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Biomedical subjects

S Ohta

Publications and source records attributed to S Ohta.

At least 739 records · Page 41Linked to original sources

[Interstitial pneumonia after CMC (CDDP, MMC, CPM) therapy].

Six patients receiving CDDP, MMC, and CPM chemotherapy for adjuvant chemotherapy after a resection due to lung cancer developed interstitial pneumonia. They were re-admitted for dyspnea, shortness of breath, and dry cough from 80 to 118 days from start of their treatment. On re-admission, their chest radiographs showed reticular infiltrates, and their laboratory data showed severe hypoxemia. The pathological findings of a transbronchial lung biopsy showed a thickening of the alveolar septa. Steroid therapy resulted in a complete resolution in one patient and a partial resolution the 5 others. One year later, two patients had died, one patient remains in complete resolution, but a shortness of breath still exists in the remaining three patients. Considering the disadvantages of that shortness of breath can cause to daily life, we should be more cautious about administering antineoplastic agents for adjuvant chemotherapy to patients with a cancer in an early stage.

Aged↗

[Effect of a calcium influx blocker, verapamil, on the sensitivity of human bladder cancer cells to adriamycin and mitomycin C].

We have investigated the effect of verapamil on the cytotoxicity of adriamycin and mitomycin C with human bladder cancer cell lines T-24 and JTC-30. The concentration of verapamil was 10 M, and adriamycin and mitomycin C were used at the concentrations ranging from 10(-2) micrograms/ml to 10 micrograms/ml. The efficacy of drugs were evaluated using cytotoxicity and colony forming assays. Judging from the results of these assays, no significant difference was observed between the drugs in combination with verapamil and drugs alone. The results indicate verapamil has no enhancement for the cytotoxic activity of the anticancer drugs when cell lines T-24 and JTC-30 are used.

Doxorubicin↗

An extremely acidic amino-terminal presequence of the precursor for the human mitochondrial hinge protein.

Mitochondrial hinge protein is a subunit of ubiquinol-cytochrome-c reductase in the respiratory chain and 'hinges' cytochrome c with cytochrome c1. The protein is encoded in the nuclear genome, synthesized in the cytosol and then imported into the mitochondria. The cDNA of the human hinge protein has been cloned and its nucleotide sequence was determined. The deduced primary structure of the amino-terminal presequence consists of 13 amino acid residues, of which 4 amino acids are acidic and only one is basic. Since the presequences of most other precursors are rich in basic amino acids, this sequence is unique for targeting mitochondria. Expression of the gene was repressed in the presence of a phorbol ester in human promyelocyticleukemia cells (HL-60), and this repression was greater than that of the ADP/ATP translocator. These findings suggest that the hinge protein, the expression of which is well regulated, is imported into mitochondria via a specific pathway.

Amino Acid Sequence↗

Combination tumor-immunotherapy with recombinant tumor necrosis factor and recombinant interleukin 2 in mice.

Recombinant human tumor necrosis factor (r-TNF) inhibits growth of various mouse tumor cell lines both in vitro and in vivo. Treatment of established tumor nodules with intratumoral (i.t.) injection of r-TNF caused hemorrhagic necrosis of tumor and temporary disappearance of tumor mass. However, a small number of tumor cells remained and later formed fresh nodules. In striking contrast, combination therapy with r-TNF and recombinant human interleukin-2 (r-IL-2) resulted in a marked inhibition of regrowth of tumor cells. More than 60% of MBL-2-bearing mice were completely cured of tumor by treatment with r-TNF and r-IL-2. Cured mice could also reject rechallenged MBL-2 lymphoma cells, indicating the generation of anti-tumor effector cells in vivo. However, lymphocytes obtained from mice cured of MBL-2 showed no significant in vitro cytotoxic activity against MBL-2 lymphoma cells. In contrast, in vitro sensitization of spleen cells from cured mice with mitomycin-C-treated MBL-2 lymphoma cells resulted in the generation of cytotoxic cells against MBL-2 lymphoma cells. Moreover, spleen cells from mice cured of MBL-2 by treatment with r-TNF and r-IL-2 revealed a strong anti-tumor activity upon in vivo neutralization tests. These results strongly suggest that tumor-bearing mice can acquire systemic immunological memory after combination therapy with r-TNF and r-IL-2.

Animals↗

Antitumor effect of adriamycin entrapped in liposomes conjugated with anti-human alpha-fetoprotein monoclonal antibody.

The monoclonal antibody, 19-F-12 (IgG2b), against human alpha-fetoprotein was conjugated to liposomes containing Adriamycin, and the therapeutic effects of the conjugate were experimentally studied using the alpha-fetoprotein-producing human hepatoma strain, Li-7, maintained in BALB/c nu/nu male mice. Three i.v. injections of liposomes containing Adriamycin (7.5 mg/kg) into tumor-bearing mice significantly inhibited the tumor growth, and the therapeutic effect of the antibody-conjugated liposomes was greater than that of unconjugated liposomes, as judged from the tumor weights and histological findings. Furthermore, the experiments were repeated with Adriamycin (4-5 mg/kg) in free form, since administration of Adriamycin (7.5 mg/kg) in free form was highly toxic for the mice. The results still indicated that the therapeutic effect of Adriamycin in 19-F-12 conjugated liposomes was superior to that of free Adriamycin or Adriamycin in unconjugated liposomes. In contrast to the treatment for Li-7 in nude mice, the therapeutic effect of Adriamycin in 19-F-12 conjugated liposomes was not much different from that of Adriamycin in normal mouse IgG (IgG2b fraction) conjugated liposomes against alpha-fetoprotein-negative human breast cancer strain MX1. Tissue distribution studies after i.v. injection of Adriamycin in various forms into mice revealed that preferential delivery of Adriamycin to tumors occurred to some extent with antibody-conjugated liposomes as compared to the unconjugated liposomes. In addition, reduction of the distribution of Adriamycin to the heart was achieved by administering the drug in the liposome-entrapped form, and this enabled the use of a higher dose (7.5 mg/kg) of Adriamycin without toxic side effect.

