruction with free jejunal transfer was successful in both cases. The major advantage of the free jejunal transfer for oropharyngeal defects was discussed in comparison with cutaneous flaps. In conclusion this safety procedure is recommended for reconstruction of oropharyngeal defect.

Adult↗

[Pharmacological studies of N-(2-mercapto-2-methylpropionyl)-L-cysteine (SA 96). VI. Effects on vitamin B6, metals and skin collagen in rats].

N-(2-Mercapto-2-methylpropionyl)-L-cysteine (SA 96), an antirheumatic agent, and the main metabolite of SA 96, N-[2-methyl-2-(methylthio)propionyl]-L-cysteine (SA 679), were investigated for the effects on vitamin B6 (VB6), metals and skin collagen in rats in comparison with D-penicillamine (D-Pc). SA 96 had no effect on VB6 amount in serum and liver at doses of 30 mg/kg and 150 mg/kg, p.o., for 28 days, but SA 96 as well as SA 679 lowered the level in the liver slightly at a dose of 600 mg/kg. On the other hand, D-Pc lowered the VB6 level markedly both in serum and liver at doses of 150 mg/kg and 600 mg/kg, p.o., for 28 days. SA 96, SA 679 or D-Pc had no effect on urinary VB6 excretion. The degree of complexing of SA 96 as well as SA 679 with pyridoxal-5-phosphate in vitro was very slight as compared with D-Pc. SA 96 and D-Pc increased Cu and Zn excretion in urine, decreased Cu level both in serum and liver, and increased Zn level in serum. However, the degree of these effects of SA 96 on the metals was very slight as compared with D-Pc. SA 96 or SA 679 had no effect on skin collagen, neither soluble nor insoluble collagen, but D-Pc increased soluble collagen markedly. In addition, at a dose of 600 mg/kg, D-Pc decreased insoluble collagen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Recombinant interferon alpha-2 (Sch 30500) in patients with head and neck cancer].

Fifteen patients with advanced recurrent or metastatic carcinoma of the head and neck were treated with recombinant interferon alpha-2. Cumulative doses for evaluation of at least 1.2 X 10(8) IU were given over a period of 4 weeks. No significant regression was shown in 14 evaluable patients, 6 of which showed no change and 8 progression. Toxicities were minimum and acceptable. All patients had an episode of elevated body temperature. One patient showed transient effects on the central nervous system, which may be a dose-limiting factor. Recombinant interferon alpha-2 was therefore not recommended as a modality for the treatment of recurrent head and neck cancer.

Adult↗

[Phase II study of UFT for head and neck cancer].

A Phase II study of UFT for head and neck cancer was conducted in 10 institutions. UFT is a mixture of Futraful and uracil. Eighty-four patients entered this trial, of which 60 were evaluable. UFT was administered orally at a daily dose of 600 mg/day. Eight patients achieved complete response and 10 achieved partial response with an over-all response rate of 30.0 %. Evaluating response according to by histology, the response rate was 30.9% for cases of squamous cell carcinoma. Complete response was observed in one case of undifferentiated carcinoma. Response rate according to primary site was 33 to 40% for the nose & paranasal sinuses, mesopharynx, hypopharynx and larynx. The response rate was 28.9% for the group of patients treated previously, and 33.3% for the group previously untreated. The mean time for 50% or more regression of the tumor was 4.3 weeks. Toxic effects appeared in 40.3% of 67 evaluable cases as anorexia, nausea, vomiting, stomatitis, diarrhea etc. In one case of maxillary carcinoma, severe bone marrow suppression was observed. We concluded that UFT therapy was markedly effective for head and neck cancer.

Adult↗

[Chemotherapy with FT-207 suppository (Futraful Supo) in head and neck cancer--cooperative studies by six medical schools in Kanagawa Prefecture].

