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Biomedical subjects

B S Baker

Publications and source records attributed to B S Baker.

At least 127 records · Page 7Linked to original sources
PubMed1988

The control of alternative splicing at genes regulating sexual differentiation in D. melanogaster.

The transformer (tra) and doublesex (dsx) genes produce sex-specific transcripts that are generated by differential RNA processing. We have examined the effects of mutants in other regulatory genes controlling sexual differentiation on the patterns of processing of the tra and dsx RNA transcripts. Our results demonstrate that the genes suggested by genetic studies to act upstream of tra or dsx in the sex determination hierarchy regulate these two loci at the level of RNA processing. Our data suggest that the order of interaction of the factors controlling sex is X:A greater than Sxl greater than tra greater than tra-2 greater than dsx greater than or equal to ix greater than terminal differentiation. While these results cannot preclude regulatory interactions at other levels, the regulation of RNA splicing revealed by these experiments is sufficient to account for all of the known functional interactions between the regulatory genes in this hierarchy.

Alleles↗
PubMed1988

A molecular analysis of doublesex, a bifunctional gene that controls both male and female sexual differentiation in Drosophila melanogaster.

The doublesex (dsx) gene regulates somatic sexual differentiation in both sexes in Drosophila melanogaster. dsx has active but opposite negative regulatory functions in males and females. In males, the dsx locus represses the genes responsible for female sexual differentiation; male differentiation functions, not being repressed, are expressed. Conversely, in females, the dsx locus represses the genes involved in male sexual differentiation and the female sexual differentiation functions, not being repressed, are expressed. We have molecularly cloned the dsx locus by chromosomal walking and localized the gene within the cloned region by determining the positions of breakpoints of chromosomal rearrangements broken in dsx and in closely flanking regions. The dsx locus is about 40 kb in size. Its DNA is unique and appears to be organized in the same way in genomes of males and females. There is a developmentally and sexually regulated set of transcripts produced by the dsx locus. During the larval period, two sex-nonspecific dsx transcripts are produced. At the end of the larval period, these transcripts disappear and are replaced by a set of male-specific and female-specific transcripts. In adults, an additional male-specific transcript appears. Because genetic analysis has shown that transcription of the dsx locus must occur during the pupal period for proper sexual differentiation, we infer that the sex-specific transcripts seen during the pupal period correspond to the sex determination regulatory functions defined by mutational analysis. The regulation of dsx expression and possible roles of the other dsx transcripts are discussed.

Animals↗
PubMed1988

An altered response by psoriatic keratinocytes to gamma interferon.

To determine whether psoriatic keratinocytes differ from normal keratinocytes in their response to gamma interferon, epidermal cell suspensions from normal and from lesional and uninvolved psoriatic skin were cultured in the presence of gamma interferon and the induction of HLA-DR expression and inhibition of cell growth were measured. The addition of 10(2) units of gamma interferon/ml during a 7-day culture period significantly increased mean HLA-DR+ cell numbers in 21 epidermal suspensions of normal from 3.9 to 24.1% (P less than 0.0001), uninvolved psoriatic from 8.4 to 33.1% (P less than 0.0001), and to a lesser extent lesional psoriatic biopsies from 12.6 to 18.3% (P less than 0.01). However, the increase in HLA-DR+ cell numbers in these latter cultures was significantly less than that observed in either normal or uninvolved psoriatic epidermal cell cultures (P less than 0.0001). Furthermore, [3H]thymidine incorporation was substantially decreased by gamma interferon in 16 out of 22 (73%) cultures of normal epidermal cells; this decrease was statistically significant (P less than 0.01). In contrast, only 4 out of 11 (36%) lesional and 9 out of 21 (43%) uninvolved psoriatic epidermal cultures showed comparable inhibition of proliferation. These findings suggest that psoriatic keratinocytes have an altered response to gamma interferon; this could explain the infrequency of keratinocyte HLA-DR expression in psoriatic plaques in vivo and may also contribute to the increased epidermal proliferation that characterizes this disease.

Adult↗
PubMed1988

Epidermal DR+T6- dendritic cells in inflammatory skin diseases.

T lymphocyte and dendritic cell subpopulations were counted in three biopsies each of endogenous eczema and pityriasis rosea and two of lichen planus and compared with previous findings in psoriatic lesions. In common with psoriasis, proportionately more CD4 T cells than CD8 T cells were DR+ in both epidermis and dermis of all lesions. In addition, total numbers of epidermal dendritic cells were significantly increased in endogenous eczema and pityriasis rosea, and variably in lichen planus lesions. Interestingly, a DR+T6- subpopulation of dendritic cells was present in varying proportions in all three skin lesion types. Electron microscopy of DR+T6- dendritic cells from psoriatic lesions, using an immunogold staining technique, showed the cells to be of the Langerhans' cell lineage. DR+T6- dendritic cells are a subpopulation of Langerhans' cells which are not specific to psoriasis, but present in the lesions of other benign, inflammatory skin conditions in which CD4 T cells are preferentially activated.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

A prospective study of the Koebner reaction and T lymphocytes in uninvolved psoriatic skin.

