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Biomedical subjects

M Kajiwara

Publications and source records attributed to M Kajiwara.

At least 109 records · Page 6Linked to original sources

[Massive osteoplastic bone metastasis of hepatocellular carcinoma--a case report].

Massive osteoplastic bone tumor in hepatocellular carcinoma is very rare. A 48-year-old man was misdiagnosed as osteosarcoma of the right proximal tibia with dense sclerosis and marked periosteal spiculation. Histologically, there were many osteoids and immature trabeculi. Tumor cells with spindle nuclei were not atypical and had few mitoses. Three years later, he suddenly died of rupture of cerebral aneurysm. Autopsy revealed small hepatocellular carcinoma with distant metastases of the tibia, lumbar spine and lung. In this case, it was extremely difficult to decide whether or not we were dealing with primary malignant tumor.

Bone Neoplasms↗

[Clinicopathologic study of intramammary cancer residuals after outpatient excisional biopsy of breast cancer].

Seventy-four breast cancer patients, who had undergone outpatient excisional biopsy followed by radical mastectomy, were divided into three groups according to the types of intramammary cancer residuals: no cancer residuals--45 patients, noninvasive cancer residuals--15, and invasive cancer residuals--14. The invasive cancer residual group included nine patients with axillary metastasis and showed a significantly higher rate of five-year recurrence (8/14) than the other two groups. In some of the patients with invasive cancer residuals, the lesions were more advanced and aggressive by nature. Histopathologically, invasive cancer residuals closely correlated to the nondesmoplastic infiltrating tumor border, and noninvasive cancer residuals to intraductal cancerous spread. Most intramammary cancer residuals were found close to the wounds made by biopsy.

Ambulatory Surgical Procedures↗

Two new opioid delta-receptor ligands: a highly selective agonist and a potent selective antagonist in in vitro isolated preparations.

N,N-Diallyl derivatives of enkephalin analogues were chemically synthesized, and their biological activities were estimated in vitro isolated preparations. N,N-Diallyl-[D-Ala2, D-Leu5]-enkephalin [test compound I] at doses up to 10 microM did not inhibit the electrically-evoked contractions of guinea-pig ileum, which had been suggested to contain opioid mu- and kappa-receptors, but it significantly depressed the contractions of mouse vas deferens, which had been indicated to contain mu-, kappa- and delta-receptors, suggesting that test compound I did not act on both mu- and kappa-receptors, but acted on delta-receptors. Additionally, the Ke (equilibrium dissociation constant) values against test compound I of naloxone were approximately 30 nM and similar to those of Mr 2266, also indicating that test compound I acted as a delta agonist. Moreover, the Ke values of ICI 154129 against compound I were approximately 340 nM, strongly suggesting that test compound I acted as a delta agonist. The Ke values of bis-[N,N-diallyl-[D-Ala2, Leu5]-enkephalyl]-cystine [test compound II] against [D-Ala2, D-Leu5]-enkephalin in mouse vas deferens and morphine or ethylketocyclazocine in guinea-pig ileum were 44.9 nM and 5.00 or 11.3 microM, respectively, showing that test compound II was a potent selective opioid delta antagonist. In conclusion, among compounds synthesized, two new opioid delta-receptor ligands, one being a highly selective agonist and the other being a potent selective antagonist in in vitro isolated preparations, were found in the present study.

Animals↗

The role of bestatin-sensitive aminopeptidase, angiotensin converting enzyme and thiorphan-sensitive "enkephalinase" in the potency of enkephalins in the guinea-pig ileum.

The role of each enkephalin-hydrolyzing peptidase in the inhibitory potency of exogenously added enkephalins in the myenteric plexus-longitudinal muscle preparation of guinea-pig ileum was studied by using the relatively specific inhibitor of each enzyme. Results showed that three distinct enzymes, bestatin-sensitive aminopeptidase(s), angiotensin converting enzyme, and thiorphan-sensitive "enkephalinase", played a critical role in the inactivation of enkephalins. Additionally, these enzymes are likely to be located close to opioid receptors, since they produce a significant concentration difference of enkephalin between the surrounding organ bath and the vicinity of opioid receptors. In contrast to these three enzymes, both L-tyrosyl-L-tyrosine-sensitive dipeptidyl aminopeptidase and D-phenylalanine-sensitive carboxypeptidase are indicated not to be involved significantly in the degradation of exogenously added enkephalins in the guinea-pig ileum.

