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Biomedical subjects

K Deguchi

Publications and source records attributed to K Deguchi.

At least 19 recordsLinked to original sources

Augmentation of retinoic acid-induced granulocytic differentiation in HL-60 leukemia cells by serine/threonine protein phosphatase inhibitors.

To evaluate the involvement of protein phosphatases (PP) in differentiation of human myelogenous leukemia HL-60 cells, we made use of potent inhibitors of PP1 and PP2A, calyculin-A (CAL-A) and okadaic acid (OKA). CAL-A and OKA could augment all-trans retinoic acid (ATRA)-induced granulocytic differentiation, whereas the differentiation toward macrophage lineage by 12-o-tetradecanoylphorbol acetate (TPA) was unchanged in the presence of CAL-A. CAL-A augmented the phosphorylation of 18K, 23K and 30K proteins induced by ATRA. The PP1 and PP2A were identified and were present mainly in the cytosol of HL-60 cells. These results suggest that either PP1 or PP2A or both may be involved in regulating granulocytic differentiation of HL-60 cells.

Cell Adhesion

Plasma cytokine levels in thrombotic thrombocytopenic purpura.

Plasma cytokine levels were examined in 13 patients with thrombotic thrombocytopenic purpura (TTP). Auto-antibodies, platelet-associated immunoglobulin G, and platelet aggregating factor were detected in many of these patients and high-molecular-weight bands of von Willebrand factor multimers were reduced in 9 of 10 patients examined. Complete remission (CR) was attained in 7 of the 13 patients, but 6 died. Tumor necrosis factor (TNF), Interleukin (IL)-1 beta, IL-6, and soluble IL-2 receptor showed marked increases at onset and decreased at CR. The prognosis tended to be poor in patients with increased IL-6 and soluble IL-2 receptor levels. These findings suggest that immunological mechanisms, such as the activation of macrophage, are involved in the pathogenesis of TTP and are reflected in the plasma cytokine levels.

Adolescent

Electrophysiological follow-up of acute and chronic experimental allergic encephalomyelitis in the Lewis rat.

Cortical somatosensory evoked potentials (c-SEP) and flash visual evoked potentials (f-VEP) were serially recorded in acute monophasic and chronic relapsing experimental allergic encephalomyelitis (EAE) in the Lewis rat. In acute EAE, a significantly delayed latency and broadened peak of the c-SEP were observed corresponding to the clinical onset, and then returned to normal with the disappearance of clinical signs. In chronic EAE, the c-SEP showed the same changes as in acute EAE, also reflecting the first attack, remission and relapsing phase. However, chronic EAE, when paralysis had recovered in the relapsing phase, showed c-SEP abnormalities suggestive of subclinical active lesions. In contrast, the f-VEP showed no obvious abnormalities in acute or chronic EAE. These findings suggest that the c-SEP is an objective and sensitive index for detecting clinical and pathological changes in acute and chronic EAE in the Lewis rat.

Animals

Inhibition of platelet aggregation by the cAMP-phosphodiesterase inhibitor, cilostamide, may not be associated with activation of cAMP-dependent protein kinase.

We examined the involvement of cAMP-dependent protein kinase (A kinase)2 in the inhibition by cilostamide, a specific inhibitor of the low Km cAMP-phosphodiesterase (PDE), on 9,11-epithio-11,12-methanothromboxane A2 (STA2)-induced platelet aggregation. For comparative purposes, the PGE1 analogue, 17S-20-dimethyl-trans-delta 2-PGE1 (OP-1206) was used. OP-1206 (IC50 = 18 +/- 0.55 nM) and cilostamide (IC50 = 40 +/- 4.5 nM) were both potent inhibitors of the platelet aggregation induced by STA2 (1 microM). OP-1206 and cilostamide dose-dependently inhibited elevations in intracellular free Ca2+ ([Ca2+]i) caused by STA2. OP-1206 caused an almost complete inhibition of Ca2+ mobilization, but cilostamide did not prevent the STA2-induced elevation in [Ca2+]i to the same extent as OP-1206, even at a high concentration (greater than 200 nM). Cilostamide did not increase the cAMP level at concentrations (5-100 nm) which affected STA2-induced aggregation. OP-1206 significantly increased cAMP contents in platelets, and the degree of aggregation inhibition by OP-1206 appears to be related to the size of increase in cAMP. OP-1206 increased phosphorylation of the 50,000 mol. wt vasodilator-stimulated phosphoprotein, at concentrations of 7.9-79 nM, which inhibited aggregation induced by STA2. Cilostamide treatment resulted in a marginal increase in the 50,000 mol. wt phosphorylation at concentrations (10-100 nM) which completely inhibited the STA2-induced aggregation. (8R*, 9S*, 11S*)-(-)-9-Hydroxy-9-n-hexyloxy-8-methyl-2,3,9,10- tetrahydro-8,11-epoxy-1H, 8H, 11H-2, 7b, 11a-triazadibenzo(a,g)-cycloocta(c,d,e)trinden-1-one (KT-5720), a specific inhibitor of A kinase, not only reversed the inhibition by OP-1206 of STA2-induced platelet aggregation, but also inhibited the OP-1206-induced protein phosphorylation. However, the inhibition by cilostamide of STA2-induced aggregation was not prevented by pretreatment with KT-5720. Inhibition of the STA2-induced aggregation by OP-1206 may be associated with cAMP-dependent protein phosphorylation, while cilostamide may have inhibitory effects on STA2-induced platelet activation through mechanisms other than the activation of A kinase.

