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Biomedical subjects

G Karkavelas

Publications and source records attributed to G Karkavelas.

31 records · Page 2Linked to original sources

Sudden death due to cardiac myxoma.

Primary tumours of the heart are rare, their incidence ranging from 0.0017 to 0.28 per cent in various autopsy series (Colucci and Braunwald, 1992). Thirty per cent of these tumours are cardiac myxomas (McAllister and Fenaglio, 1978). The latter are histologically benign but potentially lethal. Sudden death is reported in 15 per cent of cases and is mainly attributed to massive embolism or mechanical interference to blood flow within the heart by the tumour (Fisher, 1983). This incidence could be due to the absence of clinical manifestations of the disease or to the presence of non-specific or subtle ones that preclude early referral for specialist evaluation (Colucci and Braunwald, 1992). Such a poor prognosis is not altogether justified, however, considering the highly sensitive and accurate diagnostic techniques and the level of surgical treatment which can be offered today (Larsson et al., 1989; Roberts, 1989; Bortolloti et al., 1990; Lyons et al., 1991). We present a case diagnosed at post-mortem of an atrial myxoma which had subtle ante-mortem manifestations. This paper should alert the clinician with regard to the need to be aware of the rather obscure clinical presentation which may accompany this potentially treatable condition.

Adolescent↗

Increased capillary endothelial leakage in portal hypertensive gastric mucosa: fluorescence microscopy in CCl4-induced cirrhotic rats.

Since portal hypertension affects the gastric mucosa, leading to congestive gastropathy and thus to increased incidence of bleeding, it is one of the possible causes of increased permeability of gastric mucosal capillaries. The aim of this study was the quantitative assessment of the permeability of the gastric mucosal endothelial cells. Eight CCl4-induced cirrhotic rats and eight matched controls were subjected to i.v. injection of FITC-albumin, and a morphometric evaluation of fluorescence in serial histological sections of the gastric mucosa was performed by a video image analysis system. Fluorescence was found to be 0.351 +/- 0.01% of the area scanned in experimental animals versus 0.073 +/- 0.005% in controls, i.e. it was significantly increased by the treatment, which implies a significant endothelial leakage into the extravascular space.

Albumins↗

Localization of the neuronal class III beta-tubulin isotype in foci of early neuritogenesis supports divergent neuroblastic differentiation potential in Wilms' tumors.

Wilms' tumors are embryonic neoplasms that have been proposed to originate from the metanephric blastema and are capable of divergent epithelial and mesenchymal differentiation. Neuroepithelial differentiation in these tumors remains controversial. The aim of this study was to examine the phenotypic profile of certain neuronal and glial antigenic determinants in a series of 21 Wilms' tumors. Immunohistochemical studies were performed by using monoclonal antibodies against the neuronal class III beta-tubulin isotype (beta III), the phosphorylated and phosphorylation-independent epitopes of neurofilament protein, and synaptophysin; antisera to gamma-enolase (neuron-specific enolase) glial fibrillary acidic protein, and S100 protein were also used. Foci of neoplastic cells with neurite-like processes that exhibited intense beta III staining were demonstrated in blastemalike areas of three of 21 tumors. In one case, Homer Wright rosettes (stained for beta III) were identified. Areas of abortive neuritic development were also labeled with antibodies to gamma-enolase. No reactivity was obtained in these foci for phosphorylated and phosphorylation-independent epitopes of neurofilament protein, synaptophysin, glial fibrillary acidic protein, and S100 protein. The remainder of the tumors (18 of 21) were negative with the panel of neural markers. Our results indicate that divergent neuroblastic differentiation, evidenced as early neoplastic neuritogenesis, may be present in the blastematous component of Wilms' tumor subsets.

Antibodies, Monoclonal↗

Effects of tamoxifen and CV 205502 on the morphology and the evolution of the noncancerous mouse mammary gland.

