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Biomedical subjects

R Fischer

Publications and source records attributed to R Fischer.

At least 523 records · Page 29Linked to original sources
PubMed1988

TPA-inducible Epstein-Barr virus genes in Raji cells and their regulation.

A number of agents including the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) can induce an abortive virus cycle in the EBV nonproducer Burkitt's lymphoma line Raji. We describe the pattern of viral RNAs transcribed in uninduced cells and in cells treated with TPA for 8 hr, as analyzed by Northern blotting. By comparing the patterns of RNAs observed in cells treated with TPA, TPA plus cycloheximide, or cycloheximide alone, we have tested whether any EBV gene in TPA-treated Raji cells would be inducible directly by TPA in the presence of protein synthesis inhibitors, similarly to immediate-early genes induced by superinfection of Raji cells with P3HR-1 virus in the presence of cycloheximide. We demonstrate here that induction of all early EBV genes is dependent on ongoing protein synthesis. The experiments do not provide an answer to whether TPA acts by activating an initial step in the cascade of virus production or whether TPA has a simultaneous pleiotropic effect on the regulation of a large number of viral genes.

Genes, Viral↗
PubMed1988

Intravascular access in pediatric cardiac arrest.

All cases of patients aged less than 48 months who presented in cardiac arrest to the Hennepin County Medical Center's emergency department (ED) during the years 1984 to 1986 were reviewed retrospectively. The ED record, initial and subsequent chest radiographs, hospital charts, and autopsy reports were analyzed. A total of 33 cases were reviewed. The average patient age was 5 months. The average time needed to establish intravascular access was 7.9 +/- 4.2 minutes. Success rates were 77% for central venous catheterization, 81% for surgical vein cutdown, 83% for intraosseous infusion, and 17% for percutaneous peripheral catheterization. Percutaneous peripheral catheterization, when successful, and bone marrow needle placement were the fastest methods of obtaining intravascular access. There were no major immediate complications, and delayed complications were minimal. Attempts at peripheral intravenous catheter placement should be brief, with rapid progression to intraosseous infusion if peripheral attempts are not successful.

Bone Marrow↗
PubMed1988

The antimitochondrial antibody anti-M9. A marker for the diagnosis of early primary biliary cirrhosis.

The clinical relevance of a new antimitochondrial antibody, anti-M9, reacting with an outer membrane-associated antigen on liver mitochondria is described. Sera from 22 anti-M2-negative patients with histologically proven primary biliary cirrhosis (PBC) who had been followed for 5-15 years were tested for anti-M9 in the ELISA using a purified M9-fraction. 18 (82%) were anti-M9-positive, and 17 of them (94%) were in stage I/II. None of the 17 anti-M9-positive/anti-M2-negative patients with early PBC progressed to stage III/IV during the observation period of 5-15 years, and in all instances anti-M9 remained of the IgM-type. In one anti-M9-positive patient anti-M2 of the IgM type appeared 2 years after the first demonstration of anti-M9. Among 156 patients with anti-M2-positive PBC, 58 (37%) had anti-M9, and 39 of them (67%) were in stage I/II. 19 of these 39 stage I/II patients (49%) had anti-M9 exclusively of the IgM-type in contrast to none of the 19 stage III/IV patients. Using the purified M9-fraction in ELISA and Western blotting, anti-M9 antibodies were confined only to patients with PBC or overlap syndromes between PBC and autoimmune chronic active hepatitis (10% of 133 patients) and were not found in patients with other hepatic and non-hepatic disorders. We conclude that the determination of anti-M9 may be helpful for the diagnosis of early and asymptomatic PBC. From follow-up studies of anti-M9-positive but anti-M2-negative patients it emerges that this antibody type may be associated with a benign course of PBC.

Antibody Specificity↗
PubMed1988

Follow-up studies with sequential bone marrow biopsies in chronic myeloid leukaemia and so-called primary (idiopathic) osteo-myelofibrosis. Evolution of histopathological lesions and clinical course in 40 patients.

