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F Gudat

Publications and source records attributed to F Gudat.

At least 163 records · Page 9Linked to original sources

Stereology of liver biopsies from healthy volunteers.

The stereological model and the base-line data of normal human liver needle biopsy-specimens are presented. Four reference systems were introduced: 1 cm3 of liver tissue, 1 cm3 of hepatocyte, 1 cm3 of hepatocytic cytoplasm and the volume of an average "mononuclear" hepatocyte. The sampling was done at three levels of magnification (1,000 X, 5,000 X and 10,000 X). A lobular differentiation was not considered. The baseline data show strikingly small variations (s.e. less than 10%) within the individual biopsy specimen and within the group of four biopsies. There is no principal difference between human beings presented here, rats, mice and dogs. Only the mean individual volume of human hepatocytes is clearly larger than in rodents. The problems and limitations of stereological work on liver biopsy specimens are discussed.

Animals↗

[Classification and infectiousness of chronic hepatitis B, defined by the Dane particle in the blood and virus components in the liver].

55 HBAg seropositive patients with chronic hepatitis B selected from a total of 217 liver biopsies were studied for the presence of HBcAg and HBsAg in the liver tissue and of Dane particles in blood by immunofluorescence and electron microscopy. Among 27 patients with non-aggressive chronic inflammation the following constellations were found: a) 19 patients (13 with nonspecific reactive hepatitis, 6 with chronic persistent hepatitis) had isolated HBsAg expression in the tissue (HBs type) and of these only 2 had rare Dane particles; b)4 patients (all with histologically very active chronic persistent hepatitis) with focal HBc- and HBsAg tissue expression (HBc+s type) and detectable Dane particles in blood; c)4 patients (1 with nonspecific reactive, 3 with chronic persistent hepatitis) with generalized HBcAg (and focal HBsAg) expression (HBc type) and multiple Dane particles in blood. Among 22 patients with aggressive inflammation (19 with chronic aggressive, 3 with "hippie"-hepatitis) focal HBcAg tissue expression (HBc+s type) was found in 17 cases and absence of HBcAg in 5 (3 with focal HBsAg, 2 completely negative by immunfluorescence), all 22 associated with Dane particles in blood, however. In a group of 6 immunosuppressed kidney transplant recipients exhibiting a high concentration of Dane particles in blood 5 patients had generalized HBcAg tissue expression (HBc type) in association with non-aggressive inflammation (1 nonspecific reactive and 4 chronic persistent hepatitis). One patient had chronic aggressive hepatitis in conjunction with focal HBcAg expression (HBc+s type). The consistent association of detectable HBcAg formation in the liver and presence of supposedly infectious Dane particles in blood has a bearing on the evaluation and classification of chronic hepatitis B. On the basis of a positive focal (HBc+s type) or generalized HBcAg tissue demonstration (HBc type and/or the direct identification of Dane particles in blood, discrimination of possibly highly infectious forms from those of low or even no infectivity has been rendered possible. This duality applies mainly to clinically and histologically benign non-aggressive forms of hepatitis presenting with a carrier state or chronic persistent hepatitis. On the basis of these and earlier findings a hypothetical concept of chronic hepatitis is presented which possesses proven diagnostic and prognostic applicability to routine liver biopsies. It is also capable of shedding new light on contradictory findings in the literature and serving as a basis for prospective epidemiologic studies.

Antilymphocyte Serum↗

[The morphological and functional integrity of cryo-preserved leukocytes].

Human peripheral blood lymphocytes were frozen by a simplified method which is described. Light and electron microscopic investigations of the frozen-thawed cells showed no significant morphological changes compared to the fresh cells; comparison of E-rosette formation and nonspecific acid esterase activity before and after cryoconservation afford evidence of a possible slight change in the percent relationship of T- and B-cells, whereas thymidine uptake values within normal range after stimulation with PHA and homologous cells demonstrate the functional integrity of the lymphocytes.

B-Lymphocytes↗

Histochemical and electron-microscopic aspects of bone tumor diagnosis.

In recent years, histochemistry and electron microscopy have been applied more and more to the investigation of bone tumors. The contributions and limitations of these methods in differential diagnosis are discussed. The levels of glycosaminoglycans in cartilaginous tumors display distinct differences between slow- and fast-growing types. All cartilaginous tumors are poor in phosphatase activity. Demonstration of these enzymes at acid and alkaline pH in bone-forming conditions reveals differences between benign and malignant tumors. Osteosarcomas display a rich activity of both phosphatases in bone-forming and in bone-free regions. Acid phosphatase may play a rôle in the breakdown of the host tissue infiltrated by the tumor. Electron microscopy of bone tumors has brought out some interesting findings. In fibrous dysplasia a particular kind of very fine fibrillar structures was observed besides the regular collagen fibrils. This may indicate retardation of collagen maturation. Cell organelles in benign and malignant bone tumors usually differ quantitatively. They resemble active fibroblasts. In bone- and in cartilage-forming tumors we observed large quantities of microfilaments in the cytoplasm. Nuclear indentations and invaginations probably indicate increased nuclear activity. The intense acid phosphatase activity demonstrated histochemically seems inconsistent with the low number of lysosomes in the cytoplasm of osteosarcoma cells, but other organelles (Golgi apparatus and vesicles) may also contain the enzyme. Virus-like particles have not been observed in human osteosarcomas up to now. Other authors have observed a correlation between the number of cell organelles and the grade of differentiation, but this was not detected in our sample of benign and malignant cartilaginous tumors. Histochemistry and electron microscopy of bone tumors are still in the early stage of material gathering. Some histochemical findings, however, can already be used as diagnostic tools.

