A case of Duchenne muscular dystrophy recovered from prolonged ischemic kidney injury which emerged with a normal creatinine level.

Duchenne muscular dystrophy (DMD) is an inherited disease characterized by progressive degeneration of the skeletal muscles. Renal dysfunction in patients with DMD has recently become more apparent as life expectancy has increased owing to advances in respiratory devices and heart failure therapies. A 23-year-old man with DMD who required nasal tube feeding was referred to our hospital with a 4-month history of renal dysfunction and anemia. The patient's serum creatinine (sCr) level was within the normal range (0.84 mg/dL), but his serum cystatin C level and estimated glomerular filtration rate calculated by cystatin C (5.90 mg/L and 7.5 mL/min/1.73 m2, respectively) indicated severe renal impairment. A urinalysis revealed elevated levels of protein and tubular markers. The patient's hemoglobin and erythropoietin levels indicated renal anemia. Hypotension, a collapsed inferior vena cava, and a poor tube feeding episode suggested that the kidney injury was due to renal ischemia, which progressed to tubulointerstitial kidney injury, an intrinsic kidney injury. The angiotensin-converting enzyme inhibitors and beta-blockers were discontinued, and extracellular fluid was infused. Thereafter, the patient's renal function recovered. Subsequently, the patient's urinary findings and anemia improved. Although advances in cardioprotective agents are expected to improve the prognosis of patients with DMD, it is important to consider that the number of patients with kidney injury due to renal ischemia may increase and that it is difficult to evaluate renal function using sCr level in patients with DMD because of decreased skeletal muscle mass.

Upfront rituximab therapy for thrombotic thrombocytopenic purpura in systemic lupus erythematosus: a case-based review.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of various autoantibodies and deposition of immune complexes on tissues. Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening hematological disorder that rarely develops in SLE, mainly caused by inhibitory or clearing autoantibody against ADAMTS13. Although B cells play critical roles in the pathogenesis of two diseases, the role of B-cell depletion therapy using rituximab (RTX), a chimeric monoclonal antibody targeting CD20, in the management of TTP associated with SLE remains unclear. We present a 27-year-old woman who manifested TTP and nephritis simultaneously at diagnosis of SLE. This patient successfully responded to high-dose glucocorticoids combined with plasma exchange, and early administration of RTX-induced sustained remission of TTP without relapse over 16 months. This literature review in light of our case demonstrates relationship between early intervention with RTX and better treatment response despite the degree of ADAMTS13 activity. Moreover, we discuss the clinical features in TTP associated with SLE, risk factors for the development of TTP in SLE, and possible outcomes based on RTX dose. It is important to consider upfront RTX as a promising treatment strategy for SLE-associated secondary TTP to improve short-term response and long-term prognosis.

A Case Demonstrating the Pathological Relationship between Granulomatous Vasculitis and Glomerular Lesion in Renal Sarcoidosis.

We experienced a rare case of tubulointerstitial angiocentric granulomatous vasculitis with focal segmental glomerulosclerosis (FSGS) and associated sarcoidosis. Our patient was an 18-year-old man who presented with exertional cough and dyspnea. He also had overt proteinuria (3.0 g/24 h), normal renal function (eGFR 95 mL/min/1.73 m2), heart failure, and hypertension. He had no previous episode of hypertension. These manifestations immediately improved after the administration of antihypertensive therapy that contained an angiotensin-converting enzyme inhibitor, calcium antagonists, beta antagonists, and diuretics. However, he, later on, developed renal dysfunction, with worsening of both proteinuria and hypertension. Renal biopsy was performed and showed epithelioid cells that were arranged concentrically around small blood vessels in tubulointerstitial granulomas. In the glomeruli, the segmental sclerotic lesions were classified as a perihilar variant of FSGS. There were no inflammatory changes, such as a mesangial lesion, inflammatory cell infiltration, fibrinoid necrosis, or crescent formation, and no glomerular granuloma. In the tubulointerstitial granulomas, the intimal elastic lamina of the interlobular arteries was reduplicated, and the intimal wall thickness of renal arterioles was remarkable. After receiving oral prednisolone therapy, the overt proteinuria resolved, the eGFR recovered from 39.4 to 60.6 mL/min/1.73 m2, and hypertension was managed more easily. Thereafter, he did not experience any recurrence. The concurrent improvement of renal function and proteinuria by steroid treatment suggested a relationship between the glomerular lesions and the tubulointerstitial granulomatous vasculitis with associated sarcoidosis.

