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Biomedical subjects

K Takada

Publications and source records attributed to K Takada.

At least 613 records · Page 34Linked to original sources

Behavioral effects of benzodiazepine antagonists in chlordiazepoxide tolerant and non-tolerant rats.

Rats were trained to respond under 3-min fixed-interval schedules of food presentation, and effects of the benzodiazepine-receptor ligands, flumazenil, 2-(4-methoxy-phenyl)-pyrazolo[4,3-c]quinolin-3(5H)-one (CGS 9895), 3-carbo-t-butoxy-beta-carboline (beta-CCtB), and beta-carboline-3-carboxylic acid ethyl ester (beta-CCE) were assessed before and after the induction of tolerance to chlordiazepoxide. Before daily administration of chlordiazepoxide, none of the antagonists produced appreciable effects on rates of responding up to doses of 32.0 mg/kg i.p. beta-CCE was the only antagonist studied at a higher dose (100.0 mg/kg i.p.), which decreased response rates. After 23 days of daily chlordiazepoxide administration (oral doses started at 10 and increased to 100 mg/kg/day by the 17th day), dose-effect curves for chlordiazepoxide were shifted to the right by about one-half log unit. Subjects were also more sensitive to the flumazenil, CGS 9895, and beta-CCtB, however, since these drugs produced only small effects in non-tolerant subjects, precise estimates of the degree of the shift in dose-effect curves could not be estimated. However, there were differences in the changes in the dose-effect curves induced by chlordiazepoxide tolerance. These results suggest differences in mechanism of action of antagonists in tolerant and non-tolerant subjects, and further that the sensitivity that is induced to antagonists in tolerant subjects is not conferred equally to all drugs having benzodiazepine antagonist activity.

Animals↗

Identification of an enhancer-type sequence that is responsive to Z and R trans-activators of Epstein-Barr virus.

We studied the regulatory region of the open reading frame BHRF1 of Epstein-Barr virus (EBV) DNA that was responsive to two trans-activators (Z and R) encoded by the BZLF1 and BRLF1, respectively. The 200-bp sequence, nucleotide numbers 53,617 to 53,817 on the EBV map, was sufficient for conferring responsiveness to Z and R. This 200-bp sequence also enhanced expression of the chloramphenicol acetyltransferase (CAT) gene from the simian virus 40 promoter in response to both Z and R, even when inserted downstream of the cat gene. The results indicate that the Z and R response sequence upstream of the BHRF1 has the properties of an enhancer.

Base Sequence↗

Porencephaly and hydranencephaly: a neuropathological study of four autopsy cases.

Four autopsy cases of porencephaly and hydranencephaly were evaluated clinico-pathologically. The patients showed profound mental retardation, convulsive seizures and spastic quadriplegia. The life spans were much shorter in the hydranencephalic cases. Pathologically, the cerebral cortex in the vicinity of the parenchymal defects often showed an abnormal cytoarchitecture, which appeared to be closely correlated with superficial glial proliferation. Several neurofibrillary tangles were found in the nucleus basalis of Meynert and the locus ceruleus in a 23-year-old porencephalic patient, and so-called grumose degeneration of the dentate nucleus in three patients, including a 2-month-old hydranencephalic boy. It is suggested that extensive cerebral defects may cause neuronal degeneration of the subcortical nuclei.

Adult↗

Synthesis of palmitoyl derivatives of insulin and their biological activities.

In order to improve the lipophilicity of peptides, bovine insulin was chosen for the chemical modification using palmitic acid. The N-hydroxysuccinimide ester of palmitic acid was used for attachment to terminal amino groups, and p-methoxybenzoxycarbonyl azide was used for protection of the glycine-A1 amino terminus. We obtained two purified derivatives of insulin, B1-monopalmitoyl- and B1,B29-dipalmitoyl-insulin, which were confirmed to be more lipophilic than the parent insulin on high-performance liquid chromatography (HPLC). The hypoglycemic effects of both products were measured in rats after intravenous and intramuscular injections. The mono derivative was more active than the di derivative and produced a longer effect duration than the native insulin after intravenous injection. The derivatives were also shown to be less immunoreactive as judged by an enzyme immunoassay.

Amino Acids↗

Serum levels and biochemical characteristics of human ovarian carcinoma-associated antigen defined by murine monoclonal antibody, CF511.

