Biomedical subjects

M J Petersen

Publications and source records attributed to M J Petersen.

At least 37 records · Page 2Linked to original sources

PubMed1995

Magnetic resonance angiography in the preoperative evaluation of abdominal aortic aneurysms.

PURPOSE: Contrast arteriography (CA) is a useful but invasive technique for the preoperative evaluation of patients with abdominal aortic aneurysms (AAA). To evaluate the use of magnetic resonance arteriography (MRA) as a preoperative study we prospectively studied 38 patients undergoing AAA repair. METHODS: All patients underwent biplane CA and MRA with use of a gadolinium-enhanced technique. Radiographic studies were then independently evaluated by blinded radiologists for anatomic findings with CA used as the standard. Studies were then independently evaluated by blinded vascular surgeons, and a surgical plan was made. RESULTS: With CA and intraoperative findings as the standards, MRA proved highly accurate in the determination of multiple key anatomic elements. The proximal extent of aneurysmal disease was correctly predicted in 87% (33/38) patients. Significant iliofemoral occlusive disease was identified with a sensitivity of 83% (5/6). Iliac or femoral aneurysms were detected with a sensitivity of 79% (22/28) and specificity of 86% (41/48). Significant renal artery stenosis was detected with a sensitivity of 71% (12/17) and a specificity of 99% (72/73). Accessory renal arteries were correctly identified in 71% (12/17). Surgeon evaluators correctly predicted the proximal cross-clamp site in 87% (33/38) of patients with use of MRA as compared with the actual operative conduct. Proximal anastomotic sites were correctly predicted in 95% (36/38) with MRA and 97% (37/38) with CA. Renal revascularization was predicted by MRA with a sensitivity of 91% (10/11) and specificity of 100% (65/65). The use of bifurcated aortic prostheses was correctly predicted by MRA in 75% (12/16), which was similar to that predicted by CA (81%, 13/16). CONCLUSIONS: MRA can provide preoperative anatomic information that is equivalent to CA for surgical planning. Because of favorable cost and patient safety considerations MRA will assume increasing importance in the preoperative evaluation of AAA.

Aged↗

PubMed1995

Sustained production of human transferrin by transduced fibroblasts implanted into athymic mice: a model for somatic gene therapy.

Somatic gene therapy has been proposed as a means of treating inherited diseases involving defective or absent plasma proteins, viral diseases, and cancer. Introduction of the gene of interest into fibroblasts and implantation of these genetically modified fibroblasts using a skin equivalent system may be an attractive model for gene therapy because skin fibroblasts are easily obtained and propagated in culture. This study evaluated expression of the gene for human transferrin (hTf) by genetically modified fibroblasts in vitro and in vivo. NIH 3T3 fibroblasts, which form non-metastasizing tumors in athymic mice, were transduced with a retroviral vector encoding hTf. The transduced cells were cloned by limiting dilution and hTf production by the cloned cells measured. Two clones of cells producing high levels of hTf were used to seed collagen-coated nylon matrices, which were maintained in culture for up to 53 d. The rate of synthesis of hTf by the seeded matrices was constant after 22 d in vitro. Matrices seeded with cloned, transduced cells were implanted subcutaneously into seven athymic mice, and plasma levels of hTf were assessed biweekly. In all animals, the plasma level of hTf was detectable at week 6 after implantation. Levels of hTf remained elevated in the animals until the implants were removed at week 12. At week 10, the level of hTf in the plasma correlated with tumor volume in tumors less than 2000 mm3 in size. The half-life of hTf in the mice was 39.5 h. In this model, gene expression did not decline for the 12-week observation period.

3T3 Cells↗

PubMed1994

Genetically modified skin to treat disease: potential and limitations.