JAK2 mutation-positive polycythaemia vera associated with IgA vasculitis and nephrotic syndrome: a case report.

We report a case of polycythaemia vera (PV) associated with IgA vasculitis. A 45-year-old man was admitted for evaluation of abdominal pain and palpable purpura. IgA vasculitis was diagnosed, and oral prednisolone therapy (30 mg/day) was initiated. On day 6, the patient developed left hemiparesis, and magnetic resonance imaging revealed acute cerebral infarction. Bone marrow biopsy results and the identification of a Janus kinase 2 (JAK2) mutation led to the diagnosis of PV. Despite steroid therapy, urine protein levels increased to 15 g/g・Cre. Renal biopsy demonstrated mild mesangial proliferation with IgA deposits, but immunosuppressive therapy was partially effective. This case suggests that PV can be a complication of IgA vasculitis and that preventive measures for thrombosis should be taken in such cases.

Projector Augmented Wave Method with Gauss-Type Atomic Orbital Basis: Implementation of the Generalized Gradient Approximation and Mesh Grid Quadrature.

The projector augmented wave (PAW) method is a powerful numerical algorithm that serves as a backend, enabling efficient density functional theory (DFT) calculations through the smoothing of valence electronic descriptions. Although it is mainly used in conjunction with plane-wave basis for solid-state systems, its generality permits the combination with other types of basis functions. In the previous study, we proposed a scheme to incorporate the PAW method into the conventional quantum chemical DFT implementation based on Gauss-type function (GTF) basis (Xiong et al., J. Chem. Theory Comput. 2017, 13, 3236-3249). The potentially high usability of the GTF-based PAW method, referred to as GTF-PAW, was previously shown, while its implementation was limited to the local density approximation (LDA). Here, we present a development of two technical extensions in this method toward practical DFT calculations. The GTF-PAW-based formulation and implementation to raise the level of the functional treatment to the generalized gradient approximation (GGA) is presented for improving reliability. In addition, we attempt to use the uniform mesh grid for DFT's quadrature in place of the conventional Becke grid, which was previously used. With the test calculations performed on illustrative molecules, it is confirmed that the conventional approach to implement GGA within GTF basis code can be straightforwardly integrated into the GTF-PAW method, allowing for the numerically stable treatment of the gradients of density. It is demonstrated that the uniform mesh grid can be used as an efficient numerical quadrature approach, which may be advantageous for handling larger systems.

[Multi-Center Joint Study on the Survey of Antiemetic Therapy for the Prevention of Nausea and Vomiting in Combination Therapy with a Mild Emetic Antineoplastic Drug].

While many studies have demonstrated the prevention of nausea and vomiting in patients receiving moderately or highly emetogenic anti-cancer agents, there are few reports of mildly emetogenic anti-cancer agents. In the present study, we performed a 2-year multi-center study to determine the types and efficacy of antiemetic therapy administered in a total of 77 cancer patients who received mildly emetogenic anti-cancer agents between September 2015 and August 2017. The effectiveness of antiemetic therapy was evaluated based on the frequency of nausea and vomiting and use of rescue medication. This information was reported by patients and collected every 24 hours for 120 hours after the administration of anti-cancer agents with a mild emetogenic risk. The combination of 5-HT3 receptor antagonist(1 or 3 mg granisetron, 0.75 mg palonosetron) and 6.6 mg dexamethasone was the most common antiemetic therapy used in our patient population. There was no significant difference in the effectiveness of all 5-HT3 receptor antagonists that were evaluated. Gemcitabine and nab-paclitaxel were the most commonly used with a total of 64 patients receiving a combination of these mildly emetogenic agents. Poor performance status was associated with failure to achieve total control(TC)of nausea and vomiting(p=0.0304), while habitual alcohol consumption was associated with TC of nausea and vomiting(p=0.0331).

