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Biomedical subjects

J M Davidson

Publications and source records attributed to J M Davidson.

At least 109 records · Page 6Linked to original sources
PubMed1988

Recombinant basic fibroblast growth factor accelerates wound healing.

Basic fibroblast growth factor (bFGF) stimulates extracellular matrix metabolism, growth, and movement of mesodermally derived cells. We have previously shown that collagen content in polyvinyl alcohol sponges increased after bFGF treatment. We hypothesized that bFGF-treated incisional wounds would heal more rapidly. After intraperitoneal pentobarbital anesthesia, male, 200- to 250-g, Sprague-Dawley rats (n = 27) each underwent two sets of paired, transverse, dorsal incisions closed with steel sutures. On Day 3 postwounding, 0.4 ml of bFGF (recombinant, 400 ng. Synergen) or normal saline was injected into one of each paired incisions. Animals were killed with ether on postwounding Days 5, 6, and 7 and their dorsal pelts were excised. Fresh or formalin-fixed wound strips were subjected to tensile strength measurements using a tensiometer. Breaking energy was calculated. Wound collagen content (hydroxyproline) was measured in wound-edge samples following hydrolysis using high-performance liquid chromatography. There was an overall significant increase in fresh wound tensile strength (13.7 +/- 1.06 vs 19.1 +/- 1.99 g/mm, P less than 0.01) and wound breaking energy (476 +/- 47 vs 747 +/- 76 mm2, P less than 0.001) in bFGF-treated incisions. There was an increase in wound collagen content which was not statistically significant and there was no difference in fixed incisional tensile strength. Histologic examination showed better organization and maturation in bFGF wounds. Recombinant bFGF accelerates normal rat wound healing. This may be due to earlier accumulation of collagen and fibroblasts and/or to greater collagen crosslinking in bFGF-treated wounds.

Animals↗
PubMed1988

Increased elastin production by progeria skin fibroblasts is controlled by the steady-state levels of elastin mRNA.

Hutchinson-Gilford progeria is a unique, rare disease with markedly accelerated aging. The average lifespan of affected individuals is 12 years. Although the biochemical basis of the syndrome is unknown, its influence appears to be primarily upon mesodermal tissues. Characteristics such as the altered appearance of the skin and the extensive and fatal involvement of the cardiovascular system led us to study elastin production in cultured skin fibroblasts from three progeroid individuals. We found tropoelastin production by progeroid cells was elevated six- to nine-fold at the protein and mRNA levels, while relative collagen synthesis was similar to control strains. There was little difference between progeroid and normal cells in expression of total protein or in total cellular mRNA content. Western blot analysis of tropoelastin from progeroid fibroblasts confirmed increased production of elastin but revealed no gross changes in the molecular mass. The significant increase in tropoelastin expression lends support to the concept that progeria results from a mesenchymal dysplasia, and offers a possible biochemical marker for the phenotype.

Adolescent↗
PubMed1988

Enhanced cold pressor response in spontaneously hypertensive rats on high-NaCl diet.

This study sought to determine whether spontaneously hypertensive rats (SHR) on a high-NaCl diet have an enhanced pressor response to acute cold exposure and to define the peripheral mechanisms involved in the enhanced pressor response. SHR and normotensive Wistar-Kyoto (WKY) rats that had been on 1 and 8% NaCl diets for 3 wk were subjected to cold exposure. After a 30-min control period, animals were exposed to cold (6 +/- 2 degrees C) for 90 min. Mean arterial pressure (MAP), heart rate (HR), and lumbar sympathetic nerve activity (LSNA) were measured continuously. In a separate group of SHR on 1 and 8% NaCl diets, an arginine vasopressin (AVP) V1 receptor antagonist (10 micrograms/kg iv) was given before cold exposure, and MAP was measured throughout cold exposure. Plasma AVP was measured before and during cold exposure in a separate group of SHR. During cold exposure, there was a significant increase (P less than 0.05) in MAP (25 mmHg) in SHR on the 8% NaCl diet only. In contrast, HR and LSNA increased similarly during cold exposure in both SHR and WKY on the two diets. AVP was similar in both SHR groups (7.1 pg/ml for 1% vs. 6.1 pg/ml for 8%) before cold exposure, but during cold exposure it increased in the 8% NaCl SHR only, reaching 17.6 pg/ml at 90 min. The AVP V1 antagonist completely abolished the cold stress-induced rise in MAP in SHR. Thus SHR on a high-NaCl diet have an enhanced pressor response to acute cold exposure compared with SHR on a normal NaCl diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Isolation and characterization of human elastin cDNAs, and age-associated variation in elastin gene expression in cultured skin fibroblasts.

