PubMed Health⌕ Search

Biomedical subjects

M Inaba

Publications and source records attributed to M Inaba.

At least 217 records · Page 12Linked to original sources
PubMed1995

Effect of bone marrow transplantation on antiphospholipid antibody syndrome in murine lupus mice.

The (NZW x BXSB)F1 (W/BF1) mouse is known to be an animal model of systemic lupus erythematosus (SLE) and immune thrombocytopenic purpura (ITP). These mice produce not only anti-DNA antibodies but also anti-platelet antibodies, resulting in decreased platelet counts. They show a high level of proteinuria, increased white blood cell (WBC) counts, hypertension, and myocardial infarction due to the high levels of anti-cardiolipin antibodies. When W/BF1 mice (4-5 months) were lethally irradiated and then reconstituted with T cell-depleted bone marrow cells of normal BALB/c mice (8 weeks), 60% of the mice survived more than one year. The WBC and platelet counts in the mice were normalized, and the levels of anti-DNA and anti-platelet antibodies decreased. The renal dysfunction was also ameliorated as indicated by a lower level of proteinuria, lower levels of serum creatinine (S-CRTN) and blood urea nitrogen (BUN), and by improved histology. The blood pressure (BP) of the treated W/BF1 mice decreased due to the improved renal functions. In contrast to the non-treated W/BF1 mice which died of myocardial infarction or renal failure by the age of 7 months, the treated W/BF1 mice showed no evidence of myocardial infarction even one year after BMT. This was due to the lower cardiolipin levels.

Animals↗
PubMed1995

Development of insulin-dependent diabetes mellitus in [(NOD + BALB/c) --> NOD] mixed allogeneic bone marrow chimeras.

To examine the possibility that the bone marrow cells of BALB/c genotype interfere with the development of insulitis and diabetes in NOD mice, we transplanted BALB/c bone marrow cells mixed with NOD bone marrow cells into NOD mice. The [(NOD + BALB/c) --> NOD] chimeras developed insulitis and diabetes, indicating that BALB/c bone marrow cells do not interfere with the development of the disease in NOD mice. Surprisingly, these mice have been reconstituted with only NOD hematolymphoid cells. When the pancreatic tissues from newborn NOD and BALB/c mice were grafted into [(NOD + BALB/c) --> NOD] chimeras, the BALB/c pancreatic tissues were rejected, whereas the NOD graft showed insulitis. Furthermore, the spleen cells of the chimeras showed responsiveness to BALB/c spleen cells in mixed lymphocyte reaction and generated cytotoxic T lymphocytes specific for the H-2d and third party targets. These findings indicate that the hematolymphoid cells (including hemopoietic stem cells) of NOD mice are more resilient than those of normal BALB/c mice, and that insulin-dependent diabetes mellitus will recur after bone marrow transplantation unless the hematolymphoid cells of NOD mice are completely destroyed by irradiation.

Animals↗
PubMed1995

Repair mechanism of lupus nephritis in (NZB x NZW)F1 mice by allogeneic bone marrow transplantation.

We have recently found that allogeneic bone marrow transplantation (BMT) can be used to treat lupus nephritis in (NZB x NZW)F1(B/WF1), BXSB, MRL/lpr and (NZW x BXSB)F1 mice. To elucidate why and how glomerular damage is repaired by BMT, serial renal biopsies were carried out using B/WF1 mice before and after BMT. Donor-derived B cells and macrophages with normal functions developed two weeks (wks) after BMT. At this stage, the macrophages did not show immune complex (IC) clearance activity. Donor-derived T cells with normal functions were generated six wks after BMT. At this stage, visceral epithelial cells macrophages and mesangial cells in the glomeruli were activated by T cells and showed marked phagocytic activity; macrophages and mesangial cells were found to be responsible for the clearance of ICs, whereas, to our surprise, epithelial cells were found to be responsible for the repair of injured basement membranes. These findings suggest that T cells with normal functions, which have the capacity to activate macrophages, mesangial cells and epithelial cells, play a crucial role in repairing IC-mediated glomerular damage.

Animals↗
PubMed1995

Cytotoxic effects of irradiation and deoxyguanosine on fetal thymus.

