Search PubMed⌕ Search

Biomedical subjects

S Mihara

Publications and source records attributed to S Mihara.

At least 91 records · Page 5Linked to original sources
PubMed1988

Effects of latamoxef on in vitro and ex vivo thromboxane A2 generation in human platelets.

Although beta-lactam antibiotics cause similar platelet abnormalities in vitro and in vivo, it is still unclear whether the mechanism(s) leading to the defects in both conditions are the same. The present work compared in vitro and ex vivo effects of latamoxef (LMOX) on aggregation and thromboxane (TX)A2 generation, determined as TXB2 generation. In the in vitro systems, LMOX interfered with both responses induced with all agonists tested (ADP, collagen and thrombin). Furthermore, although LMOX did not suppress arachidonic acid (AA)-induced TXB2 generation, it significantly suppressed the aggregation. In ex vivo systems performed with four healthy subjects, LMOX administration clearly suppressed the ADP-induced responses, but not the responses induced with the other agonists or AA. These differences observed in vitro and ex vivo are discussed from the viewpoint of different action mechanisms of LMOX under the two conditions.

Adenosine Diphosphate↗
PubMed1987

Chemosensitivity study of urological malignancies using a novel dye-exclusion method.

The chemosensitivity of several urological malignancies was determined using a novel dye-exclusion method. The tests proved to be successful in 22 out of 33 urothelial transitional-cell carcinomas, 21 out of 29 renal-cell carcinomas, and in 8 out of 13 testicular tumors, but in 0 out of 4 Wilms' tumors. At 10% of the peak plasma concentration of anticancer drugs achievable after single bolus injection, the sensitivity rates of urothelial transitional-cell carcinomas for cis-platinum, adriamycin, and carboquone were 27.3%, 13.3%, and 5.6%, respectively. At the peak plasma level, urothelial transitional-cell carcinomas were 'susceptible' to cis-platinum, carboquone, and adriamycin, the sensitivity rates being 60%, 50%, and 30%, respectively. The number of these carcinomas susceptible at the peak plasma level was significantly larger than that at 10% of the peak plasma level (P less than 0.01). However, renal-cell carcinomas exhibited a low sensitivity rate of 38% even when exposed to the peak plasma level. A similar trend was observed when tumor chemosensitivity was determined using a modified human tumor clonogenic assay. These results suggest that urothelial transitional-cell carcinomas may show good responses when anticancer drugs are given at high concentrations using methods such as intra-arterial infusion and intravesical instillation.

Antineoplastic Agents↗
PubMed1987

Somatostatin increases an inwardly rectifying potassium conductance in guinea-pig submucous plexus neurones.

1. Intracellular recordings were made from neurones in the submucous plexus of the guinea-pig caecum and ileum. 2. Somatostatin hyperpolarized more than 90% of the neurones. The lowest effective concentration was 300 pM and the maximum hyperpolarization (about 30-35 mV) was caused by 30 nM. Under voltage clamp at -60 mV, somatostatin caused outward currents which reached a maximum of 350-700 pA. 3. The hyperpolarization or outward current reversed polarity at a membrane potential (about -90 mV in control solutions) which changed according to the logarithm of the external potassium concentration. 4. The somatostatin current showed inward rectification; when the inward rectification of the resting membrane was prevented by extracellular caesium or rubidium, the inward rectification of the somatostatin current also disappeared. 5. A potassium conductance with the same properties was increased by alpha 2-adrenoceptor agonists and by delta-opioid receptor agonists; however, the effects of somatostatin were unaffected by antagonists at alpha 2- or delta-receptors. The somatostatin analogue, cyclo-aminoheptanoyl-Phe-D-Trp-Lys-(benzyl)Thr, also did not antagonize the actions of somatostatin. 6. The hyperpolarization (or outward current) was unaffected by forskolin, cholera toxin, sodium fluoride, phorbol esters or intracellular application of adenosine 5'-O-(3-thiotriphosphate) (ATP-gamma-S). However, when the recording electrode contained guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) the hyperpolarizations reversed only partially when somatostatin application was discontinued, and repeated applications caused the membrane potential to approach and remain close to the potassium equilibrium potential. 7. It is concluded that somatostatin increases the conductance of a set of inwardly rectifying potassium channels in submucous plexus neurones. The coupling between somatostatin receptor and ion channel involves a guanosine 5'-triphosphate-binding protein, but is not likely to result from changes in intracellular levels of cyclic adenosine 3',5'-monophosphate.

