Renal Cell Carcinoma and Hepatocellular Carcinoma in a Patient with Wilson's Disease.

No reports of renal cancer in patients with Wilson's disease (WD) exist. We herein report a 37-year-old Japanese man diagnosed with WD who had been treated with d-penicillamine 9 years prior. Hepatocellular carcinoma had been diagnosed at 36 years old and treated with radiofrequency ablation therapy. One year later, renal cancer and recurrent hepatocellular carcinoma had developed. The hepatocellular carcinoma was treated after renal cancer surgical resection of a clear-cell-type renal cell carcinoma, with iron, rather than copper, deposited on the renal cancer cells. This patient harbored a novel mutation, p. Leu1395Terfs in ATP7B.

Diagnostic copper imaging of Menkes disease by synchrotron radiation-generated X-ray fluorescence analysis.

Copper (Cu) is an indispensable metal for normal development and function of humans, especially in central nervous system (CNS). However, its redox activity requires accurate Cu transport system. ATP7A, a main Cu(2+) transporting-ATPase, is necessary to efflux Cu across the plasma membrane and synthesize cuproenzymes. Menkes disease (MD) is caused by mutations in ATP7A gene. Clinically, MD is Cu deficiency syndrome and is treated with Cu-histidine injections soon after definite diagnosis. But outcome of the most remains poor. To estimate the standard therapy, Cu distribution in the treated classic MD patients is analyzed by synchrotron-generated X-ray fluorescence technique (SR-XRF), which identifies and quantifies an individual atom up to at subcellular level of resolution with wide detection area. SR-XRF analysis newly reveals that Cu exists in spinal cord parenchyma and flows out via venous and lymph systems. By systemic analysis, excess Cu is detected in the proximal tubular cells of the kidney, the mucosal epithelial cells of the intestine, and the lymph and venous systems. The current study suggests that the standard therapy supply almost enough Cu for patient tissues. But given Cu passes through the tissues to venous and lymph systems, or accumulate in the cells responsible for Cu absorption.

Calcium-overloaded sympathetic preganglionic neurons in a case of severe sepsis with anorexia nervosa.

Aim: We aimed to show the status of intracellular elements in sympathetic preganglionic neurons in an autopsy case of a 55-year-old woman with severe sepsis and cardiac dysfunction with anorexia nervosa. Methods: Our methods include a case report and pathological examinations of autopsied tissues using synchrotron-generated microbeam X-ray fluorescence analysis. Results: A case report of severe sepsis and myocardial dysfunction. The patient had sudden short cardiac arrest without arrhythmia and sequelae, and echocardiogram showed negative inotropic change. The X-ray fluorescence analysis of autopsied tissues indicated an unusually high concentration of cytosolic calcium in sympathetic preganglionic neurons. However, there were no significant pathological findings of damage in the heart or the cardiovascular autonomic nuclei in the central nervous system. Conclusion: The data indicate that dysfunction of the sympathetic preganglionic neurons exists in a patient of severe sepsis and cardiac dysfunction with anorexia nervosa.

The signaling adaptor protein CD3zeta is a negative regulator of dendrite development in young neurons.

A novel idea is emergxsing that a large molecular repertoire is common to the nervous and immune systems, which might reflect the existence of novel neuronal functions for immune molecules in the brain. Here, we show that the transmembrane adaptor signaling protein CD3zeta, first described in the immune system, has a previously uncharacterized role in regulating neuronal development. Biochemical and immunohistochemical analyses of the rat brain and cultured neurons showed that CD3zeta is mainly expressed in neurons. Distribution of CD3zeta in developing cultured hippocampal neurons, as determined by immunofluorescence, indicates that CD3zeta is preferentially associated with the somatodendritic compartment as soon as the dendrites initiate their differentiation. At this stage, CD3zeta was selectively concentrated at dendritic filopodia and growth cones, actin-rich structures involved in neurite growth and patterning. siRNA-mediated knockdown of CD3zeta in cultured neurons or overexpression of a loss-of-function CD3zeta mutant lacking the tyrosine phosphorylation sites in the immunoreceptor tyrosine-based activation motifs (ITAMs) increased dendritic arborization. Conversely, activation of endogenous CD3zeta by a CD3zeta antibody reduced the size of the dendritic arbor. Altogether, our findings reveal a novel role for CD3zeta in the nervous system, suggesting its contribution to dendrite development through ITAM-based mechanisms.

Rat T-cell receptor TRAV11 (Valpha14) genes: further evidence of extensive multiplicity with homogeneous CDR1 and diversified CDR2 by genomic contig and cDNA analysis.

The antigen recognition system of NKT cells acts via an invariant T-cell receptor (TR) which recognizes CD1d and is highly conserved in mice, rats and humans. NKT cells expressing an invariant mouse TR composed of TRAV11-TRAJ18 (formerly Valpha14-Jalpha281) are positively selected by CD1d, and recognize an antigen in context with CD1d. Here we show ten distinct TRAV11 genes (previously designated by us as TRAV14) on rat Chromosome 15 (BN/SsNHsd/MCW strain). In the rat TRAV11 genes, the splicing sites, the recombination signal sequences, and the possible promoter regions were well conserved, indicating that they were functional. Predicted protein sequences of rat TRAV11 genes were analyzed, including the three loops (CDR1-3) which connect the beta-strands of the domain encoded by the TRA V-REGION and is hypervariable in sequence. The CDR1-IMGT sequence (from 27 to 32; VTPFNN) was conserved among most rat TRAV11 genes. The CDR2-IMGT sequences (from 56 to 61) were grouped into two types: type 1 [L(T/K)NKEE], and type 2 [LAYKKE]. The mRNAs of both types have a different tissue distribution. The CDR3 sequences were short and invariant, the rat TRAV11 genes being preferentially rearranged with rat TRAJ18 (Jalpha281), with the joint consisting of a single amino acid (A or G). Thus, rats had multiple TRAV11 chains with diversified CDR2-IMGT and homogenous CDR1-IMGT and CDR3-IMGT.