Previous work showed that hamster and human pancreatic tumors but not normal pancreata exhibit low-affinity cell-membrane receptors for luteinizing hormonereleasing hormone (LHRH (1)(2)(3)(4). The use of LHRH agonists for treatment of prostatic and breast cancer is based on suppression of pituitary-gonadal function and the consequent creation of a state of sex-steroid deficiency (1-4). In addition to these indirect effects, LHRH agonists and antagonists exert direct effects on these tumors (2-9) that probably are mediated by specific high-affinity LHRH receptors found on these cells (4, 5, 7, 10-13). Since 1984, it has been shown repeatedly that LHRH agonists and antagonists also suppress the growth of experimental pancreatic cancers (14-17). Exocrine pancreatic cancers could be sex steroid-sensitive (18), and the regression of experimental pancreatic cancers induced by treatment with LHRH agonists or antagonists (14-17) could be explained, in part, by the deprivation of estrogen or androgen. Direct effects mediated by LHRH receptors may also be involved, since LHRH analogues inhibit the growth of Mia PaCa-2 pancreatic cancer cells in vitro (19). Hamster and human pancreatic tumors but not normal pancreata exhibit cell-membrane receptors for LHRH (20,21). However, only low-affinity cell membrane LHRH receptors were found in pancreatic cancer cells (20,21). Here, we extend the examination of LHRH receptors in pancreatic tumor cells to include the nucleus as well as the cell membrane. In addition, we carried out electron microscopic immunohistochemical studies using an antibody to the LHRH receptor to examine (22) (25) was applied. A series of dilutions of the primary antibody in phosphate-buffered saline (PBS: 0.14 M NaCl/8 mM Na2HPO4/3 mM KH2PO4, pH 7.6)/0.05% Tween 80 from 1:10 to 1:10,000 was used for overnight incubation. Colloidal gold-conjugated secondary antibody (goat anti-rabbit IgG antibody conjugated to G10 gold particles, Janssen Pharmaceutica, Olen, Belgium) was diluted 1:50 in PBS/0.05% Tween 80 and incubated with the sections for 1 hr at room temperature. To eliminate nonspecific reactions, all grids were preincubated with normal rabbit serum (1:10) in PBS/ 0.05% Tween 80 for 15 min. Negative controls were incubated only with the gold-conjugated secondary antibody. Sections were viewed, without contrasting and after staining with uranyl acetate, in a JEM 100B electron microscope (JEOL).The average number of gold grains over various cellular structures and in the background was calculated after counting them with a Kontron (Zurich) MOP calculator. Ten photographic pictures (magnification: original, x 15,000-25,000; photooptic, x 35,000-60,000) from each sample were used for counting the grains. The values are given in grains per gm2 for each cellular compartment. LHRH receptors were measured by radioreceptor assay methods in the nuclear and membrane fraction of untreated hamster pancreatic tumor homogenates, as described previously (10,11,13,20,21). The method ofMarian and Conn (26) Abbrevi...
The programmed cell death inducing effect of the EGF receptor tyrosine kinase inhibitor alpha-cyano-3,4-dihydroxycinnamthioamide (AG213) was investigated in vitro on HT-29 human colon tumor. AG213 at concentrations between 45 to 450 microM blocks the proliferation of HT-29 cells. Morphological findings suggest that the selective tyrosine kinase inhibitor AG213 induces Clarke III type (non-lysosomal vesiculate cytoplasmic) programmed cell death; unlike ATP analog non-selective tyrosine kinase inhibitors like Genistein which were found to induce apoptosis. Cycloheximide and Actinomycin-D reduced the effect of AG213 pointing to the fact that protein and RNA synthesis are also needed for this form of cell death. Acid phosphatase activity was found in the Golgi and in the newly formed intracytoplasmic vacuoles 3 hours after AG213 treatment which disappeared by 6 hours. The induction of Clarke III cell death by tyrosine kinase inhibitors may open a new modality to selective killing of tumor cells.