Action Potentials↗
PubMed1987

A non-adrenergic, non-cholinergic slow inhibitory post-synaptic potential in neurones of the guinea-pig submucous plexus.

1. Intracellular recordings were made from neurones in the submucous plexus of guinea-pig ileum and caecum. The responses to electrical stimulation of fibre strands entering the nodes of the plexus were studied. 2. Stimuli comprising trains of pulses (20 Hz, 1-5 s) produced nicotinic excitatory post-synaptic potentials (fast e.p.s.p.s), an adrenergic inhibitory post-synaptic potential (i.p.s.p.), a slow excitatory post-synaptic potential (slow e.p.s.p.) and a fourth, hitherto unnoticed, slow hyperpolarization which followed the slow e.p.s.p. All these responses were abolished by tetrodotoxin or solutions containing a low calcium concentration. 3. The slow hyperpolarization (slow i.p.s.p.) was examined in the presence of blockers of the nicotinic and adrenergic responses, and in conditions in which the slow e.p.s.p. was prevented by desensitizing concentrations of substance P or vasoactive intestinal polypeptide. The slow i.p.s.p. was unaffected by prazosin (0.1-1 microM), propranolol (0.1-1 microM), atropine (1 microM) or naloxone (1 microM). 4. The amplitude and duration of the slow i.p.s.p. increased with increasing numbers of stimulus pulses; it had an amplitude of 17 mV and a duration of 70 s when evoked by a stimulus of 20 Hz for 3 s. 5. The slow i.p.s.p. was associated with a decrease in the input resistance of the cell. It reversed polarity at -90 mV in 4.7 mM-potassium and the extrapolated reversal potential in 0.47 mM-potassium was -145 mV; these findings indicate that the slow i.p.s.p. results from an increase in membrane potassium conductance. 6. The slow i.p.s.p. could still be recorded from submucous plexus neurones in segments of ileum which had been extrinsically denervated 6-11 days previously.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1986

Suppression by beta-lactam antibiotics of thromboxane A2 generation and arachidonic acid release in rabbit platelets in vitro.

High concentrations of latamoxef and some other beta-lactam antibiotics suppressed thromboxane A2 generation as determined from the thromboxane B2 level in the in vitro aggregation of rabbit platelets in agonist-induced stimulations. In aggregation induced with a low concentration of collagen, the suppression of thromboxane B2 generation correlated well with the suppressions of aggregation and serotonin (5-HT) release; collagen produced thromboxane A2-dependent aggregation and 5-HT release as judged from the inhibitory action of indomethacin. Latamoxef also suppressed thromboxane B2 generation when platelet stimulation was induced by thrombin or platelet activating factor at concentrations at which it did not affect either aggregation or 5-HT release. However, latamoxef did not affect platelet responses including thromboxane B2 generation induced by exogenous arachidonic acid or calcium ionophore, A23187. Beta-lactam antibiotics also interfered with arachidonic acid release from the membrane phospholipids of platelets which had been prelabelled with [3H]arachidonic acid and aggregated with collagen. These results suggest that in the in vitro aggregation of platelets, beta-lactam antibiotics interfere with some of the receptor-stimulated processes which lead to arachidonic acid release from the membranes and this, in turn, suppresses thromboxane B2 generation.

Animals↗
PubMed1986

Opioids increase potassium conductance in submucous neurones of guinea-pig caecum by activating delta-receptors.

