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Biomedical subjects

A Furukawa

Publications and source records attributed to A Furukawa.

At least 55 records · Page 3Linked to original sources

Antigen-specific B cells are required for the secondary response of T cells but not for their priming.

We studied the potential role of B cells in T cell responses using severe-combined immunodeficient (SCID) mice grafted with the thymus from fetal C.B-17 mice (TG mice). These mice developed both CD4+ and CD8+ T cells, but not B cells within 2 months after transplantation. TG mice showed normal delayed-type hypersensitivity responses against the immunizing antigen ovalbumin (OVA). Lymph node (LN) cells of TG mice proliferated well in response to concanavalin A (Con A). Further, Con A stimulation induced the production of interleukin (IL)-2, IL-6 and interferon (IFN)-gamma and the expression of IL-4 mRNA. Thus, TG mice were reconstituted without remarkable immunodeficiency. However, these T cells failed to proliferate to OVA stimulation. Response to OVA was also inhibited in SCID mice grafted with fetal C.B-17 liver cells when B cells were depleted in the proliferation assay. Unresponsiveness against immunizing antigen was restored by the addition of antigen-primed B cells, but not by naive B cells, lipopolysaccharide-activated B cells or B cells primed with sheep red blood cells. Next, we examined whether antigen-primed B cells could induce T cell responses without professional antigen-presenting cells (APC). T and B cells were purified from OVA-immunized mice by cell sorter. These T cells proliferated in response to OVA and produced IFN-gamma in the absence of non-B APC. When anti-CD80 or anti-CD86 was added in the assay, proliferation and IFN-gamma production was inhibited. These results indicate that B cells activated specifically with antigen are required for the secondary response of T cells, but not for their priming.

Animals↗

Molecular cloning and nucleotide sequences of cDNA clones of sheep and goat adrenocortical cytochromes P450scc (CYP11A1).

We isolated cDNA clones of the mRNAs for cytochromes P450scc (CYP11A1) from sheep and goat adrenocortices using the RT-PCR method. We determined the complete nucleotide sequences of the coding and 3'-flanking regions of these cDNA clones. The results confirmed the amino terminal sequence of the sheep cytochrome P450scc reported previously [Miyatake et al., Biochim. Biophys. Acta 1215,176-182 (1994)]. On the basis of comparison of the deduced amino acid sequences of various animals and rainbow trout cytochromes P450scc, and other mitochondrial cytochrome P450 isozymes, we discussed the substrate-associated and adreno-ferredoxin-binding region of cytochrome P450scc.

Adrenal Cortex↗

Development of functional rat-derived T cells in SCID mice engrafted with the fetal thymus of LEC rats which are defective in CD4+ T cells.

We reported that LEC rats are genetically deficient in the development of thymic CD4+8- cells and that this defect is caused by bone marrow (BM)-derived stem cells. To determine which BM-derived cells are responsible for the arrest of T-cell development in LEC rats, fetal thymuses of LEC rats, or LEA rats which bear the same major histocompatibility complex (MHC) as LEC rats but are immunologically normal, were engrafted under the kidney capsule of severe combined immunodeficiency (SCID) mice (LEC-TG and LEA-TG mice, respectively). We than examined the differentiation of T cells and their immunological functions in the SCID mice. A large number of rat-derived CD4+ T cells appeared in the peripheral blood, lymph nodes (LN) and spleens in LEC-TG mice. Furthermore, the peripheral LN cells in LEC-TG mice appeared to be functional. These cells produced IL-2 upon Con A stimulation, whereas LN cells from LEC rats produced no IL-2 in the same conditions. Thymopoiesis was observed at 3 weeks in LEC-TG as well as LEA-TG mice. The distribution of thymocyte subsets with respect to CD4 and CD8 expression in LEC-TG mice closely resembled that of LEA rat thymus and that in LEA-TG mice, suggesting that normal T-cell differentiation occurred in LEC-TG mice. The results indicated that BM-derived progenitor T cells of LEC rats could differentiate to functional CD4+ T cells.

Animals↗

[Evaluation of renal function using Gd-DTPA dynamic MR imaging].

