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Biomedical subjects

T Ochi

Publications and source records attributed to T Ochi.

At least 307 records · Page 17Linked to original sources

The pathology of the involved tendons in patients with familial arthropathy and congenital camptodactyly.

In 2 sisters with congenital camptodactyly and joint effusions, abnormalities in tendons were restricted to the portion within synovial sheaths. This implied a disease of the tenosynovium, rather than one of the tendon itself. In areas of chronic involvement, some tendons were replaced by fibrous tissue. Significant portions of the tendons in fingers with camptodactyly were replaced by hard scars. Congenital camptodactyly is probably the result of an intrauterine tenosynovitis, rather than an isolated congenital anomaly.

Child↗

Induction of 6-thioguanine-resistant mutants and single-strand scission of DNA by cadmium chloride in cultured Chinese hamster cells.

Inducibility of 6-thioguanine-resistant (6TGr) mutants and single-strand scission of DNA by cadmium chloride (CdCl2) was investigated in cultured Chinese hamster V79 cells. Frequency of 6TGr mutants increased concentration dependently by 24-h treatment with CdCl2 up to 3 X 10(-6) M but decreased beyond 3 X 10(-6) M. Mutagenic potency of cadmium in the absence of S9 was about half that of benzo[a]pyrene in the presence of S9 at equitoxic concentrations. Treatment of the cultured cells with cadmium after benzo[a]pyrene treatment was not synergistic but additive to the mutagenicity of benzo[a]pyrene. Single-strand scission of DNA by alkaline elution techniques was observed in the cells treated with CdCl2 for 2 h in a concentration-dependent manner. The single-strand scission by cadmium was detected only in combination with proteinase K digestion of the cell lysates, indicating formation of DNA--protein cross-linking by the metal. These biological and biochemical findings indicate that cadmium is mutagenic in mammalian cells, and its mutagenic effect seems to be accompanied by single-strand scission of DNA.

Animals↗

Mutagenicity in Salmonella typhimurium mutants of serum extracts from airborne particulates.

Airborne particulates collected from urban and non-urban air were extracted with calf serum or benzene, and their mutagenic potencies were evaluated in the Salmonella reversion assay. The serum extracts were mutagenic to strains TA98 and TA100 and contained both direct- and indirect-acting mutagens. Mutagenic activities for TA98 recovered from the particulates by serum or benzene extraction were much less in the serum extracts than in the benzene extracts. There was no significant difference in mutagenic potencies of the extracts between the urban and non-urban particulates, irrespective of the presence of S9 mix. The calculated mutagenic activities per m3 of air, however, were greater for urban air than for non-urban air, because of higher concentration of particulates in urban air than in non-urban air. Serum effectively reduced both direct and indirect mutagenic activities of the benzene extracts except for an insufficient reduction in direct mutagenicity at a high dose of benzene extracts. These findings suggest that serum could contribute greatly to decrease the mutagenicity of airborne particulates by mechanisms such as less efficient solubilization of mutagenic components and inactivation by protein binding. Biological availability of mutagens, therefore, should be considered for evaluation of actual mutagenic hazard by airborne particulates.

Air Pollutants↗

Participation of active oxygen species in the induction of DNA single-strand scissions by cadmium chloride in cultured Chinese hamster cells.

A mechanism for the induction of DNA single-strand scissions in cultured Chinese hamster cells by cadmium chloride (CdCl2) was investigated by use of the technique of alkaline elution. Inducibility of DNA single-strand scissions by cadmium was examined under an aerobic or anaerobic culture condition. About 62% of the total cellular DNA was eluted throughout the filter within 10 h of elution time by treatment with 4 X 10(-5) M CdCl2 for 2 h in our usual aerobic medium. In contrast, no difference in elution profiles of DNA was observed between untreated control cells and the cells treated with CdCl2 in the anaerobic medium which was prepared by N2 gas bubbling of aerobic medium for 60 min. Furthermore, elution of DNA from cells treated with cadmium decreased markedly in the presence of superoxide dismutase (SOD) when compared with that in the absence of SOD. Inhibition of the cell growth by cadmium was significantly protected by the presence of SOD in the medium although the cell growth was not restored to the control level. These results indicate that active oxygen species participate in Cd-induced DNA single-strand scissions and also in the growth inhibition of the cells by the metal.

Animals↗

Cadmium-induced DNA single-strand scissions and their repair in cultured Chinese hamster cells.

