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Biomedical subjects

S Coleman

Publications and source records attributed to S Coleman.

At least 73 records · Page 4Linked to original sources

Ductal morphogenesis in the mouse mammary gland: evidence supporting a role for epidermal growth factor.

Epidermal growth factor (EGF) is a potent mitogen for a variety of cells in vitro, but studies on its effects in vivo and its possible role as a natural growth regulator are few. Using slow-release plastic implants, capable of delivering EGF to small regions of the gland over a period of several days, we have shown that EGF reinitiated ductal growth and morphogenesis in growth-static glands of ovariectomized mice. The effects of implanted EGF were confined to the zone around the implant and were time and dose dependent. Unimplanted glands in the same animal were unaffected. Local effects included (1) the formation of new ductal growth points (end buds), (2) the restoration of normal end bud histomorphology and the reappearance of a stem (cap) cell layer, (3) the reinitiation of epithelial DNA synthesis, and (4) an increase in ductal diameter. No lobulo-alveolar or hyperplastic growth was seen. Competitive binding assays and autoradiography were used to characterize EGF receptor activity in growing and static glands. High and low affinity receptors were demonstrated in each tissue, while 125I-EGF autoradiography revealed differential, specific binding of the ligand to certain epithelial and stromal elements. In the epithelium, label was concentrated in the cap cells of the end buds and in myoepithelial cells of the mammary ducts. Stromal cell label was heaviest adjacent to the epithelium in the end bud flank and subtending ducts, suggesting the induction of stromal EGF receptors by mammary epithelium. Because exogenous EGF is both a mitogenic and morphogenetic factor in this tissue and can serve as a locally acting substitute for known systemic mammogens such as estrogen and prolactin, it must be considered a strong candidate for a naturally occurring mammary tissue mitogen.

Animals↗

Linkage of prion protein and scrapie incubation time genes.

A single gene (Prn-i) that affects scrapie incubation period in mice has been identified. I/LnJ mice have a very long incubation period after inoculation of scrapie prions (200-385 days) and NZW/LacJ mice have a short one (113 +/- 2.8 days). (NZW X I/Ln)F1 hybrid mice had incubation times of 223 +/- 2.8 days indicating longer incubation times were dominant. Incubation periods in the backcross progeny of (NZW/LacJ X I/LnJ)F1 X NZW/LacJ segregated into two groups (64 mice, 130 +/- 1.1 d; 66 mice, 195 +/- 1.9 d) indicating single gene control. NZW/LacJ and 20 other inbred strains have the Prn-pa allele which is identified as a 3.8 kb Xbal fragment using a hamster PrP (prion protein) cDNA probe. I/LnJ and three other Prn-pb mouse strains have a 5.5 kb Xbal restriction fragment. Analysis of DNA from 66 backcross mice indicated Prn-i is tightly linked to Prn-p, the structural gene for PrP.

Animals↗

In vivo, cAMP stimulates growth and morphogenesis of mouse mammary ducts.

In culture, cAMP is known to be mitogenic for mammary cells and several other epithelia, but evidence for a similar role in vivo has been only correlative. We have used plastic implants to cause slow release of cholera toxin and other cAMP-active agents to local areas of mammary glands in ovariectomized mice. Elevated levels of intracellular cAMP around the implants promoted vigorous growth and normal ductal morphogenesis, while distant sites were unaffected. Local effects of cAMP included restoration of normal ductal caliber, formation of new end buds, and reinitiation of DNA synthesis in both epithelium and surrounding stroma. Thus, cAMP is both a mitogenic and a morphogenetic factor in this tissue.

Animals↗

Activation of trypanosome surface glycoprotein genes involves a duplication-transposition leading to an altered 3' end.