To establish a new method for evaluating renal function using MRI, we performed dynamic Gd-DTPA enhanced MR imaging at 1.5 T in 68 subjects (71 examinations), including 23 normal volunteers, 19 patients with chronic renal failure, 22 with hydronephrosis, and 7 with renal vascular disorders. Thirty GRASS images [35/9/20 degrees /1 (TR/TE/Flip Angle/NEX)] were obtained after a bolus injection of Gd-DTPA (0.2 mmol/Kg) in each case, and were evaluated in the following respects. (1) Whether or not the initial signal increase and/or the following signal drop in cortex was observed. (2) Whether or not the signal drop in medulla and/or calyces was observed. (3) Time between initial signal increase in cortex and signal drop in medulla (Ta). (4) Time between signal drop in medulla and calyces (Tb). (5) Time between signal increase in cortex and signal drop in calyces (Tc). (6) Maximum ratio of signal intensity between cortex and medulla (Max. C/M). In normal subjects, the initial signal increase and the following signal drop in cortex, and the signal drop in medulla and calyces were observed. In patients with abnormal renal function, the characteristic signal changes described above were not seen clearly or disappeared in many cases. In normal subjects, Ta, Tb, Tc, and Max. C/M were 41.9 +/- 6.9 sec, 53.2 +/- 10.6 sec, 95.0 +/- 9.5 sec, and 1.10 +/- 0.05, respectively. In the patients, time parameters were significantly larger than those of normal subjects and C/M ratios were lower. This study suggested that dynamic Gd-DTPA renal MR imaging can serve as a new method for the evaluation of renal function.

Adolescent↗

[A preliminary study of percutaneous ethanol injection therapy for hepatocellular carcinoma: evaluation of the ethanol diffusion area by the ethanol mixed with gadolinium].

To evaluate the ethanol diffusion area after Lipoidalization in 3 patients with advanced HCC treated by Lipoidalization-PEIT combination therapy, 99.9% ethanol mixed with Gadolinium was used for PEIT (Gd-PEIT). T1-weighted MR images wear obtained 1 hr after Gd-PEIT. The area of homogeneous hyperintense change on T1-weighted MR images was taken to be the ethanol diffusion area. In all 3 patients, homogeneous hyperintensity throughout the tumor over the capsule was recognized on T1-weighted MR images after treatment. The results suggests that T1-weighted MR images after Gd-PEIT provide a valuable tool by which to directly evaluate the ethanol diffusion area for advanced HCC treated by Lipoidalization followed by PEIT.

Carcinoma, Hepatocellular↗

[Measurement of gastric emptying by magnetic resonance imaging].

The purpose of the study was to establish a new method of measuring gastric emptying using MR Imaging in human. Gastric emptying was measured in 6 healthy male volunteers aged from 28 to 43 years, using MR imaging and RI. The measurements were performed after the oral administration of liquid meal containing glucose, protein and fat. The MR imaging was performed with 0.5T superconducting magnet machine, and consecutive 12 transaxial T1 weighted spin echo images (TR/TE = 300/17) of the upper abdomen were recorded every 10 minutes for more than 1 hour. Gastric emptying curves and their T1/2 values obtained by MR imaging and RI method were correlated well in 5 of 6 cases. We concluded that a non invasive and radiation free method using MR imaging was proved to be a useful tool for measuring gastric emptying.

Adult↗

[Dynamic Gd-DTPA-enhanced MR imaging in evaluation of the function of transplanted kidneys].

The purpose of the study was to evaluate the potential of dynamic Gd-DTPA-enhanced MR imaging in assessing of the function of transplanted kidneys. Dynamic MR imaging was performed using the GRASS pulse sequence in 21 subjects (56 examinations), and in each examination 30 images were obtained after a bolus injection of Gd-DTPA. Imaging findings including signal increase and/or signal drop in cortex, signal drop in medulla, and signal drop in calyces were utilized for the evaluation of renal function. Renal function was also evaluated using the following parameters: Ta, time between the initial observation of signal increase in cortex and signal drop in medulla. Tb, time between the initial observation of signal drop in medulla and in calyces; Tc, Ta + Tb, and Max. C/M, maximum ratio of signal intensity between cortex and medulla among 30 images. In the group of patients with normal graft function (Ccr > or = 60ml/min), all imaging findings were observed. In the group of patients with mild graft dysfunction (30ml/min < or = Ccr < 60ml/min), all imaging findings but signal drop in cortex were observed. The time parameters of Ta, Tb, and Tc were significantly larger, and Max. C/M was significantly smaller than those observed in the group with normal graft function. In the group of patients with severe graft dysfunction (Ccr < 30ml/min), almost none of the findings were observed. The investigation in patients in the postoperative state revealed a close correlation of the imaging findings and the values of parameters with changes in graft function over time. The results indicated the usefulness of the method in semiquantitative evaluation of graft function, including that of patients in postoperative state. This study suggests that dynamic Gd-DTPA-enhanced MR imaging could be a valuable method for the management of transplanted kidneys.