In attempts to isolate human elastin cDNAs, a human placental lambda gt11 cDNA library was screened with a 1.3 kilobase sheep genomic DNA subclone, corresponding to the 3'-end of the elastin mRNA. The four largest clones, the largest being approximately 3 kilobase, were characterized by Northern transfer analyses, restriction endonuclease digestions and dideoxy nucleotide sequencing. Northern transfer analyses of poly(A)+RNA revealed hybridization to mRNA transcripts in the region of 3.5 kilobase. Restriction endonuclease mapping and nucleotide sequencing demonstrated distinct domains characteristic of elastin, and identified areas of variability which apparently reflects alternative splicing of the primary elastin transcripts. To demonstrate the utilization of these cDNAs for studies on elastin gene expression in human cells, elastin mRNA was examined in fibroblast cultures established from the skin of several individuals of varying ages. Northern transfer analyses and slot blot hybridizations demonstrated that elastin gene expression is initiated early during fetal development, and continues at a relatively constant level through several decades. The lowest abundance of elastin mRNA was noted in the cell cultures established for the oldest individual studied (61-year-old female). Demonstration of elastin gene expression in cultured fibroblasts provides a system to study diseases affecting the elastic fibers.

Aging↗
PubMed1988

Elastin.

Explore the source record for details and available documents.

Amino Acid Sequence↗
PubMed1988

Growth factors bFGF and TGB beta accelerate the rate of wound repair in normal and in diabetic rats.

The effects of basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF beta) on the rate of wound repair in both normal and streptozotocin-induced diabetic rats were investigated using two model systems of wound repair, namely incisional wounding and subcutaneous implantation of polyvinyl alcohol (PVA) sponges. Both models showed the expected wound-healing defects of the diabetic rats. Granulation tissue collected from the implanted PVA sponges showed that the diabetic rats had reduced amounts of collagen, DNA and protein present at the wound site at two time points tested (7 and 9 days post-implantation). Fresh tensile strength of the incisional wounds, a measure of the collagen organization in a wound, was reduced to 53% of normal in diabetic rats on day 7 post-wounding, and was only 29% of normal by day 21. Formalin-fixed tensile strength, a measure of collagen content of the wound, was 41% of normal on day 7, and 78% of normal by day 21, giving evidence that while the collagen concentration of the diabetic wounds approached that of normal wounds, it did not undergo the normal maturation process. A single injection of 2 micrograms of TGF beta directly into the incision three days after wounding resulted in little difference in the fresh and fixed tensile strength of diabetic wounds when tested at 7, 14 and 21 days post-wounding. Normal rats, however, responded well, resulting in a greater than 30% increase in both fresh and fixed tensile strength.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Chlordiazepoxide facilitates erections and inhibits seminal emission in rats.

Two experiments have been conducted to clarify the effects of the benzodiazepine chlordiazepoxide (CDP) on the different components of male rat sexual behavior. In the first experiment the effects on penile erectile reflexes (PR) of two doses (10 and 30 mg/kg, IP) of CDP were compared with those of vehicle, no-treatment and baseline pre-test in a repeated measures design. In the second experiment the different components of male sexual behavior - PR, mating behavior and spontaneous seminal emission SSE) - were extensively studied after vehicle, 3 and 30 mg/kg CDP treatments. CDP was found to increase significantly the percentage of rats showing penile reflexes, enhance the number of erections per test and shorten the latency to onset of reflexes. It lowered the percentage of animals displaying seminal emission during the PR test. In the mating behavior test, CDP abolished copulatory (and other) behavior at 30 mg/kg. It decreased the number of animals achieving ejaculation at the subataxic 3 mg/kg dose level. In the SSE 3-day test, CDP significantly reduced the weight and the number of plugs of seminal material emitted by the CDP-injected animals. The possible involvement of the serotonergic system in determining the dose-dependent increase in erections and decrease in seminal emission following CDP treatments is discussed. Clinical implications are also briefly considered.

Animals↗
PubMed1987

Epidermal growth factor increases granulation tissue formation dose dependently.

Recent studies have shown that epidermal growth factor (EGF) stimulated the rate of formation of granulation tissue in a model of wound repair (A. Buckley, et al., Proc. Nat. Acad. Sci. USA 82: 7340, 1985). Because pharmacologic doses of EGF were used previously, the relationship of EGF concentration to physiologic effects was determined in this study. Rats were implanted with subcutaneous polyvinyl alcohol sponges containing slow-release pellets formulated to release 0, 0.1, 1.0, or 10 micrograms of EGF/day. Tissue response was judged by the degree of histologic organization and vascularity, as well as several quantitative parameters: wet weight, hydroxyproline content, protein content, and DNA concentration. Each of these parameters showed consistent increases by Day 5 after implantation, when inflammation and edema had subsided. Compared with placebo controls, hydroxyproline (collagen) content was significantly increased by as little as 1 microgram/day of EGF, and DNA content was significantly increased by all dose levels of EGF. Endogenous EGF concentration in experimental granulation tissue was found to be fairly constant (30-40 ng/g wet wt); however, the increasing cellularity of the sponges may have reduced the local concentration of free EGF to low levels. Pellets releasing as little as 4 ng/hr of EGF into the surrounding tissue were able to accelerate wound healing, suggesting that the availability of this growth factor may be a rate-limiting step in wound repair.

