Twenty five thyroid tumors were investigated by immunohistochemistry for the presence of apoptosis, expression of p53, bax and bcl2. In nine adenomas (average age 40) the rate of p53 positive cells was 5.7%, while it was 13.3% for bax and 41.7% for bcl2 in the tumor cells. In six follicular carcinomas (average age 56) p53 positivity was obtained for 71.1%, while bax and bcl2 positivity constituted 3.4% and 2.5%, respectively. In ten papillary adenocarcinomas (average age 42) p53 was positive in 39.6%, but bax and bcl2 were positive in 3.4% and 3% of the tumor cells, respectively. Almost no signs of spontaneous apoptosis were found in any of the cases. Determination of p53, bax and bcl2 ratio in thyroid tumors may contribute to the differentiation between follicular adenomas and carcinomas.

Mercury(II) ions are known to accumulate in the kidney and their effect upon the renin-angiotensin system has also been described. The question, however, whether mercury(II) also exerts direct effect on the juxtaglomerular cells (JGC) to induce renin release remained to be answered. Suspension of isolated glomeruli was used to measure the mercury(II)-induced renin release in vitro. The glomeruli were isolated from female BALBc mice. HgCl2 was found to be capable of inducing renin release directly from JGC. The effect is concentration-dependent (P < 0.05, r = 0.914 and P < 0.01, r = 0.982, with and without Neutral Red vital staining) and becomes apparent already at a mercury(II) ion concentration as low as 1 μM. The renin-releasing effect of the mercury ion is to be inhibited by dithiothreitol (DTT) (renin activity 20.37 vs. 2.60 ng/ml.h in supernatant) as well as the elevated osmotic concentration of the incubating bath medium (20.37 vs. 6.84 ng/ml.h). This suggests that certain membrane sulfhydryl groups are implicated in the process on the one hand, and it is also in accordance with the known sensitivity of the renin granules to osmotic pressure on the other hand. Light and electron micrographs also demonstrate the direct, effective role of Hg(II) in the renin release process. Therefore, it is assumed that apart from its influence on tubulo-glomerular feedback a direct way of action of mercury(II) on renin release must also be taken into account.

The loop diuretic, furosemide, which has been known to elicit renin release in vivo as well as in vitro, has also been shown to induce lysosomal enzyme release. After administration of furosemide (10 mg/kg and 300 mg/kg), a significantly increased acid phosphatase activity (1.33 x 10(-4) and 1.73 x 10(-4) vs. 0.23 x 10(-4) U, p < 0.001) was detected in the urine of the drug-treated mice, accompanied by a reduction of the residual enzyme activity in the kidney (5.0% for 10 mg/kg and 18.4%--p < 0.05--for 300 mg/kg dosage). Two marker enzymes, acid phosphatase and beta-D-glucuronidase, were assayed to demonstrate that furosemide also exerts its effect in in vitro systems like renal cortex suspension (corr. coeff.: 0.899 for acid phosphatase and 0.908 for beta-D-glucuronidase, p < 0.001) and isolated lysosomes (corr. coeff.: 0.981 for acid phosphatase and 0.989 for beta-D-glucuronidase, p < 0.001 for both). This action of the drug seems to be different from the well-known furosemide-sensitive inhibition of ion transport systems and may become of clinical relevance for patients receiving high doses of furosemide.

Authors survey the cyto-biological effect of extra-renal renin-angiotensin system on the basis of literature data and of their own previous results. It is established that renin and angiotensins in extra-renal localisation take part mainly in inflammatory process. In this respect, one of the important target cell group of angiotensin system is the certain elements of mononuclear phagocyte system, on which angiotensin II has cytokine-like effect. Renin-angiotensins detected by authors in non-activated alveolar mono-phages and monocytes raise the possibility, that these cells also have independent, intra-cellular regulating renin-angiotensin.

