Ultrasonic appearance of the liver in hepatic venous outflow obstruction (Budd-Chiari syndrome): a case of pseudohepatic infarct associated with Behçet's disease.
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Behcet Syndrome↗
Biomedical subjects
S Kusumoto
Publications and source records attributed to S Kusumoto.
Adjuvant and antitumour activities of synthetic lipid A analogues.
The biological activities of synthetic glycolipids, which were chemically synthesized and based on the structure of lipid A of the lipopolysaccharide (LPS) from Escherichia coli, were examined with special reference to their adjuvant activity on the induction of delayed-type hypersensitivity, activity on the induction of tumour necrotic factor (TNF) and tumour regressive activity on line 10 hepatoma in strain 2 guinea pigs. Among them, a compound structurally corresponding to free E. coli lipid A (compound 506) as well as LPS exhibited potent adjuvant activity in the induction of delayed-type hypersensitivity in guinea pigs and TNF inducing activity in the sera of mice which were presensitized with Propionibacterium acnes. Compound 506 showed potent lethal toxicity in the intravenous administration of BALB/c mice presensitized with P. acnes. The regressive activity on line 10 hepatoma was observed by the multiple intralesional injection of squalane-treated compounds 504 and 505 in strain 2 guinea pigs.
Adjuvants, Immunologic↗
Structure-activity relationship of lipid A: comparison of biological activities of natural and synthetic lipid A's with different fatty acid compositions.
To investigate the structure-activity relationships, various biological activities, including pyrogenicity, lethal toxicity, elicitation of Shwartzman reaction, mitogenicity and tumor necrosis factor (TNF)-inducing activity, were compared among natural and synthetic lipid A's differing in fatty acid composition. In all these tests, natural lipid A's from Escherichia coli and Salmonella minnesota and synthetic LA-15-PP, which carries 3-hydroxy- and 3-acyloxy-tetradecanoyl groups at the 2, 3 and 2', 3' positions, respectively, showed the strongest activities among the tested lipid A's. In contrast, LA-16-PP, in which the amide-bound 3-hydroxytetradecanoic acid at position 2 of LA-15-PP is replaced by 3-hexadecanoyloxytetradecanoic acid, exhibited lower activity than LA-15-PP and natural lipid A's. Although LA-16-PP has been assumed to have a typical Salmonella lipid A structure (and, in fact, it has a structure corresponding to one of the components of Salmonella lipid A), the activity of this synthetic compound was not comparable to that of natural Salmonella lipid A. LA-17-PP, in which tetradecanoic acid is the sole fatty acid component, exhibited relatively strong mitogenicity and TNF-inducing activity, but very low pyrogenicity. The activities of LA-18-PP, which has ester-bound tetradecanoic acid and amide-bound 3-hydroxytetradecanoic acid, were lower than those of LA-17-PP. The results indicate that the differences in fatty acid composition of lipid A's have important influences on the biological activities studied.
Animals↗
Immunogenicity and antigenicity of synthetic Escherichia coli lipid A.
The immunogenicity and antigenicity of synthetic Escherichia coli lipid A (compound 506) and its 1- and 4'-monophosphorylated derivatives (compounds 505 and 504, respectively) and nonphosphorylated derivative (compound 503) were compared with those of bis- and 4'-monophosphorylated natural free lipid A from E. coli. The synthetic compounds under study were either coated onto sheep erythrocytes (except for the water-insoluble preparation 503) or incorporated into liposomes and used for the immunization of rabbits. Both types of immunogens (the latter representing fully synthetic immunogens) resulted in high-titered polyclonal antisera which were characterized before or after absorption in a passive hemolysis assay as well as in a passive hemolysis inhibition assay with the synthetic compounds as test antigens. All antisera were found to react with their corresponding homologous antigens coated onto sheep erythrocytes, with titers of up to 2,048, and were comparable to those antisera obtained after immunization with natural lipid A exposed on the bacterial surface after acid hydrolysis. Antisera against bisphosphorylated compound 506 were highly specific for the homologous antigens, showing no interaction with compounds 504 and 505 in the passive hemolysis test. The same held true for the absorption experiments in which glutaraldehyde-fixed sheep erythrocytes were sensitized with the respective antigens. Antisera against monophosphorylated compounds 504 and 505 exhibited, besides their expected homologous reactivity, complete cross-reactivity with compound 506, but they did not cross-react with each other. Thus, anti-504 and anti-505 antibodies recognized distinct antigenic determinants, being related to the ester linked 4'-phosphate or the glycosidically linked 1-phosphate, respectively. Both antigenic determinants were also expressed by bisphosphorylated compound 506 used as an antigen; however, upon immunization, only antibodies against compound 506 were elicited.
