bluuebunny/crossref_metadata_2025_split huggingface dataset:
Origin and maintenance of germ‐line V genes
Authors: ROTHENFLUH HARALD S. , STEELE EDWARD J. 
Published: July 2007

SummaryThe distribution of nucleotide variability within and upstream of germ‐line VH186.2‐related variable genes was studied. The data in this report of work in progress indicate non‐random selection for variability in the second antigen‐contact or complementarity‐determining region (CDR2) for 12 such genes isolated using the polymerase chain reaction (PCR) technique from genomic C57BL/6 mouse liver DNA. The translated protein sequences of these and three additional previously published genes also display a pronounced Wu‐Kabat peak of amino acid variability in CDR2. In the CDR1 and CDR2 regions of this set of related germ‐line genes, there are no silent nucleotide changes, and most amino acid replacements (or non‐synonymous changes) are non‐conservative. In contrast, there is selection against amino acid replacements in the framework regions (FW), as indicated by the significant number of silent (or synonymous) mutational changes from the VH 186.2 reference sequence. This is surprisingly similar to the Wu‐Kabat variability patterns observed in somatically mutated immune response antibodies. These data could imply similar diversification mechanisms acting on B cell‐expressed V genes in the soma (i.e. in a germinal centre) and in the germ‐line DNA of male and/or female germ cells. While always possible, we consider this unlikely. Similarly, we consider as unlikely an explanation based on a classical Darwinian model involving simple stepwise whole animal selection prior to reproduction for each VH and VL gene now phylogenetically stored in the V segment arrays of the genomic DNA. A more reasonable hypothesis for the origin and maintenance of the many germ‐line V genes would propose that there is a yet to be defined process providing a direct genetic link between somatically mutated and selected V genes and the germ‐line DNA repertoire.
Expression of membrane receptor for tumour necrosis factor on human blood lymphocytes
Authors: ZOLA H. , FLEGO L. , WEEDON H. 
Published: July 2007

SummaryUsing a monoclonal antibody against the human p75 tumour necrosis factor receptor (TNFR‐I) combined with a high‐sensitivity immunofluorescence flow cytometric procedure, a proportion of peripheral blood lymphocytes can be shown to express TNFR‐I constitutively. Approximately 50% of peripheral blood lymphocytes consisting mostly of CD4 cells and including most CD45R0‐positive cells, express TNFR‐I. Receptor expression is increased by a variety of activation signals. Only a minority (up to 30%) of tonsil B cells express measurable levels of TNFR‐I. The tonsil B cells which express TNFR‐I include both cells with a germinal centre cell phenotype and cells with the phenotype of the follicular mantle zone. Activation of B cells with antiimmunoglobulin, alone or in combination with interleukin‐4 or interleukin‐2, increases receptor expression, particularly in cells with the phenotype of mantle zone cells. The functional significance of constitutive expression of TNFR by blood and tissue lymphocytes is discussed.
Control of clonal deletion in the thymus: Implications for tolerance induction
Authors: HARTWIG MANFRED 
Published: July 2007

SummaryTolerance to foreign antigen by means of clonal deletion in the thymus can be achieved during embryonic or neonatal life, but not easily in the adult animal. It is concluded here that an immunological control by mature T cells prevents newly acquired antigen from being permanently deposited in the adult thymus. In this way, the originally established thymic antigen discrimination can be maintained successfully. Breakdown of the control circuit should permit tolerance induction even in the adult thymus.
Molecular cloning and characterization of a ruminant interleukin‐6 cDNA
Authors: ANDREWS ARNA E. , BARCHAM GARRY J. , ASHMAN KEITH , MEEUSEN ELS N. T. , BRANDON MALCOLM R. , NASH ANDREW D. 
Published: July 2007

