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Biomedical subjects

S Kusumoto

Publications and source records attributed to S Kusumoto.

At least 145 records · Page 8Linked to original sources
PubMed1988

[A study of CDDP in the treatment of patients with gastric and esophageal cancers, with special reference to the evaluation of renal functions before and after CDDP administration].

Although CDDP has been widely used for cancer chemotherapy in recent years, the problem is that it causes a renal dysfunction as a side effect. As briefly reported here, we have currently used this drug for the treatment of stomach esophageal cancers as a part of multidepartmental therapy, and obtained a finding on the therapeutic usefulness, particularly for monitoring the renal function before and after administration. The subjects were 6 patients with stomach and 11 with esophageal cancer given CDDP at the dose of 50 mg 2 courses, in principle, a single course per week. Blood transfusion was carried out in an amount of 1,000 ml before administration, 2,500 ml on the day of treatment and 1,000 ml for 3 days after administration. When the effects of CDDP on urinary BUN, Na, K, Cl, Mg, NAG, beta 2 microglobulin, Ccr and FENa levels were measured for the determination of renal functions before and after administration, NAG and beta 2 microglobulin levels were conceivably found to be useful indices.

Adult↗
PubMed1987

Reduction in antiviral activity of human interferon-gamma in acidic media with reference to structural change.

The fluorescence intensity of a unique tryptophan 36 in human interferon-gamma was drastically decreased below pH 4 with a concomitant decrease of antiviral activity. The region of residues 32-42 of human interferon-gamma was found by calculation to have a low hydrophobicity together with a high helical hydrophobic moment, and the net electric charge of this region having an amphiphilic helical structure changed significantly near pH 4. These results suggest that the region of residues 32-42 plays an important role in exhibiting antiviral activity.

Chemical Phenomena↗
PubMed1987

Endotoxic properties of synthetic pentaacyl lipid A precursor Ib and a structural isomer.

A pentaacyl precursor of lipid A biosynthesis, termed precursor Ib, and a structural isomer have been chemically synthesized. These compounds were, in comparison to synthetic Escherichia-coli type lipid A or lipopolysaccharide, analyzed for their activity in typical endotoxin test systems. It was found that both precursor Ib and the isomer exhibited similar or only slightly lower pyrogenic, lethal and Shwartzman-phenomenon-inducing activity than lipid A. All preparations were comparable in their B-lymphocyte mitogenicity, macrophage-activating capacity and immunoreactivity towards lipid A antisera. The proton nuclear magnetic resonance spectra of the 1-dephospho derivative of synthetic and bacterial precursor Ib were indistinguishable proving that the previously proposed structure for precursor Ib is correct.

Animals↗
PubMed1987

Radiotherapy for carcinoma of the uterine cervix by remotely controlled afterloading intracavitary system with high-dose-rate.

Between January 1978 and June 1985 seventy-nine patients with carcinoma of the uterine cervix were treated by a remotely controlled afterloading system (RALS) with high-dose-rate irradiation following external beam therapy. It was given once a week with a dose per fraction of 6 Gy to point A, 3 to 6 times, using applicators equipped with 1 Ci 60Co bead in each ovoid and two 1 Ci 60Co beads in a tandem 1 cm apart. Five-year survival rates were 85, 68, and 51 percent in Stages I, II, and III, respectively. Recurrences were noted in 12 patients (20%) with a minimum follow-up of 2 years: 4 patients in the parametrium, 2 in the central area, 5 in both the parametrium and central areas, and 5 in the para-aortic lymph node. Complications were noted in 13 patients (22%): temporary rectal bleeding in 7, stenosis of the sigmoid in 2, recto-vaginal fistula in 1, ileo-sigmoidal fistula in 1, and perforation of the intestine in 2 patients. The treatment results of the high-dose-rate schedule for RALS appear to be comparable to those of conventional low-dose-rate systems reported by others. Therefore a fraction dose of 6 Gy to point A once a week by RALS should be considered to be practical, economical, and acceptable to patients.

Brachytherapy↗
PubMed1987

Characterization of three species of Escherichia coli-derived human leukocyte interferon A separated by reverse-phase high-performance liquid chromatography.