3',5'-Cyclic-AMP Phosphodiesterases

In vitro anti-tumor activity of anti-c-erbB-2 x anti-CD3 epsilon bifunctional monoclonal antibody.

With the aim of developing an effective cancer immunotherapy for common epithelial cancer, a new class of bifunctional antibody (BFA) was developed; one arm of this BFA recognized c-erbB-2 gene product, and the other arm recognized CD3 epsilon, a T-cell specific surface antigen. Application of this BFA with human peripheral blood lymphocytes exhibited specific anti-tumor activity in vitro on a breast tumor cell line, ZR-75-1, which expressed abundant c-erbB-2 gene product on its cell surface. These results indicate that BFA recognizing an oncogene product on cell surface is a potential new agent for cancer immunotherapy.

Antibodies, Monoclonal

[Epidemiological and bacteriological study on gonococcal infections].

Epidemiological and bacteriological studies on Neisseria gonorrhoeae isolated in Sapporo, Japan, in 1980 and 1991 performed and the following results were obtained. 1. The range of age in the patients infected with Neisseria gonorrhoeae tended to be younger than those in the whole country. 2. Male patients in the early 20s or younger with gonococcal urethritis were often infected by bon-professional females but those in their late 20s or older were often infected from professional females, for example prostitutes and hostesses. 3. The rate of professional females who were positive to gonococci reached 17.4% and young females in their teens with cervicitis had the highest morbidity rate of gonococci than those in the older females. 4. The latent period in gonococcal infections tended to become longer gradually. 5. The isolation rate of penicillinase producing Neisseria gonorrhoeae (PPNG) showed a peak of 23.9% (61/255) in 1985, but gradually declined thereafter and it was 3.7% (1/27) in 1991. 6. An investigation on auxotype showed a decline of proto and Pro-strains and an increase of AHU-strains in non-PPNG. And most of the PPNG belonged to proto or Pro-strains. 7. With the relationship between auxotype and sensitivity to AMPC, AHU-strains were more sensitive than proto or Pro-strains.

Adolescent

Primary epidural non-Hodgkin's lymphoma in clinical stage IEA presenting with paraplegia and showing complete recovery after combination therapy.

A 70-year-old man was admitted to our hospital because of paraplegia. A spinal epidural tumor (Th VII-XI) was diagnosed by magnetic resonance imaging and resected. Histological examination of the tumor showed non-Hodgkin's lymphoma of the diffuse large cell type (Lymphoma Study Group classification), with a B cell phenotype. The clinical stage was IEA by the Ann Arbor classification. Radiation therapy of the involved field was performed (total dose: 40 Gy), followed by six courses of modified cyclophosphamide, adriamycine, vincristine, prednisolone (CHOP) therapy. He was discharged walking unaided 10 months later and has shown no evidence of relapse in the 26 months since discharge.

Aged

Late-onset homozygous protein C deficiency manifesting cerebral infarction as the first symptom at age 27.

We report a 31-year-old female who had repeated thrombosis and was diagnosed as having congenital homozygous protein C deficiency based on decreased protein C antigen and activity, and the findings of family history. This patient had shown no symptom of thrombosis until the age of 27 years, when she had cerebral infarction as the first symptom. Low molecular weight heparin was useful for disseminated intravascular coagulation (DIC) that complicated protein C deficiency in this patient.

