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Biomedical subjects

M Inada

Publications and source records attributed to M Inada.

At least 91 records · Page 5Linked to original sources
PubMed1997

Histocompatibility antigens and polymyalgia rheumatica in a Japanese patient with insulin-dependent diabetes mellitus.

A 30-year-old Japanese female developed insulin-dependent diabetes mellitus (IDDM). She later complained of muscle pains at the age of 37. Erythrocyte sedimentation rate and C-reactive protein were abnormal, with negative antinuclear antibody and rheumatoid factor tests. The diagnosis of polymyalgia rheumatica (PMR) was made. She had HLA phenotypes including A2 and without DR4, consistent with common types of Japanese PMR. Her DNA typing included DQB1*0303 which is positively associated with Japanese IDDM. It seems likely that she suffered from these diseases at a young age on the basis of having the HLA-susceptibility to both PMR and IDDM.

Adult↗
PubMed1997

Serial assessment of sympathetic reinnervation in a patient with myocardial infarction.

Resting [123I]MIBG and 201TI imaging were performed at 2 wk and 4 and 12 mo after successfully reperfused myocardial infarction. Although [123I]MIBG uptake of the infarcted segments revealed significant improvement in the early image at 4 mo, delayed image displayed decreased [123I]MIBG uptake. However, decreased [123I]MIBG uptake of the delayed image became almost uniform at 12 mo. These observations suggest that reinnervation initially occurs in norepinephrine uptake and then in retention ability. On the other hand, a 201TI defect remained in the infarcted segments at 12 mo. Thus, reinnervation can occur not only in the peri-infarct area but also in the infarcted area.

3-Iodobenzylguanidine↗
PubMed1997

Neutrophil elastase inhibitor (ONO-5046-Na) inhibits the growth of human lung cancer cell lines transplanted into severe combined immunodeficiency (scid) mice.

We examined the in vivo effects of ONO-5046xNa, a specific neutrophil elastase (NE) inhibitor, on the growth of 2 non-small cell lung cancer cell lines, EBC-1 and PC-3, transplanted into severe combined immunodeficiency (scid) mice. The daily intraperitoneal injection of ONO-5046xNa (50 mg/kg/day) completely suppressed the tumor growth in EBC-1, a human squamous carcinoma cell line which produces immunoreactive NE. By contrast, in PC-3, a human adenocarcinoma cell line which is unable to produce immunoreactive NE, the ONO-5046xNa treatment caused delayed growth of the tumor. These findings suggest that ONO-5046xNa may have a clinical role in preventing the growth of human non-small cell lung cancer.

Adenocarcinoma↗
PubMed1997

[Usefulness of magnetic resonance imaging for managing patients with prosthetic carbon valve in the mitral position].

The safety, findings and clinical usefulness of magnetic resonance (MR) imaging were assessed in patients with a prosthetic carbon valve in the mitral position. In vitro deflection, heating and image distortion due to the magnetic field of a 1.5 tesla MR machine were examined in three carbon valves (CarboMedics, St. Jude Medical and Björk-Shiley valves). In vivo MR imaging of the left ventricular horizontal long-axis, vertical long-axis and short-axis views was performed by electrocardiographically synchronized spin echo and field (gradient) echo techniques in eight patients with prosthetic mitral carbon valves, consisting of six CarboMedics valves, one St. Jude Medical valve and one Björk-Shiley valve. No deflection and significant heating was seen in all three valves in vitro. Although little image distortion was shown in the CarboMedics and St. Jude Medical valves, a small distortion toward the frequency encoded direction was seen in the Björk-Shiley valve but caused no difficulty in assessing the surrounding images. Four of the eight patients had normal sinus rhythm and the other four had atrial fibrillation. The prosthetic valves were depicted as signal voids in the images taken by both spin echo and field echo techniques in vivo. Clear structural information with little image distortion of the adjacent tissues of the prosthetic valves were obtained in all patients, although the image of the Björk-Shiley valve which contained stainless steel in the frame had a slightly stronger distortion than those of the CarboMedics and St. Jude Medical valves which contained titanium. The stainless wire suture material used to close the sternal incision was depicted as a signal void, and the areas of the signal loss were larger in the images taken by the field echo technique than those by the spin echo technique. The images taken by the spin echo technique in patients with atrial fibrillation had reduced quality due to the irregularity of repetition time. Cine MR imaging by the field echo technique showed physiological mitral regurgitant jets as signal loss within the flowing blood, which appeared as high signal intensity, bidirectionally in the bileaflet mechanical valve and unidirectionally in the monoleaflet mechanical valve. An abnormal cavity was seen behind the basal left ventricular myocardium in one patient with a CarboMedics valve. The wall of the abnormal cavity was disrupted abruptly and the rest of the wall consisted of pericardium and adjacent tissue in the image taken by the spin echo technique. The image taken by the field echo technique showed an abnormal jet flow from the basal part of the left ventricular cavity into the abnormal cavity, which was compatible with left ventricular pseudoaneurysm. Two-dimensional echocardiography and Doppler color flow mapping disclosed the abnormal cavity and the abnormal flow inside, but failed to show the connection between the left ventricle and the cavity due to reverberation of the ultrasound signal by the prosthetic valve. These findings suggest that MR imaging is a safe and promising method to assess the complications and valvular function in patients with a prosthetic carbon valve in the mitral position.

