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Biomedical subjects

M Ueda

Publications and source records attributed to M Ueda.

At least 739 records · Page 41Linked to original sources

Establishment of a CD4+ T cell clone recognizing autologous hematopoietic progenitor cells from a patient with immune-mediated aplastic anemia.

In some patients with aplastic anemia (AA), hematopoietic function is dependent on continuous administration of cyclosporine A (CyA). These AA patients may have T lymphocytes whose myelosuppressive effect is mitigated by CyA. We established a total of 29 T cell clones from the bone marrow of a CyA-dependent AA patient in relapse. Some of the CD4+ T cell clones demonstrated a specific proliferative response to irradiated autologous bone marrow cells enriched for CD34+ cells (CD34(+)-rich cells) obtained from the patient in remission. One of the T cell clones showing the best proliferative response to CD34(+)-rich cells carried the T cell receptor V beta 17 and produced interferon-gamma (IFN-gamma) only when cultured with autologous CD34(+)-rich cells. This T cell clone inhibited colony formation by colony-forming unit-granulocyte/macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E) by approximately 60% when it was cultured with autologous CD34(+)-rich cells in methylcellulose medium, although the clone did not exhibit direct cytotoxicity to the CD34(+)-rich cells. The inhibition of in vitro hematopoietic progenitor cell growth by the T cell clone was partially abrogated by the addition of CyA to the culture. These findings suggest that in some patients with CyA-dependent AA, CD4+ T cells autoreactive to hematopoietic progenitor cells exist and may play an important role in the pathogenesis of bone marrow failure.

Adult↗

Heat-shock protein 40, a novel predictor of thermotolerance in murine cells.

We have investigated the relationship between the synthesis of hsp-40, recently identified as a mammalian homologue of DnaJ protein, as well as hsp-70 and the development of thermotolerance in cells of the mouse squamous cell carcinoma line SCCVII. Thermotolerance as determined by clonogenic survival was induced not only by prior heating at 44 degrees C for 30 min but also by prior treatment with 100 microM sodium arsenite for 1 h and 5 micrograms/ml prostaglandin J2 for 4 h. These treatments concomitantly induced both hsp-70 (p72, inducible form) and hsp-40. The extent of thermotolerance correlated well with the relative amount of hsp-70 and hsp-40. These results suggest that hsp-40 is a good predictor of thermotolerance in addition to hsp-70.

Animals↗

[Study on conservative treatment of retinoblastoma--effect of intravitreal injection of melphalan on the rabbit retina].

Effects of an intravitreal injection of melphalan on the electroretinogram and on the retinal structure were studied in albino rabbits to establish the non-toxic dose for its intravitreal use. The a-wave, the b-wave, the c-wave, the oscillatory potential and the retinal structure remained unchanged after 10-micrograms injection, but moderately changed after 20-micrograms injection and greatly deteriorated after 90-micrograms injection. A 10-micrograms injection is equal to an intravitreal concentration of about 5.9 micrograms/ml, if evenly diffused in the rabbit vitreous. Considering that colony formation of in vitro retinoblastoma cells is completely suppressed by melphalan at 4 micrograms/ml concentration, an intravitreal application of melphalan could be used as a non-surgical treatment for retinoblastoma.

Animals↗

[Xeroderma pigmentosum].

Xeroderma pigmentosum (XP), an autosomal recessive disorder, is characterized by extreme sensitivity to sun exposure, a high incidence of skin cancer and frequent neurological abnormalities. Cells from XP patients of seven complementation groups (A-G) have defects in the nucleotide excision repair of UV damage, whereas the defect of another type, the XP variant, is not yet known. Recent discoveries of causative genes of XP have uncovered the molecular mechanisms of nucleotide excision repair. The analysis of gene mutation in XPA gene made a diagnosis of patients and carriers quicker and easier. Further, a relationship between the type of XPA gene mutation and clinical severity has also been uncovered. By analysing skin cancers developed on XP patients, the representative of UV-induced skin cancers, the molecular bases of UV skin carcinogenesis have also been rapidly discovered.

Animals↗

[Suppressed increase of C3 receptors on polymorphonuclear leukocytes by stimulation with C5a in diabetes mellitus].

