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Biomedical subjects

B S Baker

Publications and source records attributed to B S Baker.

At least 145 records · Page 8Linked to original sources
PubMed1985

Specific switching on of silent egg protein genes in vitro by an S-100 fraction in isolated nuclei from male Xenopus.

A soluble post-nuclear extract (S-100) specifically switches on the permanently silent vitellogenin genes in male Xenopus liver nuclei in vitro. Using cloned cDNAs to albumin, globin and vitellogenin mRNAs as hybridization probes, and heparin as an inhibitor of initiation of transcription, run-on assays with nuclei faithfully reproduced the transcriptional status of these genes in vivo. In the absence of heparin, a liver S-100 extract from female or male Xenopus treated with estradiol, but not from hormonally untreated males, induced the de novo transcription of vitellogenin genes in nuclei from hormonally naive male hepatocytes. The activation of the dormant genes was dependent on pre-incubation of nuclei with the competent extract for a minimum of 45 min at 24 degrees C before transcription was initiated. The same extract did not alter significantly the transcription of albumin and globin genes. The S-100 fraction from hormonally stimulated male hepatocytes exhibited a high degree of tissue specificity; it did not activate the transcription of vitellogenin genes in Xenopus erythrocyte and oviduct nuclei, and only slightly in nuclei from Xenopus XTC-2 cells, while a soluble extract from oviduct only slightly induced their transcription in male hepatocyte nuclei. This is the first demonstration of a hormone- and tissue-specific de novo activation of dormant genes by a soluble cell extract in isolated nuclei and offers a new approach to analyzing steroid hormone action and tissue-specific transcription factors in the regulation of gene expression.

Animals↗
PubMed1985

Sex-specific regulation of yolk protein gene expression in Drosophila.

Many of the genes in the regulatory hierarchy controlling sex determination in Drosophila melanogaster are known. Here we examine how this regulatory hierarchy controls the expression of the structural genes encoding the female-specific yolk polypeptides. Temperature shift experiments with a temperature-sensitive allele of the sex determination regulatory gene transformer-2 (tra-2) showed that tra-2+ function is required in the adult for both the sex-specific initiation and maintenance of YP synthesis. Control of the YP genes by this regulatory hierarchy is at the level of transcription, or transcript stability. The results of temperature shift experiments with abdomens isolated from tra-2ts homozygotes support the notion that the tra-2+ function acts in a cell-autonomous manner to control YP synthesis. These results provide a paradigm for the way this regulatory hierarchy controls the terminal differentiation functions for sexually dimorphic development.

Animals↗
PubMed1985

Vitellogenin genes and their products in closely and distantly related species of Xenopus.

Plasma vitellogenins from two closely related species of Xenopus, X. laevis and X. borealis, and a more ancient species, X. tropicalis, exhibited the same size on gel electrophoresis and were immunologically related. Partial peptide maps of 125I-labelled plasma vitellogenins, however, revealed marked differences in th structure and organisation of vitellogenin in the three Xenopus species. Northern blot hybridisation of liver RNA from oestrogen-treated males and females, probed with cloned vitellogenin cDNA, revealed the presence of mRNA of the same size in the three species of Xenopus, which was absent in untreated male liver. Cell-free translation of total liver RNA showed the presence of functional mRNA coding for vitellogenin subunit of the same size (Mr congruent to 210,000). Restriction endonuclease digestion patterns of genomic DNA from the three Xenopus species, using cloned X. laevis vitellogenin cDNA as the hybridisation probe, revealed significant differences in the organisation of these genes, which occur at a higher multiplicity in X. laevis and X. borealis than in X. tropicalis. Thus, despite a high degree of conservation of size, overall sequence and immunological identity of vitellogenin genes and their products in the three species of Xenopus, there is a substantial structural rearrangement during evolution of Xenopus within this multigene family.

Animals↗
PubMed1985

Mutations in genes encoding essential mitotic functions in Drosophila melanogaster.

