Zur Histopathologie der Niere beim Pseudo-Bartter-Syndrom durch chronischen Diuretikaabusus

Bei einer 38jahrigen Patientin entwickelte sich ein Pseudo-Bartter-Syndrom mit hypokaliamischer Alkalose, Hyponatriamie und Hyperreninamie infolge eines mehr als 10jahrigen Abusus von Diuretika (Furosemid, Spironolacton, Thiabutazid). Als nierenbioptische Befunde werden eine Hyperplasie des iuxtaglomerularen Apparates und der Mesangiumzellen als morphologisches Substrat des Hyperreninismus sowie eine herdformige Vakuolisierung von proximalen Tubuluszellen und eine herdformige Atrophie der distalen Tubuli beschrieben. Die Genese der tubularen Veranderungen und ihre mogliche Beziehung zu kaliopenischen, hypoxischen oder medikamententoxischen Einflussen wird diskutiert, kann jedoch nicht befri…

Hepatocellular expression of lymphocyte function—associated antigen 3 in chronic hepatitis

T lymphocyte-mediated cytolytic immune reactions are considered a major cause of hepatocyte injury in chronic viral and autoimmune hepatitis. To further investigate local immune responses, we studied the expression of lymphocyte antigens and cell-cell interaction molecules known to be involved in effector-target cell interactions by light and electron microscopy in liver biopsy specimens from patients with chronic viral and autoimmune hepatitis. CD8+ lymphocytes were found to be the predominant population of cells in the inflammatory infiltrate in chronic hepatitis B and non-A, non-B hepatitis. In contrast, CD4+ cells constituted a comparably higher proportion of cells and were more numerou…

Cytoplasmic microvesicles in chromophobe cell renal carcinoma demonstrated by freeze fracture

In the chromophobe cell type of renal carcinoma, cytoplasmic microvesicles (frequently with "inner vesicles") demonstrable by transmission electron microscopy are one of the most important diagnostic features. The present paper reports on these microvesicles in freeze fracture replicas. Their diameter is mainly between 140 and 300 micron, but smaller and very much larger vesicles may also occur. The vesicle membrane is devoid of, or contains only scanty intramembranous particles. Cytoplasmic invaginations, probably the precursors of "inner vesicles" can also be detected. Connections with the agranular endoplasmic reticulum, mitochondria or other cell components could not be documented. Larg…

HSV hepatitis in the mouse: A light and electron microscopic study with immunohistology and in situ hybridization

In order to characterize better the morphology and immune response in acute necrotizing HSV infection, murine HSV hepatitis was examined. BALB/c mice were inoculated intraperitoneally with 10(6) plaque-forming units (PFU) of HSV-1 (Lenette) and HSV-2 (D316). In both groups half the animals were pretreated with silica particles to block macrophage function. Up to 6 days after infection four mice from each group were sacrificed at daily intervals and the livers were examined by light and electron microscopy, immunohistology, in situ hybridization, combined immunohistology/in situ hybridization and titration of viral PFU. HSV-2 infected mice developed severe necrotizing hepatitis with persiste…

Human chromophobe cell renal carcinoma

Twelve renal cell carcinomas composed of "chromophobe" cells are described. This is the first report of renal chromophobe cell tumors in humans neoplasms of this cell type having been described previously only in experimentally induced adenomas in animals. By light microscopy chromophobe cells have slightly opaque or finely reticular cytoplasm when stained with haematoxylin and eosin. They may be distinguished from the clear cells of hypernephroid renal cell carcinomas by the strongly positive reaction of their cytoplasm with Hale's (1946) colloidal iron method and the weaker positive reaction with alcian blue. Vesicular structures, often containing internal vesicles, and possibly derived f…

Nephrosis in two siblings with infantile sialic acid storage disease

The diagnosis of infantile sialic acid storage disease (ISSD) was established in two siblings on the basis of typical clinical signs and the biochemical findings of hyperexcretion and intracellular storage of free sialic acid. A severe, steroid resistant nephrosis occurred in both siblings. The activities of lysosomal enzymes, including sialidase, were normal. A combined detection method for sialic acids with Limax flavus agglutinin labelling and phosphotungstic acid staining showed severely alterated sialic acid components in epithelial kidney cells and indicate a causal relationship between the nephrosis and the underlying biochemical defect. Further observations of ISSD patients with ren…

Microvascular injury and repair in acute human bacterial pyelonephritis.