The murine monoclonal antibody (Mab) against human common epithelial ovarian carcinoma, CF511, was generated by immunising mice with human fetal tissue extract from early first trimester, followed by booster injection of an ovarian cancer cell line. Mab CF511 recognised the 600 kDa sialylated glycoprotein as different from previously known tumour associated-marker antigens. Distribution of the Mab CF511-recognised antigen (CF511 antigen) in various tissues and sera was investigated. In immunohistochemical analysis, Mab CF511 reacted strongly with tumour cells of ovarian serous, clear cell, endometrioid and undifferentiated carcinoma and partially with those of mucinous carcinoma. Mab CF511 also reacted with breast carcinoma as well as lung carcinoma. In normal tissues, Mab CF511 cross-reacted with only five tissues, namely lung, breast, thyroid gland, fallopian tube and uterus. Serum levels of CF511 antigen were tested by ELISA inhibition using Mab CF511. This assay showed the circulating CF511 antigen levels to be elevated in 25 of 36 sera from patients with various clinical stages of common epithelial ovarian carcinoma compared to three of 47 and three of 111 sera from patients with other benign gynaecological diseases, including ovarian cysts, uterine fibroids with or without endometriosis and normal healthy subjects, respectively. For the relation between antigen levels and clinical stages of common epithelial ovarian carcinoma, greater than 34.0% ELISA inhibition was detected in 100% of patients with advanced stages (FIGO III and IV) compared with in 35.3% with early stages (FIGO I and II) patients. While patients with breast carcinoma (100%) and lung carcinoma (100%) also had elevated circulating CF511 antigen levels, patients with hepatoma, colorectal carcinoma and gastric carcinoma had no detectable elevation of antigen. Although the test showed a high degree of specificity, the detection of an elevated CF511 antigen level would not be so helpful in distinguishing patients with ovarian carcinoma from those with either breast carcinoma or lung carcinoma. These data suggest that CF511 antigen is a useful new ovarian tumour marker for diagnosis and management of the disease.

Adult↗

Ultrasonographical and morphological examination of subependymal cystic lesions in maturely born infants.

The clinical data and development of 8 cases with subependymal cysts detected on neurosonography in the neonatal period were studied, and the prognosis was found to vary. Also, clinico-pathological examination of 15 autopsied cases of congenital subependymal cysts (SEC) was performed, with immunohistochemical staining involving neuron-specific enolase in three cases, which revealed that congenital SEC are often complicated by various degrees of brain and heart anomalies, and suggested that SEC might occur in a wide gestational age range, with various causes. Therefore, it is important in the future to determine the agents which cause destruction of the subependymal germinal matrix.

Brain Diseases↗

A case of cross stimulation.

Cross stimulation in a dual chamber pacing system, in which the atrial stimulus intermittently captured the right ventricle, occurred immediately after pacemaker implantation in a 71-year-old man. It was prevented temporarily by reducing the pacing rate so that P wave synchronous ventricular (VDD) pacing resulted and by reducing the output of the atrial circuit from 5 to 4 volts. Cross stimulation disappeared spontaneously 14 days after surgery.

Aged↗

Cytotoxicity of galactose, tyrosine and methionine in cultured suckling rat hepatocytes: relation to liver immaturity.

Monolayers of suckling rat hepatocytes cultured for 24 hours were treated with galactose, I-tyrosine and I-methionine. The purpose was to study the reasons for the clinical improvement of patients with neonatal hepatitis after dietary restriction of these nutrients. Galactose, tyrosine, and methionine was cytotoxic on suckling rat hepatocytes, yet had no effect on adult rat hepatocytes. Furthermore, the pretreatment of suckling rat hepatocytes with dexamethasone ameliorated the cytotoxicity and induced a differentiation of the cells. These results suggested that the cytotoxicity resulted from the immaturity of suckling rat hepatocytes and therefore dietary restriction of galactose, tyrosine and methionine might be a useful treatment for patients with neonatal hepatitis.

Animals↗

Synchronous and sequential activation of latently infected Epstein-Barr virus genomes.

A lymphoid cell system was established that can induce the prompt and synchronous activation of latent Epstein-Barr virus (EBV) genomes and thus allows the identification of viral genes that are activated sequentially depending on their functions. With this system, we proved that disruption of EBV latency is initiated by activation of four EBV genes and that protein synthesis is not required prior to activation of latent EBV. The system should be an in vitro model for studying the mechanism of herpesvirus latency.

Blotting, Northern↗

Enteric solid dispersion of cyclosporin A (CyA) having potential to improve availability of CyA in rabbit.

