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Biomedical subjects

N Ohno

Publications and source records attributed to N Ohno.

At least 145 records · Page 8Linked to original sources

Modulation of the antitumor effect and tissue distribution of highly branched (1-->3)-beta-D-glucan, SSG, by carrageenan.

The action of carrageenan (CAR), a representative blocking reagent for phagocytes, on the antitumor effect and tissue distribution of highly branched (1-->3-beta-D-glucan, SSG, was examined. CAR inhibited the antitumor effect of intraperitoneally administered SSG only when applied before inoculation of the tumor, and had little effect when applied after tumor inoculation. A similar result was observed when SSG was administered intralesionally. In contrast, CAR had considerable effect on tissue distribution of i.p. SSG. The differences with respect to the results in normal mice were: 1) the distribution of SSG from the peritoneal cavity to the rest of the body was inhibited, 2) large numbers of peritoneal exudate cells (PEC) were produced and a relatively high concentration of 3H-SSG was found in the PEC fraction 48h after administration of 3H-SSG, 3) one week after administration, 3H-SSG was distributed to throughout the body but the amount of 3H-SSG distributed was lower than in normal mice, 4) a significant amount of 3H-SSG was recovered from ligaments (containing omental milky spots, peritoneum, mesentery and associated fat) in which negligible amounts were found in normal mice. The results suggest that the inhibition of the antitumor effect of SSG by CAR probably results from the prevention of the natural resistance of mice which is related to phagocytic function, and that the distribution of SSG to throughout the body is significantly modulated by CAR.

Animals↗

Resistance of highly branched (1-->3)-beta-D-glucans to formolysis.

Small molecular weight (MW) glucan derivatives could be a useful tool for studying the mechanisms of beta-glucan mediated biological activity, especially as antagonists for a beta-glucan receptor. This paper described the stability of various (1-->6) branched (1-->3)-beta-D-glucans to formolysis in the preparation of small MW derivatives. The glucans used were curdlan (linear), pachyman (few branches), GRN (one branch in every third main chain unit; 2/6), SPG (2/6), SSG (3/6), and OL-2 (4/6). Curdlan and pachyman were easily degraded to oligosaccharides by degradation for 20 min at 100 degrees C by 90% formic acid. However, branched glucans, especially the highly branched glucans, SSG and OL-2, were significantly resistant to degradation, and the majority remained high MW. SSG required a longer period and/or a higher temperature (121 degrees C treatment) to produce small MW derivatives. Branched glucans were also resistant to zymolyase (an endo-(1-->3)-beta-D-glucan hydrolase) digestion. These facts suggest that the (1-->6)-beta-D-branched residues contribute to the glucans' resistance to formic acid degradation and zymolyase digestion.

Animals↗

Metabolic 13C-labeling of an antitumor (1-->3)-beta-D-glucan, SSG, from Sclerotinia sclerotiorum IFO 9395.

A (1-->3)-beta-D-glucan, SSG, from Sclerotinia sclerotiorum IFO 9395 was metabolically labeled using [1-13C] and [2-13C]glucose, and the fate of the 13C-label was examined by 13C-NMR spectroscopy. 13C-NMR spectra of metabolically labeled SSG (13C-SSG) showed that most of the 13C-label in glucose residues of 13C-SSG were recovered from the originally labeled sites of carbon in glucose residue, and suggested little rearrangement during take-up from the medium. In the case of poor SSG producing culture conditions (reduced shaking rate), 13C-glucose incorporation in SSG molecule was similar to that in the case of high SSG-producing culture conditions. In addition, significant amounts of 13C-labeled trehalose were found in 13C-NMR spectra of the mycelium cultured in both poor and high SSG-producing conditions. These results suggested that different culture conditions affected SSG production, but not the metabolism of glucose and the biosynthetic pathway of SSG.

Antineoplastic Agents↗

Combination chemotherapy (RCM protocol: response-oriented cyclic multidrug protocol) for the acute or lymphoma type adult T-cell leukemia.

43 patients with the acute or lymphoma type ATL were treated with the new combination chemotherapy (RCM protocol: response-oriented cyclic multidrug protocol) between January 1989 and December 1991. Complete response (CR) and partial response (PR) were achieved in 20.9% and 65.1% of all treated patients respectively. The median duration of survival was 6.0 months. The survival duration of patients with a high serum lactate dehydrogenase (LDH) value (> or = 1,000 unit) and/or a poor performance status (PS) (PS 3 or 4) were also improved but not in patients with a severe leukocytosis (> or = 35,000/microliters). Toxicity was mild (grade 1 or 2) except hematologic toxicity in 4 patients (9.3%) and alopecia in one patient (2.3%). In spite of many patients with a poor PS (PS 3 or 4), our chemotherapeutic results are equal or superior to other previous reports. It seems that response-oriented chemotherapy is suitable for the ATL patients with poor prognostic factors. These results indicate that the RCM protocol is very useful as the first choice chemotherapy for the acute or lymphoma type ATL.

