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Biomedical subjects

S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 1,099 records · Page 61Linked to original sources

Local control of squamous cell carcinoma of the mobile tongue: an experience of different modalities.

From 1966 through 1983, 163 patients with squamous cell carcinoma of the mobile tongue were treated. Fifty-two patients were staged as T1N0, 77 as T2N0, 14 as T2N+, 8 as T3N0, 7 as T3N+, and 5 as T4. The follow-ups were complete. Treatment modalities varied considerably during that period, because of increasing difficulty to use radioactive sources by regulations. All T3N+ and T4 patients died shortly after treatment. Five year absolute survivals for the T1N0, T2N0, T2N+, and T3N0 patients were 87%, 60%, 27% and 63%, respectively. Local recurrence free survivals at 5 years for the T1N0, T2N0, T2N+, and T3N0 patients were 72, 48, 58, and 88%, respectively. Local recurrence free survivals seemed to be better with Ra-226 needling +/- external irradiation (EXT) than other modalities. Because many patients with local recurrence were salvaged, ultimate local-disease-free survivals should also be considered. They were 96 and 70% at 5 years for the T1N0 patients treated with Ra-226 +/- EXT, and with surgery +/- EXT, respectively; the corresponding figures for the T2N0 patients were 83 and 64%. For these reasons, Ra-226 needling may be preferable to other modalities as initial treatment. Although cervical failures did not develop after 2 years of treatment, late local recurrences were rather common, even after 5 years. Long-term follow-up is mandatory for the management of the patients, and analyzing and comparing the results.

Adult↗

Improved survival of patients with nasopharyngeal squamous cell carcinoma.

One hundred and one patients with nasopharyngeal squamous cell carcinoma (NPC) were treated with irradiation. The UICC TNM staging system (1978) was used: 6 patients were T1N0, 10 T2N0, 5 T3N0, 13 T4N0, 11 T1N+, 18 T2N+, 19 T3N+ and 19 T4N+. Since 1978, 34 patients were examined with computed tomography (CT) at first presentation. Fourteen (41%) of the 34 tumors were upstaged based on the CT findings alone. The technique of radiation therapy was markedly changed around 1978. The fields to the primary site and neck were enlarged. Two-year relapse-free survival was significantly better for the post-CT era than pre-CT era. This was mainly because of improved local-recurrence-free survival, and cervical-relapse-free survival. Improved local-recurrence-free survival, however, was appreciated in only T3 + T4 patients; there was no difference in T1 + T2 patients. It is suggested that merely enlarging radiation fields or increasing radiation doses could not be curative for some subpopulations. In order to increase local control rates further, we have started to use intracavitary irradiation with an after-loading technique as a boost. Preliminary results are encouraging.

Adolescent↗

Maxillary squamous cell carcinomas staged by computed tomography.

In 72 patients with maxillary squamous cell carcinoma, computed tomography (CT) alone was used for T-staging according to the AJC classification. Five, 31, and 36 tumors were diagnosed as T2, T3, T4, respectively. In N0 patients with a minimum follow-up of 2 years, local control rates for T2, T3, and T4 tumors were 33% (1/3), 64% (16/25) and 38% (9/24), respectively. Addition of maxillectomy to treatment seemed to have improved the local prognoses in T3 and T4 tumors. High radiation doses of 60 Gy or more seemed to be beneficial for patients with T3 tumors and without maxillectomy. CT will be of great help in classifying tumors objectively. But more importantly, it will reveal resectability and dictate treatment of choice by delineating the tumor extent precisely.

Carcinoma, Squamous Cell↗

Resonance Raman evidence for oxygen exchange between the FeIV = O heme and bulk water during enzymic catalysis of horseradish peroxidase and its relation with the heme-linked ionization.

Raman spectroscopic studies of compound II of horseradish peroxidase show that the oxygen atom in the FeIV = O group of the heme is rapidly exchanged in H2O at pH 7.0 but not in an alkaline solution (pH 11.0). This conclusion is based on studies of shift in the FeIV = O stretching mode of compound II in H2(18)O; further studies show that the FeIV = O heme is hydrogen-bonded to an amino acid residue of the protein in neutral solutions but not in the alkaline solution. Deprotonation of this residue takes place with the midpoint pH at 8.8 and accordingly corresponds to the so-called heme-linked ionization. It is concluded that this hydrogen-bonded proton plays an important part in the oxygen exchange mechanism. From this it seems clear that this hydrogen-bonded proton has an essential role in the acid/base catalysis of this enzyme and that alkaline deactivation of this enzyme can be attributed to the lack of a hydrogen-bonded proton at high pH.

Catalysis↗

The role of superoxide anion and lysosomal enzymes in anti-listerial activity of elicited peritoneal macrophages.

