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Large conjugative plasmids from clinical strains of Salmonella enterica serovar virchow contain a class 2 integron in addition to class 1 integrons and several non-integron-associated drug resistance determinants.

Two large conjugative resistance (R) plasmids from clinical strains of Salmonella enterica serovar Virchow carried a class 2 integron with the 5' conserved sequence (5'CS)-dfrA1-sat1-aadA1-3'CS gene array, which is associated with defective Tn7 transposons. In addition, each contained a different class 1 integron (with 5'CS-aadA1-3'CS or 5'CS-sat-smr-aadA1-3'CS gene arrays) linked to Tn21-Tn9 sequences, and several non-integron-associated R determinants. An intact copy of Tn7 (including the class 2 integron) was present in the chromosome of each strain.

Base Sequence↗

Characteristics and prevalence within serogroup O4 of a J96-like clonal group of uropathogenic Escherichia coli O4:H5 containing the class I and class III alleles of papG.

The recent discovery of a geographically dispersed clonal group of Escherichia coli O4:H5 that includes prototypic uropathogenic strain J96 prompted us to determine the prevalence of J96-like strains within serogroup O4 and to further assess the characteristics of such strains. We used O:K:H;F serotyping, PCR-based genomic fingerprinting, pulsed-field gel electrophoresis (PFGE), multilocus enzyme electrophoresis (MLEE), and PCR detection of the three papG alleles and of the cytotoxic necrotizing factor 1 (cnf1) and aerobactin (aer) gene sequences to characterize the 15 O4 strains among 336 E. coli isolates from three clinical collections (187 from mixed-source bacteremia, 75 from urosepsis, and 74 from acute cystitis). J96-like strains constituted approximately half of the O4 strains, or 2% of the total population. In contrast to other O4 strains, the J96-like strains characteristically exhibited specific group III capsular antigens, the H5 flagellar and F13 fimbrial antigens, a distinctive PCR genomic fingerprint, the class III papG allele (plus, in 50% of strains, the enigmatic class I papG allele), and cnf1 but lacked aer. A subset of these strains was remarkably homogeneous with respect to all these characteristics and exhibited a distinctive PFGE fingerprint and MLEE pattern. These findings clarify the epidemiological relevance of J96 as a model extraintestinal pathogen, provide further evidence of the class I papG allele outside of strain J96, and offer insights into the evolution of E. coli serogroup O4.

Adhesins, Escherichia coli↗

Comparison of replication-competent molecular clones of porcine endogenous retrovirus class A and class B derived from pig and human cells.

Vertically transmitted endogenous retroviruses pose an infectious risk in the course of pig-to-human transplantation of cells, tissues, and organs. Two classes of polytropic type C porcine endogenous retroviruses (PERV) which are infectious for human cells in vitro are known. Recently, we described the cloning and characterization of replication-competent PERV-B sequences from productively infected human cells (F. Czauderna, N. Fischer, K. Boller, R. Kurth, and R. R. Tönjes, J. Virol. 74:4028-4038, 2000). Here, we report the isolation of infectious molecular PERV-A and PERV-B clones from pig cells and compare these proviruses with clones derived from infected human 293 cells. In addition to clone PERV-A(42) derived from 293 cells, four "native" full-length proviral PERV sequences derived from a genomic library of the porcine cell line PK15 were isolated. Three identical class A clones, designated PK15-PERV-A(42), PK15-PERV-A(45), and PK15-PERV-A(58), and one class B clone, PK15-PERV-B(213), were characterized. PK15-PERV-B(213) is highly homologous but distinct from the previously described clone PERV-B(43). PK15-PERV-A(58) demonstrates close homology to PERV-A(42) in env and to PERV-C in long terminal repeat, gag, and pro/pol sequences. All three PERV clones described here were replication competent upon infection of susceptible cell lines. The findings suggest that the pig genome harbors a limited number of infectious PERV-A and -B sequences.

