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R Sedivy

Publications and source records attributed to R Sedivy.

At least 37 records · Page 2Linked to original sources
PubMed1998

Apoptotic hepatocytes in rejection and vascular occlusion in liver allograft specimens.

AIMS: Programmed cell death (apoptosis) has been described in different hepatobiliary diseases and in immune-mediated cytotoxicity. Apoptosis of hepatocytes and bile duct epithelial cells was detected in chronic liver allograft rejection. In severe acute rejection a DNA fragmentation in-situ assay showed positivity of apoptotic cells and centrilobular necrosis. Although apoptosis is triggered by ischaemia, the potential role of apoptosis in tissue damage caused by hepatic vascular occlusion after orthotopic liver transplantation has not yet been investigated. METHODS AND RESULTS: We examined biopsies for apoptotic cell death in 50 liver allografts: 29 with acute liver rejection, six without rejection, five time-zero biopsies, and 10 cases with hepatic artery thrombosis. In addition to a semiquantitative assessment of apoptotic bodies in haematoxylin and eosin stains, an in-situ end nick-labelling technique (TUNEL) was used to detect DNA fragmentation. In all cases with hepatic artery thrombosis the incidence of apoptosis was found significantly increased in comparison to acute rejection. CONCLUSIONS: As apoptosis is a mechanism in the early stages of tissue damage prior to necrosis, increased apoptosis in liver allograft biopsies might be regarded as a signal of early ischaemia indicating initial vascular occlusion.

Adolescent↗
PubMed1998

[Actinic brachial plexus lesion].

Radiation-induced brachial plexus lesions are progressive and irreversible complications. Until now, there is no way to successful prevention and treatment of this problem. In our series, relief of pain could be achieved by neurolysis in some cases, but there was no recovery of sensory and motor function. In order to improve the vascularity and nerve tissue regeneration, we performed muscle or gliding tissue flaps after neurolysis in our department. Since 1975, 25 patients who developed radiation-induced plexopathy were treated in our department. We followed 18 patients to evaluate the benefits of our surgical intervention. None of the patients had improvement of their sensory or motor impairment. Relief of severe pain was achieved in 83% either by neurolysis only with or without muscle or gliding tissue flap. In some cases, paresis worsened postoperatively. We also observed a return of severe pain after the operation.

Adult↗
PubMed1998

[Stereotactic breast biopsy: comparison of vacuum punch biopsy versus high speed core biopsy].

Since few years a new vacuum-assisted biopsy is used in addition to the common gun-needle biopsy in suspicious lesions of the mamma. Aim of our study was to compare these two techniques in regard to their histological outcome. Retrospectively, 149 of the 1997 performed biopsies and the corresponding operation specimens were evaluated. The biopsied lesions were divided in star-like densities, roundish opacities and different forms of microcalcifications. We found both stereotactical methods very accurate. In vacuum-assisted biopsies more representative material could be obtained in cases of microcalcifications. The better quality of the tissues made the histological result more reliable. In concern to other lesions in the mammogram there was no difference between the two techniques at all. In summary, both stereotactical methods revealed comparable and valuable results whereas in any form of microcalcifications we suggest to apply the vacuum-assisted method.

Biopsy↗
PubMed1998

[Fractal analysis of a breast carcinoma--presentation of a modern morphometric method].

Fractal analysis techniques are common tools in physics and image processing. In the past few years they have gained increasing attention in medical sciences, e.g., cardiology, pathology and radiology, respectively. This article intends to describe this new technique by applying fractal analysis to the instant of a breast carcinoma. One of the advantages of fractal analysis is the ability to describe an irregular and complex object by a measureable value, called the fractal dimension. The fractal dimension can be determined by using the box-counting method. We applied this technique to the mammography as well as to the histologic section of a breast carcinoma. The application of fractal analysis provides a specific measureable value of the growth pattern of a tumor. Thus, the fractal dimension serves in addition to the common used metric diameter.

Aged↗
PubMed1997

Proliferation and DNA fragmentation in meningioma subtypes.

