Differential regulation of cytokine genes in gingival epithelial cells challenged by Fusobacterium nucleatum and Porphyromonas gingivalis

IL-8 mRNA in human gingival epithelial cells (HGECs) is up-regulated by Fusobacterium nucleatum, and up-/down-regulated by Porphyromonas gingivalis in a complex interaction in the early stages (< or = 4 h) after infection. The mechanisms involved in this regulation in response to F. nucleatum and/or P. gingivalis infection, and identification of co-regulated cytokine genes, are the focus of this investigation. Heat, formalin or protease treatment of F. nucleatum cells attenuated the IL-8 mRNA up-regulation. NF-kappaB, mitogen-activated protein kinase (MAPK) p38 and MAPK kinase/extracellular signal-regulated kinase (MEK/ERK) pathways were involved in IL-8 mRNA induction by F. nucleatum. Pretreatment of P. gingivalis with heat, formalin or protease enhanced IL-8 mRNA induction. NF-kappaB, MARK p38, and MEK/ERK pathways were also involved in this induction. In contrast, down-regulation of IL-8 mRNA by P. gingivalis involved MEK/ERK, but not NF-kappaB or MAPK p38 pathways. cDNA arrays analysis revealed that mRNA down-regulation by P. gingivalis is a specific reaction that only a number of genes, e.g. IL-1beta, IL-8, macrophage inflammatory protein-2alpha, and migration inhibitory factor-related protein-14, are affected based on examination of 278 cytokine/receptor genes. These data indicate that F. nucleatum and P. gingivalis trigger specific and differential gene regulation pathways in HGECs.     

P300 and Long-Term Memory: Latency Predicts Recognition Performance

The study-test paradigm was used to investigate memory acquisition processes and the effects of repetition on long-term recognition memory. In this procedure, subjects are presented with a list of words (“targets”) to be memorized (Study series). They are later tested for recognition on a word list comprised of the target words mixed randomly with an equal number of new, distractor words (Test series). Both reaction time and the P300 component of the event-related brain potential were used as measures of processing time. During the Study series, large P300s were elicited despite a word category probability of 1.0. When the words from the Study series were divided on the basis of recognition performance, words that were subsequently recognized elicited P300s with shorter latencies than unrecognized words. P300 amplitude to words in the Study series increased with repetition while maintaining a constant latency. During the Test series, P300 latency and reaction time decreased with repetition for both target and distractor words. P300 amplitude to all words increased substantially over Test repetitions with target words eliciting larger P300s than distractor words. Words that were recognized more consistently during the Test series elicited larger and earlier P300s than words that were recognized less consistently. The P300 amplitude and latency results from both the Study and Test series are interpreted as reflecting the increased discriminability of the target words as the memory trace increases in strength.     

Intraduodenal neuropeptide levels,but not plasma levels,vary in a cyclic fashion with the migrating motor complex

The neurohormonal control of the migrating motor complex (MMC) is not fully understood. The hypothesis of the present study was that neuropeptide levels might vary with the different phases of the MMC and that a similar variation might be found in the secretions of the gastrointestinal tract. Thus, plasma and intraduodenal concentrations of vasoactive intestinal peptide (VIP), somatostatin (SOM), substance P (SP) and neurokinin A (NKA) were determined by radioimmunoassay every 10 min during two complete MMC cycles in eight male subjects. For comparison, plasma motilin (MOT) concentrations were measured. Plasma concentrations of MOT (mean peak value ± SEM; 39 ± 6 pmol L^?1), but none of the neuropeptides studied, showed a cyclic variation in plasma with the different phases of the MMC. Peak intraduodenal concentrations of VIP (79 ± 23 pmol L^?1),?SOM (2437 ± 432 pmol L^?1) and SP (718 ± 326 pmol L^?1) occurred at or at the time point before the onset of phase III of the MMC. No such correlation was observed for NKA. These results demonstrate that intraduodenal but not plasma concentrations of the neuropeptides VIP, SOM and SP show an association with phase III of the MMC. The biological relevance of this finding is yet unclear, but the results raise the possibility that gut neuropeptides may regulate fasting motility through a luminal release.     

Study of CYP2D6 gene in children with autoimmune hepatitis and P450 IID6 autoantibodies.

Cytochrome P450 IID6 is an autoantigen recognized by the sera of children affected with a subtype of autoimmune hepatitis. It was hypothesized that a mutation in the CYP2D6 gene could explain the autoimmune response in these patients. To examine this question, genomic DNA from peripheral lymphocytes (n = 9) and liver (n = 1) of 10 patients with anti-LKM-1 antibody was analysed by Southern blot for genetic association studies between a particular CYP2D6 haplotype and autoimmune hepatitis. In addition, a region of CYP2D6, from the same genomic DNA, was amplified by polymerase chain reaction (PCR) and digested by BstNI, in a search for the most prevalent 29B mutation, described in subjects who do not express the P450 IID6. Total RNA and proteins, prepared from the liver of an anti-LKM-1+ patient, were analysed by Northern and Western (immunoblot) blots respectively. Our results do not reveal any major structural change in the DNA of this patient at the CYP2D6 locus that could explain their autoimmune response. Corroborating this observation, no changes were noted either in P450 IID6 mRNA size or in the corresponding protein. However, these data do not exclude the possibility of subtle changes in the protein due to point mutations in critical regions that might trigger an autoimmune response.     