Intracellular records were made from neurones in the submucous plexus of the guinea-pig caecum. [Met5]enkephalin, [Leu5]enkephalin, [D-Ala2,D-Leu5]enkephalin (DADLE) and [D-Ser2,Leu5]enkephalin-Thr (DSLET) hyperpolarized the membrane when applied in concentrations of 30 nm-10 microM. Normorphine, [D-Ala2, MePhe4,Gly5]enkephalin-ol (DAGO), [D-Ala2,MePhe4,Met(0)5]enkephalin-ol (FK33824), dynorphin A and tifluadom had no effect at concentrations up to 10 microM. The hyperpolarization resulted from an increase in the membrane potassium conductance. Hyperpolarizations induced by [Met5]enkephalin were antagonized competitively by naloxone and by N-bisallyl[aminoisobutyrate2,3, Leu5]enkephalin (ICI 174864). The Schild plots for these antagonisms had slopes not different from one, and the dissociation equilibrium constants among individual neurones were 5-50 nM for naloxone and 5-60 nM for ICI 174864. The results indicate that the opioid receptors on guinea-pig submucous neurones which are coupled to potassium channels are of the delta-type.

Adrenergic alpha-Agonists↗
PubMed1985

Slow postsynaptic potentials in neurones of submucous plexus of guinea-pig caecum and their mimicry by noradrenaline and various peptides.

Intracellular recordings of membrane potential and membrane currents were made from neurones in the submucous plexus of the guinea-pig caecum in vitro. Fast and slow excitatory postsynaptic potentials and slow inhibitory postsynaptic potentials were recorded from the majority of neurones following focal stimulation of presynaptic fibres in the plexus. The slow inhibitory postsynaptic potential was associated with an increase in membrane conductance and reversed its polarity at -90 mV; it was reversibly blocked by yohimbine. The slow excitatory postsynaptic potential and its underlying current was associated with a decrease in membrane conductance. Two kinds of voltage-dependence both of the slow excitatory postsynaptic potential and current were observed; in 80% of cells, the excitatory postsynaptic potential and current became smaller with membrane hyperpolarization and reversed polarity at -90 mV (reversing type) but in 20% of cells both the excitatory postsynaptic potential and current simply disappeared when the membrane potential reached -70 mV (non-reversing type). The effects of acetylcholine, adenosine 5'-triphosphate, bombesin, 5-hydroxytryptamine, neurotensin, noradrenaline, substance P and vasoactive intestinal polypeptide were examined. The only substance which mimicked the slow inhibitory postsynaptic potential was noradrenaline; brief applications of noradrenaline caused hyperpolarizations which had the same time-course, reversal potential and sensitivity to yohimbine as the slow inhibitory postsynaptic potential. The non-reversing type of slow excitatory postsynaptic potential was mimicked only by adenosine 5'-triphosphate. The reversing type of slow excitatory postsynaptic potential was mimicked by bombesin, neurotensin, substance P and vasoactive intestinal polypeptide. 5-Hydroxytryptamine and vasoactive intestinal polypeptide (in some neurones) caused a depolarization with an increase in membrane conductance. All three synaptic potentials were reversibly depressed by superfusion of noradrenaline but noradrenaline did not affect the potential changes evoked by brief application of exogenous acetylcholine or substance P. It is concluded that, in guinea-pig submucous plexus neurones, the slow inhibitory postsynaptic potential is mediated by noradrenaline and results from a potassium conductance increase.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1984

Leiomyosarcoma of the breast--a case report and an electron microscopic study.

We treated a fifty six-year-old woman with leiomyosarcoma of the breast. Light microscopy showed typical findings of leiomyosarcoma and electron microscopy confirmed the smooth muscle origin of the tumor. The patient is well without evidence of metastases or local recurrence of the tumor fifty-five months after radical mastectomy.

Basement Membrane↗
PubMed1983

Perianal alveolar rhabdomyosarcoma in a child. Report of a long-term survival case.