Temperature-sensitive mutations at 15 loci that affect the fidelity of mitotic chromosome behavior have been isolated in Drosophila melanogaster. These mitotic mutants were detected in a collection of 168 EMS-induced X-linked temperature-sensitive (ts) lethal and semilethal mutants. Our screen for mutations with mitotic effects was based upon the reasoning that under semirestrictive conditions such mutations could cause an elevated frequency of mitotic chromosome misbehavior and that such events would be detectable with somatic cell genetic techniques. Males hemizygous for each ts lethal and heterozygous for the recessive autosomal cell marker mwh were reared under semirestrictive conditions, and the wings of those individuals surviving to adulthood were examined for an increased frequency of mwh clones. Those mutations producing elevated levels of chromosome instability during growth of the wing imaginal disc were also examined for their effects on chromosome behavior in the cell lineages producing the abdominal cuticle. Fifteen mutations affect chromosome behavior in both wing and abdominal cells and thus identify loci generally required for the fidelity of mitotic chromosome transmission. Mapping and complementation tests show that these mutations represent 15 loci. One mutant is an allele of a locus (mus-101) previously identified by mutagen-sensitive mutants and a second mutant is an allele of the lethal locus zw 10.--The 15 mutants were also examined cytologically for their effects on chromosomes in larval neuroblasts. Taken together, the results of our cytological and genetical studies show that these mutants identify loci with wild-type functions necessary for either maintenance of chromosome integrity or regular disjunction of chromosomes or chromosome condensation. Thus, these mutations define a broad spectrum of genes required for the normal execution of the mitotic chromosome cycle.

Alleles↗
PubMed1985

The effects of topical treatment with steroids or dithranol on epidermal T lymphocytes and dendritic cells in psoriasis.

We describe the effects of treatment with topical steroids or dithranol on T and dendritic cells in the skin of patients with chronic plaque psoriasis. Resolution of lesions by both types of topical treatments was accompanied by a marked decrease in epidermal T cells. In steroid treated lesions there was also a reduction in DR+ dendritic cells to normal numbers during treatment and the rate of disappearance of both cell types correlated with the rate of resolution. However, a significant reduction of dendritic cells was not usually observed until after the T cells had almost disappeared from the epidermis and substantial healing of lesions had taken place. Dendritic cells in steroid-treated uninvolved skin had decreased to a lower level than in normal skin. In contrast, dithranol did not affect dendritic cells, either in lesional or in unaffected psoriatic epidermis. The decrease in dermal T cells observed with both treatments was more marked in steroid-treated lesions and correlated with resolution. However, blood T cells were unaffected by both treatments. The findings provide further support for the role of T cells in the pathogenesis of psoriasis.

Administration, Topical↗
PubMed1985

Epidermal T lymphocytes and dendritic cells in chronic plaque psoriasis: the effects of PUVA treatment.

The numbers and HLA-DR expression of T cell subsets and dendritic cells in chronic psoriatic plaques were compared to previously reported findings in spontaneously resolving guttate lesions, and the effects of PUVA treatment on these cell populations studied. The chronic lesions showed a similar T helper/T suppressor (TH/TS) ratio (0.66 +/- 0.10) to resolving guttate lesions. However, in contrast to the resolving lesions which do not contain activated epidermal TH cells, a substantial proportion of the TH cells in the persistent plaques were DR+. Moreover, these persistent lesions contained markedly increased numbers of DR+ dendritic cells, approximately 20% of which were T6 negative. PUVA-induced resolution of chronic lesions was associated with depletion of epidermal TH and TS cells, and a subsequent reduction in DR+ dendritic cells. In each patient the rate of disappearance of both cell types correlated with the rate of resolution. Furthermore, the epidermal T cell depletion preceded the onset of clinical improvement. In contrast, significant reduction of the dendritic cells was generally not observed until the lesions were largely resolved. Dendritic cells decreased faster in uninvolved than in lesional skin and to a subnormal level. Dermal T cells also decreased during PUVA therapy but this did not show any obvious correlation with resolution of the lesions. Blood T cell levels were not significantly affected by the treatment. These findings support the concept that the initiation and maintenance of the psoriatic process requires activation of TH cells in the epidermis via interaction with antigen presenting cells. Furthermore PUVA treatment may clear psoriasis by interfering with such a mechanism through its effects on T lymphocytes.

