[Changes in serum interleukin 8 levels after operation of esophageal cancer: preliminary report].
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Esophageal Neoplasms↗
Biomedical subjects
H Tsumura
Publications and source records attributed to H Tsumura.
Antitumor activity of a new low immunosuppressive derivative of podophyllotoxin (GP-11) and its mechanisms.
The spin-labeled derivative of podophyllotoxin, N'-podophyllic acid-N-[3-(2,2,5,5-tetramethyl pyrrolinenyloxy)] semicarbazide (GP-11), was synthesized and tested for its antitumor activity against mouse transplantable tumors, Sarcoma-180, Hepatoma-A, P388 leukemia and Ehrlich ascites carcinoma. At an equitoxic dose, the antitumor activity of GP-11 was similar to that of etoposide (VP-16). However, the immunosuppressive effects of GP-11 were weaker than that of VP-16. In vitro, GP-11 and VP-16 inhibited the proliferation of human lymphoid leukemia Molt 4B cells and suppressed DNA and protein syntheses, but the effect of GP-11 and VP-16 on cell cycle progression was different. The mitotic index was increased by GP-11 and reduced by VP-16. On the basis of flow cytometric bromodeoxyuridine (BrdU)/DNA analysis, GP-11 and VP-16 resulted in the accumulation of cells in the S and G2/M phases. G2/M arrest by GP-11 on cell cycle progression was stronger than that of VP-16, while S arrest was weaker than that of VP-16. After the removal of drugs, the arrest by GP-11 and VP-16 still existed and was irreversible. These results may provide insights into the structure-activity relationships and the design of novel derivatives of podophyllotoxin useful in cancer chemotherapy.
Animals↗
Antitumor activity of polysaccharide from a Chinese medicinal herb, Acanthopanax giraldii Harms.
The results of experiments with Acanthopanax giraldii polysaccharide (AGP) demonstrated that it inhibited the growth of solid Sarcoma 180 and prolonged the survival time significantly. In tumor-bearing mice, AGP enhanced the phagocytosis and chemiluminescence of macrophages. By the immunofluorescent method, binding of the third component of complement (C3) cleavage product to macrophages and proportion of C3 positive cells were increased. In crossed immunoelectrophoresis, human serum C3 was converted by AGP and appeared as the 3rd peak. The height of the 3rd peak was directly proportional to doses of AGP. The residual CH50 units of human serum decreased dose-dependently. These results suggest that the antitumor activity of AGP is related to the enhancement of immune responses.
Animals↗
Gastric emptying after pancreatoduodenectomy with total stomach preservation and selective proximal vagotomy.
This study evaluates postoperative gastric emptying following a new method of pancreatoduodenectomy with total stomach preservation and selective proximal vagotomy performed on 10 patients with diseases affecting the head of the pancreas, 7 being malignant and 3 benign. Reconstruction was carried out using the Billroth I and Billroth II techniques in 5 patients each, respectively. Early postoperative gastric emptying was evaluated by the time before intragastric tube removal and the resumption of oral intake, as well as by barium gastric radiography, while late postoperative gastric emptying was evaluated by the acetaminophen method. No difference was seen in early postoperative gastric emptying between the two surgical techniques, the mean time which elapsed before intragastric tube removal being 4.4 days for the Billroth I and 4.5 days for the Billroth II patients, and the mean time until the resumption of oral intake being 6.8 days for the Billroth I and 7.0 days for the Billroth II patients. A significant delay in gastric emptying was seen in the Billroth II patients compared to a normal control group, 30 and 45 min after acetaminophen administration, but the difference in gastric emptying between the Billroth I and II patients was not significant. Moreover, both techniques impaired gastric emptying much less than Traverso's pylorus-preserving pancreatoduodenectomy.
Aged↗
Anomalous arrangement of the pancreaticobiliary ductal system without dilatation of the biliary tract.
