Search PubMed⌕ Search

Biomedical subjects

Y Tokuda

Publications and source records attributed to Y Tokuda.

At least 145 records · Page 8Linked to original sources

[Effects of steroid therapy in IgA nephropathy].

In order to estimate the effects of corticosteroid therapy in IgA nephropathy cases with daily urinary protein excretion of 1.0 g/day or more. 26 patients (8 men and 18 women, aged 32.6 +/- 14.0 years old) were subjected to this study. The results obtained were as follows: Urinary protein excretion after 1 year from the beginning of steroid therapy (1.56 +/- 1.14 g/day) was significantly (p less than 0.05) lower than that at the beginning of the therapy (4.61 +/- 6.01 g/day). In serum creatinine levels, there was no statistically significant difference with them between at the beginning (1.15 +/- 0.48 mg/dl) of steroid therapy and at the time of 1 year after (1.05 +/- 0.34 mg/dl) the therapy. As for the outcome at the end of this study setting (mean follow-up duration: 3.7 +/- 2.6 years), complete remission was attained in 7 cases, improvement in 5 cases, unchanged condition in 11 cases, increased urinary protein excretion in 2 cases and aggravated renal function in 1 case. In clinical findings at the renal biopsy, duration of the disease (3.4 +/- 1.6 months) in complete remission cases before biopsy was significantly (p less than 0.01) shorter than that in unchanged cases (65.0 +/- 40.0 months). In histological findings, rate of global sclerosing glomeruli (2.6 +/- 4.6%) in complete remission cases was significantly (p less than 0.05) lower than that (24.6 +/- 23.1%) in unchanged cases. These results suggest that steroid therapy in IgA nephropathy with persistent proteinuria of 1.0 g/day or more is beneficial, especially in cases that are in early stage of the disease with lower rate of global sclerosing glomeruli.

Adolescent↗

Bispecific antibody-directed antitumor activity of human CD4+ helper/killer T cells induced by anti-CD3 monoclonal antibody plus interleukin 2.

Freshly isolated human CD4+ T cells can not respond to recombinant interleukin 2 (rIL-2) because of their lack of p75 IL-2 receptor expression. However, we succeeded in inducing a marked proliferation of purified CD4+ T cells by activation with rIL-2 plus anti-CD3 monoclonal antibody (mAb) cross-linked to a plastic plate. The proliferated CD4+ T cells produced a significant amount of IL-2 upon stimulation with phorbol ester plus A23187. Interestingly, CD4+ T cells activated with anti-CD3 mAb plus rIL-2 revealed a strong cytotoxic activity against Fc receptor (FcR)-positive tumor cells in the presence of anti-CD3 mAb. Moreover, the CD4+ T cells could lyse FcR-negative glioma cells by targeting with bispecific mAb containing anti-CD3 mAb and anti-glioma mAb. Thus, we demonstrated that rIL-2 and immobilized anti-CD3 mAb allowed the rapid generation of human CD4+ helper/killer T cells, which may be useful for the development of a new adoptive tumor immunotherapy.

Antibodies, Monoclonal↗

Macrophage-T cell interaction is essential for the induction of p75 interleukin 2 (IL-2) receptor and IL-2 responsiveness in human CD4+ T cells.

Fresh human CD8+ T cells showed a strong proliferative response to a high concentration of interleukin 2 (IL-2) in the absence of macrophages. In contrast, CD4+ T cells revealed no significant IL-2 responsiveness in the absence of macrophages. However, if CD4+ T cells were cocultured with macrophages, they showed higher proliferative response to IL-2 than CD8+ T cells. In accordance with the magnitude of IL-2 responsiveness, freshly isolated CD8+ T cells expressed significant amounts of p75 IL-2 receptor, while fresh CD4+ T cells did not express p75 IL-2 receptor. The expression of p75 IL-2 receptor on CD4+ T cells was induced by coculture with macrophages. The macrophage-induced p75 IL-2 receptor acquisition was blocked by monoclonal antibody (mAb) against class II antigen. Moreover, the addition of anti-CD4 mAb or anti-class II mAb to the culture caused a great inhibition of IL-2 responsiveness of CD4+ T cells. These results strongly suggest that macrophage-T cell interaction through CD4 and/or class II molecules is essential for the expression of p75 IL-2 receptor and IL-2 responsiveness in human CD4+, but not CD8+ T cells.

Antibodies, Monoclonal↗

Induction of c-fos and c-myc mRNA expression by immunoglobulin G from patients with Graves' disease in thyrotrophin-dependent rat thyroid cell line (FRTL5).