Effects of irradiation and deoxyguanosine on the fetal thymus were examined both in vitro and in vivo. Fetal thymi (gestation day 15) of C57BL/6 mice that had been irradiated (0-25 Gy) or treated with various doses of deoxyguanosine (dGuo) were engrafted under the renal capsules of BALB/c nu/nu mice, and the differentiation of T cells was investigated in the engrafted thymi or spleens of these mice. After in vitro treatment of fetal thymi with 1.35 mM dGuo (which was previously reported to be an optimal dose), T cell precursors still remained in some cultures, whereas 1.80 mM dGuo was highly cytotoxic not only to T cell precursors but also to thymic epithelial cells. In contrast, 25 Gy irradiation totally eliminated the T cell precursors from the fetal thymi, though the capacity of epithelial cells to induce T cell differentiation was retained. Although irradiated thymi had the capacity to induce T cell differentiation when assayed in an in vitro organ culture system, long-term observation of thymi engrafted into BALB/c nu/nu mice revealed that, if they had been irradiated (9.5 Gy or 25 Gy), the thymi became scarred by 12 wks after their transplantation. Furthermore, the expression of cell interaction molecules such as ICAM-1 and MHC class II on the thymus stromal cells decreased after irradiation. The interaction molecules decreased 3 wks after 25 Gy irradiation and 7 wks after 9.5 Gy irradiation. The alteration in T cell subsets in the thymus (decreases in both double- and single- positive cells and an increase in double-negative cells) correlated with the decreases in the interaction molecules. This indicates that irradiation (even 9.5 Gy) impairs the T cell-induction capacity of the thymus stromal cells, resulting in an alteration of the T cell subsets followed by a change in the T cell counts in the thymus. Therefore, the long-term effects of irradiation of the thymus should be considered in cases of fetal thymus grafts or total body irradiation before bone marrow transplantation, particularly in the newborn.

Animals↗
PubMed1995

Evidence of cellular supplies to the endolymphatic sac from the systemic circulation.

Donor T lymphocytes injected into the host systemic circulation were observed to infiltrate into the host endolymphatic sac in mice. These findings suggest that the endolymphatic sac, a major immune organ in the inner ear, is supplied with immunocompetent cells from the systemic circulation. This concept is consistent with clinical reports that inner ear disorders accompany certain systemic autoimmune diseases. Bone marrow transplantation to replace autoreactive immunocompetent cells with normal cells should be considered as a potential therapy for inner ear autoimmune diseases and an alternative to conventional treatments.

Animals↗
PubMed1995

[An autopsy case of immature teratoma with choriocarcinoma in the mediastinum].

The autopsy of a 28-year-old Japanese male patient, which revealed immature teratoma combined with choriocarcinoma in the mediastinum, is presented. The tumor, which was removed after chemotherapy, was localized in the superior-anterior mediastinum. Chemotherapy was performed several times after operation. However, HCG increased again, and a roentgenogram revealed metastatic shadows in both lungs. The metastatic tumors in the lungs showed only the choriocarcinoma.

Adult↗
PubMed1995

[Emergency CABG and mitral valve replacement for anterolateral papillary muscle rupture after acute myocardial infarction].

A 74-year-old man developed sudden cardiogenic shock 5 days after the onset of acute myocardial infarction. Echocardiographic diagnosis was severe mitral regurgitation due to papillary muscle rupture. Despite the effort to support the hemodynamics with catecholamines and IABP, the patient's condition deteriorated rapidly, which necessitated emergency operation. Anterolateral papillary muscle was found to be totally ruptured. Coronary artery revascularization and mitral valve replacement were performed. Postoperative course was uneventful, with two days of IABP and three days of ventilatory support. The patient could start rehabilitation program on the 7th postoperative day. He was discharged in 2 months in NYHA class I. Reports of successful emergency operation for total papillary muscle rupture following acute myocardial infarction are rare. Involvement of anterolateral papillary muscle is rarer. Early diagnosis and surgical treatment are mandatory to save this group of patients.

Aged↗
PubMed1995

Growth of parathyroid gland in uremic patients on maintenance hemodialysis.

