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Biomedical subjects

H F Nowak

Publications and source records attributed to H F Nowak.

At least 19 recordsLinked to original sources
PubMed2001

Ultrastructure of the tunica albuginea in congenital penile curvature.

PURPOSE: We investigated the ultrastructure of the tunica albuginea in individuals with congenital penile curvature to explain the pathology of this disease. MATERIALS AND METHODS: Included in our study were 15 patients 17 to 24 years old with congenital penile curvature. Study material consisted of samples of the tunica albuginea excised from the greater curvature of the corpus cavernosum during surgical correction. Control samples were obtained from the lesser curvature on the side opposite the study material during the same operation. The 2 types of tissue were analyzed using transmitter electron microscopy. RESULTS: Ultrastructural examination of the control material revealed numerous collagen fibers that were homogenous in size and organization on cross section. Periodic striation was typical in collagen that produced fibers. In the study group the tunica albuginea structure had a chaotic pattern of collagen fibers that formed bundles with disrupted 3-dimensional organization. Diameter of the fibers differed greatly on cross section. We observed periodic widening and fragmentation of collagen fibers with the complete disappearance of striation and transformation into electron dense, fibrous granulated material. Disrupted fibroblasts without cell membrane and cellular organelles between collagen fibers were also visible. There was elastin accumulation without any morphological differences in the control and study groups. CONCLUSIONS: Our results show that ultrastructural changes in the tunica albuginea may cause congenital penile curvature, possibly by altering mechanical properties.

Adolescent↗
PubMed2001

Effect of the cytokine rhTNF-alpha on the population of mast cells in the growth of MethA fibrosarcoma--a TEM study.

The aim of the present study was the ultrastructural characteristics of mast cell (MC) involved in host antitumor responses induced by local (i.t.) administration of recombinant human tumor necrosis factor alpha (rhTNF-alpha) in the primary focus of methA fibrosarcoma. MC were involved in tumor interstitium remodeling. Numerous mitochondria, well-developed RER and Golgi apparatus, clusters of polyribosomes, considerable polymorphism of granules and differentiated lamellar structures which frequently presented myelinic forms were observed after rhTNF-alpha application. In the study numerous fibres of the fibrous tissue, richly vascularized, occurred in the peripheral and intermediate tumor zones. Cluster of MC and tumor cells were seen on the border of the necrotic foci. However, proteolytic enzymes released by MC cause interstitial lysis, ensuring the place for tumor growth, and are involved in angiogenesis. Thus, it is not clear whether MC contribute to the inhibition of tumor growth or have an adjunctive role in tumor progression.

Animals↗
PubMed2000

The antitumor effect of intraperitoneal treatment with rhTNF-alpha muteins on Ehrlich ascites tumor growth.

The intraperitoneal (i.p.) treatment with recombinant human tumor necrosis factor-alpha (rhTNF-alpha) is one of the possible therapies for tumors that are confined to the abdominal cavity. Clinical trials aiming at the exploitation of the antitumor effects of rhTNF-alpha have been largely disappointing. In this model the activity of some rhTNF-alpha derivatives was studied. Ehrlich's ascites tumor (EAT) bearing Swiss albino male mice were treated i.p. three times a week with 10 micrograms/mice of rhTNF-alpha, mutein V or mutein VI for two weeks, starting on the 4th day after tumor inoculation. Control mice received PBS. The effect of the rhTNF-alpha derivatives on the course of EAT was evaluated basing on: total ascites volume (TAV); packed cell volume (PCV); total packed cell volume (TPCV); inhibitory growth rate (IGR); cellular population of EAT fluid; morphological EAT cell changes and mean survival time (MST). In the study mutein VI had only a slight effect on MST but significant on TAV- and TPCV-IGR (p < 0.001). In mice treated with rhTNF-alpha and mutein V the enhancement of MST (p < 0.01) was accompanied by TAV- and TPCV-IGR (p < 0.001). The number of EAT cells in ascites decreased after rhTNF-alpha and mutein V administration (p < 0.001). We conclude that treatment with high-dose of this modified molecule lacking the possibility of binding with p75R and not producing so intensified side effects is likely to find wider application in therapy and prevent the ascites growth just as rhTNF-alpha dosage.

Animals↗
PubMed1999

Comparative studies on the ultrastructure of the rat lungs after intratumor treatment of Morris hepatoma with rhTNF-alpha and its muteins.