A rare case of anomalous arrangement of the pancreaticobiliary ductal system without dilatation of the biliary tract (AAPBDS without DBT) associated with mucosal dysplasia of the biliary duct is described herein. A 53 year old male with a long history of diarrhea and right upper abdominal pain was diagnosed as having AAPBDS without DBT by endoscopic retrograde cholangiopancreatography and other examinations. Excision of the gallbladder and biliary duct with a Roux-en-Y hepatico-jejunostomy was performed and subsequent pathological examination of the surgical specimens showed mucosal hyperplasia of the gall-bladder and mucosal dysplasia of the biliary duct. Considering the dysplastic changes of the biliary duct as seen in our case, and the high incidence of AAPBDS without DBT developing into carcinoma of the biliary duct, being 12.2 per cent, we suggest that pancreaticobiliary ductal diversion with excision of the gallbladder and biliary duct should also be performed for AAPBDS without DBT. However, further pathological investigations concerning the excised biliary duct in AAPBDS without DBT will be need to be carried out.
Bile Ducts↗
The substitution of cysteine 17 of recombinant human G-CSF with alanine greatly enhanced its stability.
Human recombinant granulocyte-colony stimulating factor (rhG-CSF) has one free cysteine at position 17 and has two disulfide bridges (Cys36-Cys42 and Cys64-Cys74). The Cys17 of rhG-CSF was substituted with Gly, Ala, Ser, Ile, Tyr, Arg, and Pro, or deleted using site-directed mutagenesis in order to improve its thermostability. With the exception of Pro17-rhG-CSF, all mutant proteins retained biological activity which promotes the growth of mouse bone marrow cells in vitro. Among these mutant proteins, Ala17-rhG-CSF had more than 5 times higher stability than rhG-CSF. But Ser17-rhG-CSF had almost same stability as rhG-CSF and other mutant proteins had only lower stability.
Alanine↗
Alterations in cardiac function and subcellular membrane activities after hypervitaminosis D3.
The present study was designed to induce massive accumulation of calcium in the myocardium and to evaluate the effect of calcium overload on myocardial contractile function and biochemical activity of cardiac subcellular membranes. Rats were treated with an oral administration of 500,000 units/kg of vitamin D3 for 3 consecutive days, and their hearts were sampled on the 5th day for biochemical analysis. On the 4th and 5th days, heart rate, mean aortic pressure, left ventricular systolic pressure and left ventricular dP/dt were significantly lowered in vitamin D3-treated rats, demonstrating the existence of appreciable myocardial contractile dysfunction. Marked increases in the myocardial calcium (67-fold increase) and mitochondrial calcium contents (24-fold increase) were observed by hypervitaminosis D3. Mitochondrial oxidative phosphorylation and ATPase activity were significantly reduced by this treatment. A decline in sarcolemmal Na+, K(+)-ATPase activity was also observed, while relatively minor or insignificant changes in calcium uptake and ATPase activities of sarcoplasmic reticulum were detectable. Electron microscopic examination revealed calcium deposits in the mitochondria after vitamin D3 treatment. The results suggest that hypervitaminosis D3 produces massive accumulation of calcium in the myocardium, particularly in the cardiac mitochondrial membrane, which may induce an impairment in the mitochondrial function and eventually may lead to a failure in the cardiac contractile function.
Adenosine Triphosphatases↗
Mutant protein of recombinant human granulocyte colony-stimulating factor for receptor binding assay.