High-resolution, real-time ultrasonography was performed in 245 uremic patients on maintenance hemodialysis and the growth of the enlarged parathyroid glands was compared with the clinical and biochemical signs during follow-up periods of 12 months. The total volume of the parathyroid glands was significantly correlated with the serum C-terminal parathyroid hormone (C-PTH; r = 0.379, p = 0.0001) and calcium levels (r = 0.252, p = 0.0224). After 12 months, the total volume of the enlarged parathyroid glands and serum C-PTH or calcium levels were correlated more closely than in the initial study (r = 0.615, p = 0.0001, and r = 0.489, p = 0.0002, respectively). Both the serum C-PTH levels and the total volume of the enlarged parathyroid glands increased significantly (p = 0.0001), while the ratio between the serum C-PTH levels and the volume of the parathyroid glands decreased significantly (p = 0.0001). There was no difference in the clinical and biochemical signs except for the serum aluminum levels between the patients with and without an increased gland volume. These results suggest that the growth of parathyroid glands may progress more rapidly than the increase in the serum PTH levels, independent of the serum calcium levels, in uremic patients on maintenance hemodialysis.

Adolescent↗
PubMed1995

Involvement of polyamines in the proliferation of bovine parathyroid cells.

An active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], is involved in the regulation of parathyroid cell proliferation as well as of parathyroid hormone synthesis. We examined the effects of 1,25-(OH)2D3 on the proliferation of parathyroid cells in relation to their effects on ornithine decarboxylase (ODC) activity. Exposure of bovine parathyroid cells to serum caused an elevation in [3H]thymidine incorporation, which was preceded by a rise in ODC activity. The biodegradative enzyme, spermidine/spermine N1-acetyltransferase (SAT) activity did not change by 12 h after serum exposure. Preincubation of the cells with 10(-8)M 1,25-(OH)2D3 for 48 h attenuated the serum-induced rise in ODC activity by 12 h. alpha-Difluoromethylornithine (DFMO), a specific inhibitor of ODC, inhibited the serum-stimulated [3H]thymidine incorporation. Simultaneous addition of 25 microM putrescine reversed the inhibitory effect of DFMO. In summary, it was strongly suggested that polyamine is intimately involved in the proliferation of parathyroid cells and that 1,25-(OH)2D3 inhibited parathyroid cell growth through suppression of ODC activity.

Animals↗
PubMed1995

Impaired response of human osteosarcoma (MG-63) cells to human parathyroid hormone induced by sustained exposure to high glucose.

It is known that osteopenia is frequently associated with diabetes mellitus. Although its mechanism is not well understood, impaired bone formation due to an osteoblast deficit seems to be a major factor as reflected by a fall in serum levels of osteocalcin and by the findings of low bone formation with bone histomorphometry. In the present study, we studied the effect of high glucose conditions on osteoblast by examining the responsiveness of human osteosarcoma (MG-63) cells to human parathyroid hormone 1-34 [hPTH-(1-34)]. MG-63 cells were cultured either with 5.5 mM glucose (normal glucose), 55.0 mM glucose (high glucose) or 5.5 mM glucose plus 49.5 mM mannitol (high mannitol) condition for 7 days. Both an increase in cAMP levels and an immediate increase in [Ca2+]i, induced by hPTH(1-34), were significantly lower in high glucose-treated cells than in those treated with normal glucose or high mannitol. Basal cAMP levels in the cells after a 7-day culture in high glucose conditions were significantly higher than in those in the other two groups. We concluded that high glucose specifically impaired the response to hPTH(1-34). This impairment seemed to arise from an increase in intracellular cAMP levels, which is reported to induce downregulation of PTH receptors.

Calcium↗
PubMed1995

Impaired vitamin D metabolism and response in spontaneously diabetic GK rats.

Several studies of diabetes mellitus patients have demonstrated abnormalities in calcium, phosphate and vitamin D metabolism. In an earlier study, the authors reported impaired renal processing of phosphate in spontaneously diabetic GK rats, an animal model of type II diabetes mellitus. In the present study, which represents an extension of the earlier study, vitamin D metabolism and response are examined in 20-week-old GK rats. Serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] was found to be lower in GK rats than in Wistar rats. After intraperitoneal administration of 0.5 micrograms/kg 1,25-(OH)2D, serum calcium increased in GK rats, but not in Wistar rats, while serum phosphate remained unchanged in GK rats, but increased in Wistar rats. Although serum 1,25-(OH)2D rose abruptly in 3 h and decreased thereafter in both GK and Wistar rats, the decrease in serum 1,25-(OH)2D at 6 h was more marked in GK rats than in Wistar rats. Serum 24,25-dihydroxyvitamin D was consistently higher in GK rats than in Wistar rats. Northern blotting and dot blotting with use of a cDNA probe for the 24-hydroxylase gene showed an increased expression of the gene in the kidney of GK rats. These results demonstrate impaired vitamin D metabolism in GK rats. Increased activity of 24-hydroxylase, in addition to impaired phosphate metabolism, may play a role in impaired vitamin D metabolism in GK rats.

