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Biomedical subjects

K Kuroda

Publications and source records attributed to K Kuroda.

At least 307 records · Page 17Linked to original sources

[Treatment using CDDP and radiation therapy in treating bladder tumor].

Combination therapy consisting of cis-diamine-dichloroplatinum (CDDP) and radiotherapy was used to treat bladder cancer. The subjects were 20 patients with bladder cancer we experienced since September, 1986. They were between 33 and 83 years old and consisted of 13 males and 7 females. Among the histotypes and grades, there were 3 cases of G2, 7 of G2-G3 and 10 of G3 metastatic epithelial carcinoma. The classification of primary tumors was T2 in six cases, T3a in 12 cases and T4 in two cases. In 12 cases where the bladder was preserved, this therapy was performed after TUR biopsy or TUR, and the effects were evaluated after observation periods of 5-17 months. Side effects caused by CDDP were anorexia in 15 cases, nausea and vomiting in 10 cases, leukopenia in 10 cases and thrombocytopenia in four cases. Those caused by the radiotherapy were diarrhea in seven cases and skin disorders in six cases. All of these side effects were mild and the patients recovered spontaneously.

Adult↗

[A case of venous hemangioma in the mediastinum].

A thirteen-year-old boy was admitted to our hospital for further evaluation of abnormal shadow on chest film with a low grade fever. Laboratory findings revealed within normal value except for CRP. Chest film showed a smooth round mass in right middle mediastinum. In the CT scan, it was a well-defined round mass with low density in contact with sternum. With angiography, it had no relation to the great vessels. At operation, a coagulation was on the surface of a tumor. The tumor adhered to sternum and parietal pleura firmly and to aortic arch and thymus partly. But it was removed with ease "en bloc". It was dark red in color and upper part of was cystic, and lower massive. The tumor measured 9.5 x 5.0 x 5.5 cm and weighted 320 g. Histopathological findings demonstrated venous hemangioma proved by Masson trichrome stain.

Adolescent↗

KT5926, a potent and selective inhibitor of myosin light chain kinase.

KT5926, (8R*,9S*,11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-14-n-propoxy-2,3 ,9, 10-tetrahydro-8,11-epoxy, 1H,8H, 11H-2,7b,11a-triazadibenzo[a,g]cycloocta[cde] trinden-1-one, was found to be a potent and selective inhibitor of myosin light chain kinase. The compound inhibited both Ca2+/calmodulin-dependent and -independent smooth muscle myosin light chain kinases to a similar extent. The inhibition was not affected by the concentration of calmodulin. Kinetic analyses showed that the mode of inhibition was of the competitive type with respect to ATP (Ki, 18 nM) and of the noncompetitive type with respect to myosin light chain (Ki, 12 nM). These results indicated that KT5926 directly interacted with the enzyme at the catalytic site. KT5926 also inhibited other protein kinases, but with relatively high Ki values; the values for protein kinase C, cAMP-dependent protein kinase, and cGMP-dependent protein kinase were 723, 1200, and 158 nM, respectively. Ca2(+)-ATPase, Na+/K(+)-ATPase, hexokinase, and 5'-nucleotidase were not inhibited by KT5926 at less than 10 microM. The effect of KT5926 on serotonin secretion and protein phosphorylation induced by platelet-activating factor or phorbol ester was examined in rabbit platelets. KT5926 inhibited the phosphorylation of a 20-kDa protein but had no effect on the phosphorylation of a 40-kDa protein, thereby indicating that the compound exerts its selective inhibition of myosin light chain kinase in intact cells. The compound inhibited serotonin secretion induced by platelet-activating factor, but its potency was significantly less than that of K-252a, (8R*,9S*,11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9, 10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b, 11a-triazadibenzo[a,g]cycloocta [cde]trinden-1-one, which inhibited the phosphorylation of both the 20-kDa protein and the 40-kDa protein. Phorbol ester-induced secretion was not suppressed by KT5926. These results provide the evidence that both the 20-kDa protein phosphorylation by myosin light chain kinase and the 40-kDa protein phosphorylation by protein kinase C substantially contribute to the secretion response in platelets.