Acute inflammatory cell-capillary endothelial cell interactions, related to injury and repair, were investigated light and electron microscopically in acute human bacterial pyelonephritis. In inflammatory infiltrate-adjacent microvessels, the small capillaries were completely occluded by leukocyte plugs and the large capillaries were densely filled with acute inflammatory cells adhering to the endothelium. Severe damage to small and large capillaries was observed around endothelium adherent, degranulated neutrophil granulocytes containing phagocytosed bacteria. There were spaces in the endothelium, degradation of the vascular basement membrane, of the perivascular interstitial matrix and of…

Klassifikation der Nierenzellkarzinome/Tumoren und ihre Beziehung zum Nephron-Sammelrohrsystem

After a controversial phase of nomenclature (including--among others--the terms "hypernephroma" and "hypernephroid carcinoma") a cytomorphologically defined subtyping of renal cell tumours (adenomas, carcinomas, oncocytomas) is offered, based on new electron microscopical and histochemical observations. These data are in part supported by cytogenetical findings reported in the literature. Phenotypical/histogenetical relations to different parts or cell types, respectively, of the nephron-collecting duct system could be demonstrated. Chromophobe cell carcinoma and oncocytoma exhibit features of the intercalated cells.

Characterization of cells involved in the formation of granuloma. An ultrastructural study on macrophages, epitheloid cells, and giant cells in experimental tubulo-interstitial nephritis.

In experimental tubulo-interstitial (anti-basement membrane) nephritis of the rat, granulomatous inflammation develops around immunologically altered tubular basement membranes. The present light- and electron microscopic studies indicate that in the course of the granulomatous reaction, tissue monocytes evolve from blood monocytes and pursue two independent pathways of differentation. On the one hand they may differentiate into macrophages ("distant from tubules") or, alternatively, into epitheloid cells ("adjacent to tubules"). The latter, through cell fusion, develop into multinucleated giant cells of the Langhans' type. The cytoplasmic components of the epitheloid cells and the multinuc…

MACOP-B chemotherapy for the treatment of high grade and intermediate grade non Hodgkin's lymphoma.

Between Nov. 1985 and Nov. 1988, sixty-three patients with high grade malignant (hg) and intermediate grade malignant (img) Non Hodgkin's Lymphoma (NHL) were treated with MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin). Thirty-seven patients received MACOP-B as an upfront treatment modality, whereas twenty-six patients had relapsed disease and received MACOP-B as a salvage protocol. Four weeks after termination of therapy, 75% of patients with de novo NHL and 72% of the patients with relapsed NHL were in complete remission (CR). In the group of newly diagnosed NHL, 22% achieved partial remission (PR) and 3% no change (NC), whereas in the group wi…

Interstitielle Nephritis bei atypischer Manifestation eines Sj�gren's Syndrom

A patient was observed with interstitial nephritis which resulted in renal tubular acidosis (distal type), tubular proteinuria and defective urinary concentrating ability in the absence of edema, elevated arterial blood pressure, glomerular proteinuria or abnormal urinary sediment. The presence of interstitial nephritis was established by renal biopsy which showed dense infiltrates in the interstitium, interstitial fibrosis and thickening and splitting of the pericapillary basal membranes. Immunofluorescence was non contributory. Extrarenal symptoms were discrete (arthralgia of both hands, Raynaud's syndrome upon cold exposure). Mixed connective tissue disease (MCTD) was suspected because o…

Formation of basement membrane in extracapillary proliferates in rapidly progressive glomerulonephritis

In the extracapillary proliferations (crescents) of the glomeruli in glomerulonephritis, basement membranes appear and in addition "secretory bodies" are formed in the cisternae of the rough endoplasmatic reticulum. The findings permit the conclusion that proliferated visceral epithelial cells are involved in the crescent formation to a greater extent than previously assumed.

Endotheliotropic (hemolytic) nephroangiopathy and its various manifestation forms (thrombotic microangiopathy, primary malignant nephrosclerosis, hemolytic-uremic syndrome).

In hemolytic-uremic syndrome (HUS) various lesion types in the kidneys are observed in childhood. These are designated as the “glomerular type=G type” (essentially identical with thrombotic microangiopathy), as “arterial type=A type” (essentially identical with primary malignant nephrosclerosis (PMN)) or as “mixed type=G/A type”. With reference to characteristic cases, the most important morphological findings are described. In adults, in whom other diagnostic terms are used besides HUS, the same nephropathological types are observed. In the two phases of life, there occurs in addition renal cortical necrosis in subtotal nephroangiothrombosis. The G type and A type also have a different cli…

Cell fusion as a mechanism for the formation of giant cells (Langhans’ type)

The formation of multinuclear giant cells of the Langhans' type in tubulo-interstitial auto-immune nephritis in the rat has been investigated by means of autoradiography. While in the majority of giant cells all nuclei were radiolabeled, in a few both labeled and unlabeled nuclei were present. This latter finding represents strong evidence in favour of the hypothesis that giant cells do not form by endomitotic processes but rather through fusion of certain precursor cells. According to previous studies this precursor cell population consists mainly of epitheloid cells, i.e. modified monocytes.

