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Biomedical subjects

N Kasai

Publications and source records attributed to N Kasai.

At least 163 records · Page 9Linked to original sources

Structure of ferricytochrome c' from Rhodospirillum rubrum at 6 A resolution.

The structure of a ferricytochrome c' extracted from Rhodospirillum rubrum has been determined at 6 A resolution by the X-ray crystallographic method. The crystals, obtained by dialyzing the protein solution against polyethylene glycol 4000, belong to the hexagonal space group P6(1). Two heavy atom derivatives were obtained by soaking the native crystals in K2PtCl6 and CH3HgCl solution. The phases calculated by the multiple isomorphous replacement method gave an overall figure of merit of 0.90 at 6 A resolution. The resulting electron density map showed the molecular boundary clearly, and gave molecular dimensions of 50 X 25 X 30 A for a monomer molecule. From visual examination of this map, the cytochrome c' from Rhodospirillum rubrum has a similar chain-folding pattern to the cytochrome c' from Rhodospirillum molischianum, the structure determination of which has already been carried out.

Crystallography↗

Fatty acid composition and Shwartzman activity of lipopolysaccharides from oral bacteria.

The composition and the nature of the linkage of fatty acids and the Shwartzman activity of lipopolysaccharide (LPS) preparations derived from oral gram-negative bacteria including Bacteroides gingivalis, Bacteroides loesheii, Eikenella corrodens, Fusobacterium nucleatum, and Actinobacillus actinomycetemcomitans were examined. 3-Hydroxylated and nonhydroxy fatty acids of various chain lengths were found in all of the LPS preparations. All nonhydroxy fatty acids were found to be ester-bound, and part of the 3-hydroxy fatty acids in the LPS of B. gingivalis, E. corrodens, F. nucleatum, and A. actinomycetemcomitans were shown to be involved in ester linkage. It was also suggested that the hydroxy group of the ester-bound 3-hydroxy fatty acid of the LPS of F. nucleatum and A. actinomycetemcomitans is at least partly substituted by another fatty acid, but in the LPS of B. gingivalis and E. corrodens it is not. The main amide-linked fatty acid of the LPS of B. gingivalis, E. corrodens, F. nucleatum, and A. actinomycetemcomitans was 3-hydroxyheptadecanoic, 3-hydroxydodecanoic, 3-hydroxyhexadecanoic, and 3-hydroxytetradecanoic acid, respectively. The results of the Shwartzman assay showed that the E. corrodens LPS was the most active among the preparations tested, and that the Shwartzman toxicity of Bacteroides LPS is extremely low.

Actinobacillus↗

Synthetic lipid A with endotoxic and related biological activities comparable to those of a natural lipid A from an Escherichia coli re-mutant.

A synthetic compound (506), beta (1-6) D-glucosamine disaccharide 1,4'-bisphosphate, which is acylated at 2'-amino and 3'-hydroxyl groups with (R)-3-dodecanoyloxytetradecanoyl and (R)-3-tetradecanoyloxytetradecanoyl groups, respectively, and has (R)-3-hydroxytetradecanoyl groups at 2-amino and 3-hydroxyl groups, exhibited full endotoxic activities identical to or sometimes stronger than those of a reference lipid A from an Escherichia coli Re-mutant (strain F515). Endotoxic activities tested include pyrogenicity and leukopenia-inducing activity in rabbits, body weight-decreasing toxicity in normal mice, lethal toxicity in galactosamine-sensitized mice and chicken embryos, and the preparation and provocation of the local Shwartzman reaction in rabbits. Compound 406, a synthetic counterpart of a biosynthetic precursor of lipid A molecule, showed by contrast only weak activities in all of the above assay systems except for the lethality in galactosamine-loaded mice. This finding strongly suggests that the presence of acyloxyacyl groups at the C-2' and C-3' positions of the disaccharide backbone is one of the most important determinant structures of the lipid A molecule for exhibition of strong biological activities characteristic of lipopolysaccharide and its lipid A moiety. The activities of the corresponding 4'-monophosphate (compound 504) and 1-monophosphate (505) analogs were considerably less than those of the parent molecule 506 and the reference F515 lipid A. Regarding other biological activities, not only compound 506 but also compounds 504, 505, and 406 showed definite activities, sometimes comparable to those of F515 lipid A and other reference natural products. These are the activation of Tachypleus tridentatus amoebocyte clotting enzyme cascade and human complement via the classical pathway, mitogenic and polyclonal B-cell activation of murine splenocytes, stimulation of peritoneal macrophages in a guinea pig, enhancement of migration of human blood polymorphonuclear leukocytes, and induction of a serum factor that is cytostatic and cytocidal to L-929 cells in Mycobacterium bovis BCG-primed mice. Relative potencies of test synthetic compounds depended on the assay systems and varied from one system to another. Dephospho-compound 503 lacked most of the biological activities that were definitely observed with phosphorylated compounds, probably because of its insolubility. This study demonstrates the successful chemical synthesis of an E. coli-type lipid A.