Animals↗

In vitro mutated beta subunits from the F1-ATPase of the thermophilic bacterium, PS3, containing glutamine in place of glutamic acid in positions 190 or 201 assembles with the alpha and gamma subunits to produce inactive complexes.

Using site-directed mutagenesis, Glu-190 or Glu-201 of the beta subunit of the F1-ATPase from the thermophilic bacterium PS3 were replaced with glutamine. It was possible to reconstitute complexes of the mutated beta subunits with alpha and gamma subunits, but the complexes did not have ATPase activity. It is concluded that carboxylic acid side chains of Glu-190 and Glu-201 of the beta subunit are essential for catalytic activity of F1-ATPase.

Bacteria↗

Isolation of a cDNA clone for human cytochrome c1 from a lambda gt11 expression library.

Antiserum directed against a purified preparation of beef heart cytochrome bc1 complex has been used to screen a human liver cDNA expression library in lambda gt11. The inserts of two recombinants, which gave strong signals, were found to represent cytochrome c1 by epitope selection using nitrocellulose filters containing the expressed proteins. The amino acid sequence deduced from the nucleotide sequence of an insert DNA revealed a high degree of homology with the sequence of bovine cytochrome c1.

Amino Acid Sequence↗

The role of ventricular and cisternal drainage in the early operation for ruptured intracranial aneurysms.

In a series of 177 patients with ruptured supratentorial aneurysms we studied retrospectively the results of early and delayed operation without aggressive removal of subarachnoid blood clots but ventricular and cisternal drainage. The early and delayed groups were comparable demographically and neurologically. The overall results for the early group were a good outcome in 65%, poor outcome in 10% and death in 24%, compared to 53, 20 and 27% respectively in the delayed group. Thus, patients with an early operation and CSF drainage had better results. Permanent ischaemic neurological deficits due to cerebral vasospasm accounted for the poor outcome in 10 and 21% of the patients in the early and delayed groups, respectively and rebleeding accounted for the poor outcome in 5 and 10% in the early and delayed groups respectively. The mean amount of haemoglobin in the cerebrospinal fluid from cisternal drainage was 6.4 g, corresponding to about 40 ml of whole blood, during the 12-day period after SAH. The level was higher in patients with larger subarachnoid clots or with symptomatic vasospasm than in those with smaller clots or without such vasospasm. Early operation combined with ventricular and cisternal drainage is considered to be a useful surgical method for patient with a ruptured aneurysm.

Adult↗

The role of lymphokine-activated cell-associated antigen. III. Inhibition of T-cell activation by monoclonal killer-blocking antibody.

The addition of monoclonal killer blocking antibodies (KBA MAb) to cultured T cells resulted in significant inhibition of T-cell responses to concanavalin A (Con A), class I antigen and class II antigen, whereas T-cell responses to phytohemagglutinin are insensitive to KBA MAb. The inhibitory effect of KBA MAb is observed only when KBA MAb is added to the culture at an early time. This indicates that the lymphokine-activated cell-associated antigen (LAA) defined by KBA MAb plays an important role in the early stages of T-cell activation. Con A-induced interleukin 2 (IL-2) receptor acquisition and IL-2 production, both of which are required for the early steps of T-cell activation, were greatly inhibited by KBA MAb. However, KBA MAb did not inhibit the action of IL-2, which is required for later stages of T-cell activation.

Animals↗

An extended middle fossa approach combined with a suboccipital craniectomy to the base of the skull in the posterior fossa.

A new approach to the base of the skull in the posterior fossa is described. This approach involves removing the petrous bone without any injury to the labyrinth, and dividing the superior petrosal sinus and tentorium cerebelli. A combined suboccipital craniectomy is used for excision of the portion of tumors that extended inferiorly. Total or subtotal removal of tumors was performed in 11 patients and partial removal in 3 patients, without any operative mortality. The facial nerve was preserved in all patients and hearing was retained in 9 of 12 patients. This approach is useful for large tumors located around the clivus.

Adolescent↗

Hydrogen evolution as a consumption mode of reducing equivalents in green algal fermentation.

Dark anaerobic fermentation in the green algae Chlamydomonas MGA 161, Chlamydomonas reinhardtii, Chlorella pyrenoidosa, and Chlorococcum minutum was studied. Our isolate, Chlamydomonas MGA 161, was unusual in having high H(2) but almost no formate. The fermentation pattern in Chlamydomonas MGA 161 was altered by changes in the NaCl or NH(4)Cl concentration. Glycerol formation increased at low (0.1%) and high (7%) NaCl concentrations; starch degradation, and formation of ethanol, H(2), and CO(2) increased with the addition of NH(4)Cl to above 5 millimolar in N-deficient cells. C. reinhardtii and C. pyrenoidosa exhibited a very similar anaerobic metabolism, forming formate, acetate and ethanol in a ratio of about 2:2:1. C. minutum was also unusual in forming acetate, glycerol, and CO(2) as its main products, with H(2), formate, and ethanol being formed in negligible amounts. In the presence of CO, ethanol formation increased twofold in Chlamydomonas MGA 161 and C. reinhardtii, but the fermentation pattern in C. minutum did not change. An experiment with hypophosphite addition showed that dark H(2) evolution of the Escherichia coli type could be ruled out in Chlamydomonas MGA 161 and C. reinhardtii. Among the green algae investigated, three fermentation types were identified by the distribution pattern of the end products, which reflected the consumption mode of reducing equivalents in the cells.

Journal Article↗