Aged↗
PubMed1996

Cyclic AMP-dependent pathway that mediates suppressive regulation of glycosaminoglycan production in cultured vascular endothelial cells.

We investigated the effect of agents which increase the intracellular level of cyclic AMP (cAMP) on the production of glycosaminoglycans (GAGs) by cultured bovine aortic endothelial cells. It was found that the incorporation of [3H] glucosamine into GAGs was significantly decreased by forskolin, 8-bromo cAMP, 3-isobutyl-1- methylxanthine and prostaglandin E1. The leakage of lactate dehydrogenase into the medium, a marker of nonspecific cell damage, were not changed by forskolin. Forskolin-induced decrease in the [3H]glucosamine incorporation occurred in both heparan sulfate and the other GAGs. The [3H]glucosamine incorporation into GAGs was suppressed by forskolin also in human aortic and human umbilical vein endothelial cells, bovine aortic smooth muscle cells, porcine kidney epithelial LLC-PK1 cells and human fetal lung fibroblastic IMR-90 cells. In conclusion, it was suggested that intracellular cAMP mediates the suppressive regulation of GAG production in vascular endothelial cells; as a result, the cell surface heparan sulfate was reduced. The cAMP-dependent pathway appears to be important as an intracellular mechanism by which endothelial production of anticoagulant heparan sulfate is regulated.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Bone morphogenetic protein-12 and -13 inhibit terminal differentiation of myoblasts, but do not induce their differentiation into osteoblasts.

Effects of bone morphogenetic protein (BMP)-12 and BMP-13, new members of the BMP family which belong to the transforming growth factor (TGF)-beta superfamily, on terminal differentiation of myoblasts were examined in C2C12 and L-6 myoblasts. When the myoblasts were cultured with BMP-12 or BMP-13, the expression of the myosin heavy chain and the formation of multinucleated myotubes mRNA in L-6 cells. The inhibitory effects of BMP-12 and BMP-13 on myogenic differentiation were similar to the effects of BMP-2, though their potencies were lower than BMP-2. Unlike BMP-2, neither BMP-12 nor BMP-13 induced alkaline phosphatase activity in C2C12 myoblasts. The differences in the biological activities of these new BMPs suggest that the intracellular signalling pathway used by BMP-12 and BMP-13 differs from that of BMP-2.

Alkaline Phosphatase↗
PubMed1996

Sustained ventricular tachycardias associated with myotonic dystrophy.

