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Biomedical subjects

M Seino

Publications and source records attributed to M Seino.

At least 19 recordsLinked to original sources
PubMed1992

Cloning of the alpha 1 subunit of a voltage-dependent calcium channel expressed in pancreatic beta cells.

The isoforms of the alpha 1 subunits of voltage-dependent Ca2+ channels expressed in human pancreatic islets were identified by using a pair of degenerate oligonucleotide primers and the polymerase chain reaction (PCR) to amplify mRNAs encoding alpha 1 subunit-like sequences. The sequences of the PCR products indicate that islets express the heart-type alpha 1 subunit as well as a second isoform whose complete sequence has not been previously reported. The sequences of cloned cDNAs encoding the human beta-cell, or neuroendocrine-type, alpha 1 subunit indicate that it is composed of 2181 amino acids. It shares 68%, 64%, and 41% identity with the sequences of the alpha 1 subunits of rabbit heart, skeletal muscle, and brain, respectively, and is predicted to have a similar structure including four homologous domains composed of six membrane-spanning segments each. RNA blotting studies indicate that the beta-cell-type alpha 1 subunit is also expressed in brain as well as in the insulin-producing cell lines RINm5F and beta TC-3; however, it could not be detected by RNA blotting in a third cell line, HIT-T15. In situ hybridization studies revealed expression of beta-cell-type alpha 1 subunit mRNA in beta cells of rat pancreatic islets, implying that this protein may play a role in the regulation of insulin secretion.

Amino Acid Sequence↗
PubMed1992

Methodological requirements for clinical trials in refractory epilepsies--our experience with zonisamide.

1. The guidelines for clinical evaluation of antiepileptic drugs (AEDs), proposed by the International League Against Epilepsy in 1989, were scrutinized through our clinical experiences with zonisamide. 2. Seizure type, seizure frequency, number of concomitant AEDs, and type of epilepsy were found to be essential factors in quantitatively determining the efficacy of a new drug. 3. The majority of patients selected according to the guidelines consist inevitably of those with complex partial seizures with or without secondary generalization. Consequently, the efficacy of new AEDs is evaluated mainly in patients with partial seizures, and it is difficult to evaluate their efficacy in those with refractory generalized seizures, either convulsive or nonconvulsive. 4. In order to avoid such predilection, patients with various types of generalized seizures who are taking one or two conventional AEDs should account for 30 to 40% of the total patient population selected for clinical drug trials.

Adolescent↗
PubMed1992

Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex.

We investigated the effect of zonisamide, a new antiepileptic drug, on voltage-dependent Ca2+ currents in cultured neurons of rat cerebral cortex. Whole-cell voltage-clamp recordings demonstrated at least two distinct voltage-dependent Ca2+ currents: (1) a low-threshold, rapidly inactivating component, T-type Ca2+ current, which is sensitive to 100 microM Ni2+, and (2) a high-threshold, slowly inactivating (long-lasting) component, L-type Ca2+ current. Zonisamide, a new anticonvulsant effective against maximal electroshock (MES) seizures in mice reduced T-type Ca2+ current in a dose-dependent manner. The mean percentage of reduction was 59.5 +/- 7.2% at 500 microM, but zonisamide had no effect on L-type Ca2+ current. A methylated analog of zonisamide, which is ineffective against MES seizures in mice, was tested at a concentration of 500 microM, and reduced neither T-type nor L-type Ca2+ current. These findings suggest that the effects of zonisamide against MES seizures might occur through the reduction of T-type Ca2+ current. Because drugs that are effective against MES seizures are thought to prevent seizure discharge spread, T-type Ca2+ channels could underlie a cellular mechanism of spreading activity in epileptic seizures.

Action Potentials↗
PubMed1992

Long-term course of childhood epilepsy with intractable grand mal seizures.

