Pemphigus Vulgaris Associated with Autoimmune Hemolytic Anemia and Elevated TNFα

A 76-year-old female was admitted with many bullae and erythema on her trunk and extremities. A biopsy specimen showed significant intercellular edema in the lower epidermis and eosinophilic infiltration into the dermis and the epidermis. Immunofluorescent staining revealed the deposition of IgG in the intercellular area of her prickle cells. From these histologic findings and the typical clinical features, we diagnosed her as having pemphigus vulgaris. Examination of her blood revealed that she also suffered from autoimmune hemolytic anemia. Despite intensive treatment with prednisolone, she finally died. This case is of interest because of its rarity and the TNFα detected significantly in the blister fluid of this patient.     

Effects of prostaglandin E2 on Th0-type human T cell clones: modulation of functions of nuclear proteins involved in cytokine production

The effects of prostaglandin E₂ (PGE₂) on cytokine productionand proliferation of the CD4⁺ human helper T cell clone SP-B21were investigated. In cells stimulated with antl-CD3 mAb, PGE₂inhibited cell proliferation and the production of all the cytokinesexamined. Addition of rlL-2 fully restored the prollferatlveresponse and partially restored the production of IL-4 and IL-5,but not that of other cytokines. In contrast, In cells stimulatedwith phorbol myrlstate acetate (PMA)/A23187, PGE₂ enhanced theproduction of IL-4 and IL-5, and only partially inhibited theproduction of other cytokines. Therefore, the effects of PGE₂vary depending on the mode of T cell activation, and the IL-4and IL-5 are regulated differently from other cytokines. Ina mobility shift assay, only the NF-B (p50/p5O) homodlmer wasobserved in a complex formed with the B sequence in unstlmulatedSP-B21 cells. When cells were stimulated with antl-CD3 mAb orPMA/A23187, a complex formation of NF-B (p50/p65) heterodlmerwith the B sequence was induced. Interestingly, PGE₂ or di-butyryl(Bt₂cAMP abolished the binding of NF-B (p50/p65) heterodlmerto the B sequence in cells stimulated with antl-CD3 mAb butnot with PMA/A23187. Our results suggest that the target ofPGE₂ action is a component in the signal transductlon pathwayleading to the activation of protein klnase C. However, theinhibition of the T cell activation signals by PGE₂ is selective.PGE₂ enhanced the complex formation with NF-AT, AP-1 and CLEOsequences when the cells were activated by either anti-CD3 mAbor PMA/A23187 stimulation. It seems therefore that PGE₂, byelevating cAMP levels, interferes with the activation pathwayfor NF-B but not for NF-AT, AP-1 or CLEO binding protein.     

Genetic polymorphism of red cell enzymes (AcP,EsD, GPT, 6-PGD) and of serum protein(Gc) in Fukushima Prefecture

Journal of Human Genetics - Genetic polymorphism of red cell enzymes (AcP, EsD, GPT, 6-PGD) and of serum protein(Gc) in Fukushima Prefecture     

Altered EphA5 mRNA expression in rat brain with a single methamphetamine treatment

Methamphetamine is a potent and indirect dopaminergic agonist which can cause chronic brain dysfunctions including drug abuse, drug dependence and drug-induced psychosis. Methamphetamine is known to trigger molecular mechanisms involved in associative learning and memory, and thereby alter patterns of synaptic connectivity. The persistent risk of relapse in methamphetamine abuse, dependence and psychosis may be caused by such alterations in synaptic connectivity. EphA5 receptors constitute large families of tyrosine kinase receptor and are expressed almost exclusively in the nervous system, especially in the limbic structures. Recent studies suggest EphA5 to be important in the topographic projection, development, and plasticity of limbic structures, and to be involved in dopaminergic neurotransmission. We used in situ hybridization to examine whether methamphetamine alters EphA5 mRNA expression in the brains of adult male Wister rats. EphA5 mRNA was widely distributed in the medial frontal cortex, cingulate cortex, piriform cortex, hippocampus, habenular nucleus and amygdala. Compared to baseline expression at 0 h, EphA5 mRNA was significantly decreased (by 20%) in the medial frontal cortex at 24 h, significantly increased (by 30%) in the amygdala at 9 and 24 h, significantly but transiently decreased (by 30%) in the habenular nucleus at 1 h after a single injection of methamphetamine. Methamphetamine did not change EphA5 mRNA expression in the cingulate cortex, piriform cortex or hippocampus. Our results that methamphetamine altered EphA5 mRNA expression in rat brain suggest methamphetamine could affect patterns of synaptic connectivity, which might be responsible for methamphetamine-induced chronic brain dysfunctions.     

Characterization of connectin-like proteins of obliquely striated muscle of a polychaete (Annelida)

Summary In obliquely striated muscle of polychaete, Neanthes sp., three kinds of connectin (titin)-like high molecular weight proteins, 4000 kDa, 1200 kDa and 700 kDa, were detected by SDS gel electrophoresis and immunoblots using antibodies to vertebrate skeletal muscle connectin and antiserum to the protein in question. The 700 kDa protein was isolated and characterized as a sheet-rich filament 170 nm long and 4 nm wide. Using polyclonal antibodies to the 700 kDa protein, the binding of the immunogold to the thick filament was only demonstrated in high ionic strength relaxing solution which solubilized some myosin. This observation suggested that the 700 kDa protein was localized below the layers of myosin in the thick filament and this localization is different from that of twitchin of C. elegans bodywall muscle that is on the surface of thick filament. The 4000 kDa protein was identified as a very thin filament linking the thick filament to the dense body. The very thin filaments were visualized in gelsolin-treated actin filament-free fibres. The 1200 kDa protein was located in the periphery of the dense body. A model of the elastic filament in polychaete bodywall muscle is presented.     

