Significance of transient left ventricular wall thickening in acute lymphocytic myocarditis

Transient left ventricular (LV) wall thickening is observed in patients with acute lymphocytic myocarditis. The present study was undertaken to clarify the significance of transient LV wall thickening in patients with this disease. The subjects comprised 25 patients with acute lymphocytic myocarditis. Echocardiography was used to measure the thickness of the interventricular septum (IVS) and the LV posterior wall (PW) at four time points after myocarditis onset – namely, on days 1–3, 6–8, 13–15, and 28–30 – to clarify the timing and frequency of wall thickening. The 25 patients were divided into a fulminant myocarditis group (n = 14) and a nonfulminant myocarditis group (n = 11), and the relationship between LV wall thickening and myocarditis severity was investigated. Left ventricular wall thickening was greatest on days 1–3 after myocarditis onset (IVS: 13.3 ± 3.2 mm; PW: 12.1 ± 2.6 mm), with this finding being noted in 14 of the 25 cases (56%). By days 6–8, the thickness of IVS had virtually normalized to 10.6 ± 1.6 mm (P < 0.0001) and that of PW to 10.2 ± 1.4 mm (P = 0.0006). The thickness of the IVS and PW on days 1–3 after myocarditis onset were 14.6 ± 3.7 and 13.0 ± 2.9 mm, respectively, in the fulminant group (P = 0.014), and 11.5 ± 0.9 and 10.9 ± 1.4 mm, respectively, in the nonfulminant group (P = 0.039). In lymphocytic myocarditis, LV wall thickening is greatest on days 1–3 after myocarditis onset and improves to near normal by days 6–8. Such transient LV wall thickening occurs in approximately 50% of cases. Left ventricular wall thickening was more marked in the fulminant compared with the nonfulminant group.     

Determination of medullasin levels for the diagnosis of multiple sclerosis

Medullasin levels in granulocytes of patients with neurological diseases and healthy volunteers were determined by the enzyme immunoassay using mouse monoclonal antibodies against human medullasin and o-phenylenediamine-H2O2 as the detection system of the enzyme activity. One hundred twenty-one out of 159 patients with multiple sclerosis (76.1%) showed positive results (above means of normals + 2SD) in this test, while only 16.9% (24/142) of patients with non-inflammatory neurological diseases had positive results. This enzyme immunoassay method for medullasin is considered to be an useful paraclinical test for the diagnosis of multiple sclerosis.     

Cytologic diagnosis of endosalpingiosis with pregnant women presenting in peritoneal fluid: a case report

The cytologic appearance of endosalpingiosis in peritoneal fluid cytology smears has not been extensively described. We report a case of endosalpingiosis in a 29-year-old pregnant female who presented with peritoneal fluid. Dense papillary epithelial clusters with indistinct ciliated cells were found in the Papanicolaou-stained smears. However, long and delicate cilia were obvious in papillary cluster with scanning electron microscopy. Cell nuclei were oval, with finely dispersed chromatin and uniform nuclear membrane. Peritoneal fluid cytology with these findings may be helpful to suggest the probable preoperative diagnosis of endosalpingiosis or benign glandular inclusions involving the pelvic peritoneum.     

Engagement of human monocyte-derived dendritic cells into interleukin (IL)-12 producers by IL-1beta + interferon (IFN)-gamma

Dendritic cells (DCs) are potent antigen-presenting cells and can induce tumour- or pathogen-specific T cell responses. For adoptive immunotherapy purposes, immature DCs can be generated from adherent monocytes using granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-4, and further maturation is usually achieved by incubation with tumour necrosis factor (TNF)-alpha. However, TNF-alpha-stimulated DCs produce low levels of IL-12. In this study, we compared the effects of TNF-alpha, interferon (IFN)-gamma, IL-1beta or IFN-gamma + IL-1beta on the phenotypic and functional maturation of DCs. Our results show that IFN-gamma, but not IL-1beta, augmented the surface expression of CD80, CD83 and CD86 molecules without inducing IL-12 production from DCs. However, IL-1beta, but not IFN-gamma, induced IL-12 p40 production by DCs without enhancing phenotypic maturation. When combined, IFN-gamma + IL-1beta treatment profoundly up-regulated the expression of CD80, CD83, CD86 and major histocompatibility complex (MHC) class II antigens. Furthermore, IFN-gamma + IL-1beta-treated DCs produced larger amounts of IL-12 and induced stronger T cell proliferation and IFN-gamma secretion in primary allogeneic mixed lymphocyte reaction (MLR) than did TNF-alpha-treated DCs. Our results show that IFN-gamma + IL-1beta induced human monocyte-derived DCs to differentiate into Th1-prone mature DCs.     

The assessment of cell proliferation during 9,10-dimethyl-1,2-benzanthracene-induced hamster tongue carcinogenesis by means of histone H3 mRNA in situ hybridization

The aim of this study was to investigate cell kinetics and ultrastructural changes during carcinogenesis using a hamster 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced tongue cancer model. Five squamous cell carcinomas, five dysplastic epithelia, seven hyperplastic epithelia, and four normal epithelia were obtained from 21 hamster tongues by applying 1.0% acetone solution of DMBA on the left lingual mucosa after scratching with a root canal broach. Ultrastructural examination revealed that the number of microvilli increased, whereas that of desmosomes decreased during carcinogenesis. Cell proliferation was analyzed by means of 5-bromodeoxyuridine (BrdU) immunohistochemistry and in situ hybridization (ISH) for histone H3 mRNA. The BrdU and histone H3 mRNA labeling indices (LIs) were lowest for normal epithelium, higher for hyperplastic and dysplastic epithelia, and highest for squamous cell carcinoma. Cytoplasmic histone H3 mRNA and nuclear BrdU were localized in virtually identical areas of serial sections. The correlation coefficient for the relationship between these two LIs was 0.97 (P 0.001). These results suggest that the assessment of cell proliferation using H3 mRNA ISH will be a useful technique for investigating biological behavior during carcinogenesis.     

