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Biomedical subjects

S Mitsuhashi

Publications and source records attributed to S Mitsuhashi.

At least 55 records · Page 3Linked to original sources

Effect of simple shear flow on photosynthesis rate and morphology of micro algae.

The convective motion of micro algal suspension gives an advantageous effect on the photosynthetic rate in the bioreactor, however, the nature of convective effect on the photosynthesis has not been fully understood. The purpose of this study concerns the nature of photosynthetic rate in a well-defined hydrodynamic shear flow of Spirulina platensis suspension, generated in a double rotating coaxial cylinders. The double rotating coaxial cylinders was installed in the incubator chamber with the controlled illumination intensity and temperature. Two kind of experiments, short and long term experiments, were performed to evaluate the direct effect of shear flow on the photosynthetic rate. The short term experiment indicates that the simple shear flow enables to augment the photosynthesis of Spirulina suspension and simultaneously causes the cell destruction due to the excessive shear stress. The long term experiment for 100 hours reveals that the growth rate and the morphology of Spirulina is sensitive to the external fluid mechanical stimulus. The long term application of mechanical stress on the algae may result in the adaptation of the photosynthetic function and morphology.

Bioreactors↗

CD30-positive lymphoma in human T-cell leukaemia virus type 1 carrier without monoclonal integration of HTLV-1.

CD30, Ki-1 antigen, an activated T-cell antigen, is a member of the nerve growth factor receptor family. This antigen is expressed on the lymphoma cells of some adult T-cell leukaemia/lymphoma (ATL/L) patients and some patients with Epstein-Barr virus infection. CD30-positive large cell cutaneous T-cell lymphomas occasionally integrate a defective HTLV-1 provirus. We describe here an HTLV-1 carrier who developed Ki-1 lymphoma with no evidence of monoclonal integration of the HTLV-1 proviral sequence.

Blotting, Southern↗

In vitro antibacterial activity of AM-1155, a novel 6-fluoro-8-methoxy quinolone.

The in vitro antibacterial activity of AM-1155 against a wide variety of clinical isolates was compared with those of other fluoroquinolones. The MICs of AM-1155 for 90% of Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecalis isolates tested were 0.10, 0.39, and 0.78 microgram/ml, respectively. The antibacterial activity of AM-1155 against gram-positive bacteria and anaerobes was comparable to those of sparfloxacin and tosufloxacin. AM-1155 inhibited 90% of most species of the family Enterobacteriaceae at a concentration of 0.39 microgram/ml. AM-1155 generally had activity comparable to that of sparfloxacin against gram-negative bacteria. AM-1155 showed moderate activity against methicillin- and quinolone-resistant S. aureus. AM-1155 demonstrated bactericidal activity at the MIC. The frequency of occurrence of spontaneous mutants resistant to four times the MIC of AM-1155 was < 1 x 10(9) for S. aureus, Escherichia coli, and Pseudomonas aeruginosa. AM-1155 strongly inhibited the supercoiling activities of DNA gyrases purified from E. coli and S. aureus.

Anti-Infective Agents↗

Mechanisms of high-level resistance to quinolones in urinary tract isolates of Pseudomonas aeruginosa.

Twenty-eight strains of Pseudomonas aeruginosa with various degrees of norfloxacin resistance were isolated from patients with urinary tract infections. P. aeruginosa strains (norfloxacin MICs, 3.13 to 200 micrograms/ml) were transformed by either pPAW207 or pNF111 plasmid DNA, which included either the gyrA or nfxB gene, respectively. For transformants with pPAW207, norfloxacin MICs decreased 8- to 128-fold. It was suggested that moderate and high degrees of resistance to norfloxacin were expressed as a result of alterations in gyrA. No strain manifesting only an alteration in nfxB permeability was observed. The MICs of norfloxacin (200 micrograms/ml) for two P. aeruginosa strains, GN17605 and GN17434-2, were decreased following transformation not only by pPAW207 but also by pNF111. Analysis of outer membrane proteins disclosed the presence of a 54,000-Da protein in these parent strains that was not expressed in the pNF111 transformants. The level of accumulation of norfloxacin by the pNF111 transformant of GN17605 was higher than that by the parent strain. The norfloxacin susceptibility of DNA gyrase subunit A purified from GN17605 was only 1/35th that of the gyrase containing a subunit A from P. aeruginosa PAO1. These findings suggest that GN17605 is a gyrA-nfxB double mutant and that strain GN17434-2 possesses double mutations in both nfxB and some unknown gene.

Anti-Infective Agents↗

In vitro antibacterial activity and beta-lactamase stability of SY5555, a new oral penem antibiotic.