Duchenne muscular dystrophy with platypnea-orthodeoxia from Chilaiditi syndrome.

INTRODUCTION: Chilaiditi syndrome is a rare pathophysiology in which the colon or other organs are interposed between the diaphragm and liver, and respiratory or digestive symptoms sometimes manifest. Although there have been some cases of Chilaiditi syndrome complicating neuromuscular disorders, none have described resulting respiratory or digestive symptoms. CASE PRESENTATION: Our patient was a 20-year-old man with DMD who had been receiving noninvasive positive-pressure ventilation during the night. He experienced respiratory distress when changing from a supine to sitting position. Ventilator adjustment did not relieve the respiratory distress. Abdominal computed tomography revealed marked constipation and interposition of the transverse colon between the diaphragm and liver, indicating Chilaiditi syndrome. The right side of the diaphragm was elevated by the interposed transverse colon when the respiratory distress was present on chest radiograph, but not when symptoms were absent. The patient was diagnosed with platypnea-orthodeoxia attributed to Chilaiditi syndrome. The respiratory distress was improved by the relief of constipation, in addition to the usage of the ventilator throughout the day. CONCLUSION: The rare symptoms and pathophysiology of DMD complicated by Chilaiditi syndrome are reported and discussed herein.

Progressive supranuclear palsy and Parkinson's disease overlap: A clinicopathological case report.

We describe a woman with a 13-year history of postural instability, vertical gaze palsy and dopa-responsive parkinsonism - a clinical profile that corresponds to progressive supranuclear palsy (PSP) and Parkinson's disease (PD). The patient died at the age of 82 years. Neuropathological features included neuronal loss and gliosis in the substantia nigra, locus ceruleus, dorsal motor nucleus of the vagus, thoracic intermediolateral nucleus and nucleus basalis of Meynert, in addition to the typical pathology of PSP. Immunohistochemical studies demonstrated that PSP-tau pathology was localized in the central nervous system, but Lewy body-related α-synucleinopathy was extensive in the central and peripheral nervous systems. Although PSP and PD may represent independent processes, this case could provide insight into a common defect in either protein phosphorylation or the proteinase surveillance system that contributes to human aging.

Extensive cortical spongiform changes with cerebellar small amyloid plaques: the clinicopathological case of MV2K+C subtype in Creutzfeldt-Jakob disease.

We report a clinical case report of the MV2K+C subtype of sporadic Creutzfeldt-Jakob disease (sCJD). The patient was a 72-year-old woman who exhibited progressive dementia over the course of 22 months. Diffusion-weighted MRI during this period showed abnormal hyperintensity in the cerebral cortex in the early stage. The clinical course was similar to that of previously reported patients with the MV2K or MV2K+C subtype of sCJD. However, histopathological examination revealed unique features: severe extensive spongiform changes with perivacuolar deposits in the cerebrum and basal ganglia, plaque-like PrP deposits in the cerebrum, and only mild changes in the cerebellum with small amyloid plaques (∼20 µm in diameter), smaller than those in the MV2K subtype or variant CJD (40-50 µm in diameter). Molecular analysis showed a methionine/valine heterozygosity at codon 129 and no pathogenic mutation in the PrP gene (PRNP). Western blot analysis of the protease-resistant PrP (PrP(Sc) ) in the right temporal pole revealed the type 2 pattern, which is characterized by a single unglycosylated band, in contrast to the doublet described for the typical MV2 subtype of sCJD. The other intermediate band might exist in the cerebellum with kuru plaques. Therefore, small amyloid plaques in the cerebellum can be crucial for MV2K+C subtype.

Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in the Japanese population based on comprehensive mutational analyses.