Twenty-nine children with childhood epilepsy characterized by frequent grand mal (generalized tonic-clonic) seizures in spite of maximal doses of antiepileptic drugs and by an early onset of seizures (before 1 year of age) were followed up for more than 5 years. The children were divided into 3 groups: severe myoclonic epilepsy in infancy (SME), no SME, and intractable childhood epilepsy with generalized tonic-clonic seizures (GTC). In all the 3 groups, the grand mal seizures persisted, whereas the other types of seizures tended to disappear as the patients aged, and the prognosis for mental development was poor. In the majority of cases in all the 3 groups, the waking grand mal seizures altered to sleep grand mal seizures with aging. Two pairs of monozygotic twins with SME suggested that genetic factors play a role in this epileptic syndrome. Intractable childhood epilepsy with GTC is distinguished by the absence of other types of generalized seizures. It cannot be regarded as an epileptic syndrome, but its pathogenesis and treatment require further studies.

Child, Preschool↗
PubMed1992

Conditions for omitting invasive long-term monitoring before surgical resection in patients with temporal lobe epilepsy.

The omission of invasive long-term monitoring before surgical resection in patients with epilepsy should be permitted only for those in whom the epileptogenic focus is presumed to localize unilaterally in the mesial aspect of the temporal lobe. The localization may well be confirmed through noninvasive measures. Retrospective analyses of data obtained from noninvasive investigations (scalp-recorded and sphenoidal EEGs, neuroimages, and electroclinical seizure manifestations) were carried out in 58 patients. The localization of their epileptogenic focus was subsequently confirmed by the implantation of both intracerebral and subdural electrodes; the focus had an amygdalohippocampal origin in 41 patients and a lateral temporal origin in 17 patients. From the comparison of noninvasive findings between these two groups, we propose the following indispensable conditions for omitting an invasive evaluation: 1. Appearance of focal epileptic discharges unilaterally in the sphenoidal lead observed during the simple phase of partial seizures, or unilateral discharges with predominancy in the sphenoidal lead during the early phase of complex partial seizures. 2. Interictal spikes on scalp-recorded EEGs localizing unilaterally in the anterior region of the temporal lobe, and if bilaterally independent, presenting with unilateral predominancy in a ratio of greater than 4:1. 3. Presence of autonomic signs in the initial phase of signal symptoms. 4. Neuroimaging findings in the mesial temporal region: elongated T2 on MRI and hippocampal atrophy, or a tumorous lesion. The lateralization conforms to interictal and ictal paroxysmal EEG findings. There were 8 patients with seizure of amygdalohippocampal origin who satisfied all the indispensable condition, but not a single patient with seizures of lateral temporal origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Neuropsychological evaluation before and after surgical treatment of temporal lobe epilepsy.

We present the results of pre- and postoperative neuropsychological evaluations of 58 patients with temporal lobe epilepsy who underwent a chronic intracranial EEG monitoring and a subsequent standard anterior temporal lobectomy. Wada's test provided valuable information on the speech dominant side and on the focus localization. Some warning signs as well as verbal automatisms indicated the effect for focus localization and lateralization. The results of interictal neuropsychological tests suggested that each subgroup of TLE performed differently. A postoperative neuropsychological performance has improved in many tests that may be explained by the diminished epileptic bombardment resulting from the resection.

Adolescent↗
PubMed1992

Comparing the anticonvulsive effects of dapsone on amygdala-kindled seizures and hippocampal-kindled seizures in rats.

