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Biomedical subjects

M J Scott

Publications and source records attributed to M J Scott.

At least 55 records · Page 3Linked to original sources
PubMed1997

Angiotensin II receptor blockade in Syrian hamster (T0-2) cardiomyopathy does not affect microscopic cardiac material properties: implications for mechanisms of tissue remodeling.

This study delineates the role of angiotensin II type I (AT1) receptor in the remodeling of Syrian cardiomyopathic hamsters. Twelve cardiomyopathic (T0-2) hamsters received L-158,809 treatment and libitum in their drinking water (27 micrograms/ml) and 9 cardiomyopathic and 9 normal FL-B hamsters received tap water from 1 to 4 months of age. Although pharmacologically effective with regard to complete suppression of the blood pressure response to angiotensin II infusion, L-158,809 did not diminish the progression or severity of cardiomyopathy. Heart weight/100 g body weight and left ventricular wall thickness adjusted for body weight of both L-158,809 and cardiomyopathic control hamsters did not differ and exceeded those of F1-B controls (p < 0.05). Myocardial material properties (e.g., stiffness and density) of cardiomyopathic hamsters treated with L-158,809 were not affected. Thus, the progression of fibrosis, calcification, and necrosis in T0-2 cardiomyopathic hamsters was not sensitive to AT1 receptor blockade.

Angiotensin II↗
PubMed1997

Client compliance with exposure treatments for posttraumatic stress disorder.

Clients with posttraumatic stress disorder (PTSD) do not wish to "relive" their trauma, but exposure based treatments try to ensure that they do. While such treatments have proven efficacy in controlled outcome studies, how acceptable are they in routine clinical practice? The attempted clinical application of two such exposure treatments is briefly reported here. In the first, only 1 of 14 clients completed the image habituation procedure for homework in the manner described by its authors. In the second (N = 37), only 57% complied with an audiotape exposure treatment, and compliance was related to initial symptom severity and to severity of comorbid depression. Exposure based treatments are not 'treatment of choice' for some clients.

Abreaction↗
PubMed1997

Spread of an enteric 'marker' organism during evisceration of New York dressed poultry in a simulated kitchen environment.

1. Five volunteers, with experience of eviscerating poultry or game birds in the home, each eviscerated three New York dressed chicken carcases that had been artificially inoculated in the colon with a readily identifiable "marker' strain of Escherichia coli. 2. In all cases, evisceration resulted in breakage of the intestines at one or more sites, often with leakage of gut contents, or extrusion of faeces from the cloaca because of pressure on the colon during the manipulations involved. 3. The marker organism was detected in the vent region and abdominal cavity of each carcase and sometimes on the breast and back, which appeared to reflect the degree of handling during evisceration, because the hands of each individual became heavily contaminated. 4. With some individuals, the marker also spread beyond the immediate preparation area and was detected on exposure plates. 5. Results support the view that evisceration of poultry in a domestic environment could lead to cross-contamination of other foods with any food-borne human pathogens present.

Animals↗
PubMed1997

Dermatophagia: "wolf-biter".

Dermatophagia is a neurodermatitis akin to onychophagia, onychotillomania, trichotillomania, dermatothlasia, neurotic excoriations, and other conditions in which persons have a neurotic habit or compulsion to self-multilate their skin or its appendages. Dermatophagia is a habit or compulsion, consciously or subconsciously, to bite one's own skin. We believe "dermatophagia" is a more appropriate term for this disorder than the descriptive term "wolf-biter".

