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Biomedical subjects

R E Gordon

Publications and source records attributed to R E Gordon.

At least 55 records · Page 3Linked to original sources
PubMed1993

Distribution of c-myc oncoprotein in healthy and atherosclerotic human carotid arteries.

PURPOSE: Smooth muscle cell (SMC) proliferation is a central event in the development of arteriosclerotic plaque. Regulation of this proliferative process is controlled in part by the action of specific peptide growth factors that may influence early cell-cycle regulatory gene expression. Such "early" response genes include the protooncogene c-myc, which has been implicated in the induction of cell proliferation and differentiation. We compared the distribution of the c-myc protooncogene product in healthy and atherosclerotic human carotid arteries to determine its cellular and tissue localization. METHODS: Samples of six carotid artery plaques from six patients were rapidly frozen in liquid nitrogen at the time of carotid endarterectomy. Three nondiseased human carotid arteries obtained at organ harvest from brain-dead organ donors were similarly prepared. Frozen sections were labeled with a polyclonal rabbit anti-c-myc antibody that recognizes the 64 kd c-myc human protein. The percentages of cells positive for c-myc (c-myc index) and the intensity of antibody labeling were determined. RESULTS: Normal human carotid artery demonstrated minimal, isolated cell staining, with single scattered grains of immunocytochemical staining product seen in SMC nuclei. The myc index was 14.7% +/- 3.5% positive cells. In comparison, SMCs from carotid plaque showed a significant predominance of c-myc immunoreactive cells (89.8% +/- 4%; p < 0.001). The intensity of c-myc staining was greater in plaque SMCs, with many of the cells demonstrating confluence of immunocytochemical precipitate throughout 50% of SMC nuclei. CONCLUSIONS: Although the exact role of enhanced expression of the c-myc protooncogene in atherosclerosis is unclear, a cooperative influence of abnormal early cell-cycle gene expression and humoral factors may initiate the atherogenic process. The c-myc gene and other protooncogenes are early molecular markers of cell-cycle activity, which may be important in the development of atherosclerosis and occlusive vascular disease.

Adult↗
PubMed1993

Saphenous vein angioscopy: a valuable method to detect unsuspected venous disease.

PURPOSE: The presence of preexisting saphenous vein lesions adversely affects graft patency. Despite careful preoperative venous duplex examination and meticulous intraoperative evaluation, clinically significant saphenous vein disease may remain undetected. We evaluated angioscopy as a means to better detect these vein lesions. METHODS: Ninety saphenous vein remnants, obtained at bypass surgery, were perfusion fixed for subsequent angioscopic and histologic evaluation. The specimens were categorized by independent examiners on the basis of the angioscopic or light microscopic findings. Of the 90 vein remnants, 66 were normal by angioscopic criteria. Fifty-three (80%) of these angioscopically normal vein segments were normal histologically, and all 24 angioscopically abnormal saphenous vein remnants showed disease on microscopic examination. RESULTS: Angioscopy correctly identified sclerotic vein segments (n = 20) by irregular white plaques, whereas postphlebitic veins (n = 3) demonstrated multiple lumens, fibrous strands, and thickened opaque valve cusps on angioscopic evaluation. Absence of an angioscopic lumen was confirmed histologically in occluded veins (n = 2). Angioscopy failed to identify thick-walled (n = 10) and varicose (n = 2) vein segments as abnormal; one sclerotic segment was normal angioscopically, thereby lowering the sensitivity of angioscopy. CONCLUSIONS: Angioscopy detected unsuspected preexisting saphenous vein disease in five patients undergoing arterial reconstruction with saphenous vein. Because the use of angioscopy is a reliable means of prospectively assessing the vein for most preexisting lesions, its routine use may ultimately improve graft patency.

Angioscopy↗
PubMed1993

Saphenous vein biopsy: a predictor of vein graft failure.

