Rituximab therapy in nephrotic syndrome due to AH amyloidosis

This is an electronic version of an article published in Amyloid 2009, Vol. 16, No. 3 : Pages 178-180. Amyloid is available online at: http://informahealthcare.com/doi/pdf/10.1080/13506120903090940We report a patient with AH amyloidosis associated with lymphoplasmacytic leukemia that has remained in a stable state with a nephrotic syndrome for 17 months since the commencement of cyclic rituximab therapy aimed at suppression of pathogenetic gamma heavy chains. Free light chains in serum and CD20-positive cells in peripheral blood were useful as hematological markers in the patient. Rituximab might be a potent therapeutic option for AH amyloidosis associated with a B-cell lymphoproliferative disorder.ArticleAMYLOID. 16(3):178-180 (2009)journal articl

Up-Regulation of the Brain and Purkinje-Cell Forms of Dystrophin Transcripts, in Becker Muscular Dystrophy

Farrando Sicilia, Jordi; Llauradó Grau, Josep M. ; Fuente Fuente, Carlos; Montes, Antoni

Steatogenesis in adult-onset type II citrullinemia is associated with down-regulation of PPARα

AbstractSLC25A13 (citrin or aspartate–glutamate carrier 2) is located in the mitochondrial membrane in the liver and its genetic deficiency causes adult-onset type II citrullinemia (CTLN2). CTLN2 is one of the urea cycle disorders characterized by sudden-onset hyperammonemia due to reduced argininosuccinate synthase activity. This disorder is frequently accompanied with hepatosteatosis in the absence of obesity and ethanol consumption. However, the precise mechanism of steatogenesis remains unclear. The expression of genes associated with fatty acid (FA) and triglyceride (TG) metabolism was examined using liver samples obtained from 16 CTLN2 patients and compared with 7 healthy individuals. Although expression of hepatic genes associated with lipogenesis and TG hydrolysis was not changed, the mRNAs encoding enzymes/proteins involved in FA oxidation (carnitine palmitoyl-CoA transferase 1α, medium- and very-long-chain acyl-CoA dehydrogenases, and acyl-CoA oxidase 1), very-low-density lipoprotein secretion (microsomal TG transfer protein), and FA transport (CD36 and FA-binding protein 1), were markedly suppressed in CTLN2 patients. Serum concentrations of ketone bodies were also decreased in these patients, suggesting reduced mitochondrial β-oxidation activity. Consistent with these findings, the expression of peroxisome proliferator-activated receptor α (PPARα), a master regulator of hepatic lipid metabolism, was significantly down-regulated. Hepatic PPARα expression was inversely correlated with severity of steatosis and circulating ammonia and citrulline levels. Additionally, phosphorylation of c-Jun-N-terminal kinase was enhanced in CTLN2 livers, which was likely associated with lower hepatic PPARα. Collectively, down-regulation of PPARα is associated with steatogenesis in CTLN2 patients. These findings provide a novel link between urea cycle disorder, lipid metabolism, and PPARα

The combined effect of the T2DM susceptibility genes is an important risk factor for T2DM in non-obese Japanese: a population based case-control study

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder. Recently, several genome-wide association studies (GWAS) have identified many novel susceptibility loci for T2DM, and indicated that there are common genetic causes contributing to the susceptibility to T2DM in multiple populations worldwide. In addition, clinical and epidemiological studies have indicated that obesity is a major risk factor for T2DM. However, the prevalence of obesity varies among the various ethnic groups. We aimed to determine the combined effects of these susceptibility loci and obesity/overweight for development of T2DM in the Japanese.</p> <p>Methods</p> <p>Single nucleotide polymorphisms (SNPs) in or near 17 susceptibility loci for T2DM, identified through GWAS in Caucasian and Asian populations, were genotyped in 333 cases with T2DM and 417 control subjects.</p> <p>Results</p> <p>We confirmed that the cumulative number of risk alleles based on 17 susceptibility loci for T2DM was an important risk factor in the development of T2DM in Japanese population (<it>P </it>< 0.0001), although the effect of each risk allele was relatively small. In addition, the significant association between an increased number of risk alleles and an increased risk of T2DM was observed in the non-obese group (<it>P </it>< 0.0001 for trend), but not in the obese/overweight group (<it>P </it>= 0.88 for trend).</p> <p>Conclusions</p> <p>Our findings indicate that there is an etiological heterogeneity of T2DM between obese/overweight and non-obese subjects.</p

Low HER2 expression is a predictor of poor prognosis in stage I triple-negative breast cancer

