Search PubMed⌕ Search

Biomedical subjects

K Deguchi

Publications and source records attributed to K Deguchi.

At least 181 records · Page 10Linked to original sources

[Bacteriological evaluations of combination effects with cefotiam and other antimicrobial agents against methicillin-resistant Staphylococcus aureus. II. Synergistic actions of cefotiam with arbekacin and minocycline].

We assessed the bacteriological efficacies of cefotiam (CTM) plus arbekacin (ABK) and CTM plus minocycline (MINO) therapies against methicillin-resistant Staphylococcus aureus (MRSA) in an in vitro system. The results are summarized as follows. 1. Both of CTM+ABK and CTM+MINO demonstrated almost perfect antibacterial activities against MRSA strains at ABK and MINO concentrations of MIC levels as clinically expected plasma ABK or MINO levels, and also showed antibacterial activities at ABK or MINO concentrations of sub-MIC levels. But no results suggesting antagonism were obtained. 2. The potent antibacterial effect of CTM+ABK or CTM+MINO against MRSA strains was considered to be the result of damage to the cellular membrane of target strains by ABK or MINO with ABK or MINO concentrations at MIC or sub-MIC levels and by the subsequent antibiotic effect of CTM. 3. A combination of drugs which are different from each other in mechanisms of action and points of action is likely to show a consistent antibacterial effect, but a combination of drugs which are competitive to each other because they share mechanism and point of action possibly cause antagonism.

Aminoglycosides↗

[Antimicrobial activities of cefminox against recent clinical isolates].

Against main clinical isolates at our center in 1990 to 1992, the minimum inhibitory concentrations (MICs) of cefminox (CMNX) and some other comparable cephems were determined. The results are summarized as follows. 1. As to the strains resistant to cephems including CMNX, annual increases were observed for Streptococcus pneumoniae among Gram-positive bacteria and Proteus vulgaris among Gram-negative bacteria. Moreover, cephem-resistant strains of Escherichia coli were constantly isolated, and there were signs indicating that cephem-resistant strains would increase among strains of Klebsiella pneumoniae. 2. The annual increases in cephem-resistant strains of S. pneumoniae and P. vulgaris may respectively reflect the recent increases in the incidence of benzylpenicillin (PCG)-insensitive strains of S. pneumoniae (PISP) and multi-drug resistant strains including oxime type cephems and new quinolones introduced into clinical use in the latter half of the 1980s. 3. Concerning antimicrobial activities of CMNX against recent clinical isolates, the same problems as described above will remain. However, these tendencies have been observed only with regard to MIC90. No remarkable changes have been noted for MIC50 or MIC80 at this time.

Cephamycins↗

[Therapeutic efficacy of cefodizime in combination with aminoglycosides against systemic infections caused by Pseudomonas aeruginosa in immunocompromised tumour bearing mice].

In vivo synergistic effects of cefodizime (CDZM) were investigated in combination with aminoglycosides (AGs), sisomicin (SISO) or dibekacin (DKB) against Pseudomonas aeruginosa in immunocompromised tumour bearing mice. Fractional effective dose (FED) indices showed that either synergistic or additive effects were observed between CDZM and AGs. The synergistic intraperitoneal bactericidal effect of CDZM in combination with SISO or DKB was also observed in immunocompromised tumour bearing mice. The post antibiotic effect (PAE) of AGs was prolonged by the addition of CDZM. Moreover, the strong synergistic bactericidal effects of CDZM and AGs against P. aeruginosa were observed in the presence of immunocompromised tumour bearing murine polymorphonuclear leukocytes (PMN). These results suggest that the strong therapeutic efficacy of CDZM in combination with AGs was caused by synergistic bactericidal effect of CDZM and AGs in the presence of PMN.

Animals↗

[Effects of a combination therapy consisting of arbekacin and ampicillin of methicillin-resistant Staphylococcus aureus].

Investigations were made on effects of a combination therapy consisting of arbekacin (ABK) and ampicillin (ABPC) against methicillin-resistant Staphylococcus aureus (MRSA). The following conclusions were drawn. 1. A frequency of FIC index to be < or = 0.5 upon a combination therapy consisting of ABK and ABPC against MRSA was 48.7%, hence this therapy showed better antibacterial effects than the other 8 combination therapies consisting of ABK and other antibiotics previously studied. 2. A combination therapy consisting of ABK and ABPC against MRSA was better than any other combination therapy because ABPC had a higher binding affinity with penicillin-binding protein 3 of MRSA, and because a high antibacterial activity of ABPC was maintained during the combination therapy. ABPC did not lose antibacterial activity largely because MRSA dose not produce beta-lactamase, or most of MRSA produces little beta-lactamase activity. 3. Our data indicate that the success of a combination therapy against MRSA depends upon the effects of the drug under sub MIC concentrations.

Aminoglycosides↗

[Cyclosporine therapy of adult onset Still's disease with disseminated intravascular coagulation].