The aim of the present study was the comparative analysis of morphological changes found in the lungs of Buffalo rats in the course of Morris hepatoma 5123 after i.t. treatment with recombinant human TNF-alpha (rhTNF-alpha) and its muteins. Modification of the native TNF-alpha molecule and synthesis of mutagenized analogues can prevent undesirable symptoms observed in the case of therapeutic administration of rhTNF-alpha. TNF-alpha has been shown to interact with two distinct membrane receptors (TNF-R): p55R and p75R. Mutagenized mutein V binds selectively with p55R. Mutein VI fails to recognize either TNF-R. The cytokines were applied in a dose of 10 micrograms protein in a cycle of 8 days. The control group consisted of tumor-bearing animals which were given PBS. Ultrastructural examinations were based on transmission electron microscope (TEM). Mutein VI-receiving animals showed enhanced changes of cytotoxic nature. Severe damage to endothelial cells (necrosis inclusive) was observed. Blood vascular lumen showed accumulation of neutrophils and monocytes. Features of enhanced activity of endothelial cells were noted. Focally, within pulmonary alveoli conglomerates of fibrin and fragments of damaged cells were found, with erythrocytes, neutrophils and macrophages in their vicinity. The epithelium of pulmonary alveoli showed signs of considerable damage, including necrosis. The lumen of pulmonary capillaries in rhTNF-alpha-treated animals showed a predominance of eosinophils and monocytic cells. Features of endothelial stimulation were observed, although without a tendency to form microthrombi. Much less pronounced changes both in the lung capillary bed and in the alveolar epithelial cells were noted in the mutein V-given animals. Our findings confirm the possibility of peripheral activation of cells involved in the cytokine-induced antitumor response. Mutein V with the smallest effect on the lung tissue rebuilding seems to be a rhTNF-alpha derivative which can delimit the undesirable symptoms in the course of antitumor therapy reduced to i.t. injections.

Animals↗
PubMed1997

Protective effect of human recombinant tumour necrosis factor-alpha against lung metastases of the Morris hepatoma in rats.

The effect of intratumour (i.t.) administration of human recombinant tumour necrosis factor-alpha (hrecTNF-alpha) on Morris 5123 hepatoma spontaneous lung metastases was studied. Tumour was implanted in the skeletal muscles of the right hind limb of Buffalo rats. Two weeks after the implantation treatment with cytokine started. The cytokine was injected i.t. in a single dose of 10 micrograms in 4- and 8-day cycles. In control animals PBS was administered, respectively. Then all rats were necropsied and the extent of lung metastases was determined. Data were expressed as volume of lung metastases. In this study we observed significant antimetastatic effects of hrecTNF-alpha (p < 0.05) determined by reduced volume of lung metastases in treated animals.

Animals↗
PubMed1997

Alveolar epithelial cells after intratumour administration of HREC TNF-alpha mutein VI.

The aim of this study was to explore the effect of intratumour mutein VI-Hrec TNF-alpha administration upon the ultrastructural changes within the pulmonary tissue, with special attention paid to type II alveolar epithelial cells. The experiment was carried out on Buffalo rats with implantable Morris hepatoma series 5123 in the skeletal muscles of the limb. Mutein VI-Hrec TNF-alpha was administered in a dose of 10 micrograms once a day in a cycle of eight days. Control animals were given saline (PBS). Ultrastructural changes within the pulmonary tissue were evaluated in the electron transmission microscope (TEM), with special attention paid to alveolar epithelial cells. In the animals receiving hrec TNF-alpha mutein VI, damage to the alveolar epithelial cells was found. In the later period (14 days after the mutein treatment), repairing processes were observed, accompanied by intensified fibrotic processes in the interalveolar septal interstitium, with the subsequent pulmonary tissue rebuilding. The study confirmed the possibility of a peripheral action of hrec TNF-alpha mutein VI after its administration to the experimental Morris hepatoma and found the alveolar epithelial cells to be a key element of the pulmonary tissue subjected to the cytokine effect.

Animals↗
PubMed1997

Quantitative and morphological changes in BAL-isolated cells after the administration of TNF-alpha into Morris hepatoma.