The availability of cyclosporin A (CyA) administered as an enteric solid dispersion preparation of which the composition is CyA:HCO-60:HP-55 = 1:2:8 was evaluated in rabbits. The additives are surfactant (polyoxyethylated, 60 mumol, castor oil derivative, HCO-60) and enteric coating material (hydroxypropylmethyl cellulose phthalate, HP-55), which are generally used as pharmaceutical additives. Both the systemic and lymphatic availabilities of CyA from this solid preparation were measured in rabbits after intrastomach administration, 7 mg CyA/kg, and were compared with those from conventional oily solution, Sandimmun. The mean systemic availability of CyA from the solid preparation was 57% which is about 1.5 times greater than that obtained from Sandimmun. The amounts of CyA transferred into the thoracic lymphatics within 12 h from solid dosage form and Sandimmun are 0.62 +/- 0.16(S.D.)% and 0.13 +/- 0.05% of the administered CyA dose. These results support the usefulness of the new solid dosage form of CyA.

Animals↗

Enteric solid dispersion of ciclosporin A (CiA) having potential to deliver CiA into lymphatics.

Solid dispersions composed of three components, ciclosporin A (CiA), surfactant (HCO-60) and a pharmaceutical additive, were prepared. As an additive, cellulose acetate phthalate (CAP), methacrylic acid and methacrylic acid methylester copolymer (Eudragit L-100) and hydroxypropylmethylcellulose phthalate (HP-55), which are generally used as enteric coating materials, were employed. The dissolution behavior of CiA from these enteric solid-dispersion system was studied according to the paddle method of JP XI in comparison with that of Sandimmun, an olive oily CiA solution as a reference. Solid dispersion of CiA preparation did not dissolve in the 1st test fluid (pH 1.2) in 2 h. In the 2nd fluid (pH 6.8), about 80% of CiA was dissolved within 12 min, though the dissolution rate was dependent on both the quality and quantity of the additives. An in vivo systemic and lymphatic availability study was performed with rats whose carotid artery and thoracic lymph duct were cannulated. After intrastomach administration of each CiA preparation to rats at a dose of 7 mg/kg, blood and lymph samples were collected for 6 h. One of the HP-55 preparations gave the highest plasma CiA level, Cmax = 0.99 +/- 0.20 (S.E., n = 4) micrograms/ml, and also showed the highest lymphatic availability, the percentage of dose delivered to the lymphatics in 6 h was 1.98 +/- 0.10% and the maximum lymph CiA level was 76.8 +/- 12.86 micrograms/ml. Lymphatic availability of CiA from Sandimmun was 0.78 +/- 0.11% and the peak plasma CiA level was 0.46 +/- 0.10 microgram/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Targeted and sustained delivery of aclarubicin to lymphatics by lactic acid-oligomer microsphere in rat.

We examined targeted delivery of an anticancer drug, aclarubicin (ACR), to the lymphatic system in rats by encapsulation of the drug in microsphere (MS) prepared from nontoxic and biodegradable L-lactic acid-oligomer with an average molecular weight (Mw) of 3600. ACR was released at an almost constant rate from two kinds of ACR-MSs having different size (1-5 microns and less than 1 micron) over 20 d in phosphate-buffered saline at 37 degrees C. The intraperitoneal administration of both ACR-MSs (dose of ACR; 5 mg/kg) to rats sustained an almost constant ACR level (300-400 and 400-600 ng/ml) in the lymph of the thoracic duct during over 10 d, and the ACR level in the blood was extremely low, although intraperitoneal injection of ACR alone gave lower level of ACR in the lymph than in the blood level within 12 h.

Aclarubicin↗

Is recombinant human granulocyte colony-stimulating factor (G-CSF) orally available in rats?

Oral availability of recombinant human granulocyte colony-stimulating factor (G-CSF) was investigated in rats by measuring the blood total leucocyte (BTL) counts. Oral test G-CSF solution was prepared with 10% HCO-60 (polyoxyethylated, 60 mumol, castor oil derivative), 1% DK ester (sugar ester) or 10% MYS-40 (polyethyleneglycol monostearate), in which the G-CSF concentration was 500 or 250 micrograms/ml. Each test solution was injected into the duodenum of three rats at the G-CSF dose level of 300 or 600 micrograms/kg, and BTL counts were monitored for 48 h. All of the test G-CSF solution raised the BTL levels within 24 h after injection. In particular, the HCO-60 solution increased the BTL levels over 2 times as compared to the predose level at 600 micrograms/kg dose and the effect was apparently dose-dependent. A short-term study suggested that the effect of G-CSF on the BTL level appeared at the fastest at about 5 h after administration of HCO-60 test solution, 300 micrograms/kg. In view of the pattern of BTL dynamics obtained after i.v. injection of HCO-60 solution at 25 and 50 micrograms/kg, the increase of BTL levels observed after oral administration of the HCO-60 solution is considered to be due to the orally supplied G-CSF.