Molecular definition of disease at the level of the gene and advances in recombinant DNA technology suggest that many diseases are amenable to correction by genes not bearing the defective elements that result in disease. Many questions must be answered before this therapy can be used to correct chronic diseases. These questions fall into safety and efficacy categories. Experience with transplanting cellular elements of skin or skin substitutes (defined as skin that possess the cell types and a dermal structure to develop into a functioning skin) to athymic rodents is considerable and is seen as a system where these questions can be answered. This paper reviews these questions and presents our early analysis of genetically modified cells in skin substitutes in vivo and in vitro. Experimental data demonstrate that both a matrix of woven nylon, housing a fibroblast generated collage, and dead dermis can be utilized to shuttle genetically modified human fibroblasts from the laboratory to an in vivo setting. Genetically modified fibroblasts do not migrate from the shuttle to the surrounding tissue. The survival of significant numbers, approximately 70%, of genetically modified fibroblasts for at least 6 weeks in these shuttles, supports this general approach as having clinical utility. It is also concluded that skin substitute systems can be used to generate a genetically modified skin in vitro that has the capacity to develop into functional skin in vivo. Further, as genetically modified keratinocytes differentiate there is increased production by the transgene, supporting the concept that keratinocytes have true potential as shuttles for therapeutic genes. This work demonstrates that transplantation of systems containing genetically modified cells of the skin can be used to experimentally define many aspects of gene therapy using skin before this technology is taken to the clinic. Examples include determining the effect of gene transduction and expression on structure and function of the genetically modified skin as well as on distant skin and an assessment of the translational capacity of the transgene as function of time and cell number.

3T3 Cells↗

PubMed1994

MR imaging (including MR angiography) of abdominal aortic aneurysms: comparison with conventional angiography.

OBJECTIVE: The purpose of this report is to compare the results of MR imaging, including MR angiography, with the results of conventional angiography in the imaging of abdominal aortic aneurysms (AAA). SUBJECTS AND METHODS: Twenty seven nonconsecutive patients with known AAA underwent both MR imaging (including MR angiography) and conventional angiography preoperatively. MR imaging was done before angiography according to the following protocol in all patients: sagittal and coronal T1-weighted images of the abdomen, followed by axial MR angiograms obtained with a multiple overlapping thin-slab acquisition (MOTSA) three-dimensional time-of-flight (3D TOF) volume centered on the renal arteries. Last, coronal MR angiograms were obtained with a dynamic contrast-enhanced 3D TOF volume centered on the aorta. Conventional angiography was subsequently performed in all patients. Data from each study were collected prospectively and analyzed in a blinded manner. For the MR studies, all sequences were used to determine the extent of the AAA and the presence of iliac aneurysms; stenotic disease of the celiac, superior mesenteric, renal, and iliac arteries and the number and location of renal arteries were determined from the MR angiograms. For evaluation of the extent of the aneurysm, results from both techniques were compared with surgical results; otherwise MR angiography was compared with conventional angiography. Confidence intervals for sensitivity and specificity were calculated at the 95% level. The McNemar test was used for comparison of proportions. RESULTS: MR angiography had a sensitivity of 100% (4/4) and a specificity of 91% (21/23) for the four stenoses of the celiac artery that were greater than 50%. For detection of renal artery stenoses of greater than 50%, present in nine arteries, the sensitivity was 89% (8/9) and specificity was 98% (49/50). MR angiography showed 100% (54/54) of all main renal arteries and 78% (7/9) of all accessory renal arteries seen on conventional angiograms. The proximal extent of the aneurysm was correctly predicted on the basis of MR findings in 100% (26/26) of patients with surgical correlation, compared with 92% (24/26) when conventional angiograms were used. This difference was not statistically significant (p > .1). MR imaging had a sensitivity of 100% (19/19) for detection of isolated aneurysms of the common iliac artery, and MR angiography had a 100% sensitivity (5/5) and specificity (103/103) for detection of stenosis greater than 50% in the common and external iliac arteries. One circumaortic left renal vein was visualized on MR images. CONCLUSION: These results suggest that MR angiography may be a useful noninvasive method for determining the presence of coexistent celiac, superior mesenteric, renal, and iliac atherosclerotic disease in patients with AAA.