Hereditary spastic paraplegia (HSP) is one of the most genetically heterogeneous neurodegenerative disorders characterized by progressive spasticity and pyramidal weakness of lower limbs. Because >30 causative genes have been identified, screening of multiple genes is required for establishing molecular diagnosis of individual patients with HSP. To elucidate molecular epidemiology of HSP in the Japanese population, we have conducted mutational analyses of 16 causative genes of HSP (L1CAM, PLP1, ATL1, SPAST, CYP7B1, NIPA1, SPG7, KIAA0196, KIF5A, HSPD1, BSCL2, SPG11, SPG20, SPG21, REEP1 and ZFYVE27) using resequencing microarrays, array-based comparative genomic hybridization and Sanger sequencing. The mutational analysis of 129 Japanese patients revealed 49 mutations in 46 patients, 32 of which were novel. Molecular diagnosis was accomplished for 67.3% (33/49) of autosomal dominant HSP patients. Even among sporadic HSP patients, mutations were identified in 11.1% (7/63) of them. The present study elucidated the molecular epidemiology of HSP in the Japanese population and further broadened the mutational and clinical spectra of HSP.

[Assessment of competence of predialysis chronic kidney disease stage 5 patients to make treatment decisions: preliminary report].

The competence to consent to treatment of 26 adults with stage 5 predialysis chronic kidney disease (CKD) (16 males, 10 females, age; 58 +/- 11 years, creatinine clearance; 10.1 +/- 3.9 mL/min)was assessed using two kinds of format: the MacArthur Competence Assessment Tool-Treatment (MacCAT-T) and mini-mental-state examination (MMSE). The MacCAT-T revealed poor ability for understanding(3.72 +/- 1.11 points; perfect score, 6 points), appreciating (2.88 +/- 0.88 points; perfect score, 4 points)and reasoning(4.30 +/- 2.11 points; perfect score, 8 points). The MMSE revealed poor performance on the attentional task. The level of attentional deficit was significantly related to both poor ability for understanding and reasoning (r = 0.432, p = 0.031 and r = 0.542, p = 0.014, respectively). These results suggest that the competence of predialysis CKD stage 5 patients to consent to treatment is impaired partly via an attentional deficit.

[Facial chorea and hemichorea due to cardiogenic cerebral embolism in the cortex and subcortical white matter].

A 62-year-old man was admitted to our hospital because of suddenly developed bilateral facial chorea and left-sided hemichorea. He had neither hemiparesis nor sensory disturbance. Diffusion-weighted magnetic resonance images of the brain showed acute cortical and subcortical infarctions at the right insula, frontal, temporal and parietal lobes. Tiapride hydrochloride was administered for his chorea. The chorea disappeared on the next day. We diagnosed him as cardiogenic cerebral embolism because he had a paroxysmal atrial fibrillation. We supposed that his chorea was induced by interruption of excitatory output from cerebral cortex to striatum and subthalamic nucleus. Contralateral cortical and subcortical infarction must be considered when a patient suddenly develops hemichorea.

[Enterococcal meningitis due to strongyloidiasis with HTLV-1 carrier].

A 40-year-old Japanese Brazilian admitted to our hospital because of headache and fever. He came to Japan 16 years ago and underwent treatment of strongyloidiasis 3 years ago. He showed neck stiffness. CRP was highly elevated, and anti-HTLV-1 antibody was positive. Examination of CSF demonstrated pleocytosis, and neutrophils were dominant. Culture of CSF yielded Enterococcus faecalis, and we diagnosed his condition as enterococcal meningitis. Enterococcal meningitis was cured by administration of ampicillin and ceftriaxone. Enhanced abdominal CT scan was performed in order to detect the infectious focus which induced enterococcal meningitis. It showed wall thickening, wall enhancement and fluid collection in duodenum and upper jejunum. Strongyloides stercoralis was detected in stool and duodenal juice and mucosa. It turned out that strongyloidiasis had persisted. Strongyloidiasis was cured by administration of ivermectin. We supposed that enteric enterococcus invaded the blood by dissemination of Strongyloides stercoralis, and meningitis was induced by hematogenous infection.

