1-乙基-6-氟-1,4-二氢-4-氧代-7-(4-芳酰硫代氨甲酰基-1-哌嗪基)-3-喹啉羧酸的合成及抗菌作用

Thirteen new 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-aroyl-thiocarbamoyl- 1 piperazinyl)-3-quinoline carboxylic acids were prepared, Their structures were characterized by elemental analysis, IR, HNMR and MS spectra.Preliminary pharmacological tests indicated that some of compounds Ia～m possess strong inhibiting activity against Escherichia coli, Bacillus subtilis and Proteus at concentration of 100 μg/ml.     

Implantation response following clinical heart-lung transplantation

Implantation response has been a critical problem following heart-lung and lung transplantation. While the precise etiology of this problem remains unclear, improvements in organ preservation would be expected to have a beneficial effect on implantation response. The time-related profile of the implantation response was studied in 20 patients who underwent heart-lung transplantation between March 1984-March 1987. In 10 operations the donors had intravenous prostaglandin E-1 pretreatment while 10 had no vasodilatation before explantation of the organs. Otherwise lung preservation and early (2 weeks) immunotherapy were similar in both groups. The implantation response was evaluated by chest films and postoperative lung functions and mechanics. Roentgenographic implantation response was evident from the first postoperative day, was less evident at the seventh postoperative day and then gradually increased during the second postoperative week. There was a tendency towards less implantation response in the PGE-1 group than in the control group, but no statistical difference was observed. Patients with severe operative bleeding problems were excluded from the study. Only peak inspiratory pressures were significantly higher in the control group than in the PGE-1 group (p less than 0.01). Other lung function studies (alveolar-capillary pO2 difference, extubation time) were not different in the groups. This study supported the hypothesis that prostaglandin E-1 may have salutary effects on graft preservation and implantation response in heart-lung transplantation. Since 1986, we have performed 16 heart-lung transplantations using graft preservation with PGE-1 and flush perfusion. Thirty-day mortality is 0% and 13 of 16 patients are surviving.     

Criteria for evaluating the clinical and practical utility of models used by nurses

Arguably, nursing, like all health care disciplines, is an applied science. Essentially, this refers to the application of theory in order to understand and respond to the health problems of clients. These theories may be drawn (borrowed) from any applied science, or generated inductively from clinical nursing practice. Alternatively, nurses may attempt to apply deductive theory (global theoretical frameworks) known as nursing models. In this paper, all theoretical approaches, irrespective of origin, are referred to as models used by nurses. Thirteen criteria by which clinicians, and others, can evaluate the clinical and practical utility of models used by nurses which are expressed in the form of questions are identified and discussed. The criteria are an extension, both in detail and in number, of those developed by Reynolds and Cormack and subsequently applied by those writers to the Johnson Behavioural System Model of Nursing. The value, or otherwise, of individual models, or of models in general, will not be discussed in this paper. However, the authors propose that if the evaluation criteria described here are applied to existing models, serious deficits will be identified in relation to their clinical and practical utility.     

Generation of female genital tract antibody responses by local or central (common) mucosal immunization

Genital antibody responses were compared in female mice immunized intravaginally (i.vag.) or intranasally (i.n.) with a bacterial protein antigen (AgI/II of Streptococcus mutans) coupled to the B subunit of cholera toxin. Serum and salivary antibodies were also evaluated as measures of disseminated mucosal and systemic responses. Although i.vag. immunization induced local vaginal immunoglobulin A (IgA) and IgG antibody responses, these were not disseminated to a remote secretion, the saliva, and only modest levels of serum antibodies were generated. In contrast, i.n. immunization was substantially more effective at inducing IgA and IgG antibody responses in the genital tract and in the circulation, as well as at inducing IgA antibodies in the saliva. Moreover, mucosal and systemic antibodies induced by i.n. immunization persisted for at least 12 months. Analysis of the molecular form of genital IgA indicated that the majority of both total IgA and specific IgA antibody was polymeric, and likely derived from the common mucosal immune system.     

Invasion and killing of human endothelial cells by viridans group streptococci

Colonization of the cardiovascular endothelium by viridans group streptococci can result in infective endocarditis and possibly atherosclerosis; however, the mechanisms of pathogenesis are poorly understood. We investigated the ability of selected oral streptococci to infect monolayers of human umbilical vein endothelial cells (HUVEC) in 50% human plasma and to produce cytotoxicity. Planktonic Streptococcus gordonii CH1 killed HUVEC over a 5-h period by peroxidogenesis (alpha-hemolysin) and by acidogenesis but not by production of protein exotoxins. HUVEC were protected fully by addition of supplemental buffers and bovine liver catalase to the culture medium. Streptococci were also found to invade HUVEC by an endocytic mechanism that was dependent on polymerization of actin microfilaments and on a functional cytoskeleton, as indicated by inhibition with cytochalasin D and nocodazole. Electron microscopy revealed streptococci attached to HUVEC surfaces via numerous fibrillar structures and bacteria in membrane-encased cytoplasmic vacuoles. Following invasion by S. gordonii CH1, HUVEC monolayers showed 63% cell lysis over 4 h, releasing 64% of the total intracellular bacteria into the culture medium; however, the bacteria did not multiply during this time. The ability to invade HUVEC was exhibited by selected strains of S. gordonii, S. sanguis, S. mutans, S. mitis, and S. oralis but only weakly by S. salivarius. Comparison of isogenic pairs of S. gordonii revealed a requirement for several surface proteins for maximum host cell invasion: glucosyltransferase, the sialic acid-binding protein Hsa, and the hydrophobicity/coaggregation proteins CshA and CshB. Deletion of genes for the antigen I/II adhesins, SspA and SspB, did not affect invasion. We hypothesize that peroxidogenesis and invasion of the cardiovascular endothelium by viridans group streptococci are integral events in the pathogenesis of infective endocarditis and atherosclerosis.     