Atypical meningioma has been introduced as tumour subtype of intermediate biological behaviour between classical and malignant meningiomas. To substantiate this three-step scale of malignancy, we assessed the proliferative activity reflected by Ki-67 (MIB1) labelling index (LI) in a series of 89 meningiomas, including 15 classical, 29 atypical, 35 anaplastic tumours, and 10 haemangiopericytomas and papillary meningiomas. The possible correlation of proliferation with the frequency of apoptosis and their relations to BCL-2 immunoexpression was investigated in seven classical, 10 atypical and 10 malignant meningiomas. Apoptosis was demonstrated by evaluation of the frequency of apoptotic figures, by the enzymatic technique of in situ tailing (IST) which stains apoptotic DNA fragments, and by DNA preparation and gel electrophoresis demonstrating DNA laddering in frozen tissues of five meningiomas. MIB1 LI revealed a highly significant increase from classical through atypical to anaplastic meningiomas (P < 0.0001); haemangiopericytomas and papillary meningiomas were well within the range of atypical meningiomas. IST indices rose with increasing malignancy and correlated with MIB1 LI (P < 0.0001): they showed a weak inverse correlation with BCL-2 immunoexpression (P = 0.05). BCL-2 expression tended to decrease with malignancy grade and was unrelated to MIB1 LI or frequency of apoptosis. Our data show that (i) apoptosis is a feature of meningiomas, significantly correlated with the malignancy scale. (ii) DNA fragmentation shows significant correlation with proliferation and inversely with BCL-2 expression; (iii) proliferation indices and frequencies of apoptosis/DNA fragmentation within meningioma subgroups corroborate the intermediate biological position of the atypical meningioma between classical and malignant meningiomas.

Antigens, Nuclear↗
PubMed1997

Epidermal growth factor attenuates Clostridium difficile toxin A- and B-induced damage of human colonic mucosa.

Epidermal growth factor (EGF) exhibits a cytoprotective effect on gastrointestinal epithelia via a receptor-mediated mechanism. We investigated the effect of EGF on Clostridium difficile toxin A (TxA)- and toxin B (TxB)-induced damage of human colon. Ussing-chambered colonic mucosa was exposed serosally to EGF before and during luminal exposure to TxA and TxB. Resistance was calculated from potential difference and short-circuit current. Epithelial damage was assessed by light microscopy and alteration of F-actin by fluoresceinated phalloidin. Luminal exposure of colonic strips to TxA and TxB caused a time- and dose-dependent decrease in electrical resistance, necrosis and dehiscence of colonocytes, and disruption and condensation of enterocyte F-actin. These effects were inhibited by prior, but not simultaneous, serosal application of EGF (20 nM). Administration of the tyrosine kinase inhibitor genistein (10(-6) M) inhibited the protective effects of EGF. We conclude that EGF protects against TxA and TxB probably by stabilizing the cytoskeleton, the main target of these toxins.

Actins↗
PubMed1997

Effect of growth factors on epithelial restitution of human colonic mucosa in vitro.

BACKGROUND: Epithelial restitution enables resurfacing of epithelial discontinuities by enterocyte migration. This study investigated the effect of basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF-1), and epidermal growth factor (EGF) on restitution of human colonic mucosa in vitro. METHODS: After base-line incubation human colonic mucosal strips, mounted in Ussing chambers, were luminally exposed to 0.5 mM sodium deoxycholate (NaDOC) for 10 min. Thereafter tissues were incubated with buffer alone or luminal buffer containing various concentrations of bFGF, IGF-1, and EGF for 3 h. Resistance (R) was calculated from potential difference (PD) and short-circuit current (Isc). All tissues were processed for light microscopy. Extent of damage was measured by morphometry. RESULTS: Luminal 0.5 mM NaDOC for 10 min caused R to drop by 43% (n = 4; P < 0.05). Compared with controls 50 ng/ml EGF induced an approximately 30% R increase until the end of the experiments (P < 0.05, n = 4, paired). Ten minutes after injury 50.2 +/- 4% of the mucosa was damaged (n = 6), and after 3 h damage was significantly reduced by EGF (17.2 +/- 3% versus 31.7 +/- 4%, 50 ng/ml EGF versus controls) (P < 0.05, n = 6 per group). Histology showed that EGF stimulated enterocyte migration over the basal lamina. Various doses of bFGF and IGF-1 did not impair restitution when compared with controls. CONCLUSION: In contrast to bFGF and IGF-1, EGF was shown to promote epithelial restitution of human colonic mucosa in vitro.