The aim of this study was to explore the effect of intratumor TNF-alpha administration upon the composition and adherence degree of cells isolated from the lungs through multiple bronchoalveolar lavages (BAL). Ultrastructural evaluation of BAL-isolated cells was performed in the scanning electron microscope (SEM). The experiment used Buffalo rats. A suspension of 3 x 10(6) cells of Morris hepatoma (5123 series) was injected to the right hind leg of the animals. After fourteen days, TNF-alpha was administered into the tumor in a dose of 1.5 x 10(4) U in 0.5 ml PBS solution. The animals of group I were given 4 doses of TNF-alpha and group II-8 doses of TNF-alpha every 24 hours. Control groups consisted of rats with injected Morris hepatoma which were given PBS solution instead of TNF-alpha (group III A, B) and animals without the hepatoma, given intramuscullary 4 or 8 TNF-alpha, respectively (groups IV A, B). No statistically significant differences were noticed between groups I and II with regard to the number of macrophages and neutrophils isolated from the rat lungs compared with control group IV. However, such differences were observed compared with group III. In group II and IV B, an increase in the adherence of isolated cells was found compared with group III, as well as arise in the number of macrophages with the largest diameters. We found a correlation between the increase in cell adherence and ultrastructural changes (in SEM) suggesting an increased activity of BAL-isolated cells.

Animals↗
PubMed1997

The ethanol effect on lung metastases development in experimental Morris 5123 hepatoma.

The experiment was carried out on 45 male Wistar rats which were divided into 3 groups: group I-15 rats which were given water to drink during the experiment, group II-15 rats obtaining 10% ethanol solution during the experiment and group III-15 rats obtaining 20% ethanol solution during the experiment. All animals were injected 0.3 ml suspension of hepatoma Morris 5123 cells directly to the liver on the 14th day of the experiment. After the 9 weeks of the experiment the animals from all groups were narcotized, decapitated and the lungs were taken into the morphometric, histological and ultrastructural examinations. They showed that ethanol has a stimulating effect on formation and development of hepatoma Morris 5123 in rat lungs. The increase of number and extensiveness of metastases as well as the increase of mean metastases focuses volume, and the increase of lung weight in animals which obtained ethanol are the exponent of the influence. On the basis of ultrastructural examinations, it can be noted that promoting activity of ethanol can be connected: a) with the increase of neoplastic cells activity, b) with changes appearing in pulmonic epithelium and endothelium of vessel enabling neoplastic cells to adhere to basal membrane as well as their crossing the vessel wall.

Administration, Oral↗
PubMed1997

Regression of Morris hepatoma in response to intralesional treatment with tumor necrosis factor muteins.

We examined the antitumor effects of human recombinant tumor necrosis factor alpha (rhTNF-alpha) and its muteins with the N-terminal amino acid sequence altered by point mutations against transplantable Morris hepatoma 5123 in rats. In vivo studies showed antiproliferative activity of the drugs in the dose range tested. For in vivo studies rhTNF-alpha and muteins were administered intratumorly (i.t.). The preparations were given at a dose of 10 microg/rat, once daily for eight days. Although the therapy was significantly effective in inhibiting tumor growth, complete growth inhibition could not be achieved. Nevertheless, there was a significant increase in survival time of tumor-bearing rats.

Amino Acid Sequence↗
PubMed1997

Tumor necrosis factor-alpha induces emphysema-like pulmonary tissue rebuilding. Changes in type II alveolar epithelial cells.

The effect of repeated doses of TNF-alpha on the histological picture of the pulmonary tissue was analyzed in the present study. Special attention was paid to the lung rebuilding processes. TNF-alpha was applied intraperitoneally for two weeks in a dose of 10 micrograms/0.5 ml PBS/24h. Morphological analysis of the pulmonary tissue was performed after 1 and 28 days following the last TNF-alpha dose. The study revealed focal pulmonary tissue rebuilding with emphysema-like changes twenty eight days following termination of TNF-alpha administration. The rebuilding processes included interalveolar septal atrophy, collagen accumulation and damage-repair changes in type II alveolar epithelial cells. It has been demonstrated that apart from the protease-antiprotease hypothesis of the lung emphysema, the inflammatory-repair hypothesis should be considered. Both hypotheses are complementary to each other and interpret the emphysema-like changes as complications of various pathological conditions of the pulmonary tissue.

Animals↗
PubMed1997

Ultrastructural evaluation of microcirculatory vessels in rheumatoid synovial membrane.