Alkaloids↗

[The effects of the intracerebroventricular administration of cimetidine on hemodynamics in conscious rats: relation to the sympathetic nervous system].

Histamine H2-receptor antagonists administered into the central nervous system have been shown to increase arterial pressure (AP) in anaesthetized animals (Paakkari et al., 1982). Few studies have been reported on the effects of centrally administered cimetidine (CIM), one of the histamine H2-receptor antagonists, in conscious animals. However, the mechanism of the pressor action of histamine H2-receptor antagonists remains unclear. The present study was designed to investigate the hemodynamic effects of intracerebroventricular (i.c.v.) CIM and the interaction between the sympathetic nervous system and histamine receptor system in conscious rats. Male Wistar rats weighing 200 gr were prepared for the experiment under a conscious and minimally restricted state. Five micrograms of i.c.v. saline (SAL-ICV group, n = 5) did not produce significant changes in mean arterial pressure (MAP) or heart rate (HR) (MAP from 85.6 +/- 3.4 to 86.0 +/- 4.3 mmHg and HR from 395.0 +/- 13.9 to 395.2 +/- 8.2 bpm, respectively). Twenty micrograms of i.c.v. phenoxybenzamine (POB-ICV group, n = 6) decreased MAP from 95.8 +/- 4.1 to 85.2 +/- 3.1 mmHg, -10.7 +/- 2.2 mmHg as delta MAP, and increased HR from 392.5 +/- 8.5 to 435.3 +/- 13.9 bpm, +42.8 +/- 6.8 bpm as delta HR. Two-hundred micrograms of intravenous (i.v.) POB (POB-IV group, n = 5) also decreased MAP from 96.0 +/- 4.3 to 71.0 +/- 5.1 mmHg, -25.0 +/- 2.7 mmHg as delta MAP, and increased HR from 395.8 +/- 10.5 to 473.0 +/- 12.4 bpm, +77.2 +/- 7.6 bpm as delta HR. The changes in MAP and HR were much greater in the POB-IV group than those in the other two groups. The subsequent i.c.v. administration of 250 micrograms of CIM induced an increase in MAP (+19.4 +/- 1.7 mmHg as delta MAP) and a decrease in HR (-36.4 +/- 3.1 bpm as delta HR) in the SAL-ICV group, which continued for at least 30 minutes producing peak effects 2 minutes after i.c.v. administration of CIM. However, an elevation of MAP caused by i.c.v. CIM was much more inhibited in the POB-ICV group than in the POB-IV group (+2.5 +/- 0.7 mmHg as delta MAP in the POB-ICV group and +5.0 +/- 1.3 mmHg as delta MAP in the POB-IV group, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Lung cancer coexisting with bullae.

Scattered reports have suggested the association of cancer with bullous disease. We report herein, two surgical cases of lung cancer arising from bullae. Both the patients were males who smoked heavily and the generation of cancer was found simultaneously with the discovery of the bulla. At thoracotomy, it was found that the cancer had arisen from the firm, scarred and contracted area adjacent to the bulla wall. On the basis of this experience and review of the literature, it is suggested that physicians should always pay careful attention to the generation and complication of cancer while treating bullous disease in heavy smoking individuals.

Adenocarcinoma↗

Propulsive force of Paramecium as revealed by the video centrifuge microscope.

Using the video centrifuge microscope we constructed, we observed the behavior of Paramecium cells in a solution of graded densities under centrifugal acceleration. Beyond 300g, they not only gather in the zone where the density is closest to theirs, but also orient themselves with their longitudinal axis parallel to the direction of centrifugation turning their anterior ends toward either centripetal or centrifugal direction. Since all of them retain still active swimming capacity, it is possible to calculate their propulsive force from the difference in density between theirs (1.04 g cm-3) and that of the upper or lower layer which they can reach. The propulsive force of single Paramecium cells thus obtained was calculated to be about 7 x 10(-4) dyn.

Animals↗

Effect of pisiferic acid and its derivatives on cytotoxicity macromolecular synthesis and DNA polymerase alpha of HeLa cells.

