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K Arimura

Publications and source records attributed to K Arimura.

At least 19 recordsLinked to original sources
PubMed2000

An overexpression of fibroblast growth factor (FGF) and FGF receptor 4 in a severe clinical phenotype of facioscapulohumeral muscular dystrophy.

We evaluated the expression of a select panel of growth factors and their receptors, including fibroblast growth factor 1 (FGF-1), fibroblast growth factor 2 (FGF-2), platelet-derived growth factor (PDGF), FGF receptor 1 (FGF-R1), FGF receptor 3 (FGF-R3), FGF receptor 4 (FGF-R4), PDGF receptor alpha (PDGF-Ralpha), PDGF receptor beta (PDGF-Rbeta), and heparan sulfate proteoglycan (HSPG), in muscle biopsy specimens from nine facioscapulohumeral muscular dystrophy (FSHD) patients using immunohistochemistry. Two cases of Duchenne-type muscular dystrophy (DMD), two of Becker-type muscular dystrophy (BMD), and one of limb-girdle-type muscular dystrophy (LGMD) were also investigated. Widespread immunostaining for FGF-1 and FGF-2 on the sarcolemma and overexpression of FGF-R4 in endomysial and perimysial connective tissue were seen in one patient with a severe clinical phenotype of FSHD who had respiratory failure. Standard histochemistry in this patient revealed marked interstitial fibrosis and lobulated fibers. The overexpression of FGF and FGF-R4 in this severe FSHD case may be associated with the muscle fibrosis and disease severity.

Adolescent↗
PubMed1999

Manganese intoxication during total parenteral nutrition: report of two cases and review of the literature.

We report two cases of manganese (Mn) intoxication during total parenteral nutrition including manganese (Mn). Both patients showed parkinsonism with psychiatric symptoms and elevated serum Mn levels. T1-weighted magnetic resonance images (MRI) revealed symmetrical high intensity lesions in the globus pallidus. Discontinuation of Mn supplementation and levodopa treatment improved the symptoms and MRI abnormalities in the both patients. Thus, careful attention should be paid to the long-term intravenous administration of Mn.

Aged↗
PubMed1999

Spontaneous regression associated with apoptosis in a patient with acute-type adult T-cell leukemia.

We describe a 76-year-old man with acute-type adult T-cell leukemia, who demonstrated a spontaneous decrease in leukemic cell number, apparently coincident with apoptotic cell death. On admission the patient's white blood cell count was 38.9 x 10(9)/l with 77% abnormal lymphocytes. He also had hypoproteinemia (4.3 g/dl) from protein losing enteropathy. After admission the leukemic cell count decreased without chemotherapy, reaching 5.9 x 10(9)/l after 2 months. Studies of peripheral lymphocytes demonstrated appearance of the apoptotic cells and DNA ladder formation from the beginning of regression. Same truncated proviral DNA was recognized in primary ATL cells through the whole clinical course. The hypoproteinemia improved with intravenous nutrition, followed by increase of the leukemic cells. This case is the first report that demonstrates tumor-cell apoptosis induced clinical regression in adult T-cell leukemia. Further, we speculate that the hypoproteinemia may have been involved in the leukemic cell apoptosis.

Aged↗
PubMed1999

Lambert-Eaton myasthenic syndrome with ophthalmoparesis and pseudoblepharospasm.

We report a patient initially diagnosed as having ocular myasthenia gravis who showed progressive ophthalmoparesis and pseudoblepharospasm together with positive acetylcholine receptor antibodies. Repeated evaluation with high-frequency repetitive stimulation revealed an incremental response and elevated titers of antibodies against presynaptic calcium channels, confirming Lambert-Eaton myasthenic syndrome. Systemic evaluation revealed no malignant neoplasm but revealed euthyroid Hashimoto's disease. Immunomodulative therapy including plasma exchange and administration of an immunosuppressent (azathioprine) combined with a potassium-channel blocker (3,4-diaminopyridine) reduced the ocular abnormalities. We conclude that the ocular manifestations in this patient were probably caused by Lambert-Eaton myasthenic syndrome.

Autoantibodies↗
PubMed1999

Polyneuropathy with minifascicle formation in a patient with 46XY mixed gonadal dysgenesis.

