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Biomedical subjects

N Minato

Publications and source records attributed to N Minato.

At least 91 records · Page 5Linked to original sources

[A case of primary Sjögren's syndrome presenting as osteomalacia secondary to renal tubular acidosis].

We report a 43-year-old female with primary Sjögren's syndrome (SjS) who presented as osteomalacia due to distal renal tubular acidosis (RTA). Osteomalacia was thought to be a rare complication of RTA in SjS, although it had been often described in association with RTA in general. In 1979, she presented with dry mouth, parotid gland swelling and leg purpura. A diagnosis of primary SjS and hyperglobulinemic purpura was made on the basis of positive staining with Rose Bengal stain, sialography of the parotid gland and histological examination of the salivary gland of the lip. She was admitted to Jichi Medical School Hospital in March 1988 with chest pain. X-ray films revealed pseudofractures of bilateral ribs. Bone scanning showed abnormal multiple accumulation of RI on the same parts. Laboratory studies on admission revealed: GOT 50 IU/ml, GPT 9 IU/ml, ALP 190 IU/ml, LDH 301 IU/ml, BUN 11.0 mg/dl, creatinine 1.0 mg/dl, uric acid 2.7 mg/dl, total protein 7.4 g/dl (gamma globulin 22.3%), sodium 141 mEq/l, potassium 3.7 mEq/l, chloride 106 mEq/l, calcium 8.9 mg/dl, and phosphorus 2.4 mg/dl. Arterial blood gas studies on room air showed: PO2 96.7mmHg, PCO2 35.5mmHg, HCO3-19.1 mEq/l, PH 7.347 and base excess -5.4 mEq/l. The urinalysis showed: specific gravity 1.008, PH 7.0, and no protein and glucose. Immunologically, antinuclear antibody was positive at 1:640 with a speckled pattern. Anti-DNA antibody was negative. Antibodies to SS.A and SS.B were 1:64 and 1:32 respectively. Distal RTA was confirmed by the sodium bicarbonate and NH4Cl loading test.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Renal Tubular↗

Identification and gene cloning of a new phosphatidylinositol-linked antigen expressed on mature lymphocytes. Down-regulation by lymphocyte activation.

Lymphocytes are shown to express a limited number of a unique category of membrane Ag, such as Thy-1, Ly-6, Ly-31, and Qa-2, that are covalently linked to the membrane phosphatidylinositol (PI). We have identified a new glycosyl-phosphatidylinositol (GPI)-anchored lymphocyte Ag, B7, by using a mAb and have determined the primary structure by cDNA cloning. B7 Ag was expressed on the majority, if not all, of the mature lymphocytes of both T and B lineages, including strongly CD3+ thymocytes, most splenic T cells, and approximately 60% of splenic IgM+ B cells, whereas the expression of B7 Ag on bone marrow cells was negligible. The expression of B7 Ag was nearly completely abolished with as little as 2 mU of PI-specific phospholipase C per ml, which did not completely eliminate Ly-6C and Thy-1 expression. Unlike the expression of other GPI-linked lymphocyte Ag, the expression of B7 was rapidly down-regulated upon the activation of T cells by mitogens or IL-2 both in vitro and in vivo. Immunoprecipitation analysis revealed that B7 Ag was an approximately 12-kDa protein. With a CDM8 expression vector, a cDNA encoding B7 Ag was cloned, and it was confirmed that the B7 Ag on cDNA-transfected cells was indeed PI-specific phospholipase C sensitive. The B7 cDNA contained an open reading frame of 222 bp including a typical N-terminal leader sequence and a characteristic sequence at the C terminus encoding hydrophobic amino acids. A computer search revealed no significant homology to any known molecule at both DNA and amino acid sequence levels. Northern blot analysis indicated that the B7 transcript was expressed on lymphohematopoietic tissues, including thymus, spleen, and bone marrow, but not on other organs, such as liver, kidney, and brain. The results indicated that B7 Ag is a new member of the GPI-anchored proteins which is selectively expressed on mature resting but not activated lymphocytes.

Amino Acid Sequence↗

Expression of murine IL-2 receptor beta-chain on thymic and splenic lymphocyte subpopulations as revealed by the IL-2-induced proliferative response in human IL-2 receptor alpha-chain transgenic mice.

