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Biomedical subjects

T Kerényi

Publications and source records attributed to T Kerényi.

At least 19 recordsLinked to original sources

Repeated biopsies in evaluation of therapeutic effects in prostate carcinoma.

BACKGROUND: Apoptosis is one of the major events following total androgen blockade (TAB). The aim of this study was to determine the predictive value of some histological parameters including apoptosis and gene products which influence apoptosis, based on repeated biopsies taken from the same patients. METHODS: At the time of diagnosis by needle biopsy TNM stage, serum PSA, Gleason's grade, apoptotic and mitotic index, Ki67, p53, and bcl(2) expression were investigated in 60 prostate carcinoma patients. Antiandrogen therapy supplemented with surgical or chemical castration was administered. Serum PSA-test and needle biopsy were repeated 13-14 weeks after starting the therapy, simultaneously with determination of the apoptotic and mitotic index, Ki67, p53, and bcl(2) expression. RESULTS: Forty-seven patients were alive at the end of the study, 13 patients died. Decrease in mitotic, increase in apoptotic index predicted favourable long-term response to antiandrogen therapy. Lower Ki67 and (mutant) p53 expression in the first and also in the second biopsy pointed to favourable effect of antiandrogen treatment. Since the ratio between Ki67 and apoptotic index strongly decreased in the survivors upon therapy, changes in Ki67/apoptosis ratio is recommended as a histologically detectable predictive factor. bcl(2) expression did not show significant correlation with the outcome of the disease. CONCLUSIONS: Histological evaluation of mitotic and apoptotic index, Ki67, and p53 expression in repeated biopsies contributes to predicting the value of the actual treatment and may be useful to institute alterations in therapy.

Age Factors↗

Study of inflammatory responses to crocidolite and basalt wool in the rat lung.

The subacute effects of crocidolite and basalt wool dusts were studied by nmeans of biochemical, morphological. and histological methods 1 and .3 mo after intrabronchial instillation. The cell count, protein and phospholipid contents, and lactate dehydrogenase (LDH) activity were determined in the bronchoalveolar lavage (BAL). Both types of fibers induced a prolonged inflammatory reaction in the lung. All the parameters studied in the experimental groups were more markedly elevated after 3 mo. Relative to the control, the protein and LDH values were increased three- to fivefold, the phospholipid content twofold, and the number of free cells in the BAL exceeded the control level up to ninefold. The inflammatory responses to crocidolite and basalt wool in the lung did not differ significantly. In spite of this, basalt wool is recoinmended as an asbestos substitute, as the use of this man-nade fiber may result in a significantly lower release of dust than that from crocidolite.

Animals↗

Connexin 43 expression in rat aortic smooth muscle after ovariectomy and hormonal replacement.

The purpose of this study was to determine the effects of ovariectomy and long-term combined sexual hormone replacement on the gap junctional protein, connexin 43 (Cx43) of aortic medial smooth muscle cells in rats. Twenty non-pregnant mature Wistar female rats were divided into five groups (four animals in each group). Group A underwent ovariectomy, Group B underwent ovariectomy and received estradiol propionate, Group C underwent ovariectomy and received medroxyprogesterone acetate and Group D underwent ovariectomy and received both hormones. Group E was sham-operated and used as control. After 15 weeks of treatment, thoracic aortas were removed and immunohistochemistry was carried out using a specific fluorescent antibody against Cx43. Tissue sections were examined by confocal laser scanning microscopy and analysed by the Scion Image program. All five different groups had the same distribution and extent of Cx43 in the aorta. Neither the ovariectomy nor the hormone replacement had any effect on the Cx43 expression of aortic smooth muscle cells in rats as compared to control animals. These results indicate that sexual steroids do not influence the gap junctional protein Cx43 of the medial layer of aorta in rats. They may suggest that the beneficial effects of estrogen are not mediated via gap junctions in the human aorta either.

Animals↗

Improving diagnostic accuracy of prostate carcinoma by systematic random map-biopsy.

Systematic random rectal ultrasound directed map-biopsy of the prostate was performed in 77 RDE (rectal digital examination) positive and 25 RDE negative cases, if applicable. Hypoechoic areas were found in 30% of RDE positive and in 16% of RDE negative cases. The score for carcinoma in the hypoechoic areas was 6.5% in RDE positive and 0% in RDE negative cases, whereas systematic map biopsy detected 62% carcinomas in RDE positive, and 16% carcinomas in RDE negative patients. The probability of positive diagnosis of prostate carcinoma increased in parallel with the number of biopsy samples/case. The importance of systematic map biopsy is emphasized.

Aged↗

Are there systemic changes in the arterial biomechanics of intracranial aneurysm patients?