Animals↗

Comparing biology majors from large lecture classes with TA-facilitated laboratories to those from small lecture classes with faculty-facilitated laboratories.

The teaching faculty for this course sought to address their own concerns about the quality of student learning in an impersonal large lecture biology class for majors, the difficulties in getting to know each student by name, and difficulties in soliciting answers and reactions from the students during the lecture. Questions addressed by this study were, Do active-learning activities in a small and personal lecture setting enhance student learning more than active-learning activities in large impersonal lectures? and Are students more satisfied with an educational experience in a small and personal lecture setting? Based on faculty perceptions of how they best relate to their students, the prediction was that the students in the experimental group with small lecture classes and increased direct contact with the teaching faculty would learn physiological principles better than the students in the control group in the large impersonal lecture portion of the course. One of the laboratory sections of this large enrollment biology course was randomly selected to be taught with separate small lectures by the teaching faculty. In addition, the teaching faculty participated in the laboratory with these students during their experiments correlated with the lecture material. The students in both groups were compared by pre- and posttests of physiological principles, final course grades, and class satisfaction surveys.

Biology↗

Human MHC class III genes, Bf and C4. Polymorphism, complotypes and association with MHC class I genes in the Finnish population.

Electrophoretically detected genetic polymorphism of human MHC class III genes, factor B (Bf) and complement C4A and C4B, was studied in the Finnish population. Bf alleles were determined in a panel of sera from 70 unrelated individuals. The common Bf alleles, Bf*S and Bf*F, had frequencies of 73% and 26%, respectively. Only in 1 individual was another allele, Bf*F1, detected. The frequencies of the C4A and C4B alleles were based on studies of 254 unrelated individuals. In this panel, five different alleles were detected at the C4A locus and four at the C4B locus. At both loci an allele without a gene product, i.e. a 'null' allele, was observed with high frequency, 11% for C4A 'null' and 17% for C4B 'null'. The association of complotypes to HLA haplotypes was analyzed in 70 chromosomes. The most common combination, defined by class I and class III alleles, was HLA-B7-S31 (13%), followed by HLA-B35-F20 (8.4%) and HLA-B8-S03 (7.1%). Some HLA-B specificities, for example B15, B27 and B40, were associated with a variety of complotypes. The importance of complotyping in HLA genetics is discussed.

Complement C4↗

Medical devices; retention in class III and effective date of requirement for premarket approval for three preamendments class III devices--FDA. Proposed rule; opportunity to request a change in classification.

The Food and Drug Administration (FDA) is proposing to retain in class III, three preamendments class III medical devices, and is proposing to require the filing of a premarket approval application (PMA) or a notice of completion of a product development protocol (PDP) for these devices. FDA believes that the suction antichoke device, the tongs antichoke device, and the implanted neuromuscular stimulator device should remain in class III because insufficient information exists to determine that special controls would provide reasonable assurance of their safety and effectiveness, and/or these devices present a potential unreasonable risk of illness or injury. The agency is summarizing its proposed findings regarding the degree of risk of illness or injury designed to be eliminated or reduced by requiring the devices to meet the statute's approval requirements and the benefits to the public from the use of the devices. In addition, FDA is announcing the opportunity for interested persons to request the agency to change the classification of any of the devices based on new information.

Airway Obstruction↗

Lupus nephritis in an anti-nuclear antibody-negative young male. The simultaneous presence of class III and class V renal lesions.

We report about a 27-year-old white male, a known case of class III lupus nephritis with a very high anti-nuclear antibody (ANA) titer, who after 10 years of complete clinical and serological remission presented with sudden development of malar rash, proteinuria and an increase in the serum creatinine. Repeated serologic studies were all negative for ANA. A repeat kidney biopsy disclosed the presence of focal segmental glomerulosclerosis lupus nephritis (class IIIc) superimposed with a new membranous lupus nephritis (class V).