A clinicopathological follow-up study was performed on 17 patients with chronic myeloid leukaemia (CML) and 23 cases with so-called primary (idiopathic) osteo-/myelofibrosis (OMF) concentrating on a comparison between clinical data and multiple sequential biopsies of the bone marrow. Histological classification of bone marrow lesions was done according to the subtypes proposed by Georgii et al. At clinical diagnosis initial trephine biopsies in CML showed in only 6/17 cases a pronounced granulocytic proliferation or CGL. In 9/23 patients with OMF a so-called hyperplastic or early hypercellular stage was encountered with a mixed megakaryocytic-granulocytic pattern without or with minimal reticulin fibres (CMGM/EMS). The histopathology of this early stage OMF as well as the later evolving advanced fibrosclerotic lesions (AMS/OMS) were by morphological aspects alone not distinguishable from cases with CML showing prominent fibrosclerotic alterations. At presentation 5/17 patients with CML displayed already some degree of reticulin fibre formation (EMS). Following serial trephine biopsies in CML with an increased megakaryocyte proliferation (CMGM), a remarkable tendency for myelofibrosis was present. The dynamics of this fibrosclerotic transformation seem to be variable in CML and OMF likewise. However, they are related to abnormal megakaryopoiesis as well as to duration respectively progress of disease, paralleled by corresponding haematological parameters. This longitudinal case control study emphasizes that histopathology of the bone marrow taken at clinical diagnosis may reflect different stages of chronic myeloproliferative diseases and therefore should be always accompanied by relevant clinical and cytogenetic findings to enable a correct diagnosis.

Adult↗
PubMed1988

Occurrence and distribution of glycoconjugates in human tissues as detected by the Erythrina cristagalli lectin.

We applied a horseradish peroxidase-Erythrina cristagalli agglutinin (HRP-ECA) conjugate for histochemical staining of tissue sections from various formalin-fixed, paraffin-embedded human tissue specimens. The HRP-ECA conjugate showed broad reactivity, but there was a distinct distribution of native (not masked by sialic acid) and sialic acid-masked ECA binding sites in the various organs. Free ECA binding sites could be detected on red blood cells, lymphocytes of thymus, tonsil, lymph node, and in mucous substances of different organs. Independent of blood group type, the vascular endothelium exhibited strong ECA reactivity. Free ECA binding sites occurred in the cytoplasm of Kupffer's cells in liver, in histiocytic cells of thymus, lymph node, tonsil, and in bone marrow. Podocytes of kidney glomerulus, syncytiotrophoblasts of placenta, megakaryocytes in bone marrow, myelin sheath of nerve, medullary thymocytes, and hepatocytes, as well as islet cells of pancreas, contained only sialic acid-capped ECA binding sites. Inhibiting studies with galactose, lactose, and N-acetyl-lactosamine, as well as other sugars, revealed that this lectin is specific for galactosyl residues. In comparison to galactose and lactose, N-acetyl-lactosamine exhibited the highest inhibitory activity on lectin binding, supporting the concept that this lectin is most reactive with N-acetyl-lactosamine-type (type 2 chain) glycoconjugates.

Blood Vessels↗
PubMed1988

Renal oncocytoma. II. Lectin and immunohistochemical features indicating an origin from the collecting duct.

The present study is aimed to gain more insight into the histochemical properties of renal oncocytomas. Ten oncocytomas and normal kidneys were investigated using several lectins (peanut agglutinin--PNA, Dolichos biflorus agglutinin--DBA and Ulex europaeus agglutinin--UEA) and antibodies against epithelial membrane antigen (EMA), Tamm-Horsfall glycoprotein (THG) and lysozyme. Lectin histochemistry revealed a characteristic binding pattern in renal oncocytomas, with strong DBA-binding and, in some cases, a weaker staining with UEA apparent in the cytoplasm of the oncocytes. PNA binding sites were evident only after enzymatic cleavage of sialic acid by neuraminidase. Comparative evaluation of normal kidneys exhibiting a strict compartmentalization of saccharide moieties in the various nephron segments revealed a similar binding pattern exclusively in interspersed collecting duct epithelium. This striking resemblance suggests that renal oncocytomas may originate from the collecting duct system. Further support for this assumption has been provided by the demonstration of strong cytoplasmic EMA reactivity in the oncocytes. In normal kidneys prominent labeling for EMA was apparent in the very same interspersed cells of the collecting ducts. THG and lysozyme failed to react in renal oncocytomas. In accordance with observations recently reported in the literature, these results clearly favor a histogenetic origin of renal oncocytomas from the collecting duct epithelium.

Adenoma↗
PubMed1988

Renal oncocytoma. I. Cytochrome c oxidase in normal and neoplastic renal tissue as detected by immunohistochemistry--a valuable aid to distinguish oncocytomas from renal cell carcinomas.