Animals↗
PubMed1995

Biological activities of 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3 on human promyelocytic leukemic HL-60 cells: effects of fetal bovine serum and of incubation time.

The hexafluorinated vitamin D3 analog, 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3[F6-1,25-(OH)2D3] is more potent than 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] regarding various physiological effects. When the biological potencies of vitamin D3 analogs were assessed 24 h after the addition by the induction of 24-hydroxylation activity in the human promyelocytic leukemia cell line, HL-60,F6-1,25-(OH)2D3 was 6 times as potent as 1,25-(OH)2D3 in a medium containing 5% fetal bovine serum. When the cells were cultured in a serum-free medium, F6-1,25-(OH)2D3 was only equipotent to 1,25-(OH)2D3. Considering a previous report demonstrating a weaker binding of F6-1,25-(OH)2D3 to serum vitamin D-binding protein (DBP) than 1,25-(OH)2D3, it seems that the resultant greater free fraction of F6-1,25-(OH)2D3 might account for its greater activity in a serum-containing medium. As assessed by the suppression of cell proliferation and the induction of cell differentiation along the monocyte/macrophage pathway which requires as long as 96 h for their assessment, the potency ratio of F6-1,25-(OH)2D3 to 1,25-(OH)2D3 increased as the levels of fetal bovine serum increased. It was of great interest that F6-1,25-(OH)2D3 was still significantly more potent than 1,25-(OH)2D3 even in a serum-free medium. Together with the data indicating the equipotency of F6-1,25-(OH)2D3 and 1,25-(OH)2D3 in the induction of 24-hydroxylation activity, it was suggested that decreased metabolic inactivation might contribute in part to the higher potency of F6-1,25-(OH)2D3 in the long-term effect.

Animals↗
PubMed1995

Influence of serum phosphate on the efficacy of oral 1,25-dihydroxyvitamin D3 pulse therapy.

In patients with a moderate degree of renal insufficiency, restriction of dietary phosphate suppresses PTH secretion by increasing serum calcitriol. However, this may not operate in advanced renal failure. The present study was designed to evaluate the influence of serum phosphate levels on PTH secretion in oral 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] pulse therapy. 22 patients with secondary hyperparathyroidism [carboxy-terminal PTH (c-PTH) concentration: 19.5+/-13.9 ng/ml, mean +/-SD] received oral doses of 1,25(OH)2D3 (3.0-4.0 micrograms) twice a week, each at the end of hemodialysis, for 12 weeks. Doses of phosphate binders remained unchanged throughout this period. Patients were divided into two groups: group A (11 subjects) with mean serum phosphate levels of less than 6.0 mg/dl and group B (11 subjects) with levels of 6.0 mg/dl and above. There was no significant difference in the average corrected serum calcium levels. The reduction in serum intact PTH levels was greater in group A than in group B. A negative correlation (r = -0.48; p < 0.05) was observed between mean serum phosphate levels and the percent decrease in serum c-PTH levels. The findings of this study indicate an important role for dietary phosphate reduction in oral 1,25(OH)2D3 pulse therapy and suggest that serum phosphate reduction may play a part in suppressing PTH secretion through a mechanism independent of 1,25(OH)2D3 and plasma calcium levels.

Administration, Oral↗
PubMed1995

[Combination therapy of doxifluridine, pirarubicin and cisplatin for human gastric cancers implanted in nude mice].