The antibacterial activity of SY5555, a new oral penem antibiotic, was compared with those of cefaclor, cefixime, and cefteram. SY5555 was more active than the comparison agents against methicillin-susceptible Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Enterococcus faecalis, Citrobacter freundii, Enterobacter cloacae, Morganella morganii, Acinetobacter calcoaceticus, Clostridium spp., and Bacteroides fragilis. Against Providencia spp., Proteus spp., and Haemophilus influenzae, SY5555 was less active than cefixime or cefteram. SY5555 was inactive against methicillin-resistant S. aureus. Enterococcus faecium, Serratia marcescens, Pseudomonas aeruginosa, and Xanthomonas maltophilia, as were the comparison agents. The bactericidal activities of SY5555, cefixime, and cefteram were at or slightly greater than the MICs for clinical isolates of Escherichia coli and Klebsiella pneumoniae. SY5555 was not hydrolyzed by various types of beta-lactamases. However, SY5555 and the comparison agents were hydrolyzed by X. maltophilia (L-1) and P. aeruginosa/pMS354 beta-lactamases, two Bush group 3 beta-lactamases, SY5555 showed a high affinity, as did cefixime and cefteram, for cephalosporinases from C. freundii GN7391 and E. cloacae GN7471 strains. These results suggest that SY5555 may be more specific than existing beta-lactam antibiotics.

Administration, Oral↗

In-vitro evaluation of the four beta-lactamase inhibitors: BRL42715, clavulanic acid, sulbactam, and tazobactam.

The in-vitro synergic activities of BRL42715, a new beta-lactamase inhibitor, clavulanic acid, sulbactam, and tazobactam combined with ampicillin, piperacillin, cephalothin, or cefoperazone were tested against various bacteria producing known types of beta-lactamase. BRL42715 showed the best synergistic activity among the inhibitors tested against strains producing penicillinases of type I, II, III, V, and that from Klebsiella pneumoniae, cephalosporinases, and oxyiminocephalosporinases (except that from Klebsiella oxytoca). Clavulanic acid combined with the beta-lactams tested showed the best synergic activity of the inhibitors against strains producing type IV penicillinase and oxyiminocephalosporinase from K. oxytoca. The 50% inhibitory doses of BRL42715 were superior to those of clavulanic acid against various types of beta-lactamases except for type IV penicillinase and the oxyiminocephalosporinase from K. oxytoca. The inhibitory activity of BRL42715 against cephalosporinases from various bacteria was 10(4) to 10(6)-fold greater than that of clavulanic acid. The synergic effects of BRL42715 and clavulanic acid on the activity of piperacillin were compared against six clinical isolates of bacteria resistant to piperacillin. The synergic activity of BRL42715 was greater than that of clavulanic acid in all six isolates.

Anti-Bacterial Agents↗

Antibacterial activity of NM394, the active form of prodrug NM441, a new quinolone.

The in vitro antibacterial activity of NM394 was compared with those of other new quinolones. NM394 showed potent and broad-spectrum antibacterial activity against 2,606 recent clinical isolates. The activity of NM394 against gram-positive bacteria was 2- to 16-fold less than that of tosulfoxacin and sparfloxacin but was comparable to that of ofloxacin. Only against Streptococcus pyogenes was the activity of NM394 equal to that of sparfloxacin. Against gram-negative bacteria, NM394 showed antibacterial activity equal to that of ciprofloxacin. Against quinolone-resistant Pseudomonas aeruginosa (norfloxacin MIC, > 6.25 micrograms/ml), the activity of NM394 was greater than those of the other agents tested. NM394 was rapidly bactericidal at concentrations near the MIC. NM394 inhibited supercoiling activities of DNA gyrase purified from Staphylococcus aureus, Escherichia coli, and P. aeruginosa; the 50% inhibitory concentrations were 18.0, 0.41, and 2.05 micrograms/ml, respectively.

Anti-Infective Agents↗

In vitro antibacterial activity and beta-lactamase stability of CP-70,429 a new penem antibiotic.

In in vitro susceptibility tests, the new penem CP-70,429 showed potent antibacterial activity against gram-positive and gram-negative bacteria except Pseudomonas aeruginosa and Xanthomonas maltophilia. CP-70,429 was stable to various types of beta-lactamases except for the enzyme from X. maltophilia and was 16- to 128-fold more active than the other compounds against beta-lactamase-producing strains of Enterobacter cloacae and Citrobacter freundii.

Anti-Bacterial Agents↗

Human plasma free activin and inhibin levels during the menstrual cycle.

