[Determination of flunarizine in serum by high performance liquid chromatography and its clinical application].
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Biomedical subjects
Publications and source records attributed to T Tagawa.
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A case of a 57-year-old man with destructive calcium pyrophosphate dihydrate (CPPD) arthropathy (pseudogout) together with pseudotumor formation in the temporomandibular joint (TMJ).
Cortical blood flow was monitored during craniotomy for bypass surgery to treat childhood moyamoya disease. The patients were hyperventilated, and changes in cortical surface blood flow were detected by a heat clearance method with plate type thermocouple probes. End-tidal CO2 was monitored during hyperventilation to avoid excessive reduction of CO2. There were three types of blood flow responses to hyperventilation: simple reduction, prolonged reduction, and increase. Simple reduction was noted in four cases and was related to constriction of basal and ethmoidal moyamoya vessels. Prolonged reduction was noted in three cases and was related to excessive constriction of basal moyamoya vessels. Increase was noted in four cases and was related to increase in blood flow from cranial vault moyamoya vessels. The results indicate that the basal moyamoya vessels are constricted by hyperventilation. This may be the cause of ischemic symptoms provoked by hyperventilation.
The aminergic and cholinergic innervation of choroid plexuses in three species of amphibia was investigated. Plexuses of the Japanese toad and the bullfrog had poor innervation by adrenergic nerves of sympathetic origin, but in the clawed toad, these plexuses were heavily innervated by adrenergic axons from ganglion cells located in the plexus stroma. Nerve fibers positive for acetylcholinesterase were not found in the plexuses, except for a few fibers with very weak enzyme activity in the clawed toad.
Xeroderma pigmentosum is an unusual neurocutaneous disorder. Recent studies have classified patients with xeroderma pigmentosum into 10 groups by somatic cell hybridization methods. In this report we describe 32 patients with Group A xeroderma pigmentosum, including 1 patient with an atypical case, who were assessed for neurological complications. Of these patients, 17 had microcephaly, 13 short stature, and 21 mental retardation. In patients over 7 years of age, sensorineural deafness and spinocerebellar signs such as nystagmus, dysarthria, tremor, and ataxia were frequently observed; no patients below 7 years of age had such neurological complications. Electroencephalographic studies revealed abnormal slow and low voltage background activity. Two patients had focal abnormal discharges, one of whom developed versive seizures. Cranial computed tomographic scans revealed abnormalities, including ventricular dilatation, cerebral atrophy, cerebellar and brainstem atrophy, and cranial bone thickening. A patient with an atypical case of Group A xeroderma pigmentosum had less skin and neurological involvement, and higher levels of postultraviolet colony-forming ability and host cell reactivation than did a typical Group A case. It is possible that these less severe cytological findings are responsible for the less severe skin lesions and neurological complications noted clinically.
The localization of immunoreactive T3 was investigated in dog and chick thyroid glands either fixed in Bouin's solution or freeze-dried and fixed with paraformaldehyde vapor, and compared with localization of 19S-thyroglobulin. Freeze-drying followed by paraformaldehyde vapor was better for the demonstration of T3 than Bouin's solution; it gave a much stronger immunoreactivity for T3. This fixative was also excellent for the demonstration of thyroglobulin. The immunoreactive T3 was detected only in the colloid and was never observed in the follicular cells, although immunoreactive thyroglobulin was present not only in the colloid but also in the follicular cells. Subsequently, in dog fetuses and chick embryos the appearance and development of immunoreactive T3 were studied. At 40 days of gestation in dog fetuses and at 9 days of egg incubation in chick embryos, immunoreactive T3 was found in the colloid of primordial follicles coinciding with the formation of the colloid. The ability of embryonic thyroid glands to synthesize T3 seems to be linked to the organization of follicles. With progressing development, the follicles stored more colloid and immunoreactive T3 within the follicular lumina. Concentrations of immunoreactive T3 in thyroids from chickens at various stages of development were also studied by radioimmunoassay. The T3 concentration was first detected at 9 days of incubation and gradually increased with embryo age; it was related to the amounts of colloid stored in the follicles.
The cyst structures of chick ultimobranchial glands were studied by electron microscopy and immunocytochemistry to characterize the type of intermediate-sized filaments present in the cells lining cyst lumina. Electron microscopy showed that the majority of the lumen-bordering cells contained extensive meshworks of intermediate-sized (7-11 nm) filaments, many of which were arranged in bundles. Apical regions of C cells directly bordering on cyst lumina were also filled with thinner (5-6 nm) filaments. Immunoperoxidase staining showed that the majority of cyst epithelial cells were stained intensely with anti-keratin antiserum, but not with anti-neurofilament antiserum, which is a specific marker for neuronal differentiation. The cyst epithelium also showed moderate-to-weak immunoreactivity for actin. Subsequently, the differentiation and maturation of cyst structures related to intermediate filament expression were studied. In 18-day-old chick embryos, keratin immunoreactivity began to appear in the cell clusters destined to form cysts and in the primordial cysts with small cavities. At this time, fine networks of intermediate filaments were already detected in the cells lining the cystic cavities. At 1 day after hatching, the cysts became a consistent feature of ultimobranchial glands. Intermediate filaments associated in bundles were observed, and the intensity of immunostaining for keratins increased. Thereafter, with progressive enlargement of cysts, numbers of intermediate filaments and intensity of keratin immunoreactivity gradually increased with age. Thus, the data indicate that in cyst epithelium keratin filaments are highly organized and may confer the structural strength necessary for cells lining cyst lumina.
