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Biomedical subjects

D Gordon

Publications and source records attributed to D Gordon.

At least 253 records · Page 14Linked to original sources
PubMed1994

Anoxia and corporal smooth muscle dysfunction: a model for ischemic priapism.

The hemodynamics of penile flaccidity, erection and detumescence requires corporal smooth muscle to function across a wide variation in pO2. The present study describes the effect of anoxia on corporal smooth muscle response to field stimulation and pharmacologic agonists and antagonists of erection. The response of isolated strips of rabbit corpus cavernosal tissue to field stimulation, phenylephrine, bethanechol, ATP and KCL was determined under oxygenated and anoxic conditions. The results can be summarized as follows: 1) Anoxia eliminated spontaneous contractile activity and reduced basal tissue tension to a minimum. 2) Neither field stimulation nor pharmacological agents (ATP, bethanechol, isoproterenol) could relax basal tension below that induced by anoxia alone. 3) Under anoxic conditions alpha-adrenergic agonists produced poorly sustained phasic contractile responses; anoxia eliminated tonic contractile responses to phenylephrine. 4) In normoxic conditions field stimulation of smooth muscle precontracted with phenylephrine produced frequency-dependent graded relaxations; under anoxic conditions field stimulation yielded contractile responses at all frequencies. Our data suggest that corporal smooth muscle tone, spontaneous contractile activity, the contractile response to alpha-agonists and field stimulated relaxation depend on the state of corporal oxygenation. The inability of alpha-stimulation to induce a tonic contraction of corporal smooth muscle under anoxia in vitro parallels the failure of penile injection of alpha-adrenergic agonists to relax ischemic priapism.

Animals↗
PubMed1994

Site-specific dexamethasone delivery for the prevention of neointimal thickening after vascular stent implantation.

BACKGROUND: Site-directed pharmacologic therapy using drug-impregnated polymers may achieve high local tissue levels at sites of arterial injury without systemic side effects. The aim of this study was to determine whether sustained, local administration of the synthetic glucocorticoid dexamethasone reduces the severity of intimal hyperplasia induced by arterial stenting in a porcine model of restenosis. METHODS: Dexamethasone-impregnated silicone polymers (20% loading by weight) were formulated and tested in vitro to determine the time course of drug release. Oversized metallic stents were implanted in both carotid arteries of 14 juvenile Yorkshire farm pigs. A dexamethasone-impregnated polymer matrix was then placed around the external surface of the stented artery on one side, and a control polymer was placed contralaterally in an identical manner. Two animals were killed 5 days after stent implantation and the remainder after 35 +/- 1 days. RESULTS: Ex-vivo dexamethasone release from the silicone polymers was estimated to be 5 mg/day for the first 3 days and 0.3 mg/day thereafter. The arterial tissue dexamethasone levels after 5 days were 1307 +/- 498 ng/g of tissue on the treated side and 7.5 +/- 1.0 ng/g of tissue on the control side. The plasma dexamethasone level was 1.6 +/- 0.3 ng/ml, with no step-up in concentration across the segment surrounded by the drug-impregnated polymer. After 35 days, macroscopic examination and computerized morphometric analysis showed a substantial difference in the extent of polymer-induced adventitial and perivascular scarring but no difference in the extent of neointimal thickening. The adventitia:media ratio was 2.99 +/- 0.33 on the dexamethasone-treated side but 4.29 +/- 0.36 on the control side (P < 0.02). The intima:media ratios were 0.48 +/- 0.09 and 0.52 +/- 0.07, respectively. CONCLUSION: Sustained, local dexamethasone therapy has potent anti-inflammatory and anti-fibrotic effects but, with the dose and route of administration used in this study, does not reduce the intimal hyperplastic response to injury in this model.

Animals↗
PubMed1994

Lipoprotein lipase is produced by cardiac myocytes rather than interstitial cells in human myocardium.