Adult↗

Significance of elevated levels of soluble factors in the cerebrospinal fluid in patients with adult T-cell leukemia.

Although it has been recognized previously that several markers are present in the cerebrospinal fluid (CSF), their clinical usefulness of these markers in the diagnosis of malignant lymphoma infiltrating to the CNS has not yet been established. In order to determine their diagnostic usefulness as markers of meningeal infiltration by lymphoma cells in patients with adult T-cell leukemia (ATL), we measured some soluble factors in the CSF of patients with ATL and non-ATL patients. Soluble CD4 (sCD4) was highly elevated in all patients with ATL and meningeal infiltration. The CSF level of the soluble interleukin-2 receptor (sIL-2R; sCD25) was markedly elevated in 13 (72.2%) of 18 patients with ATL and meningeal infiltration. Levels of sCD4 and sCD25 in the CSF of patients with ATL and meningeal infiltration were significantly higher than in non-ATL patients (p < .01 and p < .001, respectively). These findings indicate that levels of sCD4 and sCD25 in the CSF are probably associated with meningeal infiltration by leukemia cells expressing CD4 and CD25 on surface membranes. CSF levels of sCD4 in 14 (60.9%) of 23 ATL patients and sCD25 in 13 (72.2%) of 18 ATL patients without meningeal infiltration were moderately elevated. These findings suggest that a small number of leukemic cells which were not detected by conventional CSF examination may have infiltrated the meninges in these patients. Sequential measurements of sCD4 and sCD25 in CSF obtained from patients with meningeal infiltration by leukemic cells showed that sCD4 and sCD25 levels reflected the activity of leukemic meningitis and correlated with the number of cells in CSF. However, the levels of sCD4 in CSF did not fall below the limit of detection even when the number of cells in CSF became normal. It is thought that the level of sCD4 in CSF is a more sensitive marker for detecting the infiltration of leukemic cells in CSF than the number of cells present in the CSF considering the clinical course of two patients with acute type ATL. Therefore, ATL patients with meningeal infiltration should receive treatments until sCD4 levels become normal and not just until the number of cells become normal. Our results also suggest that measurement of CSF levels of sCD4 and sCD25 is useful for the differential diagnosis of aseptic meningitis and meningeal infiltration by leukemic cells in patients with smoldering ATL. We conclude that measurement of soluble factors in CSF plays an important role in diagnosis, prophylaxis and treatment of meningitis in patients with ATL.

Biomarkers, Tumor↗

[Mitral and aortic annular enlargement for small mitral annulus after mitral annuloplasty].

Mitral and Aortic valve rings were enlarged in a 70-year-old female with tiny mitral annulus after mitral annuloplasty before. She had undergone aortic valve replacement with No. 21 SJM valve and Kay's annuloplasty 10 years previously. The reoperation was needed because of mitral stenosis and tricuspid regurgitation. We applied the Manouguian technique for the enlargement of the mitral annulus because it was too small to implant a prosthetic valve, even though the Aortic prosthetic valve was functioning well. As too tight a mitral annuloplasty may make the possibility of mitral stenosis real, we should make the annulus remain wide enough.

Aged↗

[A case report of tracheal stenosis due to true aortic arch aneurysm of retroesophageal right aortic arch associated with so called vascular ring-facial syndrome].

A 63-year-old man admitted to our hospital because of dyspnea and inspiratory stridor. The X-ray computed tomography and angiogram revealed tracheal stenosis due to compression by aortic arch aneurysm of retroesophageal right aortic arch. His face was congenitally asymmetrical, and he also showed anotia, and meatal atresia. In the operation, we approached the aneurysm via median sternotomy and left thoracotomy by the 3rd intercostal space, and found atretic left aortic arch in front of trachea. So, operative diagnosis was Edwards Ib complete vascular ring associated with right aortic arch aneurysm. The aneurysm was incised and the arch and its branches were reconstructed with vascular prosthesis under ECC using selective cerebral perfusion. Postoperatively, until 5th postoperative day his condition was uneventful, and he was neurologically almost normal. But on the 5th postoperative day, his hemodynamics suddenly deteriorated because of severe pneumonia and septicemia. On the 6th postoperative day, he died in spite of earnest resuscitation. We could not find any previous reports about this rare combination of diseases.