Patients with myotonic dystrophy are reported to have a higher frequency of sudden death than the general population. Although causes of sudden death in myotonic dystrophy are suggested to be due to conduction of defects progressing, the HV interval cannot predict whether conduction system disease would develop or progress. We report two cases of myotonic dystrophy complicated with sustained monomorphic ventricular tachycardias (VT), which can cause sudden death. In Case No. 1, although the patient was treated successfully for sustained VT with verapamil in electrophysiologic studies, another sustained VT was confirmed 2 years later. In Case No. 2, the patient showed decreased left ventricular ejection fraction and late potentials, and induced sustained VT that was identical to clinically documented VT. Although VT is believed to be rare in patients with myotonic dystrophy, these cases suggest that VT is a possible cause of sudden death.

Adult↗
PubMed1996

Prevalence, resolution, and determinants of late potentials in patients with unstable angina and left ventricular wall motion abnormalities.

Although transient myocardial ischemia such as exercise-induced ischemia has not been reported to be associated with the occurrence of late potentials, the association of late potentials with more profound ischemic damage, which is represented by reversible but prolonged left ventricular wall motion abnormalities, has not been demonstrated. We prospectively evaluated 37 unstable angina patients who had reversible but prolonged wall motion abnormalities after resolution of chest pain and electrocardiogram (ECG) changes. Signal-averaged ECG (SAECG) and echocardiogram were recorded during the acute phase and before hospital discharge. Late potentials were present in 6 (16 percent) patients on the initial SAECG recording and resolved in all 6 patients on the second recording before hospital discharge. Normalization of inferior left ventricular wall motion abnormality and multivessel disease were observed more frequently in patients with late potentials on the initial recording than in patients without (p < 0.05 and p < 0.05, respectively). In conclusion, late potentials were observed in patients who had reversible but prolonged wall motion abnormalities; these late potentials were resolved with improvement of left ventricular wall motion abnormalities. These results suggest that myocardial ischemia with prolonged wall motion abnormalities is a possible mechanism of the occurrence of late potentials.

Action Potentials↗
PubMed1996

Studies of retroorbital tissue xenografts from patients with Graves' ophthalmopathy in severe combined immunodeficient (SCID) mice: detection of thyroid-stimulating antibody.

The pathogenesis of Graves' ophthalmopathy (GO) is still unclear and the possible role of TSH receptor antibody in the development of GO is controversial. However, the recent availability of severe combined immunodeficient (SCID) mice has provided a means to study of human autoimmune thyroid disease in an in vivo environment. In the present study, we xenografted human retroorbital (RO) tissues from 9 patients with GO into 9 SCID mice and the autologous peripheral blood mononuclear cells (PBMC) from 5 of 9 GO patients were engrafted into 5 separate SCID mice to reconstitute the immunological environment of human GO. Mice blood samples were taken every 2 weeks for the measurements of human IgG, thyroglobulin antibody (Tg-Ab), thyroperoxidase (TPO)-Ab, thyroid-stimulating antibody (TSAb), and interferon-gamma (IFN-gamma). Eight weeks after xenografting, mice were killed; RO tissues were analyzed histologically, SCID mice with RO tissues from 2 of 9 GO patients produced human IgG peaking at 6-8 weeks after xenografting. TPO-Abs and TG-Abs were detectable in low titer in mice with RO tissue xenografts from 3/9 and 4/9 GO patients, respectively. The mean level of IFN-gamma in SCID mice with GO RO xenografts was higher than that of a control subject (RO tissue from a non-GO patient). TSAbs were actually produced from 7 of 9 mice xenografted with GO RO tissues, and reached their peaks at 2-8 weeks after xenografting; autologous PBMC (alone, without RO tissues)-engrafted SCID mice did not produce any detectable level of TSAb. The control mouse did not produce any detectable levels of human IgG, TPO-Ab, Tg-Ab, or TSAb. Immunohistochemical analysis of orbital mononuclear cell infiltrates revealed a predominance of T lymphocytes, with a small percentage of B lymphocytes in GO RO tissue graft. In conclusion, we have successfully reconstituted the SCID mice with human lymphocytes of RO tissues from patients with GO. Autoreactive B cell clones responsible for secreting TSAb exist in GO RO tissue and may be a key factor in the initiation and/or the progression of GO.

Adult↗
PubMed1996

IFN-gamma has a protective role against thyroid-specific autoantibody production in severe combined immunodeficient (SCID) mice xenografted with Graves' thyroid tissue.