DNA lesions induced by cadmium chloride (CdCl2) were characterized using the technique of alkaline or neutral elution for cell-DNA in cultured V79 cells. A marked increase in elution of the DNA was observed on elution of the proteinase-K-digested cell lysates with alkaline eluting solution (pH 12.2) after treatment with 5 X 10(-5) M CdCl2 for 2 h. In contrast, no increase in elution of the DNA was observed when the same cell lysates were eluted with an eluting solution of pH 9.6. These findings indicate that the DNA lesions induced by cadmium were DNA single-strand but not double-strand scissions. The DNA single-strand scissions by cadmium were partly rejoined after 4 h of repair incubation. However, the DNA lesions were not rejoined up to the control level in the technique of alkaline elution, even after 20 h of repair incubation. On the other hand, an apparent increase in elution of the DNA was observed by combined treatment with cadmium and inhibitors of repair DNA synthesis, hydroxyurea (HU) and 1-beta-D-arabinofuranosylcytosine (ara-C), for 4 h when compared to elution of the DNA from the cells treated with cadmium alone or HU and ara-C. These results indicate that cadmium-induced DNA single-strand scissions accumulated as a result of inhibition of repair DNA replication by HU and ara-C. Thus, it is concluded that cadmium-induced DNA single-strand scissions were repairable and their repair might be dependent upon the excision repair mechanism.

Animals↗

Suppression of the proliferative response of human lymphocytes to cultured allogeneic HeLa cells by zinc.

Zinc added to the culture medium caused a dose-related suppression of the proliferative response of human lymphocytes to cultured allogeneic HeLa cells without any significant decrease in cell viability. In contrast to the response to HeLa cells, this metal ion moderately enhanced T lymphocyte response to mitogens such as phytohemagglutinin (PHA), concanavalin A (ConA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). These findings seem to indicate that zinc may be a crucial factor for the modulation of the T lymphocyte function. It can also be considered that the different effect of zinc on the proliferative responses of lymphocytes to allogeneic HeLa cells and to some soluble mitogens might reflect a difference in mechanisms between the two proliferative responses.

HeLa Cells↗

Immunomodulatory effect of procainamide in man. Inhibition of human suppressor T-cell activity in vitro.

Procainamide (PA) induces the production of a number of autoantibodies in a high proportion of treated individuals and in some a syndrome closely resembling systemic lupus erythematosus. The mechanism underlying this action of PA is unclear. To examine the possibility that PA might induce autoantibody formation by altering normal immunoregulatory mechanisms, the action of this drug on an in vitro model of antibody formation in man was examined. PA was found to augment the generation of immunoglobulin-secreting cells (ISC) from human peripheral blood mononuclear cells (PBM) in response to pokeweed mitogen but had no effect on pokeweed mitogen-induced tritiated thymidine incorporation. When purified populations of B and T cells were used, PA enhanced the generation of ISC in B-cell cultures supported by untreated T cells but not by T cells treated with mitomycin C. These results indicate that PA augmented B-cell responses by inhibiting suppressor T-cell activity and not by augmenting helper T-cell or B-cell function. N-Acetyl-procainamide had no effect on the generation of ISC in this system. The effect of PA on concanavalin A (Con A)-induced suppressor cell activity was also examined to determine whether PA altered the generation or expression of suppressor T-cell function. PBM were cultured with 30 microgram/ml of Con A for 48 h to generate suppressor cells. When these were co-cultured with fresh PBM, the number of ISC generated was decreased by 58.1 +/- 3.4% (mean +/- SEM, n = 6). Cells that had been similarly incubated without Con A were not inhibitory. The addition of PA to the Con A-stimulated cultures inhibited the generation of suppressor cells as indicated by the fact that the response of fresh cells co-cultured with the Con A-stimulated cells was diminished by only 27.2 +/- 4.3%. In this system too, N-acetyl-procaimamide had no effect. By contrast, adding PA only to the co-culture of Con A-stimulated cells with fresh PBM had a less marked effect on suppressor cell function. These results indicate that the major action of PA is to inhibit the generation of suppressor T-cell activity. Such an effect may explain the capacity of this agent to induce autoantibody formation in treated individuals.

Antibody Formation↗

Diagnostic significance of early diastolic time intervals in patients with hypertrophic cardiomyopathy and myocardial hypertrophy due to essential hypertension.