Bites and Stings↗
PubMed1997

Decreased vascular smooth muscle cell density in medial degeneration of human abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAAs) are characterized by structural deterioration of the aortic wall leading to progressive aortic dilatation and eventual rupture. The histopathological changes in AAAs are particularly evident within the elastic media, which is normally dominated by vascular smooth muscle cells (SMCs). To determine whether a decrease in vascular SMCs contributes to medial degeneration, we measured SMC density in 21 normal and pathological human abdominal aortic tissue specimens using immunohistochemistry for alpha-SMC actin and direct cell counts (medial SMCs per high-power field (HPF)). Medial SMC density was not significantly different between normal aorta (n = 5; 199.5 +/- 14.9 SMCs/HPF) and atherosclerotic occlusive disease (n = 6; 176.4 +/- 13.9 SMCs/HPF), but it was reduced by 74% in AAA (n = 10; 50.9 +/- 6.1 SMCs/HPF; P < 0.01 versus normal aorta). Light and electron microscopy revealed no evidence of overt cellular necrosis, but SMCs in AAAs exhibited ultrastructural changes consistent with apoptosis. Using in situ end-labeling (ISEL) of fragmented DNA to detect apoptotic cells, up to 30% of aortic wall cells were ISEL positive in AAAs. By double-labeling techniques, many of these cells were alpha-actin-positive SMCs distributed throughout the degenerative media. In contrast, ISEL-positive cells were observed only within the intimal plaque in atherosclerotic occlusive disease. The amount of p53 protein detected by immunoblotting was increased nearly fourfold in AAA compared with normal aorta and atherosclerotic occlusive disease (P < 0.01), and immunoreactive p53 was localized to lymphocytes and residual SMCs in the aneurysm wall. Using reverse transcription polymerase chain reaction assays a substantial amount of p53 mRNA expression was observed in AAAs. These results demonstrate that medial SMC density is significantly decreased in human AAA tissues associated with evidence of SMC apoptosis and increased production of p53, a potential mediator of cell cycle arrest and programmed cell death. Given the role that SMCs normally play in maintaining medial architecture and in arterial wall matrix remodeling, the induction of SMC apoptosis likely makes an important contribution to the evolution of aneurysm degeneration.

Aorta, Abdominal↗
PubMed1996

A novel site-targeted ultrasonic contrast agent with broad biomedical application.

BACKGROUND: In this work, we report a novel targetable ultrasonic contrast agent with the potential to noninvasively define and localize myriad pathological tissues for diagnosis or therapy. The agent is a biotinylated, lipid-coated, perfluorocarbon emulsion that has low inherent echogenicity unless bound to a surface or itself. METHODS AND RESULTS: In study 1, emulsions with and without biotin were suspended in buffered saline and imaged with a 7.5-MHz linear-array transducer. Neither emulsion manifested significant ultrasonic backscatter until avidin was added. Avidin-induced aggregation produced a marked enhancement in backscatter from the biotinylated but not from the control emulsion. In study 2, porcine fibrin clots in vitro were pretargeted with biotinylated antifibrin monoclonal antibodies and then exposed to avidin and then to biotinylated or control perfluorocarbon emulsions. The basal acoustic reflectivity of clots imaged with a 7.5-MHz linear-array transducer was uniformly low and was increased substantially by exposure to the targeted biotinylated emulsion. In study 3, partially occlusive arterial thrombi were created in dogs and then exposed to antifibrin antibodies and avidin in situ. Biotinylated or control emulsion was administered either in situ or systemically. At baseline, all thrombi were undetectable with a 7.5-MHz linear-array transducer. Thrombi exposed to antifibrin-targeted contrast exhibited increased echogenicity (P < .05); control thrombi remained acoustically undetectable. CONCLUSIONS: These data provide the first in vivo demonstration of a site-specific ultrasonic contrast agent and have potential for improved sensitivity and specificity for noninvasive diagnosis of thrombi and other pathological diseases.

Animals↗
PubMed1996

Different temporal and spatial distribution of TGF-beta 1 and TGF-beta 2 in rabbit vascular tissue: potential role in normal vessel growth and maturation.

