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J A Laissue

Publications and source records attributed to J A Laissue.

At least 37 records · Page 2Linked to original sources
PubMed1999

Oncocytic (Hürthle cell) tumors of the thyroid: distinct growth patterns comparedẁith clinicopathological features.

Neoplastic growth results from cell production that exceeds cell loss. We registered mitotic and apoptotic indices (MI and AI) in 97 immunohistochemically verified oncocytic (Hürthle cell) tumors of the thyroid (OT; 50 adenomas [OA], 20 atypical adenomas [aOA], and 27 carcinomas [OC]) and compared these kinetic data with histological diagnoses and other parameters. MI, although very low in all, was significantly higher in carcinomas than in adenomas. Conversely, AI did not differ as much among the 3 groups. This indicates that the magnitude of cell deletion did not play a prominent role in determining the disparate growth of the 3 types of oncocytic tumors. Cluster analysis with MI and AI per case as variables revealed the existence of 3 groups of neoplasms with highly distinct growth characteristics: (1) near-steady state (n = 78, all diagnostic categories represented); (2) progressive (n = 9, mostly carcinomas); and (3) regressive (n = 10, mostly adenomas). MI distinguished between histologically benign and malignant with the greatest discriminant power of the variables tested. Proliferative indices should thus be included in the differential diagnostic evaluation of oncocytic thyroid tumors. Our study also suggests that invasiveness and growth are 2 diverging properties of carcinomas.

Adenoma↗
PubMed1999

BCA-1 is highly expressed in Helicobacter pylori-induced mucosa-associated lymphoid tissue and gastric lymphoma.

Infection with Helicobacter pylori (Hp) induces the formation of lymphoid tissue in the stomach and the occasional development of primary gastric B-cell lymphomas. We have studied the expression of 2 chemokines that attract B lymphocytes, BCA-1 and SLC, in gastric tissue samples obtained from patients with chronic gastritis induced by Hp infection or nonsteroidal anti-inflammatory drugs, as well as from patients with Hp-associated low-grade and high-grade gastric lymphomas. High-level expression of BCA-1 and its receptor, CXCR5, was observed in all mucosal lymphoid aggregates and in the mantle zone of all secondary lymphoid follicles in Hp-induced gastric mucosa-associated lymphoid tissue (MALT). Follicular dendritic cells and B lymphocytes are possible sources of BCA-1, which is not expressed by T lymphocytes, macrophages, or CD1a(+) dendritic cells. Strong expression of BCA-1 and CXCR5 was also detected in the transformed B cells of gastric MALT lymphomas. By contrast, SLC was confined almost exclusively to endothelial cells in and outside the lymphoid tissue. Only scant, occasional SLC expression was observed in the marginal zone of MALT follicles. Our findings indicate that BCA-1, which functions as a homing chemokine in normal lymphoid tissue, is induced in chronic Hp gastritis and is involved in the formation of lymphoid follicles and gastric lymphomas of the MALT type.

Aged↗
PubMed1999

Immunohistochemical detection of somatostatin sst2a receptors in the lymphatic, smooth muscular, and peripheral nervous systems of the human gastrointestinal tract: facts and artifacts.

The cellular distribution of the somatostatin sst2A receptor protein was investigated in the lymphatic, smooth muscular, and nervous components of the human gastrointestinal tract using subtype-specific antibody R2-88 for immunohistochemical staining of cryostat and formalin-fixed, paraffin-embedded tissue sections. Germinal centers of intestinal lymphatic follicles were immunostained, exhibiting a predominantly plasma membrane localization of the receptor. Similarly, nerve fibers and cells in the submucosal and myenteric plexus were stained for sst2A. Antibody preabsorption with 100 nmol/L antigen peptide abolished staining in all of these tissues, and immunohistochemical staining correlated with the labeling observed after receptor autoradiography using the sst2-preferring radioligand 125I-[Tyr3]octreotide. Cytoplasmic immunostaining was detected in gastrointestinal smooth muscle cells and was inhibited by antibody pre-absorption with antigen peptide. However, 125I-[Tyr3]octreotide autoradiography was negative, and Western blots showed no band at the usual 70-90 kDa location for sst2A. Instead, a band was observed at 205 kDa. This band comigrated with the rabbit myosin standard, which was also stained with R2-88, although antibody sensitivity for myosin was less than 0.002% of that for the sst2A receptor. Rigorous computer-based sequence analysis demonstrated the peptide sequence chosen for antibody production was unique. Moreover, standard sequence alignment protocols were unable to identify the sequences in myosin responsible for the observed reactivity with the R2-88 antiserum. The observed cross-reactivity emphasizes the need for extensive controls to prove the specificity of immunostaining for such low abundance proteins as receptors even when the peptide sequence chosen for antibody production is unique. This study demonstrates for the first time the presence of specific sst2A receptor protein by immunohistochemistry in the human gastrointestinal lymphatic and nervous components, but not in gastrointestinal circular and longitudinal smooth muscle.