Adolescent↗

Establishment of a xenogeneic chimera without GVHD in NK cell-depleted SCID mice by grafting rat fetal liver cells.

Rat lymphopoiesis did not develop when naive SCID mice were transplanted with rat fetal liver cells. However, when SCID mice were depleted of NK cells by administration of anti-murine IL-2R beta mAb before transplantation, remarkable reconstitution of both rat T and B cells was observed in these mice without any evidence of graft-versus-host disease macroscopically or histologically. T cells in these reconstituted mice proliferated well in response to Con A and third-party rat and mouse antigens, whereas no response was seen to the stimulation with either donor rat- or host mouse-type cells. When these xenogeneic chimera mice had been immunized with SRBC, these mice exhibited DTH reaction and antibody production against the homologous antigen. These results indicate that rat fetal liver cells can differentiate to functional T and B cells in the xenogeneic microenvironment of SCID mice, if host NK cells are depleted beforehand. These rat-type T cells develop within SCID thymuses and acquire tolerance to either donor F344 rat or host SCID mouse antigens.

Animals↗

Streptococcus oralis previously identified as uncommon 'Streptococcus sanguis' in Behçet's disease.

The relation between the biochemical and serological properties of 'Streptococcus sanguis' was studied to characterize the strains isolated from dental plaque of patients with Behçet's disease and controls. Seven reference and 100 clinical strains preserved by the Behçet's Disease Research Committee of Japan were identified using established criteria and differentiated with antisera against Strep. oralis ATCC 10557, Strep. sanguis ATCC 10556 and 'Strep. sanguis' ST7, compatible with the criteria. Uncommon serovars (serotypes) KTH-1 (= ATCC 49298), KTH-2 (= ATCC 49296), KTH-3 (= ATCC KTH-4 (= ATCC 49297) and B220 (serovar KTH-1) with both IgA1 protease and neuraminidase (sialidase) were identified as Strep. oralis, whereas common serovars ST3 with IgA1 protease alone and ST7 without both enzymes were identified as Strep. sanguis and Strep. gordonii, respectively. Isolates previously ranked as uncommon serovars were identified as Strep. oralis, whereas the rest ranked as common serovars were identified as the same species as those of the grouping strains. A soft-agar technique was available for species identification except for Strep. oralis serovar KTH-1 reacting with the antiserum against Strep. gordonii ST7. The frequency of isolation of Strep. oralis was higher in Behçet's disease (52%) than in controls (38%), but no difference was observed between the properties of the two groups of isolates. Strep. oralis virulence factors may be involved in breach the mucosal barrier in patients with specific reactivity to these antigens and inducing Behçet's disease.

Behcet Syndrome↗

An interleukin-1 binding region oligopeptide from the human type I IL-1 receptor reduces acute inflammation, delayed hypersensitivity reaction, and lethal endotoxemia in animals.

The effect of an interleukin-1 binding region oligopeptide from the interleukin-1 receptor on various inflammatory responses was investigated in animal models. A synthetic peptide (KICIRIQIS) corresponding to 86-93 of the extracellular domain of the human type I interleukin-1 receptor was used. Carrageenan-induced rat paw edema, a model of acute inflammation, was dose dependently suppressed by intraperitoneal administration of the peptide. The delayed hypersensitivity reaction to sheep red cells was diminished by pretreatment of mice with the peptide at a relatively high dose. In a murine lethal endotoxemia model, animals treated with the interleukin-1 receptor peptide (10 mg/kg x 4) showed significantly better survival than vehicle-treated animals when the peptide was administered from 20 minutes after lipopolysaccharide injection. Improved survival was accompanied by suppression of lipopolysaccharide-induced production of colony-stimulating factor, although the peptide did not improve hypoglycemia. These findings suggest that the interleukin-1 receptor peptide may be a potential treatment for various inflammatory processes.