Basolateral interstitial spaces (BLIS) of the murine macula densa (MD) are dilated in kidneys fixed either by in vivo glutaraldehyde perfusion or snap freezing-freeze substitution, suggesting that macula densa intercellular spaces may be normally dilated in the functioning nephron. BLIS are also dilated in MD with luminal obstruction with "hyaline" cylinder. This finding might indicate a glomerulo-macular fluid and solute streaming, having an impact on the tubuloglomerular feedback mechanism.

Mesenchymal renal tumors in F-344 newborn rats were induced by a single dose of dimethylnitrosamine. The induced tumors were successfully transplanted into adult rats under the renal capsule. Neither the primary nor the transplanted neoplasms from various generations of grafts changed their morphological features during the tumor passage, having the same cellularity with high mitotic activity and the tendency to invade the host kidney rapidly. On the basis of lectin histochemistry and immunohistology, the tumor proved to be a mesenchymal neoplasm without any obvious capacity of the proliferating cells to differentiate into any wellknown organoid element normally found in mature renal parenchyma. However, the proliferating neoplastic cells were found to have a strong vimentin positivity with desmin expression. Ultrastructurally, myofilaments with attachment bodies characteristic of smooth muscle cells were generally present in various amounts in many tumor cells. In addition, on the basis of the physiological data and on kidney/tumor renin activity obtained, it is interesting to note that the tumor-graft-invaded kidneys retained their enzyme activity, despite the obvious loss of renal tissue including glomeruli. However, the immunohistochemical findings with anti-renin antibody have clearly shown that this is not due to a renin-producing tumor but rather to the surviving (probably) non-neoplastic arterioles retaining the capacity to produce renin. Although these arterioles have mostly been found next to necrotic areas, commonly occurring in dimethylnitrosamine-induced transplantable renal tumors, the question of a possible physiological role of renin in tumor necrosis or in angiogenesis has remained open.

Of malignancies occurring in bones, metastatic tumours are the most frequent. Due to the increase of mean life span and to other factors the incidence of tumours is growing. Nevertheless, survival chances of patients suffering from tumours are also improving due to advance in diagnostics and to the application of complex therapy. These trends have substantially increased the number of recognized and manageable bone metastases. In general, life expectations of a tumour-patient are determined by the metastases therefore, the question of diagnostics and management of bone metastases is worth of special attention. Authors have performed a clinicopathological survey of patients of the past eight years who have suffered fracture due to bone metastases and were treated surgically. In one-third of the patients the primary tumour was unknown at the time of the fracture. On the basis of the histological pattern the detection of the parent-organ, particularly in adenocarcinomas, was not possible. Independently from the radiological appearance of the metastasis simultaneous osteogenesis and osteolysis were histologically observed.

The effect of chronic furosemide treatment on the structure of the secretory cells in the mouse pancreas was studied using electron microscopy. The number of the zymogen granules increased in the cytoplasm of acinar cells; they were more densely packed and had a less electron-dense appearance than the controls. Because these ultrastructural findings resemble the changes observed in exocrine glands of patients with cystic fibrosis, the chronic furosemide-treated mouse is proposed as an experimental model for this disease.

The uptake of neutral red into the renin-containing juxtaglomerular granules does not inhibit the release of renin either in basal or in stimulated states of renin secretion. The vasodilating effect of neutral red may be due to a non-specific binding to noradrenaline-receptors in the vascular smooth muscle cells.

In den Granula juxtaglomerulärer granulierter Mäusenierenzellen wurde eine saure Phosphatase und eineβ-Glykuronidase-Aktivität nachgewiesen. (Methoden für Arylsulphatase und unspezifische Esterase waren negativ.) Es wird der Zusammenhang mit der Lysosomenart der Granula diskutiert.

The activity of hexobarbital metabolising enzymes of the liver is decreased as a consequence of both acute and chronical carbon tetrachloride damage. Simultaneous administration of estrogens was followed by more severe morphological and functional impairment although estrogens are not burdening the healthy liver. The beta receptor blocking propranolol prevented functional lesion, moderated fatty degeneration and liver cell necrosis in chronic carbon tetrachloride injury. A simultaneous estrogen administration decreased the therapeutic efficacy of beta blockade, however functional and morphological protective effects were not completely abolished. Estrogen medication should be rather avoided in hepatic damage.