Aged↗

PubMed1994

Secondary infrageniculate bypass with polytetrafluoroethylene.

Autologous saphenous vein is the preferred conduit for infrainguinal reconstructions. Patients requiring secondary infrageniculate bypass represent a challenging surgical problem. Often, patients requiring such surgery have had multiple bypass operations and lack usable saphenous vein. These patients may also be older and have complicated medical problems which may limit their total life expectancy. This report reviews 11 such patients who required secondary bypass procedures for limb salvage. All procedures were performed with thin-walled polytetrafluoroethylene (PTFE). No perioperative complications or deaths occurred. Four patients have subsequently died due to unrelated disease at 8, 12, 13, and 29 months after operation with clinically patent grafts. In the seven surviving patients, four grafts remain patent with a mean (s.d.) patency of 27(21) months. Three grafts occluded at 2, 4 and 20 months after surgery. By life table analysis, cumulative graft patency was therefore 68% at 24 months. It is concluded that in this high-risk population when no saphenous vein is available, PTFE may provide acceptable limb salvage when used in secondary infrageniculate reconstructions.

Aged↗

PubMed1993

Metalloproteinases and tissue inhibitor of metalloproteinases in mesothelial cells. Cellular differentiation influences expression.

Mesothelial cells play a critical role in the remodeling process that follows serosal injury. Although mesothelial cells are known to synthesize a variety of extracellular matrix components including types I, III, and IV collagens, their potential to participate in matrix degradation has not been explored. We now report that human pleural and peritoneal mesothelial cells express interstitial collagenase, 72- and 92-kD gelatinases (type IV collagenases), and the counterregulatory tissue inhibitor of metalloproteinases (TIMP). Our initial characterization of the mesothelial cell metalloenzymes and TIMP has revealed: (a) they are likely identical to corresponding molecules secreted by other human cells; (b) they are secreted rather than stored in an intracellular pool; (c) a primary site of regulation occurs at a pretranslational level; (d) phorbol myristate acetate, via activation of protein kinase C, upregulates expression of collagenase, 92-kD gelatinase, and TIMP, but has no effect on expression of 72-kD gelatinase; and (e) lipopolysaccharide fails to upregulate the biosynthesis of either metalloproteinases or TIMP. Of particular interest is the observation that the state of cellular differentiation has a striking influence on the expression of metalloenzymes and TIMP, such that epitheloid cells display a more matrix-degradative phenotype (increased 92-kD gelatinase and decreased TIMP) than their fibroblastoid counterparts. We speculate that mesothelial cells directly participate in the extracellular matrix turnover that follows serosal injury via elaboration of metalloproteinases and TIMP. Additionally, the reactive cuboidal mesothelium which is characteristic of the early response to serosal injury may manifest a matrix-degenerative phenotype favoring normal repair rather than fibrosis.

Adult↗

PubMed1993

Hemodynamics and aneurysm development in vascular allografts.

PURPOSE: Mechanical and immunologic factors may play a role in the development of native arterial and biologic graft aneurysms. We developed an experimental rat aortic allograft aneurysm model in which segments of infrarenal aorta were transplanted between hypertensive and normotensive rats to study these factors in this model. METHODS: Aortic allografts and autografts were inserted into spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. Effects of immunologic and antihypertensive therapy were evaluated. Graft diameters were followed up with magnetic resonance imaging and at harvest. Direct-pressure measurements were taken and dp/dtmax (force of ventricular contractions) was calculated before harvest. RESULTS: Autografts remained isodiametric and maintained their histologic architecture. Aneurysmal dilation of transplanted segments occurred in SHR host allografts but not in WKY host allografts. Histologic examination of all allograft specimens noted a rejection reaction characterized by inflammatory cell infiltration and medial smooth muscle cell loss. Antigenic enhancement accelerated aneurysm development in SHR hosts but had no significant effect on WKY hosts. Rates of allograft enlargement and final allograft diameters were similar in antihypertensive treated and untreated SHR hosts. The dp/dtmax in untreated SHR hosts was greatest and differed significantly from that in the WKY rats but only marginally from that in treated SHR hosts. CONCLUSIONS: Immunologic rejection but not abnormal hemodynamics is necessary for development of allograft aneurysm in this model.