Using a polyclonal antibody raised against bovine heart cytochrome c oxidase, the occurrence of this mitochondrial marker enzyme has been investigated in 63 kidney tumors (ten renal oncocytomas, 43 renal cell carcinomas and ten tubulopapillary adenomas) as well as in normal renal tissue by an immunoperoxidase method (PAP-technique). The differentiation between renal oncocytomas and mitochondria-rich carcinomas represents a problem of histopathology since these tumors have a different prognosis and require different patient managements. The strong immunoreactivity in renal oncocytomas contrasted with the much weaker reactivity in renal carcinomas and adenomas. Even mitochondria-rich (granular cell type) carcinomas exhibited only moderate staining intensity. Furthermore, single strongly stained oncocytes or small complexes were sometimes detected in normal renal tissue. The demonstration of marked differences in enzyme content between renal oncocytomas and granular cell carcinomas renders this method suitable for unequivocal distinction between these renal neoplasms. The antibody proved to be a valuable marker for detecting "true" oncocytic transformation in renal tumors and was useful in defining even single oncocytes or small oncocytic lesions.

Adenoma↗
PubMed1988

Endogenous as well as exogenous hormonal modulation of lectin binding sites in normal and neoplastic tissue of rat mammary gland.

Free and sialic acid conjugated binding sites for the lectin from Arachis hypogaea (peanut agglutinin, PNA) have been histochemically demonstrated in normal rat mammary tissue and in N-nitrosomethylurea (NMU) induced mammary tumors of rats. The lectin binding sites were predominantly associated with secretory activities of the normal and neoplastic breast tissue (secretory PNA binding sites). In normal breast tissue and in NMU induced mammary tumors the expression of secretory PNA binding sites was reduced after ovariectomy and by the antiestrogen tamoxifen. Estrogen stimulated the formation of free and sialic acid conjugated PNA binding sites in the presence of prolactin. In rat mammary tumors the estrogen induced formation of PNA binding sites was accompanied by an increase of the progesterone receptor concentration in the tumors. Comparative lectinhistochemical, morphological, and biochemical studies on NMU induced rat mammary tumors revealed that the expression of secretory PNA binding sites was associated with a good histologic differentiation and the presence of steroidhormone receptors. Endocrine therapeutic studies showed that tumors responding to therapy possessed higher amounts of secretory PNA binding sites than unresponsive tumors. Therefore secretory PNA binding sites represent a useful histochemical marker for hormone dependence in NMU induced mammary tumors.

Animals↗
PubMed1988

Ultrastructural morphometry on human parathyroid tissue. Morphological and functional implications.

Ultrastructural morphometry was performed on human parathyroid tissue from adenomas in chronic and acute (pernicious) hyperparathyroidism (HPT) including contralateral atrophic glands with the aim to compare the observed alterations with the corresponding clinico-functional findings. Quantitative assessment of various cell organelles, nucleus and cell perimeter revealed that significant correlations between ultrastructural features and laboratory parameters were only calculable by regarding extreme ranges of functional stages, i.e. adenomas of acute HPT (hyperparathyroid crisis) and contralateral atrophic glands. In chief cells of chronic HPT there was an inhomogeneity of measurements due to the disparate composition of the adenomatous tissue. Our results show that large complex lipid bodies and extensive accumulations of glycogen are valuable indicators of a functionally suppressed chief cell in atrophic parathyroid glands. An increased number of coated pits and vesicles is amongst other features (increase in size or number of Golgi apparatus, rough endoplasmic reticulum, mitochondria, nucleus and nucleolus as well as extension of the plasma membrane) characteristic of an endocrine stimulation.

Acute Disease↗
PubMed1988

Intestinal absorption of iron from 59Fe-labelled hexacyanoferrates(II) in piglets.

The intestinal absorption of 59Fe and 14C from hexacyanoferrates(II) was studied in piglets. KFeIII[FeII (CN)6] (I) and FeIII4[FeII(CN)6]3 (II) were labelled with 59Fe both in the Fe(III)-position (outside the complex anion, a) or in the Fe(II)-position (hexacyanoferrate anion, b). Labelling of the Fe(III)-position resulted in a 59Fe-absorption of 1.47% (Ia) and 1.34% (IIa), as judged by the 59Fe whole-body-retention measurement 14 days after oral administration. Even smaller amounts, 0.20% from Ib or 0.15% from IIb of the 59Fe-dose were absorbed and retained from the hexacyanoferrates(II) labelled in the Fe(II)-position. No 14CO2 was detected in the expired air of piglets after oral application of Fe4[59Fe(14CN)6]3, indicating that the amount of incorporated free cyanide ions can only be extremely small or even nil.