The present study was conducted to evaluate effects of autoantibodies in patients with Graves' disease on induction of c-fos and c-myc mRNA expression in rat thyroid cell line (FRTL5). IgG fractions were isolated from 11 patients with Graves' disease, and six healthy subjects, with protein A-Sepharose. FRTL5 cells which had been grown to subconfluency and deprived of TSH for a week were exposed to the IgG for an hour. Expression of c-fos and c-myc mRNAs was examined by the Northern blot method using nick-translated v-fos and c-myc probes. C-fos and c-myc transcripts were induced by IgGs from two patients with Graves' disease, which displayed much higher activities in assays for TSH binding inhibitor immunoglobulins, thyroid stimulating antibodies and thyroid growth-stimulating immunoglobulins, assessed by measuring inhibition of 125I-TSH binding to the TSH-receptor, cAMP production and 3H-thymidine incorporation in FRTL5 cells, respectively, compared with those in the remaining patients. The induction of c-fos and c-myc mRNAs by IgG from a patient with Graves' disease was suppressed by preincubation with IgGs from two patients with primary myxoedema who were known to have a blocking type TSH-receptor antibody. These data suggest that the binding of the antibodies to the TSH-receptor followed by cAMP production is related to the induction of c-fos and c-myc mRNAs and, thus, to the growth of FRTL5 cells. To our knowledge, this is the first report demonstrating that autoantibodies induce proto-oncogene mRNA expression.

Adolescent↗

Lymphoproliferative disorders of the thyroid gland: radiological appearances.

Images of lymphoproliferative disorders of the thyroid by ultrasonography (US), computed tomography (CT), 99Tcm and 67Ga scintigraphy were analysed in eight patients (two men and six women, aged 42-83 years). Seven patients were diagnosed as having primary lymphoma and one plasmacytoma. Ultrasound revealed a solid mass with homogeneous and very low echogenicity clearly distinguishable from residual thyroid tissue in five patients, diffuse hypoechoic goitre in one and multiple irregular hypoechoic nodules in both lobes in the patient with plasmacytoma (Case 8). Computed tomography demonstrated a focal low-density area in six cases of lymphoma and decreased density throughout the gland in the other two patients. 99Tcm scintigraphy showed hemilobar enlargement with decreased and uneven trapping, cold area or complete lobar defect in six patients with lymphoma and no trapping in the case of plasmacytoma. 67Ga scintigraphy demonstrated high accumulation in lymphoma and faint accumulation in the case of plasmacytoma. Radiological manifestations with a focal lesion were considered typical and diagnostic of primary thyroid lymphoma, while in one case with diffuse infiltration through the whole gland, the differential diagnosis from Hashimoto's thyroiditis could not be made. In the final case, cells infiltrated diffusely to form islands with patchy distribution among well preserved follicles, correlating with the multiple hypoechoic areas observed by US.

Adult↗

[Simple allergen skin test device Multi skit (tentative name)].

We have developed a device tentatively named Multi Skit (Mu), a simple allergen test device, in order to conduct the skin test safely, accurately and conveniently. The utility of this device was evaluated by determining how the results obtained by the intradermal test (In) and Mu were correlated with those obtained by IgE RAST (RA) in 65 AD patients. RA values concerning nine antigens were compared to results obtained by the In and Mu in terms of the positive and negative response coincidence rates, overall coincidence rates, and false-positive and false-negative response rates. The correlation between RA data obtained from the literature and the results of the scratch test (Sc) was also evaluated. The results of In and RAST values showed no correlation regardless of the food antigen used. Mu and RAST values showed correlation with respect to all 4 food antigens except soy-bean, resulting in overall coincidence rates of 66.2 to 87.7%, which were higher than those concerning the Sc. With respect to false-positive responses to environmental antigens, the rate obtained by Mu was higher than that by the Sc, but it was lower than that by the In. However, Mu was the most excellent test with respect to the other indices, i.e., positive and negative response coincidence rates, overall coincidence rates (73.9-89.2%) and false-negative responses. The mechanism of Mu makers it possible to minimize variations from one investigator to another, and the major drawback of all other skin tests. Mu is a safe and convenient screening skin test device which provides accurate and specific test results.

Adolescent↗

[The effect of a protein-bound polysaccharide (PSK) on lymphocyte subsets of peripheral venous blood and thoracic duct lymph].