The expression of transforming growth factor beta 1 and beta 2 (TGF-beta 1 and beta 2) in aortic and venous tissue from male New Zealand White rabbits, at selected time intervals after birth, was examined by the reverse transcriptase polymerase chain reaction. Stable levels of TGF-beta 1 were found in all segments derived from the aortic arch and descending aorta at each time interval. However, increasing amounts of TGF-beta 2 transcripts were observed for the aortic arch from day 4, with peaks occurring between 1 and 6 months of age, followed by progressively decreasing levels thereafter. TGF-beta 2 transcripts in the descending aorta generally did not change significantly over time. TGF-beta transcripts manifested a significantly lower expression in the vena cava than in aortic segments. Histological analysis of the vascular tissue showed cellular hyperplasia (2.5-fold greater prevalence of nuclei per field) in the aortic arch media at 1 month of age as compared with nuclei per field at 12 months and increasing thickness of the aortic arch media with time. No significant differences in relative collagen concentrations were observed among the aortic and vena cava segments. These results suggest that these TGF-beta isoforms may participate in the physiological induction and differentiation of arterial and venous tissue during early normal vascular maturation.

Actins↗
PubMed1996

Effects of ultraviolet light in vascular cells in vitro and in intact atherosclerotic explants: potential role of apoptosis in vascular biology.

Complex cell-to-cell interactions are known to participate during vascular injury and remodeling, resulting in smooth muscle cell proliferation. Mechanical interventions have yielded little benefit in limiting this process and several site-specific genetic therapies are not yet clinically available. The aim of this study was to delineate the effect of very short wavelength ultraviolet (UVC) light therapy on the viability of macrophage and smooth muscle cells. Vascular cells were both treated in vitro and in intact explanted atherosclerotic aortic segments ex vivo with UVC light. Brief exposure to short wavelength UVC light in the absence of photosensitizers elicited a differential temporal and functional response among treated cells. However, dramatic reduction in both cellular viability and proliferative capacity with eventual cell demise was observed in all UVC-treated cells. Flow cytometry and immunohistochemical analyses revealed the presence of extensive DNA fragmentation, suggestive of apoptosis as a predominant pathway of cell death in these cells exposed to UVC light. We hypothesize that selective induction of apoptosis, in contrast to necrosis, with UVC light may represent a beneficial approach to interdict the complex biologic cascade of messengers that participate in the restenotic response to vascular injury.

Animals↗
PubMed1996

Morphology of porcine aortic valve cusp elastin.

BACKGROUND AND AIM OF STUDY: While the structure and function of heart valve cusp collagen have been relatively well defined, the role and morphology of elastin remains poorly understood, despite the fact that it comprises up to 13% of the cusp dry weight. MATERIAL AND METHODS: The elastin structure of 24 hot-alkali-digested porcine aortic valve cusps was investigated with scanning electron microscopy. Elastin structures were categorized according to their morphology and a model of the distribution of these structures within the cusp was developed. RESULTS: The two main types of elastin observed, amorphous and fibrillar, were further categorized based on their morphology. Amorphous structures included continuous sheet, sheet with integrated fibers on the surface and sheet with fenestrations. Fibrillar structures identified were loose fibers, loose mesh/woven fibers and compact mesh. By imaging samples of digested fibrosa and ventricularis that had been microdissected apart, we were able to produce maps of the elastin structure in the two layers. The ventricularis contains a large continuous sheet of amorphous or compact mesh elastin that covers the entire layer. Elastin in the fibrosa is much more complex, consisting of large tubes that emerge from the aortic attachment and extend circumferentially across the cusp. The tubes, constructed of amorphous fenestrated sheet and loose mesh elastin, likely surround the large circumferential collagen bundles observed in the fibrosa. CONCLUSIONS: The elastin structures that we have identified help explain the measured mechanics of this tissue and suggest that collagen and elastin are highly integrated. As a result, we believe that elastin plays an important functional role in the cusp and that a full explanation of heart valve cusp mechanics must incorporate the contributions of both collagen and elastin.

Animals↗
PubMed1995

Male-specific lethal 2, a dosage compensation gene of Drosophila, undergoes sex-specific regulation and encodes a protein with a RING finger and a metallothionein-like cysteine cluster.