Amino Acids, Sulfur↗

Effects of 2-nicotinamidoethyl nitrate (Nicorandil) on excitation-contraction coupling in the smooth muscle cells of rabbit ear artery.

The effect of SG-75 (Nicorandil) on the neuromuscular transmission and smooth muscle membrane of the rabbit ear artery was investigated by means of intracellular microelectrodes, isometric tension recording and flux experiments. This agent caused a pronounced hyperpolarization of the cell membrane and a significant increase of the K-permeability. During perivascular nerve stimulation, the amplitude and the time constant of the falling phase of the excitatory junction potentials were reduced, causing a suppression of spike generation and of the concomitant contractile responses, but the release of [3H]noradrenaline was not affected. At high doses this agent inhibited significantly submaximal contractile responses induced by various stimuli. However, these effects could not be correlated with changes in 45Ca fluxes. It is suggested that although the effect of SG-75 could be due mainly to an increase of the K-permeability and the concomitant hyperpolarization, it might also reduce the force development by a mechanism which does not depend on a reduction of the concentration of ionized Ca in the cytoplasm.

Animals↗

Effects of Ca-antagonists on neuromuscular transmission in the rabbit ear artery.

1. The effects of three Ca-antagonists: diltiazem, nicardipine and flunarizine have been studied on excitatory junction potentials (e.j.p.s), force development and efflux of transmitter during stimulation of perivascular nerves in the rabbit ear artery. 2. Stimulation of these perivascular nerves produces excitatory junction potentials and repetitive stimulation causes facilitation. Increasing the frequency or the number of stimuli initiates an action potential and a large contraction. Both phenomena are completely suppressed by 3 X 10(-7) M TTX. 3. Ca-antagonists at 10(-5) M do not affect the resting membrane potential, but flunarizine and nicardipine at concentrations exceeding 10(-5) M reduce the amplitude of e.j.p.s and of the action potentials and also the concomitant contraction induced by nerve stimulation. Diltiazem at concentrations below 3 X 10(-5) M has no effect on e.j.p.s and action potentials while at 10(-4) M, it largely suppresses e.j.p.s, spikes and contraction. This inhibitory effect of the Ca-antagonists increases with prolonged exposure. 4. All these Ca-antagonists induce an increased release of 3H-DOPEG from the nerve terminals, but in our experiments in vitro they do not reduce the efflux of 3H-noradrenaline induced by nerve stimulation. 5. The results indicate that Ca-antagonists might affect the excitation-contraction coupling in vivo by inhibiting the Ca influx activated by endogenous noradrenaline. They do not exert an acute effect on the noradrenaline release induced by stimulation. The increased DOPEG release by Ca-antagonists remains unexplained.

Animals↗

The choice of opioid receptor subtype in isolated preparations by dynorphins.

The choice of opioid receptor subtype by dynorphins was studied in isolated preparations. Both dynorphin-(1-17) and dynorphin-(1-8) had significant inhibitory actions on the electrically evoked contractions of guinea-pig ileum, mouse vas deferens and rabbit ileum. The inhibition of contractions by dynorphin-(1-17) in three preparations was antagonized more effectively by Mr 2266 which had a high affinity to both mu- and kappa-receptors, than naloxone which had a high affinity only to mu-receptors, indicating that dynorphin-(1-17) acted on kappa-receptors in three preparations. Additionally, the inhibitory potency of dynorphin-(1-17) relative to that of ethylketocyclazocine, a representative kappa-receptor agonist, in guinea-pig ileum was similar to that in either mouse vas deferens or rabbit ileum. This also suggested that dynorphin-(1-17) acted as a kappa-receptor agonist in three preparations. The effectiveness of naloxone and Mr 2266 to antagonize the agonist action of dynorphin-(1-8) indicated that dynorphin-(1-8) acted as a kappa-receptor agonist in either guinea-pig ileum or rabbit ileum whether or not peptidase inhibitors were existed while in mouse vas deferens it acted as a delta- or kappa-receptor agonist in the absence or presence of peptidase inhibitors, respectively. Thus, the choice of opioid receptor subtype in mouse vas deferens by dynorphin-(1-8) was likely to depend whether peptidases were inhibited or not. The inhibitory potency of dynorphin-(1-8) in the presence of peptidase inhibitors relative to that of ethylketocyclazocine in rabbit vas deferens, which had been shown to contain kappa-receptors exclusively, was similar to that in either mouse vas deferens or rabbit ileum, but was significantly different from that in guinea-pig ileum. This indicates that kappa-receptors in guinea-pig ileum are different from those in other preparations although the possibility of other causes such as incomplete inhibition of peptidase(s) can not be neglected.