Tamoxifen (TAM, 0.01 mg/animal, three times a week) and the experimental prolactin-lowering CV 205502 (CV, 1 microgram/animal, daily) were administered prophylactically, alone or combined, to virgin C3H/Sy mice during the early period of promotion in this spontaneous mammary carcinogenesis system (end of 2nd-5th month of age), in order to study their influence on the morphology and evolution of the noncancerous mammary gland during therapy and after treatment cessation. During TAM administration the epithelial cells of the growing part of the gland exhibited myoepithelial- and, late in the treatment period, apoptotic-like features instead of the secretory ones expected, accompanied by intense basement membrane alterations, thickening of the surrounding connective tissue and arrested adipocyte maturation. These effects reversed progressively after drug withdrawal. The epithelial alterations were more intense and longer lasting in the TAM+CV-group, while growth arrest of the glands was observed in both groups parallel to the degree and the duration of these morphological changes. In these groups, tumor incidence was diminished, as expected, but the tumors that developed late after treatment cessation were of low histological differentiation. The above morphological observations show that TAM inhibits noncancerous mammary gland growth during the reproductive period by altering stromal and epithelial differentiation, effects that reverse progressively after treatment discontinuation and are potentiated by a prolactin-lowering agent in this animal study.

Adipocytes↗

Comparative ultrastructural localization of collagen types III, IV, VI and laminin in rat uterus and kidney.

Antibodies against collagen types III and VI have been localized by electron immunohistochemistry with two different techniques in normal rat uterus and kidney. Antibodies directed against two components of the extracellular matrix with known localization, laminin and type IV collagen, were used as controls for the specificity of the localization. The results demonstrate that types III and VI are found in the interstitium as fine (10- to 15-nm), beaded fibrils and filaments (6- to 10-nm), respectively. Both are often found associated with thick, crossbanded type I collagen fibers (30- to 35-nm) and occasionally associated with some basement membranes adjacent to the interstitium. Further, the findings suggest that collagens III and VI may connect the various components of the extracellular matrix, such as type I fibers with basement membranes and other structures, thus forming an integrated functional unit.

Animals↗

Disseminated strongyloidiasis with uncommon manifestations in Greece.

Strongyloidiasis is a human intestinal parasitosis caused by the nematode Strongyloides stercoralis. In most cases the infection is subclinical, but rarely, disseminated strongyloidiasis may occur in debilitated or immunocompromised patients, and in those who receive immunosuppressive agents. In this report, we describe an unusual case of severe disseminated strongyloidiasis, with intestinal, pulmonary and neurological manifestations, in a previously healthy male. The onset of the disease was acute with headache and neck stiffness, due to subarachnoid-ventricular haemorrhage. During a protracted clinical course the patient developed diarrhoea, abdominal pain, recurrent paralytic ileus, pneumonitis and respiratory distress, malabsorption and weight loss, diagnosis was delayed due to the complicated course and rarity of the disease. The diagnosis finally established during evaluation for malabsorption by demonstrating larvae of S. stercoralis in the jejunal mucosal biopsy and faeces. Response to mebendazole treatment was prompt with complete recovery and resolution of all systemic manifestations. Early diagnosis and treatment of strongyloidiasis in the intestinal phase is critical in the prevention of dissemination, which may prove lethal due to life-threatening complications.

Adult↗

The significance of the posterior cruciate ligament in the stability of the knee. An experimental study in dogs.

The significance of the posterior cruciate ligament in the stability of the knee was investigated in dogs and it was compared with that of the anterior cruciate ligament by studying the changes produced in the knee after transection of either ligament. Osteophyte formation and changes in articular cartilage were less prominent after division of the posterior cruciate ligament. A complete longitudinal tear of the medial meniscus was found in eight out of the 10 dogs who had undergone section of the anterior cruciate but in none of the 10 with section of the posterior cruciate. It appears that, in dogs at least, the posterior cruciate ligament is less important than the anterior in the stability of the knee.

Animals↗

Malakoplakia of the larynx.

The first case of malakoplakia of the larynx in the world literature is reported. The soft raised plaques were removed from a 61-year-old white male, who was a heavy smoker and complained of hoarseness, but was otherwise in good general condition. From the follow-up of our patient, it is concluded that malakoplakia is not of particularly bad prognosis when affecting the larynx, and that simple local excision seems to be enough to produce cure. On these grounds, the laryngologists should be aware of the entity and consider it when dealing with raised nodules or plaques in the larynx, while the pathologists should be alert to look for the Michaelis-Gutman bodies, when encountered with peculiar histiocytic reactions anywhere in the body, even in the larynx.

Hoarseness↗

A cytomorphological scheme of differentiating neuronal phenotypes in cerebellar medulloblastomas based on immunolocalization of class III beta-tubulin isotype (beta III) and proliferating cell nuclear antigen (PCNA)/cyclin.

