TRIM5alpha association with cytoplasmic bodies is not required for antiretroviral activity

The tripartite motif (TRIM) protein, TRIM5alpha, restricts infection by particular retroviruses. Many TRIM proteins form cytoplasmic bodies of unknown function. We investigated the relationship between cytoplasmic body formation and the structure and antiretroviral activity of TRIM5alpha. In addition to diffuse cytoplasmic staining, the TRIM5alpha proteins from several primate species were located in cytoplasmic bodies of different sizes; by contrast, TRIM5alpha from spider monkeys did not form cytoplasmic bodies. Despite these differences, all of the TRIM5alpha proteins exhibited the ability to restrict infection by particular retroviruses. Treatment of cells with geldanamycin, an Hsp90 inhibitor, resulted in disappearance or reduction of the TRIM5alpha-associated cytoplasmic bodies, yet exerted little effect on the restriction of retroviral infection. Studies of green fluorescent protein-TRIM5alpha fusion proteins indicated that no TRIM5alpha domain is specifically required for association with cytoplasmic bodies. Apparently, the formation of cytoplasmic bodies is not required for the antiretroviral activity of TRIM5alpha.     

Two cases of a renal epithelial tumour resembling immature nephron

Summary Two cases of renal epithelial tumours are reported in females aged 46 and 66 years respectively. In spite of the large size of the tumours, neither invasive growth nor metastasis was observed. Histologically, the tumours were composed of immature epithelial cells forming tubules with abortive glomeruloid structures. Electron microscopy of tumour cells revealed poorly developed polarity and intracytoplasmic organelles. They showed similar immunohistochemical reactions to those of developing nephrons, particularly to those of the S-shaped body. The nuclear DNA content of the tumour cells was almost euploid. We conclude that the lesions were epithelial tumours of the kidney histologically mimicking developing renal parenchyma.     

Microtubules are required for cytokeratin aggresome (Mallory body) formation in hepatocytes: an in vitro study

Mallory bodies are cytokeratin-ubiquitin aggresomes that form in hepatocytes in many different chronic liver diseases. One of the key components in aggresome formation, not yet investigated in Mallory body formation, is the role of microtubules. An in vitro tissue culture assay is required to test for microtubule involvement in Mallory body formation so that Mallory body formation can be observed in the presence or absence of microtubule-disrupting agents. In this report, a new model of in vitro Mallory body formation was developed, which uses cultured hepatocytes isolated from drug-primed mice. When hepatocytes were incubated in the presence of antimicrotubule agents, they failed to form Mallory bodies. It is concluded that intact microtubules are required for Mallory body formation.     

Cdc42 is crucial for the establishment of epithelial polarity during early mammalian development.

To study the role of Cdc42 in the establishment of epithelial polarity during mammalian development, we generated murine Cdc42-null embryonic stem cells and analyzed peri-implantation development using embryoid bodies (EBs). Mutant EBs developed endoderm and underlying basement membrane, but exhibited defects of cell polarity, cell-cell junctions, survival, and cavitation. These defects corresponded to a decreased phosphorylation and membrane localization of aPKC, a reduced phosphorylation of GSK3beta, and a diminished activity of Rac1. However, neither Rac1 nor the kinase function of GSK3beta seem to contribute to cell polarization and cell-cell contacts. In contrast, EBs expressing dominant-negative (dn) PKCzeta mimicked well the phenotype of Cdc42-null EBs, suggesting a major role of aPKC in mediating cell polarization downstream of Cdc42. Finally, aggregation experiments with endodermal cell lines suggested that Cdc42 might affect formation of adherens and tight junctions by PKCzeta-dependent regulation of the protein levels of p120 catenin and E-cadherin.     

空肠弯曲菌慢性感染诱致自身免疫反应的机理初探

用空肠弯曲菌CJ—S131株感染昆明种小鼠3个月,观察到:(1)感染鼠血清中,出现高滴度的抗ds—DNA和ss—DNA抗体;(2)Con A诱导的抑制细胞功能降低和TH/Ts细胞比值增加;(3)PFC形成和LPS诱致的淋巴细胞转化作用增强:(4)DTH和Con A及PHA诱致的淋巴细胞转化作用增强。提示,CJ—S131感染小鼠使其T_S细胞功能降低,导致T_H细胞功能偏亢,B细胞功能亢进,这可能与自身免疫反应的产生有关。     