1. Seventy-seven derivatives of pisiferic acid (2), an antimicrobial diterpenoid, were tested for cytotoxicity against HeLa cells and 9 derivatives were found to show cytotoxicity at less than 2 micrograms/ml dose (IC50). 2. Hydrophobicity was revealed to be an important factor for cytotoxicity of the derivatives. 3. Compound 2 inhibited predominantly DNA synthesis in HeLa cells as compared with RNA and protein synthesis. 4. No direct interaction between 2 and nucleic acid bases was indicated by a u.v. spectral method. 5. Several of the pisiferic acid species showed inhibitory action on HeLa DNA polymerase alpha, and the inhibitory activity was about 1/20 of aphidicolin.

Cell Survival↗

Synthesis of biologically active influenza virus hemagglutinin in insect larvae.

The hemagglutinin of influenza (fowl plague) virus was expressed in larvae of Heliothis virescens by using recombinant Autographa californica nuclear polyhedrosis virus (AcNPV) as a vector. Animals were infected with the recombinant virus either by parenteral injection or by feeding. For oral uptake, recombinant virus occluded in polyhedra obtained from cultured Spodoptera frugiperda cells after coinfection with authentic AcNPV was used. Immunohistological analyses of infected animals revealed that the hemagglutinin was expressed only in those tissues that are also permissive for the replication of authentic AcNPV. These tissues included hypodermis, fat body, and tracheal matrix. After oral infection, hemagglutinin was also detected in individual gut cells. The amount of hemagglutinin synthesized in larvae after parenteral infection was 0.3% of the total protein, compared with 5% obtained in cultured insect cells. The hemagglutinin was transported to the cell surface and expressed in polarized cells only at the apical plasma membrane. It was processed by posttranslational proteolysis into the cleavage products HA1 and HA2. Oligosaccharides were attached by N-glycosidic linkages and were smaller than those found on hemagglutinin obtained from vertebrate cells. Hemagglutinin from larvae expressed receptor binding and cell fusion activities, but quantitation of the hemolytic capacity revealed that it was only about half as active as hemagglutinin from vertebrate or insect cell cultures. Chickens immunized with larval tissues containing hemagglutinin were protected from infection with fowl plague virus. These observations demonstrate that live insects are able to produce a recombinant membrane protein of vertebrate origin in biologically active form.

Administration, Oral↗

Inhibitory effect of fumaric acid on 3'-methyl-4-(dimethylamino)azobenzene-induced hepatocarcinogenesis in rats.

Fumaric acid (FA) suppressed the carcinogenesis in the liver of rats fed 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB), and a study was performed to examine the effect of FA on deoxyribonucleic acid (DNA) synthesis and subcellular structures of hepatocytes under the anticarcinogenic regimens. Male Donryu strain rats were given 3'-Me-DAB by being fed a diet containing 0.06% 3'-Me-DAB for 50 d. They were then given a diet containing 1% FA and drinking water containing 0.025% FA for 53 to 69 weeks. Hepatocytes were isolated from the liver by the collagenase perfusion method and placed in culture, and their activity for DNA synthesis was measured in terms of the incorporation of [3H]dThd into DNA. An enhanced DNA synthesis of hepatocytes was noted in the rats given FA, indicating that FA enhanced the proliferation of hepatocytes to counteract the carcinogenic effect of 3'-Me-DAB. An electron microscopic examination indicated that the distribution of subcellular organella was almost normal in the FA-treated hepatocytes.

Animals↗

[Study on testicular tissue in animals with congenital hormone deficiency].

Of 3 kinds of animals with congenital hormone deficiency, i.e., mouse with Snell pituitary dwarfism (dw) in which hypoplasia of the pituitary anterior lobe is seen from embryonal stage and which almost lacks in growth hormone (GH), prolactin (PRL), thyroid stimulating hormone (TSH) and adrenocorticotrophic hormone (ACTH); mouse with little dwarfism lacking only in GH (lit); and mouse with congenital primary hypothyroidism in which the thyroidal gland shows hypoplasia, thyroxine (T4) in blood is not measurable and, conversely, TSH level is abnormally high (hyt), the males of dw/dw and hyt/hyt have been proved to be infertile, but it is little known about lit/lit. After performing early recovery experiment by administering GH + T4 to dw/dw, GH to lit/lit and T4 to hyt/hyt from birth, the testicles of 40-day-old mice were investigated morphologically in the normal control group, non-treated group and treated group in order to clarify the relation between hormones and the sperm-generating potency. The total number of sperm-generating cells, which consist of spermatogonia, spermatocytes, spermatids and sperms, showed remarkable decreases, compared with each control group, and the decrease in total cell number was improved favorably by treatment with hormone. In comparison with the control groups, significant decreases were showed in the spermatid number for the dw/dw group, sperm number for the lit/lit group, and spermatid and sperm numbers for the hyt/hyt group. These results indicate that GH and T4 have a potential effect on sperm-generating function.