Acid Phosphatase↗

Sanded nuclei in hepatitis B: eosinophilic inclusions in liver cell nuclei due to excess in hepatitis B core antigen formation.

In confirmation of earlier descriptions by Huang et al. (Huang S-N, Millman I, O'Connell A, Aronoff A, Gault H, Blumberg BS: Am J Pathol 67: 453, 1972) nuclear eosinophilic inclusions due to excess HBcAg particles have been identified in cases of chronic hepatitis B virus infection. As the euchromatin space of affected nuclei is "sanded" by numerous core particles with concomitant dissolution of the chromatin network, spiky, finely granular, and eosinophilic inclusions without a limiting membrane become visible in hematoxylin and eosin-stained paraffin sections. These HBcAg inclusions stain greyish pink with chromotrope aniline blue and are negative for orcein, the periodic acid-Schiff reaction, and the Feulgen reaction for DNA. Sanded nuclei were detected, although not always and only few in number, exclusively in HBAg-positive patients when a focal (as in chronic aggressive hepatitis) or a generalized core formation (as in immunosuppressed kidney transplant recipients) could be demonstrated by electron microscopy or immunofluorescence. Therefore, the positive finding of sanded nuclei in a persistent hepatitis B virus infection indicates an excessive core formation the extent of which should be verified by specific methods.

Cell Nucleus↗

Etiologic and prognostic significance of isolated acute renal hypoxic change (so-called tubular necrosis or shock kidney) in kidney transplants.

20 biopsies were studied in order to determine whether or not the pathologist is able to predict on morphological grounds the etiology and prognosis of acute renal hypoxic change in renal transplants. We concluded that: 1) Intertubular blood stasis seems to be pathognomonic of peripheral vascular rejection and/or renal artery thrombosis. 2) A focal distribution of acute tubular luminal dilatation suggests peripheral vascular rejection. 3) The finding of lymphatic casts suggests the presence of ureteric obstruction. 4) Linear fluorescent staining of the peripheral glomerular basement membrane appears to be due to leakage of plasma proteins in the presence of endothelial damage. 5) The histological distinction between camouflaged rejection and genuine shock kidney is impossible in a biopsy. 6) The precise cause of acute renal hypoxic change and the prognosis of kidney transplants with this alteration often cannot be determined.

Acute Kidney Injury↗

Acute intermittent porphyria with relapsing acute pancreatitis and unconjugated hyperbilirubinemia without overt hemolysis.

A 36-year-old woman was admitted to hospital with a first attack of acute intermittent porphyria. At the same time increased serum levels of amylase and lipase as well as an increased amylase clearance to creatinine clearance ratio were observed, permitting the diagnosis of acute pancreatitis. The etiology of the latter could not be determined. In addition, elevation of indirect bilirubin without evidence of hemolysis was observed Gilbert's syndrome was suspected. 40 weeks after the first episode, a second attack of identical abdominal pain was noted, with elevation of pancreatic enzymes in the serum. There is evidence that acute intermittent porphyria and acute relapsing pancreatitis may have some etiological connection in this patient.

Acute Disease↗

[Hepatitis in drug addicts (follow-up study with biopsies) (author's transl)].

Viral hepatitis, proven by biopsy in 44 patients known to be drug addicts or confirmed drug takers had serial clinical, biochemical and (half of them) biopsy studies between 1971 and 1974. At the time of the first biopsy the period of addicition averaged 28.8 months. 30 of the 44 patients had had jaundice. At the time of the last biopsy, 20 of the 44 had chronic persisting and three had chronic active hepatitis, i.e. more than half had a chronic form. A further 12 patients had "hippie" hepatitis, a special form of acute viral hepatitis with piecemeal necrosis, histological evidence of possible change to a chronic state. There was no case of complete healing during the period of observation. The high rate of chronic hepatitis is thought to be due to partially insufficient immune response. The clinical and even biochemical course in most of the patients was remarkably mild. Severe clinical forms are rare and were not observed at all in the described group. It would therefore, seem that the prognosis is generally good, in contrast to chronic hepatitis in non-addicts.