A mouse model of hepatocellular carcinoma: ectopic expression of fibroblast growth factor 19 in skeletal muscle of transgenic mice

Most mouse models of hepatocellular carcinoma have expressed growth factors and oncogenes under the control of a liver-specific promoter. In contrast, we describe here the formation of liver tumors in transgenic mice overexpressing human fibroblast growth factor 19 (FGF19) in skeletal muscle. FGF19 transgenic mice had elevated hepatic alpha-fetoprotein mRNA as early as 2 months of age, and hepatocellular carcinomas were evident by 10 months of age. Increased proliferation of pericentral hepatocytes was demonstrated by 5-bromo-2'-deoxyuridine incorporation in the FGF19 transgenic mice before tumor formation and in nontransgenic mice injected with recombinant FGF19 protein. Areas of small cell dysplasia were initially evident pericentrally, and dysplastic/neoplastic foci throughout the hepatic lobule were glutamine synthetase-positive, suggestive of a pericentral origin. Consistent with chronic activation of the Wingless/Wnt pathway, 44% of the hepatocellular tumors from FGF19 transgenic mice had nuclear staining for beta-catenin. Sequencing of the tumor DNA encoding beta-catenin revealed point mutations that resulted in amino acid substitutions. These findings suggest a previously unknown role for FGF19 in hepatocellular carcinomas.     

Pagetoid variant of actinic keratosis with or without squamous cell carcinoma of sun-exposed skin: a lesion simulating extramammary Paget's disease

BACKGROUND: Extramammary Paget's disease usually occurs in anogenital skin. We present five cases of squamous cell carcinoma in situ of sun-exposed skin and non-squamous cell carcinoma in situ actinic keratosis that displayed atypical keratinocytes disposed in intraepithelial cell nests and immunohistochemical staining simulating extramammary Paget's disease. METHODS AND RESULTS: Two pilot cases--one squamous cell carcinoma in situ and one non-squamous cell carcinoma in situ actinic keratosis with formation of intra-epidermal nests of atypical keratinocytes with a pagetoid spread pattern--were encountered at our institution. Fifty-four consecutive cases of squamous cell carcinoma in situ including bowenoid actinic keratosis and 34 cases of non-squamous cell carcinoma in situ actinic keratosis were reviewed to identify pagetoid spread of atypical cells. Representative sections of all cases with pagetoid spread of atypical keratinocytes were submitted for special stains for mucin, and immunostaining for cytokeratin 7 (CK7), cytokeratin 20 (CK20), cytokeratin CAM 5.2 (CAM 5.2), carcinoembryonic antigen (CEA), vimentin and S100 protein. In the group of squamous cell carcinoma in situ, 10 cases displayed pagetoid spread of atypical keratinocytes with cytoplasm ranging from clear to pale and atypical hyperchromatic nuclei. One review squamous cell carcinoma in situ was multicentric with three separate lesions. The atypical keratinocytes tended to form well to poorly defined cell groups extending from the basal cell layer to the corneal layer. No similar cases were identified in the group of non-squamous cell carcinoma in situ actinic keratosis. Two pilot cases and three of 10 review cases with a total of seven separate lesions displayed a moderate to marked immunohistochemical reactivity for CK7 similar to extramammary Paget's disease. CEA immunoreactivity was also detected in two of these cases. In addition, two of 44 squamous cell carcinomas in situ without pagetoid spread of atypical keratinocytes showed a moderate reactivity for CK7 in very occasional atypical keratinocytes. The remaining seven squamous cell carcinomas in situ with pagetoid spread of atypical keratinocytes were not immunoreactive for CEA and CK7. Immunostaining for CK20, vimentin, S100 protein was negative in all atypical cells in all study cases. CONCLUSIONS: Actinic keratosis, particularly squamous cell carcinoma in situ of sun-exposed skin, may have histopathological and immunohistochemical features similar to extramammary Paget's disease and probably represents a variant of actinic keratosis. Awareness of the pagetoid variant of actinic keratosis arising in sun-exposed skin is helpful to avoid the over-diagnosis of extramammary Paget's disease.