A patient with mixed gonadal dysgenesis showed glove and stocking-type sensory impairment and slowing of motor and sensory nerve conduction. Sural nerve biopsy revealed minifascicular formation with decreased density of myelinated fibers. As far as we are aware, this is the first report of polyneuropathy with minifascicular formation in 46XY mixed gonadal dysgenesis.

Adult↗
PubMed1999

Multiple episodes of thrombosis in a patient with Becker muscular dystrophy with marked expression of utrophin on the muscle cell membrane.

We previously reported a patient with Becker muscular dystrophy (BMD) who exhibited a benign clinical phenotype and marked expression of utrophin on the muscle cell membrane. The patient developed multiple episodes of thrombosis (middle cerebral and femoral arteries) in the course of the disease. We re-examined the biopsy muscle specimen from the patient immunohistochemically as to the expression of procoagulant or anticoagulant factors. We found a lower expression of thrombomodulin on the muscle cell membrane in the BMD patient compared with other BMD or Duchenne muscular dystrophy (DMD) patients. Although utrophin up-regulation in muscle is thought to prevent the muscle wasting in dystrophin-deficient DMD or BMD, the data obtained in the present study indicate that up-regulated utrophin may have an unexpected influence on the function of the vascular or coagulation system.

Adolescent↗
PubMed1999

Positive inotropic effect of insulin-like growth factor-1 on normal and failing cardiac myocytes.

OBJECTIVE: The acute administration of growth hormone (GH) or insulin-like growth factor-1 (IGF-1) improves cardiac performance, possibly contributing to the beneficial effects of GH therapy on heart failure (HF). GH can induce the production of IGF-1 and thus the actions of GH may be mediated through its IGF-1 induction. However, these effects have not yet been demonstrated in failing hearts and the cellular basis of GH or IGF-1-induced inotropic effects remains unknown. We examined the direct effects of GH and IGF-1 on the contractile function and intracellular calcium ([Ca2+]i) homeostasis in normal and failing myocytes. METHODS: To determine whether GH and IGF-1 have a direct effect on myocardial contractility and whether the GH/IGF-1-induced effect was the results of changes in Ca2+ activation, cell shortening and [Ca2+]i transient were simultaneously measured in the left ventricular myocyte preparations, isolated from normal and rapid pacing-induced HF dogs. RESULTS: Basal shortening of HF myocytes was reduced by 64% (p < 0.01). In normal and HF myocytes, GH (0.4-40 x 10(-3) IU/ml) had no effect on either cell shortening or [Ca2+]i transients. In normal myocytes, IGF-1 exerted a positive inotropic effect in a time- and dose-dependent manner (25-500 ng/ml), associated with a parallel increase of [Ca2+]i transient amplitude. IGF-1 increased the shortening magnitude in normal (121 +/- 5% increase from baseline, p < 0.05) and HF (118 +/- 4% increase from baseline, p < 0.05) myocytes. It also increased [Ca2+]i transient amplitude in normal and HF cells by 124 +/- 4 and 125 +/- 7%, respectively. The percent increase of cell shortening and [Ca2+]i transient amplitude was comparable between normal and HF myocytes. Furthermore, IGF-1 did not shift the trajectory of the relaxation phase in the phase-plane plots of cell length vs. [Ca2+]i, indicating that it did not change myofilament Ca2+ sensitivity. CONCLUSIONS: In both normal and HF conditions, IGF-1 exerted an acute direct positive inotropic effect in adult cardiac myocytes by increasing the availability of [Ca2+]i to the myofilaments, possibly explaining the beneficial effect of GH on HF.

Actin Cytoskeleton↗
PubMed1999

Role of Ca2+ availability to myofilaments and their sensitivity to Ca2+ in myocyte contractile dysfunction in heart failure.