Abnormalities, Multiple↗

[A successful case of emergency CABG using PCPS due to acute myocardial infarction].

A successful case of emergency CABG (Coronary Artery bypass Grafting) by using PCPS (Percutaneous Cardio Pulmonary Bypass) for a 60-year-old with shock due to acute myocardial infarction was reported. He developed shock due to acute myocardial infarction before arrival at our hospital. He was resuscitated by PCPS. Coronary angiography revealed that LMT was 99% stenosed and LAD just proximal was totally occluded. Emergency CABG was performed to LAD and CX using saphenous vein grafts. Post-operative course was uneventful and the patient was discharged at hospital two months after the operation. PCPS is useful for bridge until emergency CABG.

Cardiopulmonary Bypass↗

[The hazards of coronary revascularization under hypothermic ventricular fibrillation].

Since January 1992 till June 1994, we experienced 22 cases of coronary revascularization (CABG) under hypothermic ventricular fibrillation (Vf) in patients with unclampable ascending aorta (Group 2). We compared them with patients undergoing conventional CABG with cardioplegic cardiac arrest (Group 1). All these 362 cases were primary isolated CABG. Comparing preoperative patient profile, patients of Group 2 were older (Group 1: 64.3 +/- 8.5, Group 2: 68.2 +/- 6.7 year old, p < 0.05), had more unstable angina (Group 1: 20.3%, Group 2: 54.5%, p < 0.001), and had more severe NYHA classification (Group 1: 2.22 +/- 0.55, Group 2: 2.73 +/- 0.46, p < 0.05) than Group 1. There were no significant difference between both groups about other factors. Comparing post operative complication, low output syndrome (Group 1: 2.6%, Group 2: 18.2%, p < 0.005) perioperative myocardial infarction (PMI) (Group 1: 4.4%, Group 2: 36.4%, p < 0.0001) ventricular tachycardia (VT) (Group 1: 1.4%, Group 2: 18.2%, p < 0.0001), respiratory failure (Group 1: 3.8%, Group 2: 18.2%, p < 0.005), and post operative hospital death (Group 1: 2.9%, Group 2: 18.2%, p < 0.0005) occurred more frequent in Group 2 than Group 1. Other complication (renal failure, wound infection, cerebrovascular accident, rethoracotomy for bleeding) equally occurred in both groups. Long Vf time (mean 92.8 minutes) and low perfusion pressure during Vf (mean 60.0 mmHg) were suspected to be major cause of high incidence of PMI and VT in Group 2. But there were no correlation between Vf time, perfusion pressure and occurrence of PMI and/or VT.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

[Risk factors of wound infection following cardiac surgery and antimicrobial prophylaxis].

To make investigation about risk of wound infection following cardiac surgery, we analyzed cases of primary aorto-coronary bypass surgery and/or primary valvular surgery. Cases required respirator for longer than 2 days, and those with drainage tube for longer than 5 days were excluded from this study, because these cases had antimicrobial agent postoperatively as therapeutic use rather than prophylactic use. Those received preoperative antimicrobial agent for infectious endocarditis and so on were also excluded for the same reason. 523 cases were entered this study. These cases received cefazolin (CEZ) postoperatively as prophylaxis. Sternal wound and leg/groin wound were separately analyzed. Risk factors (age, sex, diabetes mellitus, unstable angina, use of intraaortic balloon, internal thoracic artery harvest, re-exploration, previous myocardial infarction, NYHA classification, emergent operation, operation time, extracorporeal circulation time, blood product use, preoperative blood hemoglobin concentration, preoperative serum albumin, preoperative creatinine clearance (Ccr), duration of drainage tube insertion, body surface area, daily dose of CEZ, duration of prophylaxis) were examined using univariate (Chi square test was used for contingency table analysis, unpaired t test was used to compare averages) and multiple regression analysis. For sternal wound infection, only Ccr showed significant (P = 0.027) correlation. For leg/groin wound infection, 2 factors (smaller daily dose of CEZ: P = 0.009, more severe NYHA class: P = 0.03) showed significant correlation. To investigate appropriate duration of CEZ prophylaxis, cases were divided into 2 groups, those had CEZ within 48 hours postoperatively (group S) and those had CEZ for longer than 48 hours (group L).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[A case report of successful surgical treatment of acute postinfarction left ventricular free wall rupture using the percutaneous cardiopulmonary support system].