Animals↗

The choice of opiate receptor subtype by neo-endorphins.

The choice of opiate receptor subtype by alpha- and beta-neo-endorphin was studied in isolated preparations. Neo-endorphins had significant inhibitory actions on the electrically evoked contractions of guinea-pig ileum, mouse vas deferens and rabbit ileum as well as on the rabbit vas deferens which had been shown to contain kappa-receptors exclusively. Mr 2266, a relatively specific kappa-receptor antagonist, was more effective than naloxone, a relatively mu-receptor antagonist, to antagonize the agonist actions of neo-endorphins in either the guinea-pig and rabbit ileum or in the rabbit vas deferens. By contrast, in the mouse vas deferens, the effectiveness of Mr 2266 to antagonize the agonist actions of neo-endorphins was low and similar to that of naloxone. The potencies of neo-endorphins relative to that of ethylketocyclazocine, a representative kappa-receptor agonist, in the guinea-pig ileum were similar to those in the rabbit ileum but were significant different from those in the mouse vas deferens. The data indicate that neo-endorphins act as kappa-receptor agonists in either the guinea-pig and rabbit ileum or in the rabbit vas deferens while in the mouse vas deferens they act on opiate receptor subtypes other than kappa- and mu-receptors.

Animals↗

General features of electrical and mechanical properties of smooth muscle cells in the guinea-pig abdominal aorta.

The membrane potential in smooth muscle cells of the guinea-pig's abdominal aorta has a mean value of -57.2 mV. These cells are electrically connected and the space and time constant are 0.66 mm and 180 ms respectively. An increased K-concentration elicited a contraction at 20 mM and the maximum was reached at 77 mM. The maximum depolarization produced by a tenfold increase of [K]0 was 45 mV. Tetraethylammonium at concentrations exceeding 2 mM, depolarized the membrane, increased the membrane resistance and reduced the rectifying properties of the membrane. Only at 20 mM a small active response could be induced by outward current pulses. Low concentrations of noradrenaline (less than 10(-8) M) hyperpolarized the membrane, while higher concentrations (greater than or equal to 10(-7) M) depolarized. Isoprenaline at concentrations below 10(-7) M also hyperpolarized, but it depolarized from 10(-5) M onward. Acetylcholine at concentrations over 10(-8) M hyperpolarized the cells without exerting an effect on the resting tension, but it reduced a noradrenaline induced contraction. Low concentrations of caffeine (less than or equal to 2 mM) hyperpolarize the membrane, while higher concentration (greater than or equal to 5 mM) depolarize. Caffeine is found to be a more efficient releaser of cellular Ca than noradrenaline. This might be due to the weak beta-agonist action of noradrenaline appearing at high noradrenaline concentrations. The hypothesis is supported by the finding that a beta-stimulation increases the Ca-uptake in the intracellular store. The study of the electrophysiological effects of different stimuli do not suggest an important role for electromechanical coupling in this tissue.

Abdomen↗

Fibrous histiocytoma of the nasal cavity and maxillary sinus.

Two cases of fibrous histiocytoma were presented; Case 1: a 46-year-old man with a tumor filling the left nasal cavity and maxillary sinus, and Case 2: an 80-year-old man with a tumor of the right maxillary sinus destroying its surrounding wall. Histologically, the former was dominated by storiform pattern and onion-like structures, and the latter by osteoclast-like multinucleated giant cells. After radical surgery, Case 1 was free of recurrence for more than one year, and Case 2 showed recurrence although still maintaining fairly good health. A total of 29 cases hitherto reported arising in the nasal, paranasal and nasopharyngeal regions were reviewed, pitfall of differential diagnoses was commented especially in our two cases, criteria of malignancy were discussed, and the necessity of repeated samplings was emphasized because of paucity and unfamiliarity of fibrous histiocytoma arising, in particular, from the upper respiratory tract.