OBJECTIVE: Contractile function is depressed at the isolated myocyte level in heart failure (HF), which could result from the decreased availability of intracellular calcium ([Ca2+]i) to the myofibrils and/or the depressed sensitivity of myofilaments to [Ca2+]i. However, the cellular basis of contractile dysfunction remains unestablished. METHODS: We isolated left ventricular myocytes from dogs with rapid pacing-induced HF. Cell shortening and [Ca2+]i transients were measured by indo-1 fluorescence and the myofilament Ca2+ sensitivity was analyzed by the shortening-[Ca2+]i relation in intact myocytes as well as by the pCa tension relation in skinned cells. RESULTS: Peak cell shortening magnitude was depressed in HF, associated with a parallel decrease of [Ca2+]i transient amplitude. There was a significant positive correlation between these two variables (r = 0.71, P < 0.01). In contrast, myofibrillar sensitivity to Ca2+, determined by both intact and skinned myocytes, was comparable between control and HF. Further, there was no significant difference in Ca2+ sensitivity between control and HF even at shorter (1.8 microns) or longer (2.2 microns) sarcomere length. CONCLUSIONS: Using both intact and skinned cellular preparations, a potential defect in myocyte contractile function in HF was a reduction in Ca2+ availability to the myofilaments, rather than the inherent defects in myofilament sensitivity to Ca2+.

Actin Cytoskeleton↗
PubMed1999

Alteration of p16 (CDKN2) gene is associated with interleukin-2-induced tumor cell growth in adult T-cell leukemia.

Because tumorigenesis frequently involves the dysfunction of cell cycle-related proteins, we examined the effect of mutations in CDK inhibitor p16 and its linked genomic loci p15, cl.B, and 1063.7 on the growth of primary adult T-cell leukemia (ATL) cells. Southern blot analysis of primary ATL cells showed a significantly higher incidence of p16 gene alteration in acute ATL than in chronic ATL [67.7% (23/34) vs. 26.1% (6/23), respectively; p<0.003]. Similarly, polymerase chain reaction (PCR) analysis of p16 exon 2 revealed a higher incidence of alteration in acute ATL than in chronic ATL [52.9% (18/34) vs. 26.1% (6/23), respectively; p<0.05]. PCR-single strand conformation polymorphism analysis of exons 1 and 2 of p16 showed no mutations in the patients, with normal pattern by Southern blotting or PCR analysis. Notably five of six chronic ATL patients with abnormal p16 genes progressed to acute crisis within 4 months. PCR analysis of the p16 linked loci 1063.7, p15 exon 2, and cl.B found homozygous deletion in 55.9%, 20.6%, and 2.9% of acute ATL cells and 39.1%, 13.0%, and 0% of chronic ATL cells, respectively, showing no relationship of homozygous deletion in either loci with disease subtypes. In most cases, deletions were seen in multiple genes, including p16. Acute ATL cells had a higher frequency of multigene deletions than chronic ATL cells [44.1% vs. 17.4%; p<0.05]. When leukemic cells were analyzed for interleukin 2 (IL-2) responsive growth, only p16 gene alteration was directly associated with leukemic cell growth activity. Among leukemic cells showing high IL-2 responsiveness, 73.1% (19/26) had p16 gene alteration vs. 27.8% (5/18) of leukemic cells that showed low IL-2 responsiveness (p<0.005). p16 gene alteration was found in 73.3% (14/19) of leukemic cells showing high autonomous growth rates but in only 40.0% (10/25) of those leukemic cells showing low autonomous growth (p<0.03). These results suggest the following: alteration of p16-related genomic regions in ATL is usually a wide rearrangement including the p16 gene; within this region, only p16 gene alteration is associated with disease aggressiveness; and p16 gene deletion may be a proximate event in leukemogenesis.

Blotting, Southern↗
PubMed1999

NF-kappaB involvement in the activation of primary adult T-cell leukemia cells and its clinical implications.

The HTLV-I provirus-encoded Tax protein induces NF-kappaB in Tax-transfected Jurkat T cells or HTLVL-I- infected T cells in vitro. Tax induction of NF-kappaB is presumed to be involved in proliferation and activation of primary leukemia cells in vivo. Recent studies have demonstrated that NF-kappaB activities in human T cells are mediated by at least four c-Rel-related DNA binding proteins - p50, p55, p75 and p85. We examined the significance of NF-kappaB induction in primary adult T cell leukemia cells and the induction kinetics of each of the four NF-kappaB species. Marked NF-kappaB activity was detected using an electrophoretic mobility shift assay (EMSA) in the primary cells of patients with acute disease, but little activity was noted in the cells of chronic patients. NF-kappaB activity was enhanced in a time-dependent manner in acute type cells cultured with mitogen-free medium; there was no induction of activity in chronic type cells. UV crosslinking demonstrated all four species of NFkappaB complex - high levels of p50 and lower levels of p55 and p75, in acute type cells; chronic type cells showed only the p50. As a control, normal resting T cells similarly showed only p50; control cells showed little change in activity when cultured without mitogenic stimulation, analogous to chronic type ATL. Northern blotting revealed enhancement of c-rel (encoding p85) and KBFI (encoding p50 and p55) expression in acute type cells during culture, while there was no significant enhancement of mRNAs in chronic type ATL cells or unstimulated normal T cells. Northern blotting also revealed that Tax is upregulated at the mRNA level in acute- but not chronic-type cells during culture. Expression of c-rel and KBF1 mRNAs in acute type cells appeared to be related to Tax mRNA expression. These results suggest that Tax is capable of inducing nuclear expression of all four NF-kappaB species in primary ATL cells of acute type patients, with marked effects on p55, p75, and p85. Tax induction of NF-kappaB species is regulated, at least in part, at a pretranslational level involving increases in c-rel and KBF1 mRNA.

