Biomedical subjects
Publications and source records attributed to N Kasai.
Lysozyme from Streptomyces globisporus has been crystallized in a form suitable for X-ray structure analysis using ammonium sulfate as a precipitant. The crystals are hexagonal, space group P6(1)22 (P6(5)22) with unit cell dimensions: a = b = 129 A, c = 143 A. There are three or four molecules per asymmetric unit. The crystals diffract X-rays to at least 3.0 A resolution.
The resistance in mice against Listeria infection was augmented by treatment with recombinant human tumor necrosis factor (TNF). To elucidate this phenomenon, we examined the effect of TNF on macrophage activation. TNF-treated macrophages had listericidal activity in vitro and superoxide anion production. In addition, macrophage migration was inhibited in the presence of TNF. Therefore, activation of macrophages by TNF was similar to activation by macrophage-activating factor or macrophage-migration-inhibitory factor.
Squamous differentiation of thyroid carcinoma was studied clinicopathologically and immunohistochemically in 29 autopsy cases. Tumor cell nests with squamous differentiation (CNSD), which histologically resembled squamous cell carcinoma, were found in 6 cases (20.7%). All of these 6 cases with CNSD had areas of undifferentiated carcinoma, representing 31.6% of 19 cases with undifferentiated carcinoma, and all but one case also showed coexisting papillary carcinoma. The CNSD were histologically associated with undifferentiated carcinoma in 5 cases, and with papillary carcinoma in one case; the CNSD were occasionally intermingled with these types of carcinoma, and there were findings suggesting a histological transition between the CNSD and undifferentiated carcinoma or papillary carcinoma. Immunohistochemistry revealed that all the CNSD were reactive with antibodies for keratin and vimentin, whereas thyroglobulin and desmin were not expressed. It was concluded that the CNSD examined here were most probably due to extensive squamous differentiation (squamous metaplasia) in undifferentiated carcinoma and papillary carcinoma. In addition, the present results may explain the fact that cases diagnosed solely as squamous cell carcinoma sometimes show a prognosis similar to that of undifferentiated carcinoma, and may well represent extensive squamous differentiation in such tumors rather than true squamous cell carcinoma of the thyroid.
We produced a computer program that draws pedigree charts for inbred strains of animals such as mice or rats. This program is composed of four subprograms, which are (1) inputting the data, (2) drawing pedigree charts, (3) listing the data which have been input, and (4) backup of the system and the data. Pedigree charts and lists of data can be displayed on a TV screen and printed out on the papers. Using this program, we drew the pedigree charts of the inbred strains of rats which we are maintaining by brother-sister inbreeding in our institute and found that there were three sublines in one of the strains, WKAH/Hkm, because of unsuitable maintenance. This program is very convenient to draw the pedigree charts and useful for checking the maintenance of inbred strains or the strains of animal models of human diseases.
The usefulness of continuous intracranial pressure (ICP) monitoring and the correlation between ICP and electroencephalographic findings were investigated in a 6-year-old boy with acute encephalitis. On admission he was comatose in a decerebrate posture. ICP was continuously monitored by the epidural transducer and controlled with hyperventilation, fluid restriction and administration of mannitol, glycerol and pentobarbital to keep below 20 mm Hg. The inotropic agents such as dopamine and dobutamine were also given to maintain the cerebral perfusion pressure (CPP) at 50 mm Hg or greater. At the same time with ICP monitoring, EEG records were obtained with scalp electrodes at monopolar T3-A1 and T4-A2 regions according to the 10-20 international system on an analog tape simultaneously with a data recorder. The records were digitized at 50 samples/sec, and the high-order auto-regressive (AR) power spectrum was calculated with a minicomputer PFU-1200 (Fujitsu Co Ltd.). At pressures greater than 25 mm Hg in ICP, the total power of the high-order AR activity of EEG was apparently decreased. The results indicated that the AR power spectral analysis of EEG is sensitive method for obtaining valuable information regarding the electrical brain activity and intracranial pressure.