The in vitro effect of superoxide anion and lysosomal enzyme activity on the killing of Listeria monocytogenes EGD (listeria) by peritoneal macrophages (PM) was investigated. Generation of superoxide anion by PM stimulated with phorbol myristate acetate (PMA) was significantly increased by intraperitoneal injection of Lactobacillus casei YIT 9018 (LC9018) or Corynebacterium parvum (CP), but not by injection of peptone. However, superoxide anion generation by LC9018-elicited PM stimulated with listeria was not increased any more than that by peptone-elicited PM, and generation of superoxide anion by the PM was affected by the difference in stimuli. The killing of listeria by LC9018- or CP-elicited PM in vitro was significantly less than that by peptone-elicited PM or resident PM. Significant correlation was observed between the anti-listerial activity of PM and the intracellular killing of listeria by PM. On the other hand, beta-glucuronidase and beta-N-acetyl-D-glucosaminidase activities of LC9018-elicited, CP-elicited, or resident PM were significantly weaker than those of peptone-elicited PM, and no significant correlation was observed between the increase in beta-glucuronidase and beta-N-acetyl-D-glucosaminidase activities and the increase in anti-listerial activity. These results suggest that increase in the activity of lysosomal enzymes such as beta-glucuronidase and beta-N-acetyl-D-glucosaminidase is not correlated with the anti-listerial activity of PM, and that superoxide anion has very little effect on the anti-listerial activity of PM in vitro.

Animals↗

A morphological study on the effects of collagen gel matrix on regeneration of severed rat sciatic nerve in silicone tubes.

The present study is a chronological morphological examination on the effects of collagen gel matrix on regeneration of severed sciatic nerves. The nerves (5 mm length) were resected, and both the distal and proximal stumps were inserted into a silicone tube with 5 mm gap in between. In the test side, the gap in the tube was then injected with liquid collagen which gels in the tissue when reconstructed with a certain buffer solution. The gap space in the tube of the control side was left empty. In a chronological examination of the tissue in the tube, considerably more rapid growth of sprouting axons toward the distal stump in the test side was revealed in comparison with the control side. The cells, including both fibroblasts and larger Schwann cells, were less in number. More orderly directions were observed in the collagen matrix than in the control tube. The result indicates that regeneration of the peripheral nerves in the silicone tube can be improved, by using appropriate exogenous fine materials, collagen matrix.

Animals↗

Regulation of nerve growth factor action on Nsp100 phosphorylation in PC12h cells by calcium.

Previous work from these laboratories has shown that in PC12 cells the phosphorylation of a specific soluble protein is decreased by treatment with nerve growth factor. This protein, designated Nsp100, and its kinase have been separated and partially purified from PC12 cells. The present studies have been designed to investigate the role of calcium in this action of nerve growth factor. It is shown here, using PC12h cells, that A23187, a calcium ionophore, and high levels of K+, a depolarizing stimulus, also decrease phosphorylation of Nsp100. Furthermore, the actions of nerve growth factor as well as those of A23187 and high levels of K+ are prevented by treatment of the cells with the calcium chelator EGTA. It is also shown that agents that raise levels of cyclic AMP in the cells, specifically dibutyryl cyclic AMP and cholera toxin, also decrease phosphorylation of Nsp100 but, in addition, increase phosphorylation of tyrosine hydroxylase. The action of these latter agents on Nsp100 is blocked by EGTA, but their action on tyrosine hydroxylase is not, indicating that even agents such as cholera toxin act on Nsp100 through a Ca2+-dependent mechanism.

Animals↗

Presynaptic muscarinic and alpha-adrenoceptor-mediated regulation of GABA release from myenteric neurones of the guinea-pig small intestine.

The effects of cholinomimetic and sympathomimetic drugs on the release of [3H]-gamma-aminobutyric acid ([3H]-GABA) evoked by high K+ from the isolated small intestine of the guinea-pig were investigated, in the presence of tetrodotoxin. Acetylcholine and oxotremorine, at concentrations ranging from 10(-9) to 10(-6) M inhibited the evoked release of [3H]-GABA in a concentration-dependent manner, while nicotine was without effect. Scopolamine and pirenzepine inhibited the effect of oxotremorine, while hexamethonium had no effect. The IC50 values for scopolamine and pirenzepine of the oxotremorine (3 X 10(-8) M)-induced inhibition were 1.02 X 10(-9) M and 9.78 X 10(-10) M, respectively. Noradrenaline, but not isoprenaline inhibited the evoked release of [3H]-GABA. Clonidine (10(-10)-10(-6) M) reduced the evoked release of [3H]-GABA in a concentration-dependent manner, but phenylephrine had no effect. The inhibitory effect of clonidine was antagonized by yohimbine but not by prazosin. These findings provide evidence for the localization of M1-muscarinic and alpha 2-adrenoceptors on GABAergic nerve terminals and their involvement in the presynaptic control of the release of GABA from the guinea-pig small intestine.

Animals↗

Visualization of moving fluid: quantitative analysis of blood flow velocity using MR imaging.

