Biomedical subjects

Itsuro Endo

Publications and source records attributed to Itsuro Endo.

10 recordsLinked to original sources

PubMed2006

[Treatment of malignancy-associated hypercalcemia].

Malignancy-associated hypercalcemia (MAH) is caused by tumor over-production of parathyroid hormone-related protein (PTHrP), or by locally enhanced bone resorption in metastatic lesions of solid cancers. Medical treatment of MAH includes hydration by saline infusion, loop diuretics to promote urinary calcium excretion and anti-resorptives such as calcitonin and bisphosphonates. Particularly, bisphosphonates are the current mainstay for MAH treatment : they not only inhibit osteoclastic bone resorption to ameliorate hypercalcemia but can also alleviate bone pain and can even prevent cancer cell expansion in bone metastatic lesions.

Bone Neoplasms↗

PubMed2006

[Primary hyperparathyroidism].

Primary hyperparathyroidism is the most frequent cause of hypercalcemia in ambulatory patients. Elevated serum parathyroid hormone in the presence of persistent hypercalcemia is the diagnostic sine qua non for primary hyperthyroidism. Since examination of serum calcium became a routine diagnostic test, most patients with primary hyperparathyroidism are asymptomatic at the time of diagnosis. Primary hyperparathyroidism in most of patients is caused by parathyroid adenoma, and parathyroid hyperplasia and cancer are rare causes of the disorder. Parathyroidectomy is the primary treatment of choice for primary hyperparathyroidism by any cause. Parathyroidectomy should be performed in most of patients with primary hyperparathyroidism, but asymptomatic or only mildly hypercalcemic patients are treated according to the guidelines for surgical treatment established by the NIH Consensus Development Conference in 2002. For patients with osteoporosis who are not indicated for or decline surgical procedures can be treated with bisphosphonates.

Humans↗

PubMed2005

Delayed motor and sensory neuropathy in a patient with brainstem encephalitis.

Bickerstaff's brainstem encephalitis (BBE), Miller Fisher syndrome (MFS) and Guillain-Barré syndrome (GBS) are thought to be closely related and to form a continuous spectrum. However, chronic polyneuropathy in BBE has not been reported. We report the temporal profile of anti-ganglioside antibody titer in a case of BBE-like brainstem encephalitis complicated with chronic polyneuropathy. A 71-year-old Japanese woman presented with drowsiness and cerebellar ataxia in addition to mild weakness in distal limb muscles. Anti-GalNAc-GD1a IgG and anti-GalNAc-GM1b IgG antibodies were positive in her serum. Brain magnetic resonance imaging revealed high-intensity signals in the midbrain, pons, and middle cerebellar peduncles on T2-weighted images. Central nervous system manifestations improved after immunomodulating therapy that included prednisolone, plasmapheresis and intravenous immunoglobulin. Nevertheless, the distal muscle weakness was exacerbated when the anti-GalNAc-GD1a IgG titer was elevated. Nerve conduction study indicated motor and sensory neuropathy which was developed motor dominant axonal damage. These findings suggest that anti-ganglioside antibodies, including anti-GalNAc-GD1a IgG, may be involved in a common autoimmune mechanism in BBE-like brainstem encephalitis and chronic motor dominant axonal neuropathy. However, the fact that the latter manifestation exacerbated after the improvement of former one possibly indicates different thresholds of neurologic symptoms mediated by anti-ganglioside antibodies in the present patient.

Aged↗

PubMed2004

Isolated cranial neuropathy associated with anti-glycolipid antibodies.

We describe seven patients with isolated cranial neuropathy in whom serum anti-glycolipid antibodies were detected. Trigeminal sensory neuropathy was found in four patients, who had exhibited symptoms for 2 months to 4 years. The other three patients showed facial nerve palsy with or without ophthalmoparesis. Temporal profile analysis of anti-glycolipid antibodies revealed that titers of anti-glycolipid IgM antibodies against GM2 and LM1 gradually decreased in patients having chronic trigeminal sensory neuropathy. In patients with acute trigeminal sensory neuropathy, elevation of anti-LM1 antibody titers continued over 12 months although anti-GalNAc-GD1a antibody disappeared. On the other hand, titers of anti-glycolipid antibodies rapidly decreased in patients with acute facial nerve palsy with or without ophthalmoparesis. We conclude that anti-glycolipid antibodies may play an important role in the development of isolated cranial neuropathy in some patients.

Action Potentials↗

PubMed2003

Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors.

Although rachitic/osteomalacic myopathy caused by impaired vitamin D actions has long been described, the molecular pathogenesis remains elusive. To determine physiological roles of vitamin D actions through vitamin D receptor (VDR) in skeletal muscle development, we examined skeletal muscle in VDR gene deleted (VDR -/-) mice, an animal model of vitamin D-dependent rickets type II, for morphological changes and expression of myoregulatory transcription factors and myosin heavy chain isoforms. We found that each muscle fiber was small and variable in size in hindlimb skeletal muscle from VDR -/- mice, although overall myocyte differentiation occurred normally. These abnormalities were independent of secondary metabolic changes such as hypocalcemia and hypophosphatemia, and were accompanied by aberrantly high and persistent expression of myf5, myogenin, E2A, and early myosin heavy chain isoforms, which are normally down-regulated at earlier stages. Moreover, treatment of VDR-positive myoblastic cells with 1,25(OH)2D3 in vitro caused down-regulation of these factors. These results suggest that VDR plays a physiological role in skeletal muscle development, participating in temporally strict down-regulation of myoregulatory transcription factors. The present study can form a molecular basis of VDR actions on muscle and should help further establish the physiological roles of VDR in muscle development as well as pharmacological effects of vitamin D on muscle functions.