Animals↗

PubMed1992

Magnetic resonance imaging of small arteries.

Magnetic resonance imaging (MRI) with receive-only surface coil technology was used to visualize and quantitative luminal diameters of small arteries in the rat. MRI measurements of normal and aneurysmal aortas, over a diameter range of 1-3 mm, were closely correlated with direct measurements made visually at laparotomy: measured differences averaged 0.16 mm, and the least-squares regression line (R2 = 0.97, P < 0.001) compared favorably to the line of equivalence, X = Y. This noninvasive but precise imaging modality demonstrates the potential value of using MRI to evaluate the diameter of small vessels, including the postoperative monitoring of arterial bypass graft patency in peripheral regions.

Abdomen↗

PubMed1992

Ultraviolet A irradiation stimulates collagenase production in cultured human fibroblasts.

This study was designed to investigate the biochemical mechanisms responsible for the connective tissue changes seen in actinically damaged skin, which is characterized histologically by diminution and ultrastructural alterations of collagen fibrils and deposition of elastotic material in the papillary dermis. We hypothesized that ultraviolet light could stimulate synthesis of interstitial collagenase in the skin, resulting in collagen degradation. Monolayer cultures of human fibroblasts or keratinocytes were irradiated with ultraviolet A (UVA) or ultraviolet B (UVB) radiation and interstitial collagenase or its inhibitor, TIMP (tissue inhibitor of metalloproteinases) assessed in the conditioned medium with Western immunoblots 24 h after irradiation. Northern blot analysis of the irradiated fibroblasts with a cDNA probe representing collagenase was also performed. Cell viability was greater than 90% with all doses of UV radiation studied. A dose-related increase in immunoreactive collagenase was detected in the medium of fibroblasts irradiated with 0-10 J/cm2 of UVA radiation as well as a parallel increase in the collagenase mRNA in the irradiated cells. UVA radiation stimulated collagenase synthesis in both neonatal and adult fibroblasts. TIMP production in UVA-irradiated fibroblasts increased to a lesser degree than did collagenase and its increase did not parallel the increase in collagenase. UVB (0-100 mJ/cm2) did not stimulate collagenase production by fibroblasts. In contrast to the stimulation of collagenase production by fibroblasts, a slight decrease in immunoreactive collagenase was seen in UVA-irradiated keratinocytes. These data suggest that direct stimulation of collagenase synthesis by human skin fibroblasts by UVA radiation may contribute to the connective tissue damage induced by ultraviolet radiation leading to photoaging.

Cells, Cultured↗

PubMed1992

Synthesis and regulation of keratinocyte collagenase.

We have recently demonstrated that human keratinocytes synthesize and secrete procollagenase and tissue inhibitor of metalloproteinases (TIMP) in culture. We have examined the response of keratinocyte collagenase production to the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), interleukin-1, extracellular matrix proteins and phagocytosis. Collagenase production in keratinocytes was markedly stimulated by TPA and paralleled the morphologic changes induced by the phorbol ester. Synthesis of collagenase increased six- to 34-fold with TPA, whereas the level of TIMP rose only three-fold. Interleukin-1 did not stimulate collagenase production by the keratinocytes, in contrast to its effect on cultured fibroblasts. When keratinocytes were plated on type I or type IV collagen, they synthesized increased amounts of collagenase compared with cells cultured on laminin or in the absence of matrix. TIMP synthesis was not increased by collagen. Finally, phagocytosis of latex beads did not augment collagenase production by the keratinocytes.

Cells, Cultured↗

PubMed1992

Circulating activated T lymphocytes in autoeczematization.