This immunohistochemical study compares the localization of the neuronal class III beta-tubulin isotype (beta III) to that of the proliferating cell nuclear antigen (PCNA)/cyclin in 46 cerebellar neuroblastic tumors (medulloblastomas). Both class III beta-tubulin (beta III) and PCNA/cyclin reactivities were present in all tumors, but the topographic distribution and cytomorphologic features of stained cells varied considerably between classic and desmoplastic medulloblastomas. Four neoplastic phenotypes, representing gradations of neuronal differentiation, were identified: [Allegranza 1991] apolar, blast-like PCNA/cyclin(+) cells devoid of beta III reactivity (Nb1); [Bravo et al. 1987] apolar, often binucleated and/or fusiform, PCNA/cyclin (+) cells with pronounced beta III staining in their protoperikarya and their growth cones (Nb2); [Burger et al. 1987] beta III-immunoreactive immature polar neurons with varying degrees of neuritic development, reading to significant neuritogenesis in the "pale islands" of desmoplastic medulloblastomas (Nb3). The majority of Nb3 phenotypes were PCNA/cyclin (-), although subpopulations of such polar tumor cells exhibiting PCNA staining were also identified; and [Burger et al. 1991] beta III-immunoreactive, PCNA/cyclin (-) mature ganglion-like cells (Nb4). A high PCNA/cyclin labeling index (> 80%) was obtained in 20 poorly differentiated classic medulloblastomas while, significant intratumoral staining heterogeneity was observed in 23 cases of desmoplastic medulloblastomas and 3 cases of "medulloblastomas with ganglion cells": A high labeling index (LI)(> 80%) in the reticulin-impregnated poorly differentiated areas of tumor contrasted with sharp decline of PCNA staining and a very low LI (< 10%) in areas of overt neoplastic neuritogenesis ("pale islands") displaying strong beta III reactivity. Neoplastic ganglion cells were beta III (+)/PCNA (-). Our findings indicate that the majority of differentiating neuronal phenotypes undergoing cytomorphological changes of neuritic development (Nb3), and all neoplastic ganglion cells (Nb4 phenotypes) are PCNA (-), in contrast to actively proliferating, poorly differentiated, tumor cells that are PCNA (+). Although PCNA staining corresponded in part, to beta III (-) blast-like elements (Nb1), a co-expressive pattern of staining for beta III and PCNA/cyclin also was observed in subpopulations of poorly differentiated tumor cells (Nb2), indicating that transformed neuroblasts are capable of expressing differentiation-associated neuronal cytoskeletal proteins while still remaining in the proliferative compartment of the cell cycle. Our observations suggest that only neuritogenesis and acquisition of ganglionic phenotype are significant maturational events in medulloblastomas (indicating entry into the quiescent phase of the cell cycle) and provide further support for the neuronal lineage and differentiation potential of these cerebellar embryonal tumors.

Adolescent↗

Immunohistochemical phenotyping and PCNA detection in gastrointestinal stromal tumors.

The immunohistochemical profile and the expression of proliferating cell nuclear antigen (PCNA) were studied in a series of 44 mesenchymal tumors of the gastrointestinal tract (GIT). On routinely hematoxylin-eosin stained sections 31 cases were classified as leiomyomas or leiomyomatoid tumors, 12 as leiomyosarcomas and 1 as a neurilemmoma. Immunohistochemical stains for smooth muscle antigen (SMA), S-100 protein, glial fibrillary acidic protein (GFAP), vimentin and desmin were performed with the peroxidase-antiperoxidase method on paraffin sections. The streptavidin-biotin method for PCNA immunostaining was applied using the monoclonal antibody PC 10. On the basis of immunohistochemical findings, 32 cases were identified as leiomyomatoid tumors or leiomyosarcomas (SMA positive, S-100 protein negative), 2 cases as nerve sheath tumors (SMA negative, S-100 protein and GFAP positive), whereas 8 cases presented a mixed phenotype (SMA positive and S-100 protein positive). Two cases were negative for both SMA and S-100 protein. All tumors showed positive immunostaining for vimentin and a negative one for desmin. There was a correlation between the histologic grade and proliferating score, displayed by PCNA expression in tumors of smooth muscle origin. The PCNA expression in tumors of mixed phenotype was intermediate to that seen in leiomyosarcomas (high expression) and in leiomyomas (low expression).