In Drosophila the equalization of X-linked gene products between males and females, i.e. dosage compensation, is the result of a 2-fold hypertranscription of most of these genes in males. At least four regulatory genes are required for this process. Three of these genes, maleless (mle), male-specific lethal 1 (msl-1) and male-specific lethal 3 (msl-3), have been cloned and their products have been shown to interact and to bind to numerous sites on the X chromosome of males, but not of females. Although binding to the X chromosome is negatively correlated with the function of the master regulatory gene Sex lethal (Sxl), the mechanisms that restrict this binding to males and to the X chromosome are not yet understood. We have cloned the last of the known autosomal genes involved in dosage compensation, male-specific lethal 2 (msl-2), and characterized its product. The encoded protein (MSL-2) consists of 769 amino acid residues and has a RING finger (C3HC4 zinc finger) and a metallothionein-like domain with eight conserved and two non-conserved cysteines. In addition, it contains a positively and a negatively charged amino acid residue cluster and a coiled coil domain that may be involved in protein-protein interactions. Males produce a msl-2 transcript that is shorter than in females, due to differential splicing of an intron of 132 bases in the untranslated leader. Using an antiserum against MSL-2 we have shown that the protein is expressed at a detectable level only in males, where it is physically associated with the X chromosome. Our observations suggest that MSL-2 may be the target of the master regulatory gene Sxl and provide the basic elements of a working hypothesis on the function of MSL-2 in mediating the 2-fold increase in transcription that is characteristic of dosage compensation.

Amino Acid Sequence↗
PubMed1995

Cholesterol feeding modulates spatial expression of TGF-beta 1 and beta 2 in aortas of Watanabe rabbits.

Several cytokines have been identified as markers of early atherosclerotic disease during vascular injury and remodelling. Of particular importance, transforming growth factor-beta (TGF-beta 1) has been found to be crucial in promoting connective tissue deposition resulting in both intimal and medial hyperplasia. However, the expression of TGF-beta 1 and beta 2 during cholesterol feeding in the Watanabe rabbit, an established model of hypercholesterolemia, has not been evaluated. Accordingly, we examined the expression of TGF-beta 1 and beta 2 signal from aortic segments of 10 heterozygous Watanabe rabbits with the use of reverse transcription-polymerase chain reaction (RT-PCR) amplification during normal non-supplemental diet and during 0.5% supplemental cholesterol feeding for a period of two months. TGF-beta transcripts from the aortic tissue were quantified at the end of the feeding interval. For Watanabe rabbits fed regular chow, the expression of both TGF-beta 1 and beta 2 is reduced in the aortic arch as compared with the descending aorta. In contrast, Watanabe rabbits fed high cholesterol diets manifested a differential expression of TGF-beta isoforms depending on the spatial location within the aorta. In the aortic arch, increased transcript signals for both TGF-beta 1 and beta 2 were noted as compared with rabbits on normal chow. The lesions found in the aortic arch are typified by abundant foam cells and proliferating smooth muscle cells. Analysis of the TGF-beta 1 and 2 profile on these same cell elements in vitro results in a similar expression of increased mRNA isoforms for TGF-beta 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

A second superoxide dismutase gene in the medfly, Ceratitis capitata.

We report the first case of two Cu/Zn Sod genes (ccSod1 and ccSod2) that have been cloned and sequenced from an insect, the medfly, Ceratitis capitata. Biochemical evidence suggested the presence of two Sod genes in the medfly. The two genes are isolated using different molecular strategies: ccSod1 via cross-hybridization to a genomic library using a heterologous probe and ccSod2 from cDNA using a homologous probe generated by PCR. Sequence analysis shows that ccSod1 and ccSod2 are different genes. The inferred amino sequences show that all essential residues of the active site are strictly conserved, which suggests both genes encode functional Cu/Zn superoxide dismutase (SOD). Phylogenetic analysis by the maximum parsimony method with bootstrap resampling of previously known Cu/Zn SOD reveals two monophyletic groups, vertebrates and insects. The position of ccSOD2 in this phylogeny is undefined with respect to dipteran ccSOD1, vertebrate, plant, fungal, and extracellular Cu/Zn SOD, which suggests that the duplication detected in Ceratitis is ancient, perhaps as old as the origins of the arthropod phylum in the Cambrian more than 500 million years ago. In situ hybridization to polytene chromosomes places the genes on different chromosomes, which is consistent with an ancient gene duplication.

