Immunodiscrepancy (IMDI)
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Diagnosis, Differential↗
Biomedical subjects
S Falk
Publications and source records attributed to S Falk.
Characterization of the beta 2-microglobulin endocytic pathway in rat proximal tubule cells.
The uptake mechanism(s) of low-molecular-weight proteins by proximal tubule cells remains incompletely characterized. We utilized a biochemical and semiquantitative morphological approach to better characterize the endocytic pathway of an anionic protein, beta 2-microglobulin (beta 2M), in the rat proximal tubule. Indirect immunogold techniques revealed beta 2M was taken up via a classic receptor-mediated endocytic pathway. In vitro biochemical and morphological characterization of iodinated beta 2M and gold-conjugated beta 2M (gold-beta 2M) binding to isolated brush-border membrane vesicles (BBMV) documented specific and quantitatively similar binding interactions of the modified beta 2M with BBMV. Kinetic characterization of the in vivo endocytic pathway of gold-beta 2M was undertaken using microinfusion of individual tubules. beta 2M initially bound at the apical surface, was internalized into subapical coated vesicles and delivered to endosomal-like structures within 5 min, and, finally, was concentrated in lysosomal-like structures within 15 min. This uptake was inhibited by excess unconjugated beta 2M. In addition, we directly showed that uptake did not occur across the basolateral surface. Finally, by passing solubilized BBMV over beta 2M affinity columns we were able to isolate binding activity.
Animals↗
Splenic haematopoiesis in primary (idiopathic) osteomyelofibrosis: immunohistochemical and morphometric evaluation of proliferative activity of erytro- and endoreduplicative capacity of megakaryopoiesis (PCNA- and Ki-67 staining).
Using monoclonal antibodies against proliferating cell nuclear antigen or PCNA (PC10) and the Ki-67 antigen (MIB1), an immunohistochemical and morphometric study was performed on routinely processed splenic tissue from ten patients with primary (idiopathic) osteomyelofibrosis (OMF). To determine the proliferation capacity of erythroid precursors and the endoreduplicative activity of megakaryocytes, corresponding antibodies (Ret40f and CD61) were applied in combination with the cell-cycle markers (sequential double-immunostaining). Morphometric analysis revealed no significant differences in PCNA or Ki-67 reactivity in either cell lineages. In comparison with previous studies on normal bone marrow, in splenic tissue showing myeloid metaplasia, the numbers of PCNA-labelled proerythroblasts, erythroblasts and megakaryocytes were conspicuously increased. Considering the ineffective erythropoiesis in OMF, there seemed to be a disproportional enhancement in PCNA and Ki-67 immunostaining of the red cell lineage. Similarly, the small size of megakaryocytes in advanced, OMF-associated myeloid metaplasia was in keeping with an impairment of endoreduplicative activity. In addition to various other contributory factors, anaemia in OMF may be partially caused by secondary folate (haematinic) deficiency. From experimental studies this defect is known to cause an abnormal arrest in the S-phase of the cell-cycle, comparable to that characterising pernicious anaemia. As a sequel of this pathomechanism, an undue overexpression of PCNA and Ki-67 has to be assumed, that is not necessarily associated with DNA synthesis or cell cycling.
Aged↗
Primary angiosarcoma of the spleen. A clinicopathologic study of 40 cases.