Adult↗

Isolation of a novel histone deacetylase reveals that class I and class II deacetylases promote SMRT-mediated repression.

The transcriptional corepressor SMRT functions by mediating the repressive effect of transcription factors involved in diverse signaling pathways. The mechanism by which SMRT represses basal transcription has been proposed to involve the indirect recruitment of histone deacetylase HDAC1 via the adaptor mSin3A. In contrast to this model, a two-hybrid screen on SMRT-interacting proteins resulted in the isolation of the recently described HDAC5 and a new family member termed HDAC7. Molecular and biochemical results indicate that this interaction is direct and in vivo evidence colocalizes SMRT, mHDAC5, and mHDAC7 to a distinct nuclear compartment. Surprisingly, HDAC7 can interact with mSin3A in yeast and in mammalian cells, suggesting association of multiple repression complexes. Taken together, our results provide the first evidence that SMRT-mediated repression is promoted by class I and class II histone deacetylases and that SMRT can recruit class II histone deacetylases in a mSin3A-independent fashion.

Amino Acid Sequence↗

[Comparison of HLA class I and DR class II antigen frequency in Polish patients, in relation to different stages of the disease].

The aim of this study was to analyze the association between HLA class I and class II DR frequency in the different stages of sarcoidosis in Polish population. 88 patients and 30 healthy controls have been typed. Patients were divided into three groups depending on radiological findings. In the first group were 28 cases presenting the regression of the disease. In the second were 33 patients in stable stage II or III and in the third group 27 patients with pulmonary fibrosis (stage IV). The typing was performed by NIH method using commercial sera. There were no statistically significant differences between studied group in HLA-A class I. The frequency of HLA B-18 was statistically more frequent in patients with sarcoidosis compared to healthy controls. HLA-DR1 was not present in third group of patients and the difference was significant compared to healthy controls.

Adult↗

Regulatory modules shared within gene classes as well as across gene classes can be detected by the same in silico approach.

Transcriptional regulation depends on the binding of transcription factors to their corresponding binding sites. The response to cellular signals is often mediated by the cooperative binding of transcription factors to well defined regulatory modules consisting of at least two transcription factor binding sites. Such regulatory modules can be responsible for the common regulation of genes within a gene class or confer a common function to promoters belonging to different gene classes. We developed in silico models representing a common framework of potential regulatory sites specific for one promoter class (actins). We also generated models for two different functional promoter modules both of which confer responsiveness to tumor necrosis factor (TNF) and interferon (IFN) to a variety of promoters. All models exhibited high selectivity, e.g. the mammalian muscle actin promoter model produced no false negatives in a database search.

Actins↗

Medical Devices; hematology and pathology devices; reclassification of automated blood cell separator device operating by filtration principle from class III to class II. Final rule.

The Food and Drug Administration (FDA) is reclassifying the automated blood cell separator (ABCS) device operating by filtration principle, intended for routine collection of blood and blood components, from class III to class II (special controls). The special control requirement for this device is an annual report with emphasis on adverse reactions to be filed by the manufacturer for a minimum of 3 years. The agency is taking this action in response to a petition submitted under the Federal Food, Drug, and Cosmetic Act (the act) as amended by the Medical Device Amendments of 1976 (the 1976 amendments), the Safe Medical Devices Act of 1990 (the SMDA), and the Food and Drug Administration Modernization Act of 1997 (FDAMA). The agency is reclassifying the automated blood cell separator devices operating by filtration principle into class II (special controls) because special controls, in addition to general controls, are capable of providing a reasonable assurance of safety and effectiveness of the device.

Device Approval↗

Functional classes of cortical projection neurons develop dendritic distinctions by class-specific sculpting of an early common pattern.