Administration, Oral↗
PubMed1988

Primary (essential) thrombocythemia versus polycythemia vera rubra. A histomorphometric analysis of bone marrow features in trephine biopsies.

A morphometric analysis of bone marrow biopsies was performed in 25 patients each with clinical diagnoses of primary (essential) thrombocythemia (PTH) and polycythemia vera rubra (P. vera) according to the rigid diagnostic criteria of the Polycythemia Vera Study Group to reveal significant differences in the histomorphologic features between these disorders. In comparison with control specimens of patients without any hematologic disease, megakaryocyte proliferation was most prominent in PTH, even exceeding that of P. vera with concomitant thrombocythemia (11 of 25 cases with a platelet count greater than 600 X 10(9)/L). Moreover, in P. vera there were wide ranges of megakaryocyte sizes, consisting of micro-megakaryocytes as well as giant forms with highly segmented nuclei (four nuclear lobes), which gave the cells a pleomorphic appearance. As compared with the normal bone marrow, the amount of neutrophilic granulopoiesis and erythropoiesis was not significantly increased in PTH, in contrast to P. vera. Similar results were obtainable regarding the density of reticulin (argyrophilic) fibers: a normal content was encountered in the control specimens and PTH, whereas P. vera displayed a minimal-to-slight increase. Finally, the bone marrow of P. vera was totally devoid of stainable iron while hemosiderin deposits were detected in about two-thirds of the patients without hematologic disorders and in PTH. The characteristic differences revealed by this morphometric study may lead to an improvement of the controversial histologic diagnosis in these disorders.

Biopsy↗
PubMed1988

Ultrastructure of megakaryocytes in the human bone marrow of patients with primary (essential) thrombocythemia.

An ultrastructural study was performed on bone marrow specimens in 10 patients (5 males/5 females, median age 53 years) with primary (essential) thrombocythemia (PTH) and an excessive elevation of the platelet count (1,625 +/- 783 x 10(9)/l). In contrast to a not severely altered neutrophilic granulo- and erythrocytopoiesis, megakaryocytes showed conspicuous large to giant forms. These were characterized by a highly lobulated nucleus containing several nucleoli and an extensive intermediate zone of the cytoplasm with many Golgi fields, numerous profiles of the so-called demarcation membrane system and an abundance of alpha-granules and some dense bodies. Our results demonstrate that ultrastructure of the megakaryocytes in PTH does not reveal gross abnormalities, but features which are compatible with an enforced thrombocytogenetic activity in accordance with the excessively elevated platelet count. Similar changes have been described in animal experiments with induced thrombocytopenia and stimulation of platelet shedding. Evaluation of thrombocytogenesis suggests that it may be mediated by a process of fragmentation with partitioning of the extensive intermediate zone into numerous prospective platelet territories followed by segregation.

Bone Marrow↗
PubMed1988

Morphometric assessment of bone marrow fiber content in acute nonlymphatic leukemia at presentation.

The number of intersections of reticulin fibers per sq mm of fat cell-free marrow parenchyma with the lines of a grid ocular (i/sq mm) represents an objective measure of the bone marrow reticulin fiber content. This method was used to assess the reticulin fiber content of bone marrow biopsies from 50 cases of acute nonlymphatic leukemia (ANLL) at presentation and 20 controls. Seventeen (34%) of the 50 patients with ANLL showed fibrosis, i.e., had a reticulin fiber score above the upper 99% confidence limit of the mean of 20 normal control biopsies. The frequencies of marrow fibrosis, as defined above, were 47% (16 of 34) in the combined subtypes of undifferentiated (M0), myeloid (M1), myelomonocytic (M4) and monocytic (M5) acute leukemia and 7% (1 of 15) in the combined subtypes of acute myeloid leukemia with partial maturation (M2) and acute promyelocytic leukemia (M3) (P less than .01). The fibrosis scores of M0/M1/M4/M5 patients were significantly higher than those of M2/M3 patients (P less than .05) and of controls (P less than .005). Finally, the survival of patients with and without fibrosis was not different.

Acute Disease↗