In order to differentiate hypertrophic cardiomyopathy (HCM) from myocardial hypertrophy due to essential hypertension (HT), echocardiogram, apexcardiogram and phonocardiogram were simultaneously recorded in patients with HCM (n = 22), HT (n = 34) and normal subjects (N) (n = 22). The following early diastolic time intervals were measured: 1) IIA-O time, 2) IIA-MVO time (IRT) and 3) MVO-O time. The IIA-O time was 119 +/- 9 msec in N, 159 +/- 31 in HT (p less than 0.001, vs N) and 228 +/- 57 in HCM (p less than 0.001, vs N and HT, respectively). The IIA-MVO time was 66 +/- 11 msec in N, 95 +/- 18 in HT (p less than 0.001, vs N) and 102 +/- 24 in HCM (p less than 0.001, vs N). The MVO-O time was 53 +/- 9 msec in N, 66 +/- 21 in HT and 126 +/- 48 in HCM (p less than 0.001, vs N and HT, respectively). These results showed that among the early diastolic time intervals HT was abnormal only in the IIA-MVO time. On the other hand, HCM had abnormalities not only in the IIA-MVO time but also in the MVO-O time. Both the IIA-MVO and the MVO-O times in hypertrophic non-obstructive cardiomyopathy were prolonged significantly as compared to those in obstructive one. Analysis of early diastolic time intervals may be very useful to differentiate HCM, especially of the non-obstructive type, from HT.

Cardiomegaly↗

A mechanism for the stimulation by inorganic mercury of [3H] thymidine incorporation into DNA in cultured Molt-4F cells.

Mercuric chloride at a narrow range of concentration (2 to 2.5 X 10(-5)M) facilitated [3H]thymidine incorporation into acid-insoluble material (DNA fraction) of cultured human T lymphoid cells, Molt-4F, after 72-hr culture with the metal. This effect by mercury was observed in spite of the decrease in growth rate and DNA contents of the cells. Thymidine kinase activity in Molt-4F cells treated with 2 X 10(-5)M mercury decreased to 50 to 60% of the control activity. The stimulation of [3H]thymidine incorporation into the cells by mercury, therefore, might be independent of the increase in thymidine kinase activity. 3H-Thymidine incorporation by the control cells decreased as culture time passed. In contrast to the control, [3H]thymidine incorporation by mercury-treated cells increased until 72-hr culture. [3H]Thymidine uptake by the control cells after 24, 48, or 72-hr culture increased until 20 min of incubation period, but thereafter no increase in the uptake was observed until 60 min. On the other hand, [3H]thymidine uptake by the cells treated with mercury for 24 to 72 hr increased linearly until 60 min of incubation period. These results seemed to indicate that the mercury stimulation of [3H]thymidine incorporation might be attributable not to the actual increase of DNA synthesis but to the suppression of the culture time-dependent decrease in the incorporation by the control cells.

Cell Line↗

Effect of prazosin on serum lipids.

On the premise that serum lipids may be correlated with the increased mortality from coronary heart disease seen in Japan despite successful antihypertensive therapy, we undertook an open, noncomparative study to determine the effect of prazosin on serum lipid. All patients were adults (mean age of 59, with a range of 45 to 72), and all had a sitting blood pressure greater than 160 mm Hg systolic or 90 mm Hg diastolic. After a stabilization period of 2 to 4 weeks, prazosin was started at 0.5 mg t.i.d. This dose was maintained for 1 week and was then titrated upwards to achieve optimal antihypertensive effect. Maximum dose permitted was 12 mg/day. All patients were treated for at least 12 weeks. Concomitant therapy was allowed in patients who had been stabilized on other drugs prior to entry into the study. At the end of 12 weeks of therapy, prazosin (at an average dose of 4.5 mg) had lowered blood pressure by an average of 10/9 mm Hg in the sitting position, 11/7 mm Hg in the supine position, and 19/13 mm Hg in the standing position. Pulse rate did not change. Total cholesterol and triglycerides were essentially unchanged, and LDL and VLDL decreased by 4.5%. However, high density lipoprotein (HDL) cholesterol increased by 12.5%. These changes were statistically significant and yielded an increase of 20.3% in the cholesterol ratio. No side effects were noted in any patient, and none of the patients discontinued therapy during the study. This is an ongoing study, in which 14 patients have so far completed the 12 weeks of therapy. On the basis of these preliminary results, prazosin would seem to be an effective and safe antihypertensive agent with considerable favorable effects on serum lipids.

Aged↗

Survival of host mast cells after establishment of hematopoietic chimerism by graft-versus-host reaction in nonirradiated F1 hybrid mice.

Since the tissue mast cell has been shown to be progeny of the multipotential hematopoietic stem cell (CFU-S), and the CFU-S is a sensitive target of graft-versus-host (GVH) reaction, we examined whether or not the mast cell is also the target of GVH reaction. Giant granules of C57BL/6-bgJ/bgJ mice were used as a marker of donor cells. When 10(8) spleen cells of C57BL/6-bgJ/bgJ mice were injected into nonirradiated (C57BL/6 X CBA)F1 hybrid mice, erythrocytes and neutrophils became of donor type in about one-half of the recipient mice. In the bone marrow and spleen of the chimeric mice, the CFU-S was of donor type as well. In contrast, mast cells of host type remained in many tissues of the chimeras. Moreover, mast cell precursors with capabilities of proliferation and differentiation were preserved in the skin of chimeras. The present results suggest that the effect of systemic GVH reaction on mature mast cells and the mast cell precursor fixed in the skin is significantly less severe than that on the CFU-S itself.

