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Biomedical subjects

M Sanada

Publications and source records attributed to M Sanada.

At least 19 recordsLinked to original sources
PubMed1995

Mechanism of enhanced antipseudomonal activity of BO-2727, a new injectable 1-beta-methyl carbapenem.

The mechanism of the enhanced activity of BO-2727 against imipenem-resistant Pseudomonas aeruginosa was studied by using a set of four isogenic strains derived from beta-lactamase-deficient P. aeruginosa PAO4089 (blaJ blaP). Complementation of the blaJ and blaP mutations conferred greater resistance to biapenem, panipenem, and imipenem than to BO-2727 and meropenem, most notably in the outer membrane protein D2-deficient strain. The higher levels of resistance to biapenem, panipenem, and imipenem can be explained by the slow but significant hydrolysis by beta-lactamase, whereas the reduced levels of resistance to BO-2727 and meropenem would be attributable to their stability in the presence of high levels of beta-lactamase and the fact that they cause only low induction of beta-lactamase. It is also noted that the activity of BO-2727 against the beta-lactamase-deficient strain was less affected by the loss of the D2 porin than was that of meropenem, indicating that BO-2727 in comparison with meropenem can overcome an intrinsic resistance caused by the loss of D2. Moreover, comparative in vitro resistance studies have shown that BO-2727 and meropenem selected fewer resistant cells than other carbapenems. In conclusion, BO-2727 exhibited improved activity against imipenem-resistant P. aeruginosa, probably because of its ability to overcome loss of the D2 porin and beta-lactamase hydrolysis.

Anti-Bacterial Agents↗
PubMed1995

[Epstein-Barr virus associated natural killer cell leukemia: report of an autopsy case].

A 20-year-old female was admitted because of high fever, hepatosplenomegaly, severe hepatic dysfunction and coagulopathy. Peripheral blood showed pancytopenia and granular lymphocytes bearing the natural killer cell phenotype (CD2+CD3-CD16+CD56+CD57-TCR alpha beta-TCR gamma delta-) constituted 97% of leucocytes. Southern blot analysis of DNA obtained from peripheral blood mononuclear cells showed germ-line configuration of TCR beta, gamma and delta chain genes. EBV-DNA was detected in a single episomal form by using EBV-terminal repeat probe. Bone marrow findings were consistent with hemophagocytic syndrome and administration of VP-16 was effective transiently. After ten months she died from massive gastrointestinal bleeding. An in situ hybridization study identified EBV-RNA (EBER-1) in atypical lymphocytes infiltrating bone marrow, spleen and lymph nodes. Sections of liver showed steatosis and infiltration of T cells (CD3+ and EBER-1-negative) in the portal areas and few atypical lymphocytes in sinusoids. The patients developed an EBV-associated clonal proliferation of natural killer (NK) cells, but the clinical features were suggestive of chronic active EBV infection or virus-associated hemophagocytic syndrome (VAHS) rather than leukemia. Bone marrow transplantation for NK cell leukemia is an issue to be discussed.

Adult↗
PubMed1995

[Effect of intravaginal administration of cisplatin (CDDP) suppositories to uterine cervical cancer--blood and tissue concentrations and the therapeutic effects].

Four patients with cervical cancer (squamous cell carcinoma: two cases of stage Ib, one of stage IIa, adenocarcinoma: one of stage Ib), were treated preoperatively by intravaginal administration of CDDP (20 mg) suppositories with pessary 7 times every other day. The uptake, distribution and antitumor effect of CDDP were investigated. Results were as follows. 1) Serum total platinum (Pt) concentration varied between individual patients. Cmax profile (0.17-0.57 micrograms/ml) of Pt was observed at 12 hours after the total dose of 140 mg administration in all patients. 2) The tissue Pt concentration showed high values in the cervix (average 55.4 micrograms/g), followed by the vagina (13.13), endometrium (3.17), uterine wall (0.64), ovary (0.57), lymph node group: parametrial (1.14), obturator (0.34), inguinal (0.28), external iliac (0.51), internal iliac (0.42) and common iliac (0.54). Para-aortic node value was too low to detect. 3) Colposcopic findings were disappearance of bleeding and reduction of tumor outgrowth. Microscopic findings were degeneration and necrosis of cancer nest from the surface to about 2 mm depth of the cervix. In conclusion, it may be necessary to improve CDDP penetration from the tumor surface for effective local chemotherapy.

Adenocarcinoma↗
PubMed1994

Pharmacokinetics and safety of BO-2727, a new injectable 1-beta-methyl carbapenem antibiotic, and its effect on the faecal microflora in healthy male volunteers.