SummaryBy hybridization with a human interleukin‐6 (IL‐6) cDNA fragment a corresponding ruminant (ovine) cDNA was isolated from a lipopolysaccharide (LPS)‐stimulated alveolar macrophage library. The nucleotide sequence of the cDNA and the predicted amino acid sequence of the protein showed significant homology to the human and murine molecules. Ovine IL‐6 cDNA encodes a polypeptide of 208 amino acids that, based on analysis of human IL‐6, is processed to a protein of 180 amino acids. Northern blot analysis and the 7TD1 bioassay were used to analyse regulatory aspects of IL‐6 production by primary ovine fibroblasts. Both LPS and recombinant ovine IL‐1α were shown to induce IL‐6 mRNA with peak levels occurring at 1 h post‐stimulation and declining thereafter. When fibroblasts were pretreated with cyclohexamide prior to stimulation the level of induction by LPS and IL‐1α increased dramatically and peak levels were observed at 5 h post‐stimulation. The level of secreted IL‐6 increased rapidly over the first 24 h and continued to increase over the next 48 h.
Inhibition by anti‐sperm monoclonal antibodies of the penetration of zona‐free hamster oocytes by human spermatozoa
Authors: GARCÍA‐FRAMIS V. , MARTORELL R. , MARQUEZ C. , BENET J. , ANDOLZ P. , MARTINEZ P. 
Published: July 2007

SummaryFourteen mAb specific for human sperm membrane antigens were selected to investigate their inhibitory effect on fertilization. The antigens were not expressed in other human somatic tissues but were present in sperm from other species. The antibodies were purified from ascites fluid produced in mice. The zona‐free hamster egg penetration assay was used for the evaluation of the blocking ability of these antibodies. The inhibition rate was generally related to a decrease in the number of adherent sperm. Three groups of antibodies were distinguished: (i) four mAb that have high inhibition at concentration; (ii) four mAb with an intermediate inhibitory effect, that is more dependent on the antibody concentration tested; and (iii) six mAb with little or no effect at any concentration. The presence of antibodies leads to a lower penetration index, or number of penetrating sperm per oocyte.MAb specific for head antigens promote high inhibition of fertilization; these antibodies show a patchy staining on the sperm head. The antibodies localized in the midpiece have an intermediate inhibitory effect. No inhibition is detected with the equatorial region binding pattern. Sperm agglutination does not play any role in the inhibition caused by the antibodies described here.
Molecular associations involving CD 16, CD45 and ζ, and γ chains on human natural killer cells
Authors: ALTIN JOSEPH G. , PAGLER ELOISA B. , KINNEAR BEVERLEY F. , WARREN HILARY S. 
Published: July 2007

Summaryζ (CD3‐ζ) and γ (FcεRIγ) chains associate with CD 16. the low affinity receptor for IgG (FcλRIII) on human NK cells and are essential for the cell surface expression of CDI6 and for CD16‐mediated effector functions. This study has investigated whether, on NK cells, molecules other than CD16 associate with ζ, and γ chains, as a method of identifying other NK cell surface molecules important in NK cell function. Cell surface biotinylated NK cells were lysed in digitonin, and the lysates immunoprecipitated with mAb to CD 16, ζ, and γ and the immunoprecipitates analysed by SDS‐PAGE. CD 16 mAb co‐precipitated ζ and γ chains (16 and 12kD. respectively) and in addition molecules of 24. 32–35, 100, 150 and 180–200 kD. Also, C, mAb co‐precipitated ζ chain, and molecules of 24–26, 32–35. 48, 50–66, 100, 150 and 180–200 kD; and γ co‐precipitated ζ, chain, and molecules of 24–26, 29, 32–35, 37, 45, 49, 50–66 and 100 kD. While significant amounts of ζ, and γ were co‐precipitated with CD 16, 10 to 12‐fold more ζ and γ were immunoprecipitated with their respective mAb. Furthermore, depletion of CD 16 from the lysate resulted in only a partial (10–12%) depletion of ζ, and γ indicating that only a relatively small proportion (10–12%) of these molecules are associated with CD 16. Interestingly, substantial amounts of molecules with electrophoretic mobility similar to CD16 (50–66 kD) were co‐precipitated with ζ, and γ chain mAb from lysates depleted of CD16. In contrast to NK cells where I, associated with a number of different molecules, the majority of ζ, in T cells was found to be associated only with the TCR: CD3 complex. NK cells showed a strong association between CD45, CD 16 and a 33 kD molecule and often a strong association of ζ, with CD l6, CD45 and an unidentified molecule of −150 kD. Our results show first, that CD16, ζ and γ each can be efficiently labelled by cell surface biotinylation, and second, that CD 16, C, and γ each can form a complex with each other, and with a number of additional molecules including a 33 kD molecule and CD45 potentially important in NK cell function.
A 3.5 kb deletion in the glycophorin C gene accounts for the Gerbich‐negative blood group in Melanesians
Authors: SERJEANTSON S. W. , WHITE B. S. , BHATIA K. , TRENT R. J. 
Published: July 2007