A preparation of recombinant human leukocyte interferon A (rIFN-alpha A) obtained from Escherichia coli cells was found by reverse-phase high-performance liquid chromatography (HPLC) to contain three species. The three species, named Mf-1, Mf-2, and Ms in the order of their elution, were separated and characterized to elucidate their structural differences. The amino acid compositions, the amino-terminal amino acid sequences (Cys1-Asp2-Leu3-), and the carboxy-terminal amino acids (Glu) of the three species agreed with those predicted from the cDNA sequence, although the sequence analysis yields of Mf-2 and Ms were extremely low. They were found to have the same disulfide bonds, Cys1-Cys98 and Cys29-Cys138, by amino acid analysis of the tryptic peptides, but the recovery of the peptides linked by a Cys1-Cys98 disulfide bond for Mf-2 and Ms was extremely low. The results demonstrate that although the primary structures of the three species are almost identical, small difference(s) exists among them especially at the amino-terminal portion.

Amino Acid Sequence↗
PubMed1987

Activation of the human complement cascade by bacterial cell walls, peptidoglycans, water-soluble peptidoglycan components, and synthetic muramylpeptides--studies on active components and structural requirements.

Cell walls isolated from 29 strains of 24 gram-positive bacterial species, whose peptidoglycans belong to the group A type of Schleifer and Kandler's classification, with one exception (Arthrobacter sp.), were shown to activate the complement cascade in pooled fresh human serum mainly through the alternative pathway and partly through the classical one. The complement-activating effect of cell walls (5 species) possessing group B type peptidoglycan, except those of Corynebacterium insidiosum, was weaker than that of the walls with group A type peptidoglycan. Preparations of peptidoglycan isolated from cell walls of Staphylococcus aureus, Streptococcus pyogenes, and Lactobacillus plantarum also activated the alternative pathway of the complement cascade, but less effectively than the respective parent cell walls. A water-soluble "polymer" of peptidoglycan subunits (SEPS), which was prepared from Staphylococcus epidermidis peptidoglycans by treatment with a cross-bridge degrading endopeptidase, retained most of the complement-activating ability of the parent cell walls. A peptidoglycan "monomer," SEPS-M, which was obtained by hydrolysis of the glycan chain of SEPS with endo-N-acetylmuramidase to disaccharide units did not activate complement. In conformity with this finding, neither synthetic N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) nor MDP-L-Lys-D-Ala activated the complement cascade. Among several lipophilic derivatives of MDP, 6-O-(3-hydroxy-3-docosylhexacosanoyl)-MDP-L-Lys-D-Ala (BH48-MDP-L-Lys-D-Ala) and 6-O-(2-tetradecylhexadecanoyl)-MDP (B30-MDP) were shown to activate complement through the alternative as well as the classical pathway and exclusively through the classical pathway, respectively. The finding that a D-isoasparagine analog of B30-MDP caused the same effect as the parent molecule strongly suggests that the activation of complement by B30-MDP is different from that caused by cell wall peptidoglycans and a water-soluble "polymer" of peptidoglycan subunits.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Requirement of a properly acylated beta(1-6)-D-glucosamine disaccharide bisphosphate structure for efficient manifestation of full endotoxic and associated bioactivities of lipid A.

Several synthetic acylated glucosamine monophosphates, with structures corresponding to the nonreducing or reducing moiety of the lipid A of the Escherichia coli or Salmonella minnesota type, and a synthetic compound corresponding to a biosynthetic disaccharide lipid A precursor (designated Ia or IVA) were examined for their endotoxic and related bioactivities in comparison with those of the synthetic and bacterial parent molecules, i.e., acylated beta(1-6)-D-glucosamine disaccharide bisphosphates. Some of the test monosaccharide compounds were definitely active in most of the in vitro assays. Their activities, except for complement activation, however, were weaker than those of the reference compounds, synthetic and bacterial acylated disaccharide bisphosphates. The differences between the test monosaccharide and disaccharide compounds were much more apparent in in vivo assays, in which the test acylated glucosamine monophosphates were scarcely active, though some test compounds exhibited weak lethal toxicity in galactosamine-loaded mice and were weakly active in pyrogenicity, immunoadjuvant activity, and possible tumor necrosis factor and alpha and beta interferon-inducing ability in Mycobacterium bovis BCG- and Propionibacterium acnes-primed mice, respectively. Mixture at an equimolar ratio of acyl glucosamine monophosphates, each of which has the structure of the reducing or nonreducing moiety of the reference disaccharide compound, did not restore the endotoxic or associated bioactivities of the corresponding parent molecules. No essential differences in bioactivity were noted between synthetic and bacterial monosaccharide compounds, i.e., lipid X, whose structure corresponds to the reducing moiety of E. coli-type lipid A.