The safety and pharmacokinetics of BO-2727, a new injectable 1-beta-methyl carbapenem antibiotic, and its effect on the faecal microflora were evaluated in single- and multiple-dose studies involving twenty-four healthy male adult volunteers following a preliminary safety evaluation of 25, 50 and 125 mg iv doses in six volunteers. BO-2727 was administered by iv infusion over 30 min. There was a good correlation between BO-2727 concentrations assayed by HPLC and a microbiological method; the HPLC results were used in the pharmacokinetic analysis. The single-dose study indicated that plasma concentration versus time curves at doses of 250, 500 and 1000 mg were well described by a two-compartment open model. The mean (+/- S.D.) elimination half-life ranged from 1.41 +/- 0.21 h to 1.54 +/- 0.10 h, and the peak plasma concentrations (Cmax) and the area under the plasma concentration versus time curves increased linearly with the dose. The mean urinary recoveries within the first 24 h were 70.63 +/- 5.24% to 77.38 +/- 4.55% of the dose. The highest concentration of BO-2727 in saliva was 0.72 mg/L which was reached 1 h after the start of the 1000 mg infusion and accounted for approximately 1% of the Cmax. No BO-2727 was found in faecal samples collected 24 and 48 h after a single 1000 mg dose. In the multiple-dose study, BO-2727 500 mg bd was administered for 4.5 days. There were no obvious differences in plasma concentrations and urinary recoveries between the single- and multiple-dose regimens. BO-2727 did not accumulate as determined by plasma concentrations and urinary recoveries. No marked changes in the aerobic and anaerobic faecal microflora were observed during multiple-dose administration. There were no significant adverse reactions, and likewise no abnormalities in physical and laboratory examinations that were definitely related to the drug.

Adolescent↗
PubMed1994

[Photodensitometry: microdensitometry (MD): digital image processing method (DIP)].

The principles of microdensitometry (MD) and digital image processing method (DIP), as well as the application of these methods to measure bone mineral density in clinical practice, were mentioned in the report. MD and DIP assess bone mineral content and bone mineral density by analyzing relative contrast of the metacarpus II on X-ray image. However, the parameters obtained by these methods have been reported to be closely related to lumber vertebral bone mineral density and whole-body bone mineral content as measured by dual energy X-ray absorptiometry (DXA). Being easy to use, MD and DIP are adequate for the screening of osteoporosis. Once any reduction in bone mineral content or bone mineral density is shown by MD or DIP, it is recommendable to measure bone mineral density of vertebrae and femoral neck by DXA.

Absorptiometry, Photon↗
PubMed1993

Alteration in expression of Serratia marcescens porins associated with decreased outer membrane permeability.

The porin expression of two clinical isolates of Serratia marcescens, which overproduced cephalosporinase and had decreased outer membrane permeability, were studied in comparison with those of reference strains. Separation of the porin proteins assessed by SDS-PAGE containing urea revealed that both clinical isolates overexpressed a single porin of 44 and 43 kilodalton (kDa), respectively. In contrast, the in-vitro porin deficient mutant, which was derived from the reference strain IFO3736 as latamoxef-resistant, showed decreased outer membrane permeability, but produced low levels of all three peptidoglycan associated porins of 45, 44 and 43 kDa, and overexpressed 39 kDa OmpA protein. These observations suggested that the clinical isolates had a different mechanism of latamoxef resistance compared with the mutant and overexpressed possible narrow transport channels of 44 or 43 kDa. The 45 kDa porin may facilitate a more effective channel than the other two proteins. Heterogeneity of porin profiles between biotypes was also suggested. The two isolates were also resistant to penicillins and cephalosporins tested, but imipenem was the most active agent and inhibited the isolates at 1.56 mg/L.

Anti-Bacterial Agents↗
PubMed1993

Synergic activity of imipenem/cilastatin combined with cefotiam against methicillin-resistant Staphylococcus aureus.

The synergic activity of imipenem/cilastatin combined with cefotiam was studied in a mouse bacteraemia model. Combinations of imipenem plus cefotiam in ratios from 1:5 to 1:160 were more effective than either imipenem alone or cefotiam alone (P < 0.05). Synergy was observed against both beta-lactamase producing and beta-lactamase non-producing MRSA. Staggered combinations of imipenem with cefotiam (each drug was administered at a different time) were studied in an in-vitro pharmacokinetic system to clarify relationships between killing kinetics and pharmacodynamics of the combinations. In the in-vitro system, cefotiam (1 g over 30 min) administered 2 h after imipenem administration (250 mg over 30 min) reduced viable cell counts to an undetectable level and maintained this for 4 h, while the simultaneous administration of imipenem and cefotiam maintained an undetectable cell count for only 2 h. Furthermore, imipenem administered after cefotiam showed no synergy. These results indicate that the timing of dosing of each antibiotic influences synergy, and administration of cefotiam 2 h after imipenem is more effective than the other regimens.