IntroductionTriple-negative breast cancer (TNBC) is negative for hormone receptors and human epidermal growth factor receptor 2 (HER2). In stage I TNBC, adjuvant therapy or follow-up are performed according to risk factors, but clinical trial data is scarce. In recent years, it has been reported that HER2-low cases (1+/2+ and in situ hybridization negative) have different prognoses than HER2-0 cases. However, the risk of recurrence and risk factors in this HER2-low population for stage I TNBC have not yet been investigated.MethodsHerein, out of 174 patients with TNBC who underwent surgery from June 2004 to December 2009 at the National Cancer Center Hospital (Tokyo), we retrospectively examined 42 cases diagnosed as T1N0M0 TNBC after excluding those treated with preoperative chemotherapy.ResultsAll patients were female, the median age was 60.5 years, and 11 cases were HER2-low and 31 cases were HER2-0. The median follow-up period was 121 months. Postoperative adjuvant therapy was administered in 30 patients and recurrence occurred in 8 patients. HER2-low cases showed a significantly shorter disease-free survival (HR: 7.0; 95% CI: 1.2– 40.2; P=0.0016) and a trend towards shorter overall survival (hazard ratio [HR]: 4.2, 95% confidence interval [CI]: 0.58–31.4) compared with that of HER2-0 cases. HER2 was also identified as a factor for poor prognosis from the point- estimated values in univariate and multivariate analyses after confirming that there was no correlation between the other factors.ConclusionFor patients with stage I TNBC, the HER2-low population had a significantly worse prognosis than the HER2-0 population

Electrophysiological features of familial amyloid polyneuropathy in endemic area

The process of deterioration of peripheral nerve function in familial amyloid polyneuropathy (FAP) with amyloidogenic transthyretin (ATTR) Val30Met has not been systematically evaluated hitherto. We performed nerve conduction studies in 69 patients with FAP with ATTR Val30Met from one of the endemic areas in Japan. Sensory conduction velocity (SCV), motor conduction velocity (MCV), the size of the compound muscle action potential (CMAP) and distal latency (DL) were measured in the ulnar and tibial nerves. SCV was evaluated using the orthodromic method with needle recording electrodes. These electrophysiological parameters were compared with clinical stage of FAP and duration of neuropathy. When subjects noted minimal neuropathic symptoms only in the feet, motor and sensory nerve function in both the hands and feet had already been disturbed. Sensory nerve action potential on the foot disappeared more rapidly than CMAP. CMAP on foot muscle rapidly decreased during the initial 2 years and completely disappeared within 10 years. The duration of illness and deterioration parameters (CMAP of the abductor digiti minimi muscle, MCV and SCV of the ulnar nerve and DL of both ulnar and tibial nerves) were linearly correlated. CMAP was the most sensitive and reliable parameter to evaluate motor nerve degeneration in FAP.</.ArticleAMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS. 18(1):10-18 (2011)journal articl

Insights into Land Plant Evolution Garnered from the Marchantia polymorpha Genome.

The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage. Relative to charophycean algae, land plant genomes are characterized by genes encoding novel biochemical pathways, new phytohormone signaling pathways (notably auxin), expanded repertoires of signaling pathways, and increased diversity in some transcription factor families. Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant. PAPERCLIP

An Abnormal MRI Signal in Both Lateral Geniculate Bodies Is a Diagnostic Indicator for Patients with Behçet's Disease

A few case reports involving Behçet's disease have described visual field defects ascribed to the lateral geniculate body; however, no cases of lesions in both lateral geniculate bodies have been reported. A 50-year-old male who had fever and genital ulceration 3 months earlier noticed visual field defects. A T2-weighted MRI and FLAIR image showed high-intensity lesions in both lateral geniculate bodies. The posterior end of the optic tracts and lateral geniculate bodies were bilaterally enhanced with gadolinium. Because of the presence of three (aphthous stomatitis, genital ulceration and uveal inflammation) of the four major symptoms, the patient was diagnosed with an abortive type of Behçet's disease and started predonisolone at a dose of 0.5 mg/kg, after which he showed a rapid improvement of all symptoms. The lesions in the lateral geniculate bodies had disappeared on the MRI images taken 2 weeks after treatment onset. In addition to Behçet's disease, several case reports have observed lesions in both lateral geniculate bodies. Their visual field defects disappeared within half a year, in parallel with the healing process of the primary diseases. The pathogenesis of the lesions in both lateral geniculate bodies in these cases is believed to be related to the underlying disorders, especially vascular involvement from inflammation. The appearance of lesions in both lateral geniculate bodies on MRI scans may indicate the presence of systemic inflammatory diseases such as Behçet's disease, but further examinations are required