A new mutant protein of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was produced for the studies on receptors for human G-CSF. The mutant protein [(Tyr1, Tyr3]rhG-CSF), the biological activity of which was almost equal to that of rhG-CSF, was prepared by the replacement of threonine-1 and leucine-3 of rhG-CSF with tyrosine. The radioiodinated preparation of the mutant protein showed high specific radioactivity and retained full biological activity for at least 3 weeks. The binding capacity of the radioiodinated ligand was compared with that of [35S]rhG-CSF. Both radiolabeled ligands showed specific binding to murine bone marrow cells. Unlabeled rhG-CSF and human G-CSF purified from the culture supernatant of the human bladder carcinoma cell line 5637 equally competed for the binding of labeled rhG-CSFs in a dose-dependent manner, demonstrating that the sugar moiety of human G-CSF made no contribution to the binding of human G-CSF to target cells. In contrast, all other colony-stimulating factors and lymphokines examined did not affect the binding. Scatchard analysis of the specific binding of both labeled ligands revealed a single class of binding site with an apparent dissociation constant (Kd) of 20-30 pM and 100-200 maximal binding sites per cell. These data indicate that the radioiodinated preparation of the mutant protein binds the same specific receptor with the same affinity as [35S]rhG-CSF. The labeled mutant protein also showed specific binding to human circulating neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
IL-3 specifically inhibits GM-CSF binding to the higher affinity receptor.
The inhibition of binding between human granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor by human interleukin-3 (IL-3) was observed in myelogenous leukemia cell line KG-1 which bore the receptors both for GM-CSF and IL-3. In contrast, this phenomenon was not observed in histiocytic lymphoma cell line U-937 or in gastric carcinoma cell line KATO III, both of which have apparent GM-CSF receptor but an undetectable IL-3 receptor. In KG-1 cells, the cross-inhibition was preferentially observed when the binding of GM-CSF was performed under the high-affinity binding condition; i.e., a low concentration of 125I-GM-CSF was incubated. Scatchard analysis of 125I-GM-CSF binding to KG-1 cells in the absence and in the presence of unlabeled IL-3 demonstrated that IL-3 inhibited GM-CSF binding to the higher-affinity component of GM-CSF receptor on KG-1 cells. Moreover, a chemical cross-linking study has revealed that the cross-inhibition of the GM-CSF binding observed in KG-1 cells is specific for the beta-chain, Mr 135,000 binding protein which has been identified as a component forming the high-affinity GM-CSF receptor existing specifically on hemopoietic cells.
Binding, Competitive↗
The influence of clinical use of antibiotics and the sensitivity of strains isolated from postoperative infections--a comparison of nosocomial pathogens with strains isolated from the bacterial flora of patients.
In the present study, we investigated how the recent clinical use of antibiotics have altered the antibiotic susceptibility of strains isolated from postoperative infections, especially Gram-negative rods. For Pseudomonas aeruginosa, serogroup E strains accounted for about 20 per cent of postoperative infections, but were unable to be isolated from either the feces of patients on admission or from the appendix contents of patients with appendicitis. It therefore appeared that serogroup E strains were responsible for the nosocomial infections in our department. The strains of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa serogroup E, which we assumed to be nosocomial pathogens, acquired a high level of resistance to antibiotics soon after third-generation cephems became widely used. On the other hand, the antibiotic susceptibility of Enterobacter cloacae, Citrobacter freundii, and the serogroups of Pseudomonas aeruginosa other than E, which were considered to originate from the bacterial flora of patients, did not vary throughout the several years of the study period.
Bacteria↗
Effect of continuous intravenous infusion of secretin preparation (secrepan) in patients with hemorrhage from chronic peptic ulcer and acute gastric mucosal lesion (AGML).
The purpose of the present study was to investigate the hemostatic effect of continuous intravenous infusion of secrepan (secretin preparation, Eisai Company Ltd. Tokyo) on gastroduodenal hemorrhage in patients with chronic peptic ulcer and AGML (acute gastric mucosal lesion). The patients consisted of 37 cases of bleeding ulcer (13 cases of chronic peptic ulcer and 24 cases of AGML). Secrepan was infused at a rate of 2 U/kg/hr for the first 3 days and 0.5 U/kg/hr for the next 4 days. The cumulative hemostatic rate in the chronic peptic ulcer group was 53.9% after 36 hours, and 76.9% after 48 hours of infusion, but no significant change in rate was observed thereafter. The cumulative hemostatic rate in the AGML group was 52.2% after 36 hours, and 95.7% after 72 hours of infusion. The hemostatic rate in chronic peptic ulcer and AGML cases with only slight or moderate bleeding was 100%, and no recurrent hemorrhaging was observed. The hemostatic rate in chronic peptic ulcer cases with severe bleeding was 62.5% and in AGML cases with severe bleeding was 93.3%, and 7 of 15 cases showed recurrent hemorrhage. Our findings indicated that continuous intravenous infusion of secrepan had more favorable effects on AGML cases, than on chronic peptic ulcer cases.