Glomerul�re Amyloidose des Menschen ? unter besonderer Ber�cksichtigung der Proteinurie und der Amyloidogenese

Light and electron microscopic investigations were carried out on kidney biopsies in renal amyloidosis cases. Particular attention was paid to the relationships between glomerular amyloidosis and proteinuria.

The obsolescent renal glomerulus ? Collapse, sclerosis, hyalinosis, fibrosis

By light and electron microscopical examination it is shown that four structural components can contribute to obsolescent glomeruli: capillary basement membranes, enriched mesangium matrix, “vascular” hyalin and collagen fibers. Each of these components can bring about glomerular damage alone. One non-reactive form — a glomerular collapse with only basement membrane remnants — can be separated from three reactive forms: the accumulation of mesangium matrix (sclerosis or matrix-sclerosis), deposition of vascular hyalin (hyalinosis in the narrow sense), and fiber development within the former urinary space (fibrosis or fibro-sclerosis). The use of the term “fibrinoid” in place of the descript…

Cytomorphological typing of renal cell carcinoma--a new approach.

Aktuelle Pathologie der Glomerulonephritis

Ausgehend von der Glomerulonephritis-Lehre von Volhard und Fahr (1914) und den grundlegenden pathologisch-anatomischen Untersuchungen zu diesem Thema von Theodor Fahr (1925, 1934) wird der aktuelle Stand der Glomerulonephritis-Problematik dargestellt. Die — z.T. methodisch bedingten — Fortschritte besonders der Nephropathologie und der Immunnephrologie haben dazu gefuhrt, das die sachgerechte Charakterisierung eines glomerulonephritischen Krankheitsbildes heute nur durch die Synopse der drei Kategorien — Immunpathogennese, Pathomorphologie und Klinik — moglich ist. Jede dieser Kategorien hat ihre eigene Systematik. Die Nosologie der verschiedenen GN-Formen ergibt sich aus der (konstanten od…

Kommentar zum Beitrag von I. Klempa et al. Transplantathyperparathyreoidismus ?Tumor�hnliches Wachstum und autonome Funktion menschlicher Autotransplantate von hyperplastischen Epithelk�rperchen

Angioma-Like Pseudometamorphosis in Wilms' Tumors Subjected to Preoperative Radio- and Chemotherapy

Six Wilms' tumors (stage III-V), which had undergone preoperative irradiation and chemotherapy, were examined histologically. While mesenchymal and differentiated epithelial tumor elements were preserved to a large extent, blastemic tumor structures were almost completely lacking. Instead, pseudoangioma-like structures similar to cavernous hemangioma prevailed. As demonstrated by transitional pictures, the pseudoangioma-like pattern is a result of the fact that blastemic tumor elements are replaced by blood after therapy-induced necrosis and lysis. The clinical advantages of preoperative treatment are briefly discussed, especially for patients with advanced tumors.

Endocytotic activity in epitheloid and Langhans’ giant cells

In the experimental tubulo-interstitial (anti-basement membrane) nephritis in the rat, electron microscopic studies after the in vivo microinjection of native ferritin in areas of granulomatous inflammation near the surface of the kidney indicate that epitheloid and multinucleate Langhans’ giant cells are capable of endocytosis and particularly of micropinocytosis. This suggests the possibility that endocytotic activities as well as secretion phenomena are important in the immune defense mechanisms linked with these “specifically” developed cells.

