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Biomedical subjects

H Nakada

Publications and source records attributed to H Nakada.

At least 91 records · Page 5Linked to original sources

[In vitro activities of newly developed quinolones, fleroxacin, lomefloxacin and sparfloxacin against Mycobacterium tuberculosis].

In vitro antituberculous activities of three newly developed quinolones, fleroxacin (FLRX, AM-833), lomefloxacin (LFLX) and sparfloxacin (SPFX, AT-4140) were evaluated in comparison to that of ofloxacin (OFLX) using M. tuberculosis strains isolated from patients and the Ogawa egg medium. SPFX was apparently more active than OFLX, but both FLRX and LFLX were less active. SPFX inhibited completely the growth of all 20 strains of M. tuberculosis isolated from patients who were not previously treated with OFLX in a concentration of 1.25 micrograms/ml. However, this agent inhibited the growth of only 4 strains (28.6%) of 14 OFLX-resistant M. tuberculosis in a concentration of 1.25 micrograms/ml, suggesting a partial cross-resistance between SPFX and OFLX.

Anti-Infective Agents↗

A monoclonal antibody directed to Tn antigen.

A murine monoclonal antibody, MLS 128, that was assigned to an anti-Tn antibody has been established by immunizing mice with human colonic cancer cells (LS 180). MLS 128 bound to mucin glycopeptides from LS 180 cells and their asialo forms to the same extent as well as to ovine submaxillary mucin (OSM) and asialo OSM. Special non-sialylated GalNAc residue(s) attached to a certain peptide region in the antigens seems to be involved in the binding since N-acetylgalactosaminidase treatment of the antigen abolished the binding and pronase digestion diminished the binding markedly.

Acetylgalactosamine↗

Occurrence of tetra- and pentasaccharides with the sialyl-Le(a) structure in human milk.

The occurrence of two novel oligosaccharides in human milk was investigated. These oligosaccharides were purified by affinity chromatography on a column of an immobilized monoclonal antibody, MSW 113. Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. This constitutes the first evidence for the occurrence of N-acetylglucosamine or galactose as the reducing-end residue of human milk oligosaccharides. These two oligosaccharides bound MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but to another sialyl-Le(a) structure-directed monoclonal antibody, NS-19-9, only weakly.

Antigens, Tumor-Associated, Carbohydrate↗

Transmission of Chlamydia pneumoniae in young children in a Japanese family.

Chlamydia pneumoniae strain TWAR was isolated from the respiratory tract of a 5-year-old girl suffering from pneumonia. The IgM and IgG antibody titers to TWAR were 1:32 and 1:128, respectively. Cultures and serology for other common bacterial and viral respiratory pathogens were negative. Although she was treated with 35 mg/kg/day rokitamycin, TWAR was repeatedly isolated after treatment. Her 3-year-old sister developed acute bronchitis, and TWAR was isolated from her nasopharynx. She was treated with 43 mg/kg/day erythromycin with prompt improvement, and TWAR was not isolated after treatment. Although her mother, grandmother, and 8-month-old sister suffered from respiratory illness during these periods, TWAR was not isolated from them. The repeated isolations from the index patient suggest that infection was transmitted from sister to sister. This case represents the first reported isolation of TWAR from young children in the same household and the first from Japan.

Adult↗

Increased accumulation of cytosine arabinoside in human leukemic cells and enhancement of its cell-killing activity by uridine.

The effects of uridine(UR) on the cell-killing activity of cytosine arabinoside(ara-C) against human leukemic cells, MOLT-4, and on ara-C accumulation in cells were studied. The 50% lethal dose(LD50) of ara-C as determined by clonogenic assay was decreased to 5.0 x 10(-8) mol from 9.0 x 10(-7) mol after 3 days exposure to 10(-3) mol of UR. The accumulation of 3H-ara-C at 24 and 48 h was significantly increased in culture medium containing 10(-8) mol of 3H-ara-C and 10(-3) mol of UR (5,129 +/- 123.5 vs 2,554 +/- 115.5 cpm/10(5) cells at 24 h, p less than 0.01, and 5,772 +/- 123.2 vs 1,372 +/- 51.8 cpm/10(5) cells at 48 h, p less than 0.01). It is noteworthy that cell-killing activity of ara-C against human leukemic cells was enhanced by the combination with a nucleoside(UR), but not with antileukemic agents.

Cell Survival↗

Three novel oligosaccharides with the sialyl-Lea structure in human milk: isolation by immunoaffinity chromatography.