Lymphocytes from the human (h) IL-2R alpha chain transgenic mice (TGM) constitutively express high affinity binding sites for hIL-2, consisting of transgenic h-IL-2R alpha and endogenous murine IL-2R beta, and therefore easily proliferate in vitro in response to hIL-2. Our study was undertaken to clarify the hIL-2-responsive lymphocyte subsets in the TGM, which should most likely reflect the normal distribution of m IL-2R beta expression. In both thymus and spleen, the majority of expanded cells by hIL-2 was CD3+CD4-CD8+ TCR alpha beta+ cells. The proliferation of CD4+ cells was not observed at all from either organ despite the expression of transgenic hIL-2R alpha. Potent cellular proliferation was also observed from the thymocytes that had been depleted of CD8+ cells, the expanded cells consisting of CD3- (15-40%) and CD3+ populations (60-85%). Among CD3+ cells, approximately the half portion expressed TCR alpha beta, whereas the other half was suggested to express TCR gamma delta. A variable portion (5-20%) of the CD3+ cells expressed CD8 (Lyt-2) in the absence of Lyt-3, and the CD3+CD8+ cells were confined preferentially to the TCR alpha beta- (TCR gamma delta+) population. In the culture of splenocytes depleted of CD8+ cells, however, the proliferated cells were mostly CD3-CD4-CD8-TCR-Mac1-, whereas a minor portion (10-30%) was CD3+CD4-CD8-TCR alpha beta- (TCR gamma delta+. Analysis of TCR genes at both DNA and mRNA levels confirmed the phenotypical observations. These results strongly suggested that IL-2R beta was constitutively and selectively expressed on the primary murine thymocytes and splenic T and NK cells, except for CD4+ cells in both organs.

Animals↗

Analysis of natural killer activity and natural killer cell subsets in patients with bladder cancer.

In order to analyze the state of the natural resistance system of bladder cancer patients in vivo, we measured natural killer (NK) activity and NK cell subsets of peripheral blood lymphocytes (PBL) from 46 patients with bladder cancer and 25 age- and sex-matched healthy volunteers. The mean NK activity in patients with low-stage bladder cancer was similar to that in the controls, while NK activity in patients with high-stage bladder cancer was significantly depressed. The mean proportions of Leu7+ cells in patients with both low-stage and high-stage bladder cancer were significantly higher than that in the controls. The mean proportion of Leu11 a+ cells in patients with low-stage bladder cancer was similar to that in the controls, while in patients with high-stage bladder cancer it was significantly higher. This study demonstrates the abnormal immunological state of bladder cancer patients: namely, abnormalities exist not only in NK activity but also in the proportions of circulating NK cell subsets.

Antibodies, Monoclonal↗

Intraoperative ultrasonic imaging of the ascending aorta in ischemic heart disease.

In an attempt to locate any atherosclerotic lesion in the ascending aorta and to prevent embolization, intraoperative B-mode ultrasonography was performed in 100 patients with ischemic heart disease (31 women and 69 men). Ultrasonography was carried out with a 10-MHz probe placed directly on the ascending aorta. Ultrasonic imaging demonstrated an atherosclerotic lesion in the lower half of the aorta in 76 patients (76%), a lesion in the upper half of the aorta in 89 patients (89%), and a lesion at the orifice of the innominate artery in 99 patients (99%). Prospective palpation identified an atherosclerotic lesion in 12 (25%) of 48 patients. Thoracic computed tomography in 79 patients showed calcification in the lower half of the aorta in 6 patients (7.6%) and in the upper half of the aorta in 11 (13.9%). Palpation and thoracic computed tomography underestimated the frequency of atherosclerotic lesions. Intraoperative ultrasonography accurately identified atherosclerotic disease. This technique allows the surgeon to modify cannulation, aortic clamping, and operative technique to reduce the risk of perioperative stroke due to embolization of atherosclerotic debris from the ascending aorta.

Aorta↗

Isolation and expression of the full-length cDNA encoding CD59 antigen of human lymphocytes.

