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Biomedical subjects

M Ohtsuka

Publications and source records attributed to M Ohtsuka.

At least 163 records · Page 9Linked to original sources

[A case of sarcoidosis presenting with high fever and acute respiratory failure].

A 55-year-old man was admitted with complaints of remittent fever (39 degrees C) and dyspnea on exertion which began ten days previously. His family and past histories were non-contributory for diagnosis except his occupation as a stone mason for 26 years. The chest X-ray film taken on admission showed diffuse small nodular shadows associated with small amounts of pleural effusion and bilateral hilar adenopathy. Arterihl blood gas analysis showed severe hypoxemia and hypocapnea (Pao2 32.2 Torr, Paco2 31.6 Torr). The serum level of LDH was 985 IU/L and ACE was 49.0 IU/L, lysozyme was 28.8 micrograms/ml. Biopsied materials of the lung obtained by TBLB, liver and bone marrow showed non-caseating epithelioid granuloma without caseating necrosis. T-lymphocyte ratio increased in BALF. The patient was diagnosed to have sarcoidosis. The administration of prednisolone was initiated, which resulted in a marked improvement of clinical data including chest X-ray films, BGA, LDH, ACE and lysozyme.

Acute Disease↗

Inhibition of colony-stimulating factor-1 activity by monoclonal antibodies to the human CSF-1 receptor.

Four of 12 monoclonal antibodies (MoAbs) directed to different epitopes in the extracellular domain of the human colony-stimulating factor-1 receptor (CSF-1R, the c-fms proto-oncogene product) specifically inhibit CSF-1 binding to receptor-bearing cells. All four antibodies abrogated CSF-1-dependent colony formation by human bone marrow-derived macrophage precursors and by mouse NIH-3T3 cells expressing a transduced human c-fms gene. In addition, one of these antibodies (designated MoAb 2-4A5) interfered with the ligand-independent proliferation of NIH-3T3 cells transformed by an oncogenic, mutant c-fms allele. Unlike CSF-1 itself, neither MoAb 2-4A5 nor the other three inhibitory antibodies (MoAbs 12-2D6, 12-3A1, and 12-3A3) induced CSF-1R internalization or degradation. These antibodies should prove useful not only for identifying and quantitating CSF-1R on receptor-bearing cells but for abrogating specific receptor signals that govern the proliferation and survival of human mononuclear phagocytes.

Alleles↗

Monoclonal antibodies to the human CSF-1 receptor (c-fms proto-oncogene product) detect epitopes on normal mononuclear phagocytes and on human myeloid leukemic blast cells.

The first monoclonal antibodies (MoAbs) to epitopes in the extracellular domain of the human c-fms proto-oncogene product (receptor for the macrophage colony stimulating factor, CSF-1) were used with flow cytometric techniques to study receptor expression on normal human peripheral blood monocytes, bone marrow cells, and leukemic blasts. On normal cells CSF-1 receptors were restricted in their expression to cells of the mononuclear phagocyte lineage. CSF-1 receptors were detected on leukemic blasts from 15 (30%) of 50 children with acute myeloid leukemia, compared with four (15%) of 26 adults. By contrast, detectable CSF-1 receptors were uniformly absent on blasts from 19 children with acute lymphoblastic leukemia. CSF-1 receptors on normal monocytes and myeloid leukemia cells could be induced to downmodulate by incubation with either human recombinant CSF-1 or phorbol esters, confirming that the receptors had functional ligand-binding sites and responded to transmodulation by inducers of protein kinase C. The numbers of receptors per cell and the percentage of positive cases were highest for leukemic blasts with cytochemical and morphological features of monocytes. However, CSF-1 receptors were also detected on a subset of leukemic blast cells with features of granulocytic differentiation (FAB subtypes M1 through M3). Southern blotting analyses of DNA from 47 cases of acute myeloid leukemia demonstrated no rearrangements within the 32 kb of genomic sequences that contain CSF-1 receptor coding exons or in the 50 kb upstream of the first coding exon. Analysis of the upstream region of the c-fms locus revealed that sequences representing the terminal 112 untranslated nucleotides of c-fms mRNA map 26 kb 5' to the first coding exon, suggesting that at least one c-fms promoter is separated from the receptor coding sequences by a very long intron. Whereas expression of the CSF-1 receptor in myeloid leukemic blasts is not restricted to cells with monocytic characteristics, the apparently aberrant pattern of receptor synthesis in a subset of cases with granulocytic features appears not to be due to chromosomal rearrangements within 50 kb upstream of sequences encoding the receptor.

Antibodies, Monoclonal↗

Hypersensitivity pneumonitis induced by toluene diisocyanate: sequelae of continuous exposure.

