A case of leukemia cutis.

We report a case of leukemia cutis with atypical skin manifestations, presented with generalized various sized dark brownish to erythematous patches with plaques on the whole body of a 42-year-old man. Skin lesions developed 6 months ago and had no signs of itching or tenderness. He complained of sustaining fevers with abdominal discomfort. Laboratory findings showed elevation of leukocyte count and peripheral blood smear revealed 86% of lymphocyte. Histologic examination showed diffuse infiltration of abnormal cells that appeared to be leukemic in nature.     

Differential contribution of the FcRγ chain to the surface expression of the T cell receptor among T cells localized in epithelia: analysis of FcRγ-deficient mice

The function of the Fc receptors γ chain (FcR_γ) for the expression of the T cell receptor (TCR) complex and for T cell development, especially for T cells localized in epithelia, was investigated by analyzing FcR_γ-deficient mice. In wildtype mice, CD8αα⁺β^?TCRαβ⁺ T cells of intestinal intraepithelial lymphocytes (i-IEL) utilized CD3ζ homodimers and ζ-FcR_γ heterodimers, whereas CD8α α⁺β^?TCR_γδ⁺ i-IEL used ζ-FcR_γ and FcR_γ homodimers in the TCR complex. On the other hand, these T cells in FcR_γ-deficient mice contained only ζ homodimers. The surface expression of the TCR complex was reduced in CD8αα⁺β^?i-IEL and dendritic epidermal T cells (DETC) in these mice, whereas the development of these T cells was normal. The degree of reduction appeared to depend on the expression level of FcR_γ. In contrast to these populations, TCR_γδ⁺ intraepithelial T cells in reproductive organs (r-IEL) were dramatically decreased, suggesting that the development of r-IEL is FcR_γ-dependent, probably due to the predominant usage of FcR_γ homodimers in the TCR complex. These results indicate that the FcR_γ chain contributes differently to the TCR expression and to the development of T cells localized in epithelia.     

CM1 ligation initiates apoptosis in a caspase 8-dependent manner in Ramos cells and in a mitochondria-controlled manner in Raji cells

Burkitt lymphoma (BL) is a tumor with the characteristics of germinal center B cells. We previously reported that the CM1 (centrocyte/-blast marker 1) molecule is expressed only in germinal center B cells, specifically, in a subpopulation of centroblasts and centrocytes. In the present study, we investigated the apoptosis induced by anti-CM1 in the Ramos and Raji human BL cell lines. The Ramos is protected from apoptosis by the crosslinking of sIgM and the calcium ionophore by the ligation of CD40 with anti-CD40 monoclonal antibodies (mAb) or soluble CD40 ligand (sCD40L). In this investigation on the effect of CM1 on apoptosis in BL cell lines, we found that cellular signaling by CM1 induces apoptosis and decreases cell viability, in BL cell lines cultured for 24 hours with protein-G agarose beads conjugated anti-CM1 mAb. Stimulation by CD40 ligated with sCD40L protected Raji cells from CM1-induced apoptosis, but did not protect Ramos cells. Furthermore, after anti-CM1 mAb stimulation, CD95 expression was upregulated and CD40 expression was unaltered or slightly decreased in Ramos cells, whereas CD95 was downregulated and CD40 was slightly upregulated in Raji cells. The engagement of CD40 by sCD40L enhanced CD95 expression, but the level of CM1 expression was unchanged in Ramos. However, sCD40L downregulated both CD95 and CM1 expression in Raji. In addition, the caspase-8 specific inhibitor blocked CM1-induced apoptosis in Ramos cells, but not in Raji cells. Increased mitochondrial membrane permeabilization was observed only in Raji cells. Moreover, the effector caspase inhibitor, z-DEVD, blocked CM1-mediated apoptosis in both cell lines. We found that CM1-induced apoptosis is achieved via different initiation pathways, which are cell-type dependent.     

Thymocyte-thymocyte interaction for efficient positive selection and maturation of CD4 T cells

Despite numerous reports on MHC class II expression by T cells from a wide spectrum of mammalian species including humans, the biological relevance of this phenomenon has never been tested with appropriately designed animal models. To address this issue, we developed mouse models in which immature thymocytes are the only positively selecting antigen-presenting cells in the thymus. In these mice, CD4+ T cells were generated with the appropriate maturation phenotype and showed a diverse repertoire of TCR Vbetas. The CD4+ T cells were functionally competent, mediating effective allogeneic responses that involved polyclonal TCR Vbetas. These results suggest that the thymocyte-thymocyte (T-T) interaction operates as an independent pathway for CD4+ T cell selection in the thymi of species with MHC II-positive thymocytes. This T-T interaction appears to be the basis for the generation of donor MHC-restricted CD4+ T cells in xenogeneic hosts.     