We studied the effects of exogenous human IFN-gamma or neutralizing monoclonal antibody (mAb) to IFN-gamma on xenografted human Graves' thyroid tissue in severe combined immunodeficient (SCID) mice to investigate a possible role of IFN-gamma in the pathogenesis of human Graves' disease. Human thyroid tissues from four patients with Graves' disease were xenografted into SCID mice. Two weeks after xenografting, mice were divided into three groups with human IgG levels similar to each other. Mice in the first group were treated with human IFN-gamma daily for 6 weeks; mice in the second (similar) group were treated with an mAb to IFN-gamma; mice in the third group were given mouse IgG only (control group). Blood samples were taken every 2 weeks for human IgG and thyroid-specific autoantibodies (Tg-Ab, TPO-Ab, and thyroid-stimulating antibody). After 6 weeks' treatment, mice were killed, and the thyroid xenograft was examined for thyrocyte HLA-DR expression. Human IgGs were produced equally in all three groups; mice treated with IFN-gamma showed significantly lower amounts of thyroid autoantibodies than those in the control group. Thyrocyte HLA-DR expression was markedly increased in xenografts from mice with IFN-gamma administration. On the other hand, anti-IFN-gamma mAb injection caused only slight suppression of HLA-DR expression on xenografted thyroid cells. In conclusion, IFN-gamma may down-regulate the production of thyroid-specific autoantibodies but not human IgG, at least under these circumstances; there thus may be specific inhibitory effects of IFN-gamma against thyroid-specific autoantibody production of intrathyroidal plasma cells, and this animal model may help to elucidate the possible role of cytokines in the pathogenesis of Graves' disease.

Animals↗
PubMed1996

Does appropriate endurance exercise training improve cardiac function in patients with prior myocardial infarction?

OBJECTIVE: The objective of the present study was to determine whether appropriate endurance exercise training improves cardiac function in patients with prior myocardial infarction. METHODS: Twenty-nine patients with prior myocardial infarction were divided into three groups (Group 1: control, Group 2: low-intensity training, Group 3: high-intensity training). Low and high training intensities were determined according to the gas exchange threshold of each patient. The patients in Groups 2 and 3 performed 15 min of home-based physical training safely, twice a day, 5 days a week for 2 months. Prior to and following this training, each patient performed two constant work rate tests (moderate and heavy intensity) and a symptom-limited incremental exercise test. RESULTS: Heart rates at rest and during exercise were decreased significantly after 2 months in all three groups. Stroke volume at rest increased significantly after 2 months only in Group 3. Stroke volume after 6 min of heavy-intensity exercise increased significantly in Groups 2 and 3. However, the ejection fraction at 6 min of heavy-intensity exercise increased significantly only in Group 3. The maximal work rate attained during incremental exercise testing increased significantly in Groups 2 and 3. This parameter did not significantly change in the control group. CONCLUSIONS: Effects of physical training on maximal exercise capacity were noted in both exercise training groups. However, improvement in cardiac function (such as stroke volume), both at rest and during exercise, was noted only in the high-intensity training group. Our results suggest that relatively high-intensity training may improve exercise capacity and cardiac function of patients with prior myocardial infarction.

Adult↗
PubMed1996

Determinants of activation by complement of group II phospholipase A2 acting against Escherichia coli.