The percutaneous cardiopulmonary support system (PCPS) was used in a 75-year-old female with a blow out type heart rupture of the posterior wall complicating acute myocardial infarction. The patient was transported to the operating room with the PCPS and IABP in place, and had the ventricular rupture repaired as well as CABG. Although the postoperative cardiac function was satisfactory she sustained ischemic cerebral stroke and went on to die of aspiration pneumonia 166 day later. PCPS buys time to enable surgical repair of the heart, but how to protect the brain remains as a problem to be solved.

Aged↗

[Surgical treatment of infective endocarditis: application of DNA probe method].

DNA probe method is a new bacteriological method for diagnosis of bacteria. The authors tried to apply the method to diagnosis of bacteremia and treatment of infective endocarditis. We could diagnose the patient's illness as bacteremia with this method even when blood cultures are not positive. We suggest that cardiac surgery should be performed in case bacteria is detected repeatedly with DNA probe method. Therefore it is useful for decision whether cardiac surgery for patients with active infective endocarditis should be done or not.

Adolescent↗

The alpha 3 chain of type IV collagen prevents activation of human polymorphonuclear leukocytes.

Our initial observation that type I collagen activates polymorphonuclear leukocytes (PMN) prompted the testing of the activating potential of type IV collagen. It was noted, however, that type IV collagen isolated from bovine lens capsule did not activate PMN but rather prevented their stimulation by N-formylmethionyl-leucyl-phenylalanine, phorbol myristate acetate, or type I collagen. This observation led to the present study, which demonstrates that the inhibitory effect of lens capsule type IV collagen resides in the noncollagenous (NC1) domain of the alpha 3 chain and specifically in the region comprising residues 185-203 of the NC1 domain of both the human and bovine molecules. Synthetic peptides from the same region of the NC1 domains of the alpha 1, alpha 2, alpha 4, and alpha 5 chains did not possess the inhibitory effect seen with the alpha 3 chain. The sequence S-N-S (residues 189-191) is unique to the peptide of the alpha 3 chain, and substitution of either serine with alanine abolishes the inhibition. Type IV collagen isolated from the mouse Engelbreth-Holm-Swarm (EHS) tumor, a molecule that lacks the alpha 3 chain, did not prevent PMN activation but instead stimulated the secretion of elastase and type IV collagenase. Incubation of PMN with intact lens capsule type IV collagen or a peptide comprising residues 185-203 of the alpha 3 (IV) chain resulted in a 3-fold increase of intracellular cAMP, whereas, Ca2+ levels remained unchanged. Incubating PMN with forskolin or with dibutyryl-cAMP resulted in the inhibition of O2- production and degranulation by PMN, thus mimicking the effects of type IV collagen and the alpha 3 (IV) 185-203 peptide. The data suggest that type IV collagen, through its alpha 3 chain, down-regulates PMN activation and thus decreases the potential for damage as these cells traverse the capillary wall. Our in vitro experiments suggest that the higher the content of the alpha 3 (IV) chain is in a basement membrane, the wider would be its capacity for self-protection.

8-Bromo Cyclic Adenosine Monophosphate↗

Preparation and properties of metabolically 3H- or 13C-labeled (1-->3)-beta-D-glucan, SSG, from Sclerotinia sclerotiorum IFO 9395.

Metabolically labeled (1-->3)-beta-D-glucan (SSG) obtained from the culture filtrate of Sclerotinia sclerotiorum IFO 9395, with the radio (3H) or the stable isotope (13C) was prepared. The specific radioactivity of 3H-SSG was increased in accordance with the amount of D-[3H]glucose added, and was 15-20 kBq/mg SSG when 222 kBq/mL of D-[3H]glucose was added. Physicochemical analyses of 3H-SSG suggested a structural similarity between SSG and 3H-SSG. 13C NMR spectra of 13C-labeled SSG (13C-SSG) revealed that a strong signal of the 13C-nucleus was observed at the C-1 or C-2 position when D-[1-13C]glucose or D-[2-13C]glucose was used, respectively, suggesting that most of the glucose residues in SSG were directly taken up from the medium. In addition, part of the 13C-nucleus was incorporated into the SSG molecule at all carbon atoms after metabolic degradation and reconstruction of the glucose molecule. Analyses of the culture filtrate and the mycelium of the fungus suggested that part of the glucose was also metabolized to trehalose and mannitol.

Ascomycota↗

Elevated soluble CD4 levels in the cerebrospinal fluid in patients with adult T-cell leukemia.