Animals↗
PubMed1993

In vitro activity of a new carbapenem antibiotic, BO-2727, with potent antipseudomonal activity.

BO-2727, a new 1-beta-methyl-carbapenem, was active at concentrations of 6.25 micrograms/ml or less against gram-positive and gram-negative bacteria, including some imipenem- and/or meropenem-resistant (MICs, > or = 12.5 micrograms/ml) Pseudomonas aeruginosa strains, against which it proved generally fourfold more active than imipenem and meropenem. BO-2727's antipseudomonal activity and its broad spectrum merit further investigation for clinical use by itself, since it was stable in the presence of renal dehydropeptidase I.

Anti-Bacterial Agents↗
PubMed1993

[Electrocardiographic study of sinus bradycardia associated with enterohemorrhagic Escherichia coli O157: H7 infection].

A severe outbreak of hemorrhagic colitis occurred at a kindergarten in Saitama, Japan in October, 1990. Children who were affected by enterohemorrhagic E. coli O157: H7 infection showed apparent bradycardia as well as severe bloody diarrhea, generalized convulsion, or hemolytic uremic syndrome. Cardiac involvement such as bradycardia observed in the patients of this outbreak has not been described in previous reports about EHEC infection, while bradycardia has been well known in typhoid fever due to salmonella typhosa infection. Electrocardiographic examination was performed to evaluate bardicardia, utilizing electrocardiography at rest and Holter's twenty-four hour electrocardiography. In the report, we demonstrate that the bradicardia was due to reduced frequency of sinus node. Both average heart rate and average minimum heart rate of the patients at night (74.0 +/- 5.6 BPM and 57.0 +/- 5.1 BPM, respectively) decreased significantly, as compared with controls (84.6 +/- 9.3 BPM and 66.3 +/- 8.0 BPM respectively) (p < 0.01). CVRR of the patients (0.120 +/- 0.019, respectively) increased significantly as compared with controls (0.090 +/- 0.010, respectively). These results indicate that an activated parasympathetic nervous system, that is, activation of the vagal nerve, might have induced the sinus bradycardia observed in the patients with EHEC infection.

Bradycardia↗
PubMed1993

[Primary splenic lymphoma complicated by malignant rheumatoid arthritis and bladder cancer].

A 64-year-old man had been found to have primary splenic lymphoma (stage III) seven years after the diagnosis of rheumatoid arthritis (RA). Histological diagnosis of the lymphoma was diffuse, medium sized cell type (LSG) or intermediate lymphocytic lymphoma (ILL). Splenectomy and ten courses of CHOP regimen produced continuing remission. After tow years, he suffered from peripheral neuropathy due to vasculitis of polyarteritis nodosa (PN) type. He was treated with prednisolone (PSL) and cyclophosphamide (CPM) for malignant rheumatoid arthritis. One year later, evaluation for intermittent hematuria revealed bladder cancer and he underwent total cystectomy. He has been treated with small doses of PSL under observation. The high incidence of ILL in lymphomas developing in patients with autoimmune diseases of the thyroid and salivary glands has been reported. This case suggests an association between antecedent RA and splenic lymphoma, the influence of splenectomy and chemotherapy on occurrence of rheumatoid vasculitis, and a causal relationship between CPM and bladder cancer.

Arthritis, Rheumatoid↗
PubMed1992

Resistance to a new catecholic cephem, BO-1341, in Pseudomonas aeruginosa PAO.

Two distinct types of mutant resistant to the catecholic cephem BO-1341 were isolated spontaneously from Pseudomonas aeruginosa PAO2146: (i) a mutant (CCB5-type) which produced beta-lactamase constitutively, and which appeared to result from a mutation in the regulatory gene (blaI at 41 min) controlling the structural gene (blaP at 25 min); (ii) a mutant (CCB7-type) with specific resistance to BO-1341. Induction of beta-lactamase production in strain CCB7 by BO-1341 was diminished markedly when compared with that in the parent strain. This was not the case for ceftazidime or cefoxitin, suggesting impaired uptake of BO-1341 as an explanation for the resistance. Electrophoretic analysis demonstrated increased production of a 55 kDa protein in the periplasmic space and a 84 kDa outer membrane protein. These data suggested that specific resistance to BO-1341 might involve quantitative alterations in the composition of the outer membrane and periplasmic proteins.

Cefoxitin↗
PubMed1992

[Anti-Pr2 cold agglutinin disease with polyneuropathy evolving to malignant lymphoma].