Dapsone, an antileprosy drug, was administered to rats with amygdala (AM)-kindled seizures or hippocampal (HIPP)-kindled seizures to elucidate its anticonvulsive efficacy. Adult male Wistar rats were subjected to kindling stimulations 2 weeks after electrode-implantation. The subjects were tested once a day for 7 successive days after inducing three generalized (stage 5) seizures to study the effects of dapsone. Dapsone had an inhibitory effect on stage 5 seizures at 12.50 mg/kg in the AM-kindled rats and at 6.25 mg/kg and 9.375 mg/kg in the HIPP-kindled rats. Thus, there was a distinct difference in the effective dose for generalized seizures between the AM-kindled rats and the HIPP-kindled rats. The inhibitory action of dapsone on stage 5 seizures may be due mainly to the elevation of the afterdischarge-triggering threshold at the stimulation site of the AM or HIPP. Such inhibitory action appears prominently at serum concentrations of about 13 micrograms/ml in AM-kindled rats and about 6 micrograms/ml in HIPP-kindled rats. The level of 6 micrograms/ml almost equals the therapeutic serum concentration of dapsone used in the treatment of leprosy.

Amygdala↗
PubMed1992

Somatostatin receptors, an expanding gene family: cloning and functional characterization of human SSTR3, a protein coupled to adenylyl cyclase.

We previously reported the cloning of two distinct somatostatin receptor (SSTR) subtypes, SSTR1 and SSTR2. Although both SSTR1 and SSTR2 bound somatostatin specifically and with high affinity, neither was coupled to adenylyl cyclase, a major cellular effector of somatostatin's actions. Here we report the cloning and functional characterization of a third member of the SSTR family. Human SSTR3 is a protein of 418 amino acids and has 45% and 46% identity with human SSTR1 and SSTR2, respectively. RNA blotting studies showed that SSTR3 mRNA could be readily detected in brain and pancreatic islets. The pharmacological properties of human SSTR3 were characterized by transiently expressing the human SSTR3 gene in COS-1 cells. Membranes from cells expressing human SSTR3 bound the somatostatin agonist [125I]CGP 23996 specifically and with high affinity, with a rank order of potency of somatostatin-28 = CGP 23996 > somatostatin-14 > SMS-201-995. Studies using cells transiently coexpressing the human dopamine D1 receptor and human SSTR3 showed that somatostatin was able to inhibit dopamine-stimulated cAMP formation in a dose-dependent manner, indicating that SSTR3 was functionally coupled to adenylyl cyclase. These results indicate that the diverse biological effects of somatostatin are mediated by a family of receptor with distinct, but overlapping, tissue distributions, unique pharmacological properties, and potentially different functions.

Adenylyl Cyclases↗
PubMed1992

The effects of intrarenal infusion of recombinant human erythropoietin on mean arterial pressure and renal hemodynamics in anesthetized rabbits.

The effects of recombinant human erythropoietin (rHuEPO) on mean arterial pressure (MAP) and renal hemodynamics were studied in anesthetized rabbits without renal failure. Intrarenal infusion of rHuEPO at a rate of 100 U/min for 30 min resulted in no change in MAP, renal blood flow, or renal vascular resistance. rHuEPO also produced no significant change in glomerular filtration rate filtration fraction, or arterial hematocrit. These results demonstrate that rHuEPO has no direct effects on MAP or renal hemodynamics in anesthetized rabbits without renal failure.

Anesthesia↗
PubMed1992

Is rolandic discharge a hallmark of benign partial epilepsy of childhood?

A longitudinal study was conducted in 89 children with partial seizures who had rolandic discharges on their interictal EEGs. The clinical characteristics and seizure prognosis were compared in children without an organic background (idiopathic) and in children with an organic background (symptomatic). Since rolandic discharges and sylvian seizures were found in the symptomatic children and their seizure outcome was favorable, it is likely that they are symptomatologically close to benign childhood epilepsy with centrotemporal spikes. Some of the symptomatic patients may have had complex partial seizures, although rolandic discharges were the principal EEG finding. Their seizure prognosis was as unfavorable as that of the patients with other symptomatic partial epilepsies. The rolandic discharges disappear in an age-related manner in idiopathic patients, but tend to persist in the symptomatic ones. The presence of rolandic discharges was not considered a hallmark of a benign outcome. Instead, the presence of sylvian seizures heralds a benign outcome of partial epilepsies regardless of whether they are idiopathic or symptomatic.

Adolescent↗