Acute Disease↗
Toxin involvement in methicillin-resistant Staphylococcus aureus enteritis in gastroenterological surgery.
The authors investigated the production of toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxins (SE) by Methicillin-resistant Staphylococcus aureus (MRSA) isolates to clarify the pathogenesis of postoperative MRSA enteritis in patients undergoing gastroenterological surgery. Regarding the percentage of TSST-1 producing strains, there was a significant difference between type II MRSA strains (68.8%) and type IV MRSA strains (4.2%). Among type II strains, all those producing staphylococcal entorotoxin (SE) type C (SEC) also produced TSST-1, although other strains that produced SEB without TSST-1 were commonly isolated. Strains producing SEA were potent producers of SE which was considered to be responsible for enteritis. Therefore, we hypothesized that the strains which produced both SEA and SEC tended to cause enteritis associated with TSS-like symptoms owing to the high titer of these toxins.
Bacterial Toxins↗
[Study of the host factors in the occurrence of the postoperative infections--special reference to the pathogenicity of the Enterococcus and MRSA].
A study of the pathogenicity of the Enterococcus and Methicillin resistant S. aureus (MRSA) was made of 781 cases with gastroenterological surgery. The results obtained were summarized as follows. In this study 215 strains were isolated from clinical specimens. In these strains 13% was isolated from the postoperative mixed infection and only 7% occurred in single infection. Most of the single infections by the Enterococcus occurred in the cases with changes in host resistance, such as terminal cancer, disorder of the glucose tolerance, malnutrition and/or organ failures. Seventy-three strains were isolated from clinical specimens. In these strains 10% were the postoperative mixed infection and 40% were single infection. Incidence of the infection by the MRSA was significantly high compared with that by the Enterococcus. Single infection by the MRSA occurred even in the cases with normal host resistance. Strains producing enterotoxin C (single or plus A) were frequently isolated in MRSA enteritis or pneumonia. However, 60 percent of the patients in whom MRSA were detected in their abdominal drains had no signs of infection. These results suggest that the occurrence and severity of the MRSA infection relate with site of the infection and production of the exotoxin.
Enterococcus↗
Pressure distribution on articular surfaces: application to joint stability evaluation.
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Biomechanical Phenomena↗
[An attempt to treat esophageal cancer by intraoperative local administration of oil bleomycin].
Intraoperative local chemotherapy was performed on patients with esophageal cancer, using oil bleomycin (oil BLM). Oil BLM was injected into the muscular layer of the thoracic esophagus to be resected, 2 ml (30 mg of BLM base) each near the anal and oral stumps of the esophagus. BLM concentrations in the regional lymph nodes which were determined were elevated, and the tumor tissue of the esophagus also showed high levels. The evidence has been recognized in this study that oil BLM which features lymphogenous transport and tissue accumulation spreads fast in the entire esophageal wall and is transported to and retained in the regional lymph nodes. Side effects from local administration of oil BLM or recurrence of cancer has not so far been observed. Judging from the results of this study, intraoperative local administration of oil BLM seems to be effective for adjuvant chemotherapy.
Bleomycin↗
Beta-lactamase in gram-negative rods: the relationship between penicillinase and R plasmids in gram-negative rods.