Lipoprotein lipase (LPL) may play an important role in myocardial metabolism by releasing free fatty acids from triglycerides for oxidation by myocytes. However, studies in species other than humans have differed in their conclusions as to whether LPL is produced by cardiac myocytes or interstitial cells. The location and source of LPL in human myocardium were determined on formalin-fixed samples from 25 cardiomyopathy patients and seven control patients. LPL protein was detected immunohistochemically on cardiac myocytes, adipocytes, and endothelial cells, as well as on interstitial cells consisting of both vascular pericytes and smooth muscle cells. In all 32 patients, in situ hybridization localized LPL mRNA to cardiac myocytes and adipocytes, but LPL mRNA was not detected in interstitial cells. Quantitative in situ hybridization failed to reveal correlations between LPL mRNA levels and New York Heart Association functional class, left ventricular ejection fraction, or beta-adrenergic agonist therapy. Also, quantitative in situ hybridization demonstrated apparently linear loss of detectable myocardial mRNA after onset of ischemia, with a disappearance half-time of approximately 26 hours. In summary, LPL is produced primarily by cardiac myocytes rather than by interstitial cells in human myocardium. Furthermore, LPL protein is present on cells with and without detectable LPL mRNA, suggesting that LPL is translocated from sites of synthesis to sites of utilization.

Adipocytes↗
PubMed1994

Does platelet-derived growth factor-A chain stimulate proliferation of arterial mesenchymal cells in human atherosclerotic plaques?

Previous studies have indicated the focal presence of growth factors and focal low levels of cell proliferation in human atherosclerotic plaques. Using human carotid plaques and an antibody to platelet-derived growth factor (PDGF)-A chain, we have begun to assess growth factor significance by spatially correlating growth factor gene expression with actual cell proliferation. Since PDGF is a mitogen for smooth muscle and related cells and since inflammatory cells (eg, macrophages) can also proliferate in these lesions, it was important to exclude inflammatory cell proliferation from this consideration. Therefore, we have used a triple immunolabeling approach, combining the above anti-PDGF-A chain antibody with an inflammatory cell cocktail (CD68+CD45 for monocyte/macrophages and lymphocytes) and adding an anti-proliferating cell nuclear antigen (PCNA) antibody to mark proliferating cells. In the carotid atherosclerotic plaques, PDGF immunostaining was distributed focally, preferentially in the fibrous cap and vascularized regions, and was present in two distinct patterns: cytoplasmic and diffuse extracellular staining. When we considered colocalization within the same cells, cytoplasmic PDGF-A staining did not appear to colocalize with inflammatory markers. PCNA nuclear staining combined with PDGF cytoplasmic staining of the same cell was detected extremely rarely. Considering colocalization within the same microscopic fields, PDGF-A staining was detected more frequently than noninflammatory PCNA positivity. Quantitative logistic regression analysis demonstrated that localization in vascularized regions and (independently) the presence of PDGF-A are good predictors of noninflammatory cell proliferation, within the same microscopic fields. Therefore, PDGF-A and other factors especially associated with vascularized regions may be involved in the regulation of mesenchymal cell proliferation in human atherosclerotic plaques.

Antibodies↗
PubMed1994

Catheter-mediated pulmonary vascular gene transfer and expression.

The study and treatment of pulmonary diseases may be greatly facilitated by in vivo expression of specific recombinant genes in the pulmonary vasculature and lung parenchyma. To evaluate the feasibility of gene transfer to the pulmonary vasculature, cationic liposomes and adenoviral vectors encoding a human placental alkaline phosphatase (hpAP) gene were delivered into a pulmonary artery of 24 pigs by percutaneous right heart catheterization. Pulmonary tissue was harvested within 20 minutes or 5, 14, or 28 days later and was analyzed for gene transfer and expression. Five days after exposure to liposomes or adenoviral vectors, transfer of DNA and expression of mRNA were demonstrated in transfected lung tissue. Recombinant alkaline phosphatase protein was observed in both the vasculature and in alveolar septa but not in the bronchi. Expression of hpAP protein was observed at 5 days, was diminished at 14 days, and was absent 28 days after gene transfer with both liposome and adenoviral vectors. No major adverse effects of gene expression were detected by histological examination of the transfected lung segments compared with control segments. Gene transfer to the lung by either vector was not associated with significant biochemical abnormalities or histological changes 5, 14, or 28 days later in other organs, including carotid artery, heart, liver, spleen, kidney, skeletal muscle, ovary, and testes. These studies demonstrate that after intravascular gene delivery to the lung, recombinant genes are expressed in the vasculature and alveoli. This approach may provide a useful model for the experimental study of pulmonary vascular diseases, including pulmonary fibrosis and pulmonary thrombosis disorders.