Current theories on the development of intracranial aneurysm suggest that there is a general weakness of vascular connective tissue. Potential systemic alterations in arterial wall biomechanics were tested in the present study. A three-dimensional in vitro stress-strain analysis was made in the 0-200-0 mmHg pressure range on cylindrical segments excised from the anterior cerebral artery, the radial artery and from the arteria dorsalis pedis of aneurysm patients and of control cadavers. In the anterior cerebral artery from aneurysm patients (intracranial artery segments directly not affected by the aneurysm or by the subarachnoid bleeding), we found the wall thickness to be larger (0.1480+/-.019 versus 0.091+/-0.004 mm), the radius/wall thickness ratio smaller (9.7+/-1.4 versus 14.1+/-1.2), and the tangential wall stress lower [(0.122+/-0.019)x10(6) versus (0.181+/-0.016)x10(6) N/m2 at 100 mmHg] than in control subjects. Reduced radius was found in the extremity arteries studied. Elastic parameters, as incremental distensibility and elastic modulus, were remarkable similar. Our study demonstrates changes in the geometry of walls of arteries not directly affected by aneurysm formation, and it thus confirms systemic vascular pathology in this disease. At the same time, these data show that the molecular and morphological defects of arterial connective tissue formation generally thought to induce intracranial aneurysms will probably not affect the components responsible for the passive elastic properties of the vascular wall.

Adult↗

Tenascin expression and angiogenesis in breast cancers.

The expression and the distribution of tenascin as well as the extent of blood vessel formation (angiogenesis) were investigated in 70 invasive human breast carcinomas. Formalin-fixed, paraffin-embedded specimens were stained with monoclonal antibody against tenascin-C (DAKO and Biogenex). Anti-CD31 antibody (Biogenex), an acknowledged marker of stromal angiogenesis, was used to detect endothelial cells. Tenascin immunostaining was positive in the tumours around the persisting normal ducts, around tumour-cell nests, in the neostroma, in some tumour cells, and it was found in or around vascular channels. Tumour vascularity was assessed by quantitative vascular grading (Chalkley point count) and was related to the localization and intensity of tenascin immunoreactivity. 19 tumours (27.1%) were scored as low, 35 (50%) as medium, and 16 (22.9%) as having a high vascular grade. The positive correlation between the vascular grade and the tenascin immunopositivity in tumour stroma was observed. Our results suggest that tenascin expression may be associated with endothelial cell activation and may play an important role in tumour angiogenesis.

Adult↗

Cellular autofluorescent pigment and interstitial fibrosis in smoker's lung.

The mechanisms by which cigarette smoking lead to bronchopulmonary diseases are incompletely understood. The most characteristic lesion is a chronic macrophage-alveolitis accompanied by slight fibrosis and emphysema. The macrophages contain a ceroid-like granular autofluorescent pigment in their lysosomes. Using immunohistochemical methods, open lung-, transbronchial biopsies and cells obtained by broncho-alveolar lavage from cigarette smokers were studied: anti-human macrophage serum and anti-human elastase, immune sera against type I, type III collagens and fibronectin were used in the demonstration of the cellular components of alveolitis and the connective tissue constituents of fibrosis. The characteristic red-brown autofluorescent pigment of the macrophages was also found in an extra-alveolar location mainly in peribronchial, septal and pleural scars. Similar emission colour occurred focally in the elastic laminae of fibrotic alveoli and sclerotic arteries. Granular fluorescent pigment was found in many bronchial epithelial cells. The epithelial pigmentation was associated with increased transcription of nucleic acid proteins, revealed by colloid silver (AgNOR) reaction. The results suggest that the autofluorescent pigment substances in macrophages may indicate or also play a role in the development of pathological connective tissue and epithelial changes of smoker's lung, in addition to the known mediators and enzymes.

Adult↗

Changes of DNA-acridine orange binding in monocytes and endothelial cells of hypertensive arteries.

The interactions of monocytes and endothelial cells were examined employing acridine orange (AO) binding to chromatin as an electron microscopic probe for studying changes in nuclear activity. The number of AO labeled nuclei were determined in adherent and sub-endothelial monocytes, and endothelial cells either associated with or devoid of monocytes in mesenteric arteries of renal hypertensive and normotensive rats. No AO-positive cell nuceli were found in the few adherent monocytes in the normotensive rats while in hypertensive rats 63% of the adherent monocytes and 86% of the subendothelial monocytes were labeled by AO. The number of AO-positive cell nuclei increased in the endothelium from 2% in normotensive rats to 17% in hypertensive animals. Fifty-seven percent of these endothelial cells were associated with monocytes adhering to their surfaces. Thirty-nine (52%) of AO-positive and 24 (52%) of AO-negative cell pairs represented 84% of cell pairs with identical nuclear activity. These findings indicate a sequential interaction of monocytes and adjacent endothelial cells recognized at the nuclear level. According to other experimental work the binding capacity of chromatin for AO increases as cell nuclei are reactivated by stimulation of cell proliferation. In addition, AO labeling of chromatin visualized electron microscopically is confined to three of the four stages of the cell cycle. Therefore AO labeling in the present experiments might indicate the reentrance of monocytes and endothelial cells into the cell cycle.