A 53-year-old male was diagnosed as having ataxic polyneuropathy associated with IgM-kappa monoclonal gammopathy in January 1988. Plasmapheresis and chemotherapy with chlorambucil and Melphalan-Prednisolone were effective for his neuropathy, but hemolytic anemia appeared in February 1989. The diagnosis of low-titer cold agglutinin disease (IgM-kappa) with anti-Pr2 specificity was made. Hemolytic anemia became refractory to high-dose corticosteroids, and fever, hepatosplenomegaly and severe pancytopenia appeared in January 1990. Bone marrow involvement of malignant lymphoma (mu, kappa) was found, and he died of pneumonia and gastrointestinal bleeding after the start of chemotherapy. Postmortem examination revealed a widespread infiltration of malignant lymphoma, diffuse, large cell (B-cell) type. Erythrophagocytic histiocytes also increased in bone marrow, liver, spleen and lymph nodes, as if there were hemophagocytic syndrome associated with lymphoma present. In addition to the high thermal amplitude of cold agglutinin in this case, the systemic activation of histiocytes induced by the development of malignant lymphoma may be responsible for progressive hemolysis and severe pancytopenia.

Anemia, Hemolytic, Autoimmune↗
PubMed1992

[Evolution to megakaryoblastic leukemia observed in myelodysplastic syndrome with erythrolekemia-like features].

A 63-year-old man was admitted because of anemia and thrombocytopenia. The bone marrow was hypercellular with 66.6% erythroblasts with dysplasia and 19.8% blasts. Cytogenetically, MAKA (major karyotypic aberrations) containing 5q-, -7, -17, with karyotypic instability was observed. A diagnosis of erythroleukemia (FAB M6) was made. Six months later, immature neutrophils increased in the peripheral blood, and blasts and promyelocytes increased to 25.8% and 20.0% of marrow cells, respectively. Three months later, blasts asts increased to 33.0% in the peripheral blood. They were ultrastructually positive for platelet peroxidase. Phenotypically, 69% and 63% of blasts were positive for CD41b (GPIIb/IIIa) and CD42a (GPIb), respectively. Bone marrow biopsy showed marked proliferation of blasts and dysplastic megakaryocytes accompanied by reticulin fibrosis. These findings suggested evolution to megakaryoblastic leukemia (FAB M7). In most cases, M6 defined by the FAB criteria is stem cell disorder with multilineage involvement and major erythroid component. M6-like features may be observed in the evolutive phase to acute leukemia from myelodysplastic syndrome (MDS).

Chromosome Aberrations↗
PubMed1992

[Autoimmune hemolytic anemia induced by alpha-interferon therapy in a case of IgG-kappa type multiple myeloma].

A 47-year-old male case of IgG-kappa type multiple myeloma was treated with VMCP and recombinant human alpha-interferon (IFN-alpha 2a). The direct Coombs test was positive before treatment. Hemolytic anemia associated with massive hematuria was observed during the administration of 9 million IU IFN-alpha 2a per day for 2 weeks. The hemolytic symptoms rapidly improved after withdrawal of IFN-alpha 2a. This clinical course suggests that IFN-alpha as an immunomodulator was responsible for the progression of autoimmune hemolytic anemia in a case of multiple myeloma.

Anemia, Hemolytic, Autoimmune↗
PubMed1991

In-vitro activity of imipenem combined with beta-lactam antibiotics for methicillin-resistant Staphylococcus aureus.

The in-vitro activity of imipenem combined with beta-lactam antibiotics was studied for 25 strains of methicillin and imipenem-resistant Staphylococcus aureus (MRSA) in comparison with that of fosfomycin combined with cefmetazole. Using the chequerboard agar dilution method, strong synergy was seen for all strains for imipenem with cefoperazone, cefotiam, cefpiramide or piperacillin. All fractional inhibitory concentration indices (FIC indices) of these combinations were less than or equal to 0.12. For the combination of imipenem with cefotiam the synergy was found to be bactericidal, but was not affected by the temperature of incubation, the concentration of sodium chloride in the medium or beta-lactamase production. However, for the combination of fosfomycin with cefmetazole only 44% of the strains with a mean FIC index of 0.55, showed synergy. The remaining 56% of strains showed either partial synergy (44%) or additive activity (12%). The combinations of imipenem with the beta-lactam antibiotics were more effective than that of fosfomycin with cefmetazole.

Anti-Bacterial Agents↗
PubMed1991

Preferential hydrolysis of cis configuration compounds at the 3,4 position of monobactams by beta-lactamase from Morganella morganii.

Carumonam and BO-1166 (cis configuration) were inactivated by beta-lactamase of Morganella morganii more rapidly than were aztreonam and BO-1165 (trans configuration), as demonstrated by spectrophotometric analysis and microbiological assay. An active enzyme was recovered more rapidly from the inactivated enzyme-monobactam complex derived from the cis form of monobactams than from the complex derived from the trans form of monobactams. This result suggests that the configuration at the 3,4 position on the azetidinone ring of monobactams, together with the chemical structure of the side chains attached to the azetidinone ring, may play an important role in the stability of monobactams to the beta-lactamase of M. morganii.

Aztreonam↗