Since morphological lesions in microcirculatory vessels are often difficult to be found in the light microscope, the electron microscope investigations were performed on the synovial membrane biopsy specimens from 70 patients with rheumatoid arthritis (RA). Most common lesions referred to venules, capillaries and arterioles were swelling and proliferation of endothelial cells, adherence of lymphocytes, monocytes and neutrofiles to the endothelium, their margination and diapedesis. Also destructive changes in the endothelial cells, basement membrane thickening due to their multiplication and microthrombi were observed. Platelet aggregates, fibrin, fragments of desintegrated cells and deposits of granulofibrillary substance corresponding to fibrinoid necrosis were frequently seen. In 7 patients, lesions of this kind were found only in electronograms. It can be assumed that the evaluation of ultrastructural changes in the microcirculatory vessels may be of great significance as a complementary diagnostic examination in future determination of RA progression and further prognostication.

Adult↗
PubMed1997

Microenvironment of Morris hepatoma 5123 metastases to the lungs--ultrastructural analysis of intratumour injections of rhTNF-alpha.

We analysed the effect of rhTNF-alpha on the development of Morris hepatoma 5123 spontaneous metastases to the lungs of Buffalo rats. After intratumour administration of the cytokine the lungs were found to contain scarce metastatic foci. In precapillaries and capillaries neoplastic cells were single or in small clusters, without contact with endothelial cells. Endothelial cells showed high pinocytic activity and frequently tightly closed vascular lumen. The stroma of interalveolar septa and the capillary bed contained multiple eosinophils. Moreover, eosinophils, histiocytes and monocytes mixed with abundant collagen fibres were found on the margin of single small metastatic foci and among necrotic neoplastic cells.

Animals↗
PubMed1996

Type II alveolar epithelial cells and free alveolar cells after intratumor TNF-alpha administration.

The experiment used Morris hepatoma 5123 series growing in muscles of the Buffalo rats. A suspension of 3 x 10(6) neoplastic cells was injected into the right hind leg of the animals. After fourteen days, TNF-alpha was administered into the tumour in a dose of 1.5 x 10(4) U/24 hours in 0.5 ml PBS solution. The group I animals were injected for 4 days and group II for 8 days. Control groups consisted of rats with injected Morris hepatoma which were given PBS solution instead of TNF-alpha (group III A and B) and animals without the hepatoma, given 4 or 8 TNF-alpha, respectively (groups IV A and B). In the present study, we have explored the effect of intratumor TNF-alpha administration on the composition of cells isolated from the lungs through multiple bronchoalveolar lavages (BAL). Ultrastructural evaluation of the pulmonary tissue was done using a transmission electron microscope (TEM), with special attention paid to type II alveolar epithelial cells and free alveolar cells. Examinations in TEM in groups I, II and IV (A and B) found, in the lumen of alveoli, an increase in the number of alveolar macrophages (AM) with morphological features of intensified activity and AM with numerous secondary lysosomes containing material of phospholipid structure. Also, numerous type II alveolar epithelial cells with emptied lamellar bodies were observed. The above mentioned changes were especially marked after eightfold TNF-alpha administration. In groups I, II and IV (A and B), compared with group III, a significant increase was found in the total number of cells isolated by BAL as well as in the number of cells with positive reaction in staining according to Beckstead's method. It may indicate that the changes in the parameters mentioned above are related to TNF-alpha action. The results obtained indicate the possibility of systemic effect of TNF-alpha after its administration into the experimental Morris hepatoma.

Alkaline Phosphatase↗
PubMed1996

Dynamics and phases of changes in the primary focus of Morris hepatoma under local application of cytokine hrecTNF-alpha.

Biological activity of cytokine hreeTNF-alpha was tested on a transplantable Morris hepatoma 5123 in Buffalo rats. Local effects of hrecTNF-alpha activity were evaluated basing on morphological examinations. The cytokine effects on tumor biometric parameters and body mass of experimental animals were analyzed. It has been found that hrecTNF-alpha considerably decreases body mass and reduces studied parameters of the tumor, the changes being statistically significant. Three consecutive phases of the neoplasm regression have been distinguished. Phase I revealed prevailing hemorrhagic necrosis of the central and intermediate zones, with numerous thrombi in the vascular lumen and fibrinoid necrosis of vascular walls. Phase II presented a number of cellular infiltrations, clearance of necrotic foci and initial angiogenesis and fibroplasia. Phase III showed intensified angiogenesis and proliferation of the connective tissue in the peripheral and intermediate zones.

Animals↗