Differential expression of lactoseries carbohydrate epitopes HNK-1, CD15, and NALA by olfactory receptor neurons in the developing chick

 The formation of the nasal lining with its sensory and its nonsensitive respiratory epithelium requires a spatially ordered pattern of cellular differentiation. Aiming at identifying cell recognition molecules that may be involved in cellular differentiation steps, we applied a panel of antibodies to terminal carbohydrate sequences of the lactoseries on the developing chick olfactory epithelium. This approach is based on the idea that these terminal sugar residues may be involved in certain steps of maturation. Restricted expression of three epitopes NALA, HNK-1, and CD15 was observed in olfactory receptor neurons. The first immature olfactory receptor neurons were observed by day 3 of incubation, expressing the HNK-1 epitope, whereas a total epithelial staining was observed for NALA. By day 9 of incubation high numbers of HNK-1 positive immature olfactory receptor neurons were observed. At the same time mature olfactory receptor neurons showed immunoreactivity for CD15, whereas NALA was still expressed throughout the whole epithelial cell population. However, there was a pronounced staining in the population of mature olfactory receptor neurons. Around hatching only CD15 was detectable in (mature) olfactory receptor neurons, whereas HNK-1 and NALA immunoreactivity have switched to glandular and sustentacular cells respectively. The differentiation-dependent expression patterns of these three cell surface molecules suggest them as suitable markers to explore mechanisms that determine embryonic olfactory receptor neurogenesis. Accepted: 15 October 1997     

A novel missense mutation (I344K) in the SPG4gene in a Korean family with autosomal-dominant hereditary spastic paraplegia

 Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurodegenerative disorders characterized by slowly progressive spasticity and weakness of the lower extremities. Among eight loci linked with autosomal-dominant (AD)-HSP, the SPG4 locus on chromosome 2p22 accounts for about 40% of all patients. Recently, mutations in a new member of the AAA protein family, called spastin, have been identified as responsible for SPG4-linked AD-HSP. Here, we describe a novel missense mutation (c.1031T>A; I344K) in exon 7 of the SPG4 gene identified in a Korean family with typical clinical features of pure AD-HSP. The mutation affects the third amino acid of the highly conserved AAA cassette domain, which is the most fore part of the domain altered by a missense mutation reported so far. Clinical presentations of affected individuals carrying the I344K mutation were not different from those of pure AD-HSP with SPG4 mutations reported previously. However, it is noteworthy that neither urinary dysfunction nor involvement of upper extremities was noticed in this family. To our knowledge, this is the first report of genetically confirmed AD-HSP in Korea. Received: February 20, 2002 / Accepted: May 21, 2002     

IL-6阳性细胞在小鼠胸腺内的定位

目的：检测IL－6阳性细胞在小鼠胸腺的分布。方法：采用免疫酶细胞化学，免疫荧光双染及免疫电镜技术方法原位显示小鼠胸腺不同部位IL－6阳性神经的表达情况。结果：光镜免疫酶组织化学确定了IL－6阳性细胞的分布范围，即IL－6在胸腺皮质和髓质的某些特定的细胞表达；进一步采用免疫荧光双染色及免疫电镜技术对IL－6阳性细胞进行了解析，确定了小鼠胸腺内IL－6阳性细胞主要是胸腺实质中不同形态的巨噬细胞，IL－6不存在于胸腺上皮细胞及胸腺细胞。结论：巨噬细胞是小鼠胸腺IL－6的主要来源，参与胸腺细胞发育微环境的构成。     

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.     

Personality, manual preference and neuroendocrine reactivity in hirsute subjects

Behavioral and neuroendocrine differences may be postulated in hirsute subjects since central effects of gonadal steroids are well established. We conducted a controlled clinical study with 25 consecutive young hirsute participants compared with 20 consecutive controls. Neuropsychological evaluation included the Minnesota Multiphasic Personality Inventory (MMPI) and the Edinburgh Inventory of Manual Preference (EIMP). Neuroendocrine reactivity was assessed by the adrenocorticotropic hormone (ACTH) and cortisol responses to corticotropin releasing hormone (CRH). Hirsute participants presented a flattened personality profile with lower neurotic triad scores--146 +/- 20 versus 166 +/- 28. Left-hand preference was more common in hirsute participants--4/21 versus 0/20. Decreased ACTH [area under the curve (AUC)--36 +/-2 8 vs. 72 +/- 63 pg/ml h] and cortisol (AUC--18 +/- 4 vs. 25 +/- 10 microg/dl h) responses to CRH were found in the hirsute group. In the hirsute group, higher manual preference scores were associated with lower ACTH responses to CRH, while the opposite association was found in the control group. In the hirsute group, the hyporeactive hypothalamic-pituitary-adrenal (HPA) axis was associated with lower behavior-deviant scores, while in the control group, the hyporeactive HPA axis was associated with more psychopathology. We conclude that personality and HPA axis reactivity are different in hirsute female participants when compared with controls, with a trend for differences regarding handedness. Personality and handedness are differently associated with HPA reactivity. Distinctive features in hirsute participants are probably established very early during ontogenic development.     