Animals↗

Japanese summer-type hypersensitivity pneumonitis: studies using Cryptococcus antigen.

Sixty-six patients, diagnosed as Japanese summer-type hypersensitivity pneumonitis at Osaka Prefectural Habikino hospital between 1973 and 1980, were studied. The diagnosis was based on the clinical features and summer-seasonal nature of the disease. The presence of an aetiological agent within patients' home environment was suggested by the recurrence of acute symptoms of high fever, cough and dyspnoea 5-8 hr after coming home from hospital, and by spontaneous improvement on leaving home. Immunological studies revealed the presence of anti-Cryptococcus antibody in sixty-four of sixty-five patients' sera, by indirect immunofluorescence against Cryptococcus neoformans. Precipitating antibody against culture supernatant protein-antigen of Cr. neoformans was detected in more than 80% of sera obtained from patients during the active stage of the disease. The positive result on inhalation provocation-challenge, using culture supernatant protein-antigen, suggested that Cr. neoformans or antigenically related Cryptococcus species may cause Japanese summer-type hypersensitivity pneumonitis.

Adolescent↗

Primary culture of chondrocytes embedded in collagen gels.

Chondrocytes isolated from sternal cartilage of 13-day embryonic chicks were dispersively embedded inside the collagen gels in Ham's F-12 medium containing fetal calf serum. Viability, three-dimensional growth and deposition of extracellular matrix in the living cultures were evidenced by increased cell number, morphology and autoradiographic observations, respectively. The cells increased 2- to 3-fold in 1 week and occupied ' chondrocytic lacunae' surrounded by 'territorial matrix'. A more extensive development of the tissue-like structure was produced by high density cultures. Exogenous collagen seemed to be incorporated or rearranged into the newly formed matrix. This new culture method may provide suitable conditions for differentiated chondrocytes to accumulate metachromatic matrix in vitro.

Animals↗

Is captopril effective in primary pulmonary hypertension?

Several vasodilating agents have been used for the treatment of primary pulmonary hypertension (PPH). However, no effective therapy is currently available for this distressful disease. We tried to use an angiotensin-I converting enzyme inhibitor, captopril, for one woman suffering from PPH. Her initial treatment with furosemide, digoxin and spironolactone had shown little effect. Further administration of captopril improved her clinical condition from NYHA IV to II and made it possible to treat her at our out-clinic. No adverse effect has been found. We would like to appreciate captopril as one of the effective drugs in the treatment of PPH.

Captopril↗

Effect of mercuric chloride on the proliferative response of human lymphocytes to cultured HeLa cells or a lectin.

Proliferative responses of human lymphocytes to cultured allogeneic HeLa cells and to PHA were employed as in vitro cellular immune systems to investigate effects of mercuric chloride on the both proliferative responses. When stimulator HeLa cells were pretreated with mercury, proliferative response of lymphocytes to HeLa cells in the mixed cell culture was suppressed dose-dependently. The response of lymphocytes treated with mercury to HeLa cells was suppressed markedly, even at 15-min exposure to 1 X 10(-5) M HgCl2. The response of lymphocytes to PHA as well as that to HeLa cells was suppressed by mercury treatment, even at 15-min exposure. A possible mechanism for the suppressive effect of mercury on the mixed cell reaction was discussed; mercury modification of molecules at the cell surface of the stimulator cells or responder cells and effects of mercury on macrophages.

Cell Division↗

Effect of splenectomy on establishment of hematopoietic chimerism in nonirradiated mice.

When spleen cells (1.5 x 10(8)) from beige C57BL/6 (bgJ/bgJ, Chediak-Higashi syndrome) mice were injected into nonirradiated (C57BL/6 x CBA)F1 hybrid mice, the hematopoietic stem cells of the hybrid host were eradicated by graft-versus-host (GVH) reaction, and peripheral neutrophils of the host changed from normal type to beige type with giant sudanophilic granules in 20 days after the cell injection. Effect of splenectomy on the establishment of such hematopoietic chimerism was investigated. The splenectomy carried out either before or after the cell injection reduced the proportion of mice in which more than 90% of peripheral neutrophils became of beige type. Since the mortality of mice which received splenectomy at various days prior to or after the cell injection paralleled the proportion of establishment of chimerism, the splenectomy does not seem to affect directly the establishment of chimerism but indirectly through the modification of the intensity of GVH reaction.

Animals↗