Amino Acid Sequence↗
PubMed1994

Furrowing surface contraction wave coincident with primary neural induction in amphibian embryos.

We predicted, and have now observed, a surface contraction wave in axolotl (Ambystoma mexicanum) embryos that appears to coincide temporally and spatially with primary neural induction and homoiogenetic induction, and with involution of the chordomesoderm. The wave starts from a focus anterior to the dorsal lip of the blastopore and spreads as an ellipse, until part of it encounters the rim of the blastopore and vanishes there. The remaining arc then continues over the dorsal hemisphere until it reforms an ellipse that decreases in size. About 9 to 12 hours after it begins, the wave vanishes at a focus diametrically opposite its point of origin. The wave involves both local contraction and furrowing in the monolayer ectoderm. To a good approximation, the hemispherical portion of the ectoderm traversed by the wave becomes neuroepithelium, while the ectoderm not traversed by the wave becomes epidermis. The wave might provide a mechanism to determine the time and location at which neuroepithelial differentiation occurs.

Ambystoma mexicanum↗
PubMed1994

Post-traumatic stress disorder without the trauma.

Examples are reported of PTSD cases showing full symptomatology (intrusive imagery, avoidance behaviour, disordered arousal) in the absence of a single, acute, dramatic trauma of the kind required by the current DSM-III-R definition. Such trauma is thus not a necessary condition for PTSD, and other evidence shows it to be not a sufficient condition. It is suggested that the DSM-III-R Axis IV distinction between acute and enduring psychosocial stressors be incorporated into the definition to distinguish two pathways to stress disorder, post-traumatic (PTSD) and prolonged duress (PDSD). Differential treatment implications of the two routes are noted.

Adult↗
PubMed1994

Expression of metalloproteinases and tissue inhibitors of metalloproteinases in human osteoblast-like cells: differentiation is associated with repression of metalloproteinase biosynthesis.

To more clearly define the expression of metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs) within the human osteoblast (hOB) lineage, normal hOB and human osteogenic sarcoma cells possessing various levels of alkaline phosphatase (a marker of commitment to the osteoblast lineage) were treated with bone-resorbing agents to determine their effect on the production of interstitial collagenase, stromelysin, 72-kilodalton (kDa) gelatinase, 92-kDa gelatinase, TIMP-1, and TIMP-2. The results revealed that 1) normal hOB release copious amounts of 72-kDa gelatinase, TIMP-1, and TIMP-2; 2) hOB production of 72-kDa gelatinase and TIMP-2 is not regulated by agents that promote bone resorption (e.g. phorbol-12-myristate 13-acetate, recombinant human interleukin-1 beta, tumor necrosis factor-alpha, PTH, and vitamin D3); 3) normal hOB fail to secrete collagenase, stromelysin, or 92-kDa gelatinase when cultured on plastic or a type I collagen substratum, even in response to bone-resorptive agents or mononuclear cell-conditioned medium; 4) in contrast, certain of the osteogenic sarcoma cell populations produce collagenase, stromelysin, and 92-kDa gelatinase, especially when exposed to bone-resorbing stimuli; 5) in general, the capacity for metalloenzyme production by osteogenic sarcoma cell lines varies inversely with their alkaline phosphatase expression; and 6) the most committed (highest alkaline phosphatase) osteogenic sarcoma cell line, SAOS-2, precisely mimics the metalloproteinase profile of normal hOB. The results suggest that the expression of most metalloproteinases is under strict repression within the differentiated normal hOB, and cellular development is associated with diminished capacity to elaborate such enzymes.

Cell Differentiation↗
PubMed1994

Linear keloids resulting from abuse of anabolic androgenic steroid drugs.

Anabolic androgenic steroid use by professional and amateur athletes is widespread. Dermatologic side effects are among the most frequent complications. Linear keloids are an unusual manifestation. Athletes rarely volunteer, or even admit, that they are taking such steroids. These drugs are taken in cycles and gas chromatography--mass spectrometry is the preferable urinary test for detecting their presence.

Anabolic Agents↗