PURPOSE: To determine why some vein grafts fail, we prospectively studied the relationship between the histologic condition of the greater saphenous vein (GSV) at the time of grafting and subsequent stenosis of the vein graft. METHODS: Ninety-four remnant segments of GSVs were obtained at the time of infrainguinal bypass in 91 patients and were perfusion fixed before histologic and ultrastructural examination. All bypass grafts were evaluated clinically and by duplex ultrasonography at regular intervals from 1 to 30 months after operation. All 24 grafts that developed lesions that caused thrombosis (failed grafts) or flow reduction (failing grafts) underwent arteriography and appropriate operative or other interventional correction of the causative lesion. RESULTS: There was no significant difference in the incidence of coronary artery disease, kidney disease, hypertension, or history of smoking in patients with normally functioning and failed or failing grafts. Diabetes occurred with an increased frequency in failed or failing grafts (p = 0.056). At the time of their insertion, GSVs that subsequently developed significant lesions had thicker walls (0.72 +/- 0.33 mm) compared with normally functioning grafts (0.58 +/- 21 mm; p < 0.02). Most of this difference was related to a significantly thicker intima (0.27 +/- 0.17 vs 0.11 +/- 0.7 mm; p < 0.0001). Another significant finding was the presence of subendothelial spindle-shaped cells greater than five cell layers thick. This occurred more often in pregraft biopsies from grafts that developed significant lesions (70.4% vs 7.5%, p < 0.0001). Electron microscopic examination of these cells demonstrated a subpopulation of poorly differentiated cells with few fibers and many vesicles. Four of 24 (17%) failed or failing grafts had evidence of vein wall calcification at the time of vein grafting. This was seen in only one (1.4%) of 70 normally functioning grafts without lesions (p < 0.005). CONCLUSIONS: We conclude that GSVs with thick and calcified walls or hypercellular intima at the time of grafting are at increased risk of developing intragraft lesions that may lead to graft failure. Frequent duplex ultrasonography surveillance is particularly warranted for such high-risk grafts.

Aged↗
PubMed1993

A comparison of rural family practice in the 1930s and today.

Two hundred forty-four consecutive diagnoses and procedures appearing on the patient billing records between June 1934 and September 1935 of a general physician practicing in rural southwestern Minnesota were compared with 286 diagnoses and procedures taken from the billing records of patient visits made over a 2-week period to a modern family physician practicing in a comparable rural community in southwestern Ohio. The most common items on the billing records of the physician of the 1930s were follow-up incision and drainage of abscess, 26 (10.7%); diphtheria immunization, 24 (9.8%); follow-up drainage for mastoiditis, 17 (7.0%); and scrotal tap for epididymitis, 14 (5.7%). Many of these patient encounters were at the patient's home. The most common items on the records of the modern physician practicing in rural southwestern Ohio were upper respiratory tract infection, 13 (4.5%); hypertension, 12 (4.2%); hyperlipidemia, 11 (3.9%); and history-taking and physical examination (adult), 10 (3.5%). This study suggests that there are great differences between the diagnostic profiles of the first third of the 20th century and modern family physicians. Many of the common diagnoses seen by the physician of the 1930s required a procedure to be performed. Many of the problems treated by the contemporary family physician did not even exist for the early 20th century general physician. Some of the differences between the modern physician and his predecessor can be explained by the introduction of antibiotics in the late 1930s and early 1940s.

Family Practice↗
PubMed1993

Co-localization of von Willebrand factor and type VI collagen in human vascular subendothelium.

The binding of von Willebrand factor (vWF) to subendothelium constitutes an important initial step in the process of platelet adhesion to exposed subendothelium following blood vessel injury. We previously demonstrated that vWF is present in human vascular subendothelium and recently found that a 150 kd vWF-binding protein, which we extracted from subendothelium, is type VI collagen. Although we have established that vWF and type VI collagen bind in vitro, it is not known whether these two proteins are associated in the vascular subendothelium in situ. We, therefore, 1) investigated the morphological effects of our biochemical extraction procedure on human umbilical veins by scanning and transmission electron microscopy, 2) analyzed the subendothelial extract by immunofluorescence for the presence of vWF and collagens and by electron microscopy for morphological characteristics, and 3) localized vWF and type VI collagen in subendothelium by immunofluorescence and by single- and double-label immunoelectron microscopic studies with protein A-conjugated gold particles. We found that the surface exposed following de-endothelialization is composed of microfibrils and contains very little fibrillar collagen. The subendothelium is stripped after sodium dodecyl sulfate-urea extraction, and the extract itself contains immunoreactive vWF and type VI collagen but no immunoreactive type I or III fibrillar collagens. Immunofluorescence and immunoelectron microscopic studies showed that vWF and type VI collagen are both present in subendothelium, where both co-localized to microfibrils. In conclusion, vWF that binds to type VI collagen in vitro, also co-localizes with type VI collagen in subendothelium, where both are associated with microfibrils. Type VI collagen, therefore appears to serve as a biologically significant binding site for vWF in vivo and may thereby play a role in mediating platelet adhesion to exposed subendothelium following vascular injury.

