Secretory breast cancer in a 7.5-year old boy.

Breast cancer is extremely rare in children, and consequently no consensus has been reached on the optimal treatment modalities. The medical history and treatment plan for a 7.5-year old male breast cancer patient is described. Radical mastectomy with sentinel node biopsy was performed in October 2002. As no malignant cells were detected in the sentinel node, and no BRCA1-2 mutations were detected, no further radio- or chemotherapy was performed. A "wait-and-see" policy was decided on. Further treatment will be given if this becomes necessary with the development of metastases.

A novel method of macropathologic and arteriographic examination of carotid specimens obtained from autopsy.

Twenty carotid bifurcations were examined. During autopsy, carotid bifurcations were removed in toto. Unfixed carotids were ligated and cannulated for injection of an angiographic contrast medium followed by injection of a tissue-embedding medium at physiologic pressure and temperature. The carotid bifurcation was frozen and cut manually in 3-mm cross-sections. Photographs were then taken of every slice. Angiography, filling with tissue-embedding material, and sectioning were successful in all cases. In the macropathologic sections, the extent, configuration and location of atherosclerotic lesions could be identified.

Isolation of rare opportunistic pathogens in Hungary: case report and short review of the literature. Rhodococcus equi.

Rhodococcus equi is a well-established pathogen in foal pneumonia and is increasingly recognized as a pathogen in immunocompromised humans. We have isolated a Gram-positive coccobacillus from 8 blood samples and lung tissues of a renal transplant patient. Colony morphology, growth in Lowenstein-Jensen medium, 21 biochemical reactions, the characteristic morphological cycle (coccus-rod-coccus) and the CAMP test established the R. equi diagnosis. Histological studies of 2 lung biopsy specimens revealed numerous microabscesses with aggregates of polymorphonuclear leukocytes surrounded by abundant foamy macrophages. Our isolates proved to be sensitive to majority of antibacterial drugs. The appropriate therapy (amoxicillin-clavulanate) proved to be effective, however six months later a relapse was observed. Data show that in spite of its rare occurrence, R. equi infection represents a diagnostic and therapeutic challenge. The taxonomical, epidemiological, clinico-pathological, diagnostic and therapeutic data of R. equi are discussed.

Analysis of the role of apoptosis and cell proliferation in renal cystic disorders.

Cell proliferation and apoptosis were studied in 8 patients with inherited polycystic kidney disease and in 34 patients with acquired cystic kidney conditions including solitary and multilocular cysts and segmental tubular dilation. Intact renal tissue of 20 surgically removed tumorous kidneys served as control. Cell proliferation and apoptosis were demonstrated by immunohistochemical and in situ end-labeling methods. The percentage of positively stained nuclei was calculated and statistically analyzed. Both apoptosis and cell proliferation were significantly higher (p<0.001) in polycystic kidney disease. The percentage of positively stained nuclei in the whole kidney tissue with acquired cysts did not differ from controls although cell proliferation was significantly higher (p<0.001) in cells lining the cysts. Apoptotic cells were rarely found in the cystic epithelium or were even absent in these cases. Our data indicate that while polycystic kidneys seem to be characterized by abnormal cell survival, acquired renal cysts have different behavior in which so far unknown intracellular changes are more likely to cause tubular distension probably through induced cell proliferation.

Evaluation of apoptosis and cell proliferation in experimentally induced renal cysts.

Cell proliferation and apoptosis in renal cysts induced by streptozotocin, alloxan and ferric-nitrilotriacetate were investigated in rats. In the kidneys of all treated animals dilated tubules at the cortico-medullary region, large cysts, glomerular cysts and tubular dilation in the medullary area were found. Both cell proliferation and apoptosis were increased in the epithelium of the non-dilated tubules, in the mesangial and interstitial cells. Cells lining the dilated tubules or cysts demonstrated apoptosis but their proliferating activity was low. By calculating the proliferation-apoptosis ratio we found that alloxan did not change the balance between the two mechanisms. Meanwhile streptozotocin resulted in an increased apoptosis and ferric-nitrilotriacetate in an increased cell proliferation. p53 expression might be responsible for the uncontrolled proliferation in rats treated with ferric-nitrilotriacetate as this oncoprotein was diffusely present in tubular cell nuclei. The observed apoptosis seemed to be independent of bcl-2 oncoprotein expression. We assume that the initial factor in such cystogenesis should be a cellular injury due to direct toxic or to the diabetogenic effect of the drugs. The latter is more likely as all the animals were hyperglycemic and insulin treatment following administration of streptozotocin prevented the morphologic changes.