[Elevated plasma concentration of IP-10 in patients with type 2 diabetes mellitus].

Recent studies have shown the important role of proinflammatory cytokines and chemokines in the pathogenesis of atherosclerosis and diabetes mellitus(DM). Interferon-inducible protein of 10 kD (IP-10/ CXCL10), a member of the C-X-C chemokine superfamily, is a potent chemoattractant for activated T lymphocytes and is reported to be involved in various disease states including atheroma plaque formation, inhibition of tumor angiogenesis and maintenance of podocyte function. However, the involvement of IP-10 in type 2 DM, especially in its vascular and renal complications, is largely unknown. To elucidate the etiopathological role of IP-10 in type 2 DM, we measured the concentrations of IP-10 together with IFN-gamma, TNF-alpha, IL-18, IL-6 and MCP-1 in plasma samples from 103 type 2 DM patients with various degrees of nephropathy. A significant difference in the plasma level of IP-10 was observed between the patients and the control subjects (183.3+/-12.5 pg/m/ vs 65.6+/-9.3 pg/ml, p<0.05). IP-10 correlated IL-18, IL-6, TNF-alpha and MCP-1. The IFN-gamma level was below the detectable range. IP-10 levels became higher with the progression of nephropathy : IP-10 levels were 148.9+/-14.5, 174.2+/-17.2 and 231.9+/-31.3 pg/m/ in patients with an urinary albumin creatinine ratio of <30, 30 to 300 and >300 microg/mg Cr, respectively. Similarly, IL-18, IL-6, MCP-1 and TNF-alpha levels in patients with overt albuminuria were significantly higher as compared with those without albuminuria (IL-18, 367.3 45.6 vs 203.5+/-17.6 pg/ml; IL-6, 1.61+/-0.26 vs 0.87+/-0.13 pg/ml; TNF-alpha, 1.83+/-0.48 vs 0.61+/-0.07 pg/ml; p<0.05, respectively) in consistent with previous reports. These results suggested that IP-10 may have an etiopathogenic role in type2 DM and diabetic nephropathy as one of the downstream effectors of proinflammatory cytokines.

[Superior sagittal sinus thrombosis as first manifestation of essential thrombocythemia].

A 52-year-old previously healthy woman was admitted to our hospital for status epilepticus in November 1999. She had not taken oral contraceptives. After treatment with intravenous diazepam and phenytoin, she did not develop seizures anymore. When she became alert, there was a mild left hemiparesis. Lumbar puncture showed an opening pressure of 145 mm H2O, and the cerebrospinal fluid was acellular. Cranial MR imaging demonstrated thrombosis of the superior sagittal sinus and fresh infarction in the right frontal lobe. Plasma fibrinogen, fibrin degradation product, and prothrombin fragment 1 + 2 levels were elevated. Proteins S and C activities and anti-thrombin III levels were within the normal range. Lupus anticoagulant and anti-cardiolipin antibody were negative. She was treated with continuous heparin infusion for ten days and with oral warfarin thereafter. Six months after the first admission, platelet count became more than 400 x 10(3)/microliter. In July 2002, she developed slowly progressive monoplegia of the left arm. Cranial MR imaging demonstrated patent superior sagittal sinus, fresh infarction in the right parietal lobe, and old small infarction in the right corona radiata. The patient was maintained on warfarin and 100 mg of aspirin thereafter. In September 2002, platelet count was 737 x 10(3)/microliter. Bone marrow examination showed increased megakaryopoiesis with normal erythroid and myeloid series and no chromosomal aberrations. Serum C-reactive protein and iron levels were in the normal range. An abdominal ultrasound demonstrated mild splenomegaly. Thus, we made a diagnosis of essential thrombocythemia (ET). ET causes thrombotic events in the course of the disease at a rate of 7% per year. Cerebral infarction is not uncommon, but occurrence of cerebral sinus thrombosis has been rarely reported. Recently, several cases have been reported in which cerebral infarction was the first manifestation of ET even with platelet counts lower than 600 x 10(3)/microliter. To our knowledge, there have been no reported cases of ET presenting with cerebral venous sinus thrombosis. Platelet count should be monitored in the patients with venous sinus thrombosis of undetermined etiology.

