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J A Laissue

Publications and source records attributed to J A Laissue.

At least 73 records · Page 4Linked to original sources
PubMed1994

Spatial distribution of mitosis, apoptosis and small blood vessels in malignant diffuse follicular-center-cell lymphomas: a nearest-neighbor analysis.

To better comprehend the relationships between cell birth and cell death in neoplastic disorders, the topography of these events needs to be considered. We applied a computerized nearest-neighbor analysis to malignant, diffuse follicular-center-cell lymphomas in order to examine the spatial distribution of pyknotic (apoptotic) cells/bodies (A) and mitotic figures (M) in relation to capillaries (C) and venules (V). The results revealed a complex dispersion pattern, with significant aggregations of A and M, in addition to an even greater random distribution component. The greatest clustering displayed by A was around capillaries (A-C, 42% reduction of object frequency between the first and second distance class), followed by A-A (33%), A-V (24%) and A-M (12%). Additional values for mitotic figures were: M-M (45%), M-V (33%) and M-C (22%). These findings may reflect the relative importance of inherent properties of the neoplastic and host factors, respectively, in the regulation of cell birth and cell death rates.

Adult↗
PubMed1994

[Diarrhea due to rare forms of colitis: microscopic (lymphocytic, collagenous) colitis and spirochetosis].

Lymphocytic and collagenous colitis, uncommon entities that are identifiable by histopathologic examination only, and intestinal spirochetosis may cause chronic diarrhea. Data on incidence, histopathology, and diseases associated with these infrequent forms of colitis are reviewed. Etiology and pathogenesis of lymphocytic and collagenous colitis are still unknown, but immuno-inflammatory factors may be involved in both forms as well as, in collagenous colitis, primary disorders of collagen metabolism or drug-induced toxic effects. The significance of intestinal colonization by spirochetes is disputed; however, recent results indicate that these microorganisms are capable of inducing disease.

Adult↗
PubMed1994

The value of octreotide scintigraphy in patients with lung cancer.

We evaluated octreotide scintigraphy in 81 untreated patients who were suspected of having bronchial carcinoma. Octreotide scintigraphy visualized the primary tumour in all of 40 patients with non-small-cell lung carcinoma (non-SCLC), and all of 26 patients with SCLC. In the remaining patients, other bronchial disease and metastases from extrapulmonary carcinomas were also visualized. Mediastinal lymph node involvement and distant metastases were recognized in 5 of 15 and 1 of 7 patients with non-SCLC, respectively. In vitro, none of the non-SCLCs were shown to bear somatostatin receptors. We postulate that the visualization of non-SCLC during octreotide scintigraphy is caused by binding of labelled octreotide to activated leucocytes or to proliferating neuroendocrine cells around the tumours. In patients with SCLC, radiologically suspected lymph node involvement was visualized for 21 of 25 sites. Distant metastases, especially to the liver and abdomen, were missed for 14 of 20 sites, most probably because no laxatives were administered and single photon emission tomography of the abdomen was not performed. The failure to recognize liver metastases is most probably due to a comparable uptake of radioactivity by the surrounding normal liver tissue. In 15 of 26 patients, previously unrecognized tumour sites were suggested during octreotide scintigraphy, leading to a downstaging of 5 of 14 patients with limited disease. Unexpected cerebral metastases were suggested in five patients with either limited or extensive disease. In all four of these for whom follow-up was available, cerebral metastases became manifest 5-8 months after octreotide scintigraphy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Immunohistochemical analysis of p53 protein overexpression in liver cell dysplasia and in hepatocellular carcinoma.

