PubMed Health⌕ Search

Biomedical subjects

J A Laissue

Publications and source records attributed to J A Laissue.

At least 91 records · Page 5Linked to original sources

Recurrent cutaneous anaplastic large cell (CD30+) lymphoma associated with Epstein-Barr virus. A case report with 9-year follow-up.

CD30-positive large cell cutaneous T-cell lymphomas are known to be associated with the human T-cell leukemia/lymphoma virus type I. We present a case of anaplastic large cell lymphoma that recurred three times during 9 years at different sites. Molecular studies [polymerase chain reaction (PCR), in situ hybridization] showed Epstein-Barr virus (EBV) genome in biopsy samples of this first reported case of EBV-associated cutaneous anaplastic large cell lymphoma. This case was human T-lymphotropic virus-1 and -2 negative by PCR. The results add some evidence to the hypothesis that EBV may be a factor in the pathogenesis of cutaneous lymphoproliferative lesions.

Base Sequence↗

[Lymphoid follicles of the human large bowel mucosa: structure and function].

Little is known about morphology and function of human solitary lymphoid follicles (LF), a component of the gut-associated lymphoid tissue. We have studied 156 LF in situ from 10 colorectal resection specimens by use of serial frozen sections and immunohistochemistry (APAAP technique) and found 8 to 10 LF per cm2, i.e. 11,000 to 14,000 LF in the whole organ. Two types were identified: (1) One type, located in the colon, displayed a pit-like follicle-associated epithelium (FAE). A large part of this LF extended into the submucosa. (2) The other type was noticed mainly in the tunica mucosa of the rectum and had a flat FAE. All LF exhibited a rather constant structure. The main elements were FAE, dome region, B-lymphocyte region with surrounding T-lymphocyte area including high endothelial venules, and a lymph sinus that delimited the LF against the submucosa. One out of five LF contained a germinal center. Marked differences were found between the immunological effector cell population of the LF and that of the lamina propria. These observations denote (1) a striking compartmentation of these cells in the gut mucosa; (2) a marked similarity of the immunomorphology of LF to that of Peyer patches; (3) a functional analogy: The LF belong to a physically discrete compartment that constitutes the afferent limb of the local immune system, as the Peyer patch does. The lymphomonocytic elements of the lamina propria belong to the efferent limb. Results of in vitro studies, generally based on a mixture of cells from both compartments, may thus not reflect the conditions found in vivo.

Antigens, CD↗

[Interactive tumor diagnosis: pathology and oncology].

Biopsies will supply the best answers when the clinician submits a well-defined diagnostic problem to his pathologist before the biopsy is done, when he is aware of the limitations of the biopsy technique, when the pathologist makes optimal use of the available techniques as well as expertise and knows the limitations of a diagnosis based on morphology alone, and when treating physicians and pathologists keep up close communication before, during and after diagnostic procedures.

Biopsy↗

Radioprotection of cultured cells by preincubation in medium containing deuterium oxide.

Pretreatment with deuterium oxide (D2O) has been shown to protect mice against lethal effects of X-rays. In contrast, X-irradiation of cultured mammalian cells in D2O-containing medium has previously been reported to result in increased cell killing. Therefore, the effects of preincubation in medium containing 20% D2O on radiosensitivity were tested, using cells of a heat-sensitive cell-cycle mutant (21-Tb) of the murine mastocytoma P 815-X2. The mutant cells proliferate at 33 degrees C and are arrested in G1 phase in a state of reversible proliferative quiescence at 39.5 degrees C. Prior to irradiation with single X-ray doses of 0-10 Gy, the cells were cultured in normal or D2O-containing medium, either for 96 h at 33 degrees C ('proliferating cells'), or for 72 h at 33 degrees C followed by 24 h at 39.5 degrees C ('arrested cells'). After X-irradiation the cells were resuspended in normal medium, and cell survival was determined by the capacity of cells to form colonies in fibrin gels. Preincubation in medium containing 20% D2O resulted in a radioprotective effect on both proliferating and arrested cells, particularly at the higher X-ray doses. This radioprotection was manifested as a decreased slope of the semilogarithmic survival curves, whereas pretreatment with D2O had no significant effect on postirradiation repair as judged from Dq values. These results support the interpretation that the increase in postirradiation survival may be attributed to incorporation of deuterium into cellular metabolites during the period of preincubation.

Cell Line↗

Heavy water enhances the antineoplastic effect of 5-fluoro-uracil and bleomycin in nude mice bearing human carcinoma.

