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Biomedical subjects

E Kunze

Publications and source records attributed to E Kunze.

At least 73 records · Page 4Linked to original sources
PubMed1984

Alteration by prolactin of surface charge and membrane fluidity of rat 13762 mammary ascites tumor cells.

Intraperitoneal injection of ovine prolactin (100 micrograms/d) in Fischer 344 rats bearing transplantable 13762 mammary ascites tumor (MAT) cells modifies the surface charge density and membrane fluidity of the tumor cells. In each of five experiments the mean electrophoretic mobility (epm) of MAT cells taken from prolactin-treated rats was significantly lower than that of cells from nonhormone-treated controls. Prolactin concentrations were increased in vivo by (a) direct intraperitoneal injection of ovine prolactin; (b) subcutaneous implantation of diethylstilbestrol-containing silastic capsules to produce pituitary prolactin secreting tumors; or (c) a single subcutaneous injection of polyestradiol phosphate, a long-acting estrogen. In an effort to establish that the prolactin effect was a direct one, two in vivo protocols were used: (a) MAT cells were coincubated with anterior pituitary halves obtained from nontumor-bearing littermates; or (b) rat or ovine prolactin was added to serum-free culture media containing MAT cells. In both protocols, the epm of the prolactin-treated cells was significantly lower. The isoelectric focusing pH of whole cells was increased by prolactin treatment from 4.93 to 5.12, consistent with a reduction in the number of surface carboxyl groups. The fluidity of membranes of treated cells was drastically increased, as measured by spin-label probe rotation rates. These combined results imply that the hormone exerts its effect by stimulating events in the cell that lead to a reduction of the average density of carboxylic acid residues on the tumor cell surface.

Animals↗
PubMed1984

Inhibition of tumor development in the regenerating rat urinary bladder stimulated to proliferate by cyclophosphamide.

The present study deals with the effect of stimulation of urothelial proliferation on experimental bladder carcinogenesis. To induce proliferative activity of the bladder mucosa cyclophosphamide (cp) was intraperitoneally administered to rats in a single dose (100 mg/kg). N-Butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) was used as carcinogen and administered by gavage in 3 fractionated doses when proliferation of the urothelium was highest at 28 and 40 hr as well as 7 days following the injection of cp. Contrary to our original working hypothesis, tumor development proved to be inhibited in the bladder following initial stimulation of urothelial proliferation by cp. After administration of a low total dose of BBN (300 mg/kg) and an experimental period of 6 and 12 months none of the rats pretreated with cp developed a tumor in the regenerating bladder, whereas solitary transitional cell papillomas were observed in 6.7% of the control animals with a quiescent bladder. Following administration of BBN at a high total dose (1.300 mg/kg) and an induction time of 4, 6 and 12 months papillomas and non-invasive papillary transitional cell carcinomas occurred in only 21.6% of the rats initially receiving cp but in 48.1% of the control animals without stimulation of urothelial proliferation by cp. After treatment with BBN alone there was a far larger number of rats with multiple tumors in the quiescent bladder. The reduction in the incidence of tumors following administration of cp is not attributable to a prolongation of the latency period or induction time. It is an open question which mechanisms are responsible for the observed inhibition of experimental bladder carcinogenesis. An increased DNA repair induced synchronously with the stimulated replicative de-novo DNA synthesis or a decreased activity of urothelial enzymes metabolizing BBN to its ultimate carcinogen are proposed as the most likely explanations.

Animals↗
PubMed1984

Effect of the uroprotector sodium 2-mercaptoethane sulfonate (Mesna) on the proliferation of the bladder urothelium in the rat after administration of cyclophosphamide.

