Pancreatic mass lesions associated with raised concentration of IgG4

Autoimmune pancreatitis (AIP) is a recognized benign disease characterized by irregular narrowing of the pancreatic duct, swelling of parenchyma, lymphoplasmacytic infiltration and fibrosis, and a favorable response to corticosteroid treatment. In this condition, the whole pancreas is diffusely affected. Recently, however, a few cases with locally affected lesions were reported, with some of them showing features similar to cancer. We reviewed 138 patients with pancreatic mass lesion, of which 17 were not initially diagnosed despite examinations. Serum IgG4 levels were elevated in seven of them. Their biopsy specimens had a similar appearance to those of AIP. We considered that they should be diagnosed as AIP or conditions related to AIP. Among the 10 patients without elevated IgG4, 4 patients were diagnosed as pancreatic cancer after follow-up, 1 presented with an islet cell tumor, 1 presented AIP with sclerosing cholangitis, and the other 4 had chronic pancreatitis.     

Clear cell carcinoma of the pancreas: an adenocarinoma with unusual phenotype of duct cell origin

Although clear cell carcinoma has been found in various organs, only six cases have been reported in the pancreas. Moreover, the histogenesis of clear cell carcinoma of the pancreas remains controversial. We report a case of clear cell carcinoma of the pancreas in a 61-year-old woman, with an unusual pheno- or genotype detected by histochemical, immunohistochemical, and K-ras oncogene analyses. Histologically, the pancreatic tumor was predominantly composed of clear cell nests with scanty fibrous stroma and scattered duct-like structures. Neither clear cell nor duct-like components of the tumor showed mucin production. Immunohistochemical analysis of neoplastic cells showed a positive reaction to antibodies against cytokeratins 8 and 19, carbohydrate antigen 19-9, and α-1-antitrypsin, and showed no reaction to antibodies against carcinoembryonic antigen, neuroendocrine markers, trypsin, amylase, and HMB45. K-ras analysis revealed no mutation at codon 12 in either clear cell or duct-like components. The patient has had no recurrence as yet. The pancreatic carcinoma in our patient may be of duct cell origin, but the results of histochemical, immunohistochemical, and gene analyses and patient’s outcome were unusual compared with those of previous cases.     

Positive association between T-182C polymorphism in the norepinephrine transporter gene and susceptibility to major depressive disorder in a japanese population

Norepinephrinergic neurotransmission in the central nervous system appears to have a major impact on the symptomatology in major depressive disorder and the human norepinephrine transporter (NET) gene is one of the key candidates for genetic studies in major depressive disorder. The authors established a new allele-specific PCR-based genotyping procedure and examined whether the NET T-182C polymorphism was associated with the susceptibility to major depressive disorder in a Japanese population. This study included 145 patients with major depressive disorder (according to DSM-IV) and 164 healthy volunteers. There was a significant difference in the genotype distribution between major depressive disorder patients and healthy volunteers (p = 0.02), and the C/C genotype was associated with lesser susceptibility to major depressive disorder. The NET T-182C polymorphism may be in part related to the pathophysiology of major depressive disorder in a Japanese population.     

Expression and possible role of neuronal calcium sensor-1 in the cerebellum

Neuronal calcium sensor-1 (NCS-1) is a member of EF-hand calcium-binding protein superfamily, which is considered to modulate synaptic transmission and plasticity. In this mini-review, we first summarize distribution of NCS-1 in the cerebellum. NCS-1 is mainly detected in postsynaptic sites, such as somata and dendrites of Purkinje cells, stellate/basket cells and granule cells. In addition, GABAergic inhibitory stellate/basket cell axon terminals also contain NCS-1. Secondly, we describe cerebellar compartmentation defined by NCS-1. The NCS-1 immunostaining displayed characteristic parasagittal-banding pattern in the Purkinje cell layer and molecular layer, whereas there were no apparent bands in the granule cell layer. The alternating positively and negatively NCS-1-labeled Purkinje cell clusters contributed to this cerebellar compartmentation. In contrast, stellate/basket cells were uniformly NCS-1-positive throughout the cerebellum. Interestingly, NCS-1 and zebrin II exhibited a similar parasagittal-banding pattern. But it is noteworthy that NCS-1-negative/zebrin II-positive Purkinje cell clusters were detected selectively in anterior lobule vermis and paraflocculus. These results suggest that NCS-1 defines a novel pattern of cerebellar cortical compartmentation. Lastly, we describe recent data suggesting some relationship between NCS-1 and cerebellar long-term depression-related molecules, and discuss the possible role of NCS-1 in the cerebellum.     