A new method for the measurement of blood flow using magnetic resonance imaging has been developed. The flow velocities are calculated from the distances that the fluid has moved. The distances are directly visualized by a new pulse sequence. In a phantom study, the measured flow rates showed very good correlation with actual flow rates of up to 20 l/min (3 m/sec). In a volunteer study, pulsatile flow velocities of a large artery were measured with electrocardiographic gating. The flow pattern of a cardiac cycle at the abdominal aorta is similar to that revealed by other methods of measurement, such as Doppler ultrasound. This method allows reasonably accurate quantitative analysis of blood flow in the large arteries.

Blood Flow Velocity↗

Degradation of [125I]iodoglucagon by normal rat plasma in radioimmunoassay mixture containing aprotinin and its prevention by p-chloromercuriphenyl sulfonate and leupeptin.

Degradation of [125I]iodoglucagon during RIA of glucagon would result in erroneously high values for immunoreactive glucagon (IRG). Normal rat plasma was found to have high activity for glucagon degradation that was not suppressed by the aprotinin and EDTA routinely added to the RIA system. About 30% of the added radioactive glucagon was degraded during RIA in assay mixture at pH 7.4 containing 0.2 ml normal rat plasma, and the IRG value was calculated to be 150-180 pg/ml plasma. The degradation was completely inhibited by addition of 2 mM p-chloromercuriphenyl sulfonate (PCMS) plus 0.25 mM leupeptin as protease inhibitors, and in their presence the IRG value was about 80 pg/ml. The glucagon-degrading activity was about half as much in assay mixture at pH 8.8 as in that at pH 7.4, but the degradation still affected the accuracy of IRG values. When rat plasma was incubated with [125I]iodoglucagon in the assay conditions used for RIA and then subjected to Bio-Gel P-6 filtration, three new peaks of radioactivity were found in low mol wt fractions, with decrease in the peak corresponding to [125I]iodoglucagon, whereas on similar treatment in the presence of PCMS and leupeptin all the radioactivity was recovered in the glucagon fraction. The average recoveries of authentic glucagon as IRG in the absence and presence of the inhibitors were less than 60% and more than 90%, respectively. These findings indicate that determination of plasma IRG in rats by RIA with assay mixture containing aprotinin gives spuriously high values owing to degradation of the radiotracer, and that PCMS and leupeptin should be added to the sample and assay mixture to prevent this degradation.

4-Chloromercuribenzenesulfonate↗

Treatment of Kearns-Sayre syndrome with coenzyme Q10.

We studied the metabolism of coenzyme Q10 (CoQ) and the effects of CoQ therapy in five patients with Kearns-Sayre syndrome (KSS). Although the mitochondrial fraction was increased in muscles from KSS patients, CoQ content was slightly low. CoQ synthesis was normal in fibroblasts from KSS patients. Administration of 120 to 150 mg/d of CoQ improved abnormal metabolism of pyruvate and NADH oxidation in skeletal muscle. CoQ therapy decreased CSF protein concentration and CSF lactate/pyruvate ratio. ECG abnormalities and neurologic symptoms also improved.

Adult↗

DJ-7141, a new alpha-2 agonist with only a mild hypotensive action.

The pharmacological profile of a newly synthesized imidazole derivative, DJ-7141, was examined with special reference to alpha-2 adrenoceptors. In the rat vas deferens and dog mesenteric artery, DJ-7141 at concentrations over 10(-9) M selectively acted on the presynaptic alpha-2 adrenoceptors on the sympathetic nerve terminals and inhibited the contractions induced by electrical transmural stimulation. The potency of DJ-7141 was almost the same as those of clonidine and guanabenz. DJ-7141 also acted on the postsynaptic alpha-2 adrenoceptors to contract the dog saphenous vein. However, no alpha-1 agonist and antagonist actions were found at concentrations showing presynaptic alpha-2 agonist activity. In contrast to DJ-7141, clonidine produced an apparent contraction in the dog mesenteric artery, and the response was inhibited by prazosin. In urethane-anesthetized rats, clonidine at doses ranging from 0.003 mg/kg to 0.03 mg/kg produced a marked and prolonged hypotension, while DJ-7141 at such doses failed to produce a reduction of blood pressure. From these results, it is suggested that, in contrast to clonidine and other alpha-2 agonists, DJ-7141 is a unique alpha-2 agonist which shows high affinity to peripheral alpha-2 adrenoceptors but only a mild hypotensive activity.

Adrenergic alpha-Agonists↗

Further dopaminergic supersensitivity to dopamine agonists by subchronic administration of haloperidol in rats treated with colchicine.

Effects of subchronic administration of haloperidol on the circling behavior induced by dopamine agonists were examined in rats treated with colchicine. Methamphetamine and apomorphine produced contralateral or ipsilateral rotation in colchicine-treated rats, and these circling behaviors were significantly increased by subchronic treatment with haloperidol. These results suggest that development of supersensitivity following colchicine and subchronic haloperidol may occur through different mechanisms.

Animals↗