Colon↗
PubMed1997

Sudden, unexpected death of a young marathon runner as a result of bronchial malformation.

Deaths of young athletes are mainly caused by cardiac problems. Noncardiac deaths are infrequent and related to heat stress, drugs, sickle cell trait, and asthma. Herein, we report the case of a 28-year-old man, who collapsed during a marathon race, within sight of the finish line. Despite immediate resuscitation, he died shortly after hospitalization. Autopsy findings revealed neither unambiguous cardiac nor previously published noncardiac causes. Traumatic or drug-related death was excluded as well. We did find, however, focally hyperinflated pulmonary areas adjacent to atelectasis, interstitial emphysema, and mucosal infoldings of several bronchi. Histologically, two-thirds of medium-sized bronchi presented paucity of cartilages. Hence, the resulting flaccidity of the bronchial wall might cause bronchial obstruction, which we related to the genesis of this sudden and unexpected death.

Adult↗
PubMed1996

Transpalatine excision of a cavernous hemangioma of the infratemporal fossa.

Hemangiomas of the head and neck region can represent a therapeutic challenge depending on their size, location and symptoms. We report a case of a 40-year-old woman who presented with a 2-cm encapsulated cavernous hemangioma in the infratemporal fossa (ITF). Extensive workup included CT, MRI and angiography. A transoral/transpalatine approach avoiding osteotomy was used for surgical excision. After an unremarkable postoperative course the patient has remained disease-free after a 2-year follow-up period. We suggest this surgical approach as an alternative in carefully selected cases of circumscribed small, benign lesions of the ITF.

Adult↗
PubMed1996

The potential role of apoptosis (programmed cell death) in a chaotic determined carcinogenesis.

The proposed hypothesis may interpret apoptosis as a dynamic parameter by means of chaos theory. Regular tissue renewal is determined by the quantity of mitosis and cell death (mainly apoptosis). These two components are describable as so-called 'limit cycle attractor' representing a reference cycle of the tissue system. If tissue kinetics remain within these limits, the system stays in a homeostatic equilibrium. Disruptive factors such as genetic alterations may have the ability to destabilize this homeostasis and induce the quasiperiodic development which represents one way in which a system becomes chaotic. The inhibition of apoptosis prevents the elimination of mutation-affected cells which leads to an uncoordinated proliferation of a mutated cell clone. Thus, this clone represents an independent oscillator which effects a new attractor: it is called 'torus' attractor. Additional perturbations induce the chaotic 'strange attractor': the system is bound to shift into chaos, morphologically detectable as cancer.

Animals↗
PubMed1996

Protein kinase C tissue localization in human colonic tumors suggests a role for adenoma growth control.

BACKGROUND & AIMS: Protein kinase C (PKC) has been implicated as a mediator of growth control during colorectal carcinogenesis, but the mechanisms involved are still a matter of dispute. The aim of this study was to analyze PKC patterns and tissue distribution to gain further insight in PKC function during tumor development in the gut. METHODS: PKC isoenzymes alpha, beta 1, beta 2, delta, and eta and the proliferation antigen Ki67 were analyzed in formalin-fixed normal, premalignant, and malignant specimens using immunohistochemistry. RESULTS: In normal colonic mucosa, protein levels of all PKC isoenzymes followed an increasing gradient from the bottom to the top of the crypt, staining mainly terminally differentiated, resting cells. Atypical crypts observed in the normal mucosa adjacent to tumors expressed higher levels of Ca(2+)-dependent isoenzymes than the surrounding tissue. In tumors, the number and abundance of PKC isoenzymes was inversely related to proliferation in 7 adenomas and 9 carcinomas. Areas containing PKC-beta 1 as the only isoenzyme had the highest proliferation rates (50%-82% Ki67-positive cells). CONCLUSIONS: The data suggest a function of PKCs, especially PKC-beta 1, in colorectal carcinogenesis and tumor growth control.

Adenocarcinoma↗
PubMed1996

Epidermal growth factor promotes rapid response to epithelial injury in rabbit duodenum in vitro.