To identify the primary structure of CD59 antigen and to elucidate its function, a full-length cDNA clone of CD59 was isolated. The cDNA sequence contained an open reading frame that encodes an 128-amino-acid peptide. The amino-terminal 25 amino acids represented a typical signal peptide sequence and the carboxy-terminal hydrophobic amino acids were characteristic for phosphatidylinositol-anchored proteins. The predicted mature protein sequence showed 35% homology with murine Ly-6C.1 and 31% with Ly-6A.2. The number and the distribution of cysteine residues were conserved, implying that the CD59 represented a human homologue of murine Ly-6. RNA blot hybridization analysis revealed the expression of CD59 mRNA in placental, lung, and pancreatic tissues. The mRNA was not only expressed in T-cell lines but in some of monocytic, myeloid, and B-cell lines. In all of these tissues and cell lines, at least four mRNA species were detected. DNA blot hybridization analysis revealed a rather simple genomic structure, which suggested a single gene as compared with the complex multigene family of murine Ly-6.

Amino Acid Sequence↗

Natural killer cell activity in workers exposed to benzidine and beta-naphthylamine.

To investigate the effects of benzidine (BZ) and beta-naphthylamine (BNA) on the immune system in man, the activity of natural killer (NK) cells as well as the relative number (percentage) of Leu 11a positive cells in peripheral blood lymphocytes were measured in 63 dyestuff workers exposed to BZ and BNA (aromatic amines, AA). The cytotoxic potential per NK cell (unit NK cell activity) was approximated by dividing the NK activity per fixed numbers of unseparated mononuclear cells by the percentage of Leu 11a positive lymphocytes that mediated NK activity. Thirty one of these workers had previously been treated for bladder cancer and then cured (ex-cancer AA workers) whereas the remaining 32 had not been diagnosed as having bladder cancer (non-cancer AA workers). There was no significant difference in the gross NK activity per unseparated peripheral mononuclear cells among ex-cancer AA workers, non-cancer AA workers, and the control group (p greater than 0.05). The relative number of Leu 11a positive cells, on the other hand, was significantly higher in AA workers than in the control group (p less than 0.01). The unit NK cell activity, as a result, was significantly more reduced in both ex-cancer and non-cancer AA workers than in the control group (p less than 0.05 and p less than 0.01, respectively). Between ex-cancer and non-cancer AA workers, no significant difference was observed in terms of unit NK cell activity. These results indicated that the function of NK cells per se was impaired in AA workers whereas the number of circulating NK cells was relatively increased.

2-Naphthylamine↗

[A case of mixed connective tissue disease exacerbated by griseofulvin complicating aseptic meningo-encephalitis and disseminated intravascular coagulation].

A variety of drugs have been implicated in causing or exacerbating SLE (drug-related lupus). Griseofulvin, the most commonly used agent in the treatment of fungal infections in the skin, has been shown to be a possible SLE-activating drug in several case reports. In the literature, however, any similar drug reactions have not been reported in MCTD, despite sharing features of SLE. The first case of drug (griseofulvin)-exacerbated MCTD was described and discussed. The patient was a 36-year-old woman with a six-year history of MCTD and subclinical Sjögren's syndrome. She developed aseptic meningo-encephalitis and disseminated intravascular coagulation after two weeks of continuous oral administration of griseofulvin 375 mg per day for trichophytosis of the feet. Following cessation of griseofulvin with anticoagulants, antibiotics, and high dose steroids at the same time, she greatly improved within one week.

Adult↗

[Mitral valve replacement with preservation of ventricular annular continuity].