We analysed p53 protein immunoreactivity in hepatocellular carcinomas (HCCs) and in liver cell dysplasia (LCD) of patients from an area in Northern China, using five anti-p53 protein antibodies recognizing different epitopes of the protein. In HCCs, the overall prevalence of p53 protein immunoreactivity was 78.3%. However, prevalence was strongly influenced by the type of antibody used, ranging from 67.5% for antibody PAb-1801 to only 10.8% for antibodies PAb-421 and DO-7. p53 protein immunoreactivity was not related to type or grade of HCC. In contrast to former reports, p53 protein staining was restricted to nuclei only when using the CM-1 antibody, whereas two other antibodies yielded both, nuclear and cytoplasmic or membrane staining, and no nuclear staining was observed with antibodies PAb-421 and DO-7, the latter two, however, demonstrating cytoplasmic and membrane staining. For LCD, three subtypes were morphologically and karyometrically defined. Nuclei of some LCD cells were p53 immunoreactive, but positivity was restricted to the small cell variant of LCD. Positivity was different for cirrhosis with or without associated HCC, amounting to 18.9% in the former and 39.4% in the latter. Interestingly, p53 protein immunoreactivity also occurred in a set of small hepatocytes not showing the typical feature of LCD and therefore classified as simple regenerating liver cells.

Antibodies↗
PubMed1994

Intestinal vessels express a high density of somatostatin receptors in human inflammatory bowel disease.

BACKGROUND/AIMS: The neuropeptide somatostatin exerts multiple functions in the gastrointestinal tract and may also play a regulatory role in inflammatory bowel disease, as several other neuropeptides do, e.g., substance P or calcitonin gene-related peptide. Therefore, the expression of somatostatin receptors was evaluated in tissue sections of diseased intestines and compared with controls. METHODS: Somatostatin receptors were measured in intestinal samples of 6 patients with Crohn's disease, 3 with ulcerative colitis, and 7 controls using somatostatin receptor autoradiography with 125I-[Tyr3]-octreotide or 125I-[Leu8,D-Trp22,Tyr25]-somatostatin-28 as radioligands. Substance P receptors were measured similarly on adjacent sections. RESULTS: Somatostatin receptors are present in high density in most intramural veins, but not in arteries, of intestines in florid Crohn's disease or ulcerative colitis. The receptors are specific and of high affinity for somatostatin-14 and -28, as well as for octreotide. Somatostatin receptors remain undetectable in the veins of noninflamed control intestine. Substance P receptors are identified in the somatostatin receptor-positive veins and also in arteries. CONCLUSIONS: The expression of receptors for somatostatin in veins of inflamed intestines suggests an active involvement of this peptide in the pathophysiology of inflammatory bowel disease and perhaps of inflammation in general.

Adult↗
PubMed1994

Immunohistochemical detection of bcl-2 protein in liver lesions: bcl-2 protein is expressed in hepatocellular carcinomas but not in liver cell dysplasia.

A proto-oncogene, bcl-2, encodes a protein that inhibits programmed cell death (apoptosis) and may play a role in cell and tissue differentiation. As bcl-2 appears to be involved in the turn-over of stem or precursor cells, it is thought to be operational in carcinogenesis pathways. However, apart from certain lymphomas, only limited data are available on the frequency of its expression in solid tumors. Immunohistochemical analysis with an antibody specific for bcl-2 protein was used to detect the protein in hepatocellular carcinomas and in one of the putative precursor lesions, liver cell dysplasia. We detected bcl-2 protein in 5 of 37 hepatocellular carcinomas. Immunoreactivity was not related to type, grade, or extent of PCNA staining of the tumours. No bcl-2 protein staining was observed in three types of liver cell dysplasia. Thus, bcl-2 is abnormally expressed in some hepatocellular carcinomas but not in potential tumour precursor cells.

Carcinoma, Hepatocellular↗
PubMed1994

[Oral non-Hodgkin lymphomas and Epstein-Barr virus].

The oropharynx is the site of primary infection and further propagation of the Epstein-Barr virus (EBV). From here, virus is shed to saliva and infects peripheral blood lymphocytes. Eight oral Non-Hodgkin lymphomas (NHL) were investigated for the presence of EBV both by immunohistochemistry for the latent membrane protein (LMP) and a PCR-strategy for general and subtype-specific viral sequences. All but one NHL turned out to be negative both by LMP and PCR. EBV general sequences and of the two viral subtypes A and B were found in an HIV-1+ patient. It is concluded that it is not the localisation which predetermines NHLs to EBV-positivity but merely the underlying disease (this study) or the type of tumour (previous studies).

Antigens, Viral↗
PubMed1994

Three types of liver cell dysplasia (LCD) in small cirrhotic nodules are distinguishable by karyometry and PCNA labelling, and their features resemble distinct grades of hepatocellular carcinoma.