Animals↗
PubMed1987

Genital responses in noncopulators and rats with lesions in the medical preoptic area or midthoracic spinal cord.

To determine whether genital dysfunction participates in the sexual inactivity of noncopulator and MPOA-lesioned rats, penile reflexes and spontaneous seminal emission (SSE) were investigated in such animals. The display of penile reflexes was either the same or enhanced in these animals, relative to controls. Noncopulators and MPOA-lesioned rats also did not differ from controls in SSE. Plasma testosterone levels showed no differences between noncopulators and sexually active controls but tended to be elevated in rats bearing MPOA lesions. Finally, SSE did not differ between rats with midthoracic spinal cord transections and controls, suggesting that SSE is not under supraspinal inhibition.

Animals↗
PubMed1987

Alpha 2-adrenoceptor antagonists and male sexual behavior: I. Mating behavior.

Three alpha 2-adrenoceptor antagonists yohimbine, idazoxan, and imiloxan were compared by examining the effects of a single injection on male rat copulatory behavior. Dose ranges were: yohimbine: 0.25-8.0 mg/kg; idazoxan: 0.25-8.0 mg/kg; imiloxan: 12.5-50.0 mg/kg. Yohimbine and idazoxan administration produced significant increases in the number of animals copulating to ejaculation and all three drugs increased the rate of copulation as evidenced by reductions in ejaculation latency and intercopulatory interval. Only yohimbine significantly reduced mount latency and postejaculatory interval, but yohimbine and imiloxan significantly reduced intromission latency and idazoxan showed a similar trend. The highest yohimbine dose suppressed sexual activity. A time-course experiment with yohimbine (2.0 mg/kg) and idazoxan (4.0 mg/kg) showed stimulation at 75 min and a trend at 5. To further explore the arousal-stimulating capacity of the two more effective drugs, a mounting test with genital anesthetization was used. Yohimbine but not idazoxan showed marked increases in mounting at 1.0-4.0 mg/kg. Both drugs had a suppressive effect at the highest doses. These data support the involvement of alpha 2-adrenoceptors in the regulation of male sexual behavior, specifically by facilitating sexual arousal, with no effects on ejaculatory threshold, as measured by intromission frequency. Yohimbine is the most globally effective agent and it is likely that factors other than yohimbine's alpha 2-antagonism may play a role in its unique, consistent and broad behavioral effects.

Adrenergic alpha-Antagonists↗
PubMed1987

Alpha 2-adrenoceptor antagonists and male sexual behavior: II. Erectile and ejaculatory reflexes.

Three alpha 2-adrenoceptor antagonists, yohimbine, idazoxan, and imiloxan, all shown to have stimulatory effects on sexual arousal/motivation, were studied to identify their possible effects on the other two major components of male copulatory behavior: erection and ejaculation. Genital reflex ex copula tests were used in order to assess these two responses without the confounding factors of mating behavior. Dose ranges were yohimbine: 0.25-4.0 mg/kg; idazoxan: 1.0-8.0 mg/kg; and imiloxan: 12.5-50.0 mg/kg. Lower doses of two of the drugs significantly enhanced the frequency of erections, while the third (yohimbine) showed a strong trend in that direction. At higher doses, all three alpha 2-antagonists produced significant reductions in the number of rats showing penile reflexes, including both erections and ejaculations. In those rats which did show penile reflexes, higher doses of yohimbine (4.0 mg/kg) inhibited the frequency of erections, while the higher dose of idazoxan showed a trend towards such inhibition. Thus, profound, largely inhibitory effects of these agents were demonstrated at dose ranges which have been shown to enhance sexual arousal. These data indicate that within the nervous system alpha 2-adrenoceptor antagonists can modulate erectile and ejaculatory mechanisms quite independently from effects on arousal/motivation.

Adrenergic alpha-Antagonists↗
PubMed1987

Neurochemical correlates of male sexual behavior.