Expression of the genes for variant surface glycoproteins 117 and 118 in Trypanosoma brucei is accompanied by the appearance of an extra copy of these genes, the expression-linked copy, which differs in the surrounding restriction enzyme sites from the corresponding basic copy of the genes. We present direct evidence that the expression-linked copy is the one used for messenger RNA synthesis. By S1-nuclease-protection experiments we show that cloned basic-copy genes contain the nucleotide sequence of the corresponding messenger RNA except for the last 100 to 150 nucleotides before the poly(A) tail. Comparison of the 3'-terminal sequence of the 117 basic-copy gene and the 117 complementary DNA shows that this region differs by multiple point mutations, insertions and deletions, the differences starting within the coding sequence. Genomic blots demonstrate that a Bsp I site in the 3'-terminal part of the 118 complementary DNA is present in the expression-linked copy but not in the basic-copy gene. We conclude that expression-linked copies are the active genes, and that the generation of expression-linked copies involves a duplication--transposition in which the 3' end of the gene is replaced.

Amino Acid Sequence↗

Manganese pollution in the city environment and its relationship to traffic density.

As lead is phased out of gasoline, other additives with anti-knock properties, particularly organic manganese compounds, are being substituted. Unavoidably, such compounds go through the combustion process, are eliminated in exhaust gases, and become part of the city environment. To obtain some indication of the extent of this new pollution street soils from various locations in a heavily trafficked city (Newark, NJ) were analyzed for manganese and lead by atomic absorption. Highly signigicant inverse relationships were found between the concentrations of both contaminants and distances from major traffic arteries. Strong circumstantial evidence is thus provided that: 1) manganese pollution is occurring, along with lead, in the city environment; 2) this new pollution is related to traffic density; and 3) the most likely sources are automobile exhausts. This suspicion is further strengthened by the significant correlations observed between manganese and lead contents in children's blood, suggesting a common source for both. Substantiation of the safety of this practice of adding manganese to gasoline is needed.

Automobile Driving↗

Coxa vara: surgical outcomes of valgus osteotomies.

Since the 1950s, valgus-producing femoral osteotomy has been the preferred treatment for significant coxa vara. Despite well-performed surgeries, the literature cites recurrence rates of 30-70%. The present study reviews our past 15 years of surgical experience for coxa vara; 26 children with 37 affected hips were retrospectively evaluated for outcome following valgus osteotomy. Both congenital and acquired types of coxa vara were included. Overall recurrence rate following valgus osteotomy was 50%. Age at time of surgery, type of surgery, and type of implant and etiology were found to have no bearing on recurrence. However, if Hilgenreiner's epiphyseal angle was corrected to < 38 degrees, 95% of children had no recurrence of varus. In contrast, head-shaft angle was found not to be a reliable indicator of appropriate correction. Only six of 37 hips required pelvic osteotomy (five Pemberton, one Chiari) for dysplasia, and four of these had developmental dysplasia of the hip as the underlying etiology for their coxa vara. However, if the proximal femur was corrected and maintained before age 10, 83% of children had excellent acetabular depth, spherical congruency, relief from pain, and correction of Trendelenburg gait at latest follow-up.

Child↗

Complications of long arm-catheters: a randomized trial of central vs peripheral tip location.

BACKGROUND: This two-part study initially evaluated complications associated with catheters inserted via upper extremity veins. The second prospective phase compared thrombotic risk of peripheral catheter tips vs a central vein terminus. METHODS: Patients from public institutions with infectious diseases were observed throughout their inpatient and outpatient use of IV catheters. Seventy-two and 39 patients enrolled in phase 1 and phase 2, respectively. Phase 1 consisted of prospective observations and analysis of complications and associated risk factors. Phase 2 randomized patients to a catheter tip location in the superior vena cava or the axillosubclavian-innominate vein and compared the incidence of thrombosis, phlebitis, and infection. RESULTS: In phase 1, there was an increased risk of thrombosis with peripheral tip localization (61% vs 16%, p < .05). Phase 2 confirmed increased thrombosis with tips in the axillosubclavian-innominate vein compared with the superior vena cava (60% vs 21%, p < .05) with an improved survival for central tip catheters (p < .02). Catheters associated with thrombosis were more likely to become infected (r = 0.48, p < .02). CONCLUSIONS: The experience supports use of the long arm catheter as an effective device for parenteral therapy. A novel method for placing these catheters makes most patients candidates for this approach. Placing a long arm-catheter's tip in the central venous circulation reduces the risk of thrombosis. A high incidence of tip misdirection indicates a need for radiographic confirmation before use.

Adult↗