Epitopes↗
Synthetic Salmonella-type lipid A antigen with high serological specificity.
A synthetic compound (compound 516), beta(1-6)-linked D-glucosamine disaccharide 1,4'-bisphosphate, which is acylated by (R)-3-hexadecanoyloxytetradecanoyl, (R)-3-hydroxytetradecanoyl, (R)-3-dodecanoyloxytetradecanoyl, and (R)-3-tetradecanoyloxytetradecanoyl groups at positions 2,3,2', and 3', respectively, exhibited in vitro antigenic reactivity of high specificity comparable to that of free lipid A from Salmonella minnesota R595. This was confirmed by an enzyme-linked immunosorbent assay and an enzyme-linked immunosorbent assay inhibition test with monoclonal and conventional antibodies. The results of comparative analysis performed with several synthetic lipid A analogs as well as three monosaccharide derivatives suggested that the complete structure involving both phosphate groups at the C-1 and C-4' positions and the 3-acyloxyacyl groups at the C-2, C-2', and C-3' positions of the glucosamine disaccharide are required for the expression of the serological specificity of Salmonella-type lipid A. This was deduced from the observations that compound 506, a synthetic Escherichia coli-type lipid A which has the same structure as that of compound 516, except that 3-hydroxytetradecanoyl group is substituted for an acyloxyacyl residue at the C-2 position, exhibited significantly reduced antigenic reactivity as compared with compound 516 and that the replacement by the hydrogen atom of the phosphoryl group at the C-1 position or by 3-hydroxytetradecanoyl or tetradecanoyl groups of acyl residues at the 2, 3, 2', and 3' positions of compound 516 results in a marked reduction of reactivity with monoclonal antibodies 5G and 36G. Similar results were obtained by assays with conventional rabbit antibodies, but the structural difference between compounds 516 and 506 could not be distinguished by these polyclonal antibodies. The results of cross-reactions among synthetic analogs with monoclonal antibodies 161M and 1-9M, which have been confirmed to exhibit different serological specificities from the 5G or 36G antibody, also suggested that the nature and linkage of fatty acyl residues as well as the backbone structure of lipid A play an important role in determining serological specificity of the lipid A molecule.
Antigens, Bacterial↗
Adjuvant activity of 6-O-acyl-muramyldipeptides to enhance primary cellular and humoral immune responses in guinea pigs: adaptability to various vehicles and pyrogenicity.
Thirteen 6-O-acyl-N-acetylmuramyl-L-alanyl-D-isoglutamines (6-O-acyl-MDPs), including four inactive D-isoasparagine and L-isoglutamine analogs, were tested for their pyrogenicity and immunopotentiating activity to stimulate primary humoral and cellular immune responses in guinea pigs to a model protein antigen, ovalbumin, when administered in various vehicles. Among them, derivatives whose muramic acid residue was substituted by alpha-branched (and beta-hydroxylated) higher fatty acids at the carbon-6 position, especially 6-O-(2-tetradecylhexadecanoyl)-MDP (B3O-MDP) and, to a lesser extent, 6-O-(3-hydroxy-2-docosylhexacosanoyl)-MDP (BH48-MDP) and its L-serine analog [BH48-MDP(L-Ser)], were found to exert strong adjuvant activity in both the induction of delayed-type hypersensitivity and the stimulation of circulating precipitating antibody levels when combined with nonirritating vehicles (liposomes, squalene-in-water emulsion, and phosphate-buffered saline). These vehicles did not efficiently support the adjuvant activity of MDP, the parent molecule of the above lipophilic derivatives. Pyrogenicity tests showed that introduction of alpha-branched higher fatty acid groups but not of straight, long-chain fatty acids at the 6-position of the muramic acid residue resulted in marked decrease of the pyrogenicity inherent to MDP via intravenous administration.
Acetylmuramyl-Alanyl-Isoglutamine↗
Adjuvant activity of 6-O-acyl-muramyldipeptides to enhance primary cellular and humoral immune responses in guinea pigs: dose-response and local reactions observed with selected compounds.