Összefoglaló. Bevezetés: A szédülés gyakori panasz, amellyel a betegek felkeresik a sürgősségi osztályt. Emellett fontos tünet, hiszen kihívást jelent mind a diagnosztika, mind a terápia szempontjából, és nagy hatással lehet a betegek életminőségére. Célkitűzés: Kutatásunk célja annak vizsgálata, hogy mennyire befolyásolta a szédülés a betegek életminőségét a sürgősségi osztály elhagyását követően. Módszer: A vizsgálat időtartama alatt 879, szédülést panaszoló beteg jelent meg a Semmelweis Egyetem sürgősségi osztályán. Részükre kérdőív került kiküldésre, amely tartalmazta a ’Dizziness Handicap Inventory’ (DHI-) kérdőívet is. Megkeresésünkre 308 beteg (110 férfi, 198 nő; átlagéletkor: 61,8 ± 12,31 SD) válaszolt, az általuk visszaküldött kérdőíveket részletesen elemeztük. Eredmények: A leggyakoribb diagnózisok közé a benignus paroxysmalis positionalis vertigo, a centrális egyensúlyrendszeri eltérések és a szédülékenység tartoztak. Az elemzés alapján különbség volt látható a fizikális, a funkcionális és az emocionális pontszámok között. Kiemelendő, hogy a legmagasabb értékeket a fizikális csoportban regisztráltuk. A részletes otoneurológiai kivizsgáláson átesett betegek DHI-értékeit összevetettük azokéival, akik nem jártak ilyen vizsgálaton, a két csoport értékei között azonban nem volt szignifikáns különbség (p = 0,97). Emellett a DHI-érték emelkedése volt látható a végleges diagnózisig eltelt idő függvényében. Következtetés: A végleges diagnózisig eltelt idő, illetve a megfelelő kivizsgálás hiánya jelentős hatással van a szédülő betegek életminőségére. Lényeges a kivizsgálás, a mielőbbi diagnózis és a részletes egyensúlyrendszeri vizsgálat szerepe, ugyanakkor az utóbbi indokolt esetben kell, hogy történjen. Orv Hetil. 2021; 162(30): 1216–1221. Summary. Introduction: Dizziness and vertigo are among the most common complaints in the emergency department. This may require interdisciplinary cooperation due to their complex presentation in the department and the effects on the patients’ quality of life. Objective: Our study aimed to assess the effect of an acute vertigo episode on the quality of life after patients’ discharge from the emergency department. Method: 879 patients examined at the Semmelweis University emergency department with vertigo and dizziness were included in the study. A questionnaire, including the Dizziness Handicap Inventory (DHI), was addressed to this population. We received 308 answered questionnaires back (110 males, 198 females; mean age 61.8 years ± 12.31 SD), which were further analyzed. Results: The most frequent diagnoses were benign paroxysmal positional vertigo, central lesions and dizziness. According to the analysis of the DHI questionnaire, a difference between physical, functional and emotional scores was shown, whereas the highest scores were registered in the physical group. The DHI questionnaire scores of patients undergoing a neurotological examination and those who did not were further compared, whereas no significant statistical difference was indicated (p = 0.97). In addition, an increase in DHI scores was seen depending on the time elapse for the definitive diagnosis. Conclusion: The absence of adequate examination and a late diagnosis of the dizziness cause have a significant impact on the quality of life of patients. Therefore, substantial investigation, early diagnosis, and detailed vestibular examination are essential, but the latter should take place in justified cases. Orv Hetil. 2021; 162(30): 1216–1221.
Aluminum is a common element in our environment, but has been proved to be toxic, mainly in chronic renal insufficiency. Most cases of ALU intoxication occur during hemodialysis due to treatment of aluminum-containing drugs. In the present case, we describe visceral manifestations of aluminum deposition in a middle aged, multidialysed, male patient. Light and polarization microscopy examinations and X-ray microanalysis revealed amorph, extracellular aluminum deposits in various parenchymal organs causing failure of heart, lung and kidney functions. There were no anamnestic data concerning aluminum-containing drugs or occupational exposure.
Glomeruli of normal rat kidneys were studied by scanning electron microscope. A three-dimensional image is presented of the outer and the inner surface of the glomerular capillaries. The findings are compared with their correlates as seen in transmission electron microscopy. The possible application of scanning electron microscopy in the examination of renal disease is briefly discussed.
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