Acridine Orange↗

Passive geometric and elastic properties of human cadaver common carotid artery segments after intraluminal enzyme digestion with the aid of a four-way double balloon catheter.

A combined intraluminal nonenzymatic-enzymatic digestion procedure was carried out in situ on the common carotid arteries of 21 human cadavers with the aid of a four-way double balloon catheter. Denaturing pretreatment with NaOH, 2.5 mol for 20 min followed by crude pancreatic extract, 20 mg/ml for 20 min were used. Mechanical properties of cylindrical segments were measured in vitro, and compared with contralateral control segments. The inner radius increased and wall thickness decreased significantly at each pressure level in the 0-200 mmHg (0-26.7 kPa) intraluminal pressure range. Volume of wall material per unit length of the segment decreased by 11.6%, cross-section of the lumen at 100 mmHg (13.3 kPa) intraluminal pressure increased by 13.6%. These results show that the internal layers of human arteries can be removed by enzyme digestion increasing the lumen, while intact (medial and adventitial) layers still can give sufficient strength to the arterial wall.

Arterial Occlusive Diseases↗

[The effect of endothelial interaction on the binding capacity of DNA acridine orange in hypertension].

Interaction of monocytes and endothelial cells were examined by acridine orange reaction in arteries of normotensive and hypertonic rats. The method is suitable for electron microscope study of DNA template activity. Activity of gen was compared in surface bound and subendothelial and in nonadhesive endothelial cells bound to monocyte. Acridine orange positivity, indicative of genic activity, was not found in few monocytes adhered in arteries of normotensive animals, while 62% of adhesive monocytes of hypertonic and 86% of ones accessed to endothelial space contained the products of acridine-orange-chromatin reaction in its nuclear, showing with it the gene derepression quickly ensuing in acute hypertensive vascular lesions. Only 2% of endothelial cells of pseudo-operated normotensive animals showed acridine orange positivity, while 17% of endothelial cells of hypertonic animals were positive. In the latter animals, 57% of endothelial cells showed acridine orange positivity, if monocytes adhered to their surface. In 84% of monocyte-endothelial pairs connected to each other, the nuclei have activity of same sign. Results show intensive activation of genes of monocytes in relation with adhesion and migration to vascular wall. Presumably, both hypertonia and monocyte adhesion have contributed to the increase of template activity of endothelial cells.

Acridine Orange↗

The use of nonspecific esterase in assessing the effectivity of cryotherapy on the uterine cervix.

Cryotherapy of the uterine cervix can produce tissue damage of various depths. It is very important to be familiar with the extent of tissue damage in standardizing the treatment and assessing its effect. In the present work nonspecific esterase reaction was applied for the early study of tissue damage. It was found that this method can be used with benefit in the early assessment of the effect of freezing. The enzyme reaction was primarily a sensible marker of cell damage in the cervical cells.

Adult↗

Ultrastructural alterations in the ectocervical epithelium after cryotherapy.

The central problem of the cryosurgery of the uterine cervix in gynaecological practice is the extension in depth of the tissue impairment. The ultrastructural alterations were studied in the surgical material of portioplasties performed two hours after cryotherapy of the non-malignant ectocervical changes of fertile women. For control, the unfrozen regions of the same cervix were used. The vacuolization of the cytoplasm and partial fragmentation of the mitochondria appear to be detectable and reversible changes. Parallelly, severe irreversible nuclear impairments can be demonstrated in the basal and parabasal layers of the cervical epithelium. The relative connective tissue insensitivity, in contrast to the damage of the epithelium, verifies the advantage of cryosurgery in the therapeutic applicability.

Cervix Uteri↗

Tubular reabsorption of protein by porcine kidneys during neonatal alimentary proteinuria.

The ability of renal proximal tubular cells to reabsorb protein early in postnatal life was investigated using goat haemoglobin as tracer. The haemoglobin was intracardially administered to newborn piglets. The kidneys were fixed for light and electron microscopy 4 h later. Piglets killed immediately after birth and those allowed to suck colostrum for 4 h were used as controls. The proximal tubular cells of newborn, unsuckled piglets already contained absorptive vacuoles. Haemoglobin was absorbed in some absorptive vacuoles of the proximal tubules. The tracer was also demonstrable in the urine, mainly in the form of methaemoglobin. Although proximal tubular cells of newborn piglets are able to absorb protein, this absorption is of limited extent and excess protein is voided with the urine.