Adjuvants, Immunologic↗

[Early invasive squamous cell carcinoma of the tongue--report of a case].

A 65-year-old woman with early invasive squamous cell carcinoma of the tongue is reported. Atypical but not definitely malignant epithelium was detected by cytology, although the gross appearance of the glossal lesion looked like early invasive squamous cell carcinoma. On the surgical material, the basal and para-basal cell layers were occupied by cancer, but the upper portion of the epidermis from the prickle cell layer through the surface of the mucosa was histologically benign. In such cases, to obtain the correct diagnosis on cytology, repeated examinations as well as using a sharp instrument like a curatte are necessary.

Aged↗

[A case of anaplastic transformation of thyroid carcinoma in the cervical lymph node metastasis].

A case of a well-differentiated thyroid carcinoma with an area of anaplastic transformation in the cervical lymph node metastasis is reported. The combination of postoperative radiotherapy with chemotherapy, followed by total thyroidectomy and left radical neck dissection was undertaken for the cervical lymph node metastasis with anaplastic progression, and the patient is living, well and tumor-free more than two years after surgery. This case suggests that neck dissection is necessary for well-differentiated thyroid carcinoma with lymph nodes metastasis to prevent the development of anaplastic transformation in the future.

Carcinoma, Papillary↗

A new crystal form and preliminary crystallographic data for ferricytochrome c' from Rhodospirillum rubrum.

A new crystal form of ferricytochrome c' from the photosynthetic bacteria, Rhodospirillum rubrum, has been obtained by dialysing protein solution against polyethylene glycol 4000. The crystals belong to the space group P61 (or its enantiomorph P65) with unit cell dimensions: a = b = 51.63 A and c = 155.39 A. The asymmetric unit contains one dimer molecule of 28,000 molecular weight and the solvent content of the unit cell is approximately 38%.

Crystallization↗

Autoradiography of ganglioside antigens separated by high-performance thin-layer chromatography with their antibodies.

An improved method is described for the detection of ganglioside antigens with the antibodies on thin-layer chromatograms. The method involves the following steps: Separation of gangliosides on a high-performance thin-layer chromatographic plate, application of antibody solution, and detection of bound antibody with [125I]staphylococcal protein A. Using specific antibodies against gangliosides GM4, GM1, GD3, and asialo GM1 ganglioside, the method allowed positive identification of these antigens on thin-layer plates. It also provides a convenient means of assessing the specificity of an anti-glycolipid antibody.

Antibodies↗

Hepatic drug-metabolizing enzyme system and endotoxin tolerance: structural requirement of LPS in induction of an early tolerance.

The alteration of hepatic drug-metabolizing enzyme activities in mice given Salmonella endotoxin by single or multiple intraperitoneal injections was investigated. An essentially the same biphasic, early and late phase, endotoxin tolerance was observed in the animals receiving a single injection of endotoxin or repetitive daily injections. The results of reciprocal cross tolerance tests using lipopolysaccharide and free lipid A preparations derived from Salmonella minnesota, Salmonella typhimurium, E. coli, Pseudomonas aeruginosa, and Chromobacterium violaceum suggested that lipid A moiety plays an important role in the induction of early endotoxin tolerance to endotoxin response.

Animals↗

[Case of occlusion of vertebrobasilar artery after subarachnoid hemorrhage due to rupture of posterior inferior cerebellar artery aneurysm].

An autopsied case of ruptured saccular aneurysm at the junction of posterior inferior cerebellar artery and vertebral artery with which the aneurysm and basilar artery were occluded was reported. A 20-year-old female was admitted to our hospital because of consciousness disturbance and convulsion. CT scan revealed subarachnoid hemorrhage. Four vessel angiography did not show any aneurysms nor arteriovenous malformations but revealed occlusion of vertebrobasilar artery. Continuous ventricle drainage was performed but she died 5 days after the onset. On autopsy, a ruptured saccular aneurysm at the junction of right vertebral and posterior inferior cerebellar arteries, and occlusion with thrombosis of vertebrobasilar artery were found. We discussed how the aneurysm and main arteries were embolized just after the attack of subarachnoid hemorrhage. It is considered that the severe increased intracranial pressure in posterior fossa after subarachnoid hemorrhage and decreased blood pressure caused hemostasis of ruptured aneurysm while spreading the thrombosis in main trunks of vertebrobasilar artery.

Adult↗

Poorly differentiated carcinoma of the thyroid. A clinicopathologic entity for a high-risk group of papillary and follicular carcinomas.