Acute Disease↗
PubMed1999

Poor outcome of autologous stem cell transplantation for adult T cell leukemia/lymphoma: a case report and review of the literature.

A limited number of patients with adult T cell leukemia/lymphoma (ATL) who received autologous stem cell transplantation (ASCT) have been reported. We report here a case of fatal systemic Candida krusei infection in a female patient with ATL undergoing ASCT. All of the eight patients (including seven patients in the literature) with ATL who received ASCT developed relapse of ATL or death due to ASCT complication, irrespective of subtype or remission state of ATL, source or selection of SCT or conditioning regimen. At present, ASCT appears to provide little benefit for ATL in contrast to that for other types of aggressive non-Hodgkin's lymphoma.

Adult↗
PubMed1999

Expression of vascular endothelial growth factor in sera and lymph nodes of the plasma cell type of Castleman's disease.

To evaluate the possible involvement of vascular endothelial growth factor (VEGF) in the pathogenesis of Castleman's disease, we studied VEGF levels in sera and supernatants of cultured lymph nodes from two patients with the plasma cell type of Castleman's disease, and analysed the expression of VEGF immunohistochemically in the lymph nodes. Clinically, one patient was classified as the localized type and the other as the multicentric type. Histologically, mature plasma cells and hyalinized vessels were prominent in the interfollicular region. The VEGF levels of the sera and the supernatants of cultured lymph nodes of both patients were higher than those of normal controls. VEGF was strongly expressed in plasma cells in the interfollicular region of the lymph nodes of both patients, but rarely in normal lymph nodes. Our results suggest that VEGF may be involved in the marked vascular proliferation in the interfollicular region of the lymph nodes of the plasma cell type of Castleman's disease.

Adult↗
PubMed1999

Reversible F-wave hyperexcitability associated with antibodies to potassium channels in Isaacs' syndrome.

We report a case of Isaacs' syndrome showing F-wave hyperexcitability which was reversible after either epidural block or plasmapheresis. A 14-year-old girl with progressive muscle cramp and myokymia in the legs showed high amplitude, long duration, polyphasic F-waves after either tibial nerve or peroneal nerve stimulation. Potassium current of PC-12 cell membrane was suppressed by her serum, IgM of which strongly reacted with proteins of approximately 50 kDa of the lysates of a PC-12 cell line. After an epidural nerve block with 1 per cent lidocaine 10 ml, the myokymia temporally improved, during which time the hyperexcitable F-waves became normalized. We treated her with double filtration plasmapheresis, which resulted in remarkable improvement of myokymia; simultaneously, the abnormal F-waves showed a decrease in amplitude, duration, and in the number of phases. We concluded that there was hyperexcitability of the proximal site of motor fibers in our patient, and possible immune mechanisms gave rise to the myokymia and unusual F-wave features.

Adolescent↗
PubMed1999

Potassium current suppression in patients with peripheral nerve hyperexcitability.