Molecular targets of dietary polyphenols with anti-inflammatory properties

There is persuasive epidemiological and experimental evidence that dietary polyphenols have anti-inflammatory activity. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) have long been used to combat inflammation. Recently, cyclooxygenase (COX) inhibitors have been developed and recommended for treatment of rheumatoid arthritis (RA) and osteoarthritis (OA). However, two COX inhibitors have been withdrawn from the market due to unexpected side effects. Because conventional therapeutic and surgical approaches have not been able to fully control the incidence and outcome of many inflammatory diseases, there is an urgent need to find safer compounds and to develop mechanism-based approaches for the management of these diseases. Polyphenols are found in many dietary plant products, including fruits, vegetables, beverages, herbs, and spices. Several of these compounds have been found to inhibit the inflammation process as well as tumorigenesis in experimental animals; they can also exhibit potent biological properties. In addition, epidemiological studies have indicated that populations who consume foods rich in specific polyphenols have lower incidences of inflammatory disease. This paper provides an overview of the research approaches that can be used to unravel the biology and health effects of polyphenols. Polyphenols have diverse biological effects, however, this review will focus on some of the pivotal molecular targets that directly affect the inflammation process.     

Clinical Comparison of Distal Pancreatectomy with or without Splenectomy

The spleen may be preserved during distal pancreatectomy (DP) for benign disease. The aim of this study was to compare the perioperative and postoperative courses of patients with conventional DP and spleen-preserving distal pancreatectomy (SPDP) for benign lesions or tumors with low-grade malignant potential occurred at the body or tail of the pancreas. A retrospective analysis was performed for the hospital records of all the patients undergoing DP and SPDP between January 1995 and April 2006. One-hundred forty-three patients underwent DP and 37 patients underwent SPDP. There were no significant differences in age, sex, indications of operation, estimated blood loss, operative time, and postoperative hospital stay between the two groups. Pancreatic fistula occurred in 21 (13.3%) patients following DP and in 3 (8.1%) following SPDP without a significant difference (p=0.081). Portal vein thrombosis occurred in 4 patients after DP. Splenic infarction occurred in one patient after SPDP. Overwhelming postosplenectomy infection was observed in one patient after DP. SPDP can be achieved with no increase in complication rate, operative time, or length of postoperative hospitalization as compared to conventional DP. Additionally, it has the advantage of reducing the risk of overwhelming postsplenectomy infection and postoperative venous thrombosis.     

Redox regulation of mammalian heat shock factor 1 is essential for Hsp gene activation and protection from stress

The activation of eukaryotic heat shock protein (Hsp) gene expression occurs in response to a wide variety of cellular stresses including heat shock, hydrogen peroxide, uncoupled oxidative phosphorylation, infection, and inflammation. Biochemical and genetic studies have clearly demonstrated critical roles for mammalian heat shock factor 1 (HSF1) in stress-inducible Hsp gene expression, resistance to stress-induced programmed cell death, extra-embryonic development, and other biological functions. Activation of mammalian Hsp gene expression involves the stress-inducible conversion of HSF1 from the inactive monomer to the DNA-binding competent homotrimer. Although Hsp activation is a central conserved process in biology, the precise mechanisms for stress sensing and signaling to activate HSF1, and the mechanisms by which many distinct stresses activate HSF1, are poorly understood. In this report we demonstrate that recombinant mammalian HSF1 directly senses both heat and hydrogen peroxide to assemble into a homotrimer in a reversible and redox-regulated manner. The sensing of both stresses requires two cysteine residues within the HSF1 DNA-binding domain that are engaged in redox-sensitive disulfide bonds. HSF1 derivatives in which either or both cysteines were mutated are defective in stress-inducible trimerization and DNA binding, stress-inducible nuclear translocation and Hsp gene trans-activation, and in the protection of mouse cells from stress-induced apoptosis. This redox-dependent activation of HSF1 by heat and hydrogen peroxide establishes a common mechanism in the stress activation of Hsp gene expression by mammalian HSF1.     