Adult↗
PubMed1984

Sex- and tissue-specific, but hormonally independent, demethylation at the 3'-end of Xenopus vitellogenin gene B1.

We describe three HpaII-specifying sequences in 6 kbp of DNA at the 3'-end of Xenopus vitellogenin gene B1 (two within the coding sequence and one downstream) which remain methylated in all tissues of adult male Xenopus. These sites are however fully demethylated exclusively in adult Xenopus liver parenchymal cells but not in oviduct, kidney or erythrocytes. Developmental studies suggest that this tissue- and sex-specific demethylation may occur gradually after metamorphosis. The methylation of these 3'-sites is independent of transcriptional activation by oestrogen of vitellogenin genes in male or female Xenopus.

Animals↗
PubMed1984

Epidermal T lymphocytes and HLA-DR expression in psoriasis.

Double staining immunofluorescent techniques and monoclonal antibodies were used to study the numbers, distribution, HLA-DR expression and relationship of T-cell subpopulations and dendritic cells in psoriatic skin. In the dermis there was a definite increase in both T helper and T suppressor cells in uninvolved skin of psoriatic patients, and the appearance of clinical lesions was not associated with any detectable change in the numbers of these cells in the dermis. In contrast, eruption of skin lesions was associated with an increase in the numbers of epidermal HLA-DR+ dendritic cells and also with epidermal influx and activation of T helper cells, while resolution of lesions coincided with increased epidermal entry and activation of T suppressor cells. Both the T helper and T suppressor cells were preferentially found adjacent to epidermal dendritic cells. These findings suggest that the clinical activity of psoriasis may be dependent upon the interaction of T helper and suppressor cells with antigen-presenting cells in the epidermis.

Antibodies, Monoclonal↗
PubMed1984

T-cell subpopulations in the blood and skin of patients with psoriasis.

Monoclonal antibodies were used to determine, simultaneously, the proportions of T-cell populations in the peripheral blood and in the skin lesions of fifty-one patients with psoriasis. The results were analysed in relation to the extent, age and clinical type of the skin lesions. In the group of patients with extensive lesions, a significant reduction in the number of total T (TT) and T helper/inducer-cells, (TH), but not in T suppressor/cytotoxic cells (TS) was observed in the peripheral blood. Furthermore, the skin TH/TS ratio was greater in late guttate and in chronic plaque lesions than the corresponding ratio in the blood. These findings suggest that there is an active selective recruitment of TH cells into established psoriatic lesions. In contrast, the TH/TS ratio in early guttate lesions was the same as in the blood, and significantly lower than in the plaque lesions. An additional finding was a decrease of TS, and a corresponding increase of null cells in the blood of patients with chronic plaque psoriasis. These observations provide further evidence for the participation of T cells in the pathogenesis of psoriasis.

Antibodies, Monoclonal↗
PubMed1983

A gene controlling condensation of heterochromatin in Drosophila melanogaster.

A temperature-sensitive lethal mutant of Drosophila melanogaster was used to identify an essential cell cycle function that is necessary for the mitotic condensation of heterochromatic but not of euchromatic portions of the genome. This mutant is an allele at a locus (mus-101) identified earlier by the use of mutagen-sensitive mutants. The data suggest that the mutagen-sensitive and repair-defective phenotypes of viable mus-101 mutants result from a disruption in chromosome organization.

Animals↗
PubMed1983

The dual functions of a sex determination gene in Drosophila melanogaster.

The wild-type function of the sex transforming gene transformer-2 (tra-2) is shown to be required for normal spermatogenesis in XY males. A temperature-shift experiment using the tra-2ts2 allele suggests that tra-2+ must function during the middle stages of spermatogenesis to ensure development of functional sperm. Our results, taken together with those of T. Schüpbach (1982, Dev. Biol. 89, 117-127) indicate that the tra-2+ gene functions in the male germ line and thus, in contrast to all other sex determination loci examined to date (doublesex, intersex, transformer), its action is not limited to the soma. Orcein-stained testis preparations from tra-2 males reveal a spermiogenic defect similar to that associated with dominant male sterile (X; autosome) translocations.

