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Biomedical subjects

R E Gordon

Publications and source records attributed to R E Gordon.

At least 19 recordsLinked to original sources

Hyperosmolarity associated with diabetes insipidus alters hepatocyte structure and function but not survival after orthotopic liver transplantation in rats.

BACKGROUND: This study was designed to evaluate the effect of donor hyperosmolarity secondary to diabetes insipidus, an almost universal occurrence among brain-dead patients, on hepatic function. METHODS: In vitro (isolated liver perfusion) and in vivo (hyaluronic acid and indocyanine green uptake, arterial ketone body ratio, orthotopic liver transplantation) experiments were conducted using Brattleboro rats, with hereditary hypothalamic diabetes insipidus, and Sprague-Dawley rats, with normal pituitary function. ATP content and recovery after cold preservation were measured during the perfusion. RESULTS: Cold-preserved livers from hyperosmolar rats were observed to have elevated hepatic enzyme release and decreased bile production compared with normosmolar controls. Moreover, in these livers, the recovery of ATP after cold preservation was completely absent. Transmission electron microscopy of liver biopsies collected from hyperosmolar rats demonstrated profound ultrastructural changes, particularly in the mitochondria, that were not evident in the biopsies from normosmolar rats. All the experimental groups demonstrated similar hyaluronic acid uptake, whereas indocyanine green uptake was markedly impaired in the hyperosmolar group, suggesting that hepatocyte and not sinusoidal endothelial cell function is adversely affected by hyperosmolarity. The arterial ketone body ratio was profoundly compromised by chronic and, to an even greater degree, by acute hyperosmolarity. Survival after transplantation using hyperosmolar donors was not affected in this study. CONCLUSIONS: These results are an important step toward understanding the mechanism whereby brain death, a complicated pathophysiologic phenomenon, adversely affects the hepatic allograft.

Adenosine Triphosphate

In vitro studies of the interactions between platelets and amniotic membranes: a potential treatment for preterm premature rupture of the membranes.

OBJECTIVE: Thus far there is no satisfactory treatment for preterm premature rupture of the amniotic membranes. To evaluate the use of platelets to seal the membranes, we investigated in vitro interactions between platelets and the membranes. STUDY DESIGN: Platelet aggregation in the presence of amnion, chorion, and amniotic fluid was quantified. Platelet adhesion to the fetal membranes was investigated by electron microscopy. In addition, a model system was designed to evaluate the capacity of platelets to seal a standardized puncture in the membranes. RESULTS: Platelets aggregated in response to amnion but not to chorion or amniotic fluid. Adhesion and activation occurred on connective tissues underlying amnion and chorion but not on the amniotic epithelium. Platelets sealed a puncture in fetal membranes, and the platelet plug was visualized by electron microscopy. CONCLUSIONS: Exposed connective tissue of amniotic membranes was demonstrated to trigger platelet adhesion, aggregation, and activation, and platelets were shown to seal a standardized puncture in fetal membranes. Our results indicate that platelets might be useful for treatment of ruptured membranes after needle puncture.

Amnion

The significance of subendothelial von Willebrand factor.

von Willebrand factor (vWf) serves to bridge between receptors on the platelet cytoplasmic membrane and the extracellular matrix. In addition to circulating in plasma, vWf is deposited into the extracellular matrix of the subendothelium where it is associated with type VI collagen microfibrils, but not with the elastin-associated microfibrils which are present in the deepest portion of the subendothelium at the zone of the internal elastic lamina. The reaction of platelets to type VI collagen in flow systems is qualitatively different from the shear rate dependent adhesion and aggregation response which is observed with fibrillar type I collagen, exhibiting a response only at low shear rates. The adhesion response to type VI collagen is dependent upon vWf, GP Ib and the GP IIb-IIIa complex. Platelets exposed to purified fibrillin-containing elastin-associated microfibrils adhere and aggregate at low shear rates; this response appears to involve GP IIb-IIIa but not GP Ib. The data are consistent with the hypothesis that type VI collagen is a physiologically relevant binding site for vWf in subendothelium.

Animals

Localized amyloidosis of the seminal vesicle. Possible association with hormonally treated prostatic adenocarcinoma.