We evaluated clinical effects of mitral valve replacement with preservation of ventricular annular continuity in 53 patients with isolated mitral stenosis and regurgitation. The patients were divided into 3 groups; Group 1: the patients had conventional mitral valve replacement, Group 2: with preservation of posterior leaflet ventricular annular continuity (VAC) (33 patients), and Group 3: preservation of both anterior and posterior leaflet (8 patients). Operative technique was described for pure mitral regurgitation and mitral stenosis. There was one patient died within 30 days operatively in each group. In Group 1 the patient died for poor LV function, in Group 2, the patient died for postoperative GVHD, and in Group 3, the death caused by postoperative LV rupture. We have observed no late death. Minor thromboembolization in early stage were seen in 2 cases of Group 2 and there were no apparent correlation with operative technique. Postoperative cardiac catheterization data (Pulmonary Artery wedge pressure, C.O, LVEF, LVEDV1) showed no significant difference among these 3 groups. Segmental wall contraction in left ventriculography demonstrated good contraction in Group 2 and Group 3 compared with that of Group 1. Left ventricular contraction index with heart rate corrected mean Vcf (Vcfc) and left ventricular end-systolic wall stress (sigma es) relation using two dimensional cardiac echogram demonstrated almost normal range in the groups 2 and 3. These findings suggests that mitral valve replacement with preservation of ventricular annular continuity has beneficial effects on postoperative left ventricular function and requires to be further investigated.

Adolescent↗

IL-7 promotes thymocyte proliferation and maintains immunocompetent thymocytes bearing alpha beta or gamma delta T-cell receptors in vitro: synergism with IL-2.

IL-7 induced the proliferation of normal thymocytes and the effect was synergistically potentiated by a small dose of IL-2, which by itself hardly affected thymocyte proliferation. No synergism was observed between IL-7 and any one of the other lymphokines including IL-1, IL-3, and IL-4. The thymocyte culture stimulated with IL-7 and IL-2 consisted of single positive (CD4+CD8- and CD4-CD8+) and double negative (CD4-CD8-) populations, and double positive (CD4+CD8+) cells were completely deleted. Both single positive and double negative thymocytes expressed CD3, but only the former exhibited V beta 8 and V beta 6 in an expected proportion (approximately 30% in BALB/c mice) and the latter none at all. Immunoprecipitation of the cultured thymocytes by anti-TCR gamma antibody, on the other hand, revealed the presence of a TCR gamma chain. Taken together, these results indicated that the thymocyte cultured with IL-7 and IL-2 consisted of mature T cells bearing alpha beta or gamma delta TCR. Experiments using preselected thymocyte subpopulations indicated that double negative cells responded to both IL-7 and IL-2 with positive synergism when combined, while thymocytes enriched for single positive cells preferentially responded to IL-7 with little response to IL-2 and no detectable synergism. Double positive thymocytes showed no proliferation in response to IL-7 and IL-2. In contrast to single positive thymocytes, splenic T cells hardly responded to IL-7, although significant proliferation was induced in the presence of a low dose of IL-2. Thymocytes cultured with IL-7 and IL-2 showed little nonspecific cytotoxic activity, but responded to Con A or alloantigen, whereas those stimulated with a high dose of IL-2 alone exhibited potent cytotoxic activity. These results indicated that IL-7 was involved in the generation of immunocompetent T cells in the thymus in concert with IL-2.

Animals↗

Expansion of natural killer cells but not T cells in human interleukin 2/interleukin 2 receptor (Tac) transgenic mice.

Transgenic mice expressing both human IL-2 and the L chain of IL-2-R constitutively had an unusual expansion of Thy-1+/CD3-4-8- large granular lymphocytes, which bore the elevated NK activity. Unexpectedly, the transgenic mice had neither T cell expansion nor autoreactive antibodies. The increase in number and activity of NK cells seems to be responsible for both the severe interstitial pneumonia and lymphocyte depletion in the spleen that we found in these transgenic mice. In addition, we found the selective loss of Purkinje cells in the cerebellum of the mice, which gave rise to their disturbed gait. All the transgenic mice died by 4 wk of age.

Animals↗

Two types of antibodies inhibiting interleukin-2 production by normal lymphocytes in patients with systemic lupus erythematosus.

Decreased interleukin-2 (IL-2) production by lymphocytes in vitro has previously been demonstrated in patients with systemic lupus erythematosus (SLE). In the present study, we examined whether inhibitory factors in SLE patient sera are involved in defective IL-2 production. Our results indicate that purified IgG fractions of some SLE sera inhibit IL-2 production at 2 distinct phases of the IL-1-dependent IL-2 production system in vitro: first, by binding to adherent cells and probably inhibiting IL-1 production by macrophages, similar to the action of anti-HLA-DR antibodies, and second, by binding to T cells and blocking the interaction of IL-1 and T cells.