We have studied the occurrence and specific features of liver cell dysplasia (LCD) in Chinese patients showing liver cirrhosis with or without hepatocellular carcinoma (HCC). Three types of LCD (SLCD, LLCDo, LLCDe) were morphologically defined, and these types were further analyzed using karyometry, estimation of nucleic acid content and density, and PCNA immunostaining. Features found for three types of LCD were compared with those of normal hepatocytes (NLC), simple regenerating hepatocytes (SRLC), and cells of HCCs covering different grades. The results show that 1) karyometry and nucleic acid parameters allow an objective separation of LCD types both from NLC and SRLC; 2) karyometric features of LLCDe are most close to those of highly differentiated HCCs, whereas nuclear size and chromatin composition of SLCD closely reflect those of poorly differentiated HCCs; 3) the frequency of LCD clusters was higher in cirrhotic livers carrying HCC, being about double for all three LCD types; 4) the highest PCNA labelling occurred in the small cell group of LCD (SLCD), still, however, being smaller than that of simple regenerating hepatocytes. Based on these findings it is suggested that, similar to atypical adenomatous hyperplasia, LCDs of distinct morphotypes may represent precursor lesions for HCC, and some cellular forms may mimick cell types known to occur in experimental carcinogenesis.

Carcinoma, Hepatocellular↗
PubMed1994

Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation.

Interleukin-8 (IL-8) is a potent cytokine for recruitment and activation of neutrophils. To visualize its distribution in the intestinal mucosa and to understand better its possible role in the induction and promotion of inflammatory bowel disease, expression of the IL-8 gene was analyzed in resected bowel segments of 14 patients with active Crohn's disease or ulcerative colitis. In situ hybridization with IL-8 anti-sense RNA probes revealed strong and specific signals in the histologically affected mucosa. The number of cells expressing IL-8 gene correlated with the histological grade of active inflammation. In accordance with the characteristic histological signs of active disease, IL-8-expressing cells were diffusely distributed over the entire affected mucosa in patients with ulcerative colitis, whereas in patients with Crohn's disease, IL-8-expressing cells showed a focal distribution pattern. Cells expressing IL-8 were mainly located at the base of ulcers, in inflammatory exudates on mucosal surfaces, in crypt abscesses, and at the border of fistulae. Analysis of semi-serial sections pointed to macrophages, neutrophils, and epithelial cells as possible sources of this cytokine in active inflammatory bowel disease. We consistently failed to detect IL-8 messenger RNA in the mucosa of uninvolved bowel segments and in normal-appearing control mucosa of patients with colon cancer. In contrast, tissue specimens from two patients with acute appendicitis displayed IL-8-expressing cells in the mucosa. These results support the notion that IL-8 plays and important but nonspecific role in the pathogenesis of inflammatory bowel disease and that the production of IL-8 messenger RNA is restricted to areas with histological signs of inflammatory activity and mucosal destruction.

Adult↗
PubMed1993

In vitro autoradiographic and in vivo scintigraphic localization of somatostatin receptors in human lymphatic tissue.

Receptors for the neuropeptide somatostatin (SS) were evaluated in vitro and in vivo in various human lymphatic tissues, ie, thymus, spleen, and lymph nodes; thymic carcinoids and thymomas were also tested. The receptors were measured in vitro using receptor autoradiography on tissue sections incubated with the SS analog 125I-[Tyr3]-octreotide or 125I-[Leu8,D-Trp22,Tyr25]-SS-28. All tissues were SS-receptor positive for either radioligand, except the thymomas. In thymic tissue, the receptors were diffusely located in the medulla, presumably on epithelial cells. In the spleen, the red pulp was strongly labeled. In the lymph nodes, the germinal centers were preferentially labeled. In all tissues, the receptors were of high affinity (kd thymus, 0.84 nmol/L; kd spleen, 1.6 nmol/L; kd lymph node, 0.62 nmol/L) and specific for SS. Displacement by nanomolar concentrations of SS-14, SS-28, and octreotide was observed, as was guanosine triphosphate dependency. The in vivo visualization of somatostatin receptors was performed after injection of 111In-DTPA-octreotide and gamma-camera scintigraphy. The spleen, but not thymus or lymph nodes, were visualized. These data suggest an important role for SS in regulating immune functions through SS receptors in thymus, spleen, and lymph nodes. Furthermore, SS may regulate neuroendocrine functions in the thymus.