Antibodies, Monoclonal↗

Correlation of proliferating cell nuclear antigen assessment, histologic parameters and age with survival in patients with glioblastoma multiforme.

A series of 27 glioblastomas multiforme were studied to compare the prognostic value of age and histologic parameters known to influence survival with that of proliferating cell nuclear antigen (PCNA). The labelling index (LI) of PCNA has been found in previous studies to correlate well with flow cytometry, tritiated thymidine, bromodeoxyuridine incorporation and Ki 67. The histologic parameters estimated were endothelial proliferation, number of mitoses per high power field, cellularity and a grading of necroses. The correlation coefficients between survival and each of the histologic parameters as well as with age were found to be negative but statistically insignificant. The values of these correlations in descending order were survival/age (r = -0.22), survival/endothelial proliferation (r = -0.20), survival/mitoses (r = -0.16), survival/cellularity (r = -0.07) and survival/necroses (r = -0.04). The correlation coefficient between survival and PCNA LI was also found to be negative, higher than those between survival and other estimated parameters (r = -0.37) but in a wide variation and still statistically insignificant. Despite this variation, our finding that for PCNA LI > 35% no patient survived more than 6 months may be of clinical importance.

Adult↗

Lobar pilocytic astrocytomas of the cerebral hemispheres: II. Pathobiology--morphogenesis of the eosinophilic granular bodies.

This study provides new immunocytochemical observations on the so-called eosinophilic granular bodies (EGBs), seen predominantly (but not exclusively) in pilocytic astrocytomas. Using combined immunohistochemical and immunoelectron microscopic approaches on formalin-fixed, paraffin-embedded tissues, we have demonstrated that (1) EGBs exhibit pronounced reactivity with antibodies to serine protease inhibitors alpha-1-antichymotrypsin and alpha-1-antitrypsin; by immunoelectron microscopy, the reaction product is localized either in the form of diffuse floccular densities, or larger conglomerates of amorphous, globular material; (2) an antiserum to ubiquitin-protein conjugates, codistributes in the EGBs at the light microscopic level, while ultrastructurally is either localized in diffuse, finely granular deposits, and/or fragmented filamentous particles; and (3) that a monoclonal antibody to beta-amyloid precursor protein (beta-APP) stains smaller EGBs. The detection of serpin-like and beta-APP-like staining in EGBs may be a reflection of acute phase reactant activity in response to tumor-produced proteases. We postulate that EGBs contain complexes of serpins and hitherto unknown protease(s), which are in turn probably degraded via ubiquitin mediated mechanism(s). Although EGBs typify pilocytic astrocytomas, they may be exceptionally present in malignant astrocytomas, calling for cautious interpretation of their biologic as well as prognostic import.

Adolescent↗

The stromal Schwann cell during maturation of peripheral neuroblastomas. Immunohistochemical observations with antibodies to the neuronal class III beta-tubulin isotype (beta III) and S-100 protein.

This immunohistochemical study compares the localization of the neuronal class III beta-tubulin isotype (beta III; analogous to the beta' 1-/beta 2-tubulin isoform) to the Schwann cell-associated S-100 protein focusing on topographic relationships of Schwann-like cells to differentiating neuronal phenotypes during stromal development in human peripheral neuroblastomas. The earliest appearance of Schwann cells in poorly differentiated (classical) neuroblastomas is heralded by S-100 protein-immunoreactive cells in close association with tumor blood vessels. In subsequent stages of maturation, i.e. maturing neuroblastoma (ganglioneuroblastoma and gangliocytoma), S-100 protein-positive cells are mostly confined to the connective tissue septa dividing tumor into lobules, and are not freely interspersed with beta III-immunoreactive neoplastic neurons. Significant ensheathment of individual axon-like processes by Schwann cells occurs only in mature ganglioneuromas. beta III is localized in a full spectrum of neoplastic neuronal phenotypes, ranging from poorly-differentiated apolar neuroblasts (often signaling ensuing neuritogenesis) to mature ganglion cells, but not in Schwann cells, or other cell types of the stroma. Our observations suggest that Schwann cells in peripheral neuroblastomas are stroma-derived cells and not an expression of divergent neoplastic differentiation.

Adolescent↗