Adenoviridae↗
PubMed1994

Correlation between the BANA test and oral malodor parameters.

The purpose of the present investigation was to test the association between the BANA test (Perioscan, Oral-B), and oral malodor parameters. The subject population consisted of 52 Israeli adults, 43 of whom complained of oral malodor. Oral malodor measurements consisted of peak and steady-state volatile sulphide measurement by a portable sulphide monitor (Interscan Corp., model 1170), as well as organoleptic measurements of malodor from whole mouth, tongue, and saliva. Samples for the BANA test were obtained from four loci (shallow pocket, deep pocket, tongue dorsum, saliva); results were scored as negative (0), weak (1), or strong (2). BANA scores were significantly associated with odor-judge ratings, with the highest association obtained when BANA saliva scores and odor-judge saliva assessment were compared (r = 0.500; p < 0.001). BANA tests from the different loci were not significantly associated with sulphide monitor levels. Stepwise multiple-regression analysis of odor-judge measurements in terms of sulphide levels and average BANA scores showed that both log peak sulphide levels as well as BANA scores were significantly factored into the equations, yielding, in all cases, highly significant correlations (multiple r = 0.57, 0.50, and 0.59, respectively, with significance levels of 0.0001, 0.001, and < 0.0001, for whole mouth, tongue, and saliva malodor, respectively). The results suggest that the BANA scores are associated with a component of oral malodor which is independent of volatile sulphide measurements and suggest its use as an adjunct test to volatile sulphide measurement.

Adolescent↗
PubMed1994

Cadaverine as a putative component of oral malodor.

Whereas previous studies have shown correlations between volatile sulphur compounds (VSC) and bad breath levels, it is probable that other compounds found in the oral cavity may contribute to oral malodor. In the present investigation, the possibility that diamines (cadaverine and putrescine) are associated with oral malodor parameters was assessed. Saliva samples from 52 subjects were analyzed for cadaverine and putrescine by HPLC. Oral malodor of whole mouth, tongue, and saliva of the subjects was recorded by an experienced judge on a continuous 10-cm scale; peak and steady-state VSC intraoral levels were measured by the Interscan 1170 sulphide monitor. Log-transformed VSC and diamine levels were compared with odor judge measurements by Pearson analysis and stepwise forward multiple regression. Putrescine scores were not significantly associated with odor judge parameters or with VSC levels (p > 0.1). However, highly significant correlations (p < or = 0.003) were found between cadaverine levels and all three odor judge assessments. In contrast, associations between cadaverine and VSC measurements were non-significant. In an attempt to correlate odor judge results in terms of both VSC and diamines, we carried out stepwise forward multiple regression. Results showed that VSC and cadaverine both factor significantly in explaining each of the odor judge measurements, with multiple r values ranging from 0.545 (p = 0.0002) to 0.604 (p < 0.0001). The results suggest that cadaverine levels are associated with oral malodor, and that this association may be independent of VSC.

Adolescent↗
PubMed1994

Pseudo-sinusoidal heart rate associated with major cardiac anomalies.

Pseudo-sinusoidal fetal heart rate (pseudo-SHR) pattern, characterised by intermittent episodes of sinusoidal heart rate and normal fetal heart rate (FHR), is considered benign although its pathophysiologic mechanism remains obscure. We present a case of pseudo-SHR episodes throughout all stages of labor associated with multiple major cardiac anomalies. We suggest that when confronted with repeated episodes of pseudo-SHR pattern, the possibility of an underlying cardiac anomaly should be considered.

Abnormalities, Multiple↗
PubMed1994

Safety, immunogenicity, and efficacy of a malaria sporozoite vaccine administered with monophosphoryl lipid A, cell wall skeleton of mycobacteria, and squalane as adjuvant.