Adolescent↗
PubMed1993

Human kidney as target for somatostatin: high affinity receptors in tubules and vasa recta.

Somatostatin (SRIH) receptors were identified in human kidneys by in vitro receptor autoradiography using 125I-[Tyr3]octreotide and 125I-[Leu8,D-Trp22,Tyr25]SRIH-28 as radioligands. Characterization of the binding demonstrated a single class of high affinity binding sites with a dissociation constant (Kd) of 0.5 nmol/L. Binding depended on GTP and magnesium and sodium concentrations. SRIH-14, SRIH-28, and octreotide were able to displace the radioligand in the high affinity range, whereas biologically inactive SRIH analogs or unrelated peptides were not. Microscopic localization of these receptors revealed binding over cortical and medullary areas. In the cortex, the receptors were located in the proximal tubules. No SRIH receptors were found in the glomeruli. In the medulla, the receptors were identified in high density in medullary vasa recta. A diffuse labeling of lesser density observed in the remaining medulla corresponded to collecting tubules. The receptor concentration was 32 fmol/mg protein in the renal cortex and 304 fmol/mg protein in the vasa recta. The receptors were undetectable in the rat kidney and are, thus, species dependent. SRIH receptors in the human kidney may be the molecular basis for the actions of SRIH on renal functions and may indicate a therapeutic potential for SRIH analogs in this tissue.

Arterioles↗
PubMed1993

"Neuroendocrine" differentiation in hepatocellular carcinomas (HCCs): immunohistochemical reactivity is related to distinct tumor cell types, but not to tumor grade.

We have analyzed neuroendocrine differentiation (ND) in hepatocellular carcinomas (HCCs) of fifty patients. It turned out that ND is frequent in HCCs, and that it is not restricted to fibrolamellar hepatocellular carcinoma (FL-HCC). Multiexpression is seen in a quarter of the cases, and marker coexpression may occur within the same tumor cell. ND predominates in trabecular and mixed HCCs, but does not appear to be related to grade. Most positive cases showed a hepatocyte-like cell morphology, frequently associated with bile formation. It thus appears that the HCC cell type most likely to show ND is a hepatocyte-like one, i.e. differentiated cell, frequently polarized and producing bile, rather than a small and poorly-differentiated cell. Possible pathogenic mechanisms leading to ND in HCCs are briefly discussed.

Adult↗
PubMed1992

Pharmacologic interactions between the resistance-modifying cyclosporine SDZ PSC 833 and etoposide (VP 16-213) enhance in vivo cytostatic activity and toxicity.

Cyclosporin A reverses multidrug resistance (MDR) and increases the in vivo cytostatic activity and toxicity of the anticancer agent etoposide (VP 16-213). SDZ PSC 833 (PSC 833), a non-immunosuppressive, non-toxic cyclosporin and very active modifier of P-gp 170-mediated MDR, elicits similar effects when administered with adriamycin. The underlying mechanisms, however, are not yet understood. The present pharmacological interaction study with PSC 833 and VP 16-213 was carried out to reveal the nature of this enhancement of cytostatic activity and toxicity. Rats pre-treated with either PSC-833 or solvent received a single dose of VP 16-213. Plasma levels of VP 16-213 were measured by high-performance liquid chromatography (HPLC). The resulting increase in cytostatic activity and toxicity of VP 16-213 mediated by PSC 833 was paralleled by marked changes in the pharmacokinetic parameters of VP 16-213 in vivo. Bioavailability and blood levels of VP 16-213 were significantly increased 30 min after administration if PSC 833 had been given before. The disappearance rate of VP 16-213 from the intravascular compartment was considerably slowed down by PSC 833. In drug-sensitive xenografts of human colon carcinoma, the PSC-833-induced pharmacologic changes in vivo could be counteracted by dose reduction of VP 16-213 while a full therapeutic potential was maintained. Doses of VP 16-213, 1.5 to 2 times smaller, combined with PSC 833, were as effective in terms of tumor-growth inhibition as the maximum tolerated dose of VP 16-213 alone. Thus, pharmacologic interactions between PSC 833 or other resistance modifiers and VP 16-213 and other cytostatic agents require careful attention if they are to be used in humans to overcome MDR.