In April, 1991, a 61-year-old man was admitted to our hospital because of pancytopenia and disseminated intravascular coagulation (DIC). Five years prior to admission he had developed high fever, skin eruption and arthralgia which had been improved by antibiotics, but recurred. Steroid therapy was ineffective for pancytopenia and DIC. Laboratory findings were as follows: RBC count, 274 x 10(4)/microliters; WBC count, 470/microliters; Platelets, 6.4 x 10(4)/microliters; fibrinogen, 153mg/dl; FDP, 67.0 micrograms/ml; FDP-D.Dimer, 13040ng/ml; thrombin-antithrombin complex, > 60.0ng/ml; and plasmin alpha 2-plasmin inhibitor complex, 10.3 micrograms/ml. As we suspected adult onset Still's disease on the basis of clinical course, we treated him with methylprednisolone pulse therapy, which was, however, ineffective. leukocytopenia, thrombocytopenia and DIC improved after cyclosporine treatment. Since cyclosporine is known to be very effective to autoimmune diseases, we speculate that in this patient immunological mechanism may be involve in the pathogenesis of DIC.

Cyclosporine↗

[Antibacterial activities of arbekacin against recently isolated methicillin-resistant Staphylococcus aureus (I)].

Against 200 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated from 1990 to 1991, minimum inhibitory concentrations (MICs) of a total of 15 antibacterial agents including arbekacin (ABK) were determined. In addition coagulase types of the tested strains were determined and classified according on their origins. 1. Among the coagulase types of 200 strains, type II were 63.5%, type IV 18.5%, type VII 11.0% and the other types 7.0%. Type II strains were prevailing among those isolated from the respiratory tract specimens and type IV among those from the surgical specimens. These results were in agreement with other recent reports including our previous ones. 2. The MIC50 of methicillin, 6 cephalosporins (CEPs), imipenem, fosfomycin (FOM), gentamicin, tobramycin and clindamycin for 200 strains ranged from 50 to > 100 micrograms/ml. On the other hand, MIC50 and MIC90 of ABK, minocycline (MINO) and vancomycin (VCM) were 0.78 and 3.13 micrograms/ml for ABK, 0.39 and 50 micrograms/ml for MINO, and 0.78 and 1.56 micrograms/ml for VCM. 3. The MIC90 of ABK against coagulase type IV strains was rather high, 12.5 micrograms/ml. However, the strains inhibited by 6.25 to 12.5 micrograms/ml of ABK were isolated even in our studies performed in 1986, 1988 and 1989. Further studies are therefore required to confirm whether appearance of these strains used in the present study inhibited at relatively high concentrations of ABK is due to the use of ABK. 4. It is reported that, at present, most of the MRSAs spreading in Japan are acceleratedly acquiring resistance to many drugs, and especially, they are developing high resistance against beta-lactams. ABK showed potent antibacterial activities even against these strains. Since ABK has been shown to display potent activities against MRSA in combination with beta-lactams or FOM, we believe ABK is one of the useful aminoglycoside antibiotics for the treatment of MRSA infections.

Aminoglycosides↗

[Antimicrobial activities of aspoxicillin of fresh clinical isolates].

The Antimicrobial activity of aspoxicillin (ASPC) in terms of minimum inhibitory concentration (MICs) was compared with those of other penicillin antibiotics (PCs) against clinical isolates sent to us from medical institutions throughout Japan in 1988, 1990 and 1992 and strains isolated and identified from samples collected from patients with various infections. 1. The MIC80's of ASPC against Staphylococcus aureus, Enterococcus spp., Escherichia coli, Bacteroides fragilis group were almost the same as those against these isolates in 1985 to 1986. 2. A trend for increasing susceptibility to PCs including ASPC was observed in the isolates of S. aureus and Haemophilus influenzae. This trend in S. aureus was attributed to the appearance of non beta-lactamase producing strains associated with the development of highly resistant strains among the methicillin-resistant S. aureus (MRSA) as well as to a tendency toward yearly decreasing frequency of MRSA. The trend for the increased susceptibility in H. influenzae was related to the decrease in the number of beta-lactamase production strains. 3. The frequency of the strains highly resistant to PCs including ASPC increased. 4. No PCs-resistant strains were observed among the so-called beta-streptococci, while among alpha-streptococci and Streptococcus pneumoniae there was a trend for decreasing frequency of strains with lower susceptibility to PCs or those with resistant to PCs. These strains may be variants which were also resistant to cephems and had penicillin-binding proteins (PBPs). Meanwhile, a high frequency of highly PCs-resistant strains were noted among Enterococcus faecium. In view of the fact that the PCs-resistance of E. faecium is known to be related to PBPs, the pattern of the susceptibility of the recent clinical isolates to beta-lactams is considered to be multimodal.

Amoxicillin↗

[Therapeutic efficacy of cefodizime in combination with minocycline against systemic infection caused by methicillin-resistant Staphylococcus aureus in immunocompromised tumour bearing mice].

The in vivo synergistic effect of cefodizime (CDZM) in combination with minocycline (MINO) against methicillin-resistant Staphylococcus aureus (MRSA) was investigated. A study of fractional effective dose (FED) index showed that either synergistic or additive effect was observed between CDZM and MINO. The postantibiotic effect (PAE) of MINO was not altered by the addition of CDZM. However, a strong synergistic bactericidal effect of CDZM and MINO against MRSA CT-18 was observed for more than 14 hours in the presence of immunocompromised tumour bearing murine polymorphonuclear leukocytes (PMN). These results suggest that the strong therapeutic efficacy of CDZM in combination with MINO was caused by synergistic bactericidal effect of the 2 drugs in the presence of PMN.

Animals↗

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↗