We have determined the structures of three novel oligosaccharides isolated from human milk using the monoclonal antibody MSW 113. These oligosaccharides were purified by affinity chromatography on a column of the immobilized monoclonal antibody and by high-performance liquid chromatography. From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly.

Carbohydrate Sequence↗

A new antitumor antibiotic, FR900840. III. Antitumor activity against experimental tumors.

FR900840 [2S)-2-amino-2-carboxyethyl (3R)-2-diazo-3-hydroxybutyrate), a new antibiotic with antitumor activity was isolated from the fermentation broth of Streptomyces sp. No. 8727. Its antitumor activity was examined in three mouse tumor systems and ten human tumor systems. FR900840 had no clear effect on mouse ascitic tumors, P388 and L1210, and the B16 melanoma line, but had prominent antitumor effects on several human solid tumors. Its antitumor activity against A549 human lung adenocarcinoma was stronger than those of vinblastine, doxorubicin and cisplatin. These results suggest that FR900840 may become a useful prototype antitumor drug.

Adenocarcinoma↗

[Treatment of acute lymphocytic leukemia in adult].

Since April, 1978 to October, 1988, 66 acute lymphocytic leukemia (ALL) patients aged 15 to 79 (21 L1, 43 L2, 2 L3/6 Ph1+) were treated with 3 different therapeutic protocols. The drugs used for induction were VCR (VDS) + Pred, followed by DNR + VCR (VDS) + 6MP + Pred and VCR (VDS) + L-asp + Pred in protocol I, Ad + VCR + Pred in protocol II and DNR + VCR + Pred in protocol III. Complete remission (CR) was attained in 72.7% of 66 patients. The CR rate of each group as followings; 71.4% in protocol I and 75.0% in protocol II and III, respectively. The median duration of remission was 10.2 months + and the probability of being in continuous CR at 3 years was 21.9%. For the 48 patients in remission the median survival was 17.8 months and the probability of being alive at 3 years was 24.3%. The intensified induction and consolidation therapy is expected in the cure oriented treatment of adult ALL.

Adolescent↗

[Treatment of chronic myelogenous leukemia (CML)--VP(M) regimen starting during its chronic phase, and the second nation-wide survey on the long-term survivors of CML in Japan].

Eighty-three patients in the chronic phase of Ph1-positive chronic myelogenous leukemia (CML) have been treated with busulfan or other alkylating agents in a conventional way hitherto acknowledged. During its chronic phase, 31 cases of these 83 had received an additional intermittent therapy every 4 to 6 months, consisting of vincristine 2 mg or vindesine 3 mg per week, prednisolone 20 to 30 mg per day, and partly 6-mercaptopurine 50 to 100 mg, combined with allopurinol 200 to 300 mg per day for 2 to 3 weeks. The 50% survival of these patients using the Kaplan-Meier's method was 73, 7 months and 5-year survival was 70.2%, while those of the remaining patients were 41.2 months and 13.4%, respectively. The second nation-wide survey of long-term survivors of CML in Japan was attempted. CML totalling 195 surviving over 7 years from the initial diagnosis and 113 of CML surviving over one year from the blastic crisis had been collected by the end of March 1988. The longest survivors of the former group was for 21.3 years, while the latter 4.6 years. In addition, recent increase of the annual incidence of the above both groups was clarified. These results strongly support the progress of chemotherapy of CML in recent years.

Adolescent↗

[Thrombolytic therapy of pulmonary thromboembolism--result of 18 patients].

In Japan, pulmonary thromboembolism (PTE) is rare and the therapy of this disease, especially the thrombolytic therapy, has not been established yet. We studied the effect of thrombolytic therapy by urokinase (UK) in eighteen patients with PTE. We also compared the results with those in Europe and the United States. Eighteen patients (male 7, female 11) were 27 yo to 77 yo (mean 55 yo). Seven cases were mild and 11 cases were moderate to severe. The initial dosage of UK administration was 2.4 x 10(5) to 7.2 x 10(5) IU with the mean of 4.1 x 10(5) IU, which was approximately the double of those in Europe and the US. The duration of UK therapy was 1 to 9 days with the mean of 4.8 days. It was longer than in Europe and the US (12-24 hours). Total amount of UK in each case ranged 4.8 x 10(5) to 42 x 10(5) IU (mean 19.3 x 10(5) IU) with the daily dosage of 4.0 x 10(5) IU in average. They were almost half of those in Europe and the US. Clinical signs and laboratory findings subsided in 1-7 day by UK administration in 14 cases (87%) with the reduction of defects on perfusion lung scans and all of these cases survived. No severe complications were found in any cases. We conclude that the thrombolytic therapy with UK in Japan might be acceptable from the results of this present study. However, the prospective study of thrombolytic therapy on a larger scale remains to be done in the future.