Concomitant with the extensive use of antibiotics, the number of multiple antibiotic-resistant strains has been increasing. Since resistance is mainly mediated by R plasmids, we undertook to investigate the characteristics of R plasmid-determined beta-lactamase in 6 Gram-negative rods. The beta-lactamase produced by each organism was classified by its substrate: type P which attacks penicillins, type C which attacks cephalosporins, and type C/P which attacks both penicillins and cephalosporins. Though the chromosomally mediated beta-lactamase of almost all Gram-negative rods is classified as type C, R plasmid-mediated beta-lactamase is almost equally active against both penicillins and cephalosporins. Therefore, we suggest that type C/P beta-lactamase was mediated by R plasmids in Gram-negative rods which already produced chromosomally mediated type C beta-lactamase. The strains which produced type C/P beta-lactamase tended to be more resistant to antibiotics than the other beta-lactamase producing strains. Among type C/P strains, the sensitivity to cephalosporins varied with the bacterial species, whereas all these strains were highly resistant to penicillins. Even for piperacillin, which is stable to cephalosporinase, the MIC at which the cumulative percentage of strains inhibited was 50% (MIC50) was over 50 micrograms/ml in all strains tested.
Cefazolin↗
Immunological response of monkeys infected intranasally with human parainfluenza virus type 4.
This report describes our attempt to establish an experimental animal model for human parainfluenza virus type 4A (HPIV-4A) and 4B (HPIV-4B) infection, which was used to study the immune response to the viruses. Monkeys were inoculated intranasally with the viruses, and at 10 weeks post-infection they were re-infected with homologous subtype viruses. Virus-specific IgM and IgG serum antibodies were measured by ELISA. A small peak of IgM antibody was detected in the monkeys re-infected with HPIV-4B, whereas this response was not detected after re-infection with HPIV-4A. Virus-specific IgA and IgE antibodies were not detected in sera following infection and re-infection with HPIV-4. However virus-specific IgA and IgE antibodies were found in the saliva and nasal exudates of monkeys infected with either HPIV-4A or -4B. Re-infection of monkeys with HPIV-4B also stimulated an IgA and IgE response. To our knowledge this is the first description of an experimental animal. The kinetics of haemagglutinin-inhibition and neutralization (NT) antibodies were similar to that of virus-specific IgG antibodies. The NT titres of sera from HPIV-4A-infected monkeys were enhanced by the addition of complement, whereas complement did not affect the NT activity of sera obtained from HPIV-4B-infected animals. Antigenic specificities of IgG antibody induced by HPIV-4 infection were analysed with radioimmunoprecipitation followed by SDS-PAGE. Anti-NP, -HN and -F antibodies appeared 2 weeks after infection, and the highest titres were found 2 weeks after re-infection. Anti-F antibody production followed a biphasic pattern previously observed in mumps virus infection.
Animals↗
In vitro and in vivo interferon production in NOD mice.
The production of interferon-alpha/beta (INF-alpha/beta) and interferon gamma (IFN-gamma) in NOD and ICR mice was studied in vitro and in vivo. The in vitro IFN-alpha/beta production in the spleen cells of NOD mice, which were stimulated with either Newcastle disease virus (NDV), Sendai virus, poly(I:C) or lipopolysaccharide (LPS), was very similar to the IFN-alpha/beta production in the spleen cells of ICR mice. Contrastingly, the in vitro IFN-gamma production in the spleen cells of NOD mice, which were stimulated with either concanavalin A (Con A), phytohemagglutinin (PHA) or pokeweed mitogen (PWM), was greater than the IFN-gamma production in spleen cells of ICR mice. The in vivo IFN-alpha/beta production in NOD mice induced by NDV was also very similar to that in ICR mice, whereas the in vivo IFN-gamma production in the BCG-sensitized NOD mice, which was induced by purified protein derivative (PPD), was greater than that in the ICR mice. These results may indicate that NOD mice have abnormalities on the IFN-gamma production.
Animals↗