Aged↗

Roles of stored calcium on the mechanical response evoked in smooth muscle cells of the porcine coronary artery.

Effects of acetylcholine (ACh), caffeine and procaine on the membrane and mechanical properties of the intact and skinned muscle cells of the porcine coronary artery were investigated using the micro-electrode and isometric tension recording methods.1. ACh (10(-8)-10(-5)m) had no effect on the membrane potential and membrane resistance, as assessed from the current-voltage relationship.2. Caffeine possessed dual actions on the membrane property, i.e. a low concentration (0.3-1 mm) hyperpolarized and a high concentration (over 1 mm) depolarized the membrane, while caffeine (over 0.3 mm) consistently increased the ionic conductance of the membrane. Procaine (over 1 mm) depolarized the membrane and decreased the ionic conductance of the membrane.3. The spike and contraction evoked by outward current pulses in the presence of 10 mm-TEA were suppressed by treatment with caffeine (5 mm) or procaine (3 mm), but the spike was slightly and the electrically induced contraction was significantly suppressed by ACh (10(-6)m) due to the marked increase in resting tension.4. In Ca-free 2 mm-EGTA containing solution, the K-induced contraction (118 mm) rapidly ceased, but not the contraction evoked by ACh (10(-5)m) or caffeine (5 mm). The ACh-induced contraction rapidly ceased in the presence of 1 mm-procaine; however, over 5 mm-procaine was required to abolish the caffeine-induced contraction.5. The pCa-tension relationship was measured in saponin-treated skinned muscles. The minimum concentration of free Ca required to produce contraction was 2 x 10(-7)m, while maximum contraction was observed at 10(-5)m-free Ca. The maximum amplitude of Ca-induced contraction observed in skinned muscles was larger or the same as that evoked by ACh in the intact muscle. ACh (10(-5)m), caffeine (5 mm) and procaine (5 mm) had no effect on the pCa-tension relationship.6. After Ca has been loaded in skinned muscles, caffeine and replacement of K with choline (116 mm) in the Ca-free EGTA containing solution produced the contraction. However, the application of ACh did not result in a release of the stored Ca, and procaine suppressed the release of Ca activated by caffeine.7. The present results indicate that ACh activates the muscarinic receptor distributed on the plasma membrane, thus releasing the stored Ca. However, this mechanism may not be a prerequisite for direct action of ACh on the Ca releasing site. The possible mechanism of ACh action on the Ca releasing site, mainly sarcoplasmic reticulum, was discussed in relation to actions of caffeine and procaine, particularly with regard to the functional relations between plasma membrane and sarcoplasmic reticulum.

Acetylcholine↗

[Clinical studies with cefmenoxime in the otorhinolaryngeal field (author's transl)].

We conducted a therapeutic trial with cefmenoxime in the field of otorhinolaryngology on a total of 14 subjects including 7 cases of otitis media, 5 cases of peritonsillar abscess, 1 case of chronic sinusitis and 1 case of congenital aural fistula. 1. The effective rate for peritonsillar abscess was extremely high being judged 'markedly effective' in 3 cases and 'effective' in 2 cases. 2. The effective rate for otitis media was also remarkably high; it was judged effective in 85.7% of the cases. It is thought that this is probably due to the fact that therapy and supervision were carried out on inhospital patients. 3. The 1 case of chronic sinusitis and the 1 case of congenital aural fistula were each judged 'effective' and 'markedly effective'. The only side effect observed was a slight case of skin eruption in 1 of the patients.

Adolescent↗

Effects of vasodilator agents on smooth muscle cells of the coronary artery of the pig.