This study was undertaken to clarify the susceptibility to infection of patients with diabetes mellitus. The complement system is activated through the classical and/or the alternative pathways to produce many kinds of anaphylatoxins in the inflammatory process. One of the anaphylatoxins, C5a, possesses both the strong biological activity of a chemotactic factor and the increasing effect of CR1 and CR3 expression on polymorphonuclear leukocytes (PMNs). It is well known that the complement receptors, CR1 and CR3, on PMNs play important roles in the phagocytosis. We studied the changes of the expression of these receptors on PMNs in non-insulin dependent diabetes mellitus after the stimulation with recombinant human C5a. PMNs from 11 patients with non-insulin dependent diabetes mellitus and 11 normal controls were tested. There was no significant difference of CR1 and CR3 expression on PMNs after the addition of 10 ng/ml C5a between patients with diabetes mellitus and normal controls. However, by the stimulation with 50 ng/ml C5a, the increase of the CR3 expression on PMNs of patients with diabetes mellitus was significantly smaller than normal controls (p < 0.02). The increase of the expression of CR1 on PMNs was not significantly different the two groups. It is suggested that the small increase of the CR3 expression on PMNs by the stimulation with C5a is one of the factors of the susceptibility to infection in patients with diabetes mellitus.

Adult↗

Assessment of the effects of aging and medication on salivary gland function in patients with xerostomia using 99mTC-scintigraphy.

To examine the effect of aging and medication on xerostomia, the salivary gland function was evaluated in 20 patients with xerostomia using 99mTc-scintigraphy and the measurement of unstimulated whole saliva (USWS). All of the patients showed USWS volume of less than 2ml/10min. The patients were divided into 2 subgroups based on age (under 65 and 65 and older) and medication status (patients who were on medication which reduced salivary secretion and patients who were not on such medication). The scintigraphic results, such as the maximum radioisotope (RI) count, RI secretion velocity and the volume of USWS, were compared between the subgroups. The maximum RI count and the RI secretory velocity in the submandibular gland and the volume of USWS revealed significantly different functional disturbances between relatively younger patients (under 65) and older patients (65 and older). There was no difference when the scintigraphic results and the volume of USWS measurements in medicated patients were compared with the results of similar tests performed on non-medicated patients. When the medicated and non-medicated groups were separated by age, an increase in age still diminished the volume of USWS in medicated patients. This result might be related to an organic change in the submandibular gland in older patients which was suggested by the scintigraphic results.

Adolescent↗

Leiomyosarcoma of the maxillary gingiva: a case report.

An unusual case of leiomyosarcoma (LMS) of the maxillary gingiva is discussed here; this case presents a unique pattern of tumor growth and a long period between initial discovery and correct pathological diagnosis. The tumor was incompletely resected twice by a private dentist over a period of 3 years, with a clinical diagnosis of epulis, no pathological examination was conducted during this period. When it was finally removed, the tumor was very large (50 x 35 x 12 mm in size and 18 g in weight), consisting of an easily hemorrhagic mass originating in the gingival mucosa with the growth pattern of a polyp. Following an extensive surgical excision and a unilateral radical neck dissection, the patient has been free of LMS for 8 years. In light of this case, we strongly emphasize the importance of conducting a pathological examination, even though clinical examination seems to indicate a diagnosis of epulis or granulation. In this way, the presence of LMS can be ascertained in a timely manner with better prognosis for treatment and recovery.

Adolescent↗

The clinical and histopathological effects of combined chemotherapy using cisplatin and peplomycin to treat cancer of the tongue.

Combined chemotherapy (PP therapy) using cisplatin (CDDP) and peplomycin (PEP) was performed as induction chemotherapy for 31 patients with cancer of the tongue, and the clinical and histopathological effects were investigated. As the primary clinical effect, complete response (CR) was observed in three cases, partial response (PR) in 20 cases, minor response (MR) in six cases and no change (NC) in two cases, with a clinical response rate of 74.2%. The histopathological effects of the chemotherapy in the following cases showed these histological Grades: 0 or I in four cases, IIa in 12 cases, IIb in eight cases, III in six cases and IV in one case. Fifteen of the 31 patients who received PP therapy showed a histological Grade of IIb or better, representing 48.4% of the histopathological response rate. With regard to the mode of invasion of the tumor, the histopathological response rate was 90.0% in patients with invasive Grades 1 and 2, 41.7% in those with invasive Grade 3 and 16.7% in those with invasive Grade 4C. There were no patients with invasive Grade 4D in whom the therapy was histopathologically effective. In other words, the histopathological effect significantly decreased as the invasive Grade increased. With regard to the relationship between clinical effects and histopathological effects, there was one CR patient who showed a histological Grade of IIa. Thus, it is noteworthy that clinical effects were not necessarily consistent with post-chemotherapeutic histopathological effects.