Acylation↗
PubMed1987

The immunogenicity and antigenicity of lipid A are influenced by its physicochemical state and environment.

We investigated the immunogenicity and antigenicity of synthetic lipid A and partial structures thereof. Included in the study were compounds which varied in the position of phosphate (1-mono-, 4'-mono-, and 1,4'-bisphosphates) and in the acylation (type, number, and distribution of fatty acids) and, in the case of monosaccharide compounds, the nature of the backbone sugar (D-glucosamine, D-glucose, 3-amino-3-deoxy-D-glucose, and 2,3-diamino-2,3-dideoxy-D-glucose). With the aid of the passive-hemolysis and passive-hemolysis-inhibition assays and by absorption experiments, five distinct antibody specificities were detected in polyclonal rabbit antisera raised against sheep erythrocyte-coated lipid A and lipid A incorporated into the membrane of liposomes (liposome-incorporated immunogens). Three antibody specificities reacted with disaccharide antigens specific for a 1-mono-, 4'-mono-, and 1,4'-bisphosphorylated beta-1,6-linked D-glucosamine disaccharide. Two antibodies reacted with either 1- or 4-phosphates of acylated D-gluco-configured monosaccharides and exhibited no cross-reaction with each other. However, they cross-reacted with disaccharide antigens with phosphate groups in the appropriate positions. We found that the physicochemical state and the environment of lipid A modulated its immunoreactivity. The immunogenicity was best expressed by erythrocyte-coated and liposome-incorporated immunogens. The antigenicity of lipid A was also greatly influenced by its physical surroundings. The reaction pattern of the above antibodies was highly specific in the hemolysis assay and in absorption experiments (the antibody reacted with antigen embedded in a cell membrane), whereas some cross-reactivities were observed in inhibition studies (the antibody reacts with antigen in aqueous solution). By using liposome-incorporated antigens as inhibitors, nonspecific reactions were avoided and specific ones were enhanced. Thus the antibodies described above against lipid A recognize epitopes in the hydrophilic backbone, the exposure of which depends on the intrinsic physicochemical properties of lipid A on the one hand and the physical environment on the other.

Animals↗
PubMed1987

Structural requirements of muramylpeptides for induction of necrosis at sites primed with Mycobacterium tuberculosis in guinea pigs.

Intracutaneous injection of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) in guinea pigs caused an extensive necrotic reaction in footpads prepared by injection of heat-killed Mycobacterium tuberculosis in water-in-mineral-oil emulsion. We examined a variety of analogs and derivatives of muramylpeptides for their ability to provoke this reaction. A maximum and a minimum structure responsible for the necrotic reaction were found to be N-acetylglycosaminyl-beta(1-4)-N-acetylmuramyl-tripeptide (GlcNAc-MurNAc-L-Ala-D-isoGln-meso-A2pm) and MDP, respectively. An unexpected finding was that GlcNAc-MurNAc-tetrapeptides having L-amino acids at their C termini, unlike comparable compounds having C-terminal D-amino acids, exhibited definite necrosis-inducing activity, probably due to their tendency to undergo in vivo degradation to GlcNAc-MurNAc-tripeptide. Introduction of some acyl groups, especially the stearoyl group, to the 6-O position of the muramic acid or the peptide moiety of muramylpeptides increased the necrosis-inducing activity of the parent molecules. However, this was not observed with 1-thio-muramic acid analogs of MDP. Modification of the alpha- or gamma-carboxyl groups of the glutamic acid residues of muramylpeptides tended to decrease their necrosis-inducing ability. Analogs and derivatives of muramylpeptides which are capable of inducing necrosis at a primed site, with few exceptions, exhibited powerful adjuvanticity against ovalbumin in guinea pigs. However, the reverse was not necessarily true.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Optimal positioning for CT examinations of the skull base. Experimental and clinical studies.