The relationship between histologic type and survival of 258 thyroid malignancies has been analysed. A new clinicopathologic entity, poorly differentiated carcinoma of the thyroid, is proposed. Papillary and follicular carcinomas of the thyroid showed no significant difference in survival rates. Both tumors were histologically separated into well differentiated and poorly differentiated carcinomas, so that thyroid cancer, deriving from follicular cells, was divided into well differentiated, poorly differentiated, and anaplastic carcinomas. The characteristic histology of poorly differentiated carcinoma was the presence of solid, trabecular and/or scirrhous patterns. Poorly differentiated carcinoma was found in 13.6% of all thyroid malignancies, and its prognosis was worse than that of well differentiated carcinoma. The differences of survival rates among well differentiated, poorly differentiated and anaplastic carcinomas were statistically significant. Prognostic data support the suggestion that the clinicopathologic entity of poorly differentiated carcinoma is of value in determining management and survival of thyroid cancer patients.

Adenocarcinoma↗

The monoclonal antibody A2B5 is specific to ganglioside GQ1c.

The neural specific monoclonal antibody A2B5 was found to interact with GQ1c but not with Gq1b, nor did it interact with other glycolipids such as GM1, GD1a, GD1b, GT1a, GT1b and GA1. Since GQ1c is enriched in embryonic chicken brains but not in adult chicken brains, this antibody should be useful as a tool in assessing the role of GQ1c in neuronal maturation.

Animals↗

Immunobiological activities of synthetic lipid A analogs and related compounds as compared with those of bacterial lipopolysaccharide, re-glycolipid, lipid A, and muramyl dipeptide.

Thirteen acylated and phosphorylated derivatives of beta-1,6-linked glucosamine disaccharide (lipid A analogs), which were synthesized after the structural model of Salmonella-type lipid A, and seven similar derivatives of glucosamine monosaccharide (lipid A-related compounds) were studied for their immunobiological activities. These included mitogenicity and polyclonal B cell activation enhancement of migration of monocytes and polymorphonuclear leukocytes derived from human peripheral blood, stimulation of guinea pig peritoneal macrophages, activation of human complement, and stimulation of serum antibody production and induction of delayed-type hypersensitivity against ovalbumin in guinea pigs. Comparisons were made with lipid A, RE-glycolipid, lipopolysaccharide of natural sources, and a well-known synthetic adjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine. Some of the lipid A analogs were found to manifest the mitogenic, polyclonal B cell-activating macrophage-stimulating, complement-activating, and immunostimulating activities, although the observed activities were generally far less than those of natural products in intensity and efficiency. Other immunobiological effects exhibited by most of the synthetic lipid A analogs were the enhancement of migration of monocytes and polymorphonuclear leukocytes. It is premature to draw definite conclusions on structure-activity relationships, since a few compounds which were active in some assay systems were scarcely active in other assays. However, an indisputable fact was that beta-1,6-glucosamine disaccharide 1 alpha,4'-diphosphate, which carries two amide-bound (R)-3-hydroxytetradecanoyl and three ester-bound tetradecanoyl residues, and thus has the structure most closely resembling natural lipid A among test compounds in this study, was definitely active in all of the present assay systems. However, its potency was generally much less than natural products. Some of glucosamine monosaccharide derivatives, especially N-(R)-3-[(R)-3-hydroxytetradecanoyloxy]tetradecanoyl glucosamine, also exerted all of the in vitro activities described above. This fact suggests that a glucosamine disaccharide structure may not necessarily be a prerequisite as far as the in vitro immunobiological activities tested are concerned.

Acetylmuramyl-Alanyl-Isoglutamine↗

[Combination chemotherapy (BEAM regimen) for head and neck cancer].

Twenty-eight patients with head and neck cancer were treated with a combination of bleomycin, cyclophosphamide, adriamycin, and methotrexate (BEAM regimen), consisting cyclophosphamide 600 mg/body and adriamycin 40 mg/body on day 1, bleomycin 15 mg/body and methotrexate 20 mg/body on days 1 and 5. Dose modifications were performed according to patient's conditions. Of 18 evaluable patients, 3 patients showed a complete response and 3 patients showed partial response with an overall response rate of 33.3%. In this study, the patients who had already been treated with surgery, radiotherapy, or chemotherapy produced good results. The median duration of response was 4.0 months in the complete responders, and 1.0 month in the partial responders. The median survival was 12.7 months in the complete responders 1.4 months in the partial responders, and 5.6 months in non-responders. The most frequent major toxic effects were leukopenia (66.7%), nausea (60%), and alopecia (57.3%) in the patients receiving the maximum dose of the drugs. Careful monitoring of patients is imperative during this treatment.

Adult↗