The antineoplastic effect of heavy water on the growth of xenotransplanted human carcinoma was compared to that of 2 cytostatic drugs. Seven-week-old BALB/c-nu/nu mice were inoculated subcutaneously with a poorly differentiated oropharyngeal squamous-cell carcinoma, or with variants of carcinoma of the large intestine. After tumor inoculation, 3 subgroups of mice were treated by: (i) moderately deuterated drinking water; (ii) i.p. injections of 5-Fluoro-uracil (5-FU) or Bleomycin; (iii) a combination of deuterated drinking water and of the cytostatic drugs. Control mice were not treated. Heavy water delayed growth of all carcinoma variants. The cytostatic drugs slowed down the growth of the 2 poorly differentiated tumor variants. Conversely, 5-FU did not retard the growth of the moderately well differentiated colon carcinoma. Heavy water combined with either cytostatic drug showed synergistic effects in the 2 poorly differentiated tumor variants. The tumors of treated animals weighed 36% to 90% less than those of control animals. The antineoplastic effects were more conspicuous in poorly than in moderately well differentiated tumor variants. Cytokinetic parameters such as labelling indices following application of 5-125I-Iodo-2'deoxyuridine, and of Ki-67, a monoclonal antibody (MAb) directed against an antigen of proliferating cells, or mitotic indices and tumor volume doubling time, combined with the results of histologic evaluation of the tumors, suggested an underlying deuterium-induced prolongation of tumor-cell cycle times and a reduction of the growth fraction.

Adenocarcinoma↗

[Precancerous and early stage colorectal carcinoma: clinico-pathological implications].

With regard to the clinical implication and importance of carcinoma prevention, the histogenesis and pathobiology of the precancerous lesions and conditions of the colorectum are described. Polyps, dysplasia (with and without ulcerative colitis), adenomas and polyposis syndromes are defined, and their potential as markers for an increased risk for colorectal cancer is estimated. For the time being, the prevention of colorectal cancer is only possible by interrupting the multistage carcinogenesis in due course, i.e. during the precancerous stages. The exact knowledge of the latter is the rational of the clinical procedures.

Adenomatous Polyposis Coli↗

Boron neutron capture therapy of intracerebral rat gliosarcomas.

The efficacy of boron neutron capture therapy (BNCT) for the treatment of intracerebrally implanted rat gliosarcomas was tested. Preferential accumulation of 10B in tumors was achieved by continuous infusion of the sulfhydryl borane dimer, Na4(10)B24H22S2, at a rate of 45-50 micrograms of 10B per g of body weight per day from day 11 to day 14 after tumor initiation (day 0). This infusion schedule resulted in average blood 10B concentrations of 35 micrograms/ml in a group of 12 gliosarcoma-bearing rats and 45 micrograms/ml in a group of 10 similar gliosarcoma-bearing rats treated by BNCT. Estimated tumor 10B levels in these two groups were 26 and 34 micrograms/g, respectively. On day 14, boron-treated and non-boron-treated rats were exposed to 5.0 or 7.5 MW.min of radiation from the Brookhaven Medical Research Reactor that yielded thermal neutron fluences of approximately 2.0 x 10(12) or approximately 3.0 x 10(12) n/cm2, respectively, in the tumors. Untreated rats had a median postinitiation survival time of 21 days. Reactor radiation alone increased median postinitiation survival time to 26 (5.0 MW.min) or 28 (7.5 MW.min) days. The 12 rats that received 5 MW.min of BNCT had a median postinitiation survival time of 60 days. Two of these animals survived greater than 15 months. In the 7.5 MW.min group, the median survival time is not calculable since 6 of the 10 animals remain alive greater than 10 months after BNCT. The estimated radiation doses to tumors in the two BNCT groups were 14.2 and 25.6 Gy equivalents, respectively. Similar gliosarcoma-bearing rats treated with 15.0 or 22.5 Gy of 250-kilovolt peak x-rays had median survival times of only 26 or 31 days, respectively, after tumor initiation.

Animals↗

The epithelium of the human endolymphatic sac: immunohistochemical characterization.

