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Biomedical subjects

S Ishida

Publications and source records attributed to S Ishida.

At least 19 recordsLinked to original sources

Anticonvulsant effect of liposome-entrapped superoxide dismutase in amygdaloid-kindled rats.

Amygdaloid-kindled rats received intravenous human copper-zinc superoxide dismutase (CuZn-SOD) either in free form or entrapped within liposomes (SOD-L), at 5, 10 or 20 mg/kg. The animals were stimulated at the generalized seizure-triggering threshold 5 min, 2 h and then every 24 h after the drug was given, until 5 consecutive stage 5 seizures were induced. Free CuZn-SOD had little or no effect. However, SOD-L, particularly at 10 mg/kg, had a prolonged anticonvulsant effect, although there was great individual variation in the onset and duration of seizure suppression. This effect of SOD-L may be due to the ability of liposomes to act as a depot for the sustained release of drugs.

Amygdala

Changes of plasma des-gamma-carboxy prothrombin levels in patients with hepatocellular carcinoma in response to vitamin K.

The effect of menaquinone-4 (MK-4, vitamin K2) was studied on des-gamma-carboxy prothrombin (DCP or PIVKA-II) levels in three subjects with vitamin K deficiency and five patients with hepatocellular carcinoma (HCC) with positive DCP. The half-life of DCP in HCC patients after intravenous MK-4 administration (50 mg daily for 14 days) was determined to be 60 hours, identical to that found in vitamin K-deficient subjects who received MK-4. When a single dose of MK-4 (10 mg) was given intravenously to three patients with HCC and elevated DCP, the levels decreased with a reduction rate identical to that in vitamin K-deficient subjects for the first 1 to 3 days, followed by an increase reaching the previous level in 7 to 10 days. Changes in plasma coagulant activity were compared between subjects with vitamin K deficiency and those with HCC before and after a single dose of MK-4 (10 mg). The activity increased in DCP-positive patients with HCC as in vitamin K-deficient subjects who received the same single dose of MK-4. The increase was greater in HCC patients with higher DCP levels. These results suggest that the level of plasma DCP in patients with HCC responded to vitamin K with the same sensitivity as that in vitamin K-deficient subjects. When patients with HCC underwent effective tumor therapy (resection or arterial embolization), the reduction rate (slope of DCP decline) was found to be identical to that in vitamin K-deficient subjects given with MK-4. In patients with less effective therapy, the reduction rate was smaller, or there was an increase in DCP. These observations strongly suggest that sequential measurements of the DCP reduction rate after treatment for HCC are useful for assessing therapeutic effects.

Aged

Rapid DNA diagnosis of herpes simplex virus serotypes.

The presence of nucleotide sequences specific for each of herpes simplex virus (HSV) serotypes was demonstrated. These sequences were applied for dot DNA-DNA hybridization and for PCR for rapid DNA diagnosis of HSV infections. These sequences were found by molecular cloning of HSV-DNA fragments after digestion of DNA by KpnI enzyme. The type 1-specific sequence was found around the 5' end of BamHI B-fragment in the L region of type 1 DNA (corresponds to alpha gene 27, promoter-regulatory region) and the type 2-specific sequence was around the junction region of the L and S of type 2 DNA (corresponds to a' sequence). Both simple dot blot hybridization and PCR of HSV DNA's, employing these type-specific nucleotide sequences, were proven to be much more useful than immunofluorescence in terms of type-specific diagnosis of HSV infections.

Base Sequence

An ESR-CT imaging of the head of a living rat receiving an administration of a nitroxide radical.

Three-dimensional ESR imaging of a living rat has been performed by an L-band ESR system, which is composed of an L-band ESR spectrometer, a field gradient coil, and a data processor. The imaging was carried out by Lauterbur's method. A nitroxide, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (Carbamoyl-PROXYL), was used as an imaging agent in saline solution at a concentration of 0.2 M and administered intraperitoneally to obtain a constant concentration in the head for about an hour. It took about 40 min to obtain one set of ESR-CT images. The cross-sectional images were made, both as coronal and horizontal images. In the images of the rat head the nitroxide-rich region was clearly distinguished from the deficient region. The nitroxide-deficient areas corresponded well to the brain of the rat.