Annexin A2的结构和功能及其与疾病的关系

Annexins是一类钙依赖性膜磷脂结合蛋白。Annexin A2是Annexins家族中的一个重要成员,存在于细胞膜、胞质和胞外。Annexin A2蛋白在细胞膜构架的形成、膜聚合、内吞和胞吐中均扮演重要角色。Annexin A2还参与某些病理过程,与心血管疾病、血液病、肿瘤等多种疾病相关。文章简要综述了Annexin A2分子的结构、生化特征、生物学功能及其与疾病的关系。     

Effect of hypothermia on renal sodium reabsorption

Summary The relationship between sodium reabsorption and oxygen consumption was studied in an isolated rabbit kidney preparation perfused with blood at 37, 28 and 19° C. When the temperature was lowered from 37° C to 28° C and to 19°C the rate of oxygen consumption and of the maximal P.A.H. excretion (Tm P.A.H.) decreased more than that of sodium reabsorption.TheQ ₁₀ for sodium reabsorption is about 1.8, while that for maximal P.A.H. excretion is 2.5. Some hypothesis on the possible mechanisms of the lowQ ₁₀ of the Na⁺ reabsorption are forwarded.Preliminary reports have been published [Boll. Soc. Ital. Biol. Sper.43, 1019–1023 (1966) and44, 1784–1787 (1967);45, 860–862 (1969) and45, 863–865 (1969)].     

Immunohistochemical localization of substance P and substance P receptor (NK1) in the olivary pretectal nucleus of the rat

The olivary pretectal nucleus (OPN) is the first central nucleus in the pupillary light reflex arc (PLR). Substance P (SP) is a neuropeptide present in the OPN. The present immunohistochemical study, performed at the ultrastructural level, aimed to determine the synaptic localization of SP and SP receptor in the OPN. Three types of SP-positive terminals were found. The most abundant type was of retinal origin, characterized by electron-lucent mitochondria and round vesicles, organized in glomerular structures, making asymmetric synaptic contacts with dendrites, and profiles containing pleomorphic vesicles, also making synaptic contacts with dendrites. The second type of SP-immunoreactive terminal contained electron-dense mitochondria and pleomorphic vesicles. This type made symmetric synaptic contacts and may originate from the ventral part of the lateral geniculate nucleus. The third type of SP-immunoreactive terminals contained electron-dense mitochondria, clear round vesicles, and made an asymmetric synaptic contact. This type originates from the contralateral OPN. SP receptors of the NK1 subtype were revealed to be on dendrites and were part of the glomerular-like arrangement. On account of the present observations, it can be concluded that retinal projections to the OPN use SP as a neuromodulator and synapse on NK1 receptor-containing dendrites of large neurons projecting to the Edinger-Westphal nucleus. Since SP also modulates the parasympathetic component of the PLR, we postulate that SP plays a modulating role in all components of the PLR.     

Cell-mediated immunity in leprosy and transfer of delayed hypersensitivity reactions

Eighty-nine patients with leprosy, 65 classified as lepromatous and 24 as tuberculoid, were examined in this study. Skin test responses to protein antigens and dinitrochlorobenzene (DNCB) were depressed in lepromatous patients compared to controls. Tuberculoid patients did not exhibit a significant depression to microbial antigens, but they showed a definite depression in the ability to be sensitized with DNCB. The transfer of delayed hypersensitivity reactions to tuberculin, trichophytin, and lepromin (Fernandez and Mitsuda reactions) was accomplished in lepromatous and indeterminate leprosy patients using viable lymphocytes from donors presenting positive reactions to these antigens. The lepromin reaction was also transferred to patients with South American blastomycosis and cutaneous leishmaniasis. The positive reactions of adoptive immunity were confirmed by histologic examination of skin biopsies.     

Immunochemical characterization of mouse brain-associated theta (Thy-1) antigen.

The Thy-1 antigens or rat brain and thymus have been isolated and chemically characterized, but those of mice have not been identified. Moreover, it is uncertain whether the antigens are glycolipids or glycoproteins. This study with highly purified preparations of gangliosides GM₁, ¹GD_1a, GD_1b and GT_1b from bovine brain and several ganglioside fractions from mouse brain showed that Thy-1 activity does not reside in gangliosides, but rather in the chloroform-methanol-insoluble residue of brain remaining after extraction of gangliosides. The antigen could be solubilized from this residue with a non-ionic detergent. The antigenic activity of the solubilized preparation was heat-labile but resistant to periodate. The chemical properties of the Thy-1 antigen of mouse brain are discussed.     

Source Localization of P300 from Oddball, Single Stimulus, and Omitted-Stimulus Paradigms

Three different auditory stimulus paradigms were used to elicit P300 potentials. Normal subjects were tested on the classical rare target stimulus, single-stimulus and omitted-stimulus conditions. Noninvasive identification of the cerebral sources of the event-related potentials (ERPs) was performed using spatio-temporal multiple dipole modeling (BESA software) with individually sized spherical head models. The grand average data of each condition was first independently modeled and these models were used as starting values for modeling each individual subject's data. Models for the rare-stimulus condition and single-stimulus condition both consisted of 6 dipoles. Models for the omitted-stimulus condition consisted of 2 dipoles. The dipole locations of the final individual 6-dipole models for the rare and single-stimulus conditions did not differ significantly from each other or from one previous result obtained from a another group of subjects (Tarkka et al. 1995). Super-imposition of the dipole coordinates on the sterotaxic brain atlas suggests that bilateral deep medial temporal lobe structures are the major contributors to rare and single-stimulus P300s. Because both the wave form morphology and the source model of the P300 elicited by single stimulus were close to those of the rare-stimulus P300 it may be that the underlying neural mechanisms eliciting these P300 potentials are essentially the same.