A panel of monoclonal and polyclonal antibodies has been used to study the epithelium of the extraosseous part of the human endolymphatic sac (ES) by immunohistochemistry. The ES epithelium reacted with several epithelial markers such as Lu-5, different anticytokeratins, antiepithelial membrane antigen, and anticarcinoembryonic antigen. Unexpectedly, all epithelial cells also revealed a strong positive reaction for the mesenchymal marker vimentin and for S-100 protein. 'Neuroendocrine', a neurosecretory antigen, and neuron-specific enolase reactivity was detected in a few epithelial cells. The results support the assumption that the ES epithelium is metabolically active and capable of secretion and resorption. These findings are in keeping with results of functional experiments in animals. The demonstration of neurosecretory antigen and neuron-specific enolase in some cells indicate that the epithelium may also have paracrine functions.

Antibodies, Monoclonal↗

Human endolymphatic sac: evidence for a role in inner ear immune defence.

In an immunohistochemical study, monoclonal and polyclonal antibodies have been used to identify cells and structures in the extraosseous part of endolymphatic sacs (ES) which were removed at autopsy from 30 persons. Intraluminal, intraepithelial, intravascular and perisaccular cells expressed the leukocyte common antigen. Immunostaining with antibodies against the CD4 and CD8 antigens revealed the predominance of CD4-positive T lymphocytes in the ES. A few lymphoid cells were found to express the major histocompatibility antigen class II. Interdigitating cells of the Langerhans type were rarely found in the epithelial layer. B lymphocytes were present in the lumen and the stroma of the ES and IgA- or IgG-containing cells in the stroma only. IgA, secretory component and the J chain were detected within epithelial cells and in the lumen of the ES. Macrophages were observed in the lumen and the stroma. Our findings are in accordance with previously published data in animals and man and give further evidence of an important role of the ES in inner ear immune defence.

Antibodies, Monoclonal↗

Preparation of human temporal bone for immunohistochemical investigation.

Successful treatment of progressive sensorineural hearing loss with corticosteroids and cyclophosphamide has promoted the notion of a new entity 'autoimmune hearing loss'. In this context, we have examined sera of patients suffering from idiopathic sensorineural hearing loss, in order to study the binding of humoral antibodies to structures of the normal human inner ear. Investigations were carried out with indirect fluorescence techniques on temporal bones obtained at autopsy. To minimize the possibility of artifacts, we suggested that indirect immunofluorescence with the patients' sera should yield a reproducible positivity on sections of at least three normal temporal bones. In this study, we describe a method for removal and preparation of human temporal bone which ensures reproducible immunohistochemical results.

Adolescent↗

Immunologic structures and functions of the gut.

The intestine is richly populated with lymphoid tissue capable of initiating and effecting a wide variety of immunologic reactions. These reactions have consequences not only for the gut itself but for the body in general, and have established the importance of the gut as an immunologic organ. Among the outer and inner surfaces of our body, the 200 to 300 m2 of the gut contrast with the 2 m2 of the skin, and the 80 m2 of the lung. At the inner surface of the intestine, our organism contacts intimately bacteria, parasites, enzymes, toxins, a wide variety of dietary substances and their breakdown products. The essential barrier against the permanent antigenic burden is the mucosa. Its integrity depends on the continual replication, maturation, and metabolism of its constituents. Additional defense functions are exerted by the mucus, lysozyme, phagocytes, other cells, humoral factors and biological response modifiers involved in inflammatory and immune reactions. Some of these factors are being produced very close to the surface at which they act. The sum of the mechanical, humoral, cellular, immunologic and non-immunologic defense factors of the intestinal mucosa constitutes the mucosal block. However, the block is not complete. Rather, a continuous antigenic uptake through the epithelial layer takes place. The specialized structures of Peyer's patches, solitary lymph follicles, appendix vermiformis and their associated epithelium allow a controlled antigen uptake (sampling). Because of the heavy antigenic load, the intestine can be described as the most important immunologic contact organ of our body. The antigens may give rise to local and systemic immune reactions with antibody production, or the suppression of systemic immunologic responses to ingested antigens ("oral tolerance").

Animals↗

Multiple hamartomas of the breast.

We report the unusual case of two distinct hamartomas in one of the breasts of a 20-year-old woman. Hamartoma (adenolipoma, fibroadenolipoma, lipofibroadenoma) of the breast, a rare benign lesion, occurs in females. It is unilateral and displays an organoid structure. It is composed of lactiferous ducts, mammary glands, and connective and fatty tissue, surrounded by a pseudocapsule. It causes enlargement of the breast, usually without localized lesion on palpation. Mammographic and intraoperative findings, however, are characteristic. As the microscopic features of hamartoma are similar to those of other related benign lesions of the breast, diagnosis may be difficult by histologic examination alone; in addition, knowledge of radiologic, surgical and clinical findings may be required.