Animals

Effects of postnatal electroshock convulsions on epileptogenesis of the amygdala and hippocampus in adult rats.

Adult rats which received repeated electroshock convulsions (ESCs) during postnatal development underwent electrical kindling of the amygdala (AM) and hippocampus (HIPP). Completion of kindling, especially AM kindling, was significantly faster in the groups with ESCs from the neonatal to late infantile age than in the control group. It is discussed that especially the late infantile age in the postnatal development was supposed to play an important role in the faster kindling brought about by postnatal convulsions and that the faster kindling was due in part to abbreviation of the partial seizure process. However, the neonatal ESC group showed significantly delayed completion of HIPP kindling.

Amygdala

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

Effects of vagal stimulation on cesium-induced early afterdepolarizations and ventricular arrhythmias in rabbits.

BACKGROUND: Previous evidence has shown that increased sympathetic tone enhances the cesium chloride (Cs)-induced early afterdepolarizations (EADs) and ventricular tachycardias (VTs). METHODS AND RESULTS: We assessed the effects of vagal stimulation on Cs-induced EADs and ventricular arrhythmias in the rabbit heart. Monophasic action potentials (MAPs) of the left ventricular endocardium were recorded simultaneously with surface ECG. Two protocols were used: 1) While in their intrinsic sinus rhythm, 11 rabbits were given three intravenous Cs injections (1 mM/kg) 20 minutes apart, and the effects of vagal stimulation on the ventricular arrhythmias thus induced were examined. 2) Under constant atrial pacing (cycle length, 250 msec), EAD amplitude was measured after Cs injection (1 mM/kg) without (five rabbits, control group) or with (four rabbits, vagal stimulation group) vagal stimulation. We observed the following. 1) Cs produced EADs and VTs of polymorphic (PVT) and monomorphic (MVT) types. During PVT, the take-off potential of repetitive premature action potentials in MAP recordings was about the same as the peak level of EADs, and during MVT, the take-off potential was the level of full repolarization. Vagal stimulation suppressed PVT but not MVT. Vagal stimulation after spontaneous termination of MVT restarted MVT of the same morphology at a rate much slower than the preceding sinus rate. 2) EAD amplitude was significantly smaller in the vagal stimulation group than in the control group. CONCLUSIONS: The results suggest that PVT originated from triggering by EADs, whereas MVT was of different origin, and that vagal stimulation suppressed PVT by decreasing the amplitude of EADs.

Action Potentials

Dose-dependent pharmacokinetics of glycyrrhizin in rats.

The dose-dependent pharmacokinetics of glycyrrhizin (GLZ) was investigated by measuring drug disappearance from plasma and biliary excretion in rats. The decline in plasma concentration was biexponential after an i.v. dose of 5, 10, 20, or 50 mg/kg. Dosage, however, had a marked effect on the pharmacokinetics, with a greater-than-proportional increase in area under the plasma concentration curve (AUC) at doses of 20 and 50 mg/kg, even though the increase was proportional at doses of 5 and 10 mg/kg. There was also a significant increase of the steady-state distribution volume (Vdss), as well as significant decreases in total body (CLtot) and biliary (CLB) clearances, at 20 and 50 mg/kg from those at 5-10 and 5-20 mg/kg, respectively. The AUC, Vdss, and renal clearance (CLR) at a given dose showed no significant difference between rats with and without bile fistulas. The plasma unbound fraction (fp) (0.006-0.026) increased with increasing plasma GLZ concentration over the observed range (2-900 micrograms/ml). No significant change in Vdss for unbound GLZ was observed between the doses, indicating that the distribution of GLZ into tissues is not changed by an increase in dose. On the other hand, a dose dependency in CLtot for unbound GLZ was observed and confirmed to be attributed to dose dependency in CLB for unbound GLZ since there was no significant difference in CLR or metabolic clearance for unbound GLZ between the doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Glycyrrhizin binding site on human serum albumin.