OBJECTIVE: Localized seminal vesicle amyloidosis is an unusual finding in surgical pathology material. Previous studies have demonstrated that the amyloid is directly produced by the seminal vesicle epithelial cells. We investigated the possible association of seminal vesicle amyloid in patients hormonally treated for prostate carcinoma. METHODS: Cases were collected from over 200 prostate needle biopsies, seminal vesicle biopsies, and prostatectomy specimens from the surgical pathology files at The Mount Sinai Hospital, New York, NY. None of the patients with seminal vesicle amyloidosis had a chronic inflammatory disorder, serum or urine protein abnormalities, or other identifiable masses. RESULTS: Six cases of localized seminal vesicle amyloidosis were found in the surgical pathology material examined. Five of the six cases had prostatic carcinoma, and one case was seen in a biopsy for benign prostatic hyperplasia. Four of the five carcinoma cases had prior hormonal treatment (luteinizing hormone-releasing hormone agonist with an antiandrogen agent, and one patient, in addition, had received radiotherapy). The amyloid deposits were limited to the seminal vesicle lamina propria without involvement of vascular walls. The amyloid reacted with Congo red staining that was sensitive to potassium permanganate. Immunohistochemically, all cases were negative for AA amyloid, beta 2-microglobulin, and kappa and lambda light chains. CONCLUSION: We raise the possibility that in some instances, prior hormonal therapy may act as a seminal vesicle epithelial stimulant for the elaboration of this protein.

Adenocarcinoma

The role of the family physician in the day care setting.

Injuries and infectious respiratory, gastrointestinal and dermatologic diseases are common in day care settings. Most day care injuries are contusions, abrasions and cuts involving the head and extremities. Impact-absorbing surfaces under playground equipment, safely-proofing of all play areas, increased staff supervision, and staff and parental education might reduce injuries by as much as 75 percent. Respiratory illnesses are the most common day care infections. Chemoprophylaxis with rifampin is required for all close contacts of children infected with Haemophilus influenzae type B and Neisseria meningitidis. Diarrheal illness may be caused by viral pathogens, bacterial agents such as Shigella, Campylobacter or Salmonella, or parasitic infections caused by Giardia lamblia and Cryptosporidium. Strict hand-washing procedures, especially before food preparation and after toileting, may reduce diarrheal illness by 50 percent. Head lice (Pediculosis capitis) and scabies are common dermatologic infections spread by direct contact and through clothing, bedding and hair brushes. Screening and treating affected children with permethrin preparations and thoroughly washing bedding and clothing are necessary to stop outbreaks. Use of universal precautions for the handling of stool is essential to prevent the spread of both ordinary diarrheal illnesses and serious infections such as hepatitis A and B, human immunodeficiency virus and cytomegalovirus.

Child

Asbestos exposure and ovarian fiber burden.

Epidemiologic studies suggest increased risk of epithelial ovarian cancer in female asbestos workers and increased risk of malignancy in general in household contacts of asbestos workers. Ovaries were studied from 13 women with household contact with men with documented asbestos exposure and from 17 women undergoing incidental oophorectomy. Ovarian tissue was examined by analytic electron microscopy. Significant asbestos fiber burdens were detected in 9 out of 13 women with household asbestos exposure (69.2%), and in 6 out of 17 women who gave no exposure history (35%). Three exposed women had asbestos counts over 1 million fibers per gram wet weight (23%), but only 1/17 women without an exposure history had a count that high (6%). Although asbestos has been documented as a contaminant of some older cosmetic talc preparations, the chrysotile and crocidolite types of asbestos we detected are more indicative of background and/or occupational exposure. This study demonstrates that asbestos can reach the ovary. Although the number of subjects is small, asbestos appears to be present in ovarian tissue more frequently and in higher amounts in women with a documentable exposure history.

Asbestos

The relationship between perineal cosmetic talc usage and ovarian talc particle burden.

OBJECTIVE: Epidemiologic studies support the hypothesis of a dose-related risk of epithelial ovarian cancer with perineal talc usage exposure. Frequency and duration of talc has not been previously correlated with ovarian talc content. STUDY DESIGN: Ovaries were studied from 24 women undergoing incidental oophorectomy who were interviewed regarding talc usage. Twelve subjects reported frequent perineal talc applications; the twelve controls reported no use. Ovarian tissue blocks were digested and analyzed by polarized light microscopy and analytic electron microscopy to identify and quantify talc. RESULTS: Talc was identified in all 24 cases by either light or electron microscopy. Talc particle counts were completely unrelated to reported levels of perineal talc exposure. CONCLUSIONS: The detection of talc in all ovaries demonstrates that it can reach the upper genital tract. Widespread exposure to talc during diapering may contribute to the ubiquitous presence of talc in ovarian tissue.