The long-term survival of alveolar rhabdomyosarcoma of the perianal region in a 13-month-old infant is described. Local excision with chemotherapy consisting of vincristine, actinomycin D, and cyclophosphamide over a period of two years has resulted in eight years of tumor-free survival with normal growth and development. Our case and review of the literature suggest that local excision with chemotherapy may be an appropriate treatment for Group I perianal rhabdomyosarcoma in children.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1982

Botryoid rhabdomyosarcoma of the gallbladder in a child.

The first case of botryoid rhabdomyosarcoma of the gallbladder in a child is described and compared with previously reported cases from the world literature. Despite its rarity, rhabdomyosarcoma of the liver and biliary system should be considered when an obstructive jaundice is seen in children. Radical surgery with additional chemotherapy and radiotherapy are necessary for long-term survival.

Adolescent↗
PubMed1981

Thyrotropin-dependence of the distribution of peroxidase in rat thyroid gland.

After male rats were injected daily with propylthiouracil, whale thyrotropin, or thyroxine for several days, the thyroid glands were examined for their ultrastructural localization of peroxidase. The propylthiouracil treatment caused a marked increase in the number of round, peroxidase-positive vesicles in the apical and middle regions of cytoplasm, and brought about a formation of granular reaction products in the colloid lumen adjacent to the elongated microvilli. Such changes became evident after 2 days of the drug treatment and increased with the time of the effect, until the whole colloid lumen was filled with the reaction products and very elongated microvilli. The effect of exogenous thyrotropin was essentially similar, to a lesser degree, to the drug effect mentioned above. The thyroxine treatment diminished the population of the small vesicles, as usually seen in the case of normal rat thyroids. When the thyroids of thyrotropin-stimulated and unstimulated rats were homogenized and fractionated into particulates fractions and a soluble fraction, almost all the peroxidase activity was contained in the former in both cases. Based on these results, the dynamics and the physiological role of the intracellular peroxidase are discussed.

Animals↗
PubMed1977

A radioimmunoassay method for 1-beta-D-arabinofuranosyluracil using antibodies directed against 1-beta-D-arabinofuranosylcytosine.

Above pH 7.0 1-beta-D-arabinofuranosyluracil (ara-U) shows marked pH-dependent cross-reactivity with antibodies directed towards 1-beta-D-arabinofuranosylcytosine. Since this peculiar phenomenon has not been observed with other nucleosides and nucleotides thus far tested, it is probably the result of base-catalyzed tautomerism of ara-U to its enolic form which renders it more structurally similar to 1-beta-D-arabinofuranosylcytosine. By performing the radioimmunoassay at both pH 6.2 and 8.6 we could determine 1-beta-D-arabinofuranosylcytosine and ara-U simultaneously. This method for ara-U assay is simple, fairly reliable, and applicable to blood level studies.

Animals↗
PubMed1977

A radioimmunoassay for 1-beta-D-arabinofuranosyluracil with reference to cross-reactivity of 1-beta-D-arabinofuranosylcytosine with an antibody.

Antibodies directed against 1-beta-D-arabinofuranosyluracil have been produced in rabbits by immunization with a conjugate of 1-(5-O-succinyl-beta-D-arabinofuranosyl)uracil with human serum albumin. Two of four antibodies so obtained showed high specificity for 1-beta-D-arabinofuranosyluracil and allowed the development of a sensitive and reliable radioimmunoassay for this substrate. On the other hand, one antibody had a high affinity for 1-beta-D-arabinofuranosylcytosine. The binding of 1-beta-D-arabinofuranosylcytosine to this antibody was practically constant between pH 5.2 and 9.0, whereas 1-beta-D-arabinofuranosyluracil binding was affected drastically by pH. The pH-binding profile for 1-beta-D-arabinofuranosylcytosine and 1-beta-D-arabinofuranosyluracil was reminiscent of the specificity of ara-C-specific antibodies, which we previously obtained after immunization of rabbits with 1-(5-O-succinyl-beta-D-arabinofuranosyl)cytosine as a hapten.

Antibodies↗