The chemotherapy of malignant tumors with oxazaphosphorine cytostatics, e.g., cyclophosphamide (CP) and ifosfamide, is limited by their severe urotoxic side effects. As a result of cytotoxic damage, the proliferation of the urinary bladder urothelium is considerably stimulated during an intensive reparative regeneration. The recently developed uroprotector sodium 2-mercaptoethane sulfonate (Mesna) allows regional detoxification limited to the kidneys and lower urinary tract and thus protects against damage by aggressive oxazaphosphorine metabolites. The object of the present quantitative autoradiographic investigation was to study urothelial proliferation in the bladder of rats after administration of CP alone and in combination with Mesna. 20 h after intraperitoneal injection of a single dose of CP alone (100 mg/kg), the urothelium showed a steep rise of the 3H-thymidine (3H-TdR) labeling index which reached a peak of 17.6% at 30 h. Thereafter, the 3H-TdR index rapidly dropped. A second peak of 4.4% was observed after 7 days. With supplementary intravenous administration of a single dose of Mesna (100 mg/kg) 15 min before treatment with CP, the labeling index was substantially lower than after administration of CP alone. Thus, maximal values of only 1.6 and 1.9% were observed at 35 h and 7 days, respectively. Histopathological examination of the bladders showed severe necrotizing and ulcerative cystitis, 10, 20 and 25 h after administration of CP alone whereas with additional treatment with Mesna only slight edema of the lamina propria developed. The results obtained clearly demonstrate the protective action of Mesna on the urothelium of the lower urinary tract against the urotoxic effects of CP.

Animals↗
PubMed1983

Histology and histogenesis of two different types of inverted urothelial papillomas.

Inverted papillomas are rare tumors of the lower urinary tract. Among 1829 reclassified tumors of the urinary bladder, renal pelves, ureters, and urethra, there were 40 (2.2%) inverted papillomas. The great majority of these were localized in the bladder. Because of distinctive histologic features and patterns of growth it is possible to differentiate between two basic types of inverted papillomas which were termed "trabecular" and "glandular." The trabecular type consists of widely branched, anastomosing cords of urothelial cells originating directly from the overlying transitional epithelium. The trabeculae are arranged horizontally or perpendicularly to the surface epithelium and occasionally exhibit peripheral palisading of the cells. The glandular type is characterized by multiple round to oval islands of proliferated urothelial cells together with pseudoglandular and true glandular structures which are often still connected with the surface urothelium. The gland-like structures are lined by stratified urothelium, the true glands by mucus secreting columnar epithelium. Sometimes glandular metaplasia of an intestinal type with goblet cell formation could be observed. Inverted papillomas of the trabecular type arise histogenetically from a proliferation of the basal cells of the urothelium. The glandular type develops apparently from a proliferative cystitis cystica and glandularis which, therefore, should be considered a potentially preneoplastic lesion. The predominant view of the biological behavior of inverted papillomas is that of a benign neoplastic lesion. Morphologic findings supplied some arguments in favor of a low grade malignant potential of these tumors. However, their malignant transformation seemed to be much lower than that of exophytic papillomas.

Adult↗
PubMed1983

Inhibitory effect of partial cystectomy on experimental carcinogenesis in the urinary bladder.

It was our aim in the present animal experiments to study the influence of stimulation of proliferative activity on carcinogenesis in the urinary bladder. Stimulation of urothelial proliferation was achieved by a one-third resection of the bladder. N-butyl-N-(4-hydroxybutyl)- nitrosamine (BBN), which was used as a carcinogen, was administered by gavage in three fractionated doses when proliferative activity was highest at 30, 45, and 70 h postoperatively. Contrary to our working hypothesis, the incidence of urinary bladder tumors proved to be significantly reduced by partial cystectomy. After administration of a low total dose of BBN (300 mg/kg bodyweight) and an experimental period of 6, 12, and 18 months, only 2.6% of the rats with a partial cystectomy, but 12.6% of the control animals with an intact bladder had developed papillomas and noninvasive papillary transitional cell carcinomas. Following administration of BBN at a higher total dose (1,300 mg/kg bodyweight), bladder tumors occurred after an induction period of 4, 6, and 12 months in 27.4% of the partially cystectomized and 48.1% of the nonoperated rats. Multiple tumors were found more frequently in the controls than in the operated animals. The reduction in the tumor incidence following one-third resection of the bladder evidently does not depend on a prolongation of the latency period or induction time. From findings in analogous experimental models it is conceivable that the observed inhibition of experimental bladder carcinogenesis is brought about by an increased capacity of the proliferating urothelial cells to repair carcinogen-induced DNA damage. Further studies are required to elucidate the significance of a stimulated proliferation for the repair system and neoplastic transformation of the urothelium.