Morphology of cystic renal lesions. Lectin and immuno-histochemical study.

Renal cystic disease include heritable, developmental and acquired disorders. Morphological features were extensively studied mainly in cases of autosomal dominant polycystic and experimentally induced cystic disorders. We report the immunohistochemical (cytokeratin, epithelial membrane antigen, vimentin, Tamm-Horsfall protein, proliferating cell nuclear antigen) and lectin-binding (soybean agglutinin, Dolichos biflorus agglutinin) profile of cystic kidneys from 9 surgically removed and 21 autopsy cases. The primary renal diseases displayed great diversity. Beside polycystic kidney diseases we studied cysts associated to renal neoplasm, hemodialysis, nephrosis syndrome and chronic transplant rejection. Cystic epithelium demonstrated positive reactions with distal tubular markers (epithelial membrane antigen, cytokeratin) or collecting duct (soybean agglutinin, Dolichos biflorus agglutinin) and Henle loop markers (Tamm-Horsfall protein) but the latter in lesser extent. The large number of the vimentin positive cases are suggestive to dedifferentiation or cellular regeneration. The former might be underlined by the diffuse cytoplasmic or basolateral membrane staining of the epithelial membrane antigen in some cystic epithelial cells. Not the cystic epithelium but rather the neighbouring non-dilated tubular cells and interstitial cells presented proliferative activity which was most intense in areas where vimentin and variable nephron segment markers in the same tissue were expressed. Positive reaction of the type IV basement membrane collagen and the rate of the inflammation failed to show similar connection. This finding suggests the importance of the inflammatory cells in the development and/or expansion of the cysts.

Induction of renin release from isolated glomeruli by inorganic mercury(II).

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 microM. 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.

Furosemide-induced lysosomal enzyme release in mouse kidney in vivo and in vitro.

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.

[Pathogenic properties of coagulase-negative staphylococci in experimental infections]. / Koaguláz-negatív staphylococcusok patogenetikai tulajdonságai experimentalis fertözésekben.

The frequency of persistence of three Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus saprophyticus strains, respectively, was studied in BALB/c mice at the 10th day of intraperitoneal (ip) challenge. 245 out of 416 mice survived after infections with four bacterial suspensions of different colony forming units (CFU) of each strain. Staphylococci persisted in 61 mice (24,9%). The main sites of persistence were the kidneys, while cocci were rarely isolated from the spleen and the liver. S. epidermidis persisted with a significantly higher rate than the other two species, because S. epidermidis in 28,8%, S. haemolyticus in 4,9%, and S. saprophyticus in 3,6% were reisolated from the organs of the respective infected and surviving animals. The organ persistence was proportional to the amount of bacteria injected. The persistence resulted in subacute microabscesses in the organs. Reisolates of persisting bacteria remained stable in phenotype and genotype concerning antibiotic resistance patterns and biochemical activities for the taxonomic implication, whereas cell surface properties characterizable with phage types altered considerably during persistence. It is concluded that cocci of all three Staphylococcus species are invasive and can persist to a certain extent in the organs of animals with normal immune system, too, after artificial inoculation into the peritoneum i. e. to the serosal surfaces.

Comparison of the effect of hypoxia on the secretion of the atrial natriuretic factor in spontaneously hypertensive and normotensive rats.

The effect of short lasting hypoxia on blood pressure, plasma atrial natriuretic peptide level and number of specific atrial granules were studied in 26 male spontaneously hypertensive and 24 normotensive Wistar rats. A great difference occurred in ANP secretion between hypertensive and normotensive rats. In the hypertensive animals elevated plasma ANP concentration (130 +/- 27 pg/ml) and decreased granularity in the right atria (73 +/- 2) were found on the first day of hypoxia with a slight elevation in urinary sodium content versus normotensive controls. The blood pressure also decreased although not significantly (190 +/- 14 mm Hg). In Wistar rats increased plasma ANP (130 +/- 34 pg/ml) and decreased atrial granularity versus normotensive controls (72 +/- 10 in the left and 113 +/- 16 in the right atrium) were observed only on the third day of hypoxia without changes in blood pressure and natriuresis. In SHR the rapid but short timed ANP release might be of right atrial origin and probably the consequence of a continuous and perhaps increased secretion of the peptide in normoxic conditions too. In Wistar rats the plasma ANP elevation could be secondary due to the increased plasma level of different vasoactive hormones to hypoxia. In the altered effect of ANP in hypertensive and normotensive hypoxic animals, structural and functional changes in the vascular bed may play a role.

