Detection of nephritogenic antigen from the Lewis rat renal tubular basement membrane

Immunopathogenicity of trypsin-solubilized or non-solubilized renal tubular basement membrane (TBM) of the Lewis (LEW) rat was investigated. Autoimmune tubulointerstitial nephritis (TIN) was induced in BALB/c mice by immunization with trypsin-solubilized LEW rat TBM, while immunization with non-solubilized TBM did not produce the disease. Based on this preliminary experiment we studied the characterization of immunogenic and nephritogenic TBM antigen of the LEW rat. TIN was characterized by severe mononuclear cell infiltrates with multi-nucleated giant cells in the interstitium, tubular destruction and intensive IgG and C3 deposits along the TBM. Anti-TBM antisera and eluate from the nephritic mouse kidneys reacted with the TBM of normal LEW rat kidney by immunofluorescence. LEW rat TBM was also detected immunofluorescently by using antisera from BALB/c mice immunized with autologous trypsin-solubilized TBM. A competitive inhibition test revealed a higher titer of anti-TBM antibody in the eluate than in the adsorption-treated antisera per microgram IgG. Immunoblotting showed one reactive band with a molecular weight of 45,000 daltons, and the blotting patterns in tryptic TBM of the Brown Norway (BN) and LEW rats appeared similar. Amino acid analysis of nephritogenic LEW rat tryptic TBM showed that it contained no hydroxyproline and hydroxylysine, suggesting that this TBM preparation was not collagenous. These findings suggest that tryptic digestion contributes to the release of nephritogenic antigen from the LEW rat TBM and that this antigen system might participate in the immune system involved in the anti-TBM associated TIN that is well known to be induced by non-digested TBM of TBM antigen positive animals.     

Alexithymia and regional gray matter alterations in schizophrenia

Alexithymia is characterized by deficits in emotional self-awareness. Although alexithymia refers to a deficit in recognizing one's own emotions, some studies have focused on the relation between alexithymia and impaired social cognition. An association between alexithymia and schizophrenia has been previously reported, but the brain structures involved remain unclear. The present study investigated associations between alexithymia and specific brain structures to determine whether these regions overlapped with key structures underlying social cognition. Twenty-one patients with schizophrenia and 24 age-, gender- and education level-matched healthy controls underwent structural magnetic resonance imaging. Alexithymia was assessed using the 20-item Toronto Alexithymia Scale (TAS-20). We applied voxel-based morphometry to investigate the correlation between TAS-20 scores and regional brain alterations. TAS-20 scores were significantly higher in patients than controls. Bilateral ventral striatum and left ventral premotor cortex volumes were negatively correlated with TAS-20 total scores in controls, while left supramarginal gyrus (SMG) volume was negatively correlated with TAS-20 total scores in patients. These results suggest that schizophrenia is associated with alexithymia, and that gray matter alterations of the left SMG constitute a key pathology underlying alexithymia in schizophrenia. This association may be related to deficits in self-other distinction, self-disturbance, and language processing in schizophrenia.     

Brain volume and dysexecutive behavior in schizophrenia

Objective

Behaviors associated with frontal/executive impairments are common in patients with schizophrenia. Our aim was to reconfirm that morphological brain abnormalities in schizophrenia patients would overlap the areas underpinning frontal systems behavior, and examine whether any specific association exists between abnormalities of brain structures and frontal behavioral deficits in schizophrenia patients.

Method

Twenty-six schizophrenia patients and 26 matched healthy controls underwent structural magnetic resonance imaging and their frontal function was assessed by a self-rating questionnaire, Frontal Systems Behavior Scale (FrSBe). We applied voxel-based morphometry (VBM) to investigate regional brain volume alternations.

Result

Compared with healthy controls, schizophrenia patients showed reduced gray matter volume in multiple frontal and temporal structures, namely, the bilateral dorsolateral prefrontal cortices (DLPFC), bilateral medial prefrontal cortices, left ventrolateral prefrontal cortex, bilateral anterior cingulate cortices, and bilateral superior temporal gyri. The scores on the executive dysfunction subscale of the FrSBe were correlated with volume reduction in the bilateral DLPFC in the patient group.

Conclusion

Our result suggests that pathology of the DLPFC could be the neural basis of real-life dysexecutive behaviors in schizophrenia patients.