Psammoma bodies and optically clear nuclei in bronchiolo-alveolar cell carcinoma. Diagnosis by fine needle aspiration biopsy with histologic and ultrastructural confirmation

The fine needle aspiration cytology of two cases of bronchiolo-alveolar cell carcinoma of the lung having unusual features is reported. One case demonstrated numerous psammoma bodies in the cytologic smears, whereas the other case showed an abundance of cells with optically clear nuclei. Both peripherally located tumors were resected and confirmed as primary bronchiolo-alveolar cell carcinoma by histologic and ultrastructural examination. We believe this to be the first report describing these unusual features of bronchiolo-alveolar cell carcinoma diagnosed by fine needle aspiration cytology. Presented is a discussion of psammoma bodies and optically clear nuclei seen in primary and metastatic tumors of the lung. This will aid in the diagnosis of these cases.     

Nicotinic receptors in human brain: topography and pathology

Brain nicotinic acetylcholine receptors (nAChR) are a class of ligand-gated channels composed of and β subunits with specific structural, functional and pharmacological properties. They participate in the physiological and behavioural effects of acetylcholine and mediate responses to nicotine. They are associated with numerous transmitter systems and their expression is altered during development and ageing as well as in diseases such as autism, schizophrenia, Alzheimer's disease, Parkinson's disease and Lewy body dementia. Nicotinic receptors containing a number of different subunits are highly expressed during early human development. Disorders believed to be associated with abnormal brain maturation involve deficits in both 4β2, in the case of autism, and 7 possibly in addition to 4β2 nAChRs in the case of schizophrenia. In ageing and age-related neurodegenerative disorders nAChR deficits are predominantly associated with 4-containing receptors, although some studies also indicate the involvement of 3 and 7 subunits. Whilst ageing appears to be associated with reductions in subunit mRNA as well as protein expression, in Alzheimer's disease only protein loss is apparent. Nicotinic therapy may be of benefit in a number of neurological conditions, however studies evaluating further both the distribution of specific subunit involvement and the correlation of nAChR deficits with clinical symptoms are required to inform therapeutic strategy.     

The cerebrospinal fluid transferrin/tau proteins. A study by two-dimensional polyacrylamide gel electrophoresis (2D) and agarose isoelectrofocusing (IEF) followed by double-antibody peroxidase labeling and avidin-biotin amplification

The cerebrospinal fluid (CSF) transferrin/Tau proteins were studied by two-dimensional polyacrylamide gel electrophoresis (2D) followed by immunoblotting and by agarose isoelectrofocusing (IEF), and subsequent double immunofixation, peroxidase staining and Avidin-Biotin Complex (ABC) amplification. The pattern of the Tau protein was similar but not equal to that of the transferrin (Tf). When a genetic variant of Tf was present in the serum, the same variant was also observed in the corresponding CSF Tf and in the Tau fraction. After neuraminidase treatment, both serum and CSF Tf moved to the Tau position on IEF and 2D. On 2D, no desialized precursors of the Tau proteins were detected, whereas the Tf precursors were always detected. No synthesis of the Tau globulin in the brain can, therefore, be inferred. In CSF not treated with neuraminidase, Tf is the only sialoglycoprotein clearly desialized, showing that the Tau fraction cannot be generated by neuraminidase action at CSF level. In fact, the treatment of serum and CSF proteins with neuraminidase produced a clear shift in the isoelectric mobility of all sialoglycoproteins. We clearly demonstrate that the Tau globulin is the result of neuraminidase activity not located in the CSF compartment. We suggest that Tf could be desialized by the action of neuraminidase at the brain level and then be "washed" into the CSF. Brain utilization of Tf, meeting the brain iron requirement, seems likely.     

Selected Topics in the Pathology of the Thyroid and Parathyroid Glands in Children and Adolescents

The goals of this chapter in keeping with the overall general themes of this special edition will be (1) to highlight aspects of development of the thyroid and parathyroid glands with particular focus on the role and contribution of the neural crest (or not) and how this may impact on the pathology that is seen, (2) to emphasize those lesions particularly more commonly arising in the pediatric population that actually generate specimens that the surgical pathologist would encounter, and (3) highlight more in depth specific lesions associated with heritable syndromes or specific gene mutations since the heritable syndromes tends to manifest in the pediatric age group. In this light, the other interesting areas of pediatric thyroid disease including medical thyroid diseases, congenital hypothyroidism, anatomic variants and aberrations of development that lead to structural anomalies will not be emphasized here.