Acute Disease↗

Expression of CD44 splice variants in bladder cancer.

BACKGROUND: Recently, it was noted that CD44 participates in a wide variety of cell-cell or cell-matrix interactions including tumor metastasis and the altered expression of CD44 splice variants is helpful in the diagnosis of colon and breast cancer. The purpose of the study was to investigate altered expression of CD44 in bladder cancer. METHODS: Thirty-three surgical specimens of 22 patients and seven bladder cancer cell-lines were analyzed by various methods including RT-PCR-Southern blotting. Northern blotting, and flow-cytometric analysis. RESULTS: In RT-PCR analysis, the hematopoietic variant and numerous additional variants were detected in all cell-lines and almost all surgical specimens. In three out of seven cell-lines of bladder cancer (42.9%), especially numerous larger bands (ladder pattern) were detected using RT-PCR. These three cell-lines expressed a smaller quantity of CD44 mRNAs and CD44 molecules than the other four cell-lines. In eighteen out of 22 (81.8%) bladder cancer specimens, we detected larger variants that exceed 1500 base pairs, compared with the detection in four out of eleven (36.4%) visually normal mucosa specimens (P < 0.05). However, there was no correlation between the expression of the larger variants and clinicopathological features. CONCLUSION: The quantitative and qualitative change of CD44 variants were demonstrated in bladder cancer.

Aged↗

Split tolerance between spleen and lymph node cells in severe combined immunodeficiency mice grafted with AKR fetal liver cells.

Severe combined immunodeficient (SCID) mice defective in stem cells for T and B cells appear to be an ideal host for construction of chimeric mice. When bone marrow cells are used as a source of stem cells, however, host SCID mice do not always show sufficient reconstitution. In this study, fetal liver cells from AKR embryos were transplanted into SCID mice without prior irradiation. This treatment induced full reconstitution of lymphopoiesis as evaluated by flow cytometry analysis and serum Ig production 2 months after transplantation. Thus, fetal liver cells seem to be a better source for reconstitution of SCID mice than bone marrow cells. Lymph node (LN) cells of these mice (FLT mice) had no proliferative or cytotoxic activities against either host-type (C.B-17) or donor-type (AKR) spleen cells. However, spleen cells from FLT mice exhibited marked proliferative and cytotoxic activities against C.B-17 cells, with no activities against AKR cells. Split tolerance against C.B-17 cells in spleen and LN cells was not a transient phenomenon, since similar results were obtained from a cytotoxic T lymphocyte assay 4 months later. In spite of the strong host reactivity in vitro, aberration of clonal deletion or development of a graft-versus-host disease was not seen in FLT mice. As IL-2 induced the host reactivity of LN cells in a mixed lymphocyte reaction, potentially host-reactive T cells were present in LN but were rendered anergic. Tolerance in FLT mice seems to be regulated by a peripheral mechanism. We supposed that the split tolerance in FLT mice was induced by the different antigenicity between the spleen and LN.

Animals↗

B cells are required as APC for antigen-specific T cell proliferation but not for the differentiation or priming of those T cells.

We studied the influences of B cells on functional differentiation of T cells using SCID mice grafted with fetal thymus of C.B-17 mice (TG mice). T cells were shown to be reconstituted in TG mice without B cell development. These mice showed normal DTH response to SRBC and OVA. LN cells of these mice produced cytokines including IL-2, IL-4, IL-6 and IFN-gamma according to Con A stimulation. Thus, majority of T cell functions seem to differentiate in the absence of B cells. However, T cells of TG mice failed to proliferate in response to immunizing antigens in vitro, although they responded well to stimulation with Con A. This unresponsiveness of T cells in TG mice to these antigens was restored when antigen-primed B cells were added to the proliferation assay. Such an inability of T cells in antigen-specific proliferation was not seen in SCID mice grafted with C.B-17 fetal liver cells, in which B cells as well as T cells were efficiently reconstituted (FLT mice). T cell proliferation to immunizing antigen was also abrogated in FLT mice when B cells were depleted from lymphoid population. These results indicate that T cells can functionally differentiate and be primed in the absence of B cells, but they require B cells to proliferate in response to foreign antigens.