Animals↗
PubMed1982

Region-specific effects on chromosome integrity of mutations at essential loci in Drosophila melanogaster.

Two mutagen-sensitive loci of Drosophila melanogaster, mus-105 and mus-109, previously identified by viable alleles, are shown to specify essential functions. Lethal alleles at the loci produce larvae that have degenerate imaginal discs and die at the larva-pupa boundary. Our data suggest that the causes of lethality are intolerable levels of cell death produced by high frequencies of chromosome aberrations (in excess of 0.5 aberration per cell per cycle). The pattern of aberrations is a locus-specific character. In mus-105 mutants the most common aberrations are breaks and exchanges in euchromatic portions of the genome whereas in mus-109 mutants the most common aberrations are breaks at heterochromatin-euchromatin junctions. The sensitivity of these junctions to breakage in mus-109 mutants is a property of all such junctions whether natural or produced by a rearrangement that juxtaposes heterochromatin and euchromatin. Larvae carrying the combination of two viable mutants, mus-105(A1) mus-109(D1), die at the larva-pupa boundary and display a high frequency of aberrations (0.7 per cell vs. 0.075 for either mutant alone) clustered at euchromatin-heterochromatin junctions. This synergistic interaction suggests there is a class of lesions that can be repaired by both mus-105(+) and mus-109(+). Thus, the apparent euchromatic specificity of mus-105(+), which was inferred from the pattern of predominantly euchromatic breakage observed in mus-105 mus-109(+) flies, is in fact generated by the wild-type function of mus-109(+) masking an effect of mus-105 in the heterochromatin. The fact that lethal mutants at the mus-105 and mus-109 loci have small imaginal discs coupled with the observation of a maternal effect of mus-105 suggests a paradigm for the control of cell division during the life cycle of Drosophila.

Alleles↗
PubMed1982

Sex determination in Drosophila melanogaster: analysis of transformer-2, a sex-transforming locus.

The transformer-2 (tra-2) locus is one of a set of regulatory loci that control sex determination in Drosophila melanogaster. Temperature-shift experiments with temperature-sensitive tra-2 mutants demonstrate that within single cell lineages tra-2+ function is required at several times, and probably continuously, during development for the occurrence of a series of determinative decisions necessary for female sexual differentiation. Analysis of the effects of tra-2 in the genital disc demonstrates that the tra-2+ function is necessary in females both to prevent male sexual differentiation and to permit female differentiation. These and other results support the model that the tra-2+ and tra+ loci act to control the expression of the bifunctional doublesex (dsx) locus.

Animals↗
PubMed1982

Specificity of immunoglobulin E in coccidioidomycosis and correlation with disease involvement.

Serum immunoglobulin E (IgE) antibodies were quantitated in 26 patients with active pulmonary coccidioidomycosis, 59 patients with active disseminated disease, 12 patients in clinical remission, and 91 healthy subjects. Significant differences were obtained in IgE serum levels of patients with active disease versus healthy subjects (P less than 0.0001). Patients with pulmonary coccidioidomycosis did not differ in their IgE levels when compared with patients with disseminated disease. However, serum IgE levels were significantly increased in patients with disease involving two or more organ systems when compared with patients with pulmonary disease or extrapulmonary disease involving a single organ system (P less than 0.02). Total serum IgE correlated with anti-Coccidioides IgE (P less than 0.001), but with only six exceptions, patients with anti-Coccidioides IgE also exhibited IgE antibodies to 1 or more of 12 common allergens. The correlation between hyperproduction of IgE and disease severity coupled with the depressed cell-mediated immune status of patients with this disease suggests a defect(s) in the T-lymphocyte population which functions to regulate IgE synthesis.

Allergens↗