Dog kidneys were subjected to one, two, or three hours' normothermic ischemia in situ and were then excised for biochemical and histological evaluation. The uptake of para-aminohippurate (PAH) by cortical slices progressively decreased with prolongation of the ischemia, but active transport was never abolished. Glycine uptake and oxygen consumption were only reduced to a modest extent by the ischemia. The intracellular ion levels were drastically altered, with loss of potassium and gain of sodium and chloride, and considerable increases in tissue water were observed. Acid phosphatase was liberated by the whole organ into the venous blood and by the incubated slices into the incubation medium, but both biochemical and histochemical techniques showed that the total quantity of the enzyme in the cells was hardly changed. The histochemical reaction product was localized exclusively in the lysosomes. Morphological damage was slight after one or two hours' ischemia, but more pronounced after three hours, when some cells were seen to be detached from the basement membrane. These relatively minor changes seem insufficient to predict the ultimate fate of the organ after ischemia.

The changes of the juxtaglomerular index values in the superficial, deep and whole cortical areas of rat kidneys after unilateral papillectomy were analyzed. On the papillectomized side the JGI values showed an increase in the deep, and a decrease in the superficial cortical zone. The changes proved to be significant during the whole experimental period in the juxtamedullary index and between the 4–14 postoperative days in the superficial index values. The tendency of the changes of JGI in the contralateral kidneys was similar to those of the papillectomized kidneys, but significant differences were registered less constantly. These changes are probably the consequences of haemo- dynamic factors. Papillectomy is considered an incompetent model for studying the regulatory function of macula densa in the synthesis of renin.

DBA/1 and DBA/2 mice infected with the Rauscher leukemia virus developed a biphasic erythroleukemia. Transitory regression of the disease was closely associated with the appearance of tumor-specific antibodies and the exacerbation was preceded by the gradual decrease of antibody titer. The antibody-dependent cellular cytotoxicity could be detected earlier, than the complement-dependent cytotoxicity. Moreover, in each case the titer of antibody-dependent cellular cytotoxicity was higher than that of complement-dependent cytotoxicity. The results suggest that the antibody-dependent cellular cytotoxicity is mainly responsible for the rejection of tumor cells.

1. Complete mechanical occlusion of the ileum was produced in dogs and the loops above and below the obstruction were examined functionally and morphologically 4 or 7 days later. 2. The intraluminal pressure in the occluded loop never exceeded 8 cm water. 3. The mucosa above the obstruction secreted water and ions into the lumen in vivo, though it absorbed glucose normally. Mucosal slices also absorbed amino acids and monosaccharides normally in vitro. 4. The mucosa below the obstruction absorbed ions and glucose in vivo and non-electrolytes in vitro to a slightly smaller extent than normal intestine. 5. The morphological changes above the occlusion included shorter, plumper villi and shorter crypts, a reduction in histochemically stainable brush-border enzymes, but an increase in acid phosphatase. Below the obstruction, there was atrophy of the villi and crypts and reductions in all enzymes studied. 6. The results suggest that the mucosa above the occlusion possesses an intact and almost normal epithelial layer, but that it has been stimulated to secrete in vivo, presumably by intraluminal factors. Below the obstruction, true atrophy of the mucosa has promptly developed.

Dog kidneys were stored three hours at 4 degrees C in heparinized homologous blood. Their histological examination revealed the presence of a homogeneous precipitate in the glomerular capillaries and afferent and efferent arterioles, and histochemical analysis indicated that it consisted of glycoprotein. It is tentatively suggested that the substance is cryoglobulin, a conclusion supported by the disappearance of the deposit on reimplantation of the kidney.

The thyroid gland of homozygous Gunn rats is moderately enlarged and displays a brownish-black discoloration. Light microscopic examination discloses that the follicular cells are filled with brown granules, which are shown, under the electron microscope, to be modified colloid droplets. Most of them possess a strong acid phosphatase and a mild peroxidase activity and contain a melanin-like pigment, according to histochemical analysis.