Autoantibodies↗

Effects of the deregulated expression of human interleukin-2 in transgenic mice.

We constructed transgenic mice that carry the cDNA of human interleukin-2 (IL-2) under the control of the H-2Kd promoter. The IL-2 transgenic mice expressed human IL-2 mRNA in the thymus, spleen, bone marrow, lung, muscle and skin. Human IL-2 protein was also detected in their sera. The IL-2 transgenic mice suffered from alopecia and pneumonia, but no typical autoimmune reactions seemed to be involved in these lesions. In the epidermis of the IL-2 transgenic mice there was an increase in Thy-1+ dendritic epidermal cells (DEC), which might be involved in the skin lesion. Immune responses of their spleen cells against antigens were significantly impaired whereas their spleen cells responded well to polyclonal lymphocyte activators.

Alopecia↗

Developmental regulation of the extrathymic differentiation potential of the progenitor cells for T cell lineage.

Interleukin-2 (IL-2) generates T lineage cell lines (IL-3B series) directly from the isolated interleukin 3 (IL-3)-induced pluripotential progenitor colonies obtained form adult spleen in vitro. The phenomenon can be reproduced by the combined IL-3/IL-2 bulk culture system. In order to compare the differentiation potential of such progenitors in various ontogenical stages, we have established a number of cell lines from fetal livers (LFD series), fetal thymus (FTD15), newborn spleens (SED series), and adult spleens (SPB series) using the IL-3/IL-2 culture system. The phenotypes of cell lines varied depending upon the developmental stages; LFD lines, Thy1+CD3-CD4-CD8-B220+, FTD15, Thy1+CD3+CD4-CD8+B220-, and SPB and IL-3B lines, Thy1+CD3+CD4-CD8+B220+. Analysis of T cell receptor (TCR) genes revealed that all of the TCR genes (alpha, beta, gamma, and delta) were in germ line configurations in LFD lines. In LFD17 and 19, from 17 and 19 gestation days (GD) respectively, however, germ line transcripts or TCR beta gene were detected, suggesting that they were in the earliest phase of T cell commitment. In LFD14 line from GD14 fetal liver, no such transcript could be detected. In contrast, FTD15 showed complete rearrangement of every TCR gene with full-length TCR alpha and beta gene mRNA. On the other hand, all of the SED, SPB, and IL-3B series of lines exhibited the rearrangement of every TCR gene with productive TCR alpha and beta gene mRNA. The results indicated that progenitors in postnatal spleen, in contrast to those in fetal liver, had the potential to rearrange and express the TCR genes in extrathymic conditions in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Proliferative responsiveness of B cells from autoimmune NZB mice to anti-immunoglobulin and interleukin-4.

Proliferative responses of B cells to anti-IgM antibody and recombinant interleukin-4 (rIL-4) were studied in autoimmune NZB mice. While anti-IgM antibody and rIL-4 act synergistically on resting B cells to induce proliferation in BALB/c and C57BL/6 mice, they failed to produce synergistic effect on NZB B cells, although these NZB B cells responded better to the individual stimulus with anti-IgM antibody or rIL-4. Cell-fractionation analysis of NZB splenic B cells using Percoll density centrifugation showed marked increase in low-density B cells and decrease in high-density B cells. Proliferative response patterns of each subpopulation of NZB B cells were not different from those of control BALB/c B cells, except for higher response of NZB B cells to anti-IgM antibody. Thus, the accumulation of large low density B cells, probably resulting from in vivo activation, may partly account for the altered responsiveness of NZB B cells as a whole.

Animals↗

[A case report of thrombosed St. Jude Medical valve in aortic position].

We report a successful elective re-aortic valve replacement following thrombolysis therapy with Urokinase. Patient was a 56-year-old male with acute heart failure caused by thrombosed St. Jude Medical valve in aortic position. The thrombosed valve occurred 6 years after the implantation due to poor control of anticoagulation therapy. Surgical findings demonstrated the origin of thrombus at the hinge area. Prompt diagnosis and adequate therapy is essential for the thrombosed valve especially in case of mechanical valve. Thrombolysis therapy should be considered if possible, although emergency operation is always indicated.

Aortic Valve↗