Adult↗

[Factor VIII].

Explore the source record for details and available documents.

Factor VIII↗

[Midterm result of free arterial graft for myocardial revascularization].

Free arterial grafts has been used as grafts for coronary artery bypass grafting (CABG) since April 1993 in our unit and midterm patency was confirmed by coronary angiogram in 32 patients. Of 32 free arterial grafts. 23 right internal thoracic artery grafts (RITAG), 7 gastroepiploic artery grafts (GEAG) and 2 left internal thoracic artery grafts (LITAG) were placed to 38 coronary arteries including 6 grafts for sequential bypass. 20 grafts were placed in the left circumflex artery. 11 to the diagonal branch, 5 to the left anterior descending artery and 3 to the right Free arterial grafts has been used as grafts for coronary artery bypass grafting (CABG) since April 1993 in our unit and midterm patency was confirmed by coronary angiogram in 32 patients. Of 32 free arterial grafts. 23 right internal thoracic artery grafts (RITAG), 7 gastroepiploic artery grafts (GEAG) and 2 left internal thoracic artery grafts (LITAG) were placed to 38 coronary arteries including 6 grafts for sequential bypass. 20 grafts were placed in the left circumflex artery. 11 to the diagonal branch, 5 to the left anterior descending artery and 3 to the right coronary artery. Coronary angiography later than 6 months after operation revealed the patency rate of 100% for LITAG and RITAG and 81.8% for GEAG. In total 36 free arterial graft remained patent and patency rate was 94.7% and the result was comparative to the midterm patency of in situ arterial graft in our series. Free arterial grafts can be expected to offer excellent long term patency and expand the indication of arterial grafts to CABG.

Coronary Angiography↗

Identification of a specific HLA class II haplotype strongly associated with susceptibility to cyclosporine-dependent aplastic anemia.

Hematopoietic function of some aplastic anemia (AA) patients is dependent on the administration of cyclosporine (CyA). To investigate whether certain HLA class II genes are associated with susceptibility to such CyA-dependent AA, we determined the HLA class II alleles of 59 AA patients treated with CyA. Among 26 patients successfully treated with CyA, 13 required a small dose of CyA to maintain stable hematopoiesis. Of these 13 AA patients, 10 shared an HLA class II haplotype of DRB1*1501-DQA1*0102-DQB1*0602. None of the 13 responders who obtained a sustained remission off CyA therapy possessed this haplotype. In the 10 patients who shared the HLA class II haplotype, single-strand conformation polymorphism analysis of each gene fragment of this haplotype failed to detect a polymorphism in the nucleotide sequence. When the AA patients were assessed for their likelihood to respond to CyA therapy, the response rate in patients with this haplotype (71%) was significantly higher than that of patients with another haplotype associated with HLA-DR2, DRB1*1502-DQA1*0103-DQB1*0601 (36%) and that of patients without HLA-DR2 (35%). These findings indicate that the CyA-dependent response of AA is closely related to an HLA class II haplotype of DRB1*1501-DQA1*0102-DQB1*0602 and suggest that, in AA patients with this haplotype, immune mechanisms play an important role in the pathogenesis of bone marrow failure.

Adolescent↗

A novel site of erythropoietin production. Oxygen-dependent production in cultured rat astrocytes.

It has been shown that neurons express erythropoietin (Epo) receptor, but the production of Epo protein in neural tissues has not been demonstrated. Cerebral cells of rat fetuses were cultured, and Epo in the spent medium was measured with an enzyme-linked immunoassay. Production of the immunoreactive Epo was dependent on O2 tension for cell culture; hypoxia enhanced the production. The immunoreactive Epo purified from the spent medium stimulated the growth of Epo-dependent myeloid cells and formation of fetal liver erythroid colonies. These biological activities were completely inhibited by the anti-Epo antiserum and the extracellular domain of the Epo receptor capable of binding with Epo. When brain Epo was compared with serum Epo, brain Epo was smaller in size and more active in vitro at low ligand concentrations. These differences appear to be caused by the different extent of sialylation. Analyses with the reverse transcription-polymerase chain reaction method indicated that the regulation of Epo production by oxygen operates at the level of its mRNA. Immunochemical staining of the immortalized clonal cells revealed that astrocytes produced brain Epo. These results provide a novel site of Epo production and suggest that Epo acts on neurons in a paracrine fashion.

Animals↗