微机在牙形刺研究中的应用

该文对微机在牙形刺研究中的应用方法上进行了探索,在大量原始资料和数据的基础上,采用了模糊聚类分析和CAI计算机程序系统的研究,在地层划分,化石组合,沉积环境分析及生油气评价等方面都取得了一定的成果。     

Susceptibility of fibronectin to degradation by various gram-negative and gram-positive oral micro-organisms

The degradative effects on tritiated human plasma fibronectin (FN) of proteases associated with twenty five Gram-negative (GN) and fifteen Gram-positive (GP) oral microbial isolates were examined. Ninety-two per cent of the GN and 20% of the GP isolates degraded the FN. In the GN group, the degradative effects were greatest for Bacteroides gingivalis and Treponema denticola, while in the GP group Streptococcus faecalis produced appreciable, and the two Lactobacillus casei isolates moderate and low, levels of FN degradation.     

Electron-microscopical evidence for heterogeneity of micronodular argyrophil cell growth in man

Hypergastrinaemia-associated changes of non-antral argyrophil cells in man are of increasing interest, because of the development of potent inhibitors of gastric acid secretion. Using an antibody against chromogranin A, we identified micronodular endocrine cell hyperplasia of the oxyntic mucosa in gastric biopsy specimens of patients with hypergastrinaemia of different backgrounds. Consecutive ultrathin sections were examined at the electron-microscopical level. Endocrine cell types within the (extraepithelial) micronodules closely resembled those in the adjacent mucosa. Micronodules were classified into two groups. The first group was composed of endocrine cells only and predominated in patients with drug-induced hypergastrinaemia and/or chronic gastritis, and in a gastrinoma/MEN I patient. The second group represented “neuroendocrine complexes”, showing a close intermingling of non-myelinated nerve fibres with endocrine cells, and was found predominantly in pernicious anaemia. Micronodular argyrophil cell growth in man is therefore heterogeneous and depends on the background of the hypergastrinaemia.     

Epilepsy is a risk factor for sudden cardiac arrest in the general population

Background

People with epilepsy are at increased risk for sudden death. The most prevalent cause of sudden death in the general population is sudden cardiac arrest (SCA) due to ventricular fibrillation (VF). SCA may contribute to the increased incidence of sudden death in people with epilepsy. We assessed whether the risk for SCA is increased in epilepsy by determining the risk for SCA among people with active epilepsy in a community-based study.

Methods and Results

This investigation was part of the Amsterdam Resuscitation Studies (ARREST) in the Netherlands. It was designed to assess SCA risk in the general population. All SCA cases in the study area were identified and matched to controls (by age, sex, and SCA date). A diagnosis of active epilepsy was ascertained in all cases and controls. Relative risk for SCA was estimated by calculating the adjusted odds ratios using conditional logistic regression (adjustment was made for known risk factors for SCA). We identified 1019 cases of SCA with ECG-documented VF, and matched them to 2834 controls. There were 12 people with active epilepsy among cases and 12 among controls. Epilepsy was associated with a three-fold increased risk for SCA (adjusted OR 2.9 [95%CI 1.1–8.0.], p = 0.034). The risk for SCA in epilepsy was particularly increased in young and females.

Conclusion

Epilepsy in the general population seems to be associated with an increased risk for SCA.     

In vitro glucocorticoid sensitivity is associated with clinical glucocorticoid therapy outcome in rheumatoid arthritis

Introduction

Genetic and disease-related factors give rise to a wide spectrum of glucocorticoid (GC) sensitivity in rheumatoid arthritis (RA). In clinical practice, GC treatment is not adapted to these differences in GC sensitivity. In vitro assessment of GC sensitivity before the start of therapy could allow more individualized GC therapy. The aim of the study was to investigate the association between in vitro and in vivo GC sensitivity in RA.

Methods

Thirty-eight early and 37 established RA patients were prospectively studied. In vitro GC sensitivity was assessed with dexamethasone-induced effects on interleukin-2 (IL-2) and glucocorticoid-induced leucine zipper (GILZ) messenger RNA expression in peripheral blood mononuclear cells (PBMCs). A whole-cell dexamethasone-binding assay was used to measure number and affinity (1/K_D) of glucocorticoid receptors (GRs).In vivo GC sensitivity was determined by measuring the disease activity score (DAS) and health assessment questionnaire disability index (HAQ-DI) score before and after 2 weeks of standardized GC treatment.

Results

GR number was positively correlated with improvement in DAS. IL-2-EC₅₀ and GILZ-EC₅₀ values both had weak near-significant correlations with clinical improvement in DAS in intramuscularly treated patients only. HAQ responders had lower GILZ-EC₅₀ values and higher GR number and K_D.

Conclusions

Baseline cellular in vitro glucocorticoid sensitivity is modestly associated with in vivo improvement in DAS and HAQ-DI score after GC bridging therapy in RA. Further studies are needed to evaluate whether in vitro GC sensitivity may support the development of tailor-made GC therapy in RA.     