The binding site of glycyrrhizin (GLZ) on human serum albumin was detected through competitive displacement experiments with GLZ and ibuprofen (IBU) (diazepam site), warfarin (WAR), salicylate (SAL) (digitoxin site), or deoxycholic acid (DCA) by means of an ultrafiltration technique. The specific binding of GLZ was subject to competitive inhibition by IBU, WAR, SAL, or DCA (1 or 4 mM). The extent of displacement was in the order of: DCA greater than IBU greater than WAR greater than SAL. Conversely, the specific bindings of WAR and DCA and the low-affinity bindings of IBU and SAL were subject to competitive inhibition by GLZ (1 or 4 mM). The extent of inhibition by GLZ was in the order of DCA greater than IBU greater than WAR not equal to SAL. In addition, the low-affinity IBU binding and the specific DCA binding showed mutual competitive inhibition at 4 mM, with almost identical displacements. It was concluded that the specific GLZ binding site on human serum albumin may be located mostly within the low-affinity IBU binding site area (probably the same as the specific DCA binding site area) and partially within the specific WAR binding site area and the low-affinity SAL binding site area.

Binding Sites

[Application of the limulus amebocyte lysate test to measurement of endotoxin in therapeutic human plasma protein fraction. Comparison with the rabbit pyrogen test].

We applied the limulus amebocyte lysate (LAL) test to the detection of bacterial endotoxins in therapeutic human plasma protein fraction (PPF) and compared the LAL-test with the rabbit pyrogen test. Two endotoxin-specific LAL-reagents were used for the colorimetric method and turbidimetric kinetic method. The amounts of added endotoxin to the PPF were correctly estimated by either method. The results of four independent assays for the 53 samples of PPF corresponded well with each other (correlation coefficient: 0.851-0.959, regression coefficient: 0.898-1.151). The amounts of endotoxin in the PPF estimated by the LAL-test significantly correlated with the rise of body temperature in rabbits (correlation coefficient: 0.547-0.642, and 0.911-0.934 for the endotoxin added samples). These results suggest that the LAL-test could be used as an alternative method for the rabbit pyrogen test to PPF.

Animals

Mexiletine and disopyramide suppress ventricular premature contractions (VPC) irrespective of the relationship between the VPC and the underlying heart rate.

The effects of mexiletine (300 mg/day, 24 patients) and disopyramide (300 mg/day, 20 patients) on ventricular premature contractions (VPCs) were studied using a 24-hour ambulatory electrocardiogram. The VPC frequency was evaluated as a function of the underlying heart rate (HR). The VPC-HR correlation was classified into 2 major types, depending on whether the frequency of the VPC increased with the increased HR (positive type) or not (nonpositive type). The effects of the drugs were assessed based on the VPC-HR correlation and on the percent reduction of the VPC frequency. Mexiletine and disopyramide significantly decreased the frequency of the VPCs of both the positive and nonpositive types. Each drug was assumed to be effective when the percent reduction of the VPC frequency exceeded 70%. Mexiletine (300 mg/day) was 58.5% effective in positive type patients and 33.3% effective in nonpositive type patients, with a total efficacy of 45.8%. Disopyramide was effective in 50% of total cases with 44.4% in positive type patients and 54.5% in nonpositive type patients. However, the efficacy of these drugs on the 2 different types of VPCs was the same statistically. The findings strikingly contrasted those obtained with diltiazem and atenolol, which predominantly suppressed VPCs of the positive type which share similar characteristics with a triggered activity in vitro. We conclude that the mode of action of class I antiarrhythmics on the VPCs differs from that of class II or IV antiarrhythmics, as viewed from the VPC-HR relationship, and that the difference probably comes from the different arrhythmogenesis for positive and nonpositive types of VPCs, in addition to the different electrophysiological actions of mexiletine and disopyramide.