The role of inhibin in gonadal function and reproduction has been confirmed by the measurement of plasma inhibin levels, but there has been no clinical data available on activin because of the lack of a good assay method. We measured plasma free activin levels during the normal menstrual cycle using a newly developed competitive protein binding assay with follistatin as the binding protein. Plasma inhibin levels were measured simultaneously using an alpha-subunit N-terminal fragment RIA with recombinant inhibin as the reference standard. Four normal women, aged 23-29 years, were investigated by obtaining plasma at 3-day intervals. Plasma inhibin levels showed some variation during the follicular phase, but a parallel rise in inhibin and progesterone was observed during the luteal phase. These findings confirmed those of previous studies. In contrast, plasma free activin levels did not show any substantial changes during the menstrual cycle. This study suggests that activin has no endocrine role in modulating the pituitary-gonadal axis during the normal menstrual cycle, while changes of inhibin reflect cyclic gonadal function and indicate an endocrine role for this protein in modulating gonadal activity.

Activins↗

Activin and inhibin secretion by cultured porcine granulosa cells is stimulated by FSH and LH.

Follistatin-free activin and inhibin levels were measured in the culture medium of porcine granulosa cells by a competitive protein binding assay and N-fragment RIA, respectively. Cultures were maintained for 6 days in MEM containing 10% fetal calf serum. FSH and HCG (1-1,000 IU/L) were added on day 2 to cultures containing 1 x 10(5) cells/ml and the medium was changed every 2 days. Granulosa cells secreted a large amount of progesterone, which indicated their luteinization. Activin and inhibin were both secreted throughout the 6 day culture period. Both of them increased equally in response to FSH and HCG in a dose-dependent manner on day 4, but their responses became discrepant on day 6, when the activin response decreased while the response of inhibin increased. This study demonstrated that cultured porcine granulosa cells secrete both activin and inhibin under the control of FSH and LH. The activin response was lost before that of inhibin, suggesting the role of activin at an earlier stage of luteinization.

Activins↗

Demonstration of biological activity of a growth hormone-releasing hormone-like substance produced by a pheochromocytoma.

The biological characteristics of a growth hormone-releasing hormone (GHRH)-like substance produced by a pheochromocytoma were studied. Analysis by gel filtration chromatography combined with the use of two distinct GHRH antisera that recognize the N- and C-termini of authentic GHRH(1-44)NH2 indicated molecular heterogeneity of the immunoreactive GHRH in the tumor extract, but a component corresponding to GHRH(1-44)NH2 was the predominant form. The biological activity of this immunoreactive component was assessed in vitro by measuring its ability to induce growth hormone release from dispersed rat anterior pituitary cells. At concentrations of 0.125-2.0 nmol/l, the test materials induced a dose-related increase in growth hormone release from the cells into the incubation medium (range 992 +/- 68-1872 +/- 32 ng.1.7 x 10(5) cells-1 x 3 h-1), similar to that observed with synthetic GHRH(1-44)NH2. (control value 640 +/- 30 ng.1.7 x 10(5) cells-1 x 3 h-1). This suggests that immunoreactive GHRH in the tumor has almost the same biological activity as the synthetic product and that a combination of pheochromocytoma and acromegaly is not always fortuitous because both diseases may be caused by a single neoplasm.

Adrenal Gland Neoplasms↗

Demonstration of the deposition of hemosiderin in the kidneys of patients with paroxysmal nocturnal hemoglobinuria by magnetic resonance imaging.

Hemosiderinuria caused by intravascular hemolysis is a characteristic clinical feature of an acquired hemolytic disorder, paroxysmal nocturnal hemoglobinuria (PNH). We examined the deposition of hemosiderin (iron) in the kidneys of 6 patients with PNH using magnetic resonance imaging (MRI). Three patients with autoimmune hemolytic anemia (AIHA), a hemolytic disorder showing extravascular hemolysis, served as controls. In five of the six patients with PNH, a characteristic T2-weighted MRI of the kidneys, suggesting the deposition of iron (hemosiderin) predominantly in the renal cortex, was obtained. Hemosiderin-deposition was not revealed in the kidneys of any of the patients with AIHA. We conclude that MRI is a sensitive means of detecting hemosiderin deposited in the renal cortex of patients with PNH and that this feature is considerably specific for diseases showing intravascular hemolysis, as represented by PNH.

Aged↗

Structures of enzymatically modified products of arbekacin by methicillin-resistant. Staphylococcus aureus.

Only a limited number of strains of methicillin-resistant Staphylococcus aureus (MRSA) moderately resistant to arbekacin (ABK) have been isolated clinically. Three inactivated products of ABK have been obtained by reaction with excess amounts of a crude enzyme preparation extracted from an ABK-resistant MRSA strain (MIC, 25 micrograms/ml). The 2"-O-phosphate was the major product together with small amounts of the 6'-N-acetate and the double modification product. The structures of these modification products were determined by MS and NMR spectral analyses.

Aminoglycosides↗

[Effect of THP-CVP regimen for elderly patients with malignant lymphoma].