Morphological observations on the extracellular space in the macula densa of the mouse kidney.

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.

[Correlation between the extrarenal renin-angiotensin system and the mononuclear phagocyte system]. / Extrarenális renin-angitotensin rendszer és a mononukleáris phagocyta szisztéma kapcsolata.

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.

Morphological and immunohistochemical characteristics of dimethylnitrosamine-induced malignant mesenchymal renal tumor in F-344 rats.

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 well-known 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.

[Clinicopathology of bone metastases causing pathological fractures]. / Patológiás törést okozó csontmetasztázisok klinikopatológiája.

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.

Suppression of renin-angiotensin system in the heart of spontaneously hypertensive rats.

Renin-like enzyme and angiotensin converting enzyme (ACE) were identified and their specific activities measured in cardiac tissues of spontaneously hypertensive rats (SHR) and their Wistar-Kyoto (WKY) normotensive controls. In addition, the enzyme activities were determined following administration of hypotensive drugs. The pH optima of cardiac renin-like enzymes were identical with those in vascular walls, the specific activity being higher in the heart. Cardiac ACE revealed similarities with the venous wall enzyme. The highest specific cardiac renin-like activity was found in the septum and that of ACE in atria/auricles. Both enzyme values were lower in the hearts of SHR than in those of normotensive controls. Following nifedipine treatment, specific renin-like activities increased in all cardiac structures studied (P less than 0.01); with nitrendipine and muzolimine less pronounced elevations were obtained. Administration of these three hypotensive drugs resulted in a stimulation of ACE in all the cardiac structures except in atria/auricles, where their activities were lowered.

The chronically furosemide-treated mouse as a possible ultrastructural model for cystic fibrosis.

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.

Aggressive infantile myofibromatosis: report of a case of a clinically progressive congenital multiple fibromatosis.

We report a case of congenital multiple fibromatosis (infantile myofibromatosis) showing the typical spindle-cellular proliferation with prominent vascularity on light microscopical observations. Electron microscopy showed the abundance of fibroblasts with conspicuous collagen and reticulin fibers together with numerous cells sharing the characteristics of both fibroblasts and smooth muscle cells (myofibroblasts). Neither visceral involvement nor ossification has been detected during the 4-year-long follow-up period. However, the clinical course has shown a slow, continuous, protracted though destructive proliferation of subcutaneous myofibroblastic nodules. These findings are contrasted with previous reports that claimed that the presence of myofibroblasts indicates benign behavior and results in the regression of fibromatous lesions.

The effect of adrenalectomy on the proteinuria of spontaneously hypertensive rats and normotensive controls.

Urinary proteins were studied by quantitative and electrophoretic methods in 6-month-old spontaneously hypertensive rats and normotensive controls. Protein analysis was carried out before and after adrenalectomy and during gluco- or mineralocorticoid treatment. Urinary protein excretion was significantly diminished after adrenalectomy both in the hypertensive and control groups. The original level of protein excretion was restored only by glycocorticoid treatment. Normal or pathologic electrophoretic pattern of urinary proteins was not influenced by the experimental procedure. Moderately non-selective glomerular proteinuria persisted in the spontaneously hypertensive rats referring to a definitely damaged glomerular barrier. One protein fraction of about 130,000 dalton molecular weight disappeared from the urine of hypertensive animals after adrenalectomy and reappeared after glucocorticoid treatment only. This fraction probably represents the dimeric form of albumin. Quantitative changes of urinary protein excretion can be explained by haemodynamic factors.

The pharmacological relevance of vital staining with neutral red.

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 nonspecific binding to noradrenaline-receptors in the vascular smooth muscle cells.