Levels of the soluble form of the leukocyte surface antigen CD4 (sCD4) were measured by enzyme linked immunosorbent assay (ELISA) in the cerebrospinal fluid (CSF) of patients with adult T-cell leukemia (ATL) and other malignant and non-malignant diseases. All patients with ATL and meningeal infiltration had markedly elevated levels of sCD4 in the CSF (53.7 +/- 34.9 U/ml). ATL patients without CSF pleocytosis often had elevated levels of sCD4 (15.1 +/- 9.2 U/ml). Non-ATL patients with CSF pleocytosis had elevated levels of sCD4 (23.3 +/- 12.2 U/ml) and those without CSF pleocytosis also showed elevation of sCD4 levels (16.8 +/- 9.3 U/ml). However, the mean levels of sCD4 in CSF from these patients were significantly lower than ATL patients with meningeal infiltration. Soluble CD4 in the CSF from healthy volunteers were below the detectable limit. We conclude that meningeal infiltration of CD4(+) ATL cells is strongly associated with elevated sCD4 levels in CSF, and some part of sCD4 in CSF may be originated from the native cells in the CNS as a response of inflammatory stimulations. Therefore, measurement of sCD4 may be useful in the diagnosis of meningeal infiltration and/or meningeal irritation in patients with ATL.

CD4 Antigens↗

Detoxification of lipopolysaccharide (LPS) by egg white lysozyme.

Recent studies carried out by our group suggest that lysozyme binds to bacterial lipopolysaccharide with a high affinity to produce a complex, and inhibits various biological activities of lipopolysaccharide. Although the basic structure of lipopolysaccharide is independent of the species and strains of Gram-negative bacteria, many structural factors such as O-antigenic polysaccharide, lipid A, substituted groups, and associated molecules, affect the biological activities of lipopolysaccharide. In this study, we prepared lysozyme/lipopolysaccharide complexes using various structures of lipopolysaccharide and compared the activity and physicochemical properties. Native and dansylated lysozyme were found to bind to all tested lipopolysaccharides. The mitogenic activity and TNF production by all tested lipopolysaccharides were significantly reduced by complex formation in vitro. Administration of the complex prepared by various lipopolysaccharides produced significantly less quantities of TNF in the septic shock model. These results suggested that binding of lysozyme to lipopolysaccharide is important for the host both in pathophysiological responses to lipopolysaccharides and in the modification of lipopolysaccharide biological activity.

Animals↗

Binding of lysozyme to lipopolysaccharide suppresses tumor necrosis factor production in vivo.

Endotoxin (lipopolysaccharide [LPS]) released during gram-negative bacterial infection induces varieties of cytokines which directly and/or indirectly cause shock, disseminated intravascular coagulation, and death. We previously showed that lysozyme (LZM) was an LPS-binding protein and inhibited various immunomodulating activities of LPS. In this study, we examined the effect of LZM on the LPS-triggered septic shock model induced by carrageenan treatment and assessed by tumor necrosis factor production. The data presented in this report strongly suggest that LZM-LPS complex formation completely abrogates tumor necrosis factor production and the mortality caused by LPS and that LZM may be useful for the treatment of endotoxin shock.

Animals↗

Differential expression of colony-stimulating factor (CSF) in murine macrophage clones: interferon-gamma-mediated inhibition of CSF production.

Bioassay and northern blot analyses revealed that, among several functional murine macrophage (M phi) clones, lipopolysaccharide (LPS) stimulation generated in distinct induction levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and macrophage colony-stimulating factor (M-CSF). When compared with these induction profiles, the M phi clones could be classified into two types; G type (G-CSF GM-CSF-M-CSF+) and GM type (G-CSF +/- GM-CSF M-CSF+) of M phi clones. Unlike G-CSF and GM-CSF that were inducible factors, M-CSF mRNA was constitutively expressed without stimulation and was differentially controlled between the G and GM types; LPS induction decreased M-CSF mRNA in the former, but increased it in the latter. Further northern blot analysis revealed that interferon-gamma (IFN-gamma) suppressed constitutive expression of M-CSF mRNA, and that costimulation with both LPS and IFN-gamma reduced expression of G-CSF and M-CSF mRNA in the G type of M phi clone, but induced higher expression of GM-CSF and M-CSF mRNAs in the GM type of M phi clone compared with LPS alone. However, in either case, IFN-gamma completely inhibited LPS-induced production of active CSF of the M phi clones, which was observed even in IFN-gamma pretreatment, and also abrogated autoactivation of GM-CSF. Our present results suggested that murine M phi clones had differentially regulated expression of CSFs and that IFN-gamma had a regulatory function of inhibiting CSF production of murine M phi s.

Animals↗