Animals↗
PubMed1999

Death receptor-mediated suicide: a novel target of autoimmune disease treatment.

In the thymus, based on the reactivity of their T-cell receptor with self-MHC and antigenic peptides, developing immature T-cells undergo positive and negative selection. Cells recognising self-peptides and MHC with high affinity are considered autoreactive, and thus potentially harmful, and are eliminated by induction of apoptotic cell death. Thymic negative selection is, however, only incomplete and autoreactive T-cells escape into the periphery. It is not the presence of autoreactive mature T- and B-lymphocytes as the underlying cause of tissue destruction and development of autoimmune diseases, but their uncontrolled and excessive clonal expansion upon activation by self-antigen. Thus, potent regulatory mechanisms must keep these autoreactive cells under control to avoid their inappropriate activation. Recent evidence indicates that death receptors of the tumour necrosis factor receptor family play a central role in mediating antigen receptor-induced suicide of autoreactive T-lymphocytes. Defects in these apoptosis-inducing regulatory mechanisms may result in the development of autoimmune diseases. Therefore, enhancing the cell's own suicide program, offers a most attractive therapeutic target for the treatment of autoimmune diseases.

Journal Article↗
PubMed1999

T-cell-rich B-cell non-Hodgkin's lymphoma mimicking Hodgkin's disease.

We report on a patient with recurrent T-cell-rich B-cell lymphoma (TCRBCL), initially misdiagnosed as a lymphocyte-rich Hodgkin's disease. This case exemplifies the diagnostic problems of TCRBCL and the need for immunophenotypic analysis to differentiate TCRBCL from Hodgkin's disease, nodular paragranuloma and peripheral T-cell lymphoma. A rather unusual aspect is the long disease-free interval between the excision of the node in and the late relapse in 1996. The significance of the abundant T-cell infiltration in this B-cell neoplasm will be discussed and the concepts concerning antitumor response will be reviewed. Based on epidemiological data and the clinical behaviour TCRBCL does not seem to represent a distinctive pathological entity.

Adult↗
PubMed1998

Neuropathology of ablation of rat gliosarcomas and contiguous brain tissues using a microplanar beam of synchrotron-wiggler-generated X rays.

Adult-rat-brain tissues display an unusually high resistance to necrosis when serially irradiated with parallel, thin slices of a microplanar (i.e., microscopically thin and macroscopically broad) beam of synchrotron-wiggler-generated, approx. 35-120 keV (median approx. 50 keV) Gd-filtered X rays at skin-entrance absorbed doses of 312 to 5000 Gy per slice. Such microplanar beams were used to irradiate young adult rats bearing right frontocerebral 9L gliosarcomas (approx. 4 mm diameter), through a volume of tissue containing the tumor and contiguous brain tissue, either in a single array or in 2 orthogonally crossed arrays of tissue slices. Each array included 101 parallel microplanar slices, 100 microm center-to-center distance, each slice being approx. 25 microm wide and 12 mm high, with skin-entrance absorbed doses of 312.5 Gy or 625 Gy per slice. Compared with unirradiated controls with a median survival time of 20 days after tumor initiation, the median survival time was extended in irradiated rats by 139 days (625 Gy, crossed arrays), 96 days (312 Gy, crossed arrays) or 24 days (625 Gy, single array). The tumors disappeared in 22 of the 36 irradiated rats, 4/11 even after unidirectional microbeam irradiation. The extent and severity of radiation damage to the normal brain in rats with or without tumor was graded histopathologically. Correlation of those grades with radiation doses shows that loss of tissue structure was confined to beam-crossing regions and that only minor damage was done to zones of the brain irradiated unidirectionally.

Animals↗
PubMed1998

Cellular kinetic differences between Hodgkin's and anaplastic large cell lymphomas: relation to the expression of p34cdc2 and cyclin B-1.