This report presents evidence of changes in the concentration of monoamine neurotransmitters and their metabolites in homogenates of spinal cord and brain areas of male rats related to specific events of their mating behavior. Intact male rats were allowed to copulate with receptive females and decapitated immediately after either the first intromission or the first ejaculation. Non-mating control animals were exposed to other males, instead of females. The concentration of monoamines (norepinephrine, dopamine and serotonin) and some of their major metabolites (DOPAC and HIAA) in homogenates of discrete brain areas (parietal cortex, preoptic region, mediobasal hypothalamus) and lumbosacral spinal cord were measured by HPLC-ED. Results suggest that sexual arousal is associated with both increased dopaminergic activity in the preoptic region and inhibition of descending monoaminergic signals to the lumbosacral cord, whereas ejaculation is accompanied by increased activity of the serotonergic, as well as dopaminergic, innervation of the preoptic region. These findings give neurochemical support to notions of central monoamines involvement in sexual behavior suggested by previous pharmacological studies.

Animals↗
PubMed1987

The gene coding for tropoelastin is represented as a single copy sequence in the haploid sheep genome.

The identity of the primary in vitro translation products of fetal sheep nuchal ligament elastin mRNA was confirmed as two distinct polypeptides of 63 Kdal and 65 Kdal in both rabbit reticulocyte and wheat germ extract cell-free translation systems. Both polypeptides were co-translationally processed by a microsomal membrane signal peptidase, with the removal of 20-25 amino acid residues. A single (3,5 kb) RNA species encodes both tropoelastin polypeptides. Restriction endonuclease mapping of sheep genomic DNA by hydridization with two radiolabelled genomic DNA fragments containing sequences coding for sheep tropoelastin (pSE1-1,3 and pSE1-0.7,) indicated the presence of a single elastin gene. The elastin gene copy number was further quantitated by comparison of hybridisation of pSE1-1.3 and pSE1-0.7 to slot-blots and Southern transfers of sheep genomic DNA and to standard curves constructed with each clone. These results clearly demonstrate that each of these sequences is represented only once per haploid genome, suggesting that the two tropoelastin polypeptides are products of a single elastin gene.

Amino Acid Sequence↗
PubMed1987

Differential effects of cartilage-derived growth factor stimulation of collagen secretion by bovine aortic and microvascular endothelial cells.

Cartilage-derived growth factor (CDGF), a protein closely related to basic fibroblast growth factor, is known to have both mitogenic and chemokinetic properties in microvascular endothelial cells (MVEC). Because of the angiogenic properties of CDGF and its rate in accelerating wound repair, the capacity of this factor to stimulate both proliferation and matrix synthesis was compared in distinct populations of vascular endothelial cells: MVEC from bovine adrenal cortex and macrovascular endothelial cells from the bovine aorta (BAEC). No significant differences in the responses to mitogenic stimulation using CDGF (5-100 units/ml) were observed using MVEC and BAEC. Only rapidly dividing MVEC, however, showed significant increases in collagen secretion in the presence of CDGF. The differential responsiveness of these two cell populations to a defined growth factor underscores the phenotypic diversity of endothelium.

Animals↗
PubMed1987

Androstenedione may organize or activate sex-reversed traits in female spotted hyenas.

Spotted hyenas (Crocuta crocuta Erxleben) present a unique syndrome of reversal in behavioral and anatomical distinction between the sexes: females are heavier and more aggressive than males and dominant over them. The female's external genitalia include a false scrotum and a fully erectile pseudopenis through which mating and birth take place. Results of studies of circulating testosterone levels in wild spotted hyenas do not account for the "male-like" characteristics of the female. Androstenedione, however, is consistently higher in females than in males, particularly during early infancy. Experiments on rodents show that androstenedione can be a potent organizer of anatomical and behavioral differentiation. This study suggests that it may also produce the profound virilization of female spotted hyenas.

Aging↗
PubMed1987

Developmental initiation of elastin gene expression by human fetal skin fibroblasts.

Elastin synthesis is initiated in many organs during the latter part of fetal development. By birth, accumulation of elastin in elastic fibers accounts in large part for the integrity and resilience of skin, blood vessels, and lungs. Developmental studies in several connective tissues of nonhuman vertebrates indicate that elastin synthesis is rapidly initiated during fetal life and that its expression is largely controlled by the abundance of its mRNA. Previous evidence for elastin synthesis in the developing human fetus has been derived from either histologic inference or studies of net accumulation. We now report that the developmental induction of cutaneous elastin synthesis appears to be stably reflected in cell culture. Production of elastin by human skin fibroblasts increased 7- to 14-fold between 17 and 19 weeks of gestation, reaching the levels found in neonatal skin fibroblasts. Consistent with other developmental studies, elastin synthesis was found to be under pretranslational control with relative mRNA levels increasing 6- to 15-fold by 19 weeks of gestation. Under the same circumstances, collagen expression and total protein synthesis were relatively constant among all strains examined. Human skin fibroblasts may thus be a useful system for examining developmentally regulated elastin gene expression.

Elastin↗