We demonstrate in rat neocortex that the distinct laminar arrangements of the apical dendrites of two classes of layer 5 projection neurons, callosal and corticotectal, do not arise de novo, but are generated later in development from a common tall pyramidal morphology. Neurons of each class initially elaborate an apical dendrite in layer 1. Layer 5 callosal neurons later lose the segments of their apical dendrite superficial to layer 4, generating their characteristic short pyramidal morphology. The apical dendrite of layer 5 callosal neurons later lose the segments of their apical dendrite superficial to layer 4, generating their characteristic short pyramidal morphology. The apical dendrite of layer 5 callosal neurons is actively eliminated, rather than passively displaced, as superficial cortical layers expand. Corticotectal neurons and callosal neurons superficial to layer 5 maintain their apical dendrite to layer 1. Therefore, this selective dendritic loss occurs in a neuron class-specific manner and, within the callosal population, in a lamina-specific manner. Based on our additional observations and other studies, this phenomenon can be extended to other types of cortical projection neurons. These findings show that selective dendritic elimination plays a major role in shaping the functional architecture characteristic of the adult cortex.

Animals↗

An open-label, randomized comparative pilot study of a single-class quadruple therapy regimen versus a 2-class triple therapy regimen for individuals initiating antiretroviral therapy.

OBJECTIVE: To examine the antiviral potency and tolerability profile of a single-class four drug (quadruple) nucleoside reverse transcriptase inhibitor (NRTI) regimen compared with a 2-class standard-of-care regimen. METHODOLOGY: A three-centre, randomized, open-label comparative pilot study of zidovudine/lamivudine/efavirenz (triple) versus abacavir/lamivudine/zidovudine/tenofovir (quadruple) therapy in HIV-1-infected, treatment-naive individuals. Both regimens were taken without regard to food and consisted of a twice-daily regimen and 3 pills/day. The study power was based on time-weighted average changes in HIV-1 RNA load. RESULTS: A total of 114 individuals (56 triple, 57 quadruple) received at least one dose of medication. Patients were well matched at baseline for viral load (mean 5.26 log10 versus 5.13 log10, respectively) and CD4 cell count (median 193 versus 153 cells/mm3, respectively). The two regimens performed similarly with regards to all endpoints. At week 48, by intention-to-treat, missing=failure analysis, 68% of triple- and 67% of quadruple-drug treated patients had an HIV-1 RNA <50copies/ml (P>0.05). On-treatment analysis showed 40/40 (100%) of triple- and 39/40 (97.5%) of quadruple-drug treated patients (P=0.996) had responded to <50copies/ml. No unexpected adverse events were reported. Changes in total cholesterol and triglycerides were modest but significantly favoured the quadruple therapy regimen at multiple time points. CONCLUSION: This pilot study suggests a quadruple NRTI-based regimen provides similar antiviral potency, tolerability and administrative characteristics to a 2-class triple therapy regimen. These findings should be confirmed in a more fully powered study. Potent quadruple NRTI-based regimens may have advantages for some individuals with regards to salvageability, tolerability and drug interactions.

Adenine↗

Functional epitope analysis of the human CD4 molecule. The MHC class II-dependent activation of resting T cells is inhibited by monoclonal antibodies to CD4 regardless whether or not they recognize epitopes involved in the binding of MHC class II or HIV gp120.

This study was designed to define regions on the human CD4 molecule important for the class II-dependent activation of resting, polyclonal CD4 T cells. With the use of mAb to known epitopes on CD4, we assayed the degree of CD4 saturation and functional effects on T cell activation over a range of antibody concentrations in parallel titration experiments. This approach allows a quantitative comparison of different reagents, regardless of parameters such as affinity for CD4. In sharp contrast to results reported for preactivated T cells and CD4 transfected T cell hybridomas, all 22 CD4 mAb tested did inhibit proliferative responses of freshly isolated CD4 T cells to MHC class II Ag. At the lowest saturating concentration of each antibody, T cell proliferation was reduced by 45 to 82%. Inhibition did not depend on antibody-induced modulation of CD4 expression. Strikingly, no correlation was found between the functional effects and the specificity of the mAb for different epitopes on CD4, such as the putative binding sites for MHC class II or HIV glycoprotein gp120.