The ultimobranchial glands of the chicken were examined by electron microscopy and immunocytochemistry using a calcitonin antiserum. Electron microscopy confirmed the presence of C-cells, containing numerous secretory granules storing calcitonin, in the luminal lining of cyst-like structures found in these glands. These cells were furnished with prominent microvillar projections at their luminal surface, and the cytoplasm of the apical region was filled with fibril material. Furthermore, the cells contained prominent junctional complexes and desmosomes at their apico-lateral surfaces. In these C-cells, secretory granules were concentrated near the lumen and some were attached to the apical cell membrane. The luminal content of the cysts had a colloid-like and flocculent appearance, and was frequently seen attached to the cytoplasmic projections or apical cell membrane of the C-cells. Since the cysts progressively increase in volume and number with age, it is suggested that they may partly play a role in the storage of excess or unneeded hormonal products.
In order to elucidate the functional significance of somatostatin in thyroid C cells, the alterations of immunoreactive somatostatin in the cells were investigated under various experimental conditions, i.e., hypercalcemia, hypocalcemia, and antithyroid drug treatment. Guinea pigs and rabbits, in which almost all C cells reveal the intense immunoreaction for somatostatin in addition to calcitonin, were used as experimental animals. After chronically induced hypercalcemia, somatostatin immunoreactivity conspicuously diminished coinciding with the decrease of calcitonin; somatostatin as well as calcitonin was responsive to induced hypercalcemia. After hypocalcemic tetany induced by injection of Escherichia coli L-asparaginase, C cells exhibited very intense immunoreactions for both calcitonin and somatostatin. After chronic treatment of ethylenethiourea, immunoreaction of somatostatin in C cells was the same as that of calcitonin. That is, when immunoreactivity for calcitonin remained unchanged, immunoreactivity for somatostatin was also intensive. However, when immunoreaction of calcitonin became very weak, the reaction of somatostatin was also weak. Thus, in all experimental conditions examined the alterations of immunoreactive somatostatin in C cells completely coincided with those of calcitonin. It seems likely that somatostatin in thyroid C cells exerts the synergistic effect on calcitonin action.
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Clorazepate dipotassium is rapidly decarboxylated to yield desmethyl diazepam. The antiepileptic effect of clorazepate was studied in 29 epileptic children with refractory seizures. Their ages were ranged from one year 9 months to 20 years (mean 11 years 6 months). Serum clorazepate levels were also determined in 16 patients. The mean initial dose was 0.91 mg/kg/day, and the dose was increased up to 3 mg/kg/day. Within several days after initiation of clorazepate therapy, a decrease in seizure frequency was seen in patients in whom clorazepate was effective. Excellent results (decrease in seizure frequency by more than 80%) were obtained in 7 patients (24.1%), a moderate improvement with a 50 to 80% decrease was seen in 7 patients (24.1%), and a partial improvement with less than 50% decrease was seen in 7 patients (24.1%). No benefit was seen in 8 patients (27.7%). Serum clorazepate levels in patients with excellent results were 31 to 77 ng/ml (mean 55 ng/ml), those in patients with a moderate improvement were 130 to 225 ng/ml (mean 163 ng/ml), and those in patients with a partial improvement were 142 to 518 ng/ml (mean 273 ng/ml). Serum clorazepate levels in patients with no benefit were 34 to 97 ng/ml (mean 56 ng/ml). There was no direct relationship between serum clorazepate levels and clinical response. The results of this study indicate the efficacy of clorazepate for epileptic children with refractory seizures.
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A good correlation of Doppler internal carotid blood velocity determinations with hemispheric blood flow measurements by the 133-xenon inhalation method was demonstrated in 14 epileptic patients without abnormal CT findings. The highest correlation was seen between the flow of gray matter (F1) and the internal carotid end-diastolic velocity (d) (left side r = 0.841, right side r = 0.817). As end-diastolic velocity (d) well correlated with the value obtained by the 133-xenon inhalation method, the d value was compared between 77 healthy children and 13 patients with intractable epilepsy. The mean d value of both internal carotid arteries in patients was 16.7 +/- 2.9 mm (mean +/- SD), and that of healthy children 20.9 +/- 4.3 mm, the difference being statistically significant. The low cerebral blood flow in patients might be due to multiple antiepileptic drugs administered and/or mental retardation and cerebral hypofunction related to seizures.