Cognitive Behavioral Therapy of Minor Depressive Symptoms in Elderly Chinese Americans: A Pilot Study

There is a high prevalence of suicide amongelderly Chinese, and particularly among elderly Chinesewomen in Mainland China with a prevalence of 19.6 perhundred thousand. Since Chinese individuals may much more highly value education, acognitive-behavioral package originated by RicardoMunoz, Ph.D. was adapted for Chinese American subjects.The material was videotaped in eight sessions,approximately 25 minutes in length, to be shown to communitysubjects who were at least 40 years and over. Inaddition, a videotape of muscular relaxation techniqueswas made. A manual written in Chinese about the content of each class, was given to each subject whenhe/she attended. The experimental group showedsignificant improvement in the scores in the HamiltonDepression Scale, including the Somatic Subscale in the Hamilton Anxiety Scale. There was nosignificant improvement in the control group on any ofthe measures. Thus the study suggests the efficacy ofpsychoeducational classes in reducing symptoms ofdepression in non-patient community elderly. Other studiesare being conducted among Korean Americans and JapaneseAmericans in the United States, and also in the Orientamong Japanese elderly.     

Plasma cell leukemia with lobulated nuclei: One case report

The case of an 80-year-old man with plasma cell leukemia characterized by basophilic cytoplasm, and extensive lobulated nuclei is described. In spite of the peculiar morphologic nuclei, the diagnosis was based on the presence of M protein and Bence Jones protein in the serum and urine, immunophenotypic characteristics, immunoglobulin gene rearrangement, and findings of transmission electron microscopy.     

RAS-blocking bisphosphonate zoledronic acid inhibits the abnormal proliferation and differentiation of juvenile myelomonocytic leukemia cells in vitro

Juvenile myelomonocytic leukemia (JMML) is a clonal myeloproliferative/myelodysplastic disorder of early childhood with a poor prognosis. JMML cells are characterized by hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF) caused by a continuously activated GM-CSF receptor-retrovirus-associated sequence (RAS) signal transduction pathway through various molecular mechanisms, resulting in spontaneous GM colony formation in vitro. Bisphosphonate zoledronic acid (ZOL), a RAS-blocking compound, suppressed colony formation from bone marrow (BM) cells of 8 patients with JMML and 5 healthy control subjects without and with GM-CSF (10 ng/mL), respectively, in a dose-dependent manner in clonal culture. At 10 microM ZOL, however, spontaneous GM colony formation from JMML BM cells decreased to 3%, but the formation of G colonies containing granulocytes, but no macrophages, was enhanced, whereas 40% of GM colonies were retained and G colony formation was not affected in culture of normal BM cells with GM-CSF. In suspension culture, cytochemical and flow cytometric analyses showed that 10 microM ZOL also inhibited spontaneous proliferation and differentiation along monocyte/macrophage lineage of JMML BM cells but not the development of normal BM cells by GM-CSF. The inhibitory effect of ZOL on JMML cells was confirmed at a single-clone level and observed even at 3 microM. The current result offers a novel approach to therapy in JMML.     

Pitavastatin, an HMG-CoA reductase inhibitor, exerts eNOS-independent protective actions against angiotensin II induced cardiovascular remodeling and renal insufficiency

Angiotensin II (Ang II) plays a pivotal role in cardiovascular remodeling leading to hypertension, myocardial infarction, and stroke. Pitavastatin, an HMG-CoA reductase inihibitor, is known to have pleiotropic actions against the development of cardiovascular remodeling. The objectives of this study were to clarify the beneficial effects as well as the mechanism of action of pitavastatin against Ang II-induced organ damage. C57BL6/J mice at 10 weeks of age were infused with Ang II for 2 weeks and were simultaneously administered pitavastatin or a vehicle. Pitavastatin treatment improved Ang II-induced left ventricular hypertrophy and diastolic dysfunction and attenuated enhancement of cardiac fibrosis, cardiomyocyte hypertrophy, coronary perivascular fibrosis, and medial thickening. Ang II-induced oxidative stress, cardiac TGFbeta-1 expression, and Smad 2/3 phosphorylation were all attenuated by pitavastatin treatment. Pitavastatin also reduced Ang II-induced cardiac remodeling and diastolic dysfunction in eNOS-/- mice as in wild-type mice. In eNOS-/- mice, the Ang II-induced cardiac oxidative stress and TGF-beta-Smad 2/3 signaling pathway were enhanced, and pitavastatin treatment attenuated the enhanced oxidative stress and the signaling pathway. Moreover, pitavastatin treatment reduced the high mortality rate and improved renal insufficiency in Ang II-treated eNOS-/- mice, with suppression of glomerular oxidative stress and TGF-beta-Smad 2/3 signaling pathway. In conclusion, pitavastatin exerts eNOS-independent protective actions against Ang II-induced cardiovascular remodeling and renal insufficiency through inhibition of the TGF-beta-Smad 2/3 signaling pathway by suppression of oxidative stress.