To study the effects of a protein bound polysaccharide (PSK) on the immune system in normal animal, lymphocytes subsets of both peripheral (PBL) and thoracic duct lymphocytes (TDL) were analyzed in 6 week old male SPF Wistar-Imamichi rats before and after free feeding of forage which contained 2% of PSK. PBL and TDL were obtained at the time before, 4 weeks after and 8 weeks after administration of PSK. Age matched rats without administration of PSK were used as a control. Following the peripheral blood cell counts were carried out, lymphocytes subsets such as ratio of total T cells helper/inducer T (Th) cell, suppressor/cytotoxic T (Ts) cell and B cell were assayed using W3/13, W3/25, 0 X 8 and 0 X 4 monoclonal antibodies with laser flow cytometric technique (Orthospectrum III Orthodiagnostics). In terms of the PBL, number of total T cells and Th cells in PSK treated group were significantly lower than that of controls. However no statistical different could be obtained between these two groups in relation to the number of Ts cells and B cells. On the other hand, the number of T cells and Th cells in TDL of PSK treated groups were significantly higher than that of controls while Ts cell and B cell number did not show no apparent differences between these two groups. These findings indicate that oral administration of PSK have a potency to accelerate the transport of T cells from blood stream to lymphatic channel and also regulate their distribution in a normal healthy animals.

Animals↗

[Application of a new compact and cell dense continuous culture system for LAK cells generated from cryo-preserved lymphocytes].

Recently, the adoptive immunotherapy using lymphokine activated killer (LAK) cells has been applied for various cancer patients. It is quite useful to generate LAK cells from cryo-preserved lymphocytes in order to make a rational treatment schedule. We made basic studies on the induction of LAK cells from frozen lymphocytes using our high yield continuous cell culture system. It was demonstrated that our culture bag can be used to proliferate frozen lymphocytes cultured in interleukin-2 (IL-2) to thirty four-fold the initial cell number in 14 days with comparable cytotoxicity to that of fresh lymphocytes cultured in the same system.

Cryopreservation↗

Sonography of subacute thyroiditis: changes in the findings during the course of the disease.

Fifteen patients with subacute thyroiditis were studied with thyroid sonography. There were local hypoechoic areas in all patients during the active phase of the disease. Among 6 patients who underwent follow-up studies during the course of treatment, 3 had recurrence or aggravation of clinical symptoms such as painful swelling of the thyroid region, which was associated with, and sometimes preceded by, spread or reappearance of the sonographic abnormality. All 6 patients showed complete disappearance of the hypoechoic area when they were in remission. The thyroid sonography is useful not only for the initial diagnosis but also for the follow-up of these patients during the course of the disease.

Adult↗

Fundamental study on the mechanism of DNA degradation in tissues fixed in formaldehyde.

The mechanism of DNA degradation and its clinical applications were examined. When purified lambda phage and extracted liver DNA were fixed in phosphate buffered formaldehyde, the DNA did not degrade, but there was incomplete digestion with endonuclease. Rat liver tissues were fixed under various conditions and DNA extracted. Immediate fixation with buffered formaldehyde at low temperature, or the addition of EDTA to buffered formaldehyde blocked the DNA degradation. Analysis of pulsed field gel electrophoresis also showed that DNA was degraded before extraction. These results suggest that tissue nuclease has an important role in DNA degradation in tissue. Furthermore, formaldehyde fixation at low temperature, which may take time and which decreases slightly the staining capacity, is useful for the extraction of intact DNA. For clinical application, the detection of provirus was examined. Genomic DNA was extracted from a necropsy sample of adult T cell leukaemia fixed in formaldehyde; human T cell leukaemia virus type-I (HTLV-I) provirus was successfully detected by Southern blotting.

Animals↗

Giant congenital capillary hemangioma of pericranium--case report.

The authors report a newborn male infant with a giant congenital capillary hemangioma of the pericranium. An elastic mass, measuring 6.5 x 6.9 x 3.9 cm, was located in the parieto-occipital region. Neurological examination revealed no abnormality. Angiographically, the tumor was fed symmetrically by the bilateral superficial temporal, occipital, and middle meningeal arteries. At surgery, the encapsulated tumor appeared to have arisen from the periosteum and was removed completely. Histological diagnosis was capillary hemangioma. Capillary hemangioma is a common benign tumor in infancy and usually present as a strawberry mark or port-wine stain. However, when the tumors seat relatively deeply as in the present case, they produce little or no discoloration in the overlying skin. Angiography is then useful to differentiate capillary hemangioma from other lesions and to choose an appropriate treatment.

Angiography, Digital Subtraction↗

Changes of brainstem auditory evoked responses (BAERs) in a brain stem ischemic model using embolization technique in cats, a preliminary study.

In order to evaluate brain stem dysfunction related to ischemic process, the authors monitored the Brainstem Auditory Evoked Responses (BAERs) with time in a brain stem ischemic model. 19 adult mongrel cats were divided into two groups: embolization (n = 14) and sham operated control (n = 5). Embolization was done by injecting cylindrical silicone embolus to the right vertebral artery. Each successful embolization of the basilar artery was then confirmed by vertebral angiography. BAERs were monitored before embolization and then 5-10 min, 15 min, 30 min, 60 min, 3 hr and 6 hr after embolization. The presence of ischemic lesion caused by embolization was confirmed by injecting 2% Evans blue solution 30 min before sacrificing the animals. Leakage of the dye was observed. In embolized animals, significant (Student t test, p less than 0.05) delay of interpeak latencies of waves 1-3, 3-5, and 1-5 was observed 15 min after embolization. This delay became more significant (p less than 0.01) 30 min after embolization. These results provide evidence for the usefulness of BAERs monitoring which can be used to complement other diagnostic methods for patients with vertebrobasilar insufficiency and/or infarction.