Our study was designed to compare cellular kinetic parameters of classical Hodgkin's disease (HD) with those of anaplastic large cell lymphomas (ALCL-C, common type; and ALCL-HL, Hodgkin's like), with a particular focus on the G2/M transition. These disorders share some phenotypic properties, e.g., CD30 positivity of putative neoplastic cells. The percentages of cells expressing p34cdc2 (p34) and cyclin B-1 (cyclin-B), which form a complex (maturation/mitosis promoting factor, MPF) regulating the G2-M phases of the cell cycle, were also registered. Highly significant differences between HD and ALCL-C were recognized: a) in HD, evidence for abortive mitosis (i.e., difficulty to proceed beyond the metaphase stage) and consequent multinucleation and/or deletion of CD30+ cells was prominent, in contrast to ALCL-C. This was associated with a markedly lower fraction of large atypical cells (LAC) expressing cyclin-B in the cytoplasm and the nucleus (C + N) in HD than in ALCL-C; b) the extent of multinucleation of CD30+ cells in HD, but not in ALCL-C, was correlated with the %p34+ LAC; c) the proportions of LAC expressing p34 and/or cyclin-B (C) were positively related to the percentages of cyclin-B (C + N)+ LAC in ALCL-C but not in HD; d) in HD, in contrast to ALCL-C, the size of the fraction of cyclin-B (C + N)+ LAC did not correlate with the ana/telophase indices (ATI, reflecting successful completion of mitosis) and the magnitude of cell loss; e) in ALCL-C, the percentages of p34+ LAC were positively correlated with ATI or the degree of CD30+ cell deletion, but inversely in HD. With regard to all parameters mentioned above, ALCL-HL tended to take an intermediate position between HD and ALCL-C, but sided more with the latter. In conclusion, our present results suggest a derangement of MPF kinetics and functions that is more profound in HD than in ALCL-C.

CDC2 Protein Kinase↗
PubMed1998

Localization of receptors for vasoactive intestinal peptide, somatostatin, and substance P in distinct compartments of human lymphoid organs.

Regulatory peptides, such as vasoactive intestinal peptide (VIP), somatostatin (SS), or substance P (SP), are considered to play a role in immune regulation. To localize the targets of these peptides in the human immune system, their receptors have been evaluated with in vitro receptor autoradiography in lymph nodes, tonsils, appendix, Peyer's patches, spleen, and thymus. The three peptide receptors were detected in all lymphoid tissues tested, but, unexpectedly, usually in distinct compartments. In lymph nodes, palatine tonsils, vermiform appendix, and Peyer's patches, VIP receptors were found in the CD3 positive zone around lymphoid follicles; SS receptors in the germinal centers of secondary follicles; and SP receptors mainly in interfollicular blood vessels. In the spleen, VIP receptors were detected in periarterial lymphatic sheaths, SS receptors in the red pulp, and SP receptors in the central arteries. In the thymus, VIP receptors were present in cortex and medulla, SS receptors in the medulla, and SP receptors in blood vessels. For comparison, cholecystokinin (CCK)-A and -B receptors were not demonstrated in any of these tissues. These results suggest a strong compartmentalization of the three peptide receptors in human lymphoid tissues and represent the molecular basis for the understanding of a very complex and interactive mode of action of these peptides.

Autoradiography↗
PubMed1998

[Respiratory insufficiency and absent left radial pulse after hemicolectomy].

A 65 year old female developed right thoracic pain, productive cough and fever four weeks after hemicolectomy because of a cancer of the sigmoid. In spite of antibiotic treatment the condition of the patient deteriorated and she was admitted to the hospital with pneumonia of an upper lobe. Chest X-ray visualized prominent proximal pulmonary arteries. Progressive respiratory failure developed and blood gas analysis revealed hypocapnic hypoxemia. The patient had to be intubated and ventilated mechanically. Later, left arm blood pressure measurements could no longer be taken and the radial pulse was missing. Thereafter, an ischemic syndrome of the right leg developed. Embolectomy from the superficial femoral artery was carried out the same day. The patient died five days later. Autopsy revealed an almost complete occlusion of the pulmonary arteries. The organization of thrombotic material indicated recurrence. Emboli were also found in the systemic circulation. A large patent foramen ovale together with signs of pulmonary arterial hypertension are indicative of paradoxical thromboembolism.

Aged↗
PubMed1998

Hodgkin's disease-like lymphoproliferative disorders in patients with different underlying immunodeficiency states.