Forty primary splenic angiosarcomas occurring in 21 men and 19 women, 19-84 years old (median 59 years) are reported. Patients presented with splenomegaly (35 of 38, 92%), abdominal pain (33 of 40, 83%), and systemic symptoms such as fatigue (2 of 40, 5%), fever (4 of 40, 10%), and/or weight loss (16 of 40, 40%). Five (13%) experienced splenic rupture associated with hemoperitoneum. Abnormal laboratory findings included cytopenia (31 of 34, 91%), leukocytosis (8 of 21, 38%), and thrombocytosis (1/39, 3%). Most spleens weighed 500-1,000 g (mean, 1,180 g). The cut splenic surfaces showed multiple hemorrhagic nodules that were frequently associated with infarction, although some had a diffuse pattern of involvement. Microscopically, there were a variety of histologic patterns displayed by the vasoformative component. A honeycomb or sponge-like pattern was common in some, whereas others simulated a cavernous hemangioma or normal splenic sinuses (pseudosinusoidal pattern). Papillary endothelial tufts and solid proliferations of spindled to round to epithelioid cells were also seen. Factor VIII-related antigen was detected in 19 of 23 cases, BMA-120 in 18 of 23, UEA-1 receptor in 18 of 23, and vimentin in 23 of 23 as well as CD68 antigen in 1 of 23 cases. S-100 protein and cytokeratin were not found in any of the 23 cases studied. Metastases in 22 of 32 patients (69%) were to the liver (13 patients), bone or bone marrow (7 patients), lymph nodes (1 patient), and brain (1 patient). Three patients had concomitant malignancies and one had a prior history of a mixed B-cell lymphoma 5 years previously that had been treated with chemotherapy. Follow-up in 38 patients revealed that 30 (79%) are dead at a median interval of 6 months (range 0-48 months) and 8 are alive 5-21 months after diagnosis. These findings indicate that splenic angiosarcoma is an aggressive neoplasm with a high metastatic rate and an abysmal prognosis. Recognition of the wide range of histologic patterns is of diagnostic value but no apparent prognostic significance.
Adult↗
In vitro culture of common acute lymphoblastic leukemia blasts: effects of interleukin-3, interleukin-7, and accessory cells.
We investigated the effects of interleukin-3 (IL-3), IL-7, IL-1, and IL-6, of irradiated bone marrow-derived fibroblasts (Fb) and of in vitro matured peripheral blood macrophages (M phi), on the survival, proliferation, and maturation of purified blasts from nine common acute lymphoblastic leukemias (cALLs) in 7-day suspension culture. Exposure to IL-3, IL-7, IL-1, and IL-6 resulted in a mean 2.8-, 1.5-, 1.4-, and 1.6-fold stimulation of 3H-thymidine (3H-TdR) incorporation, respectively. Cocultures of cALL blasts with irradiated M phi, either allowing direct cell-cell contact or preventing it by membrane filters, or with irradiated Fb, resulted in a mean 31.7-, 4.1-, and 11.2-fold increase of 3H-TdR incorporation, respectively. Southern blot analysis of immunoglobulin and T-cell receptor (TCR) gene rearrangements before and after culture indicated exclusive proliferation of the leukemic clone in three of eight samples, whereas additional generation of nonleukemic cells was found in five samples. Polyclonal growth pattern corresponded to the detection of heterogeneous cell populations using FACS analysis. Survival of cALL blasts as defined by the detection of cells coexpressing both CD10 and CD19 after culture was supported by accessory cells in five of eight samples. No evidence of induced lymphoid maturation was found under any culture condition. Our data demonstrate supportive effects of stromal cells on cALL growth, which cannot be replaced by IL-3 or IL-7.
Blotting, Southern↗
[Spontaneous splenic rupture in acute malaria tropica].
A 44-year-old man developed bouts of fever (up to 40 degrees C) seven days after returning from a holiday in Kenya. Malaria prophylaxis with chloroquine had been correctly undertaken. Concentrations of lactate dehydrogenase and total bilirubin were raised (493 U/l and 3.55 mg/dl, respectively). Blood smear revealed the ring forms of Plasmodium falciparum. Thereupon the patient was given mefloquine in decreasing doses (750/500/250 mg) at intervals of 8 hours. The following night he had a circulatory collapse and complained of pain on pressure, especially in the left upper abdomen. Abdominal sonography showed a slightly enlarged spherical spleen with an echo-poor band and fluid collection in the rectovesicular pouch, indicating rupture of the spleen. A splenectomy was performed. Subsequently the number of malaria organisms in the blood smear gradually fell and signs of haemolysis disappeared. Splenic rupture is a very rare complication of acute malaria. It is presumably caused by marked stasis in the splenic sinuses with deformed parasite-containing red blood cells.
Acute Disease↗
Primary large cell lymphoma of the splenic sinuses: a variant of angiotropic B-cell lymphoma (neoplastic angioendotheliomatosis)?
A case of large cell lymphoma of B-cell lineage originating in the splenic sinuses is described. In addition to widening the spectrum of primary malignant lymphomas of the spleen, this case raises the possibility that variants of angiotropic large cell lymphomas may exist that do not involve blood vessels but do involve the spleen and lymph node sinuses.