Animals↗

HLA and sarcoidosis in the Japanese.

One hundred fourteen patients with sarcoidosis, who were diagnosed as having sarcoidosis histologically, have been typed for HLA class 1 (A, B, and C) and class 2 (DR and DQ) antigens. Controls consisted of 478 healthy Japanese subjects. The frequencies of HLA-A1, HLA-Bw46, HLA-Cx46, HLA-DRw8, HLA-DRw9, and HLA-DRw52 were significantly increased in sarcoidosis compared to control subjects, but only four patients were positive for HLA-A1. Increased frequencies of HLA-Bw46 and HLA-Cx46 were thought to be attributable to linkage disequilibrium with HLA-DRw8. Patients with HLA-DRw52 were the most frequent (84 cases of 113). No significant differences were observed between HLA-DRw52-positive and HLA-DRw52-negative patients in their clinical features, but all of the patients with muscular involvement (six cases) were positive for HLA-DRw52. Among patients positive for HLA-DRw52, those with HLA-DR5 showed a significantly better clinical course and earlier onset of the disease than those with HLA-DRw8. These results suggest that HLA antigens may play an important role in the pathogenesis of sarcoidosis.

Adult↗

Subacute thyroiditis associated with systemic multi-organ disorders.

Subacute thyroiditis is generally thought to be a self-limited inflammatory disease of the thyroid gland. This paper describes serial observations on the clinical course of a typical patient with subacute thyroiditis. This patient showed specific features of destructive thyrotoxicosis with increases in the serum levels of acute phase reactants and in the erythrocyte sedimentation rate. She also showed signs of liver dysfunction [slightly increased alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (gamma-GTP), and leucine aminopeptidase (LAP)], slight anemia, glucose intolerance, increased pancreatic enzymes, splenomegaly, and an increase in peripheral Leu 7 positive (NK/K) cells. These abnormalities all improved with recovery from disease. These findings indicate that in this patient with subacute thyroiditis inflammation is not limited to the thyroid gland but also involves the liver, pancreas and spleen. Thus the subacute thyroiditis in this patient may be a systemic multi-organ disease.

Female↗

[Case of temporomandibular joint ankylosis in childhood. Treatment and follow-up for 12 years].

An ankylosis of temporomandibular joint (TMJ), which may be defined as the disease with the limitation of the movement of TMJ resulted from inflammations or traumas followed by fibrosis or ossification, could lead to the disturbance of mandibular development in childhood. In this report, we have experienced a case of unilateral TMJ ankylosis suspected to be caused by forceps delivery in 7-years old boy. The patient called on our hospital suffering from severe trismus and facial asymmetry. Following the conservative treatment, the operative relief of the ankylosis was performed with the procedure of the amputation of coronoid processus and condylar neck at the age of 14. Then orthodontic treatment was carried out to build a stabilized occlusion at 7 months after the operation. Five years follow-up observation elucidated that mandible developed normally without any recurrence. Judging from both clinical aspects and cephalometric analysis the result is very satisfying not only functionally but esthetically.

Ankylosis↗

Sensitivity analysis for GMDH correction modeling of MKG signals.

The purpose of this paper is to propose application of sensitivity analysis to the GMDH modeling for the correction of distorted kinesiographic signals recorded for inter-lattice points in space, and to evaluate its correction accuracy to estimate coordinates of an inter-lattice point, i.e., an observation, distorted coordinates of a nominal lattice point which is most adjacent to a given inter-lattice point is searched. Variations, i. e., differences, between distorted coordinates of the observations and their concomitant nominals are calculated. Instead of substituting kinesiographic measurements of the nominal and its neighbouring eight lattice points, the sum of the observation and its corresponding variation is substituted into the GMDH model which has been employed for the correction of distorted measurements of the aforementioned lattice point. A stereotaxic device is developed to stimulate mandibular jaw movement and determine position of a magnet transducer of a mandibular kinesiograph (MKG). Nominals of 3-D coordinates of the inter-lattice points are determined by the stimulator together with simultaneous recording of distorted output signals from the MKG which correspond to the nominals. Distorted signals are corrected on the basis of the sensitivity-oriented correction modeling. A mean estimation error of 0.16 mm (s. d., 0.19 mm) is determined for 24 inter-lattice coordinates. Thus, the application of sensitivity analysis to the GMDH modeling is confirmed to be effective.

Humans↗