Collagen↗
PubMed1992

Lesions and preferential initial localization of [S-methyl-3H]bleomycin A2 on Saccharomyces cerevisiae cell walls and membranes.

Extensive lesions were produced in cell walls of Saccharomyces cerevisiae by the bleomycin family of anticancer antibiotics (30 min to 4 h). Electron micrographs revealed that the alterations were most frequently large breaks and small interruptions or holes in cell walls, which sometimes extended into cell membranes. Large portions of cell walls were sometimes lost. Cell walls were frequently ruptured in one or more positions. More than 75% of bud scar regions in single-plane sections and all bud scars in serial sections exhibited many interruptions and breaks after 3 or 4 h of treatment. The discovery of extensive damage to cell walls was consistent with the preferential (approximately 70%) association of radiolabeled bleomycin with cell walls and perimeters of bud scar regions after short exposures (30 min). After longer exposures, the distribution of silver grains changed from a predominant association with cell walls (30 min) to an increased association with the cell cytoplasm (1 to 4 h). This correlated with increased ultrastructural damage, since damage to cell walls was generally more frequent and more severe with increasing length of treatment (30 min to 4 h) or dose (25 to 100 micrograms/ml). Although DNA lesions are believed to be the lethal properties of bleomycins, the lesions produced in cell walls are also lethal properties of the antibiotics. The distributions of lesions on cell walls suggested a generalized interaction of the antibiotic with a cell wall component. These results led us to hypothesize a mechanism of effective antifungal action for the bleomycin family of antibiotics.

Autoradiography↗
PubMed1992

Paneth cell-like metaplasia of the prostate gland.

We report two cases of Paneth cell-like metaplasia of the prostate gland, one in poorly differentiated carcinoma and the second in benign hyperplasia. By light microscopy, the Paneth-like cells were indistinguishable from Paneth cells found in the normal small intestine and ultrastructurally showed electron-dense granules typical of Paneth cells. Immunohistochemical stains were positive for prostate-specific antigen and prostatic acid phosphatase and negative for lysozyme and alpha 1-antitrypsin. The clinical significance of Paneth cell-like metaplasia is unknown and may represent an example of the multipotential metaplastic capability of actively dividing cells.

Adenocarcinoma↗
PubMed1992

Unsuspected preexisting saphenous vein disease: an unrecognized cause of vein bypass failure.

Our prior anecdotal experience with unsuspected preexisting saphenous vein disease prompted us to study its incidence, its relation to graft failure, and to identify techniques for its detection. Thick-walled, postphlebitic sclerotic occluded, postphlebitic sclerotic recanalized, calcified, and varicose vein lesions were detected in 63 (12%) of 513 infrainguinal vein bypasses. In 13 (2% to 5%) cases, severe saphenous vein disease precluded use of the vein. In the remaining 50 cases, the entire vein or a portion thereof, with minimal or unsuspected disease, was used for bypass. Early graft failures occurred in 10 (20%) of the 50 cases. The cumulative primary patency rate at 30 months for bypasses performed with diseased veins was 32%. This was significantly less than the 73% cumulative primary patency rate for bypasses with veins without detectable disease (p less than or equal to 0.001). Retrospective evaluation of preoperative duplex ultrasonography (n = 21) originally used to evaluate saphenous vein length and diameter correctly identified thick-walled, occluded, calcified, and varicose veins in 62% of cases. Intraoperative methods of vein evaluation included inspection, palpation, irrigation, catheter or valvulotome insertion to identify obstruction, and intraoperative arteriography. Histologic examination of diseased veins demonstrated a spectrum of disease with thickening of the intima and media, vein wall calcification, and luminal recanalization. We conclude that (1) unsuspected preexisting saphenous vein disease occurs in approximately 12% of cases and results in both early and late graft failures; (2) detection, in some cases, is possible with duplex ultrasonography and intraoperative techniques; and (3) diseased veins that are recanalized, calcified, or thick-walled should not be used if an alternative vein is available.