Fixation, fine structure, and immunostaining for neuropeptides: perfusion versus immersion of the neuroendocrine hypothalamus

The effects of various fixatives and fixation methods on ultrastructural morphology and the immunocytochemical localization of beta-endorphin were examined in rat brain. The mediobasal hypothalamus was preserved by vascular perfusion and/or immersion in nine different fixatives. We tested several combinations of paraformaldehyde, glutaraldehyde, acrolein, and picric acid in various isosmolar buffers. Vibratome sections were stained for beta-endorphin employing the peroxidase-antiperoxidase technique, or processed directly for electron microscopy. The ultrastructural quality of a given region was attributed to its location with respect to the blood-brain barrier, the method of fixation, and the concentrations of some of the fixative components. Immersion fixation gave better results and reduced extracellular space in the median eminence (outside the blood-brain barrier) and areas close to the hypothalamic surface. Positive immunostaining of beta-endorphin perikarya occurred only in tissue fixed with periodate-lysine-paraformaldehyde. Light to moderate fiber staining was also present in some paraformaldehyde-glutaraldehyde-acrolein combinations. However, a glutaraldehyde concentration of 1% or higher abolished all positive staining for beta-endorphin. These results emphasize the necessity of optimizing fixation for ultrastructure and for immunocytochemical staining of each individual antigen. The choice of the best fixation method depends not only on the intracellular location of the antigen but also on the relationship between hypothalamic tissue compartments and the blood-brain barrier.     

The relevance of tissue thiol histochemistry to diagnostic hematopathology

Expression analyses suggest that alterations of the antioxidant state of some diffuse large B-cell lymphomas can assist prognosis; reversibly oxidized thiols may serve as a surrogate marker for identifying such cases. Little is known about the distribution of free thiols and reversibly oxidized thiols in human tissues. We developed a staining technique that enables visualization of tissue thiols in situ using bright field microscopy and validated it using gastrointestinal tissue specimens. We used our thiol staining technique to assess benign tonsillectomy and diffuse large B-cell lymphoma specimens. The gastrointestinal series revealed the presence of free thiols within epithelial cells and cells of the lamina propria. Staining for reversibly oxidized thiols was robust in gastric foveolar cells, intestinal goblet cells and the mucus they produce. Tonsillectomy specimens exhibited diffuse presence of free thiols. Staining for reversibly oxidized thiols was confined to germinal center macrophages and sinus histiocytes. Among the diffuse large B-cell lymphoma specimens, we observed strong staining for free thiols within malignant cells. By contrast to benign B-cells, the malignant cells demonstrated pronounced and diffuse staining for reversibly oxidized thiols. We demonstrated intrinsic differences between benign and malignant cells.     

Somatostatin receptors in human cancer: incidence, characteristics, functional correlates and clinical implications.

Somatostatin receptors (SS-R) have been identified in membrane homogenates or tissue sections from several hundred tumors. SS-R were found in most neuroendocrine tumors, i.e. GH and TSH producing pituitary tumors, endocrine gastroenteropancreatic (GEP) tumors, paragangliomas, pheochromocytomas, medullary thyroid carcinomas (MTC) and small cell lung carcinomas. SS-R were also expressed in a majority of malignant lymphomas, in several brain tumors (all meningiomas, most astrocytomas) and in breast tumors. The majority of tumors expressing SS-R are rather differentiated (i.e. astrocytomas vs glioblastomas), but exceptions exist (high grade malignant lymphomas). An inverse relationship exists between SS-R and receptors for epidermal growth factor (EGF-R) incidence in lung tumors, glial tumors and most breast tumors, whereas meningiomas express simultaneously both receptors. A minority of tumors (ovarian tumors, MTC, insulinomas) express a subtype of SS-R, characterized by low affinity for the octapeptide SS analog octreotide. The function mediated by SS-R in human tumors may differ according to the tumor type. SS-R in pituitary and GEP tumor mediate hormone secretion inhibition with, in addition, possibly some antiproliferative effects. In meningiomas, however, activation of SS-R inhibits forskolin-stimulated adenylate cyclase activity, and weakly stimulates proliferation. Whereas SS-R seem to mediate antiproliferative effects in animal models and cell lines of lymphomas, breast and lung tumors, such an effect has not yet been convincingly documented in human primary tumors. The clinical implications of the presence of SS-R in tumors are manyfold: (1) as a predictive marker for efficient therapy with octreotide in pituitary and GEP tumors; (2) as a diagnostic marker: for pathobiochemical classification of tumors, using in vitro detection methods; for clinical evaluation using in vivo scanning techniques; (3) as a prognostic marker; and (4) as a potential radiotherapeutic target.     

Tumor promoters cause changes in the state of phosphorylation and apparent molecular weight of a tyrosine protein kinase in T lymphocytes

The T cell lymphoma LSTRA contains an elevated level of a tyrosine protein kinase of molecular weight of 56,000 (pp56Tcell) that is present in normal T lymphocytes. Treatment of 32P-labeled LSTRA cells with the phorbol ester 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA), followed by immunoprecipitation of pp56Tcell, revealed that PMA causes complex changes in the state of phosphorylation of pp56Tcell, and the appearance of several new forms of pp56Tcell with higher apparent molecular weights on sodium dodecyl sulfate-polyacrylamide gels. The 32P-labeled pp56Tcell from untreated LSTRA cells contains phosphotyrosine and phosphoserine in a ratio of 2:1. After treatment of LSTRA cells with PMA, the form of pp56Tcell that runs with a molecular weight of 56,000 has approximately equal amounts of phosphotyrosine and phosphoserine, while the higher molecular weight forms of pp56Tcell seen after PMA have 3-4 times more phosphoserine than phosphotyrosine. The induction by PMA of higher molecular weight forms of pp56Tcell could also be demonstrated in preparations of normal human T lymphocytes. The changes in the state of phosphorylation of pp56Tcell after treatment of cells with PMA are consistent with the possibility that pp56Tcell is an in vivo substrate for protein kinase C and provide documentation for a linkage between a mitogenic agent and pp56Tcell.