BACKGROUND & AIMS: Growth factors are mainly involved in the regulation of intestinal epithelial barrier function. This study investigated the effect of epidermal growth factor (EGF) and insulin-like growth factor 1 (IGF-1) on epithelial restitution of rabbit duodenum in vitro. METHODS: Rabbit duodenal mucosal strips mounted in an Ussing chamber were luminally exposed to 10 mmol/L HCl for 10 minutes and then incubated with buffer alone or luminal buffer containing various concentrations of EGF and IGF-1 for 3 hours. Resistance was calculated from potential difference and short-circuit current. Damage was assessed by morphometry on H&E-stained sections. RESULTS: HCl caused resistance to decrease from 112 +/- 2 to 51 +/- 4 ohms x cm2 10 minutes after injury (n = 6; P < 0.05). Postinjury treatment with 25 or 50 ng/mL luminal EGF for 3 hours stimulated resistance to recover to 94 +/- 3 and 104 +/- 3 ohms x cm2, respectively, vs. 81 +/- 3 omega x cm2 in controls (P < 0.05). Ten minutes after injury, 62% of the mucosa was damaged; 3 hours after injury, damage was reduced to 24% +/- 1.09% and 10% +/- 1.42% in the 25 and 50 ng/mL EGF group, respectively, vs. 38% +/- 0.93% in controls (n = 6 per group). EGF stimulated enterocyte migration. IGF-1 did not impair epithelial restitution. CONCLUSIONS: EGF, but not IGF-1, promoted epithelial restitution of rabbit duodenum in vitro.

Animals↗
PubMed1996

Laminin stimulates rapid epithelial restitution of rabbit duodenal mucosa in vitro.

BACKGROUND: This study investigated the effect of the basal lamina constituents fibronectin, collagen IV, and laminin on epithelial restitution of rabbit duodenum in vitro. METHODS: Rabbit duodenal mucosal sheets were mounted in Ussing chambers, luminally exposed to 10 mM HCI for 10 min, and incubated with buffer or luminal buffer containing 25-100 micrograms/ml of collagen IV, fibronectin, laminin, or polyclonal antisera directed against these proteins (diluted 1:50-1:20) for 3 h. Resistance was calculated from potential difference and short-circuit current. Mucosal damage was assessed by morphometry on hematoxylin- and eosin-stained sections. RESULTS: Acid exposure caused a 40% drop in resistance (119 +/- 5 versus 71 +/- 5 Ohm.cm2 before versus after injury; P < 0.05, n = 6) and mucosal damage of 58 +/- 4% (n = 6). Three hours after injury resistance was 102 +/- 6, 117 +/- 4, and 48 +/- 5 Ohm.cm2 in the control, laminin, and anti-laminin groups, respectively. Furthermore, 36 +/- 2%, 16 +/- 2%, and 64 +/- 5% of the mucosa was damaged in the control, laminin, and anti-laminin groups, respectively, 3 h after injury (P < 0.05 versus controls). Laminin promoted epithelial wound closure by stimulation of enterocyte migration, which was inhibited by anti-laminin. Fibronectin, collagen IV, anti-fibronectin, and anti-collagen IV did not impair restitution. CONCLUSION: Our results show that laminin promotes electrophysiologic restoration and epithelial restitution of rabbit duodenum in vitro. We therefore suggest that laminin plays an important part in the orchestration of epithelial integrity and barrier function.

Animals↗
PubMed1996

Fractal tumours: their real and virtual images.

Autonomous and uncoordinated proliferation of epithelia leads to various well-known growth patterns such as expansive (cauliflower-like), radiating infiltrative, polycyclic, and roundish-ovoid figures. All attempts to describe such natural growth patterns graphically by Euclidean geometry have failed and remain no more than works of art. However, fractal geometry is a new tool for the characterization of irregularly-shaped and complex figures. Moreover, behind a fractal structure there is a basic power-law which provides the opportunity to simulate these forms artificially. A prerequisite for achieving this goal of simulating tumour growth by computer is to establish whether typical tumour growth patterns are fractal. Hence, an investigation was undertaken of 20 tumours (malignant, metastases or benign) exhibiting the above-mentioned typical patterns. If tumour outlines are fractal they have to possess a fractal non-integer dimension which significantly exceeds the integer Euclidean dimension. The fractal dimension of tumour outlines was determined using the box-counting method. Almost all tumours presented a fractal dimension and virtual tumour images were created by utilizing available fractal software. In conclusion, the determination of the fractal dimension of solid neoplasms may be an additional morphometric parameter for growth assessment and it probably provides further opportunity to simulate cancer growth and infiltration by computer animation.