Animals↗

PubMed2003

Complicated paraneoplastic neurological syndromes: a report of two patients with small cell or non-small cell lung cancer.

Paraneoplastic neurological syndromes are frequently associated in patients with small cell lung cancer (SCLC) and antineuronal antibodies are involved in the autoimmune mechanism. Multiple syndromes are sometimes complicated in a single patient with SCLC. However, little is known about non-SCLC-associated neurological manifestations. We report two patients with complicated paraneoplastic neurological syndromes. Patient 1 showed paraneoplastic limbic encephalitis (PLE), paraneoplastic sensory neuropathy (PSN) and Lambert-Eaton myasthenic syndrome (LEMS) associated with SCLC. Patient 2 developed opsoclonus-ataxia and probable PLE associated with non-SCLC. Analysis of various antineuronal antibodies revealed that anti-Hu and P/Q-type voltage-gated calcium channel (VGCC) antibodies were positive in Patient 1 but any antibodies were not in Patient 2. Brain MRI demonstrated high intensity signals in temporal lobes particularly on fluid-attenuated inversion recovery (FLAIR) or diffusion-weighted images. These findings suggest that complicated paraneoplastic neurological syndromes occur in non-SCLC as well as SCLC and that unidentified antineuronal autoantibodies may underlie the pathophysiology.

Autoantibodies↗

PubMed2003

Dermatomyositis with peripheral nervous system involvement: activation of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) in vasculitic lesions.

We describe two cases of dermatomyositis (DM) with nervous system involvement. Polyneuropathy was observed in both patients, and cerebral vasculitis was suspected in one patient. Histological examination of biopsied specimens of skeletal muscles, skin and sural nerves revealed vasculitis. Furthermore, vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) were overexpressed in vasculitic lesions. Although, VEGF and VEGFRs were not detected in biopsied specimens of skeletal muscle from normal subjects, they were observed in one of two patients with DM who did not exhibit neuropathy. These findings suggest the possibility that VEGF overproduction is associated with development of vasculitis in some cases of DM complicated with peripheral neuropathy.

Aged↗

PubMed2003

[Effect of calcium and vitamin D on skeletal muscle].

Patients with vitamin D insufficiency often exhibit muscle weakness and/or atrophy which can be cured by vitamin D and Ca supplementation. However, its molecular mechanism is largely unknown. The direct effects of vitamin D on skeletal muscle cells include induction of transcription factors such as c-myc (genomic action) ;and activation of Ca channels, Src tyrosine kinase and MAP kinase (non-genomic action). Recent studies on VDR gene knockout mice revealed that VDR also regulates expression of the MyoD family of transcription factors in skeletal muscle. Thus, vitamin D and Ca appear to regulate proliferation, maturation and function of skeletal muscle through these complex actions.

English Abstract↗

PubMed2002

Diurnal fluctuation of edema synchronized with plasma VEGF concentration in a patient with POEMS syndrome.

A case of POEMS syndrome in a 49-year-old Japanese woman is reported. The patient exhibited prominent edema in her legs at night, but her edema usually improved by the following morning. The plasma concentrations of VEGF in the patient showed diurnal fluctuations; plasma VEGF levels peaked at night and decreased in the daytime. Immunocytochemical study demonstrated the expression of VEGF in IgA- and lambda-positive plasma cells in bone marrow. The results indicate that VEGF was produced at least by plasma cells and that VEGF production was regulated by circadian rhythm in synchronization with the development of edema.

Anti-Inflammatory Agents↗

PubMed2001

Apoptosis-related changes in skeletal muscles of patients with mitochondrial diseases.

Much interest has recently been shown in apoptosis-mediated roles in the pathophysiology of mitochondrial diseases, because mitochondrial defects are implicated in a wide variety of degenerative diseases. We investigated whether apoptotic events occurred in skeletal muscles of patients with mitochondrial diseases, including chronic progressive external ophthalmoplegia (CPEO), Kearns-Sayer syndrome (KSS), and mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). In a immunohistochemical study, stainings for 8-hydroxy-deoxyguanosine (8-OH-dG), 4-hydroxy-nonenal (4-HNE), Mn-SOD, Bcl-2, cytochrome c, DNase I and Bcl-x L showed a pronounced granular distribution in the cytochrome c oxidase (COX)-negative ragged-red fibers (RRFs). On the other hand, the signals for Bax, p53, Fas and caspase 3 were not obviously increased in RRFs. In situ labeling of DNA breaks demonstrated preferential signals not only in myonuclei but also in subsarcolemmal regions of RRFs, indicating that mitochondrial as well as myonuclear DNA is fragmented in RRFs. An immunoblotting study demonstrated that cytochrome c was increased in the cytosol of diseased muscles and that DNase I was increased in mitochondria, compared to that of normal muscles. No difference was observed between protein bands at 20 kDa corresponding to caspase 3 in diseased and normal muscles. These findings demonstrate that these mitochondrial diseases harbor unique apoptosis-related changes that differ from caspase 3-dependent apoptosis. It is thought that these changes are induced by superoxide overproduction and cytochrome c release resulting from an inherent mitochondrial defect and that the events are associated with DNase I activation.

Adult↗