Acquired neuromyotonia (Isaac's syndrome) is considered to be an autoimmune disease, and the pathomechanism of nerve hyperexcitability in this syndrome is correlated with anti-voltage-gated K(+) channel (VGKC) antibodies. The patch-clamp technique was used to investigate the effects of immunoglobulins from acquired neuromyotonia patients on VGKCs and voltage-gated Na(+) channels in a human neuroblastoma cell line (NB-1). K(+) currents were suppressed in cells that had been co-cultured with acquired neuromyotonia patients' immunoglobulin for 3 days but not for 1 day. The activation and inactivation kinetics of the outward K(+) currents were not altered by these immunoglobulins, nor did the immunoglobulins significantly affect the Na(+) currents. Myokymia or myokymic discharges, with peripheral nerve hyperexcitability, also occur in various neurological disorders such as Guillain-Barré syndrome and idiopathic generalized myokymia without pseudomyotonia. Immuno-globulins from patients with these diseases suppressed K(+) but not Na(+) currents. In addition, in hKv 1.1- and 1.6-transfected CHO (Chinese hamster ovary)-K1 cells, the expressed VGKCs were suppressed by sera from acquired neuromyotonia patients without a change in gating kinetics. Our findings indicate that nerve hyperexcitability is mainly associated with the suppression of voltage-gated K(+) currents with no change in gating kinetics, and that this suppression occurs not only in acquired neuromyotonia but also in Guillain-Barré syndrome and idiopathic generalized myokymia without pseudomyotonia.

Adolescent↗
PubMed1999

Statistically significant differences in the number of CD24 positive muscle fibers and satellite cells between sarcoglycanopathy and age-matched Becker muscular dystrophy patients.

OBJECT: The aim of this study was to reveal variations in the patterns of expression of the cell surface proteins in regenerating fibers and those in the number of satellite cells to gain an understanding of the pathological processes involved in sarcoglycanopathy. METHODS: We have reported that there is a reduction of the beta-1 subunit of laminin, heparan sulfate proteoglycan (HSPG), and HCAM (CD44) in Japanese patients with sarcoglycanopathy. Here, we investigated immunohistochemically the expression of the neural cell adhesion molecule (NCAM), which is a marker for human regenerating muscle and satellite cell, and CD24, which appears to be expressed in the early stages of the regeneration process. PATIENTS: We investigated six Japanese patients with sarcoglycanopathy, and compared to age-matched Becker muscular dystrophy. RESULTS: We found that the incidences of muscle fibers with increased NCAM were not statistically different between the two groups. However, the incidences of muscle fibers with increased CD24 and those of NCAM positive satellite cells were very low in sarcoglycanopathy and were statistically different between sarcoglycanopathy and age-matched Becker muscular dystrophies. CONCLUSION: The poor expression of CD24 and the fewer satellite cells in sarcoglycanopathy without significant difference in the number of total regenerating fibers suggest that a different regeneration process is involved in sarcoglycanopathy compared to that in other types of muscular dystrophy.

Adolescent↗
PubMed1999

Eosinophilic pneumonia with eosinophilic gastroenteritis.

A 48-year-old man was admitted to our hospital with cough, fever and dysphagia. He had a past history of bronchial asthma and surgery for nasal polyp. Chest radiograph and computed tomography showed atelectasis in the right lower field and infiltrative shadow in the left lower field and overall thickening of the esophageal wall. Transbronchial lung biopsy (TBLB) specimens revealed infiltration of eosinophils and lymphocytes under the bronchial mucosa. Gastrointestinal tract biopsy specimens showed submucosal infiltration of eosinophils. These findings led to a definite diagnosis of eosinophilic pneumonia associated with eosinophilic gastroenteritis, a disease which has been rarely reported.

Asthma↗
PubMed1999

[Increased vascular endothelial growth factor (VEGF) is causative in Crow-Fukase syndrome].

Crow-Fukase syndrome is a rare multisystem disorder characterized by polyneuropathy, organomegaly, endocrinopathy, skin changes and M-protein. We have examined levels of vascular endothelial growth factor/vascular permeability factor (VEGF) in serum with Crow-Fukase patients. Serum VEGF levels in Crow-Fukase syndrome were about 15 to 30 times higher than control and other neurological disorders. Most of the characteristic manifestations may be well explainable by the biological function of VEGF except polyneuropathy. We examined the direct effects of VEGF on blood nerve barrier function using blood brain barrier model of rat and intraneural injection of recombinant VEGF. As the result, VEGF affected blood nerve barrier and increased microvascular permeability, thereby inducing endoneurial edema. After increasing the permeability of the blood nerve barrier by VEGF, serum components toxic to nerves such as complements and thrombins may induce nerve damage. Our results suggest that overproduction of VEGF plays an important role in the pathogenesis of Crow-Fukase syndrome.

Animals↗