1 Effects of the vasodilator agents, papaverine, diltiazem, and sodium nitroprusside (SNP) on the electrical and mechanical activities of the smooth muscles of the coronary artery of the pig were compared.2 At a concentration of 10(-5) M, papaverine hyperpolarized and increased the ionic conductance of the membrane, SNP slightly hyperpolarized but diltiazem had no effect on the membrane potential and membrane ionic conductance.3 At a concentration of 10(-5) M, diltiazem abolished the spike evoked by outward current pulses in the presence of tetraethylammonium (TEA) 10 mM, while papaverine and SNP slightly reduced spike amplitude.4 The K-induced contraction produced by any given concentration of [K](o) over 20.2 mM was suppressed by diltiazem and SNP dose-dependently in concentrations greater than 10(-6) M; higher concentrations of papaverine were required to suppress contraction.5 The acetylcholine (ACh)-induced contraction was suppressed by diltiazem and SNP at concentrations greater than 10(-6) M and by papaverine in concentrations over 10(-5) M.6 In saponin-treated skinned muscles, papaverine, diltiazem and SNP had no effect on the pCa-tension relationship, i.e. these agents had no effect on the Ca receptor of contractile proteins. Furthermore, the caffeine-induced contraction in skinned muscles (after Ca loading) was not affected by these agents, i.e. the mechanism of Ca release by caffeine in skinned muscles was not affected.7 Chlorpromazine, an agent interacting with calmodulin, antagonized the contractile effect of calcium on skinned muscle fibres.8 The results obtained are discussed in relation to spike and contraction generating mechanisms, i.e. the effects of these agents on Ca influx and Ca release from stored sites. The results indicated that at equimolar concentrations diltiazem suppressed the mechanical response in the coronary artery of the pig more than SNP or papaverine.

Acetylcholine↗

Neuromuscular transmission and smooth muscle membrane properties in the guinea-pig ear artery.

Effects of noradrenaline and alpha-adrenoceptor blocking agents on neuromuscular transmission of the guinea-pig ear artery were assessed using the micro-electrode method.1. The mean membrane potential, and length and time constants of the longitudinally oriented muscle cells were -64.5 +/- 5 mV (n = 150), 1.03 +/- 0.16 mm (n = 15) and 410 +/- 40 msec (n = 7) respectively. From the current-voltage relationship, weak outward current pulses produced an anomalous rectification of the membrane while stronger intensities produced a normal rectification of the membrane with a depolarization over 10-15 mV.2. Brief stimulation (0.1-0.5 msec) of the tissue produced an excitatory junction potential (e.j.p.). Facilitation produced by repetitive stimulation was evident only on very rare occasions. Higher stimulus intensities caused a stepwise increase of the amplitude of e.j.p.s.3. Spontaneously generated miniature excitatory junction potentials (m.e.j.p.s) were recorded from the muscle membrane. In many cells, the interval and amplitude histograms of m.e.j.p.s showed skew curves. On rare occasions, a bell-shaped amplitude distribution (quantal release of packeted noradrenaline (NA)) was observed.4. NA (> 3 x 10(-7)m) depolarized the membrane and increased the membrane resistance, as measured from the amplitude of the electrotonic potential. Phentolamine suppressed the NA-induced depolarization. However, high concentrations of phentolamine (> 10(-5)m) depolarized the membrane and increased the membrane resistance.5. NA (10(-8)m) caused no change in membrane potential though it suppressed the amplitude of an e.j.p. produced by a single stimulus, but did not suppress the amplitude of the subsequent e.j.p.s evoked by repetitive stimulation (0.2-2.0 Hz). A higher concentration of NA (3 x 10(-7)m) depolarized the membrane and markedly suppressed the amplitude of e.j.p.s. On the other hand, NA (10(-8) or 2 x 10(-8)m) generated burst discharges of m.e.j.p.s between silent periods or random generation.6. Phentolamine (10(-6)m) markedly enhanced the amplitude of e.j.p.s and caused a smooth facilitation in response to a train of stimuli with no effect on the membrane potential. A stepwise change in the amplitude of e.j.p.s was no longer observed at any given stimulus frequency and intensity.7. Phenoxybenzamine (10(-7)m) suppressed the amplitude of e.j.p.s with no change in the membrane potential.8. The results led to the conclusion that, at a concentration which has no effect on the post-junctional muscle membrane, NA and phentolamine seemed to be more effective on prejunctional adrenoceptors, while phenoxybenzamine seemed to have a greater effect on post-junctional adrenoceptors. NA depresses adrenergic transmission by negative feed-back, while the enhancing action of phentolamine can be explained partly by blocking of prejunctional adrenoceptors and, in addition, by an increase of NA release.

Animals↗