Mitochondrial and chromosomal DNA alterations in human chromophobe renal cell carcinomas

Renal cell tumours are characterized by the loss of chromosome 3p and trisomy of 5q segments (common, non-papillary renal cell carcinoma), or by trisomy of chromosomes 7 and 17 and loss of the Y chromosome (papillary renal cell carcinoma), or by random karyotype changes and mitochondrial DNA alterations (renal oncocytoma). We have studied by means of RFLP analysis the genomic and mitochondrial DNA in 11 chromophobe renal cell carcinomas, which have a unique morphology among kidney cancers. We found a loss of the constitutional heterozygosity at chromosomal regions 3p, 5q, 17p, and 17q, a combination of allelic losses that has not been found in other types of renal cell tumours. Three of the…

Freeze-fracture features of epithelioid cells, multinucleated giant cells, and phagocytic macrophages

The freeze-fracture morphology of epithelioid cells, multinucleated giant cells (Langhans' type), and phagocytic macrophages was investigated. The intensely folded and interdigitating surface membranes of epithelioid cells and multinucleated giant cells displayed no specialized areas of cell contact. The size of the intramembranous particles (IMP) and the fact that the area density of IMPs was higher in the cytoplasmic (P) faces than in the external (E) faces of the cell membranes agreed with observations in other eukaryotic cells. The area densities of the IMPs suggest lower transport rates of molecules across the cell membranes of granuloma cells than of certain epithelial cells. Small pi…

Intercalated cells as a probable source for the development of renal oncocytoma

Renal oncocytoma is a distinct type of epithelial tumor said to arise from the collecting duct system. Here we show that in nine of ten oncocytomas the tumor cells expressed an analog of the erythrocyte anion exchanger band 3. In the normal kidney band 3 is confined to the basolateral surface of the majority of intercalated cells which comprise up to 50% of the cortical collecting duct epithelium. Carbonic anhydrase c is another protein abundant in intercalated cells, and this was also expressed in six of the ten oncocytomas investigated. Immunoreactivity specific for band 3 and carbonic anhydrase c was not detected in any of the 20 renal cell carcinomas examined. At favourable section plan…

Manifestation and ultrastructural typing of amyloid deposits in the heart

Using light and electron microscopy, 65 cases of amyloid deposits in the heart were examined. Five different groups were distinguished: I. isolated atrial amyloidosis, II. senile cardiac amyloidosis, III. cardiac amyloid accompanying chronic infections and tumors, IV. cardiac amyloid accompanying plasma cell dyscrasia, V. idiopathic cardiac amyloidosis. Seen structurally, no principal differences in the precise localization of the amyloid deposits were found in any of the groups investigated. Amyloid is always deposited in the vicinity of cells with myocytic cell differentiation (i.e. the heart muscle cells, non-striated muscle cells of the vessels), whereby the relevant basement membranes …

Differentiation of granuloma cells (epithelioid cells and multinucleated giant cells): a morphometric analysis

Morphometric analysis disclosed distinct differences between blood monocytes, tissue monocytes (i.e. immature macrophages), epithelioid cells and multinucleated giant cells as well as phagocytic macrophages (i.e. mature macrophages) in the granuloma model of autoimmune (anti-TBM) tubulo-interstitial nephritis. The numerical density of lysosomes decreased slightly in tissue monocytes compared with blood monocytes but showed a pronounced increase during the formation of epithelioid cells. The lysosomal compartments of epithelioid cells and multinucleated giant cells resembled each other very closely, but the giant cells obviously produced additional lysosomes of small diameter (80-120 nm). Ph…

Histopathology and Classification of Renal Cell Tumors (Adenomas, Oncocytomas and Carcinomas)

The term renal cell tumors (adenomas and carcinomas) subsumes the tumors deriving from the uriniferous tubule epithelium of the kidney. Precise analysis shows that the renal cell tumors display different cell types which build up the individual tumor alone or in combination with each other. Three categories of basic elements are distinguished in the characterization of renal cell tumors: Cytological elements = tumor cell types: Clear, chromophobe, chromophilic (basophilic, eosinophilic), oncocytic, spindle-shaped/pleomorphic. Histological elements = growth patterns: Compact, acinar (nest-like), tubulopapillary (tubular, papillary), cystic. Cytological grading of malignancy: G I, G II, G III…

Acute human pyelonephritis: Leukocytic infiltration of tubules and localization of bacteria

The fine structural details of how leukocytes appear in the lumen of tubules and the localization of bacteria in the tubulo-interstitial space were studied by light and electronmicroscopy in renal cortical biopsy specimens from three patients with acute pyelonephritis. The cells of interstitial infiltrates infiltrated and sometimes disrupted the cortical collecting tubules preferentially, while inflammatory infiltration of the proximal and distal convoluted tubules occurred more rarely. Since the emigration of tubular wall-localized individual leukocytes into the lumen was not observed even in long series of thin sections, focal inflammatory disruption of the uriniferous ducts was considere…