Epstein-Barr virus (EBV)-associated lymphoproliferative diseases are a frequent occurrence in immunodeficient patients. Most commonly seen are polymorphic B-cell lymphoproliferative disorders and malignant B-cell lymphomas. Classical Hodgkin's disease (HD), however, is rare in these patients. In the present study, we attempted to characterize cases resembling HD in patients with a variety of underlying immunodeficiency states using clinical aspects, immunohistochemistry, in situ hybridization, and polymerase chain reaction. All of the six cases that we investigated presented clinically with B symptoms and a short, devastating course. Histologically, they showed a lymphocytic depletion and multiple cells that resembled HD and Reed-Sternberg cells. Many of those were atypical blast cells that stained positively for B-cell surface antigens, such as CD20 and CD79a, whereas others were of the typical HD and Reed-Sternberg phenotype. Another frequent finding, especially in the extranodal sites, was a perivascular arrangement of large blast cells intermingled with small lymphoid cells. All of the cases were EBV-associated (proved latent membrane protein-1 immunohistochemical analysis, EBV-encoded RNA in situ hybridization, and polymerase chain reaction for subtypes A and B), with a frequent coinfection of type A and B. This was in contrast to ordinary HD, which is characterized by single infection of only one strain, i.e., the subtype A in Western countries. Three cases showed clonal B-cell populations, at least at terminal stages of the disease. We describe a lymphoproliferative disorder in immunodeficient patients with features of HD that, in some respects, resembles an EBV-driven lymphoproliferative disorder seen in cases of fatal infectious mononucleosis. We conclude that clinical and pathologic features of these disorders might cause some problems for histologic differential diagnosis and might represent a separate entity of their own in immunodeficient patients.

Adult↗
PubMed1997

Growth patterns of diffuse non-Hodgkin's lymphomas estimated from mitotic and apoptotic indices.

Growth rates of neoplasms could be calculated only on the basis of mitotic and apoptotic indices (MI and AI, respectively), assessed on tissue sections, if the duration of mitosis and apoptosis (Tm and Ta, respectively) in vivo were known. For humans, this is practically never the case. What use then can be made of MI and AI to arrive at a relative, crude estimate of the state of growth? As a model system to study this problem, we chose diffusely growing stage I + II non-Hodgkin's lymphomas (dNHL, n = 94). Cluster analysis revealed the existence of 3 highly distinct groups of dNHL (clusters I, II and III) in the MI vs. AI per case plot, with a roughly linear relation between both parameters. Most nosologic entities defined by the REAL classification comprise cases that were represented in more than one cluster. We adopted the simple formula GI (growth index) = XMI - AI, where X (= Ta/Tm) remains to be evaluated. Based on the assumption that spontaneous regressions of dNHL are rare but do occur, we estimated that X = 2 or, possibly, 3 are best fits for the pooled dNHLs studied. With the assumption of X = 2, (i) 2MI - AI gave relatively lower values for dNHL than proliferative indices such as %Ki-67+ cells; (ii) values for 2MI/AI per cluster showed a pattern inverse to that for %bcl-2+ cells; and (iii) a plot of 2MI - AI vs. 2MI/AI per case allowed the recognition, especially among NHLs with a low cell turnover, of cases where accumulation of presumably longer-lived cells is an important factor in determining growth.

Adolescent↗
PubMed1997

Cellular kinetic and phenotypic heterogeneity in and among Burkitt's and Burkitt-like lymphomas.

This study asks whether the known genotypic heterogeneity within and between endemic or sporadic Burkitt's lymphomas (eBLs and sBLs, n = 10 each), and Burkitt-like lymphomas (BLLs, n-12), is reflected in divergent cytokinetics and related immunophenotypes. There was strong evidence that eBL and BLL grow markedly faster than sBL, as shown by differences in mitotic and apoptotic indices. Furthermore, in BLL, the median percentage of neoplastic cells immunoreactive for the bcl-2 protein was much higher than that observed in eBL and sBL. The reverse was true for the median fraction of cells containing c-myc protein. In eBL and sBL, the median fraction of bcl-6 protein-positive cells reached values above 50 per cent, while cells of 8/12 BLLs did not contain detectable amounts of this protein. This observation indicates that in this respect, eBL and sBL resemble normal germinal centres of lymphatic tissue much more than do BLL. Evidence for infection of neoplastic cells by the Epstein-Barr virus (EBV) was observed in 9/10 cases of eBL and in 3/10 of sBL, but not in BLL. EBV-positive lymphomas were associated with distinctly lower apoptotic indices and smaller median percentages of bcl-6-positive cells than EBV-negative tumours.

Adolescent↗
PubMed1997

TUNEL-positive hepatocytes in alcoholic liver disease. A retrospective biopsy study using DNA nick end-labelling.

Alcohol-induced damage to the liver results in a wide array of typical alterations. Whereas the mechanisms involved in the pathogenesis of fatty change, hepatocyte ballooning, Mallory body formation and fibrosis have been studied in detail, little is known about hepatocyte apoptosis in alcoholic liver disease (ALD). In this retrospective study we analysed parenchymal cell death in ALD systematically by the use of in situ DNA nickend labelling (ISEL/TUNEL). We show that increased hepatocyte TdT labelling occurs in ALD. Labelling is observed more frequently in parenchymal areas exhibiting advanced damage (ballooning degeneration with or without Mallory bodies, cholestasis and perisinusoidal fibrosis). In addition, hepatocyte TdT labelling is higher where there is septal fibrosis and nodular remodelling. Conversely, it is not elevated in ballooning hepatocytes themselves, but rather in the apparently normal hepatocytes in their vicinity.