Animals↗

A surgical case of giant mediastinal tumor in a child associated with rib deformity.

A five-year-old boy was admitted, complaining of a persistent cough. Chest film showed a smooth round mass in right mediastinal region and deformity of 6th rib. CT studies revealed the presence of a well-defined mass with low density. Pulmonary arteriography demonstrated hypovascularity in right pulmonary field. Preoperative diagnosis was a benign neurogenic tumor originated from intercostal nerve located at the posterior mediastinum. At operation, a large round smooth mass was found adhered to chest wall and, in part, parietal pleura, and it was removed completely. The sixth rib with deformity was also resected partly. The specimen measured 9.5 x 5.0 x 4.0 cm and weighed 175 g. Histopathological findings demonstrated that the tumor proved to be ganglioneuroma.

Child, Preschool↗

Mechanism of the damaging effect of dermatomyositis mononuclear cells on cultured human skin fibroblasts.

We further studied the mechanism of action of peripheral mononuclear cells (MNC) from patients with dermatomyositis (DM) to strikingly suppress fibroblast proliferation in vitro. Attachment of MNC to fibroblasts was closely related to the mechanism. Most of attached MNC were activated T lymphocytes. Conditioned medium alone did not show any effects on fibroblasts. T8 positive cells and monocytes were essential to elicit the effect. Study of 51Cr release demonstrated that DM MNC augmented cytolysis of fibroblasts. It might be concluded that DM MNC possess T lymphocyte mediated cytotoxicity on fibroblasts and this causes the inhibition of fibroblast proliferation.

Adolescent↗

Uranyl-ion catalyzed oligonucleotide synthesis from adenosine-5'-phosphorazolide. The effect of azoles as nucleotide activating groups.

Polymerization of azole-activated nucleotides was conducted in an aqueous medium with uranyl ion as a catalyst. Imidazole, 2-methylimidazole, 4-methylimidazole, triazole, nitrotriazole, tetrazole and 2-methylbenzimidazole were used as an activation group for adenylic acid. Oligoadenylates up to the hexadecamer were obtained in high total yield under the optimum condition. The azole compounds had large effect on the rate of polymerization, the yield and the chain length of the resulting oligoadenylates.

Adenine Nucleotides↗

[A case of retroperitoneal abscess accompanying pregnancy].

A 40-year-old pregnant woman, who suffered a continuous episode of fever and anemia since the 26th week of pregnancy, was referred to our clinic for evaluation of her left flank pain and tumor. As retroperitoneal tumor was suspected by retrograde pyelography, sonography and CT, translumbar tumorectomy was performed under general anesthesia. The histological diagnosis was retroperitoneal abscess.

Abscess↗

[Detection of Chlamydia trachomatis in urethra of patients with urogenital infection].

Between January, 1984 and August 1986, we examined 151 male patients with urogenital infections including 114 cases of urethritis, 18 cases of epididymitis, 19 cases of prostatitis at the outpatient clinic of the department of urology, Toho University's Ohmori Hospital. The positive rate for Chlamydia trachomatis from the urethra based on cell cultures was 29.0%, (30.5% for urethritis, 27.8% for epididymitis, and 21.1% for prostatitis). The positive rate for non-gonorrheal urethritis was 33.0% and chlamydia infections were complicated by gonorrheal urethritis in 23.3% of the cases. The mean age of the patients with positive Chlamydia trachomatis was 31.9 years. The route of infection in 77.8% of the cases was sexual intercourse the most common cause of which was infection from a prostitute in 62.1% of the cases. The latent period was in most cases from 2-3 weeks.

Adult↗