Antibodies, Monoclonal↗

Fracture strength of Class I versus Class II restored premolars tested at the marginal ridge. 2. Cavosurface bonding and cavosurface plus internal enamel bonding.

The purpose of this study was to test the difference between the strength of the marginal ridge of extracted teeth with a Class I composite resin restoration and the strength of the marginal ridge of teeth with a Class II amalgam restoration with retention grooves. A statistically significant difference in fracture strengths was found among groups. No statistically significant difference was found among restored preparations, beveling technique, and restorative material. Statistically significant differences in fracture strength were found between the whole tooth group and treatment groups; between the whole tooth group and Class II amalgam restoration group; and between the unrestored tooth preparation group and all other tooth groups.

Acid Etching, Dental↗

Effects of the novel class Ia and class III antiarrhythmic agent RS-87337 on myocardial conduction in the anaesthetised dog.

The effects of the novel Class Ia/III antiarrhythmic compound RS-87337 on canine myocardial conduction were compared with those of the Class I antiarrhythmic disopyramide. RS-87337 had no effects on intra-atrial (I-A) or intra-ventricular (I-V) conduction parameters up to 10 mg.kg-1 i.v. (n = 6). Only one incidence of atrioventricular (A-V) block occurred at 10 mg.kg-1 at a pacing frequency of 261 beat.min-1. Disopyramide (5-10 mg.kg-1 i.v., n = 6) produced a frequency-dependent I-A conduction block and also significantly increased resting and paced A-V conduction times. Overall, disopyramide exhibited atrioselectivity while RS-87337 appeared more selective for ventricular conduction, possibly produced by a balance of its mixed Class Ia/III properties. RS-87337 was not cardiodepressant in the normal canine myocardium and produced no adverse effects on conduction parameters at doses up to 10 mg.kg-1 i.v.

Animals↗

[Expression of class I and class II markers on populations of leukemic cells].

The study of class I and class II antigen expression on leukemic cells brought the following conclusions: most of the leukemic cells show a slower number of class I antigenic sites than normal peripheral blood lymphocytes (PBL) but, in most cases, this does not hinder HLA typing; contrarily to normal PBL, leukemic cells seem to carry "non HLA" antigens (and/or non classical HLA antigens) which are probably responsible of the false positive reactions frequently observed at the time of HLA typing; most of the leukemic cell types express DR antigens (except those belonging to the T lineage) but DQ antigen expression (and in some cases MT antigen expression) varies depending on the cell type studied: well defined on mature B hemopathies, DQ expression is often lower than DR expression on acute leukemic cell types.

HLA Antigens↗

Transformation of LMTK- cells with purified class I genes. V. Antibody-induced structural modification of HLA class I molecules results in potentiation of the fixation of a second monoclonal antibody.

A potentiation phenomenon was observed with HLA-A3 and CW3 transformed murine L cells between anti-HLA class I B10.6 (potentiated) and B10.8 (potentiating) monoclonal antibodies (m.Ab.). Further studies of this phenomenon with these transformed L cells indicated that: 1) no significant specific binding of B10.6 m.Ab. to HLA-A3 and CW3 transformed L cells could be demonstrated by conventional radioimmunoassay or cytofluorometric study in the absence of B10.8 m.Ab.; 2) potentiation of the fixation of B10.6 m.Ab. was induced by other anti-HLA class I m.Ab., which all reacted with the same cluster of antigenic determinants; 3) potentiation reflects an increased specific fixation of B10.6 m.Ab. to HLA class I molecules implicating its combining site; 4) potentiation was mediated by B10.8 Fab fragments. These results indicate that potentiation of the fixation of B10.6 m.Ab. to the HLA-A3 and CW3 molecules expressed by the transformed L cells reflects conformational changes of these molecules after interaction with B10.8 m.Ab.

Animals↗