Absorption↗

[Intima and subintimal space as the site of the initial lesions in the formation of arteriosclerosis].

Experiments were conducted under various conditions, including hypoxaemia, endothelial damage by means of balloon catheterisation, cholesterol feeding, administration of lipofundin, and obstruction of lymphatic drainage. As a result, damage to endothelial cells along with increase in permeability is considered to be the initial process in the development of arteriosclerosis. This is followed by penetration of plasma, formation of fibrinoid in the subendothelial layer and in the media as well as by a number of cellular phenomena, the latter including adhesion of thrombocytes, penetration of monocytes into the intimal space, and proliferation of smooth muscle cells. Cellular, fibromuscular lesion is, eventually, caused as a result of those processes.

Arteries↗

Local enzymatic treatment of atherosclerotic plaques.

Fat rich and fibromuscular lesions experimentally induced in animals as well as human atherosclerotic plaques were locally digested enzymatically with the help of a newly developed double balloon catheter. The technique was most successful if applied to fat rich intimal proliferation of hypercholesterolemic rabbits, while the fibromuscular plaques of dog femoral arteries and of human common carotid arteries were less sensitive to the treatment. Osmotic or denaturing pretreatments increased the efficiency of the different proteolytic enzymes. Thrombotic complications and leukocytic infiltration developed in dogs surviving the enzymatic digestion by 2 days. A perfect enzymatic dissolution of the fibromuscular plaques was not achieved but the enzymatic digestion appeared to offer the organism a chance to complete the dissolution by its own means. The passive mechanical properties of the treated human carotid arteries changed favorably. The technique requires skill and a competent background in vascular surgery. Nonetheless the local enzymatic treatment might serve either as an adjunct to angioplasty or as an alternative treatment.

Aged↗

Connective tissue proteins on the injured endothelium of the rat aorta.

Type V collagen (TVC), fibronectin (FN), and laminin (LAM) were detected on the endothelial surface of mechanically injured rat aortas with the help of monospecific antisera and protein A - gold conjugates, carbon film surface replicas, and conventional embedding techniques. Deendothelialized tracks were produced in the thoracic aorta, and the presence of the connective tissue proteins on the luminal surface of the endothelium was studied. The changes in the distribution of the proteins during repair of the endothelial surface was followed for up to 6 days after injury. From 1 to 3 days after injury small numbers of gold particles, indicating the presence of TVC, were found between the adherent platelets on the freshly deendothelialized subendothelial matrix and in higher amounts on cell debris and collagen fibers. On the sixth day after injury, however, the amount of TVC between the sparsely distributed platelets on the deendothelialized areas was significantly higher than it was previously. FN and LAM were readily detectable on the subendothelial matrix and on the damaged marginal endothelial cells. These proteins were especially obvious on both margins of the tracks even from the first day after treatment. FN was found also in connection with fibrin precipitations as well as on the surface of some platelets and monocytes. The amount of FN and LAM present on the damaged area decreased slightly up to the sixth day. Monocytes and leukocytes adhered mostly at the margin of the wound area in the vicinity of the lesions on the endothelium. FN and LAM were often detectable under and around these adherent cells. Little of the connective tissue proteins was found on the uninjured and on the regenerated endothelial cells. The results showed subtle transitory changes in the surface pattern of the subendothelial connective tissue matrix of the injured intima. The adhesion of blood-borne cells may have been induced by FN and LAM on the endothelial surface near the lesions, and later partly prevented by increasing amounts of TVC on the surface.

Animals↗

Presence of connective tissue proteins on the endothelium of the rat aorta.

The microdistribution of type V collagen, fibronectin, and laminin on the luminal surface of perfusion-fixed normal rat aortic endothelium has been studied by an immunoelectron microscopic method using monospecific antibodies and a protein A-gold complex. Gold particles indicating the presence of these biologically active connective tissue proteins were localized in groups on and in the vicinity of the interendothelial border. They were also found on the small flaps of cell junctions as well as on certain cell projections and scattered on the cell surface. Correlative transmission electron-microscopic examinations proved the specificity of these localizations. The endothelial cells of the aorta differed markedly in the amount of scattered connective tissue proteins on their surface, suggesting that there are several types of aortic endothelial cells with distinct functional differences. The findings provide evidence that connective tissue proteins may contribute to the surface pattern of the normal endothelium, especially on cell borders. It is likely that these proteins influence functions such as the permeability and chemotactic activity of the endothelium pertinent to the development of vascular disease.

Animals↗