Cardiac Complexes, Premature

[A patient with gigantic heterotopic gray matter with epileptic seizures].

We report a patient with partial seizure and gigantic heterotopic gray matter. A 23-year-old young man was admitted to our hospital with complaints of frequent epileptic seizures and psychiatric symptoms. There was psychomotor delay in infancy. At the age of 4 years, afebrile convulsions appeared on several occasions. Seizures characterized by a lapse of consciousness started at the age of 13 years. He often stayed in a fantasy world and became very emotional at such time. Cranial CT demonstrated an irregularity in the wall of right lateral ventricle and disappearance of the posterior horn on the same side. This lesion, adjacent to that wall, had a signal intensity that was similar to that of the gray matter on each sequence in MRI. Histopathology of this lesion showed a number of large and small neurons. Therefore, heterotopic gray matter was diagnosed. MRI demonstrated wide cortices suggesting polymicrogyria in the right parietal lobe. Complex partial seizures with eye deviation to the left were recognized. Interictal EEG showed frequent high voltage spikes in the right temporal, fronto-temporal and parieto-occipital areas independently. Therefore, epileptic foci were thought to exist in or around those lesions.

Adult

[Minocycline-induced pneumonia and pleurisy--a case report].

A 24-year-old woman had been treated with minocycline (MINO) for acute upper airway infection. Two days after the start of MINO therapy, she developed fever, cough, dyspnea, and bloody sputum. Her chest X-ray film revealed bilateral pleural effusions and butterfly shadow, and chest computed tomography revealed markedly increased density of pulmonary tissue in the central lung fields. Arterial blood gas analysis demonstrated severe hypoxemia. The characteristics of the pleural effusion were exudative. Based on the history of her illness and the chest X-ray findings, in addition to the laboratory findings of leukocytosis with eosinophilia and increased serum IgE, drug-induced pneumonia was suspected. Once the treatment with MINO was discontinued, her symptoms, laboratory data, and chest X-ray findings improved rapidly. Microscopic examination of a transbronchial lung biopsy specimen showed increased alveolar septal thickness with formation of Masson's bodies. Although the result of a lymphocyte stimulation test was negative for MINO, the skin test was positive for immediate response. Because of her clinical course, the possibility of induction by other drugs was excluded. This patient was therefore diagnosed to have MINO-induced pneumonia. To date, ten cases of MINO-induced pneumonia have been reported, but no previous case was associated with pleurisy.

Acute Disease

Mutants of Dictyostelium discoideum with altered carbohydrate moieties of contact site A.

Mutants of Dictyostelium discoideum were isolated and found to be defective in the epitope recognized by the monoclonal antibody 120 against the carbohydrate moieties of an integral membrane glycoprotein, contact site A, with the apparent molecular mass of 80 x 10(3). One mutant, HG764, did not express any contact site A and had lost cell contact resistant to EDTA. The others, including HG794, expressed a 68-kDa form of contact site A. In comparison with the parental strain HG592, HG794 showed weaker EDTA-resistant cell contact and the same degree of EDTA-sensitive cell contact. This suggested that the moieties which HG794 lacked were involved in EDTA-resistant cell contact. The 68-kDa contact site A in HG794 could be labeled with wheat germ agglutinin and incorporated [35S] sulfate. The modB mutant HL220 also expresses 68-kDa contact site A, although it cannot be labeled with wheat germ agglutinin. Therefore, the mutants HG794 and HL220 were compared by a complementation test. The diploid strain DG701 expressed 80-kDa contact site A and showed the same degree of EDTA-resistant cell contact as strain HG592. In its EDTA-resistant cell contact, HG794 was stronger than HL220. These results suggest that HG794 is a new mutant, and that there might be at least two processes in the glycosylation of 68-kDa contact site A to the 80-kDa form. The carbohydrate moieties recognized by monoclonal antibody 120 and by wheat germ agglutinin might be involved in EDTA-resistant cell contact.

Animals