Neue Aspekte der Amyloidose

Amyloid ist eine Substanz, die sich in ihren Grundeigenschaften bei allen Formen der Amyloidose gleichartig zusammensetzt. Aufgrund elektronenmikroskopischer Untersuchungen zeigt sich, das alle Amyloidosen nicht nur einheitliche Grundeigenschaften, sondern auch ein gemeinsames Ablagerungsprinzip aufweisen. Amyloidfibrillen finden sich immer in enger Beziehung zu Basalmembranen bzw. basalmembranartigen Substanzen, insbesondere von Zellen mit kontraktilen Eigenschaften (myozytare oder myopotente Zellen). Kollagene Fasern verschiedenen Typs weisen keine geregelte Beziehung zur Amyloidsubstanz auf. Die Entstehung und Entwicklung der Amyloidosen ist weiterhin abhangig von folgenden drei Faktoren…

The human chromophobe cell renal carcinoma: its probable relation to intercalated cells of the collecting duct.

In the present study we have examined ten cases of the chromophobe type renal cell carcinoma. This type of tumor is distinguished from the other carcinomas of the kidney with light cytoplasm (formerly called “hypernephroid”) by (a) a positive Hale’s iron colloid stain of the cytoplasm, (b) the occurrence of numerous invaginated vesicles within the cytoplasm that resemble the invaginated vesicles of intercalated cells of the collecting duct system, and (c) a positive immunoreaction of both the plasma membrane and the cytoplasm with antibodies to the epithelial membrane antigen (EMA) and carbonic anhydrase C (CAC), respectively. Unlike oncocytomas, which also express CAC and EMA, the chromoph…

Electron microscopic observations on primary hepatocyte cultures infected with herpes simplex virus Types I and II

The replication cycle of the Herpes simplex virus (HSV) strains I and II has so far been described mainly in established proliferative cell cultures. Most of the biochemical data and ultrastructural cell changes regarding the virus-cell interaction have been obtained from ‘permissive’ cells which allow almost unrestricted viral multiplication. It seems obvious, however, that the in vivo viral infections are not represented adequately by these experiments. In order to achieve a more realistic view of the ultrastructural events during HSV infection of adult tissue, cell cultures were prepared from adult mouse and rat livers and infected with several HSV strains. Established ‘permissive’ cell …

The Glomerular Lesions in Endotheliotropic Hemolytic Nephroangiopathy (Hemolytic Uremic Syndrome, Malignant Nephrosclerosis, Post Partal Renal Insufficiency)

The term "Endotheliotropic Hemolytic Nephroangiopathy" (EHN) comprises various clinically or pathomorphologically defined disease states with severe renal lesions (e.g. hemolytic uremic syndrome, malignant nephrosclerosis, post partum renal insufficiency) which, to date, have been considered as different entities. We attempted to assign accompanying glomerular changes based upon light and electron microscopy to the above mentioned clinical pictures and their various stages. The accordingly classified glomerular lesions (G1--G3 and Ga) are of critical importance in pathohistological differential diagnosis. Since it is assumed that fibrin is a causing event in the pathogenesis of the vascular…

Primary perireticulin amyloidosis in a 14-year-old girl.

A primary perireticulin amyloidosis is reported in a 14-year-old girl, which showed the symptoms of a steroid-resistant nephrotic syndrome. The diagnosis was established by biopsies of kidney and rectum. Occurrence of amyloidosis in childhood and the clinical picture are discussed and references to clinical trials carried out are given.

Chromophobe cell renal carcinoma and its variants--a report on 32 cases.

This paper reports on 32 chromophobe cell renal carcinomas observed in 697 renal cell cancers (RCC) of adults (peak in the sixth decade of life). The chromophobe cell-type differs from other types of RCC macroscopically, the cut-surface being predominantly of grey-beige colour. Histologically, there are two variants: one is the typical (light) variant (n = 22) and the other is eosinophilic (n = 10). Both variants have in common (a) reaction of the cytoplasm with Hale's acid iron colloid; (b) electron microscopic detection of cytoplasmic microvesicles (150-300 nm), frequently with 'inner vesicles', and (c) low glycogen content in comparison with the clear cell carcinoma. Immunocytochemical i…

Hepatitis A-like non-A, non-B hepatitis: light and electron microscopic observations of three cases.

To date, three types of NANBH have been distinguished by epidemiological, clinical and experimental data. We examined the liver biopsies of three patients with an acute NANBH resembling hepatitis A from the infection route, incubation period and clinical course. The liver biopsies revealed lesions with a portal and periportal predominance, thus also exhibiting parallels with hepatitis A on the histopathological level.