Adenocarcinoma↗
PubMed1992

In vitro and in vivo detection of somatostatin receptors in human malignant lymphomas.

A wide variety of primary and metastatic human neoplasms express somatostatin receptors (SS-Rs). We evaluated the SS-R status of malignant lymphomas that had been surgically removed from 31 patients by use of in vitro SS-R autoradiography with the SS analog 125I-[Tyr3]-octreotide as radioligand. Of 11 low-grade-malignancy B-cell non-Hodgkin's lymphomas, 10 were SS-R-positive, with a high receptor density restricted to the neoplastic follicles. All of the 8 intermediate-grade lymphomas were SS-R-positive. Of the B-cell lymphomas of high-grade malignancy, 7 out of 10 were SS-R-positive, often with a high density of receptors. One T-cell lymphoma and one Hodgkin's lymphoma were also positive. SS-Rs were of high affinity (KD = 1.2 nM) and specific for bioactive SS analogs. In 4 patients, the lymphomas were localized in vivo by use of gamma-camera scintigraphy after i.v. injection of the SS analog 111In-[DTPA-D-Phe1]-octreotide. Hot spots, identified in all 4 patients, corresponded to SS-R-positive malignant-lymphoma tissue, as confirmed by receptor autoradiography of the surgically removed tumors. Our data show that SS-Rs are valuable pathobiochemical tissue markers and potentially useful in vivo diagnostic tools for human malignant lymphomas.

Adolescent↗
PubMed1992

SDZ PSC 833, a non-immunosuppressive cyclosporine: its potency in overcoming P-glycoprotein-mediated multidrug resistance of murine leukemia.

Cyclosporin A (CsA, Sandimmune) is known to reverse P-glycoprotein (P-gp170)-mediated multidrug resistance as efficiently as other prototype compounds of resistance modifiers. The immunosuppressive activity and nephrotoxicity of CsA, however, may limit its clinical use. PSC-833, a new cyclosporine, exerts a similar resistance-modifying activity but lacks toxicity or immunosuppressive activity. We have tested its potency in vitro and in vivo on the L1210 leukemia cell line transfected with a full-length cDNA copy of the human mdr I gene, which showed a stable 30-fold resistance towards adriamycin as compared to the parental cell line. In vitro growth of the transfected cell was unchanged. In vivo growth was less aggressive; the survival time of inoculated mice was prolonged. In vitro, PSC-833 was at least as potent as CsA or verapamil in reversing multidrug resistance. In vivo, the drug-resistant L1210 leukemia was completely unresponsive to i.v. monotherapy with adriamycin at its maximum tolerated dose (MTD). PSC-833 enhanced the activity and toxicity of adriamycin. The MTD of adriamycin was about 3 times lower than when given alone. On this basis, the MTD of i.v. adriamycin in combination with oral PSC-833 successfully overcame refractoriness to treatment. Survival times of the mice were considerably prolonged and even some cures of leukemic mice occurred.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Distribution and localization of Epstein-Barr virus subtypes A and B in AIDS-related lymphomas and lymphatic tissue of HIV-positive patients.

Tissue samples of 21 HIV-positive patients have been studied for the presence and distribution of Epstein-Barr virus (EBV) subtypes A and B. This was done by PCR, EBER in situ hybridization, and immunohistochemical detection of EBV latent membrane protein (LMP) in AIDS-associated malignant lymphomas (16 cases) and lymphatic organs of patients without lymphoma (5 cases). Eleven cases were considered to be EBV-positive, with type A in four, and type B virus in four other cases. In patients with malignant lymphoma, EBV was localized in tumour tissue exclusively. One patient without lymphoma presented with multiple EBV genome type B-positive cells in all the lymphoid tissue samples examined. In HIV-positive patients, both subtypes of EBV, A and B, may play a role in the pathogenesis of lymphoproliferative lesions.

Adult↗