Adult↗

Heavy water delays growth of human carcinoma in nude mice.

Deuterium-enriched water has an antiproliferative effect on transplantable mouse tumors without toxic side effects. Since the response to treatment of human carcinomas growing in nude mice is deemed to be a good indicator of the potential clinical behavior of these tumors, we studied the influence of this stable isotope of hydrogen on the growth of xenotransplanted human carcinomas of various histologic types, grades, and primary sites. Seven-week-old Balb/c-nu/nu mice were inoculated subcutaneously, either with oropharyngeal squamous cell carcinomas or with carcinomas of the large intestine. After tumor inoculation, the mice were given drinking water containing 30 atom% D2O. Heavy water effectively retarded the growth of the human carcinomas. At the end of the experiment, the weight of the tumors was reduced to values ranging from 22% to 65% of the control values. The reproducible antiproliferative effect was more conspicuous in poorly differentiated carcinomas than in moderately well-differentiated variants. Since animals in both groups, kept under identical conditions, drank the same amount of water and had similar body weights, the difference in tumor growth can be attributed to the moderate deuteration of the hosts.

Aged↗

Radioprotection by pretreatment with deuterated water: cytokinetic changes in the small intestine of the mouse.

All mice partially deuterated by ingestion of 29% heavy water for 12 days survived whole body gamma irradiation (8.5 Gy) from a 60Co source, whereas 42% of nondeuterated control animals died from bone marrow failure. The incorporation of 3HTdR into enterocytic DNA, as measured by autoradiography and liquid scintillation spectrometry, was used to assess the proliferative activity of small intestinal epithelium. The sequence and the magnitude of changes in tritium activity were in good agreement. Deuteration alone resulted in a reduced proliferative activity of small intestinal crypt epithelium, particularly in the basal cell positions and the first positions of the proliferation compartment. The number of positions occupied by the proliferative compartment and the crypt length were, however, barely affected by deuteration. The radiation-induced depression of DNA synthesis in the proliferative compartment was of similar magnitude in both groups. Crypt epithelium in deuterated mice, however, displayed signs of an accelerated and/or enhanced regeneration. The cytokinetic changes in deuterated animals are consistent with a protective effect for clonogenic intestinal epithelium at the time of irradiation.

Animals↗

Central nervous system radiation syndrome in mice from preferential 10B(n, alpha)7Li irradiation of brain vasculature.

Ionizing radiations were directed at the heads of anesthetized mice in doses that evoked the acute central nervous system (CNS) radiation syndrome. Irradiations were done using either a predominantly thermal neutron field at a nuclear reactor after intraperitoneal injection of 10B-enriched boric acid or 250-kilovolt-peak x-rays with and without previous intraperitoneal injection of equivalent unenriched boric acid. Since 10B concentrations were approximately equal to 3-fold higher in blood than in cerebral parenchyma during the reactor irradiations, more radiation from alpha and 7Li particles was absorbed by brain endothelial cells than by brain parenchymal cells. Comparison of the LD50 dose for CNS radiation lethality from the reactor experiments with the LD50 dose from the x-ray experiments gives results compatible with morphologic evidence that endothelial cell damage is a major determinant of acute lethality from the CNS radiation syndrome. It was also observed that boric acid is a low linear energy transfer radiation-enhancement agent in vivo.

Animals↗

[Hodgkin's disease in a Swiss family].

Hodgkin's disease was found in five members of the same generation in a large Swiss family. At presentation, the patients were between 20 and 30 years old. The histological diagnosis was confirmed in three patients. In one woman the differential diagnosis of histiocytic non-Hodgkin's lymphoma was considered. The patient history did not provide any conclusive evidence for environmental factors shared by all patients. Three siblings had grown up in the same household. They had never been in contact with the other pair of affected sisters. No clustering of cases in time occurred, as individual cases were diagnosed at least two years apart. Antibodies against Epstein-Barr viral capsid antigen were found in four patients (IgG: 1:10 to 1:160). There was no single HLA-haplotype common to all patients. However, two affected sisters were HLA-identical (paternal haplotype: Aw24(9), Bw62(15), DRw6; and maternal haplotype: A2, B7, DR2). Their brother with Hodgkin's disease was homozygous for A-, B- and DR-antigens. He shared all these antigens with his two affected sisters (A2, Bw62(15), DR2). A genetic predisposition in combination with environmental factors, in particular subclinical Epstein-Barr virus infection, may have been responsible for the development of Hodgkin's disease in this family.

Adult↗