SummaryThe Gerbich‐negative blood group types are rare in most populations, but reach appreciable frequencies in certain Melanesian groups in Papua New Guinea. The recent cloning of the human glycophorin C (GPC) gene, that encodes Gerbich (Ge) blood group antigens, has facilitated study of its genetic variants. We have obtained partial genomic clones of a normal GPC gene, for molecular analysis of Ge: −1,−2,−3 types in Melanesians, and have shown that a 3.5 kb deletion in the GPC gene that removes all of exon 3 accounts for at least one Gerbich‐negative phenotype in Melanesians. Population distributions of GPC RFLP have shown that the deletion‐type GPC is not confined to mainland Papua New Guinea as previously thought, but occurs sporadically in Melanesians from Fiji as well as in Micronesians.
Co‐selection in immune network theory and in AIDS pathogenesis
Authors: HOFFMANN GEOFFREY W. 
Published: July 2007

SummaryCo‐selection is a term used to denote the mutual positive selection of individual members from within two diverse populations, such that selection of members within one population is dependent on interaction with (recognition of) one or more member(s) within the other population. Co‐selection is a recurring theme of the idiotypic network model that my colleagues and I have developed. This paper discusses the role that co‐selection plays in basic symmetrical network theory and in a network model that resolves the I‐J paradox. It proposes that co‐selection of helper T cells and HIV variants plays a role in the pathogenesis of AIDS. The AIDS model involves a role for the T cell receptor in the infection of T cells. Finally, a way in which a co‐selection process may potentially be used in the prevention and therapy of harmful forms of immunity is described.
Metabolic consequences of methotrexate therapy in tumour‐bearing rats
Authors: ROFE A. M. , BOURGEOIS C. S. , WASHINGTON J. M. , PHILCOX J. C. , COYLE P. 
Published: July 2007

SummaryThe metabolic response of the tumour‐bearing host to methotrexate (MTX) therapy was investigated with particular attention to effects resulting from MTX‐induced anorexia. Biochemical changes in female Dark Agouti rats bearing mammary adenocarcinomas and treated with MTX (0.5 mg/kg. 2 i.m. injections, 24 h apart) were compared with untreated (CON) tumour‐bearing rats, and tumour‐bearing rats pair‐fed (PF) to the MTX group. MTX treatment halted progression of the tumour (tumour 6% of bodyweight) while the tumour burden doubled in the CON and PF groups.A number of biochemical and haematological changes were specific to MTX treatment and did not result from decreased food intake. MTX treatment was associated with significantly decreased plasma calcium, bilirubin, alkaline phosphatase, aspartate aminotransferase and the total white cell count. Decreases in plasma albumin and total protein concentrations were observed in both MTX and PF rats. Other parameters commonly used to assess renal and liver function were not significantly affected by MTX.MTX reversed the hypoglycaemia, hyperketonaemia and hypertriglyceridaemia induced by tumour‐bearing. In contrast, PF rats had an even more pronounced hypoglycaemia and hyperketonaemia than the CON rats. Measurement of glucose uptake in vivo with 2‐deoxy[U‐14C]‐glucose showed that MTX treatment halved the glucose requirement of the tumour (8.2% of bodyweight compared to 12.2% in the control). It is concluded that the potentially adverse effects of MTX treatment on host metabolism are outweighed by the beneficial effects of a reduced metabolic demand resulting from inhibition of tumour progression.
Antigen‐specific B cells in tissues after oral typhoid vaccination
Authors: GIBSON C. E. , PENTTILA I. A. , LEONG A. S‐Y. , ZOLA H. , LABROOY J. T. 
Published: July 2007

SummarySix human subjects who were to receive elective bowel surgery for a variety of diseases were vaccinated with the oral typhoid vaccine, Ty21a. Intestinal tissue (ileum in two, large intestine in four) removed 7‐26 days after the first dose of vaccine was examined for the presence and distribution of antigen‐specific B cells. This was compared with intestinal tissue derived from two unvaccinated controls. A number of B cell differentiation antigens were also assessed on these cells by immunofluorescence using dual‐labelling. Antigen‐specific cells were found randomly distributed in the lamina propria of all the vaccinated subjects in low frequency (6 ± 0.5 to 37 ± 31 [mean ± s.e.m.] antigen specific cells/10 mm2 of tissue). The lymphocyte differentiation antigens CD45RA, CD45RO. L‐selectin, CD‐1 la CD‐38, CD‐44 and VLA‐4 were all found on antigen‐specific cells, but no particular pattern was recognizable in this small series of six subjects with different disease processes affecting the intestine.
Characterisation of a large complex intragenic re‐arrangement in the FVII gene (F7) avoiding misdiagnosis in inherited factor VII deficiency
Authors: Giansily‐Blaizot Muriel , Thorel Delphine , Khau Van Kien Philippe , Behar Catherine , Romey Marie‐Catherine , Mugneret Francine , Schved Jean‐François , Claustres Mireille 
Published: July 2007