Animals↗
PubMed1983

Absence of a complete carcinogenic effect of phenacetin on the quiescent and proliferating urothelium stimulated by partial cystectomy. A 2-year feeding study in rats.

It was the object of the present animal experiments to test whether phenacetin (PH) exerts a complete solitary carcinogenic effect on the quiescent and rapidly proliferating urothelium of the lower urinary tract of the rat. In order to stimulate proliferative activity resection of one-third of the urinary bladder was performed which is known to induce intensive reparative regeneration in the stump. PH was administered either continuously with the diet or by gavage in three single doses when proliferative activity was highest. After an experimental period of 2 years 74-83% of the animals receiving PH continuously and 49-52% of the rats after limited gavage feeding had developed uni- and bilateral hyperplasia of the epithelium of the renal papilla. Histologically, the papillary hyperplasia exhibited urothelial differentiation and a typical endophytic growth pattern. It was always associated with healed or, rarely, fresh micronecroses of the subjacent papillary tissue. The urothelial hyperplasia of the renal papilla has to be considered not a true preneoplastic, but rather a reactive proliferative lesion in the sense of a reparative hyperregeneration due to toxic necroses. There was no evidence for a complete solitary carcinogenic action of PH on the urothelium of the entire lower urinary tract. It seems most likely that a metabolite of PH realizes tumor growth only as cocarcinogen with initiation-stimulating and/or initiation-promoting effects acting together with other causative factors during multifactorial multistage carcinogenesis. Based upon the experimental findings reported here, the concept of PH as a solitary complete urothelial carcinogen for man should be reassessed.

Animals↗
PubMed1983

Proliferation-stimulating effect of phenacetin on the urothelium and papillary epithelium of rats.

In the present autoradiographic study, the effect of phenacetin (PH) on the proliferative activity of the urothelium and epithelium lining the renal papilla of rats was tested. The median 3H-thymidine-labeling index (3H-TdR index) of the bladder urothelium of rats daily fed PH for 2 years was twofold increased compared to untreated or initially partially cystectomized rats. The median 3H-TdR index of the papillary epithelium was 2-3 times higher than in untreated controls. The transitional epithelium of the renal pelves showed an approximately 2 times, and the urothelium of the ureters a 3 times increased median 3H-TdR index only when PH administration was combined with an initial one-third resection of the urinary bladder. Since after PH treatment the highest DNA synthesis consistently occurred in all rats with a resected bladder, it can be concluded that partial cystectomy increases the ability of the urothelium and the papillary epithelium to proliferate in response to the drug. The proliferation-stimulating effect of PH can be reconciled with a cocarcinogenic or promoting activity of the drug.

Animals↗
PubMed1983

[Autoradiographic studies on the protective effect of mesna in the urinary bladder mucosa of the rat during administration of cyclophosphamide (preliminary communication)].

Cyclophosphamide (100 mg/kg i.p.) produces severe bladder lesions in rats and induces an intense regeneration of the urothelium which can be followed up by 3H-thymidine incorporation. Simultaneously administered mesna (100 mg/kg i.v.) prevents these bladder lesions and no increased regeneration with 3H-thymidine incorporation can be observed.

Animals↗
PubMed1981

[Myoglobinuric renal failure in hyperosmolar diabetic coma (author's transl)].

Acute rhabdomyolysis with myoglobinuric renal failure occurred in a 66-year-old woman who was in hyperosmolar non-ketotic diabetic coma. No previous description of such a case has been found. The clinical picture was characterized by the typical findings of hyperosmolar coma, in addition to excessive serum creatine kinase and myoglobin levels and massive myoglobinuria with acute renal failure. The rhabdomyolysis became fully manifest only under insulin treatment, possibly the result of insulin-induced hypophosphataemia, which seems to be of importance in the causation of the rhabdomyolysis.

Acute Kidney Injury↗
PubMed1981

Cell cycle kinetics of regenerating urothelial cells of the rat urinary bladder after partial cystectomy.