Chi-Square Distribution↗
PubMed1991

Usefulness of the nude mouse model in mesothelioma based on a direct patient-xenograft comparison.

A patient with malignant mesothelioma experienced tumor recurrence 3 months after pleuropneumonectomy. Samples of the tumor were transplanted into nude mice to assess chemosensitivity. There was close concordance between the results in xenografts and the clinical outcome in this patient. Both mitomycin and to a lesser extent cisplatin were effective as single agents against the nude mouse xenografts, and the combination of these two drugs produced a complete response both in the patient and in the xenografts. The patient survived 18 months from onset of chemotherapy and 24 months from diagnosis. The duration of clinical complete response to chemotherapy was 14 months, despite the fact that mitomycin, the most effective agent against the xenografts, was discontinued after only two cycles because the patient developed pulmonary toxicity. This direct patient-xenograft correlation further validates the usefulness of the nude mouse model in the search for effective therapies for malignant mesothelioma, a tumor characterized by frequent refractoriness to most available agents.

Animals↗
PubMed1991

An unusual organoid tumor. Alveolar soft part sarcoma or paraganglioma?

The histogenesis of alveolar soft part sarcoma (ASPS) is a subject of continued debate. Although many recent reports suggest a muscle origin, others advocate a neuroendocrine derivation. A tumor in the chest wall of a 16-year-old woman was diagnosed and treated as ASPS. The light microscopic, electron microscopic, and immunohistochemical findings showed features of both ASPS and paraganglioma. In addition, this lesion was positive for antibody to glucagon, a characteristic of neither ASPS nor paraganglioma, although seen in a few gangliocytic paragangliomas. This case demonstrates the need for continued inquiry into the histogenesis of ASPS.

Adolescent↗
PubMed1991

Carcinoma of the colon in asbestos-exposed workers: analysis of asbestos content in colon tissue.

Epidemiological studies have indicated an increased incidence of carcinoma of the colon in asbestos workers. The present study evaluated the colon tissue asbestos burden, by light and electron microscopic analytic techniques, in patients with a history of occupational asbestos exposure and colon cancer. Asbestos fibers and/or asbestos bodies were present in colon tissue from 14 of 44 (31.8%) asbestos workers with colon carcinoma (range 142,199 to 15,231, 543 fibers/g/wet weight, mean 2,517,823). Chrysotile was identified in 9 patients and amosite in 3 patients. Both amosite and chrysotile were found in the colonic wall in one individual. Other forms of asbestos (e.g., crocidolite, tremolite, or anthophyllite) were not found. Asbestos fibers and asbestos bodies were not found in colon tissue from 20 control patients (colon carcinoma and no asbestos exposure). Asbestos fibers frequently enter and reside in the wall of the colon and are often intimately associated with tumor tissue at the site of colon carcinoma in workers with asbestos exposure and colon carcinoma.

Asbestos↗
PubMed1991

Sudden death of an elderly man with multiple malignant neoplasms.

With the lengthening of the human life span, cancer has become an increasingly important medical problem for the aged. It is not uncommon to find multiple primary neoplasms in elderly individuals. We recently investigated the death of an elderly man who had died suddenly and had three incidental malignant neoplasms, including a pleural mesothelioma, first diagnosed at autopsy. The importance of performing a complete medicolegal autopsy for epidemiological and statistical purposes is emphasized.

Adenocarcinoma↗
PubMed1991

Desquamative interstitial pneumonia associated with chrysotile asbestos fibres.

The drywall construction trade has in the past been associated with exposure to airborne asbestos fibres. This paper reports a drywall construction worker with 32 years of dust exposure who developed dyspnoea and diminished diffusing capacity, and showed diffuse irregular opacities on chest radiography. He did not respond to treatment with corticosteroids. Open lung biopsy examination showed desquamative interstitial pneumonia. Only a single ferruginous body was seen on frozen section, but tissue examination by electron microscopy showed an extraordinary pulmonary burden of mineral dust with especially high concentrations of chrysotile asbestos fibres. This report emphasises the need to consider asbestos fibre as an agent in the aetiology of desquamative interstitial pneumonia. The coexistent slight interstitial fibrosis present in this case is also considered to have resulted from exposure to mineral dust, particularly ultramicroscopic asbestos fibres.

Asbestos↗