SummaryInherited factor VII (FVII) deficiency is a rare autosomal recessive bleeding disorder mostly caused by point mutations. Large genomic re‐arrangements at F7 locus could account for a fraction of mutant alleles that remain unidentified after DNA sequencing, because they escape conventional polymerase chain reaction (PCR)‐based techniques. We report the first systematic screening of F7 for large re‐arrangements, by semi‐quantitative multiplex PCR of fluorescent fragments targeting the 9 exons and the promoter region. A well‐characterised cohort of 43 unrelated patients either apparently homozygous for a F7 point mutation or carrying at least one unidentified F7 mutant allele participated in this study. Two large F7 re‐arrangements were identified in two FVII‐deficient pedigrees, including a discontinuous deletion involving two distinct portions of F7 whose proximal and distal end junctions were characterised. A simple and efficient method for the routine detection of gross alterations of F7, which accounted for 2.3% of mutant alleles in our sample, is now available in inherited FVII deficiency. This test should complement conventional PCR‐based techniques not only in unsolved cases, but also where inheritance pattern analysis is not achievable.
The local introduction of strongly interacting species and the loss of geographic variation in species and species interactions
Authors: BENKMAN CRAIG W. , SIEPIELSKI ADAM M. , PARCHMAN THOMAS L. 
Published: July 2007

AbstractSpecies introductions into nearby communities may seem innocuous, however, these introductions, like long‐distance introductions (e.g. trans‐ and intercontinental), can cause extinctions and alter the evolutionary trajectories of remaining community members. These ‘local introductions’ can also more cryptically homogenize formerly distinct populations within a species. We focus on several characteristics and the potential consequences of local introductions. First, local introductions are commonly successful because the species being introduced is compatible with existing abiotic and biotic conditions; many nearby communities differ because of historical factors and the absence of certain species is simply the result of barriers to dispersal. Moreover, the species with which they interact most strongly (e.g. prey) may have, for example, lost defences making the establishment even more likely. The loss or absence of defences is especially likely when the absent species is a strongly interacting species, which we argue often includes mammals in terrestrial communities. Second, the effects of the introduction may be difficult to detect because the community is likely to converge onto nearby communities that naturally have the introduced species (hence the perceived innocuousness). This homogenization of formerly distinct populations eliminates the geographic diversity of species interactions and the geographic potential for speciation, and reduces regional species diversity. We illustrate these ideas by focusing on the introduction of tree squirrels into formerly squirrel‐less forest patches. Such introductions have eliminated incipient species of crossbills (Loxiaspp.) co‐evolving in arms races with conifers and will likely have considerable impacts on community structure and ecosystem processes.
A regulatory protein–protein interaction governs glutamate biosynthesis in Bacillus subtilis: the glutamate dehydrogenase RocG moonlights in controlling the transcription factor GltC
Authors: Commichau Fabian M. , Herzberg Christina , Tripal Philipp , Valerius Oliver , Stülke Jörg 
Published: July 2007

SummaryGlutamate synthesis is the link between carbon and nitrogen metabolism. In Bacillus subtilis, glutamate is exclusively synthesized by the glutamate synthase encoded by the gltAB operon. The glutamate dehydrogenase RocG from B. subtilis is exclusively devoted to glutamate degradation rather than to its synthesis. The expression of the gltAB operon is induced by glucose and ammonium and strongly repressed by arginine. Regulation by glucose and arginine depends on the transcriptional activator protein GltC. The gltAB operon is constitutively expressed in a rocG mutant strain, but the molecular mechanism of negative control of gltAB expression by RocG has so far remained unknown. We studied the role of RocG in the intracellular accumulation of GltC. Furthermore, we considered the possibility that RocG might act as a transcription factor and be able to inhibit the expression of gltAB either by binding to the mRNA or to the promoter region of the gltAB operon. Finally, we asked whether a direct binding of RocG to GltC could be responsible for the inhibition of GltC. The genetic and biochemical data presented here show that the glutamate dehydrogenase RocG is able to bind to and concomitantly inactivate the activator protein GltC. This regulatory mechanism by the bifunctional enzyme RocG allows the tight control of glutamate metabolism by the availability of carbon and nitrogen sources.
Two Japanese cases of lichen planus pigmentosus‐inversus
Authors: Kashima Aki , Tajiri Akihiko , Yamashita Atsushi , Asada Yujiro , Setoyama Mitsuru 
Published: July 2007