The cell cycle kinetics of bladder urothelial cells regenerating after partial cystectomy were investigated in 96 female Wistar rats using the percentage labelled mitoses method. In the area of resection a mean cell cycle time (TC) of 15 h was determined. The DNA synthesis phase (TS) lasted 6 h and the premitotic-postsynthetic phase together with the mitosis phase (TG2 + M) 1.5 h, thus giving a presynthetic-postmiotic phase (TG1) of 7.5 h. Similar values were found for the urothelial cells in the stump: the mean cycle time measured 14 h, the TS-phase 6 h, the TG6 + M-phase 2 h and the TG1-phase 6 h. These data are discussed with respect to known cell cycle parameters of bladder urothelium regenerating in response to cytotoxic agents and of neoplastic urothelial cells. The reported findings provide a basis for further investigations using weak carcinogens and threshold doses of potent carcinogens to test the working hypothesis that stimulation of proliferation following partial cystectomy is capable of initiating, accelerating and/or potentiating carcinogenic cell transformation in the urinary bladder.

Animals↗
PubMed1980

[Constrictive pericarditis in early infancy (author's transl)].

The unusual course of illness involving an 8-week old infant is described, which, after a staphylococcic sepsis with subsequent purulent pericarditis, developed the typical clinical symptoms of a constrictive pericarditis within a 12-day-period. There is only one similar case reported on in medical literature, involving an 8-month old infant.--Despite an immediate operation (anterior pericardectomy) the infant died 3 days later.

Humans↗
PubMed1979

[Diabetic neuropathic cachexia (author's transl)].

Marked weight loss with cachexia together with severe depression and pain from symmetrical peripheral neuropathy were noted in a 66-year-old man, known to have had diabetes for six years, which required insulin on admission to hospital. The patient died of bronchopneumonia after one year. The severe neuropathy was proven both neurophysiologically and at necropsy. There was no diabetic retinopathy and no histological evidence of renal glomerulosclerosis. There was no evidence of a malignant tumour either clinically or at necropsy.

Aged↗
PubMed1979

[Stimulating effect of partial cystectomy on regeneration of rat bladder urothelium and its significance for carcinogenesis (author's transl)].

Cell proliferation kinetics of the urinary bladder urothelium have been analyzed in a total of 218 female Wistar rats after partial cystectomy. After one-third resection of the bladder DNA synthesis started 15 h postoperatively in the bladder stump and reached its maximum at 25 h with a mean 3H-TdR index of 10.1%. In the area of resection the proliferative activity increased after 20 h and the highest 3H-TdR index was found to be 24.7% after 45 h. In the case of hemicystectomy the labeling index in the stump increased 15 h postoperatively and the highest 3H-T-dR index was determined at 20 h with 16.6%. The urothelial cells in the area of resection began to proliferate synchronously with those in the stump and the maximum of DNA synthesis was measured 35 h postoperatively with an 3H-TdR index of 24.2%. After 2 weeks the proliferative activity within the stump and operative region corresponded to that of the control urothelium. The basal cells showed absolutely the highest proliferative activity, the suprabasal cells exhibited on the other side the highest regenerative potential compared with the control urothelium. Partial cystectomy might possibly serve as an experimental model for testing low potential carcinogens, in the case where carcinogenic effects would be initiated, potentiated and accelerated via stimulation of the DNA synthesis.

Animals↗
PubMed1979

Early sequential lesions during development of experimental gastric cancer with special reference to dysplasias.

The early sequential development of gastric cancer was studied with experimental animals and examined with respect to what conclusions can be drawn for understanding carcinogenesis in man. After limited oral administration of N-methyl-N'nitro-N-nitrosoguanidine to 174 rats carcinomas developed in most cases directly from the otherwise unchanged mucosa through various successive stages of transformation, without passing through a benign-appearing proliferative or neoplastic epithelial lesion. Focal dysplasia grade I was the first recognizable change observed by light microscopy, followed by dysplasia grade II, and subsequently dysplasia grade III. In spite of very similar morphological characteristics, the experimentally induced dysplasias cannot be simply equated in their etiology and biological behavior with the dysplasias of the human stomach. Dysplasias of grade I and II commonly found in man are usually associated with a chronic gastritis; they are located in the upper third of the mucosa and are for the most part reversible. The experimental dysplasias occuring in the proliferative zone of an otherwise undisturbed mucosa must be considered potentially premalignant, as they are irreversible and develop progressively. This finding points out that in man dysplasias grade III within the regenerative zone of non-inflammatory mucosa should be considered particularly as possible precursors of gastric carcinomas.

Adenoma↗