6-O-(2-Tetradecylhexadecanoyl)-N-acetylmuramyl-L-alanyl-D-isoglutamine (B3O-MDP) and 6-O-(3-hydroxy-2-docosylhexacosanoyl)-MDP (BH48-MDP) were examined for immunopotentiating activity in stimulating the primary immune responses of guinea pigs to ovalbumin and for adverse reactions at the injection site and in the regional lymph nodes when administered in combination with several nonirritating vehicles. B30-MDP was found to potently stimulate both humoral and cellular immune responses, the latter by induction of delayed-type hypersensitivity, irrespective of the administration vehicle examined (liposomes, a squalene in water emulsion, Intralipid, phosphate-buffered saline, and Nikkol HCO-60 glucose solution), although the minimum effective dose was dependent on the vehicle used. Reactions in the footpad receiving the injection were negligible. Noticeable local reaction consisted of swelling of the lymph nodes in the region of the injection, but the swelling was only noted with higher doses and subsided 3 to 4 weeks after immunization, unlike the persistent swelling caused by the administration of water-in-mineral oil emulsions with or without B30-MDP. BH48-MDP and its L-serine analog, BH48-MDP(L-Ser), which has L-serine in place of L-alanine in MDP, in combination with the squalene-in-water emulsion, also intensely stimulated both cellular and humoral antiovalbumin immune responses, but the effects of these compounds seemed to be influenced to a greater degree by the vehicles than by B30-MDP. Thus, B30-MDP was chosen from a series of a 6-O-acyl derivatives of MDP as the most promising candidate for possible application in practical vaccines.
Acetylmuramyl-Alanyl-Isoglutamine↗
Enterogenous cyst of the cervical spinal cord in a child--case report.
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Child, Preschool↗
Comparison of survival of patients with lung cancer between elderly (greater than or equal to 70) and younger (70 greater than) age groups.
Results of radiotherapy for lung cancer in the elderly were compared with those in younger patients. A total of 129 patients were treated by radiation therapy with or without chemotherapy. Fifty-six patients (43.4%) were 70 years old or more (elderly group) at the time of treatment, and the remaining 73 patients were below age 70 (younger group). Treatment results in the elderly group were nearly the same as those in the younger group in all stages of the disease. Survival time was longer for patients with performance status (PS) of 0 to 2 than for those with PS 3 or 4 regardless of age (p less than 0.05). The survival time of the elderly group was nearly the same as that of the younger group for squamous cell carcinoma, but somewhat shorter for adenocarcinoma although the difference was not statistically significant. There was no difference in survival between the two groups when they were treated by combined radiation therapy and chemotherapy. Our results suggest that elderly patients can be treated as safely as younger patients by radiotherapy alone or combined radiation therapy and chemotherapy.
Adenocarcinoma↗
[The actual condition of outpatients in the Pedodontic Clinic at the Dental Hospital of Higashi-Nippon-Gakuen University. 1. Actual condition of outpatients at the 1st visit during the past 5 years].
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Adolescent↗
[The actual condition of outpatients in the Pedodontic Clinic at the Dental Hospital of Higashi-Nippon-Gakuen University. 2. Prevalence and treatment of dental caries in outpatients].
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Adolescent↗
Diagnosis of diffuse hepatocellular diseases using SPECT.
In the scintigraphic diagnosis of diffuse hepatocellular diseases, increased splenic uptake of colloids and splenomegaly are helpful signs. To quantify these patterns, the volume and activity of liver and spleen were measured by using single photon emission computed tomography (SPECT). The spleen-to-liver (S/L) ratios in volume and activity that were calculated from SPECT images were estimated in normal individuals and in patients with diffuse hepatocellular diseases. The maximum normal limits of S/L ratios of volume, activity, and activity/volume were predicted as 0.19, 0.087, and 0.72 (mean +/- 2 s.d.). Twenty-two of twenty-three patients (96%) with liver cirrhosis had at least two elevated S/L ratios, and three elevated S/L ratios could clearly differentiate the patient with liver cirrhosis from normal individuals. On the other hand, only six patients (32%) with chronic hepatitis had elevation of any S/L ratio. Abnormal S/L ratios of activity/volume in the range from 0.72 to 1.05 were not obvious on planar or SPECT images.
Chronic Disease↗
[Structure and chemical synthesis of lipid A].
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Chemical Phenomena↗
In vitro antigenic reactivity of synthetic lipid A analogues as determined by monoclonal and conventional antibodies.
Cross-reactivities of synthetic lipid A analogues with monoclonal and conventional antibodies against Salmonella lipid A were studied. It was shown that the in vitro antigenicity of 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, was practically indistinguishable from that of the natural E. coli lipid A preparation, and that both phosphates in positions 1 and 4' as well as ester- and amide-linked fatty acyl residues, particularly 3-acyloxyacyl group, of the glucosamine disaccharide are involved in the cross-reactivity of lipid A as important antigenic determinants.
Animals↗
Immunopharmacological activities of a synthetic counterpart of a biosynthetic lipid A precursor molecule and of its analogs.