Cell Division↗
PubMed1996

[Characterization of inflammatory infiltrates in autoimmune cholangitis: an immunohistochemical study].

Autoimmune cholangitis is clinically characterized by cholestasis and serologically by the presence of antinuclear antibodies (ANA) and a lack of antimitochondrial antibodies (AMA). Morphologic characteristics are non suppurative bile duct destruction (NSBDD), ductopenia and occasionally granulomas. The aim of the study was to characterize the inflammatory infiltrate to find about the possible mechanism of bile duct destruction in AIC. Liver biopsy material of ten patients (9 female/1 male, mean age of 45,5 a) with the clinical and serologic features of AIC were evaluated morphologically for the presence of NSBDD, ductopenia and granulomas. The inflammatory infiltrate was characterized immunohistochemically using Ab against CD3 (pan T lymphocytes), OPD 4 (helper T lymphocytes and memory T lymphocytes), CD8 (cytotoxic T lymphocytes), GB4 (activated cytotoxic T lymphocytes), L26 (pan B lymphocytes), CD56 and CD57 (NK/K cells). Lymphocyte subsets were investigated with regard to quantity and distribution within liver tissue. For control ten cases of PBC were also investigated simultaneously. NSBDD was found in five, granulomas in three cases. Portal inflammation was seen in all cases. In 9 cases T cells outweighed B cells. GB4 positive activated cytotoxic T lymphocytes were found within bile duct epithelium in five cases. All these cases showed associated NSBDD. NK/K cells were seen infrequently. Similar findings were observed in the ten cases of PBC. We therefore conclude that bile duct destruction in AIC is mediated by activated cytotoxic T lymphocytes. AIC cannot be differentiated from PBC histologically or by immunomorphology.

Antibodies, Antinuclear↗
PubMed1995

Clostridium difficile toxin B is more potent than toxin A in damaging human colonic epithelium in vitro.

Toxin A but not toxin B, appears to mediate intestinal damage in animal models of Clostridium difficile enteritis. The purpose of this study was to investigate the electrophysiologic and morphologic effects of purified C. difficile toxins A and B on human colonic mucosa in Ussing chambers. Luminal exposure of tissues to 16-65 nM of toxin A and 0.2-29 nM of toxin B for 5 h caused dose-dependent epithelial damage. Potential difference, short-circuit current and resistance decreased by 76, 58, and 46%, respectively, with 32 nM of toxin A and by 76, 55, and 47%, respectively, with 3 nM of toxin B, when compared with baseline (P < 0.05). 3 nM of toxin A did not cause electrophysiologic changes. Permeability to [3H]mannitol increased 16-fold after exposure to 32 nM of toxin A and to 3 nM of toxin B when compared with controls (P < 0.05). Light and scanning electron microscopy after exposure to either toxin revealed patchy damage and exfoliation of superficial epithelial cells, while crypt epithelium remained intact. Fluorescent microscopy of phalloidin-stained sections showed that both toxins caused disruption and condensation of cellular F-actin. Our results demonstrate that the human colon is approximately 10 times more sensitive to the damaging effects of toxin B than toxin A, suggesting that toxin B may be more important than toxin A in the pathogenesis of C. difficile colitis in man.

Actins↗
PubMed1993

Transforming growth factor-beta 1 as a signal for induction of cell death by apoptosis.

Cell death by apoptosis is a major determinant of growth of normal tissues and tumours. The present study aimed to elucidate signal factors involved in its regulation. Epithelial cells in control liver, during regression of cyproterone acetate induced liver hyperplasia, in liver (pre)neoplasia and in uterus undergoing apoptosis in vivo show immunostaining for transforming growth factor beta 1 (TGF-beta 1) as detected by anti-pre(266-278) TGF-beta 1 antibodies. Positive immunostaining is also seen in a few intact cells of hyperplastic, regressing liver apparently preparing for apoptosis, but is virtually not found in hepatocytes of normal or growing liver nor in cells undergoing death by necrosis. Recombinant latency associated protein (rLAP, dimer of the pro-region non-covalently associated with the mature region) complex and mature TGF-beta 1 induce apoptosis in isolated hepatocytes cultured in vitro. These findings suggest an involvement of TGF-beta 1 in the induction of apoptosis in certain epithelia in vivo.

Animals↗