Case 1 was a 51‐year‐old Japanese woman. She presented with an asymptomatic brown macule located on the right axilla of 2 months’ duration. The smooth macule was 2 cm in diameter with a sharp demarcation (Fig. 1A).Photographs of skin lesions in two patients. (A) Case 1. Well‐circumscribed brown macule without an active red border in the central portion of the right axilla. (B) Case 2. Symmetric distribution of brown macules without an active red border in the popliteal fossaeimageCase 2 was a 62‐year‐old Japanese man. He presented with asymptomatic, symmetric, gray–brown macules located on the groin, axillae, and popliteal region of 6 months’ duration. The smooth macules were several millimeters to centimeters in diameter and sharply demarcated (Fig. 1B).Oral or nail lesions, previous inflammatory processes in affected areas, and internal malignancies were absent. A causal relationship with drugs, recent sun exposure, or trauma could not be identified. Findings for work‐up, including blood cell count, fasting blood sugar levels, liver function, serum electrolyte levels, serum electrophoresis, urinalysis, antinuclear antibodies, and serological examinations for human hepatitis viruses and syphilis, were within normal limits or negative. The lesions gradually disappeared without medication within 6 months.Biopsy specimens showed a lymphocytic infiltrate with basal vacuolar changes and prominent melanin incontinence in the upper dermis (Fig. 2A). The band‐like lymphocytic infiltrate was moderate in Case 1 and mild in Case 2. Immunohistochemistry showed infiltrative CD8+ T lymphocytes with keratinocytic damage, indicating cytotoxic injury of the keratinocytes (Fig. 2B). Both the epidermis and the upper dermis contained CD1a+ cells (Fig. 2C). The keratinocytes focally and weakly expressed HLA‐DR (Fig. 2D). These findings were identical in samples from both patients.Light and immunohistochemical microphotographs. (A) Mild, band‐like, lymphocytic infiltrate with basal vacuolar change and prominent melanin incontinence in the upper dermis with apoptosis or necrosis of keratinocytes. (B) Epidermal infiltrate of CD8+ T lymphocytes with keratinocytic damage.

(C) CD1a+ cells in the upper dermis. (D) Keratinocytes focally and weakly express HLA‐DR (original magnifications: A, ×200; B–D, ×400)image
Distribution of clinical‐pathological types of cutaneous melanomas and mortality rate in the region of Passo Fundo, RS, Brazil
Authors: Borges Saionara Zago , Bakos Lucio , Cartell André , Wagner Mario , Agostini Aventino , Lersch Elder 
Published: July 2007

AbstractObjective  To describe the characteristics of all cases of primary cutaneous melanoma during the period 1995–2001, registered at pathology departments in the region of Passo Fundo.Methods  The sample studied consisted of 229 primary cutaneous melanoma lesions, identified by anatomopathological reports, in 218 patients. The variables evaluated were: sex, age, anatomical site, histological type, level of invasion and tumor thickness. The rate of incidence, mortality and survival curve were calculated.Results  The most frequent tumor site was in the back of men (49.5%) and in the lower limbs of women (33.1%). The most frequent clinical‐pathological type for both sexes was the superficial expansive type (superficial spreading) at 61.6%. The level of invasion was higher in men, using Clark level III (30.3%), than in women. In women the most frequent level of invasion was Clark level II (33.1%). Of the total number of lesions, 198 (47.2%) were ≤ 1 mm thick, and 23.2% of the men had thicker lesions (> 4 mm) than the women. The incidence was 5.67 per 100,000 patients‐year during this period and the mortality rate was 2.16 per 100,000 patients‐year.Conclusions  In the sample studied the most common sites were in the back of men and in the legs of women. The predominant type clinical‐pathological was superficial spreading.