A 41-year-old automobile paint sprayer showed the clinical features of hypersensitivity pneumonitis 1 week after he had begun to work with paint materials containing toluene diisocyanate. His symptoms began 6 to 8 hours after exposure to the agent and spontaneously disappeared by the next morning. He had diffuse, fine reticulonodular shadows on a chest roentgenogram and a restrictive impairment of pulmonary function. Immunoglobulin G antibody to toluene diisocyanate-human serum albumin was present in bronchoalveolar lavage fluid and sera: IgA antibody was present only in bronchoalveolar lavage fluid. Also, the patient had sensitized bronchoalveolar lymphocytes to toluene diisocyanate-human serum albumin. The histologic findings suggested hypersensitivity pneumonitis. The results of bronchoalveolar lavage, which was repeated on four separate occasions, showed lymphocytosis and a predominance of suppressor-cytotoxic T cells. The findings from serial determinations of humoral antibodies showed no changes consistent with the results of clinical and laboratory studies. In contrast, blastogenic responses of bronchoalveolar lymphocytes to toluene diisocyanate markedly decreased, and the patient showed clinical improvement despite continued exposure to the agent.

Adult↗

Suppression of atherogenesis in cholesterol-fed rabbits treated with nilvadipine, a new vasoselective calcium entry blocker.

We examined the effects of nilvadipine, a new dihydropyridine calcium entry blocker, on atherogenesis in rabbits fed a 1% cholesterol diet. The drug was given subcutaneously to the animals in hypotensive doses of 1.0 or 3.2 mg/kg/day for 10 weeks, and was well tolerated. Plasma total cholesterol increased markedly in all the cholesterol-fed rabbits, and nilvadipine had no effect on this, or on HDL-cholesterol and triglyceride levels. However, the area of Sudan IV positive intimal lesions (one of the parameters of atherosclerosis) in the aorta decreased significantly in the nilvadipine treated animals, and in addition, cholesterol and calcium content in the thoracic aorta were reduced. The reference drugs, nifedipine and nicardipine given subcutaneously in doses of 10.0 mg/kg/day either had no effect or were weaker in antiatherogenic effect than nilvadipine. The findings suggest that nilvadipine has more potent antiatherogenic activity than nicardipine or nifedipine.

Animals↗

Extended transverse rectus abdominis musculocutaneous flap.

Blood circulation within the conventional TRAM flap is not generous, and the contralateral random portion of the flap may result in fat or skin necrosis. However, this random portion can be extended safely and used for reconstruction by including the superficial epigastric vessels and the superficial circumflex iliac vessels and by anastomosing either of these to the recipient vessels. We have experienced this extended TRAM flap in two patients without any complications.

Abdominal Muscles↗

Accessory cell function of human alveolar macrophages in antigen-induced T lymphocyte proliferation.

We compared the accessory cell function of human alveolar macrophages (AM) to that of human blood monocytes (Mo) obtained by bronchoalveolar lavage and venipuncture from normal volunteers. Graded numbers of either AM or Mo were added to autologous peripheral blood T lymphocytes that were stimulated with a purified protein derivative of tuberculin (PPD). Either AM or Mo were cocultured with allogeneic T lymphocytes in mixed lymphocyte reaction (MLR) experiments. Both AM and Mo supported the PPD-induced T lymphocyte proliferation and allogeneic MLR at low ratios of AM or Mo to T lymphocytes with similar efficiency. However, AM showed marked suppressive effects at higher ratios of AM to T lymphocytes (1:1). PPD-pulsed AM, but not AM killed by physical treatments (heat, freeze-thaw, sonication), induced T lymphocyte proliferation. An indirect immunofluorescent study demonstrated that most AM express HLA-DR antigens. Furthermore, AM synthesized DR antigens with molecular weights of 33,000 and 29,000-31,000 daltons. When AM were treated with both anti-DR monoclonal antibody and complement, PPD-induced T lymphocyte proliferation and MLR were diminished. These results suggest that human AM function as accessory cells in the antigen-induced T lymphocyte proliferation and DR antigens on AM play an important role in the accessory cell function.

Antibodies, Monoclonal↗

Plasma glycosyltransferase activity after ABO-incompatible bone marrow transplantation and development of an inhibitor for glycosyltransferase activity.

Plasma glycosyltransferase activities were studied in eight patients after ABO-incompatible bone marrow transplantation. The ABO red blood cell type completely changed from the recipient type to the donor type; however, preexistent plasma glycosyltransferase activities of the recipient type did not change in seven of eight patients after marrow transplantation. Weak transferase activities of the donor type were observed in all of the patients after marrow grafting. One patient with acute and chronic graft-versus-host disease produced a very potent inhibitor that was active on both A- and B-transferase activities. Because this inhibitory activity was absorbed by a protein A-coupled Sepharose column, it was strongly suggested that this inhibitory activity was mediated by an IgG antibody for a transferase.

ABO Blood-Group System↗

[The motility of lung lymphocytes in hypersensitivity pneumonitis and sarcoidosis].