A Plasmodium falciparum circumsporozoite protein (PfCSP) recombinant fusion protein, R32NS1(81), formulated with monophosphoryl lipid A, cell wall skeleton of mycobacteria, and squalane (Detox) was administered to 12 volunteers. One volunteer had malaise and self-limited painful induration at the injection site after the second dose and declined further immunization. The other 11 volunteers tolerated the three doses of 1,230 micrograms of vaccine, but most complained of sore arms; in five cases the pain or malaise was severe enough to interfere with work or sleep. Two weeks after the third dose of vaccine, four of the 11 immunized volunteers had > or = 14 micrograms/ml of antibodies to the repeat region of the PfCSP in their serum. Two of these four volunteers did not develop P. falciparum parasitemia when challenged by the bite of five mosquitoes carrying P. falciparum sporozoites. The seven volunteers with lower levels of antibodies and 11 of 11 controls developed parasitemia. These data are consistent with other studies, and indicate that vaccine-induced antibodies against the repeat region of PfCSP can prevent effective sporozoite infection of hepatocytes in humans. The challenge is to improve the immunogenicity of PfCSP-based vaccines, and to develop methods for including PfCSP peptides as components of multitarget malaria vaccines.

Adjuvants, Immunologic↗
PubMed1994

Local expression of inflammatory cytokines in human atherosclerotic plaques.

Human atherosclerotic plaques are heterogeneous tissues containing a number of different cell types, including macrophages, smooth muscle, endothelial and other undefined mesenchymal-appearing cells. Significant numbers of macrophages are found in human atherosclerotic plaques and have been postulated to be a major source of growth factor production during atherogenesis. In vitro evidence suggested that macrophages synthesize PDGF and might therefore contribute to the growth of the vessel wall in atherosclerosis. However, examination of PDGF synthesis in human atheroma by in situ hybridization revealed that while smooth muscle, mesenchymal, and endothelial cells synthesize this growth factor macrophages did not. Our inability to detect PDGF mRNA in macrophages was not due to any problems with hybridization to this cell type. In situ hybridization studies on human atherosclerotic plaques have demonstrated that plaque macrophages contain many different mRNAs other than PDGF including tissue factor, factor XIII, apoprotein E, transforming growth factor beta, and tumor necrosis factor. Recent studies have indicated that macrophages may be a major source as well of another group of inflammatory cytokines which are members of the RANTES/SIS cytokine family. In situ hybridization studies on human carotid endarterectomy specimens using probes specific for the inflammatory cytokines RANTES, LD78, HIMAP, and MCP-1 revealed numerous cells containing the mRNAs encoding for these proteins (5%, 13%, 8%, and 16% of plaque cells respectively). This is in contrast to generally low level expression found in normal human arteries (< 1% of normal medial cells contain these mRNAs). Cells expressing these cytokines were often found associated with inflammatory zones in human atherosclerotic plaques. Serial section immunohistochemistry suggests that macrophages and/or T cells may synthesize these proteins. In addition to localization to macrophages MCP-1 expression was also detected in smooth muscle cells and mesenchymal-appearing cells with many of the morphological characteristics of cells previously seen to express PDGF. In vitro evidence suggests that these proteins may be chemotactic to monocytes and lymphocytes. The finding of increased expression of these mRNAs in human atheroma suggests they may play a role in monocyte trafficking into the atherosclerotic plaque.

Arteriosclerosis↗
PubMed1994

Interregional migration and interindustry labour mobility in Canada: a simultaneous approach.

"This paper argues that interindustry labour mobility and interregional migration are simultaneously determined processes. It estimates a bivariate probit model of migration and mobility [using data for Canada] and concludes that the interindustry mobility of labour is dominated by the availability of employment hours, and that wage differentials are a statistically significant, but small, determinant of interregional migration.... Since interindustry mobility is much larger in magnitude than interregional migration, quantity constraints in labour markets are of central importance to the adaptive capacity of the economy." (SUMMARY IN FRE)

Americas↗
PubMed1994

Myofibroblasts and their role in lung collagen gene expression during pulmonary fibrosis. A combined immunohistochemical and in situ hybridization study.