BACKGROUND AND DESIGN: Autoeczematization, the symmetric diffuse spread of a previously localized dermatitis, has an unclear etiology although some investigators have postulated that activated T lymphocytes play a role. Two estimates of activation of peripheral T lymphocytes are the cell surface expression of the HLA-DR antigen and the interleukin 2 receptor (IL-2R). We measured the percentage of circulating activated T lymphocytes in nine patients with autoeczematization compared with normal controls (n = 10), patients with stasis dermatitis (n = 6), and patients with severe (n = 10) or mild (n = 8) psoriasis. The percentage of activated T lymphocytes was determined by fluorescent, activated cell sorter analysis of peripheral leukocytes doubly stained with antibodies to T lymphocytes and HLA-DR antigen or IL-2R. RESULTS: Statistically significant elevations of HLA-DR- and IL-2R--positive T lymphocytes were seen in autoeczematization patients (P less than .004 and P less than .04, respectively) and those with severe psoriasis (P less than .004 for HLA-DR antigen and IL-2R). Percentages of HLA-DR- and IL-2R--positive T lymphocytes in patients with mild psoriasis were not significantly elevated. Two patients with autoeczematization had a reduction of their previously elevated levels of HLA-DR- and IL-2R--positive T lymphocytes after treatment. CONCLUSIONS: These data suggest a possible role for circulating activated T lymphocytes in the pathogenesis of autoeczematization and possibly in severe psoriasis.

Antigens, Surface↗

PubMed1990

Enhanced synthesis of collagenase by human keratinocytes cultured on type I or type IV collagen.

Human keratinocytes in culture are known to produce collagenase. As part of studies to ascertain the physiologic stimuli for collagenase production by keratinocytes, we wanted to determine whether extracellular matrix could modulate the production of collagenase in vitro. Immunoprecipitable collagenase from the conditioned medium of cells grown on different types of matrix was measured. Metabolically labeled human keratinocytes were cultured in 0.1 mM calcium in serum-free medium on colloidal gold-coated coverslips plus type IV collagen, type I collagen, or laminin or in the absence of matrix. Immunoprecipitation of the conditioned medium with anti-collagenase antiserum was performed and the immunoprecipitates were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, fluorography, and densitometry. The keratinocytes cultured on type IV or type I collagen produced more collagenase than did those cultured on laminin or in the absence of matrix. This effect did not reflect a general increase in secreted proteins, because the production of tissue inhibitor of metalloproteinase, or TIMP, did not increase under the same conditions. Phagocytosis of the gold salts by the keratinocytes migrating on types I or IV collagen did not account for the increased collagenase produced by these cells since the effect persisted in the absence of the colloidal gold and phagocytosis of latex beads did not augment collagenase production.

Cells, Cultured↗

PubMed1990

Characterization of cellular elements in healed cultured keratinocyte autografts used to cover burn wounds.

Biopsy specimens from unburned skin were obtained from three severely burned patients and placed into tissue culture. After 2 to 3 weeks, the cultured keratinocytes were released from the Petri dishes and transplanted onto the patient's burn wound, which had been completely excised down to muscle fascia, thereby removing all cutaneous elements. Healing cultured autografts were found to become repopulated with Langerhans cells within 3 to 6 weeks. A neodermis rich in fibronectin rapidly formed between the autografts and muscle fascia. However, using monoclonal antibodies to cytokeratins as markers of differentiation, we found that the autograft keratinocytes expressed an abnormal pattern of differentiation that was similar to the differentiation seen in hyperproliferative states such as psoriasis. In contrast, healed split-thickness graft donor sites and reepithelialized interstices of mesh grafts maintained the basal keratinocyte staining pattern of normal skin with the AE-1 monoclonal antibody.

Adult↗

PubMed1989

Constitutive production of procollagenase and tissue inhibitor of metalloproteinases by human keratinocytes in culture.