Adolescent↗

Congenital dyserythropoietic anemia with ultrastructural features of type I and II.

The autopsy and electron microscopic findings in a pair of brothers with congenital dyserythropoietic anemia (CDA) are presented. In both patients autopsy revealed severe secondary hemochromatosis, including cirrhosis of the liver and fatal heart involvement. According to current ultrastructural criteria, a mixture of CDA type I (interchromatin bridges, wide euchromatin-cytoplasmic connections) and of type II (marginal cisternae, nuclear protrusions, multinuclearity, karyorrhexis) was found in erythroblasts of one patient. In the second patient electron microscopy of bone marrow stored in formalin for several years allowed the diagnosis of CDA with marginal cisternae in retrospect. These findings illustrate the usefulness of electron microscopy for the diagnosis of CDA in unsolved cases of chronic ineffective erythropoiesis, even from formalin fixed material. For subtyping CDA into type I and II, however, other than morphological parameters should be used for definition. In the clinical management splenectomy and a drastic phlebotomy programme have been found favourable.

Adult↗

Pattern of core and surface expression in liver tissue reflects state of specific immune response in hepatitis B.

A series of 67 liver biopsies (20 kidney transplant recipients and 47 outpatients with hepatitis) was investigated for the presence of hepatitis B antigen core (HBc) and surface (HBs) components by immunofluorescence and electron microscopy. The variable appearance of the core in liver cell nuclei and of the surface in the cytoplasm allowed the recognition of expression patterns which, together with histologic parameters, could be integrated into four reaction types of diagnostic and prognostic implications: Type I (Elimination Type). No components or only occasional expression of HBc; histologically, classic lobular hepatitis; clinically, acute, self-limited viral hepatitis. Type II (HBc Predominance, or Immunosuppression Type). Abundant core expression in each liver cell nucleus and moderate appearance of HBs; histologically, nonaggressive inflammation (nonspecific reactive or portal hepatitis); clinically, mild, chronic, persistent hepatitis in transplant patients. Type III (HBs Predominance, or Nonaggressive Type). Prominent HBs expression largely in the absence of HBc; histologically, nonaggressive inflammation (nonspecific reactive and portal hepatitis) or normal liver tissue, together with ground-glass hepatocytes in light microscopy, as a correlate of HBs-containing hepatocytes; clinically, hepatitis B antigen carrier, or chronic persistent hepatitis. Type IV (HBc+s Equivalence, or Aggressive Type). Spotty expression of both components, especially of core; histologically, periportal hepatitis; clinically, mainly corresponds to chronic aggressive hepatitis and to acute hepatitis with possible transition to chronicity. As a unifying concept for these types, it is suggested that immune responsiveness determines the reaction pattern, the key mechanism being immune elimination of affected cells. Between efficient elimination (type I) and effective immunosuppression (type II), a graded elimination insufficiency is found in chronic forms (types III and IV), explaining the persistence and probably also the aggressiveness of hepatitis B virus infection.

Acute Disease↗

[Morphological characteristics and pattern of hepatitis B antigen expression in liver tissue in acute and chronic forms of hepatitis (author's transl)].

Immunofluorescent and electron microscopic methods allow the localization of hepatitis virus B-components at the cytologic and histologic level. The acute and chronic forms of viral hepatitis are re-evaluated in the light of these new findings. In HB-Ag-positive hepatitis four types of correlation between the expression pattern of HG-Ag components and different forms of hepatitis are recognized which are of diagnostic and prognostic relevance (elimination type, immunosuppression type, aggression type, and carrier type). The correlation between antigen expression, persistence of infection and type of inflammation seems to reflect the specific immune state towards the hepatitis B virus.

Acute Disease↗

[Core and surface antigen of the Dane particle in liver tissue - relation to different forms of hepatitis B (author's transl)].

The complete Dane particle consists of two serologically and morphologically different components: Core (HBc) and Surface (HBs). HBc is located almost exclusively in the liver cell nucleus and can be demonstrated by immunofluorescence and electron microscopy, but not by light microscopy. HBs is located exclusively in the cytoplasm and can be demonstrated by immunofluorescence (IF) and, if present in excess, by electron an light microscopy (as ground-glass hepatocytes). The combined analysis with IF, electron and light microscopy of biopsy specimens taken from patients with different forms of hepatitis with and without immunosuppresive therapy allows recognition of at least four different reaction patterns: 1. Immunosuppression type (= HBc-predominance type), 2. Elimination type, 3. Aggressive type (= HBc+s equivalence type, 4. Carrier type (= HBs-predominance type). The patterns of HB-Antigen components are of prognostic value as to the clinical course of hepatitis. These findings strongly suggest that immune responsiveness determins the reaction pattern, the key mechanism being immune elimination of affected cells. In addition, these findings stress the role of the immune system in regard to the variability to the clinical course of hepatitis B, and shed light on morphological correlations.

Antibody Specificity↗