[Studies on human T cell colonies (2). T cell colony formation in patients with aplastic anemia and the effects of steroid hormones on T cell colony formation].
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Biomedical subjects
Publications and source records attributed to M Fujiwara.
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The effects of tofisopam on gastric functions were examined in rats. Intracerebroventricular (i.c.v.) injection of tofisopam (50 ot 100 microgram) increased both basal gastric acid output and mucosal blood flow (MBF) in rats anesthetized with urethane, while intravenous injection of tofisopam (10 mg/kg) did not change the basal gastric acid output. Ten micrograms of tofisopam, i.c.v., a dose which did not show any effect on the basal gastric acid output, significantly inhibited the decrease in gastric acid output induced by noradrenaline (5 microgram, i.c.v.). Tofisopam (10 mg/kg, i.v. or 100 microgram, i.c.v.) showed no effect on the increase in gastric acid output induced by electrical stimulation of the lateral hypothalamic area (LHA). These results, together with the previous findings, suggest the tofisopam (i.c.v.) acts on the nucleus dorsalis n. vagi and/or LHA and competes with noradrenaline. The gastric acid output was increased remarkably under water-immersion stress, and this increase lasted during the stress-loading, but the MBF did not show a corresponding increase. Pretreatment of rats with tofisopam (100 mg/kg, intraduodenal) significantly increased the MBF and inhibited the ulcer formation caused by the stress. From these results, tofisopam may restore the unbalance between sympathetic and parasympathetic nervous tones induced by stress-loading.
The effects of optically pure d-nicotine were investigated as compared with those of the l-isomer. d-Nicotine showed qualitatively the same effects as the l-isomer in the ganglionic or neuromuscular sites and the relative potency of the d-isomer was approximately 0.06 in the case of rat blood pressure (elevation), approximately 0.2 in the cat superior cervical ganglion (stimulation and blockade) and approximately 1.0 in the neuromuscular junctions of the rat diaphragm (blockade). In the adrenergic nerve terminals of the isolated rabbit pulmonary artery, l-nicotine produced sympathomimetic effects by releasing norepinephrine from those terminals. d-Nicotine, on the other hand, did not produce such effects, but instead inhibited those effects due to the l-isomer. Because d-nicotine had no effect on the response to exogenously applied norepinephrine and blocked the 3H-efflux induced by the l-isomer from the preparations preincubated with [3H]norepinephrine, the inhibitory effect of the d-isomer was attributed to its presynaptic action. Such an inhibitory effect of d-isomer was noncompetitive, on the basis of the shift of the concentration-contraction curve with the l-isomer. Simultaneous application of both isomers produced no inhibition of the response to the l-isomer, irrespective of the concentration of d-nicotine. Occurrence of the inhibitory effect of d-nicotine was not prevented by hexamethonium. d-Nicotine did not inhibit the responses of the artery to electrical transmural stimulation. These results indicate that d-nicotine inhibits the response to l-isomer by acting neither on the nicotinic receptors nor on excitation-secretion coupling mechanisms. Furthermore, such an effect of the d-isomer would be similar to that reported in the case of l-isomer, i.e., "nicotinic desensitization."
In this study, we treated severe infections (21 cases) accompanied with induction chemotherapy in 20 patients with acute leukemia by the combination of a large dose (600 approximately 1,200 mg/day) of amikacin with other antibiotics. Infections during induction chemotherapy of acute leukemia consisted of sepsis (8 cases), pneumonia (7) and others (6), and most of causative organisms were Gram-negative bacteria, such as Ps. aeruginosa (7 strains), Flavobacterium (5), Serratia (3), Ps. cepacia (2), E. coli (2) and others. The combination chemotherapy of a large dose of amikacin with other antibiotics was found to be effective (71.4%) for such infections. Side effects were negligible except for drug eruption. Therefore, a large dose of amikacin should be given for the treatment of severe infections accompanied with induction chemotherapy of acute leukemia.