To evaluate the most appropriate CT angles for the skull base, four adult phantom skulls of various shapes were examined by CT. 15 osseous sites in each skull base were selected and the optimum angle for their delineation was determined. Using Reid's base line (0 degree), many sites could be imaged best at angles up to +20 degrees, and +10 degrees was found to be optimum. Examinations of patients using OM-line as a reference disclosed imaging rates in excess of 70% for sites other than the hypoglossal canal, the optic canal and foramen rotundum, which are in horizontal planes.

Adolescent↗
PubMed1987

A case of minute gastric cancer preoperatively diagnosed.

A case of minute gastric cancer which was preoperatively diagnosed, measuring 3 X 3 mm in diameter is reported. The X-ray examination revealed a faint barium collection surrounded by the mucosal folds. The endoscopic findings showed a small ulcerated lesion with a reddish and irregular margin and convergent folds. Radiological characteristics of the minute gastric cancer and its diagnostic approach are discussed.

Gastroscopy↗
PubMed1986

Biological activity of synthetic heptaacyl lipid A representing a component of Salmonella minnesota R595 lipid A.

A synthetic lipid A (preparation 516), containing seven acyl groups and representing one component of natural free lipid A of Salmonella minnesota R595, has been investigated for biological activity in a number of endotoxin test systems. It was found that the synthetic preparation was, in typical in vivo endotoxin tests (lethality, pyrogenicity, Shwartzman reactivity) as well as in its antigenicity and macrophage activation capacity, significantly less active than natural Salmonella lipid A. However, in other in vitro assay systems (B-cell mitogenicity, complement activation, Limulus amoebocyte lysate gelation) it expressed similar activity as Salmonella lipid A.

Animals↗
PubMed1986

Preclinical increase in activity of muscle microsomal trypsin-like protease in murine muscular dystrophy, C57BL/10-mdx.

Preclinical alterations of protease activities in skeletal muscles from 10-day-old dystrophic mouse, C57BL/10-mdx, were examined by using 10 fluorogenic peptide substrates. Among the activities tested, only Boc-Val-Pro-Arg-MCA-hydrolyzing enzyme of the muscle microsomes showed an about 6-fold higher level of activity in mdx mouse. The increase in activity was not observed in tissues other than skeletal muscle. The enzyme had a pH optimum between 8.5 and 11.0, and was inhibited with DFP and variety of trypsin inhibitors. The enzymatic activity transiently increased at 1-2 weeks of age, the preclinical or very early stage of the disease. These results imply that the increased level of a trypsin-like protease possibly present in muscle microsomes may be closely related to the manifestation of muscular dystrophy.

Aging↗
PubMed1986

Induction of human interleukin 1 by bacterial and synthetic lipid A.

Lipopolysaccharides (LPS) are well known inducers of interleukin 1 (IL 1). Here we show that synthetic heptaacyl Salmonella minnesota (compound 516) and synthetic E. coli type (compound 506) lipid A, as well as monodephospho part structures thereof, are able to induce IL 1 production in human mononuclear cells. The 4'-monodephospho part structure (compound 505) was found to be the most active IL 1 inducer as compared to compound 506 and the 1-monodephospho part structure (compound 504). Synthetic lipid A precursor Ia, lacking nonhydroxylated fatty acids (compound 406), and its 1- or 4'-monodephospho part structures (compounds 404 and 405) did not induce IL 1 production. IL 2 is not produced during stimulation with the synthetic compounds. IL 1 activity was partially heat labile and could be inhibited by a rabbit antiserum against human leukocytic pyrogen. These results show that the lipid A component of LPS is active in inducing IL 1 and that the presence of 3-acyloxyacyl residues is necessary for IL 1 induction.

Blood Physiological Phenomena↗