Adult

Chronic subdural hematoma following bypass surgery--report of three cases.

Bypass surgery is a safe procedure with low mortality and morbidity, and few reported surgical complications. Three patients developed postoperative chronic subdural hematoma (CSDH): two with stroke after superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis and one with moyamoya disease after STA-MCA anastomosis combined with encephalomyosynangiosis. The factors inducing CSDH after revascularization in the seven reported and present cases included postoperative subdural effusion associated with brain atrophy, and postoperative anticoagulant therapy such as aspirin. CSDH may occur in patients with pre-existing brain atrophy and postoperative subdural effusion. Anticoagulant therapy should be avoided at the early postoperative stage after bypass surgery.

Brain

Glucose as regulator of glucose transport activity and glucose-transporter mRNA in hamster beta-cell line.

To investigate the role of glucose in regulating glucose transporters in pancreatic beta-cells, we studied the hamster clonal beta-cell line HIT-T15, which retains responsiveness to glucose. Northern blot analysis demonstrates that GLUT2 and GLUT1 mRNA are abundant in HIT cells. After a 24-h culture with various concentrations of glucose (0-22.2 mM [0-400 mg/dl]), the GLUT2 mRNA level in HIT cells increased by 40% at 22.2 mM (400 mg/dl) glucose compared with 11.1 mM (200 mg/dl) without a change in mRNA stability. It also decreased proportionally to the reduction of glucose concentration. Glucose deprivation resulted in a decrease of GLUT2 mRNA to an almost undetectable level, with a marked increase in the degradation rate of mRNA. In contrast, the GLUT1 mRNA was not affected by glucose. We show that glucose uptake is highest in HIT cells incubated at 2.8-5.5 mM (50-99 mg/dl) glucose for 24 h, and that levels in cells cultured at 0 mM (0 mg/dl) and 22.2 mM (400 mg/dl) glucose decrease to approximately 20% of the maximum level. This decrease is consistent with the effects of glucose on glucose-stimulated insulin secretion in HIT cells. Our results indicate that glucose is involved in regulating GLUT2 mRNA and glucose uptake activity and that the glucose responsiveness of the insulin secretion correlates with the glucose-induced change in glucose uptake activity in HIT cells.

Animals

[Antibacterial activity of rokitamycin against fresh clinical isolates].

We obtained bacterial strains which were clinically isolated and identified from outpatients with various infections in medical institutions throughout Japan. Possible antibacterial activities of rokitamycin (RKM) were examined against these isolates. Minimum inhibitory concentrations (MICs) were determined through a comparative study with reference drugs. The results of the study are summarized as follows. 1. Resistance patterns of 400 isolates which were highly resistant to macrolides (MLs) with MIC values > 100 micrograms/ml were classified into 55 patterns. Staphylococcus spp. showed cross resistance to 14-membered ring MLs with 100% cross resistance observed between erythromycin (EM) and clarithromycin (CAM), and 85.2% between EM and oleandomycin (OL). Fewer isolates showed strong resistance to 16-membered ring MLs than to 14-membered ring MLs. Cross resistances observed among the Staphylococcus isolates were 100% between acetylmidecamycin (MDM-AC) and kitasamycin (leucomycin (LM)), 93.9% between MDM-AC and josamycin (JM), and 53.3% between MDM-AC and RKM. Streptococcus spp. and Peptococcus spp. showed very similar resistance patterns to both 14- and 16-membered ring MLs, but resistance patterns to RKM were quite different. Most of anaerobic streptococci and Bacteroides fragilis group had similar resistance patterns to 14- and 16-membered ring MLs, but in some cases a pattern similar to that of Staphylococcus spp. was observed. 2. When ML-resistant bacteria isolated during 1975 to 1980 were compared to those isolated in 1986 and 1989, it was observed that resistance of Staphylococcus aureus remained almost unchanged, that of Streptococcus pyogenes was lower in the later years than during 1975 to 1980, but that of Streptococcus pneumoniae increased. 3. Most of ML-resistances of the resistant isolates were inducible, but extents of induction varied depending on drugs tested. Strong inductions were observed when 14-membered ring MLs were used, but inductions were minimal with 16-membered ring MLs. RKM appeared to induce resistance to the least extent. From these results, it appears that the RKM is quite useful clinically even in the 1990s.