A 72-year-old male noted weakness in the right lower extremity in August 1979, and clumsiness of the finger movement in the right hand in April 1980. In June 1980, he became tetraplegic and was unable to stand or walk. He also developed hypesthesia in the four extremities and difficulty in voiding. On admission to this hospital (July 12, 1980), neurological examination showed spastic tetraparesis, more pronounced on the right side. Deep tendon reflexes were markedly increased in the four extremities. Chaddock reflex in the right lower extremity and Trömner reflex in the both upper extremities were elicited. Hypesthesia below the level of C4 was present with anesthesia in the Th9-11 region. Plain film and tomogram of the cervical spine showed ossification of the posterior longitudinal ligament from C3 to C6 and a lobulated nodular calcification in the posterior part of the spinal canal at the level of C4,5 intervertebral space. CT scan revealed nodular calcifications in the ligamentum flavum not only at the level of C4 but also at the level of C6. Laminectomy from C3 to C6 was performed on August 21. The ligamentum flavum with nodular calcifications was removed. His postoperative course was uneventful. Seven weeks postoperatively the patient was able to walk without assistance and had no difficulty in voiding. He was discharged on October 14 with excellent activities of daily life. The content of the nodular calcification was identified as a kind of calcium phosphate by the physico-chemical analysis. Ossification and/or calcification of the ligamentum flavum in the cervical spine is rare, while ossification of the posterior longitudinal ligament is frequently encountered in the cervical spine. Only two cases with nodular calcification of ligamentum flavum in the cervical spine have been reported. To our knowledge, this is the first case of the nodular calcification of the ligamentum flavum in the cervical spine associated with ossification of the posterior longitudinal ligament. Two dimensional analysis by CT scan was very useful in locating the lesion and deciding the operative procedure.
Five cases of subdural hematoma from arterial rupture (SDH-AR) are described and other 39 reported cases are reviewed. The average age of the patient is 59 and male to female ratio is 2:1. Fifty two percent of the patients have history of recent head injuries most of which are trivial. A very few patient have initial loss of consciousness. Approximately half of the patients with history of head trauma have long lucid interval (average of 7 days). Those patients without history of head trauma have spontaneous onset of the symptoms and some of the have acute onset of headache and loss of consciousness, simulating cerebrovascular accident. Natural history of the SDH-AR is progressing deterioration of the symptoms, resulting in coma and death. Skull fracture is seldom demonstrated in the patients with SDH-AR. Angiography shows and extracerebral avascular mass over the cerebral convexity with marked midline shift. In 3 cases including our 2 cases, extravasation of the contrast medium from the cortical artery is observed and this is a useful finding for making diagnosis of this disease. Computerized tomography reveals high density extracerebral mass with remarkable mass effect. Craniotomy discloses subdural clot and spurting arterial rupture from a branch of the cortical artery around the Sylvian fissure. In some cases, subarachnoid hemorrhage is observed but in none of the cases, cerebral contusion or laceration is present. It is presumed that the mechanism of the arterial rupture is gliding movement of the brain within the skull upon injury, tearing an arterial twig with dural attachment. Hypertension, arteriosclerosis and brain atrophy may be important contributing factors to this mechanism. Pseudoaneurysm of the cortical artery caused by closed head injury is also associated with this mechanism and may explain delayed sudden onset of the symptoms in some patients with SDH-AR.
The possible involvement of sodium action potentials in sympathomimetic effects of nicotine was investigated using isolated guinea-pig aortas. Goniopora toxin (GPT), a polypeptide isolated from coral, was used to increase the sodium influx through the fast sodium channel of the postganglionic sympathetic nerves; tetrodotoxin (TTX) was used to block this flux. Nicotine (10-300 microM) produced sympathetic nerve-mediated contractions in a concentration-dependent manner. GPT (30 nM) enhanced the responses to nicotine over the entire range of concentrations tested, yet there was no effect on resting tension. Such an effect of GPT was concentration-dependent and was apparent in concentrations over 10 nM. GPT had no effect on the responses to exogenously applied norepinephrine. TTX (100 nM) abolished this potentiating effect of GPT, but did not inhibit the usual nicotine-induced responses. The 3H-efflux induced by nicotine (100 microM) in the preparations preincubated with [3H]norepinephrine was not significantly inhibited by TTX (100 nM). GPT (30 nM) markedly augmented nicotine-induced 3H-efflux and TTX prevented this effect of GPT. These results appear to indicate that the augmentation of the nicotine-induced response by GPT in isolated guinea-pig aortas is due to a prolongation of the duration of the presynaptic action potential. The effects of nicotine on adrenergic nerve terminals may involve two mechanisms, i.e.: 1) one mediated by sodium action potentials and 2) one independent of these action potentials.