Reactivation of Epstein-Barr virus in B cells of patients with chronic hepatitis C

Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders. HCV infection of B cells is a predictive factor for lymphoproliferative disorders in patients with chronic hepatitis C, although its molecular mechanisms remain unknown. Epstein-Barr virus (EBV) is a B cell-tropic virus with the potential to cause lymphoproliferative disorders, and its reactivation is induced by several viruses and cytokines. The possibility that HCV infection triggers reactivation of EBV and induces lymphoproliferative disorders were investigated. Expression of EBV mRNAs was analyzed by RT-PCR in patients infected with HCV and control subjects, and correlations between reactivation of EBV and markers for lymphoproliferative disorders were investigated. BZLF1 mRNA, a starter molecule of reactivation, was detected in peripheral blood mononuclear cells from 12 of 52 (23%), patients infected with HCV and the frequency was higher than in healthy subjects [3 of 43 (9%), P = 0.032]. But the presence of the BZLF1 mRNA was not associated with an abnormality of markers for lymphoproliferative disorders. This study on BZLF1 mRNA expression among lymphoid cell subsets showed that reactivation of EBV was observed specifically in B cells. The BZLF1 mRNA disappeared following anti-viral therapy and remained negative after eradication of HCV in patients with a sustained viral response, while the EBER1 RNA, a marker for persistence of EBV, was detected throughout the therapy. Infection with HCV induces reactivation of EBV in B cells, but this reactivation was not associated directly with lymphoproliferative disorders triggered by HCV.     

Pael receptor induces death of dopaminergic neurons in the substantia nigra via endoplasmic reticulum stress and dopamine toxicity, which is enhanced under condition of parkin inactivation

Selective loss of dopaminergic neurons is the final common pathway in Parkinson's disease. Expression of Parkin associated endothelin-receptor like receptor (Pael-R) in mouse brain was achieved by injecting adenoviral vectors carrying a modified neuron-specific promoter and Cre recombinase into the striatum. Upregulation of Pael-R in the substantia nigra pars compacta of mice by retrograde infection induced endoplasmic reticulum (ER) stress leads to death of dopaminergic neurons. The role of ER stress in dopaminergic neuronal vulnerability was highlighted by their decreased survival in mice deficient in the ubiquitin-protein ligase Parkin and the ER chaperone ORP150 (150 kDa oxygen-regulated protein). Dopamine-related toxicity was also a key factor, as a dopamine synthesis inhibitor blocked neuronal death in parkin null mice. These data suggest a model in which ER- and dopamine-related stress are major contributors to decreased viability of dopaminergic neurons in a setting relevant to Parkinson's disease.     

Changes in interhemispheric inhibition from active to resting primary motor cortex during a fine-motor manipulation task

The effect of performance of a sensorimotor task on the interhemispheric inhibition (IHI) induced from the active primary motor cortex (M1) to the resting M1 was examined in 10 right-handed subjects. Transcranial magnetic stimulation (TMS) was performed to produce motor evoked potentials (MEP) in the resting right (Rt)-first dorsal interosseous (FDI). For the paired-TMS paradigm, a conditioning stimulus (CS) was delivered to the Rt-M1, and its intensity was adjusted from 0.6 to 1.4 times the resting motor threshold of the MEP in the left (Lt)-FDI in 0.2 steps. The test stimulus was delivered to the Lt-M1, and its intensity was adjusted to evoke similar MEP amplitudes in the Rt-FDI among the task conditions. The interstimulus interval was fixed at 10 ms. As a sensorimotor task, a fine-motor manipulation (FM) task (using chopsticks to pick up, transport, and release glass balls) was adopted. In addition, an isometric abduction (IA) task was also performed as a control task. These tasks were carried out with the left hand. The IHI from the active to the resting M1 observed during the FM task was markedly increased compared with that induced during the IA task, and this effect was not dependent on the MEP amplitude evoked in the active Lt-FDI by the CS. The present findings suggest that the increased IHI from the active to the resting M1 observed during the FM task was linked to reductions in the activity of the ipsilateral intracortical inhibitory circuit, as we reported previously.     

Distribution of inositol 1,4,5-trisphosphate receptors in rat osteoclasts

Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are Ca2+ channels that localize to intracellular Ca2+ stores such as the endoplasmic reticulum (ER). Recently, IP3Rs were found to participate in the formation of the cytoskeleton and cellular adhesions. In this study, we examined the cellular localization of type I, II, and III IP3Rs to assess their role in cellular adhesion in rat osteoclasts. Rat bone marrow cells were cultured in alpha-MEM with 10% fetal bovine serum, M-CSF, RANKL, and 1,25(OH)2D3 for 1 week to promote osteoclast formation. Type I, II, and III IP3R expression in the osteoclasts was then examined by RT-PCR. Double-staining was performed using antibodies against type I, II, and III IP3Rs and DiOC6, an ER marker, or TRITC-phalloidin, an actin filament marker. Expression of all three IP3Rs was detected in the newly formed osteoclasts; however, the localization of the type I and II IP3Rs was predominantly close to nuclear, and possibly colocalized with the ER, while the type III IP3Rs were localized to the ER and podosomes, actin-rich adhesion structures in osteoclasts. These findings suggest that type III IP3Rs are associated with osteoclast adhesion.