Chemotherapy with FT-207 suppository (Futraful supo) for head and neck cancer was studied by Six Medical Schools in Kanagawa Prefecture, and its effectiveness and side effects were examined. Seventy-five cases were treated with this drug. However, thirty-four cases were used for the final evaluation, with regard to the given dose etc. Generally, the effectiveness rate was 23.5%. Thyroid cancer, nasal cancer and paranasal sinus cancer gave the best results. All four cases of adenocarcinoma showed an effect. One case, who was given a higher dose, showed an increased effect. Also, cases which has not been treated with any other therapeutic procedure previously, showed a significant effectiveness rate. Side effects were observed in 45.2% of cases. These were largely appetite loss and so on, which concerned the digestive system. On the whole, it has been proved that FT-207 suppository (Futraful Supo) is useful as an induction chemotherapeutic drug for head and neck cancer.

Adult↗

Mechanism of hepatic megamitochondria formation by ammonia derivatives. Correlation between structure of chemicals and their ability to induce the formation of megamitochondria.

Correlation between the chemical structure and the ability to induce hepatic megamitochondria formation was studied by feeding mice and rats diets containing a wide spectrum of ammonia derivatives. Ammonia derivatives with electron-releasing groups, such as hydrazine, phenylhydrazine, hydroxylamine and aniline were effective in inducing megamitochondria. Ammonia derivatives with electron-withdrawing groups, such as formamide, sulfamic acid, acetamide were ineffective in inducing megamitochondria. Inducibility of ammonia derivatives with electron-releasing groups plus electron-withdrawing groups for the megamitochondria formation was dependent upon nucleophilicity of the chemical: 2,4-dinitrophenylhydrazine induced megamitochondria, while acetanilide did not induce megamitochondria. The megamitochondria formation induced by ammonia derivatives was a reversible process. Freeze-fracture studies on megamitochondria indicated that megamitochondria were formed by the fusion of adjacent mitochondria. Phosphorylating capacity of megamitochondria (hydrazine-induced megamitochondria, for example) were normal despite morphological changes. These data might suggest that the nucleophilicity of chemicals plays a key role in the induction of hepatic megamitochondria. These data might also suggest that the phenomenon is an adaptive process to changes of intracellular milieu.

Ammonia↗

An ATP-stimulated factor that enhances the nuclear binding of "activated" receptor-glucocorticoid complex.

A macromolecular material that enhances the translocation, or binding, of already "activated" receptor-glucocorticoid complex to nuclei in the presence of 5 mM ATP was separated from the cytosol of rat liver by DEAE-cellulose column chromatography with about 0.025 M NaCl. The molecular weight of the material was about 93,000 +/- 4,900, as determined by agarose gel filtration. After incubation at 60 degrees C for 15 min, this material still had activity to increase the nuclear binding, but on boiling for 15 min it lost its activity.

Adenosine Triphosphate↗

Separation and characterization of receptor-translocation inhibitors from AH 130 tumor cells.

The objective of this investigation was to study the relationship between glucocorticoid resistance and macromolecular receptor-translocation inhibitors ( MTIs ). MTIs in various cytoplasmic preparations are known to inhibit the "activated" receptor-steroid complex association with isolated nuclei, chromatin, or DNA. It was found that the MTI in the cytosol of AH 130 tumor cells (glucocorticoid resistant cells) appeared to be about 5 times more inhibitory than crude MTI from rat liver. Another difference between these MTI preparations was that ATP decreased the inhibition by crude MTI from rat liver, but had little effect on that of MTI from the tumor cells. Both preparations gave three fractions of material with inhibitory activity on DEAE-cellulose chromatography. The first fraction (Peak I), eluted with about 0.1 M NaCl, was the largest fraction separated from the tumor cytosol, but a minor fraction of that from liver. In the presence of 5 mM ATP, Peak I from rat liver enhanced nuclear binding, but that from the tumor did not, suggesting that these fractions were qualitatively different. The other two fractions (Peak II and Peak III), eluted with about 0.2 M and 0.3 M NaCl, respectively, were comparable in the two preparations.

Adenosine Triphosphate↗