Aged↗
Photosynthetic Light Utilization Efficiency, Photosystem II Heterogeneity, and Fluorescence Quenching in Chlamydomonas reinhardtii during the Induction of the CO(2)-Concentrating Mechanism.
The photosynthetic light-response curve, the relative amounts of the different photosystem II (PSII) units, and fluorescence quenching were altered in an adaptive manner when CO(2)-enriched wild-type Chlamydomonas reinhardtii cells were transferred to low levels of CO(2). This treatment is known to result in the induction of an energy-dependent CO(2)-concentrating mechanism (CCM) that increases the internal inorganic carbon concentration and thus the photosynthetic CO(2) utilization efficiency. After 3 to 6 h of low inorganic carbon treatment, several changes in the photosynthetic energy-transducing reactions appeared and proceeded for about 12 h. After this time, the fluorescence parameter variable/maximal fluorescence yield and the amounts of both PSIIalpha and PSIIbeta (secondary quinone electron acceptor of PSII-reducing) centers had decreased, whereas the amount of PSIIbeta (secondary quinone electron acceptor of PSII-nonreducing) centers had increased. The yield of noncyclic electron transport also decreased during the induction of the CCM, whereas both photochemical and nonphotochemical quenching of PSII fluorescence increased. Concurrent with these changes, the photosynthetic light-utilization efficiency also decreased significantly, largely attributed to a decline in the curvature parameter theta, the convexity of the photosynthetic light-response curve. Thus, it is concluded that the increased CO(2) utilization efficiency in algal cells possessing the CCM is maintained at the cost of a reduced light utilization efficiency, most probably due to the reduced energy flow through PSII.
Journal Article↗
Myelokathexis treated with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF).
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Adult↗
Splenic megakaryocytopoiesis in primary (idiopathic) osteomyelofibrosis. An immunohistological and morphometric study with comparison of corresponding bone marrow features.
An immunohistochemical and morphometric study has been performed on splenic tissue of 10 patients with primary (idiopathic) osteomyelofibrosis (OMF) to determine characteristic features of megakaryocytopoiesis in myeloid metaplasia. Using the periodic acid-Schiff reaction (PAS) and particularly the monoclonal antibody CD61 (Y2/51), all elements of this cell lineage including precursors could be identified. In comparison with bone marrow specimens from our file material (40 patients with OMF, 15 control cases) which were processed in a similar way, megakaryocytes in the spleen revealed significant differences. These differences included smaller cell sizes, a disturbed nuclear-cytoplasmic ratio, and a conspicuous increase in the relative frequency of promegakaryoblasts. In conclusion, extramedullary megakaryocytopoiesis in OMF did not only show more pronounced abnormalities of differentiation, but also a higher degree of immaturity. Our finding of a significant accumulation of megakaryocytic precursors in the spleen as opposed to the bone marrow, corroborates the so-called filtration theory which has been introduced to explain the evolution of splenic myeloid metaplasia in OMF.
Aged↗
Concomitant primary low grade non-Hodgkin's lymphoma of the spleen and breast carcinoma.
A case is described of a 71 year old woman with scirrhous breast cancer and multiple hypoechogenic lesions in the spleen. The patient was treated successfully by mastectomy and splenectomy. Morphologic examination of the spleen showed a primary, centroblastic-centrocytic, low grade non-Hodgkin's lymphoma. Eight months after splenectomy the patient still remains in complete remission.
Aged↗
[Malignant lymphomas in spleen--morphology and microenvironment].
The different entities of malignant lymphomas in the spleen exhibit characteristic stage-dependent infiltration patterns which, in conjunction with cytologic findings, may be employed for diagnostic purposes. These infiltration patterns result from complex interactions between neoplastic and non-neoplastic splenic cell populations which are only incompletely understood. These interactions are governed by intrinsic properties of the involved cell populations, e.g. surface receptors, proliferation activity, cytokine production, immunocompetence etc., as well as by extrinsic factors, e.g. splenic microanatomy and the behavior of splenic immunocompetent and accessory cells which are responsible for the highly organized splenic microenvironments.
Diagnosis, Differential↗
[In-vitro activity pattern of gallbladder muscle tissues in patients with and without gallstones--variable response to cholecystokinin, motilin and neurotensin].