Bacterial Infections

[The changes in molecular markers for hemostatic activation after t-PA therapy in case of pulmonary embolism].

We observed the changes of molecular markers for hemostatic activation in a patient with acute pulmonary embolism treated with 2 x 10(7) unit tissue plasminogen activator (t-PA). Blood samples were obtained before, just after, at 30 min, 1, 2, 6, and 24 hours after the infusion. Molecular markers included thrombin-antithrombin III complex (TAT), plasminogen-alpha 2 plasmin inhibitor complex (PIC), and thrombomodulin (TM). Marked elevation of TAT was observed from immediately after the t-PA infusion to 6 hours after, although it had been observed for only 1 hour in our previous report on the cases of acute myocardial infarction. PIC level was significantly increased during t-PA infusion but returned to almost baseline value 6 hours after the end of t-PA infusion. This finding was almost the same as the one previously reported concerning acute myocardial infarction cases. TM level increased throughout the evaluation, and remained so, even on the 7th day after t-PA infusion. Our present data revealed a clear difference between the reactive TAT increases after t-PA therapy in acute myocardial infarction cases and in acute pulmonary embolism cases. Our present data also revealed a prolonged elevation of TM during the acute period of pulmonary embolism. It is therefore necessary to keep an eye on the changes of molecular markers for hemostatic activation after t-PA therapy in acute pulmonary embolism.

Aged

[Combined effects of arbekacin with other antibiotics against methicillin-resistant Staphylococcus aureus. I. The combined effect of arbekacin with fosfomycin or clavulanic acid/ticarcillin].

As arbekacin (ABK) has a highly potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), its combined effects with fosfomycin (FOM) and clavulanic acid/ticarcillin (CVA/TIPC) against MRSA were examined. The obtained results are summarized as follows. 1. Against MRSA either combination, FOM+ABK or CVA/TIPC+ABK showed a strong antibacterial effect at the MIC or the sub MIC of ABK in the blood expected from clinical observations. The MIC of ABK by the combination use seemed to be equivalent to the MBC value. 2. Effective concentrations of antibiotics in these combinations appeared to be strongly dependent on the effective concentration of ABK and less dependent on that of FOM or CVA/TIPC. Therefore, the antibacterial activity of a combination seems to mostly depend on the antibacterial activity and the concentration of ABK. 3. As FOM and CVA/TIPC have antibacterial activities against Pseudomonas aeruginosa, combinations of ABK with these antibiotics are likely to be effective against double infection with P. aeruginosa in MRSA infected patients.

Aminoglycosides

[Combined effects of arbekacin with other antibiotics against methicillin-resistant Staphylococcus aureus. II. The combined effect of arbekacin with imipenem or cefminox].

Combined antibacterial effects of imipenem (IPM)+arbekacin (ABK) and cefminox (CMNX)+ABK against methicillin-resistant Staphylococcus aureus (MRSA) were examined and the obtained results are summarized below. 1. Either combination, IPM+ABK or CMNX+ABK, showed a strong antibacterial effect against MRSA when blood concentration of ABK were sustained at MIC as could be expected in clinical situations. While at sub MICs of ABK the antibacterial effect of these combination was slightly less than those of the previously reported combinations of ABK and other antibiotics. 2. Antibacterial effects of the combinations against MRSA were strongly dependent on the concentration of ABK and less dependent on the concentration of IPM or CMNX. As were observed in the previously tested combinations of ABK with other antibiotics, the antibacterial effect of the combination appeared to be highly dependent on the antibacterial activity and the concentration of ABK. 3. As IPM has potent antibacterial activities against Gram-negative bacteria (GNB) including Pseudomonas aeruginosa while CMNX has potent antibacterial activities against GNB except P. aeruginosa, it is likely that the combinations of IPM+ABK or CMNX+ABK are useful for treatment of infections with MRSA together with GNB.

Aminoglycosides

[Antimicrobial activities of major oral antibacterial agents against clinically isolated microbial strains from inpatients].