Hypersensitivity pneumonitis (HP) and pulmonary sarcoidosis (Sa) are characterized by an accumulation of large numbers of lymphocytes within the interstitium and the epithelial surface of the lung. Although the lymphocytes in bronchoalveolar lavage fluid (BALF) are representative of interstitial cells in these diseases, the mechanism involved in an accumulation of lymphocytes on the epithelial surface are yet unknown. To explore the possibility that the lymphocytes on the epithelial surface are migrated cells from the interstitium, we studied the motility of the BALF lymphocytes in five patients with HP and nine patients with Sa and compared them to that of peripheral blood lymphocytes. The lymphocyte migration assay was performed using blind well chemotaxis chambers and cells migrated into the cellulose nitrate membranes were assessed. The total migrated cell numbers of BALF lymphocytes in HP and Sa were 753.3 +/- 86.5 and 334.2 +/- 41.0, respectively. The migration distance of BALF lymphocytes in HP and Sa assessed with leading front method were 50.2 +/- 3.8 microns and 57.9 +/- 4.6 microns, respectively. The motility of BALF lymphocytes in HP and Sa was significantly greater than that of peripheral blood lymphocytes and the motility of BALF lymphocytes were comparable to that of PHA-activated lymphocytes. The motility of BALF lymphocytes were correlated with the proportion of lymphocytes in BALF cells and the proportion of Ia+T lymphocytes. These results suggest that BALF lymphocytes in these diseases are activated and enhanced motility may facilitate the accumulation of lymphocytes to the epithelial surface.

Alveolitis, Extrinsic Allergic↗

[Inhalation of a precursor analogue of vasoactive intestinal polypeptide (Leu17 VIP-Gly-Lys) protects ascaris-induced bronchoconstriction in dog].

We studied in vivo the effects of pre-inhalations of vasoactive intestinal polypeptide (VIP) and a precursor analogue of VIP (Leu17 VIP-Gly-Lys: preVIP) in mongrel dogs bronchoconstricted by ascaris. An inhalation of preVIP solution (2 mg/5 ml saline) gave significant protection for 120 min against increases in respiratory resistance (Rrs) and decreases in dynamic compliance (Cdyn) induced by ascaris challenges. An inhalation of VIP solution (2 mg/ml saline) also gave significant protection for 120 min against increases in Rrs induced by ascaris challenges. Protective effect of the inhalation of preVIP against ascaris-induced bronchoconstriction was more potent than that of VIP. The inhalations of preVIP and VIP solution did not change systemic blood pressure or heart rate. These results indicate that inhalations of preVIP or VIP solution would attenuate ascaris-induced bronchoconstriction in dogs without affecting cardiovascular dynamics.

Administration, Inhalation↗

[Flow cytometric analysis of T lymphocyte subsets after human bone marrow transplantation using monoclonal antibodies and dual immunofluorescence].

Using monoclonal antibodies and a dual immunofluorescence technique, we studied the abnormalities of T lymphocyte subsets after human marrow transplantation. T lymphocytes bearing HLA-DR antigen increased both in patients with acute and chronic graft-versus-host disease (GVHD). Parallel to a decrease in CD4+ cells, a CD4+ 2H4+ subset decreased and gradually recovered with time while the percentage of CD4+ 4B4+ cells increased. A significant increase of CD8+ cells observed after marrow transplant corresponded mainly to an increase in CD8+ CD11- cells. Patients with chronic GVHD tended to have a higher proportion of CD8+ CD11+ cells. These results indicate abnormalities of T cell subsets among both CD4+ and CD8+ cells after marrow grafting.

Adolescent↗

Binding of the new calcium entry blocker nilvadipine to rat aortic and guinea pig left ventricular membranes.

The binding of 3H-nilvadipine to the vascular (rat aortic) and cardiac (guinea pig left ventricular) microsomes was reversible and saturable. The results of the competitive binding experiments showed that nilvadipine had a higher affinity (Kd: 1.5 +/- 0.2 nmol/l) for the vascular binding sites than did nifedipine (Kd: 10.7 +/- 0.8 nmol/l) and nicardipine (Kd: 6.9 +/- 2.0 nmol/l), while the affinity of nilvadipine for the cardiac binding sites (Kd: 3.8 +/- 0.4 nmol/l) was similar to that of nifedipine (Kd: 3.3 +/- 0.1 nmol/l) and nicardipine (Kd: 4.2 +/- 0.3 nmol/l). The time courses of dissociation of the unlabeled dihydropyridines from the vascular binding sites were investigated using 3H-nitrendipine. Nilvadipine and nicardipine dissociated more slowly from the binding sites than did nifedipine. These results suggest that the high potency, selectivity for the vascular smooth muscle and long duration of action of nilvadipine may be related to its binding properties.

Animals↗

[A case of retrocecal appendicitis occurrence during effective chemotherapy in lung cancer].

Reported is the case of 61-year-old male patient who developed an abscess, secondary to a ruptured retrocecal appendicitis, while undergoing effective chemotherapy for lung cancer. Patients undergoing cancer chemotherapy are especially susceptible to infectious complications because chemotherapy can cause myelosuppression. To our knowledge, has been no previous reported case of retrocecal appendicitis occurring during chemotherapy for the lung cancer. Retrocecal appendicitis is a dangerous form of complication occurring in patients being treated with chemotherapeutic drugs.

Abscess↗