Adult

Morphological relationships of von Willebrand factor, type VI collagen, and fibrillin in human vascular subendothelium.

von Willebrand factor (vWF) plays an important role in the process of platelet adhesion after endothelial injury by serving as a bridge between constituents of the vascular subendothelium and platelet membrane receptors. We previously presented evidence that type VI collagen microfibrils serve as a binding site for vWF in human vascular subendothelium. However, others have proposed that vWF is not associated with type VI collagen but rather with the thicker elastin-associated microfibrils, which contain several proteins including fibrillin. We therefore investigated the relationships among vWF, type VI collagen, and fibrillin in human vascular subendothelium by immunoelectron microscopy using single- and double-labeling immunogold localization techniques. In addition, we observed the three-dimensional ultrastructure of vWF-microfibril complexes by stereo paired micrographs and stereo viewer. We found that vWF co-localizes only with the type VI collagen microfibrils in subendothelium but not with fibrillin microfibrils or striated collagen. The vWF is present in subendothelium in the form of electron-dense aggregates having diameters varying between 65 and 80 nm that are closely associated with, and enmesh, the type VI collagen microfibrils and have structural similarities to intracellular Weibel-Palade bodies. The occasional co-localization of type VI collagen and fibrillin adjacent to internal elastic lamina was observed. These results are consistent with the hypothesis that type VI collagen, but not fibrillin-containing microfibrils, serves as a physiologically relevant binding site for vWF in the vascular subendothelium, where the type VI collagen-vWF complex may play an important role modulating the hemostatic response to vascular injury.

Collagen

Radiographic detection of strut separations in Björk-Shiley convexo-concave mitral valves.

BACKGROUND: The outlet struts of Björk-Shiley convexo-concave heart valves can occasionally fracture. By December 31, 1994, 564 complete strut fractures had been reported to the manufacturer, approximately two thirds of which were fatal. There are no reliable diagnostic methods to detect valves that may be at risk for strut fracture. The outlet strut has two legs, and one leg often appears to break before the other, potentially permitting detection of the single-leg separation while the valve is still functionally intact. METHODS: We used high-resolution cineradiography and defined valve profiles to evaluate 315 patients selected on the basis of their having mitral convexo-concave valves with an estimated fracture rate of 0.46 percent or higher per year. Two examinations were scheduled six months apart, with early reimaging performed when initial ratings were indeterminate. RESULTS: Three patients had unsatisfactory studies, the most recent examinations in 277 patients were rated as apparently normal, 23 had findings considered minimally suspicious, and 1 had findings termed suspicious. The number of false negative results in this study group is unknown. Eleven cineradiograms were rated as showing probable or definite single-leg separations. All five "definite" ratings and five of the six "probable" ratings were confirmed by removal of the valves. One valve with a "probable" rating was intact. Two complete outlet-strut fractures occurred three and seven months after apparently normal radiographic examinations. Unsuspected new positive findings were not found at six months among 288 patients who completed the examination cycle. CONCLUSIONS: Cineradiographic imaging can detect some single-leg separations in mitral convexo-concave valves and may help the estimated 41,000 patients with these valves worldwide and their physicians decide about elective valve removal.

Actuarial Analysis

Additional benefit of heparin in the thrombolytic salvage of ischemic skin flaps.

Microvascular thrombosis is known to play an important part in the cessation of flow seen in a flap following ischemia and revascularization. Its reversal, using thrombolytic therapy, is associated with higher rates of successful flap salvage. Although this procedure restores patency to the microcirculation, the damaged endothelial cell layer remains highly thrombogenic and a definite risk of rethrombosis exists in the early period of reperfusion. In an inferior epigastric flap model in a rat, we investigated the effect of additional heparin (subcutaneous and intravenous administration) following a standardized urokinase washout (100,000 iu) of the ischemic flaps. Flap survival was assessed at 1 week and morphological changes in the microcirculation were observed using electron microscopy. Results showed a significant increase in flap survival in the group receiving intravenous heparin following urokinase washout and suggest that systemic heparin may play a beneficial role in the early reperfusion period following thrombolytic flap salvage.

Animals

Differential binding capacity and internalisation of bacterial substrates as factors in growth rate of Acanthamoeba spp.

Acanthamoeba spp. are free-living predators that selectively feed on bacteria. Adherence of the bacterial food source to the trophozoite membrane is followed by internalisation and digestion. Through co-cultivation of A. castellanii and A. polyphaga, individually, with Xanthomonas maltophilia, Escherichia coli, Staphylococcus epidermidis and Pseudomonas aeruginosa (despite the amoebicidal properties of the latter organism), specificity with regard to the preferred bacterial substrate was judged. X. maltophilia and P. aeruginosa adhered almost immediately forming a multilayered mantle of bacilli around trophozoites of both species of amoebae. E. coli adhered to fewer trophozoites and in smaller numbers. X. maltophilia was readily internalised after co-cultivation for 8 h, whereas P. aeruginosa, E. coli and S. epidermidis were not internalised even after co-cultivation for 24 h. These data suggest that the suitability of a bacterial food source for the Acanthamoeba spp. studied is associated not only with the proclivity with which the bacterial species binds to the trophozoite surface, but also with the rate of its internalisation.

Acanthamoeba

Cystinosis and gingival hyperplasia: demonstration of cystine crystals in gingival tissue and unusual aspects of management.

