DNA content and expression of tumour markers in germ cells adjacent to germ cell tumours in childhood: Probably A different origin for infantile and adolescent germ cell tumours

The origin of testicular germ cell tumours occurring during childhood is poorly understood. In adults, the classical seminomas and non-seminomas originate from carcinoma in situ of the testis, which can usually also be detected in seminiferous tubules adjacent to the tumours. In order to contribute with information regarding a possible association between carcinoma in situ and the childhood group of germ cell tumours, we investigated seminiferous tubules adjacent to 13 infantile yolk sac tumours, five infantile teratomas, and six adolescent germ cell tumours of various types, using morphological evaluation, immunohistochemical staining with markers for carcinoma in situ cells, and densitometric DNA measurement of the germ cells. We detected clear differences between the germ cell populations adjacent to adolescent and infantile germ cell tumours. The former were associated with both normal germ cells and carcinoma in situ cells. The presence of carcinoma in situ cells strongly suggested that the adolescent tumours arose from carcinoma in situ cells, like germ cell tumours occurring in adult men. Although we were in doubt in two cases, the infantile germ cell tumours were in general not associated with carcinoma in situ cells. The aetiology of infantile yolk sac tumours and teratomas may therefore be fundamentally different from that of adolescent and adult germ cell tumours. The origin of yolk sac tumours and teratomas remains to be elucidated.     

Evidence for the involvement of the posterior parietal cortex in coordination of fingertip forces for grasp stability in manipulation

Grasp stability during object manipulation is achieved by the grip forces applied normal to the grasped surfaces increasing and decreasing in phase with increases and decreases of destabilizing load forces applied tangential to the grasped surfaces. This force coordination requires that the CNS anticipates the grip forces that match the requirements imposed by the self-generated load forces. Here, we use functional MRI (fMRI) to study neural correlates of the grip-load force coordination in a grip-load force task in which six healthy humans attempted to lift an immovable test object held between the tips of the right index finger and thumb. The recorded brain activity was compared with the brain activity obtained in two control tasks in which the same pair of digits generated forces with similar time courses and magnitudes; i.e., a grip force task where the subjects only pinched the object and did not apply load forces, and a load force task, in which the subjects applied vertical forces to the object without generating grip forces. Thus neither the load force task nor the grip force task involved coordinated grip-load forces, but together they involved the same grip force and load force output. We found that the grip-load force task was specifically associated with activation of a section of the right intraparietal cortex, which is the first evidence for involvement of the posterior parietal cortex in the sensorimotor control of coordinated grip and load forces in manipulation. We suggest that this area might represents a node in the network of cortical and subcortical regions that implement anticipatory control of fingertip forces for grasp stability.     

Histopathological characteristics of small diameter melanocytic naevi

BACKGROUND/AIMS: The clinical definition of an atypical naevus ("dysplastic naevus" or "naevus with architectural disorder and cytological atypia of melanocytes") stresses size larger than 5 mm in diameter as a major diagnostic criterion. Because malignant melanomas and their precursors may arise in smaller lesions, a histological study of melanocytic lesions smaller than 4 mm in diameter was conducted to evaluate their histological appearance. METHODS: Two hundred and sixty one naevi smaller than 4 mm in diameter were collected and characterised by histological examination into benign naevi without architectural disorder and naevi with architectural disorder and mild, moderate, and severe atypical melanocytes according to criteria used on larger lesions. RESULTS: Small melanocytic naevi covered the same complex histological spectrum from benign naevi to severely atypical naevi when compared with larger lesions. A high proportion of small naevi (72%) exhibited features diagnostic for naevi with architectural disorder and cytological atypia. CONCLUSION: There is a discrepancy between histological and clinically defined atypical naevi. The same generally accepted criteria for the histological diagnosis of atypical naevi should be used for small melanocytic naevi in addition to large ones. Thus, small naevi exhibiting atypical features on histological examination should be categorised as atypical naevi, regardless of their small diameter.     

Modulation of activity in medial frontal and motor cortices during error observation

We used measures of the human event-related brain potential (ERP) to investigate the neural mechanisms underlying error processing during action observation. Participants took part in two conditions, a task execution condition and a task observation condition. We found that activity in both the medial frontal cortex and the motor cortices, as measured via the error-related negativity and the lateralized readiness potential, respectively, was modulated by the correctness of observed behavior. These data suggest that similar neural mechanisms are involved in monitoring one's own actions and the actions of others.     

Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions

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Imbalanced secondary mucosal antioxidant response in inflammatory bowel disease

Intestinal mucosal damage in the inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC) involves reactive oxygen metabolites (ROMs). ROMs are neutralized by endogenous antioxidant enzymes in a carefully balanced two-step pathway. Superoxide dismutases (SODs) convert superoxide anion to hydrogen peroxide (H(2)O(2)), which is subsequently neutralized to water by catalase (CAT) or glutathione peroxidase (GPO). Remarkably changed expression levels of the three isoforms of SOD in paired non-inflamed and inflamed mucosae from CD and UC patients have been previously reported in comparison to normal control mucosa. Most notable was the strong up-regulation of Mn-SOD in inflamed epithelium. It was hypothesized that in order to provide optimal protection against ROM-mediated damage, these changes should be coordinately counterbalanced by an increased H(2)O(2)-neutralizing capacity. Therefore, the same tissue samples were used to assess the levels, activities, and/or localization of the most prominent mucosal H(2)O(2)-related antioxidants CAT, GPO, glutathione (GSH), myeloperoxidase (MPO), and metallothionein (MT). Quantitative measurements showed that in both CD and UC patients, intestinal inflammation was associated with increased activities of CAT, GPO, and MPO, whereas the mucosal GSH content was unaffected and the concentration of MT was decreased. Despite this overall increase in mucosal H(2)O(2)-metabolizing enzyme capacity, immunohistochemical analysis revealed a differentially disturbed antioxidant balance in IBD epithelium and lamina propria. In the lamina propria, the risk of direct H(2)O(2)-mediated damage seemed to be restrained by the increasing numbers of CAT- and MPO-positive monocytes/macrophages and neutrophils that infiltrated the inflamed areas. On the other hand, MPO overexpression might increase the lamina propria levels of hypochlorous acid, a stable ROM with multiple pro-inflammatory effects. In the epithelium, the number of cells that expressed CAT remained unchanged during inflammation and GPO was found in only a very low and constant number of epithelial cells. In addition, the inflamed epithelium displayed decreased expression of the hydroxyl radical (OH(*)) scavenger MT. In view of the high epithelial SOD levels in inflamed IBD epithelium, it is speculated that the efficient removal of excess H(2)O(2) is hampered in these cells, thereby increasing not only the risk of detrimental effects of H(2)O(2) directly, but also those of its extremely reactive derivatives such as OH(*). Taken together, the results suggest an imbalanced and inefficient endogenous antioxidant response in the intestinal mucosa of IBD patients, which may contribute to both the pathogenesis and the perpetuation of the inflammatory processes.     

Immunohistochemical localization of DNA adducts in rat liver tissue and phenotypically altered foci during oral administration of 2-acetylaminofluorene

Histological studies using paired immunofluorescence stainingand peroxidase-anti-peroxidase staining were performed on sectionsof rat livers with an antiserum specific for the 2-acetylaminofluorene(AAF)-DNA adduct N-deoxyguanosin-(8-yl)-aminofluorene (dG-8-AF).This is the predominant adduct in rat liver DNA at 5 (80%) and28 (100%) days of AAF feeding. Nuclear staining was observedin livers of male Fischer rats fed 0.02% AAF for these timeperiods, and was not present in livers of animals fed controldiet or detected when specific antiserum, first absorbed withthe immunogen adduct, was utilized. In addition, nuclear stainingwas unchanged after incubation with RNase and abolished afterincubation with DNase. Adducts were not readily detectable whenwhole-liver adduct concentrations were less than an averageof 10⁵ adducts per cell (30–50 fmol/µg DNA). Theoverall pattern of adduct distribution in livers of AAF-fedanimals was distinctly non-uniform. A predominance of nuclearstaining was found in the periportal areas by both immunofluorescenceand immunoperoxidase procedures. In contrast, staining was veryweak in the centrilobular areas. When animals were fed AAF for28 days and control diet subsequently for 7, 14, 21 or 28 days,the overall intensity of the immunohistochemical staining decreasedwith time on control diet. However, the pattern of localizationremained the same as in livers of rats fed AAF for 28 days,with the predominance of adducts being in the periportal areas.In male rats fed 0.02% AAF for 8 weeks, foci positive for -glutamyltranspeptidase(GGT) became apparent, and the nuclei in these areas showedno immunofluorescence, indicating the absence of detectablelevels of the dG-8-AF adduct. Twenty adduct-negative areas inthe median lobes of three rat livers were positive for GGT,which suggests that loss of ability to form adducts in theseregions occurs concomitantly with early phenotypic changes.