Clinical prognostic values of vascular endothelial growth factor, microvessel density,and p53 expression in esophageal carcinomas

Vascular endothelial growth factor (VEGF) is known to play a key role in tumor angiogenesis. The tumor-suppressor gene p53 has been thought to regulate VEGF. We investigated the effect of VEGF on esophageal carcinoma and the correlation between VEGF and p53. Tissue samples were taken from 81 patients with esophageal carcinoma after surgery. VEGF and p53 expressions were examined by immunohistochemical staining. Microvessels in the tumor stained for CD34 antigen were also counted. VEGF and p53 expressions were observed in 51.3% (41/80) and 51.9% (41/79), respectively. The microvessel density was 70.9+/-6.7 (mean+/-SE) in VEGF-positive group and 68.7+/-5.1 in VEGF-negative group. However, no correlation was noted between VEGF and p53 expression. Whereas the tumor size, nodal status, depth of invasions, and tumor stage were associated with poor overall survival, VEGF expression or p53 expression was not. These results indicate that VEGF and p53 are highly expressed in esophageal carcinomas. Since the VEGF expression is not correlated with the p53 expression, microvessel density or clinicopathological findings, further studies with other angiogenic molecules are needed to determine the role in esophageal carcinomas.     

Morphometric evaluation of PGP9.5 and NCAM expressing nerve fibers in colonic muscle of patients with Hirschsprung's disease

A quantitative assessment of the density of the protein gene product 9.5 (PGP9.5), the neural cell adhesion molecule (NCAM), and the low-affinity nerve growth factor receptor (NGFR) expressing nerve fibers in the circular muscle layer in the colon was carried out by morphometric analyses from 13 patients with Hirschsprung's disease (HD). The difference in the nerve fiber density between the ganglionic and aganglionic segments was compared by calculating the ratio of the sum of the areas occupied by positively stained nerve fibers per unit area of the muscle after immunohistochemical staining on paraffin embedded tissue sections using computer software. There was an obvious difference in the density of the PGP9.5 stained nerve fibers between the ganglionic (0.0380 +/- 0.0171) and aganglionic segments (0.0143 +/- 0.01661). The NCAM-positive nerve fibers were fewer in number than those of both the PGP9.5-positive fibers and NCAM-positive fibers, which were also markedly lower in number in the aganglionic segment (0.0066 +/- 0.0076) than in the ganglionic segment (0.0230 +/- 0.0195). Immunostaining for low-affinity NGFR revealed much fainter staining in the ganglionic and aganglionic segment without a statistically significant difference in their density. Considering the fact that PGP9.5 is a very sensitive marker for nerve fibers, the results of this study reaffirm the innervation failure of the proper muscle in HD. The decreased NCAM expression level in the aganglionic segment appears to be caused not by the selective down-regulation of NCAM expression among the nerve fibers but by a markedly reduced number of nerve fibers.     

Effect of ketamine on apoptosis by energy deprivation in astroglioma cells using flow cytometry system

Apoptosis is a programmed, physiologic mode of cell death that plays an important role in tissue homeostasis. As for the central nervous system, ischemic insults can induce pathophysiologic cascade of apoptosis in neurophils. Impairment of astrocyte functions during brain ischemia can critically influence neuron survival by neuronglia interactions. We aimed to elucidate the protective effect of ketamine on apoptosis by energy deprivation in astrocytes. Ischemic insults was induced with iodoacetate/ carbonylcyanide m-chlorophenylhydrazone (IAA/CCCP) 1.5 mM/20 microm or 150 microm/2 microm for 1 hr in the HTB-15 and CRL-1690 astrocytoma cells. Then these cells were reperfused with normal media or ketamine (0.1 mM) containing media for 1 hr or 24 hr. FITC-annexin-V staining and propidium iodide binding were determined by using flow cytometry. Cell size and granularity were measured by forward and side light scattering properties of flow cytometry system, respectively. An addition of ketamine during reperfusion increased the proportion of viable cells. Ketamine alleviated cell shrinkage and increased granularity during the early period, and ameliorated cell swelling during the late reperfusion period. Ketamine may have a valuable effect on amelioration of early and late apoptosis in the astrocytoma cells, even though the exact mechanism remains to be verified.