PCR and PCR-RFLP techniques targeting the DNA topoisomerase II gene for rapid clinical diagnosis of the etiologic agent of dermatophytosis

BACKGROUND: We have focused on the DNA topoisomerase II genes of several pathogenic fungi, and developed polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP) methods targeting this gene for identification of dermatophytes. OBJECTIVE: To assess the availability of the PCR-based identification for an etiologic study of dermatophytosis, by testing these PCR and PCR-RFLP methods for stability and reproducibility. METHODS: Three hundred and fifty-six dermatophyte strains were isolated from 305 patients with tinea, and their genomic DNAs were used as templates for the PCR using primer mixes (PsT, PsME, dPsD1 or dPsD2) composed of gene-specific primers for identification of dermatophytes to the species level. The genomic DNAs of Trichophyton rubrum were further subjected to subrepeat element analysis of the nontranscribed spacer (NTS) of ribosomal DNA (rDNA). RESULTS: In this study, six dermatophyte species (T. rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Microsporum canis, Microsporum gypseum, and Epidermophyton floccosum) were obtained. In all cases, the identifications obtained from the PCR and PCR-RFLP targeting the DNA topoisomerase II gene coincided with those from the conventional morphological features-based identification technique. The sensitivity of the PCR-based identification was found to be a colony of approximately 3mm in diameter. Furthermore, T. rubrum was divided into three groups (17 types) on the basis of the sizes and numbers of the products generated from the TRS-1 region, and three types from the TRS-2 region. CONCLUSION: The PCR and PCR-RFLP targeting the DNA topoisomerase II gene were rapid, stable, and reproducible for species identification of dermatophytes, and thus are convenient tools for an etiologic study of dermatophytosis.     

Role of TGF-beta2 in the human hair cycle

Male pattern baldness is the result of premature entry into catagen due to androgens. In order to prevent hair loss, it is important to understand two critical steps, i.e., the induction mechanism of premature entry and the regression process of catagen. At the initiation, dihydrotestosterone (DHT) stimulates synthesis of transforming growth factor-beta2 (TGF-beta2) in dermal papilla cells. TGF-beta2 suppresses proliferation of epithelial cells and stimulates synthesis of certain caspases. Then TGF-beta2 triggers the intrinsic caspase network and subsequently epithelial cells are eliminated through apoptotic cell death. TGF-beta antagonists are effective in preventing catagen-like morphological changes and in promoting elongation of hair follicles in vivo and in vitro. These lines of evidence strongly suggest the presence of a "catagen cascade" in male pattern baldness, involving: (1) the conversion of testosterone to DHT by type II 5-alpha-reductase; (2) the synthesis of TGF-beta2 in dermal papilla cells; and (3) the activation of the intrinsic caspase network. These sequential events contribute to the shortening of the human hair cycle.     

Accumulation of protein-bound 4-hydroxy-2-hexenal in spinal cords from patients with sporadic amyotrophic lateral sclerosis

4-Hydroxy-2-hexenal (HHE) is a toxic, reactive aldehydic intermediate formed by nonenzymatic peroxidation of n-3 polyunsaturated fatty acids. The aim of this study was to determine the implication for HHE in the pathomechanism of amyotrophic lateral sclerosis (ALS) by immunohistochemical and enzyme-linked immunosorbent assay (ELISA) techniques using a mouse monoclonal IgG(1) antibody mAbHHE53 specific for protein-bound HHE. Immunohistochemical analysis on formalin-fixed, paraffin-embedded sections and frozen sections of spinal cords obtained at autopsy from 10 sporadic ALS patients and 10 age-matched control subjects demonstrated that protein-bound HHE immunoreactivity was seen and was prominent in the entire gray matter in the ALS cases and localized in the neurons, reactive astrocytes, microglial cells, and the surrounding neuropil, while the immunoreactivity was obscure or undetectable in the control cases. No significant protein-bound HHE immunoreactivity was seen in sections processed with omission of mAbHHE53 or in sections incubated with the antibody with an excess of the respective antigen. Competitive ELISA analysis on trypsin-digested protein extracts of fresh-frozen spinal cord samples disclosed a significant increase in protein-bound HHE level in the ALS cases compared with the control cases. Our results indicate that enhanced HHE formation occurs in the entire gray matter of sporadic ALS spinal cords and suggest that the selective vulnerability of motor neurons to HHE mediates the pathomechanism of this disease.