Animals↗

[A case of bronchial leiomyoma with obstructive pneumonia].

A 44-year-old man, who had suffered repeated episodes of pneumonia since 1984, was admitted with complaints of cough, low grade fever and sputum. Chest X-ray showed a mass shadow in the left lower lobe. Bronchofiberscopy revealed a tumor with a smooth surface which obstructed the B9 bronchus. Left lower lobectomy was performed despite the lack of evidence of malignancy because of the recurrent pneumonia. The resected specimen contained a smooth-surfaced tumor, 18 mm in size, protruding into a bronchial lumen. The pathological diagnosis was leiomyoma of the lower bronchus and the specimen showed organized pneumonia with necrosis in the left S8-S10 region. Primary benign tumors of the lung are rare and leiomyoma of the lung is particularly rare. Only 65 cases have been reported in the Japanese literature. We report here a case of leiomyoma of the lower bronchus.

Adult↗

Development of T cells in SCID mice grafted with fetal thymus from AKR mice or F344 rats.

To examine the development of T cells within an allogeneic or xenogeneic environment, we engrafted the fetal thymus from AKR mice or F344 rats under the kidney capsule of SCID mice (mTG and rTG mice). T lymphopoiesis developed in SCID mice 2 months after transplantation, although the ratio of CD4/CD8 in both experimental groups was different from that of normal control. T cells in mTG mice did not show in vitro proliferation or cytotoxicity against either host-type C.B-17 (H-2d) or donor-type AKR (H-2k) cells, while they exerted potent activities against third-party B10 (H-2b) cells. In contrast, T cells in rTG mice exhibited proliferation against both host-type C.B-17 and donor-type F344 rat cells. Consistently, graft-vs.-host disease symptoms developed in these mice and histological examination showed impressive infiltration of lymphocytes into the skin or into the mucosal layers of the stomach. Activated state of T cells in rTG mice was also evidence by the positive expression of interleukin-2 receptor. Taken together, fetal thymus appears to contain progenitor cells which are sufficient for in vivo reconstitution of T lymphopoiesis, but species-specific environment is important for the induction of tolerance. In mTG mice, V beta 6+ T cells reactive to donor Mlsa determinants and V beta 3+ T cells reactive to host Mlsc determinants were deleted, suggesting that tolerance was regulated mainly by clonal deletion. By contrast, V beta 11+ T cells reactive to Mlsf determinants were not deleted possibly due to the lack of their ligands.

Animals↗

Characterization of the ferredoxin gene transcripts in bovine liver and brain.

1. To study the expression of a ferredoxin gene in extra-adrenocortical tissues, the amounts and structures of the ferredoxin gene transcripts in bovine liver and brain were studied and compared to those of that in adrenocortex. 2. The sizes and amounts of the ferredoxin mRNAs were analyzed by means of Northern blotting, RNA slot blotting and RT-PCR. 3. The nucleotide sequences were determined for 39 ferredoxin cDNA clones from bovine liver. 4. The results indicated that the sizes of the ferredoxin mRNAs in liver and brain were the same as that in adrenocortex, however, their amounts were approx 1/30th and less than the latter, respectively. 5. Although the multiple forms of ferredoxin cDNA, differing in the poly(A) addition sites, were also found in liver, a minor form of ferredoxin cDNA, produced through alternative promoter usage and splicing, could not be detected in liver. 6. The nucleotide sequences of all hepato-ferredoxin cDNA clones obtained were identical to that of a major type of adreno-ferredoxin. 7. These results showed that the expression level of the ferredoxin gene in different tissues was controlled by the amount of mRNA.

Adrenal Cortex↗

Hemorrhagic infarction of the diseased ovary: a common MR finding in two cases.

Two patients with surgically confirmed hemorrhagic infarction of ovarian tumor due to torsion were studied with MR imaging. Histology of the two lesions were serous cystadenoma and fibroma. In both cases, a high intensity rim was observed at the periphery of the mass on T1-weighted image. This finding is thought to be a MRI sign of hemorrhagic infarction of the diseased ovary and to provide a useful clue for urgent surgery.

Aged↗