A patient with nephropathic cystinosis developed gingival hyperplasia secondary to cyclosporine-A therapy for his renal allograft. The typical crystals described on electron microscopic examination of other organs of patients with cystinosis were seen in the resected gingiva of this patient. These crystals have not been previously described in this location. Unusual aspects of the management of this patient are discussed.

Adult

Human greater saphenous vein: histologic and ultrastructural variation.

This study describes the varied histologic features and ultrastructure of human saphenous veins obtained from patients undergoing infrainguinal arterial reconstruction. Portions of 30 remnant veins were fixed at arterial pressure (100 mmHg). Vein specimens were obtained from 13 men and 17 women, with a mean age of 70.2 years. Ten veins (33%) were from diabetic patients. Samples of fixed veins were prepared for light and electron microscopy. The luminal surface contained valves and redundant intimal folds at the site of ligated side branches. Microvalves were present at the orifices of several 1-mm vein tributaries. The endothelial cells lining the intima were often discontinuous and were aligned in a variable pattern. The thicknesses of the vein walls varied from 20 to 360 microns, with increased connective tissue matrix in the intima and medial layers of thick-walled veins. Some 10% of the veins demonstrated spindle cells in the intima; these cells had a smooth muscle cell phenotype and varied with respect to the degree of cellular differentiation. Regions of vein wall calcification were occasionally seen and were always present in association with a thickened vein intima. Variations in the structure of the saphenous vein from patients undergoing bypass surgery are common. The relationship between altered saphenous vein morphology and subsequent vein graft stenosis needs to be defined.

Adult

Separation of the rabbit ciliary body epithelial layers in viable form: identification of differences in bicarbonate transport.

Sections of whole ciliary (CB) dissected from Dutch belted rabbits were incubated for 2 hr at 36 degrees C in a 30 microM Ca2+ Ringer's. This incubation resulted in the spontaneous dissociation of the two cell layers comprising this epithelium, each remaining firmly cohesive with its own basement membrane. The inner limiting membrane with its adherent non-pigmented epithelium (NPE) was then mechanically removed from the surface exposing the apical surface of the pigmented epithelium (PE). Ultrastructural examination revealed no noxious effects in most cells although gross morphological changes in the NPE cells were noted. The newly separated layers were loaded with the cell-permeable acetoxymethyl ester form of the fluorescent probe BCECF. Most cells of both layers acquired stable BCECF fluorescence indicating viability. To achieve a preliminary evaluation of differences in PE and NPE bicarbonate transport, dye-loaded tissues were perfused in a flow-through chamber which was mounted on a microscope equipped for quantitative epifluorescence. The intracellular pH (pHi) of groups of cells (5-10) was derived from the ratio of emission intensities generated by excitations at 490 and 440 nm. In Hepes-buffered Ringer's the pHis for the PE and NPE were 7.20 +/- 0.10 and 7.33 +/- 0.14 (+/- S.D., n = 6), respectively. Replacement of 28 mM Hepes by 28 mM HCO3-/5% CO2 led to a 0.13 pHi increase in the PE and a decrease of 0.27 U in the NPE. The pHi responses of the two cell layers to removal and/or reintroduction of Na+ and/or Cl- were also highly dissimilar.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Analysis of balloon dilatation of human vein graft stenoses.

Controversy continues as to whether percutaneous transluminal angioplasty (PTA) or surgical revision is the ideal modality for the treatment of failing grafts. This prompted a histopathologic analysis of failing human vein graft segments subjected to ex vivo balloon dilatation to define variables responsible for the discrepant results. Fifteen vein graft lesions from 14 patients with failing infrainguinal bypasses were recovered after surgical excision. Each graft lesion was focal and uniform in length (2.1 +/- 0.3 cm). Rings sectioned from adjacent regions of each vein graft lesion before and after balloon inflation were processed for histologic study, photomicrography, and image analysis. Angioplasty balloon size was selected on the basis of preoperative arteriograms. Graft lesions were divided into three groups based on lesion thickness and the degree of fibrosis and cellularity seen on sections stained with Masson's trichrome. The luminal area before angioplasty was not significantly different for the three groups (p > 0.2). Vein grafts with thick intimas (group 1) had significantly less luminal dilatation after angioplasty as compared with less thick intimal lesions (groups 2 and 3; p < 0.001). Those lesions with varying degrees of cellularity (groups 2 and 3) showed no significant differences in luminal diameter after angioplasty. However, the cellular lesions in group 2 consistently formed multiple intimal flaps that could produce PTA failures even with good luminal restoration. The varying histology of vein graft lesions and associated differences in intimal thickness and cellularity may be responsible for the inconsistent results following PTA. Estimates of wall thickness before angioplasty, particularly in the intimal area, may be helpful in evaluating which lesions might benefit most from PTA.

Angioplasty, Balloon

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