Transgenic mice with an expanded CAG repeat controlled by the human AR promoter show polyglutamine nuclear inclusions and neuronal dysfunction without neuronal cell death

We generated transgenic mice that expressed a highly expanded 239 polyglutamine (polyQ) repeat under the control of the human androgen receptor promoter. These transgenic mice developed progressive neurological phenotypes of muscular weakness and ataxia, small body size and short life-span. PolyQ nuclear inclusions (NIs) were remarkable and widespread but found in selective regions of the central nervous system (CNS) such as the spinal cord, cerebrum and cerebellum as well as in selective peripheral visceral organs. This distribution pattern resembled that of spinal and bulbar muscular atrophy somewhat, but was more widespread. In neuronal tissues, NIs were present in astrocytes as well as neurons. Cytoplasmic and axonal inclusions were not observed. In the CNS regions with abundant NIs, neuronal populations were well-preserved, and neither neuronal cell death, reactive astrogliosis nor microglial invasions were detected. These findings suggest that polyQ alone can induce the neuronal dysfunction that precedes gross neuronal degeneration and provides a clue for investigating molecular mechanisms that underly the pathway to neuronal dysfunction from polyQ expansion.     

Circadian Rhythm of the Resistance of Mice to Acute Pneumococcal Infection

The resistance of both male and female mice to an acute infection by type I pneumococci varied rhythmically in an approximately 24-hr cycle. Mice inoculated intraperitoneally with 10(5.4+/-0.1) organisms during the dark period of the daily cycle survived significantly longer than mice similarly inoculated during the light period. The variation in resistance was correlated with the rate of increase of bacteremia, the rate being greatest after inoculation during the light period. Neither the capacity of the blood to support growth of pneumococci in vitro nor clearance of pneumococci from the blood in vivo varied between phases of the daily cycle. Adrenalectomized mice were equally and highly susceptible to infection during both light and dark periods. Stress of mice during the light period, normally a time of relative inactivity of mice, disturbed the rhythm; resistance to infection initiated during the light period increased and equalled that during the dark period.     

A TLR4 polymorphism is associated with asthma and reduced lipopolysaccharide-induced interleukin-12(p70) responses in Swedish children

BACKGROUND: Bacterial signals play an important role in the maturation of the immune system. Polymorphisms in genes coding for receptors to bacterial components can alter the immune responsiveness of the host to microbial agents and may indicate the development of aberrant immune responses that are associated with immune-mediated diseases such as atopic diseases. OBJECTIVE: The study's objective was to investigate the relationship between TLR4 and CD14 gene polymorphisms, the LPS responsiveness of PBMCs, and the presence of asthma and allergic rhinoconjunctivitis in children. METHODS: The TLR4 (Asp299Gly) and CD14/-159 polymorphisms were determined in 115 Swedish children aged 8 and 14 years. LPS-induced IL-12(p70), IL-10, and IFN-gamma responses of PBMCs from 69 of the children were analyzed by means of ELISA. The levels of soluble CD14 in serum samples were analyzed by means of ELISA, and the total IgE levels were analyzed by means of UniCAP Total IgE (Pharmacia Diagnostics, Uppsala, Sweden). RESULTS: Decreased LPS-induced IL-12(p70) and IL-10 responses were associated with the TLR4 (Asp299Gly) polymorphism and independently with asthma, especially atopic asthma. The TLR4 (Asp299Gly) polymorphism was associated with a 4-fold higher prevalence of asthma in school-aged children (adjusted odds ratio 4.5, 95% CI 1.1-17.4) but not to allergic rhinoconjunctivitis. CONCLUSION: A TLR4 polymorphism modifies innate immune responses in children and may be an important determinant for the development of asthma. This may influence the outcome of intervention studies that use microbial stimuli as immune modulators.     

Microcystic adnexal carcinoma: an immunohistochemical reappraisal.

Even though immunohistochemical comparisons of microcystic adnexal carcinoma vs infiltrative basal cell carcinoma and desmoplastic trichoepithelioma exist, they are mostly restricted to the use of a single stain. In addition, a comparison with squamous cell carcinoma has not been reported previously. In this study, we compare the expression of cytokeratin (CK) 15, CK7, CK20, CK903, carcinoembryonic antigen (CEA), CD10, CD15 and BerEP4 in 13 microcystic adnexal carcinoma, eight desmoplastic trichoepithelioma, 10 infiltrative basal cell carcinoma, and eight squamous cell carcinoma of which five exhibited ductal differentiation. We found that the majority of microcystic adnexal carcinoma (92%) and desmoplastic trichoepithelioma (100%) cases expressed CK15 while the infiltrative basal cell carcinoma and squamous cell carcinoma cases were all negative. Forty percent of infiltrative basal cell carcinoma expressed CK7; while only two microcystic adnexal carcinoma cases (15%) and one squamous cell carcinoma with ductal differentiation (12%) expressed CK7 in the remaining three tumor categories. None of the desmoplastic trichoepithelioma expressed CK7. All tumors were strongly positive for CK903. While the neoplastic cells were negative, luminal staining of ductal structures was noted for CK7, CD15 and CEA in some of the microcystic adnexal carcinoma, desmoplastic trichoepithelioma and squamous cell carcinoma with ductal differentiation cases. Sixty percent of infiltrative basal cell carcinoma, 31% of microcystic adnexal carcinoma, and 25% of squamous cell carcinoma express CD10. BerEP4 expression was noted in 38% of microcystic adnexal carcinoma, 57% of desmoplastic trichoepithelioma, 100% of infiltrative basal cell carcinoma, and 38% of squamous cell carcinoma. In conclusion, we found CK15 to be a useful marker in distinguishing microcystic adnexal carcinoma from infiltrative basal cell carcinoma and squamous cell carcinoma with ductal differentiation. Our experience indicates that microcystic adnexal carcinoma and desmoplastic trichoepithelioma have a similar immunohistochemical profile that is, CK15+ and BerEP4+/-; thus, additional studies are needed to separate these two entities.