Synthetic lipid A analogs (compounds 404 through 406) were examined for their immunopharmacological activities. These compounds had two amide-bound and two ester-bound (R)-3-hydroxytetradecanoyl groups at the C-2 and C-2' and the C-3 and C-3' positions, respectively, of beta (1-3)glucosamine disaccharide. In all of the in vitro assays, these synthetic compounds exhibited high activities comparable to those of a reference lipid A prepared from Escherichia coli O8:K27 Re-mutant strain F515. The compounds activated the clotting enzyme cascade of the horseshoe crab, activated the human complement via the classical pathway, caused polyclonal B-cell activation, stimulated the phagocytosis of sheep erythrocytes by murine peritoneal macrophages, and enhanced the migration of human polymorphonuclear leukocytes. They also increased the thymidine uptake of splenocytes of BALB/c nu/nu and C3H/HeN mice but not those of C3H/HeJ (a nonresponder to lipopolysaccharide). A dephosphorylated derivative, compound 403, was barely active in all of the above assays except for the enhancement of polymorphonuclear leukocyte migration. However, compounds 404 through 406 were feeble in pyrogenicity and could not prepare the local Shwartzman reaction, although they were very lethal to galactosamine-loaded mice. Therefore, synthetic lipid A analogs described here were fully immunopharmacologically active in in vitro assays, but all of them were far less active than natural E. coli F515 lipid A regarding the biological activities characteristic of endotoxic lipopolysaccharides and lipid A's. The high lethal toxicity of compound 406 (1,4'-bisphosphate) to the galactosamine-loaded mice may not reflect its real toxicity to normal mice. In all activities examined, compound 406 was quite comparable to a biosynthetic lipid A precursor, a natural counterpart of compound 406. The immunopharmacological activities of these newly synthesized lipid A analogs, especially compound 406, were much stronger than those of compounds that had been synthesized earlier by using the originally proposed model of the lipid A structure. The findings described in this report justify the acylation pattern of a disaccharide backbone of lipid A, revised on the basis of recent analytical studies. The low in vivo endotoxic activities of the present lipid A analogs are most probably due to the fact that the kinds of acyl groups were different from those of the complete lipid A from E. coli, although there were no differences in the acylation positions on the disaccharide backbone.
Adjuvants, Immunologic↗
Granuloma formation by muramyl dipeptide associated with branched fatty acids, a structure probably essential for tubercle formation by Mycobacterium tuberculosis.
Muramyl dipeptide, which does not induce epithelioid granuloma when injected alone dissolved in phosphate-buffered saline, could induce extensive granulomas in guinea pigs when chemically conjugated with branched, but not linear, fatty acids. Peptidoglycan fragments of Staphylococcus epidermidis could evoke epithelioid granulomas when incorporated in a water-in-oil emulsion. These findings suggest the importance of a lipid bound to muramyl dipeptide for granuloma formation. In view of the fact that mycobacteria uniquely contain large amounts of branched fatty acids, it was proposed that the complex of muramyl dipeptide and branched fatty acids, mostly mycolic acids, is a structure in tubercle bacilli responsible for tubercle formation.
Acetylmuramyl-Alanyl-Isoglutamine↗
[A long-term survivor of small cell lung cancer].
A 60-year-old man with small cell lung cancer who has been alive seven years in good condition after the combined therapy with radiation and anticancerous drugs, is presented. Chest X-ray examinations revealed the right middle lobe atelectasis and lymph node enlargement of the right hilum. Small cell carcinoma (oat cell type) was diagnosed by cytological examinations of the sputum. The patient was given 42 Gy of telecobalt, one course of METT as chemotherapy and PSK (3.0 g X 52) and BCG-CWS (300 micrograms X 29) as immunotherapy.
Carcinoma, Small Cell↗
Further study of biological activities of chemically synthesized analogues of lipid A in artificial membrane vesicles.
In the previous paper [Eur. J. Biochem. 124, 405 (1982)], we demonstrated that chemically synthesized lipid-A analogues such as the 1-monophosphate or 1,4'-diphosphate of 6-O-(2-deoxy-2-tetradecanoylamino-6-O-tetradecanoyl-D-glucopyra nos yl)-2-deoxy-2-tetradecanolyamino-3,4-di-O-tetradecanoyl-D-gluco pyr anose enhanced immunogenicity of liposomal model membranes sensitized with amphipathic antigen when they were incorporated in the same liposomes. Here we extend the observation by testing the recently synthesized analogues including diglucosamine analogues carrying hydroxy and acyloxy fatty acids. Among the analogues tested, those which showed higher adjuvant and mitogenic activities in the liposomal system were N-acylated and O-acylated beta-1,6-linked D-glucosamine disaccharides carrying either amide-bound 3-hydroxytetradecanoic acids in addition to phosphate in position 1 of the reducing sugar or amide-bound 3-tetradecanoyloxytetradecanoic acids. The analogue carrying both amide-bound 3-hydroxytetradecanoic acids and phosphate in position 4 of the non-reducing sugar showed weak adjuvant activity and marginal mitogenic activity.
Adjuvants, Immunologic↗