Adult↗
PubMed1997

Mitotic activity and nuclear DNA damage of large cells in Hodgkin's disease: comparison with the expression of p53 and bcl-2 proteins and the presence of Epstein-Barr virus.

The roles of the bcl-2 and p53 proteins in Hodgkin's disease (HD) are poorly understood. We therefore compared their detected presence in Hodgkin and Reed-Sternberg/large atypical (H-RS/LA) cells immunohistochemically with the percentages of these cells double-labeled for CD30 and DNA strand breaks (DNA fragmentation index, DFI); mitotic indices (MI); and the EBV infection status. We found a highly significant inverse correlation between the fractions per case of H-RS/LA cells expressing bcl-2/p53 proteins and the DFI of CD30+ elements. No marked effect of these two oncoproteins on MI was noticed, although these parameters and DFI of CD30+ cells were linearly related. EBV infection of H-RS/LA cells exerted only a limited effect on the parameters tested. The results of this study suggest that overexpressed bcl-2 and, to some extent, p53 proteins in H-RS/LA cells of HD primarily counteract deletion of these cells.

Adolescent↗
PubMed1997

Cell kinetics, morphology, and molecular IgVH gene rearrangements in Hodgkin's disease.

The present study dealt with the question of whether any cellular kinetic patterns correlate with clonal rearrangement of the IgVH gene as revealed by polymerase chain reaction on DNA extracted from lymph nodes with classical Hodgkin's disease (HD) and/or from single CD30+ cells (Hodgkin [H] and Reed-Sternberg [RS] cells). In 15/4 cases with H-RS cells of B or Null phenotype, signs of such monoclonality could be detected (group I) but not in the others (group II). CD30+/H-RS cells in group I differed slightly but significantly from those in group II in that they a) exhibited a larger fraction of cells attaining the anaphase/telophase stage of mitosis, and b) produced relatively more mononucleated cells (H) at the expense of multinucleated (RS) cells. In addition, reactive lymphoid cell (CD30-) infiltrates were considerably less dense in group I that in group II. These findings suggest that the cytokinesis of H-RS cells in group I was moderately more efficient than in group II. However, signs of monoclonality were not associated with the normalization of the mitotic process, which also proved to be disturbed in group I.

Adolescent↗
PubMed1997

Hepatocyte apoptosis in hepatic iron overload diseases.

In this retrospective study, we systematically analyzed hepatocyte apoptosis in three situations of hepatic iron overload (hereditary hemochromatosis; hepatic iron overload of unknown reason; iron overload due to hyperhemolysis or exogenous iron administration). Apoptosis was assessed by use of DNA nick end-labelling. The results suggest that hepatic iron overload is associated with an increased apoptotic rate of hepatocytes, and that iron-laden hepatocytes in hemochromatosis behave, with respect to apoptosis, differently from those in other states of iron overload. The hepatocyte apoptotic rate tended to increase as a function of the degree of iron storage. As in other pathological liver changes studied so far, an elevated apoptotic rate of hepatocytes predominated in the pericentral parts of liver acini in hemochromatosis, but not in the two other groups of hepatic iron overload. Possible mechanisms for this difference are discussed, particularly with respect to a participation of the Kupffer cell system.

Adult↗
PubMed1996

Stage-related differences of mitotic and apoptotic indices, and bcl-2 protein expression in diffusely growing non-Hodgkin's lymphomas.

The present study examined whether growth characteristics of diffusely growing non-Hodgkin's lymphomas (NHL) may differ as a function of stage. Among 105 NHL of various types and sub-types (REAL [Revised European-American Lymphoma] classification), localized (Ann Arbor pathologic stages I + II) lymphomas exhibited clearly higher indices for mitotic activity, apoptosis and cell turnover, as well as a significantly lower percentage of cells containing immunohistochemically detectable bcl-2 protein, than disseminated (stages III + IV) NHL. A similar pattern emerged when high-grade (Kiel classification) lymphomas only were evaluated. Low-grade NHL showed analogous, but less marked, stage-dependent characteristics, with the exception of median percentages of bcl-2+ cells, which remained comparable in all stages. Our findings are consistent with the notion that dissemination of diffusely growing NHL is usually associated with reduced cell turnover and, in high-grade lymphomas, with the generation of longer-lived cells.

Adolescent↗