Altered expression of NDST-1 messenger RNA in puromycin aminonucleoside nephrosis.

Sulfated portions of glycosaminoglycan (GAG) side chains in heparan sulfate proteoglycan (HSPG) are thought to play an important role in charge-dependent selectivity of glomerular filtration against plasma proteins. Heparan sulfate N-acetylglucosamine N-deacetylase/adenosine 3'-phosphate 5'-phosphosulfate: unsubstituted glucosamine N-sulfotransferase (NDST) is the key enzyme regulating sulfation of GAG chains. In this study we investigated transcriptional expression of NDST-1, 1 of 4 isozymes of NDST, in glomeruli of rats with puromycin aminonucleoside (PAN) nephrosis. Nephrosis was induced in rats with a single intraperitoneal injection of 150 mg/kg PAN. On days 10 and 35, expression of NDST-1 messenger RNA (mRNA) in glomeruli was analyzed with the use of Northern-blot analysis. Immunohistochemical studies were also performed with the use of monoclonal antibodies that react specifically with the N-sulfated portion of the GAG chain of HSPG and agrin, a major core protein of HSPG in glomerular basement membrane (GBM). In addition, we studied the expression of NDST-1 mRNA in cultured glomerular epithelial cells (GECs) and glomerular mesangial cells in the presence of PAN. On day 10, when significant proteinuria developed, the ratios of glomerular expression of NDST-1 mRNA against glyceraldehyde-phosphate dehydrogenase mRNA in PAN-treated rats were decreased to 48% +/- 6% of those in controls (P<.05). Immunohistochemical studies revealed that staining for N-sulfated GAG chains of HSPG on GBM was markedly reduced on day 10 in PAN-treated rats but that staining for agrin was unchanged. In contrast, on day 35, when PAN-treated rats recovered from proteinuria, we noted no differences in glomerular expression of NDST-1 mRNA and staining intensity for N-sulfated GAG chains on GBM between PAN-treated rats and controls. Incubation of GECs for 24 hours in the presence of 50 ng/mL PAN resulted in the reduction of the expression of NDST-1 mRNA (67% +/- 12% of those in controls, P<.05). In summary, we found alteration of the expression of NDST-1 mRNA, accompanying a loss of N-sulfated GAG chains of HSPG on GBM without changes in the core protein agrin, in the course of PAN nephrosis. These data suggest an important role for this enzyme in heparan sulfate assembly in GBM and GEC and in the pathogenesis of proteinuria in PAN nephrosis.

Genomic distribution of three repetitive DNAs in cultivated hexaploid Diospyros spp. (D. kaki and D. virginiana) and their wild relatives.

To understand the genomic organization of Diospyros species with different ploidy levels, we cloned three different repetitive DNAs and compared their genomic distributions in ten Diospyros species, including hexaploid D. kaki and D. virginiana. Genomic Southern hybridization demonstrated that the EcoRV-repetitive DNA was present in tandem in the genomes of D. glandulosa (2n=2x=30), D. oleifera (2n=2x=30), D. lotus (2n=2x=30), D. virginiana (2n=6x=90) and D. kaki (2n=6x=90). All of these species except D. virginiana also contained the HincII-repetitive DNA in tandem. Fluorescent in situ hybridization showed that the EcoRV- and HincII-repetitive DNAs were predominantly located at the proximal or centromeric regions of chromosomes. The DraI-repetitive sequence cloned from D. ehretioides (2n=2x=30) was not found in the other Diospyros species tested. This suggests that D. ehretioides has a genomic organization different from that of the other Diospyros species. Speciation of hexaploid Diospyros species is also discussed with respect to the genomic distribution of the three repetitive DNAs cloned.