Animals↗

[A case of acute potassium bromate intoxication].

We experienced a case of a 44 year old man who had ingested potassium bromate solution for suicide attempt. Soon after the ingestion, nausea, vomiting, abdominal pain and diarrhea developed in him. Several hours later, he began to complain of auditory disturbance and, in addition, anuric acute renal failure occurred. Direct hemoperfusion and hemodialysis was performed on the patient for the treatment purpose. Five weeks later, he was released from hemodialysis procedure. Gradually, on the other hand, progressing anemia was observed until 90th hospital day, which slowly improved thereafter. Further, pruritus, lower leg pain, headache, tinnitus and loss of sense of taste, etc. were observed in the clinical course. Renal biopsy was performed on the 119th hospital day and the specimen showed the regenerative stage of acute tubular necrosis. In our case, acute renal failure was reversible and, many other clinical manifestations were observed. However slight anemia and irreversible severe auditory disturbance remained unimproved.

Acute Kidney Injury↗

An investigation of vascular anatomy and microvascular architecture of the brainstem in cats.

The vascular anatomy and microvascular architecture of the vertebrobasilar system, especially within the brainstem, was investigated in cats. The main branches of the basilar artery were observed and the inner diameters of these vessels were measured on vertebral angiograms. The three-dimensional microvascular architecture was constructed using molded vascular models. The arterial anastomoses between the arteries inside the brainstem were studied using contact microangiograms. The paramedian branch penetrated into the brainstem in a retrograde fashion from the cranial basilar artery, and in an anterograde fashion from the caudal basilar artery. Arterial anastomoses were noted between the circumferential arteries. The frequency of arterial anastomoses was higher and diameters of the anastomotic vessels were larger in the ventrolateral region of the brainstem than in the ventromedial region. Regarding the perforating arteries, the arterial anastomoses were present outside the brainstem. No arterial anastomoses were found inside the brainstem.

Angiography↗

A pilot study of intralymphatic interleukin-2. I. Cytotoxic and surface marker changes of peripheral blood lymphocytes.

Patients with metastatic solid tumors were treated with six escalating doses of weekly intralymphatically injected recombinant interleukin 2 (i.l. IL-2). Nine patients completed the treatment and were evaluated for immunologic features of their peripheral blood lymphocytes (PBLs). The patients' PBL counts increased 4 days after the first i.l. IL-2 injection. The cell counts remained higher than baseline in week 6 prior to the last i.l. IL-2 injection. However, the PBL number decreased below baseline 1 day after the sixth injection, and recovered to normal levels after 3 days more. Natural killer (NK) activity showed similar changes when calculated as total activity per ml of blood. In vitro 1 h treatment of PBLs with IL-2 greatly enhanced NK cytotoxicity. The enhancement was only slight in the first week of i.l. IL-2 treatment, but was significantly greater on day 35 (7 days after dose 5) and day 39 (4 days after dose 6). In contrast, the increase was similar to the baseline on day 36, the day after the sixth injection. No lymphokine-activated killer activity was detected in the patients' PBLs with or without short-term in vitro IL-2 treatment. Besides the NK cytotoxic function, lymphoid subpopulations were evaluated numerically for total T cells (CD3/OKT3), T-cell subsets (CD4/OKT4 and CD8/OKT8), B cells (OKB7), NK cells (CD56/NKH1/Leu19, CD16/Leu11), and monocytes/NK cells (CD11b/OKM1). The activation markers (HLA-DR, CD25/Tac, and CD38/OKT10/Leu17) were also included. Intralymphatic IL-2 treatment had no effect on the PBL surface marker expression in the first week of treatment. However, by week 6, the percentages of cell populations expressing the NK-associated antigens CD56, CD16, and CD11b were significantly increased. In contrast, the percentage of CD3-positive T cells showed no change or a marginal decrease. Prior to and after i.l. IL-2 treatment, the CD56-positive cells in the PBLs were predominantly CD16 positive and CD3 negative. The i.l. IL-2 treatment did not induce PBL proliferation, or changes in the expression of CD25 (Tac), HLA-DR, CD38, CD4, CD8, CD57, or OKB7 in the patients' PBL. These results indicate that i.l. IL-2 treatment does affect the total number of PBLs, the cells expressing NK activity, and NK-associated surface markers.

Antigens, Differentiation↗