Prompt killing of many strains of Escherichia coli during phagocytosis in vitro by isolated polymorphonuclear leukocytes (PMN) requires the presence of nonlethal doses of nonimmune serum (B. A. Mannion, J. Weiss, and P. Elsbach, J. Clin. Invest. 86:631-641, 1990). Because this requirement is bypassed in a phospholipase A (PLA)-rich mutant (pldA ) of E. coli, we have examined the effect of serum on bacteria] phospholipid (PL) degradation during phagocytosis of wild-type (pldA+) and PLA-deficient (pldA) E. coli. In parallel with increased killing, nonlethal doses of serum increased the degradation of prelabeled bacterial PL during phagocytosis by two- to fivefold, to nearly the same levels (ca. 50 to 60%) as those produced during phagocytosis of E. coli pldA in the absence of serum. The effects on the E. coli pldA mutant imply that there is a serum-mediated enhancement of granule-associated group II PMN PLA2 activity. At the same doses, serum promoted action against E. coli in the presence of purified rabbit and human group II PLA2 but did not activate bacterial PLA. Related PLA2s that lack specific structural determinants needed for optimal activity against E. coli treated with the bactericidal/permeability-increasing protein (BPI) of PMN are also less active than wild-type group II PLA2 against serum-treated E. coli. Treatment of E. coli with C7- or C9-depleted serum did not enhance bacterial killing or PL degradation during phagocytosis or the action of purified PLA2. In summary, these findings suggest that (i) nonlethal assemblies of the membrane attack complex promote intracellular killing and destruction of E. coli ingested by PMN, in part by promoting the action of granule-associated PLA2 against ingested bacteria, and (ii) structural determinants first implicated in PLA2 action against BPI-treated E. coli are also important in PLA2 action in concert with other host defense systems, such as complement.

Animals↗
PubMed1996

Regulation of angiotensin II type 2 receptor gene by the protein kinase C-calcium pathway.

In the present study, rat angiotensin II type 2 (AT2) receptor expression was upregulated in confluence-arrested PC12 cells compared with expression in proliferating cells. Treatment with cycloheximide inhibited the increase in mRNA levels in confluent cells. The state of growth arrest by serum deprivation was associated with increased expression of the AT2 receptor, which was markedly suppressed by exposure to the active phorbol ester 12-O-tetradecanoylphorbol 13-acetate and the calcium ionophore A23187. Similar inhibitions were also observed in myocytes isolated from neonatal rat heart. The change in AT2 mRNA levels by serum deprivation was due to the increase in the gene transcription rate. The effect of 12-O-tetradecanoylphorbol 13-acetate was mediated through decreases in gene transcription and mRNA stability, whereas A23187 affected mRNA stability. Vasoactive substances with the protein kinase C-calcium pathway, such as norepinephrine and angiotensin II, also downregulated the AT2 mRNA level in myocytes. These findings indicate that the expression of AT2 receptor in PC12 cells is regulated in a growth state-dependent manner, which is involved in confluence-induced new protein synthesis, thus providing a means by which cells can modulate their responsiveness to external angiotensin II stimulus. The activation of protein kinase C or calcium mobilization modifies this regulatory mechanism, suggesting that neurotransmitters or vasoactive substances with the protein kinase C-calcium pathway at least in part affect neuronal activity or blood pressure control by downregulating AT2 receptor expression.

Animals↗
PubMed1996

Translational regulation of angiotensin II type 1A receptor. Role of upstream AUG triplets.

The cDNA sequence of rat angiotensin II type 1A receptor (AT1AR) shows that AT1AR transcripts have AUG triplets in the 5'-leader region that may begin a short open reading frame encoding an 11-amino acid peptide. In this study, the mutational inactivation of the start codon of the short open reading frame in AT1AR-chloramphenicol acetyltransferase (CAT) reporter gene constructs resulted in a 2.6-fold increase in CAT activity, whereas CAT transcript levels were not affected. Furthermore, experiments with rat AT1AR cDNA-transfected Cos-7 cells revealed that mutagenesis of the upstream AUG increased the AT1AR protein up to 2.5-fold, although AT1AR transcript levels showed no changes. The synthetic peptide corresponding to the sequence of the short open reading frame significantly suppressed the amount of AT1AR product in the in vitro translation system. The inhibiting effect of the short open reading frame appears to operate at least in part at the level of translation initiation, because polysome analysis with transfected Cos-7 cells showed that mutagenesis of the upstream AUG resulted in a shift of AT1AR mRNA distribution from a smaller to larger fraction of polysomes. Taken together, these results show that the upstream AUG inhibits translational regulation, suggesting that the short open reading frame in the 5'-leader region of AT1AR transcripts has a certain role in the translation of AT1AR protein.

Animals↗