Between April 1990 and June 1992, a multicenter clinical trial of chemotherapy regimens was performed with patients, aged 65 years or more, suffering from malignant lymphoma. The total number of patients was 38 included 30 initial cases (median age: 72) and 8 relapsed cases (79). The chemotherapy regimen, administered every 3 weeks, included pirarubicin (30 mg/m2; day 1), cyclophosphamide (500 mg/m2; day 1), vindesine (1.5 mg/m2; day 1), and prednisolone (40 mg/m2; days 1-5) for the initial cases, and etoposide (100 mg/m2; days 1-5) in addition for relapse cases. The complete response and partial response rates were 50.0% and 40.0% in initial cases, respectively, and 50.0% and 0% in relapsed cases, respectively. The 50% survival period was 25.9 months in initial cases and 18.0 months in relapse cases. There were no serious side effects related to the regimens. Performance status deteriorated in only one case after chemotherapy. We concluded that the chemotherapy regimens were useful and safe for elderly patients with malignant lymphoma.

Aged↗

Comparative stability of carbapenem and penem antibiotics to renal dehydropeptidase-I.

Comparison has been made on the stability of 4 carbapenems and 3 penems against porcine renal dehydropeptidase-I (DHP-I). Evaluated were the carbapenems (5R,6S)-3-[[2-(formimidoylamino)ethyl]thio]-6-[(R)-1-hydroxyethyl] - 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid monohydrate, CAS 74431-23-5, in the following called FAC, (5R,6S)-3-[(S)-1-(acetimidoylpyrrolidin-3-yl)thio]-6-[(R)-1- hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0] hept-2-ene-2-carboxylic acid, CAS 87726-17-8, in the following called AHC, (4R,5S,6S)-3-[[(3S,5S)-5-dimethylcarbamoylpyrrolidin-3-yl]thio]-6- [(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2- carboxylic acid trihydrate, CAS 96036-03-2, in the following called DHC. (1R,5S,6S)-2-[(6,7-dihydro-5H-pyrazolo[1,2-a] [1,2,4]triazolium-6-yl)thio]-6-[(R)-1-hydroxyethyl]-1-methyl-ca rbapen - 2-em-3-carboxylate, in the following called DHM, and the penems (5R,6S)-6-[(R)-1-hydroxyethyl]-7-oxo-3-[(R)-2-tetrahydrofuryl]-4-thia-1 - azabicyclo [3.2.0]hept-2-ene-2-carboxylic acid sodium salt, in the following called HTC, (5R,6S)-2-carbamoyloxymethyl-6-[(1R)-hydroxyethyl]-2-penem-3-carboxylic acid, in the following called CHC, (5R,6S)-6-[(R)-1-hydroxyethyl]-3-[(3S)-(cis-1-oxotetrahydrothiophen++ +-3-yl) thio]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid, in the following called HHC. According to the comparison of the Vmax/Km ratios, the order of stability of the compounds to hydrolysis by renal DHP-I was as follows: DHM >> DHC > HHC > AHC > HTC > CHC > FAC. From this result it is particularly noteworthy that DHM has extremely high stability against renal DHP-I.

Animals↗

[Four cases of CD7-positive acute myeloid leukemia].

This report describes 4 cases of T-cell-associated CD7-positive acute myeloid leukemia (AML). Myelo-peroxidase staining of blasts was negative in 2 cases but became positive during their courses. In all cases, the myeloid determinants CD13 and/or CD33 were associated with CD7 expression. Other B-lymphoid (CD10, CD19) or T-lymphoid (CD2) markers were negative. In three cases, dual fluorescence analyses showed co-expression of CD7 and CD13 (CD33). Clinically, compared with CD7+AML, these CD7+AML patients presented higher leukocyte and blast counts in peripheral blood. All patients achieved complete remission with chemotherapeutic regimens for AML, but 3 relapsed within a short time. Systemic lymphadenopathy was found in 2 cases, and interestingly, the surface markers of the lymph-node in one case were CD7+CD33-. These cases of CD7+AML may represent a distinct subgroup that arises from particular, less different myeloid precursors, and may have poor prognosis.

Acute Disease↗

Competitive protein binding assay for activin A/EDF using follistatin determination of activin levels in human plasma.

A sensitive and specific protein binding assay for activin A/EDF (activin) was developed using follistatin as a binding protein and [125I] labelled activin as a tracer. As 50% acetonitrile (CH3CN) separated free and follistatin-bound activin, plasma pretreated with an equal volume of CH3CN was used as the assay sample and B/F separation was also done with 50% CH3CN. The recovery of the assay was 85.0% and its sensitivity was 0.5 ng/ml. Crossreactivity with inhibin A was 1.8%. The mean plasma level of follistatin-free activin in normal subjects was 1.3 +/- 0.7%. (M +/- SD) ng/ml. Plasma free activin levels were generally elevated in patients with chronic renal failure or hematological diseases associated with anemia.

Activins↗