In the preclinical study of a new combination therapy for gastric cancer, dFTP, consisting of doxifluridine (5'-DFUR), pirarubicin (THP) and cisplatin (DDP) as a modification of conventional FAP regimen (5-fluorouracil+Adriamycin+DDP), we compared antitumor and toxic effects of two sequential treatment schedules, single injection of DDP before or after 4 daily administrations of 5'-DFUR, on 5 strains of human gastric cancer bearing nude mice. Results indicated that both schedules of the dFTP regimen had potent antitumor effects. There was no significant difference between them. On the other hand, in terms of the host toxicity as observed by body weight loss, the post-DDP schedule was significantly less toxic than pre-DDP. These results suggest that dFTP regimen (post-DDP schedule) may be useful for clinical treatment of gastric cancers.

Adenocarcinoma↗
PubMed1995

Breakdown of self-tolerance by intrathymic injection of a T-cell line inducing autoimmune gastritis in mice.

Autoimmune gastritis (AIG) develops spontaneously in BALB/c mice thymectomized 3 days after birth (3d-Tx). We first confirmed our previous observations that CD4+ splenic T cells in AIG mice induced AIG in nu/nu mice, while those in normal mice suppressed the development of the disease. In addition, we found that a quantitative balance between these effector (Te) and suppressor (Ts) T cells determined either onset or prevention of the disease. Peripheralization of Ts seemed to begin around 3 days after birth, since the incidence of AIG in mice that underwent Tx 6 days after birth (6d-Tx) decreased markedly, compared with that of 3d-Tx mice; 12% in the former, while 79% in the latter. Notably, Ts existed in the 6d-Tx mice that escaped AIG. We next examined the target specificity of such Ts using syngeneic parietal cells known as autoantigens and two kinds of T-cell lines established from an AIG mouse; one is gastritis inducible in vivo, termed A-II, while another is not, named AC-II. Intrathymic injection of parietal cells into mice 3 days after birth followed by 6d-Tx completely prevented the development of AIG. In contrast, injection of irradiated A-II, but not AC-II cells resulted in AIG in 67% of the mice. No autoimmune oophoritis (AIO) was induced in female mice, implying that the breakdown of tolerance is organ specific. Taken together, peripheral tolerance for organ-specific autoantigens seems to be maintained by CD4+ Ts responding to Te, which induces the disease.

Animals↗
PubMed1995

[Polyglandular autoimmune syndrome].

Among numerous etiologies for hypoparathyroidism, one of the inheritable forms of hypoparathyroidism, called polyglandular autoimmune syndrome, appears as a complex of hypofunction of several endocrine glands, candidiasis, pernicious anemia and vitiligo. Idiopathic hypoparathyroidism in the PGA syndrome typically presents by 20 years of age. Among the three major components of the PGAI syndrome, candidiasis is usually the first manifestation. Hypoparathyroidism almost invariably precedes the onset of Addison's disease. One should keep in mind that Addison's disease can mask the presence of hypoparathyroidism and that glucocorticoid replacement therapy alone can cause hypocalcemic crisis.

Addison Disease↗
PubMed1995

Multiple elements in the 5' untranslated region down-regulate c-sis messenger RNA translation.

Expression of the platelet derived growth factor (PDGF) B-chain, the product of the c-sis proto-oncogene, is regulated both at the transcriptional and translational level. Previous studies have shown that the long 5' untranslated region (UTR) of the c-sis mRNA strongly inhibits synthesis of the PDGF-B chain. However, the assignments of down-regulatory regions within the 5' UTR were ambiguous. Expression of several site-directed point and deletion mutants of the 5' UTR of the c-sis mRNA in COS1 cells revealed that the UTR inhibited PDGF-B chain synthesis in a more complex manner than indicated by the previous studies. Abrogation of the three upstream short open reading frames by mutating each of the AUGs did not have any effect on the synthesis of the PDGF-B chain. Expression of deletion mutants revealed two partially overlapping regions, nucleotides 1-651 and 475-1022, each of which independently inhibited c-sis mRNA translation as effectively as the entire 5' UTR. Each of these regions contains a potentially strong stem-loop structure and a GC-rich element. These elements of the alternate down-regulatory regions could interact within the same region and/or with the elements of the other regulatory region to block c-sis mRNA translation. We show, in contrast to the previous reports, that the inhibition of c-sis mRNA translation cannot be attributed exclusively to any particular predicted secondary structure or a GC-rich element within the 5' UTR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