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The sensitivity of leukemic progenitor cells (L-CFU) to cytosine arabinoside (Ara-C) and daunomycin (DM) in vitro was studied using PHA -LCM two step assay for L-CFU. Continuous exposure of leukemic and normal bone marrow cells to DM as well as Ara-C in vitro appeared to be more effective than pulse exposure because colony formation was suppressed by a dose dependent fashion. The relationship between in vitro sensitivity to DM and Ara-C and that of in vivo to chemotherapy was investigated in 17 untreated and 5 relapsed patients with acute nonlymphocytic leukemia. The sensitivity of L-CFU to the two chemotherapeutic agents varied from patient to patient. These studies indicated a clear-cut relationship between in vitro drug sensitivity and in vivo response to patients whose L-CFU were sensitive to both agents and entered complete remission, whereas patients whose L-CFU were insensitive to one or both drugs in vitro failed to enter remission. This assay system appears to be useful in predicting response of patients to chemotherapy and in selecting the most effective drugs for an individual patient use.
To investigate the possible role of central noradrenergic neurons in the regulation of gastric functions, electrical stimulation of the locus coeruleus [LC] and microinjection of noradrenaline [NA] into the ala cinerea (area of the dorsal motor nucleus of the vagi [NDV] and the nucleus tractus solitarius [NTS]) were given to urethane-anesthetized rats. Unilateral electrical stimulation of the LC decreased both the basal levels and the lateral hypothalamic area [LHA]-induced increases in gastric acid output and mucosal blood flow. Microinjection of NA 0.1 and 0.5 micrograms/animal into the ala cinerea also decreased the basal levels of these gastric parameters. From these results, combined with neuroanatomical data from the literature, it is concluded that central noradrenergic inhibitory mechanisms originating from the LC seem to be involved in the regulation of gastric functions, probably at the level of the brain-stem ala cinerea.
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A case of an epidermoid cyst in the frontal base which showed homogeneous high density in noncontrast computed tomography, simulating a meningioma with calcification, is reported. Operative findings and histological examination suggested that this high density was caused by spontaneous hemorrhage into the cyst.
A 45-year-old man and a 47-year-old woman with cryptic vascular malformations of the choroid plexus in the lateral ventricle are reported. Each patient had an intraventricular hematoma, located in the right trigone and in the anterior part of the left lateral ventricle, respectively. The vascular lesion of one patient was angiographically visualized as find abnormal vessels communicating with the right anterior choroidal artery; in the other, angiography did not reveal the lesion. In the former patient, histological examination of the excised specimen led to a diagnosis of arteriovenous malformation; in the latter, a diagnosis of venous malformation was made. Both patients were successfully treated surgically.
The effects of exogenously applied prostaglandins on the contractile responses of the gallbladder and sphincter of Oddi isolated from guinea pigs were examined in normal and indomethacin-treated preparations. Indomethacin reduced the tone and the contractile responses to transmural stimulation and to exogenously applied ACh of the gallbladder, while the tone and contractile responses of the sphincter of Oddi were little affected by indomethacin. Prostaglandins E1, E2 and F2 alpha potentiated the contractile responses of the gallbladder to transmural stimulation and ACh, and furthermore, treatment with indomethacin enhanced the potentiating effects of prostaglandins E1 and E2 but not the effect of PGF2 alpha. The reduced tone and contractility of the gallbladder were restored to the control level by addition of PGE1 and PGE2 but not by PGF2 alpha. These results suggest that endogenous PGE1 and PGE2 may play an important role in neurogenic control of contractility of the gallbladder, but not of the sphincter of Oddi.
In studies on prostaglandin (PG) synthetase activity in the guinea pig gallbladder, prostaglandin E2 and F2 alpha (PGE2 and PGF2 alpha) were enzymatically formed from arachidonic acid using the 105,000-g precipitate fraction. The amount of PGE2 synthesized was about four times larger than PGF2 alpha. Indomethacin (1-3 microM) inhibited both the PG synthesis and the contractile response to transmural stimulation in the gallbladder. These findings suggest that the inhibitory effect of indomethacin on the contractility of the gallbladder is related to the inhibition of PG synthesis, and that endogenous PGE2 is involved in the contractility of this tissue.