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Biomedical subjects

B J Kerker

Publications and source records attributed to B J Kerker.

7 recordsLinked to original sources
PubMed1991

Endothelial expression of intercellular adhesion molecule (ICAM-1) is unaffected by marrow aplasia-inducing chemotherapy.

Sequential skin biopsies were obtained from five patients receiving chemotherapy for acute myelocytic leukemia. The first specimen was taken on the fourth day of initial chemotherapy and subsequent specimens were obtained at weekly intervals thereafter, until discharge. In all cases, clinically normal skin was selected as the biopsy site. A panel of monoclonal antibodies was applied to frozen tissue sections, including anti-intercellular adhesion molecule-1 (ICAM-1), anti-lymphocyte function-associated antigen-1 (LFA-1), and anti-HLA-DR. Bound antibody was detected using the avidin-biotin complex method. Endothelial cell expression of ICAM-1 and lymphocyte expression of LFA-1 were unaffected over the course of the ensuing, profound marrow aplasia. This finding suggests that this mechanism of lymphocyte trafficking in the skin remains operational despite the administration of antileukemic agents.

Amsacrine↗
PubMed1991

Disseminated hypopigmented keratoses.

We present two cases of asymptomatic, widespread keratotic eruptions in young female patients. Clinically, the lesions are well-demarcated, small, hypopigmented, flat-topped papules occurring on the trunk and extremities in a uniform distribution. Skin biopsy specimens from one patient revealed hyperorthokeratosis, papillomatosis, and a normal amount of melanin. We suggest that this is a newly recognized dermatologic entity that may be descriptively termed disseminated hypopigmented keratoses. Disseminated hypopigmented keratoses may be distinguished by clinical and histologic criteria from similar keratotic eruptions. Since the lesions of disseminated hypopigmented keratoses are both inconspicuous and asymptomatic, it is likely that the disorder is more prevalent than our two cases would suggest.

Adult↗
PubMed1990

The photoaggravated dermatoses.

The photoaggravated dermatoses are diverse diseases adversely affected by sunlight or artificial ultraviolet (UV) exposure. The role of UVR is often well-recognized, as in lupus erythematosus (LE) and bullous pemphigoid (BP). Immunologic theories for the cause of the photosensitivity in lupus erythematosus are the production of UV-DNA antibodies with subsequent immune complex formation, a partial defect in DNA repair following UV exposure, and the release or stimulation of potent cutaneous immunologic mediators. However, mechanisms are still not fully elucidated. Photosensitivity has also been described in erythema multiforme, actinic lichen planus, viral exanthems, cutaneous T-cell lymphoma, eczema, and psoriasis. Treatment is restriction of light exposure, use of high protection sunscreens, and treatment of the underlying disorder.

Animals↗
PubMed1990

Photochemotherapy of generalized granuloma annulare.

Various forms of treatment for generalized granuloma annulare have been employed with little success. The results of treatment with topical and intralesional corticosteroids, as well as systemic therapy with corticosteroids, salicylates, aspirin, niacinamide, and chloroquine, have been generally disappointing. We describe five patients with generalized granuloma annulare of several years' duration who were treated with oral psoralen plus ultraviolet A irradiation. Lesions were present on the extremities, buttocks, and trunk in the form of macules, papules, and plaques. One patient also had perforating lesions on her thighs. Flattening of the lesions with decreased erythema and pigmentation was noted as early as 1 month after initiation of treatment. Complete clearance was achieved in all patients. Maintenance therapy has been required, resulting in prolonged disease-free intervals. Although the mechanism of action of oral psoralen plus ultraviolet A irradiation in granuloma annulare is unclear, one possibility is selective elimination of the cells that are responsible for initiating the disease.

Adult↗
PubMed1987

Site-directed mutagenesis of core sequence elements 9R', 9L, 9R, and 2 in self-splicing Tetrahymena pre-rRNA.

The intron within the Tetrahymena thermophila nuclear large rRNA precursor is the best studied example of group I self-splicing introns. In this paper, we examine the structural and functional roles of four internal sequence elements which are characteristic of group I introns in the RNA-catalyzed processing reactions. Oligonucleotide-directed mutagenesis was used to generate mutations in sequence elements 9R', 9L, 9R and 2 of the Tetrahymena intervening sequence. Self-splicing activities of variant precursor RNAs were characterized by in vitro splicing following transcription with T7 or SP6 RNA polymerase. First, we confirm the proposed base pairing of sequence elements 9R and 9R' by construction and analysis of compensatory mutations. Mutations in elements 9R (G272A C274G) and 9R' (G100C C102U) each disrupt the pairing and eliminate self-splicing activity. A compensatory 9R/9R' mutation (G100C C102U G272A C274G) restores pairing and normal splicing activity. We conclude that 9R X 9R' pairing is a requirement for self-splicing. Second, we show that self-splicing activity is very sensitive to both nucleotide sequence and RNA secondary structure in the pairing segments of elements 9L and 2. Mutations within these regions at positions 266, 268, 307, and 309 can increase as well as decrease activity relative to wild type. Third, a mutation in the highly conserved nonpairing segment of element 9L (U259A A261C) increases KM for GTP from 29 to 120 microM, but does not otherwise affect splicing activity. The primary consequence of this mutation is a decrease in GTP binding energy of approximately 0.9 kcal/mol. Last, we show that a mutation in the highly conserved nonpairing segment of element 2 (A301C A302G G303C) eliminates transesterification activity, but does not affect 3' splice site hydrolysis.

Animals↗
PubMed1986

Role of conserved sequence elements 9L and 2 in self-splicing of the Tetrahymena ribosomal RNA precursor.

Oligonucleotide-directed mutagenesis has been used to alter highly conserved sequences within the intervening sequence (IVS) of the Tetrahymena large ribosomal RNA precursor. Mutations within either sequence element 9L or element 2 eliminate splicing activity under standard in vitro splicing conditions. A double mutant with compensatory base changes in elements 9L and 2 has accurate splicing activity restored. Thus, the targeted nucleotides of elements 9L and 2 base-pair with one another in the IVS RNA, and pairing is important for self-splicing. Mutant splicing activities are restored by increased magnesium ion concentrations, supporting the conclusion that the role of the targeted bases in splicing is primarily structural. Based on the temperature dependence, we propose that a conformational switch involving pairing and unpairing of elements 9L and 2 is required for splicing.

Animals↗