T lymphocyte and dendritic cell subpopulations were counted in untraumatized, uninvolved skin of 27 patients with psoriasis. Eight of the patients proved to be Koebner-positive, as determined by tape stripping and punch biopsy, and 19 Koebner-negative. In the epidermis the CD4/CD8 T cell ratio was significantly higher in the Koebner-positive vis-à-vis Koebner-negative patients (median CD4/CD8 = 1.68 and 0.75, respectively: p less than 0.05). This resulted from a small increase in CD4 and a larger decrease in CD8 epidermal T cells in the Koebner-positive group. However, numbers of epidermal dendritic cells did not differ significantly between the two groups. In the dermis the CD4/CD8 T cell ratio was also higher in the Koebner-positive than in Koebner-negative patients (median of 3.56 and 2.57, respectively). These findings demonstrate that the tendency of uninvolved skin of psoriatic individuals to become lesional after trauma is associated with a predominance of CD4 over CD8 T cells in the epidermis.

Dendritic Cells↗
PubMed1987

A molecular analysis of transformer, a gene in Drosophila melanogaster that controls female sexual differentiation.

The transformer (tra) gene regulates all aspects of somatic sexual differentiation in Drosophila melanogaster females and has no function in males. We have isolated the tra gene as part of a 200 kb chromosomal walk. The 25 kb region around tra contains four genetically identified complementation groups and at least six transcriptional units. Germ-line transformation experiments indicate that a fragment of 2 kb is sufficient to supply tra+ function. Mapping of cDNAs from tra and from the adjacent genes indicates that the tra+ transcription unit is 1.2 kb or less. This transcription unit gives rise to a 1.0 kb RNA that is female-specific and a 1.2 kb RNA that is present in both sexes. tra+ and the gene at the 3' side overlap slightly in the 3' ends of their RNA coding sequences. These results suggest that tra+ function is regulated at the level of production of the female-specific tra RNA. The fact that a tra transcript is found in males raises interesting possibilities for how tra expression is controlled.

Animals↗
PubMed1987

Sequences expressed sex-specifically in Drosophila melanogaster adults.

To obtain probes for sex-specific gene regulation during development in D. melanogaster, sequences expressed sex-specifically in adult flies were isolated by differential cDNA hybridization screens of a genomic library. Ten clones define new sex-specifically expressed genes. The remaining three isolates correspond to previously cloned genes encoding female-specific yolk proteins and chorion proteins. The pattern of expression of these genes in sex determination mutants and in germlineless flies, as well as their tissue specificities, permitted us to distinguish transcripts whose expression is dependent on correct sexual development of the soma or the germline. One of the female transcripts is expressed in nurse cells and oocytes. Five of the male-specific sequences are expressed in the testis during spermatogenesis: the remaining one is expressed in the soma. Experiments using a temperature-sensitive allele of tra-2 show that the presence of this male-specific transcript, found only in the adult paragonia, is not affected by temperature shift of X/X; tra-2ts2 adults. This is in contrast to yolk protein genes, which require tra-2 function in the adult for their expression in the female fat body.

Animals↗
PubMed1987

Sexual behavior: its genetic control during development and adulthood in Drosophila melanogaster.

Courtship behavior in Drosophila melanogaster males is an innate behavior pattern. Whether or not a fly will display male courtship behavior is governed by the action of a set of regulatory genes that control all aspects of somatic sexual differentiation. The wild-type function of one of these regulatory genes, transformer-2 (tra-2), is necessary for female sexual differentiation; in the absence of tra-2+ function XX individuals differentiate as males. A temperature-sensitive tra-2 allele has been used to investigate, by means of temperature shifts, when and how male courtship behavior is specified during development. The removal of tra-2ts function in the adult (by a shift of the tra-2ts mutant flies to the restrictive temperature) can lead to the appearance of male courtship behavior in flies that otherwise would not display these behaviors. These experiments suggest that the regulatory hierarchy controlling sexual differentiation is functioning in the adult central nervous system. More importantly, these results suggest that the adult central nervous system has some functional plasticity with respect to the innate behavioral pattern of male courtship and is maintained in a particular state of differentiation by the active control of gene expression in the adult.

Animals↗
PubMed1987

The effects of cyclosporin A on T lymphocyte and dendritic cell sub-populations in psoriasis.

Sequential skin biopsies from six patients with severe psoriasis were studied during treatment with cyclosporin. Four of the patients cleared completely and the remaining two showed a marked improvement. A subset of dendritic cells, HLA-DR+ but lacking the T6 antigen characteristically expressed by Langerhans cells (DR+ 6-), was observed in lesional epidermis. They disappeared during treatment, before clinical improvement was apparent and at a rate which correlated with clearance of psoriasis. These cells were not found in normal or uninvolved psoriatic epidermis and their number in lesional skin appeared to be related to the clinical severity of the disease. Total numbers of CD4 and CD8, and HLA-DR+ CD8 T cells were substantially reduced in both epidermis and dermis prior to clinical improvement. In contrast, there was generally no decrease in the number of HLA-DR+ CD4 T cells in the epidermis during resolution, whereas these cells were reduced by an average of 68% in the dermis. The beneficial effects of cyclosporin in psoriasis further support the hypothesis that T cells play a central role in the pathogenesis of psoriasis. The cellular changes observed in the skin during cyclosporin treatment may help to elucidate the effects of this drug on immunoregulatory mechanisms in man.

Adult↗