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The relation of chemical structure to local Shwartzman activity of lipid A preparations purified by thin-layer chromatography from five bacterial strains was examined. Two lipid A fractions from E. coli F515--Ec-A2 and Ec-A3--exhibited strong activity, similar to that of previous synthetic E. coli-type lipid A (compound 506 or LA-15-PP). The Ec-A3 fraction contained a component that appeared to be structurally identical to compound 506, and the main component of Ec-A2 fraction was structurally similar to compound 506 except that it carried a 3-hydroxytetradecanoyl group at the C-3' position of the backbone in place of a 3-tetradecanoyloxytetradecanoyl group. Free lipid A (12 C) and purified lipid A fractions, Ec-A2 (12 C) and Ec-A3 (12 C), respectively, obtained from bacteria grown at 12 C, exhibited activity comparable to Ec-A2 or Ec-A3. In these preparations, a large part of the 3-dodecanoyloxytetradecanoyl group might be replaced by 3-hexadecenoyloxytetradecanoyl group. Salmonella minnesota R595 free lipid A also contained at least two active lipid A components as seen in E. coli lipid A, but the third component corresponding to the synthetic Salmonella-type lipid A (compound 516 or LA-16-PP) exhibited low activity. A lipid A fraction, Cv-A4 from Chromobacterium violaceum IFO 12614, which was proposed to have two acyloxyacyl groups at the C-2 and C-2' positions with other acyl groups, exhibited weaker activity than the free lipid A or LPS. The purified lipid A fractions from Pseudomonas diminuta JCM 2788 and Pseudomonas vesicularis JCM 1477 contained an unusual backbone with 2,3-diamino-2,3-dideoxy-D-glucose disaccharide phosphomonoester, and these lipid A (Pd-A3 and Pv-A3) exhibited strong activity comparable to the E. coli lipid A. Thus, the present results show that the local Shwartzman reaction can be expressed by partly different lipid A structures in both hydrophilic backbone and fatty acyl residues; when they have the same backbone the potency varies markedly depending on the structure of the acyl residues.
Tumor necrosis factor (TNF)-inducing activities of lipid A preparations from P. diminuta and P. vesicularis, which contain mainly 2 mol of 2,3-diamino-2,3-dideoxy-D-glucose and 1 mol of nonglycosidic phosphate as the backbone component and have partly different fatty acid compositions, were examined. TNF was induced by injecting various lipid A fractions into mice that had previously been sensitized with Mycobacterium bovis BCG vaccine. A major component of lipid A of both strains, referred to as A3 fraction, exhibited stronger TNF-inducing activity than A2 fraction having incomplete acyl residues. The removal of ester-linked fatty acyl groups by mild hydrazinolysis of the P. diminuta lipid A results in a marked decrease of the activity. These results suggest that the structure of the hydrophobic part, including the amide-linked acyloxyacyl group(s), of the lipid A molecule play an important role in inducing TNF in the sera of mice.
Early cancers are small in size and localized; many of them have no infiltration or metastasis. It has been gradually clarified what procedure of reduced operation can be feasible without fail to its radicalness to what type of early cancer, as a result of detailed studies on the findings concerning the development of early cancers as well as evaluations of recurrent cases and distant results. Techniques of reduced operation for the treatment of cancers of the thyroid, mammary glands, female reproductive organs and stomach have been improved as early cancer patients increase in number and our understanding of the pathogenesis of early cancers is promoted.
Clinicopathologic findings on small thyroid carcinomas measuring 10 mm or less in diameter were analyzed in 78 thyroidectomied cases. The authors divided small thyroid tumors into two subgroups according to diameter: 0 less than or equal to 5 mm (classified as minute carcinoma) and 5 less than 0 less than or equal to 10 mm (classified as tiny carcinomas). Characteristics including sex, age, histologic type, extrathyroid invasion, and lymph node metastasis were examined in each subgroup. In patients with minute carcinoma, very few incidences of extrathyroid invasion and lymph node metastasis were found. However, these involvements, especially lymph node metastasis, were found more frequently in patients with tiny carcinoma. The incidence of cervical lymph node metastasis was 13% in minute carcinoma and 59% in tiny carcinoma. (P less than 0.01). These findings suggest the need for more careful observation and treatment of tiny carcinomas, especially with respect to lymph node metastasis. In accordance with World Health Organization (WHO) classification, the histologic types of thyroid carcinoma were classified into papillary and follicular carcinomas. The papillary carcinoma and follicular carcinoma ratios were compared between the two subgroups. The discovery rate of follicular carcinoma was significantly higher in minute carcinoma than in tiny carcinoma (P less than 0.005). This suggests that the papillary carcinoma/follicular carcinoma ratio (p/f) increases as the size of the carcinoma increases, and that follicular carcinoma is the "seed," or initial form, of thyroid cancer. The female-male ratio in small thyroid cancer suggests that there is no sex difference in carcinogenesis but that there is more probability for cancer development in the thyroid in women.