Antimicrobial activities were examined for major antibacterial agents against clinically isolated microbial strains which were isolated and identified from materials collected from inpatients with various infections in 1988, 1989 and 1990, and the following conclusions were obtained. 1. Among strains isolated each year, methicillin-resistant Staphylococcus aureus (MRSA) were found frequently. 2. CEPs-resistant Escherichia coli strains were observed among strains isolated each year. 3. Increasing tendencies in resistances of Citrobacter freundii, Enterobacter spp., Serratia marcescens to cephems and new quinolones were observed. 4. Increasing tendencies in resistances of Proteus vulgaris to ceftazidime (CAZ) and new quinolones appeared to exist. 5. Among strains isolated each year, resistances of Pseudomonas aeruginosa to CAZ and quinolones were observed in high rates, but also their resistances to imipenem appeared to increase. 6. Many of recently increasing multiple resistant bacteria seem to have different sites of drug action and/or to have non-hydrolytic modes of resistance.

Anti-Bacterial Agents

[Antimicrobial activities of major oral antibacterial agents against clinically isolated microbial strains from outpatients with respiratory tract infection].

Minimum inhibitory concentrations (MICs) were determined for major oral antibacterial agents for clinically isolated microbial strains from materials collected from outpatients with respiratory tract infections in 1988, 1989 and 1990, and the following conclusions were obtained. 1. Methicillin-resistant Staphylococcus aureus (MRSA) appeared to be responsible for community-acquired respiratory tract infections, but there also was a tendency showing that MRSA increased year by year. 2. A tendency was observed indicating that benzylpenicillin (PCG)-insensitive Streptococcus pneumoniae (PISP) increased year by year. 3. Beta-lactamase-producing strains of Haemophilus influenzae were observed in a certain ratio, and also those of Branhamella catarrhalis were found in high ratios. 4. A tendency of increasing resistance of Klebsiella pneumoniae to new quinolones was observed. 5. It is of a great importance to evaluate methods of selecting primary choice antibiotic agents since increasing numbers of new oral antibacterial agents are becoming rapidly available.

Anti-Bacterial Agents

[Antibacterial activities of sisomicin against fresh clinical isolates].

To investigate antibacterial activities of sisomicin (SISO), MICs of SISO as well as other aminoglycosides (AGs) were determined against many clinical isolates which were obtained in 1991. Results are summarized below: 1. No SISO-resistant strains were observed among isolates of Escherichia coli, Citrobacter diversus, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Proteus mirabilis and Morganella morganii. 2. In comparison with the results of our previous study against isolates obtained in 1986, the rate of methicillin-resistant Staphylococcus aureus (MRSA) was higher, and SISO-resistant strains were observed at a high rate among the MRSA. Also, SISO-resistant strains of Serratia marcescens increased. However, the rate of SISO-resistant strains of Pseudomonas aeruginosa decreased, and among Citrobacter freundii, Enterobacter cloacae and Proteus vulgaris, SISO-resistant strains did not increase over the years. 3. MICs of SISO against Providencia rettgeri and Providencia stuartii were high, suggesting that antibacterial activities of SISO was weak against genus Providencia. 4. For comparison, according to MICs of ofloxacin and imipenem, new quinolone-resistant strains were observed at a high rate among various organisms, and carbapenem-resistant strains were observed at a high rate among S. marcescens and P. aeruginosa. 5. SISO is still one of the useful AGs in the 1990's since it maintains its strong antibacterial activities against most clinical isolates obtained in recent years and its potential as a combination drug with beta-lactams is being reported.

Bacteria

[Combined effects of arbekacin with other antibiotics against methicillin-resistant Staphylococcus aureus. III. Combined effects of arbekacin with cefotiam or cefuzonam].

Antibacterial effects of combination use of arbekacin (ABK) with cefotiam (CTM) or cefuzonam (CZON) were evaluated against methicillin-resistant Staphylococcus aureus (MRSA) and the following results were obtained. 1. Antibacterial effects of combinations of ABK with CTM and with CZON were equally potent against MRSA at clinically expected 1 MIC of ABK in blood. However, at a sub MIC of ABK the different effects were observed between the 2 combinations. The antibacterial effect of the former was strong and that of the latter was a little weak. 2. In either combination the potency of the antibacterial activity was less dependent on the concentration of CTM or CZON, but was strongly dependent on ABK concentrations. These results suggest that antibacterial effects of the combinations were highly dependent on antibacterial potency and concentration of ABK as previously reported for combinations of ABK with other drugs. 3. The combination use of ABK with CTM appears to be useful in cases of infection by MRSA alone while the combination use of ABK with CZON appears to be useful in cases of double infection with MRSA and Gram-negative bacterium.

Aminoglycosides