Appearance of contractile filament-laden stromal cells or myofibroblasts is a characteristic of lung fibrotic lesions. The role of these cells in fibrosis and their cytoskeletal phenotype are not fully delineated. This study was undertaken to further investigate these issues using a model of lung fibrosis. Rats were treated endotracheally with bleomycin on day 0, and their lungs examined at various time points by in situ hybridization for alpha 1(I) procollagen mRNA expression and by immunohistochemistry for desmin and alpha-smooth muscle actin expression. The results show an increase in the number of cells resembling fibroblasts and strongly positive for alpha-smooth muscle actin, desmin and procollagen mRNA expression in lungs of animals treated with bleomycin, with the increase being maximal between days 7 and 14 after bleomycin treatment. Two types of newly positive cells could be discerned. The first expressing alpha-smooth muscle actin, desmin, and procollagen mRNA was localized in active fibrotic lesions. The second expressing only alpha-smooth muscle actin and procollagen mRNA was localized in fibrotic submesothelial areas. Almost all of the newly reactive alpha-smooth muscle actin-positive cells strongly express procollagen mRNA, and they constituted most of the cells actively expressing procollagen. These findings suggest that the newly appearing myofibroblast characterized by alpha-smooth muscle actin and/or desmin expression may be responsible for most if not all of the increased lung collagen gene expression in pulmonary fibrosis.

Actins↗
PubMed1994

Assessment of cartilage volume in the femorotibial joint with magnetic resonance imaging and 3D computer reconstruction.

OBJECTIVE: Our goal was the development of an accurate and objective technique to depict and quantitate articular cartilage using magnetic resonance imaging (MRI) and 3D data processing. METHODS: A method of 3D image analysis has been developed that provides a noninvasive technique of measuring cartilage volume from standard diagnostic MR images. RESULTS: Using a computer workstation, cartilage from Fast Field Echo (FFE) MR images was reconstructed into 3 dimensions (3D). The accuracy and reproducibility of both thickness and volume measurements obtained from the existing computer software was tested using calibration test objects. We describe the sources of error we encountered when attempting to quantitate cartilage using the existing computer software, the methods developed to reduce these errors, and a preliminary cartilage volume study using healthy human volunteers. CONCLUSION: We have identified errors involved in attempting cartilage volume estimations using the existing 3D computer software and have developed a data processing technique that minimizes these errors. With these objective data processing techniques we have improved the reproducibility of the technique to +/- 10-15% error. This modified technique provides a promising new method for viewing and quantifying cartilage volume from standard diagnostic MR images.

Animals↗
PubMed1994

Infection control for general practice.

This paper, which is part of a course on infection control, includes basic guidelines for infection control i the offices of general practitioners.

Disinfection↗
PubMed1993

Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans.

Direct gene transfer offers the potential to introduce DNA encoding therapeutic proteins to treat human disease. Previously, gene transfer in humans has been achieved by a cell-mediated ex vivo approach in which cells from the blood or tissue of patients are genetically modified in the laboratory and subsequently returned to the patient. To determine the feasibility and safety of directly transferring genes into humans, a clinical study was performed. The gene encoding a foreign major histocompatibility complex protein, HLA-B7, was introduced into HLA-B7-negative patients with advanced melanoma by injection of DNA-liposome complexes in an effort to demonstrate gene transfer, document recombinant gene expression, and determine the safety and potential toxicity of this therapy. Six courses of treatment were completed without complications in five HLA-B7-negative patients with stage IV melanoma. Plasmid DNA was detected within biopsies of treated tumor nodules 3-7 days after injection but was not found in the serum at any time by using the polymerase chain reaction. Recombinant HLA-B7 protein was demonstrated in tumor biopsy tissue in all five patients by immunochemistry, and immune responses to HLA-B7 and autologous tumors could be detected. No antibodies to DNA were detected in any patient. One patient demonstrated regression of injected nodules on two independent treatments, which was accompanied by regression at distant sites. These studies demonstrate the feasibility, safety, and therapeutic potential of direct gene transfer in humans.

Aged↗