Adult↗

[Chemotherapy of chronic myelogenous leukemia--VP(M) regimen initiated during its chronic phase, and evaluation of MCNU in the phase of blastic crisis].

Seventy-four patients in the chronic phase of Ph1-positive chronic myelogenous leukemia (CML) have been treated with busulfan or other alkylating agents in a conventional way. During its chronic phase, 24 of these 74 cases had received additional intermittent therapy every 4 to 6 months, consisting of vincristine 2 mg or vindesine 3 mg per week, prednisolone 20-30 mg per day and partly 6 mercaptopurine 50 to 100 mg, combined with allopurinol 200 to 300 mg per day for 2 to 3 weeks. The 50% survival of these patients using the Kaplan-Meier's method was 73.7 months and 5-year survival was 69.6%, against 40.5 months and 14.4%, respectively, in the remaining patients. Nine patients in the blastic or accelerated phase of Ph1-positive CML have been treated with new regimens including MCNU. All cases had been refractory for usual types of induction chemotherapy. The new regimen consisted of MCNU 50-100 mg, combined with vindesine or 6-MP plus allopurinol or prednisolone. Five out of 9 cases attained complete remission and 1 partial remission. The major adverse effect of this regimen was slight liver damage. MCNU could be regarded as an useful agent in the blastic phase as well as in the chronic phase of CML.

Adolescent↗

A monoclonal antibody that recognizes a cluster of a disaccharide, NeuAc alpha(2----6)GalNAc, in mucin-type glycoproteins.

The structure of an epitopic carbohydrate recognized by a monoclonal antibody, MLS 102, was determined. A disaccharide, NeuAc alpha (2----6)GalNAc, the major prosthetic group of ovine submaxillary mucin (OSM) and related synthetic glycosides, NeuAc alpha(2----6)GalNAc alpha----Ser, NeuAc alpha(2----6)GalNAc beta----Ser, and NeuAc alpha (2----6)GalNAc beta----propyl, reacted with MLS 102 to similar extents, but the reaction was considerably weaker compared to that of OSM. This difference in reactivity could be ascribed to the occurrence of a cluster of the disaccharide on OSM. Purification of MLS 102-reactive antigens from a Triton X-100 extract of LS 180 cells by means of immunoaffinity chromatography gave mucin fractions (cMLS 102 antigen) with an OSM-like domain. Correlation between the content of the disaccharide, NeuAc alpha(2----6)GalNAc, in mucins and their reactivity with MLS 102 was observed.

Antigen-Antibody Complex↗

Immunoaffinity isolation of a sialyl-Le(a) oligosaccharide from human milk.

A cancer-associated antigen, sialyl-Le(a) oligosaccharide, was isolated from human milk using a monoclonal antibody recognizing carbohydrate moieties of mucin-type glycoproteins. The structure was identified as: (Formula: see text) based on 500-MHz 1H-NMR spectroscopy. This oligosaccharide comprises 0.07% of sialyloligosaccharides in human milk. The NMR spectra of two fellow oligosaccharides, Le(a) oligosaccharide (or lacto-N-fucopentaose II) and LS-tetrasaccharide a, are also given.

Antibodies, Monoclonal↗

A monoclonal antibody that recognizes sialyl-Lea oligosaccharide, but is distinct from NS 19-9 as to epitope recognition.

A murine monoclonal antibody, designated as MSW 113, was generated using a human colonic cancer cell line, SW 1116, as the immunogen. MSW 113 was shown to be directed mainly to mucin-type oligosaccharide with sialyl-Lea antigens. The reactivity of MSW 113 to sialyl-Lea was stronger than that of NS 19-9, which is believed to be raised against the same determinant group. MSW 113 binds to sialyl-Lea-ol, LS-tetrasaccharide a, and disialyllacto-N-tetraose with higher affinities, compared to NS 19-9. These two antibodies could clearly be distinguished in that MSW 113 bound to sialic acid but not to fucose, whereas NS 19-9 bound to fucose but not to sialic acid. Thus, MSW 113 is directed more toward sialic acid-containing terminal structures while NS 19-9 is directed toward fucose-containing internal structures. MSW 113 was found to be useful for detecting antigens in the bloodstream of patients, especially those with pancreas cancer. Even NS 19-9 negative patient sera were positive for MSW 113.

Antibodies, Monoclonal↗