Data about gallbladder motility in stone disease and stone free conditions are discussed controversially. This study is aimed at to evaluate in vitro the responses of human gallbladder muscle stripes to cholecystokinin, motilin and neurotensin. Following the results, a stratification of the "stone-disease-group" seems to be necessary: 41% of the gallbladders (stone disease) demonstrate a deep reduction in contractility to cholecystokinin ("non-contractors"), whereas 59% of the gallbladders contract in the same pattern like the controls ("contractors"). Interestingly, the majority of the gallbladders in the "contractor" group demonstrate a high spontaneous activity which is absent in stone free gallbladders. Motilin and neurotensin either do not induce any effect.
Adult↗
[Local immune reactions in carcinoma in situ and cervix cancer--a histologic and immunohistochemical study].
50 conisation or hysterectomy specimens with different degrees of cervical intraepithelial neoplasia (CIN), carcinoma in situ (CiS) or invasive carcinoma, as well as controls, were studied by conventional histological methods as well as by immunohistochemistry. In CIN I and II there is a significant reduction of T lymphocytes, macrophages and T accessory cells, whereby CIN III, CiS and invasive carcinoma show a noticeable increase in the number of immunocompetent cells. The depletion of immunocompetent cells in CIN probably represent a local immunodeficiency state which permits progression of HPV-associated CIN, whilst the marked increase of accessory and effector cells in the stroma of high grade CIN and invasive carcinoma does not appear to exert control over the neoplastic cells, due to an ineffective tumour-specific activation.
Adult↗
Chronic recurrent appendicitis. A clinicopathologic study of 47 cases.
As part of a retrospective study 47 appendices from patients with a clinical and morphologic diagnosis of chronic recurrent appendicitis were studied by morphologic and immunohistochemical methods. Appendices with chronic recurrent appendicitis histologically show chronic active inflammation with increased numbers of immunocompetent cells, mostly T lymphocytes and subsequent scarring. In addition, there is an increase in the number of neural cells. Apparently the secretion of neurotropic inflammatory mediators, especially by activated and degranulating eosinophils, leads to a stimulation of nociceptive receptors and thus to the clinical symptoms. The diagnosis of recurrent chronic appendicitis is thus warranted in these cases not only clinically but also on the basis of histologic and immunohistochemical findings.
Adolescent↗
Bone marrow findings after treatment with recombinant human interleukin-3.
In a phase I/II study, bone marrow biopsy specimens and aspirates of 20 patients with malignant tumors but normal bone marrow (n = 6), bone marrow failure resulting from chemotherapy (n = 4), myelodysplastic syndrome (n = 5), and aplastic anemia (n = 5) were evaluated before and after patients were treated with recombinant human interleukin-3 (rhIL-3). This cytokine proved to be an effective hematopoietic growth factor with only mild side effects. The rhIL-3 treatment led to increased overall bone marrow cellularity with trilinear stimulation of hematopoietic cells, except in most patients with aplastic anemia. In all patients, significant eosinophilia and, in some instances, bone marrow fibrosis developed. In addition to the increase in the number of circulating neutrophilic granulocytes, platelets, and reticulocytes, an increase of peripheral blood monocytes and lymphocytes was observed. The histologic and cytologic findings support the concept that rhIL-3 stimulates the proliferation and differentiation of pluripotent hematopoietic progenitor cells. It appears to be a safe and efficient therapeutic modality in patients with bone marrow failure. Additional clinical studies are needed to determine which patients will profit most from rhIL-3 treatment.
Adult↗
Hodgkin's disease and sinus histiocytosis with massive lymphadenopathy-like changes.
Sinus histiocytosis with massive lymphadenopathy (SHML) is a disorder of unknown origin which is only infrequently associated with lymphoid neoplasms. We report the first two cases of Hodgkin's disease with simultaneous SHML-like changes in the same lymph node.
Adult↗
[Morphology of pulmonary complications in AIDS--a study of 208 biopsy and 231 autopsy cases].
In AIDS patients infectious pulmonary complications may very frequently be demonstrated by both biopsy and autopsy. Bacterial pneumonias occur much more frequently than classic opportunistic infections, e.g. P. carinii pneumonia. Usually, several complications are present concomitantly which impairs diagnosis as well as therapy. Increased survival and modern therapeutic modalities change the spectrum of AIDS-associated pulmonary complications as well as their morphology. In the present study pulmonary complications are directly responsible for the patients' death in more than 70% of the cases.
Acquired Immunodeficiency Syndrome↗