Crystals of the hydrophilic, catalytic domain (30 kDa) of pig liver NADH-cytochrome b5 reductase solubilized by the protease (cathepsin D) have been grown in a solution of polyethylene glycol by the vapor-diffusion procedure. The crystals belong to the orthorhombic system, space group P2(1)2(1)2(1) with unit-cell dimensions of a = 87.1, b = 73.2, and c = 49.0 A. The asymmetric unit contains one molecule of the enzyme. The x-ray diffraction patterns extend to 2.0-A resolution. On the other hand, the intact enzyme (35 kDa) containing the hydrophobic membrane-binding domain solubilized by the detergent (Triton N-101) has been crystallized also from the polyethylene glycol solution. The crystals are needle-shaped and still too small for x-ray diffraction study.
Lipid A that contains mainly 2,3-diamino-2,3-dideoxy-D-glucose, phosphate and fatty acids in the molar ratio 2:1:5-6 was found in Pseudomonas diminuta lipopolysaccharide. The lipid A was considered to have a diamino-sugar disaccharide structure that carries a nonglycosidic phosphomonoester group and amide-bound acyloxyacyl and 3-hydroxy fatty acyl groups. The lipopolysaccharide exhibited endotoxic activities including lethal toxicity, pyrogenicity, local Shwartzman activity, body weight-decreasing toxicity and Limulus activity. The free lipid A was also endotoxic.
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An ELISA, using viable bovine lymphosarcoma cells, was developed to detect tumor-associated antigens (TAA) expressed on lymphosarcoma cells from cows with enzootic bovine leukosis (EBL). Monoclonal antibodies (MAB) against TAA were used. Using viable-cell ELISA, MAB reacted with tumor cells from 9 cows with EBL, but not with peripheral blood lymphocytes from 10 clinically normal cows. Titers of MAB against tumor cells from 1 cow with EBL were 2,048 (direct immunofluorescence assay), 8,192 (flow cytometry), 2,048 (fixed-cell ELISA), and 16,384 (viable-cell ELISA). Viable-cell ELISA was the most sensitive method for detection of TAA. Reactivities of 7 MAB to tumor cells from cows with EBL were compared between viable-cell ELISA and a complement-dependent antibody cytotoxicity test. Of 5 MAB with no cytotoxic activity against tumor cells, 3 were reactive against tumor cells from the same cow, as determined by viable-cell ELISA, with titers ranging from 128 to 2,048.
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This paper reports the presence of GM2 ganglioside containing N-glycolylneuraminic acid (NeuGc) in human colon cancer tissues. GM2(NeuGc) was detected by two-dimensional thin layer chromatography (2d-TLC)/enzyme-immunostaining using affinity-purified chicken antibody against GM3(NeuGc) and horseradish peroxidase-conjugated rabbit anti-chicken IgG antibody. Like usual GM2 ganglioside containing N-acetylneuraminic acid (NeuAc) isolated from Tay-Sachs brain, GM2(NeuGc) in colon cancer could be converted into GM3(NeuGc) by human kidney beta-N-acetylhexosaminidase A in the presence of a GM2-specific activator protein isolated from guinea pig kidney. Three of 7 specimens of Hanganutziu-Deicher (HD) antigen-positive human colon cancer tissues so far examined expressed this unique ganglioside. In order to detect and determine specifically GM2(NeuGc) on human colon cancers, specific antibody against GM2 (NeuGc) has been prepared by immunizing chickens. By a sensitive TLC/immunostaining method using the antibody, the amounts of the antigen were determined to be 0.3-3% of total lipid-bound sialic acid. NeuGc-containing gangliosides were also detected in meconium and fetal intestinal tissues. Three species of antigenic gangliosides in pooled meconium were tentatively identified as GM3(NeuGc), sialylparagloboside and sialylhexaosylceramide on the basis of their migration positions on 2d-TLC and the results of endo-beta-galactosidase treatment. GM3(NeuGc) was the sole HD-active ganglioside in fetal intestinal tissue from one of 3 individuals tested; the other two showed no HD-active ganglioside at all. GM2(NeuGc), however, could not be detected in either meconium or fetal tissues so far examined, suggesting that this unique ganglioside is a tumor-specific antigen, at least for human intestinal tissues.
A total of five cases of atypical adenomas of the thyroid were clinicopathologically examined to clarify their malignant potential and incidence. These adenomas showed both structural and cellular atypia when compared with follicular adenoma of the usual type, A follow-up study after surgery revealed neither metastasis nor postoperative recurrence. Therefore it has been concluded that an atypical adenoma of the thyroid can be regarded as a benign neoplasm.