Production of procollagenase and tissue inhibitor of metalloproteinases was demonstrated in human keratinocyte cultures. The two proteins were immunoprecipitated from keratinocyte-conditioned medium with antibodies to human dermal fibroblast collagenase and tissue inhibitor of metalloproteinases and quantitated with enzyme-linked immunosorbent assays. Treatment of the keratinocytes with the phorbol ester, 12-0-tetradecanoylphorbol-13-acetate, produced a six to 34-fold increase in procollagenase synthesis and secretion but only a threefold increase in the production of tissue inhibitor of metalloproteinases. Collagenase and tissue inhibitor of metalloproteinases mRNAs were present in normal keratinocytes, were the same size as their fibroblast counterparts, and both increased in response to treatment with 12-0-tetradecanoylphorbol-13-acetate. These data suggest that remodeling of type I collagen may be an important function of human keratinocytes in vivo.

Cells, Cultured↗

PubMed1989

Botryomycosis caused by Moraxella nonliquefaciens.

Botryomycosis is a bacterial infection characterized by the presence of grains of organisms in the tissue. Although Staphylococcus aureus is the most common causative agent, other bacteria have been reported to cause botryomycosis. Several factors have been hypothesized to be important in the pathogenesis of botryomycosis, including foreign bodies, quantity and virulence of organisms, and host immunity. The resulting infection tends to be resistant to antibiotic therapy. We report a case of botryomycosis of the hand caused by Moraxella nonliquefaciens, an organism of low virulence not previously associated with botryomycosis, and discuss the factors that may have led to this infection. This infection was successfully treated by excision and grafting.

Adult↗

PubMed1989

Familial koilonychia.

Koilonychia is a well-recognized clinical sign of iron deficiency occurring either with or without anemia. A case of familial koilonychia with an inheritance pattern consistent with an autosomal dominant trait is presented. Comments on inherited koilonychia and other causes of koilonychia are also included. The possible causes of the nail disorder are discussed.

Anemia, Hypochromic↗

PubMed1987

Production of procollagenase by cultured human keratinocytes.

Using a collagen film assay utilizing 14C-labeled type I collagen, we demonstrated that cultured human keratinocytes produced a procollagenase after treatment with the tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). Production of collagenase paralleled alterations in cellular morphology induced by TPA. When procollagenase was immunoprecipitated with antibody to human fibroblast collagenase and analyzed on sodium dodecyl sulfate-polyacrylamide gels, the zymogen was revealed as a 56- and 51-kDa doublet. The keratinocyte-derived collagenase was a neutral metalloprotease, required activation with trypsin for detection in the collagenase assay and produced the characteristic three-quarter and one-quarter length collagen cleavage products when incubated with type I collagen at 25 degrees C. The enzyme was inhibited by serum and cysteine and was largely unaffected by serine, thiol, and carboxyl protease inhibitors. Cycloheximide inhibited the TPA-induced production of collagenase, suggesting that the procollagenase was not stored preformed in the keratinocytes. Keratinocytes treated with a tumor-promoting analogue of TPA also produced collagenase, but cells treated with cytochalasin B, interleukin-1, or two non-tumor promoting phorbol esters did not. Keratinocyte-derived collagenase may play a role in wound healing and morphogenesis.

Adult↗

PubMed1986

A case of linear IgA disease presenting initially with IgG immune deposits.

We describe a case of linear IgA bullous disease initially presenting with histopathologic and immunofluorescent findings consistent with bullous pemphigoid. Initial immunofluorescent studies demonstrated a predominance of linear IgG at the basement membrane zone (BMZ) of perilesional skin and a low titer circulating IgG anti-BMZ antibody. Repeat studies 3 years later revealed a predominance of linear IgA immune deposits at the BMZ and no circulating anti-BMZ antibody. Dapsone therapy was initiated at this time with a good therapeutic response noted. Suction blister studies, immunoelectron microscopy, split skin immunofluorescent studies and Western immune blot were performed and provided indirect evidence that the BMZ antigen in this case is distinct from the bullous pemphigoid antigen component of the BMZ.

Aged↗