bluuebunny/crossref_metadata_2025 huggingface dataset:
THE FAT COMPOSITION OF A MOUSE DIET MODIFIES THE EFFECTS OF LEVAMISOL ON GROWTH AND SPREAD OF A MURINE TUMOR
Authors: BOERYD BERNT , HALLGREN BO
Published: August 2010

The fat composition of the diet fed to C57BL/6J mice influenced the effect of Levamisol on the growth and spread of LLT. The timing of feeding of different diets as well as of the administration of Levamisol in relation to tumor transplantation was of importance. The tumor‐suppressive effect of Levamisol given on day 9 was counteracted by a diet containing 2% soy oil instead of animal fat and given from day 1. Levamisol given on day 1 counteracted the facilitation of tumor growth and spread by the soy oil diet given from day 9. The soy oil diet was shown to suppress the immune response to SRBC. We conclude that standardization of the laboratory diets is necessary.
LANGERHANS CELLS IN LABIAL MINOR SALIVARY GLANDS IN PRIMARY SJÖGREN'S SYNDROME
Authors: Oxholm Peter , Manthorpe Rolf , Oxholm Annemette , Schiødt Morten
Published: August 2010

Langerhans cells were demonstrated among the mononuclear cells in inflamed labial minor salivary glands in a patient with primary SjÖgren's syndrome. Langerhans cells were visualized by the monoclonal antibody, OKT6, by an indirect immunofluorescence technique. The possible role of Langerhans cells as antigen‐presenting cells in diseased glandular tissue in primary SjÖgren's syndrome must be further studied.
LONG‐TERM TOXICITY OF A HYDROGELIC OCCLUSIVE DEVICE IN THE ISTHMUS OF THE HUMAN OVIDUCT
Authors: BRUNDIN J. , SANDSTEDT B.
Published: August 2010

Ten women applying for sterilization volunteered for a tubal blocking procedure. An occlusive device of gamma polymerized hydrogel, a P‐block, was applied in the isthmic part of the oviduct by trans‐cervical hysteroscopy. Bilateral expulsion occurred in three and unilateral in six subjects. Six patients became pregnant. The P‐block was in position from one week to 32 months. Histologically, the reaction to the P‐block was first erosion and acute unspecific inflammation. Later there was a histiocytic and foreign‐body reaction due to dissolution of the hydrogel. When the P‐block was expelled no changes were present in the material.
ESTABLISHMENT AND CHARACTERIZATION OF CELL LINES FROM HUMAN SMALL CELL AND LARGE CELL CARCINOMAS OF THE LUNG
Authors: BERGH JONAS , NILSSON KENNETH , EKMAN ROLF , GIOVANELLA BEPPINO
Published: August 2010

Five new small cell carcinomas (SCC) cell lines and a large cell carcinoma (LCC) cell line were established from human lung cancers. The SCC cell lines had, as a group, common phenotypic properties which distinguished them from non‐SCC cell lines. However, the studies also revealed a considerable biological heterogeneity among the individual SCC cell lines. Thus, the SCC cell lines had a typical growth pattern with cell clusters in suspension or partly adherent to the bottom. All the lines examined grew in agarose with variable cloning efficiencies, and all but one line formed tumors subcutaneously in nude mice. The ultrastructure of the SCC cell lines was characteristic with dense core granules at a variable frequency. Neuron‐specific enolase was detectable in all SCC cell lines, usually in large amounts, and an inconstant production of a spectrum of polypeptide hormones was found, typical of SCC. The LCC cells proliferated in monolayers, formed colonies in agarose and grew in nude mice. Ultrastructurally, the LCC cell line differed from the SCC cell lines in having intra‐ and intercellular lumina and onofilaments. The capacity of the LCC and a previously established squamous cell carcinoma cell line (U‐1752) to produce neuron‐specific enolase and polypeptide hormones was characteristically much lower than that of the SCC cell lines. We conclude from this study that SCC cell lines, although individually distinct from one another, are quite homogeneous as a group in expressing a set of basic common neuro‐endocrine markers. However, these studies also suggest some biological relationship between SCC, LCC and SQC by virtue of their expression of some common neuro‐endocrine markers, in support of the concept of a common histogenetic origin of human lung cancers.
STAINING PATTERNS OF ORAL LESIONS OF DISCOID LUPUS ERYTHEMATOSUS BY MONOCLONAL ANTI‐KERATIN ANTIBODIES
Authors: REIBEL JESPER , SCHIØDT MORTEN , DABELSTEEN ERIK
Published: August 2010

The immunofluorescent staining patterns of oral lesions of discoid lupus erythematosus were examined by use of monoclonal antibodies AE1, AE2 and AE3. AE1 and AE2 showed suprabasal staining, whereas AE3 stained all cell layers of the epithelium. This pattern is consistent with that of other benign hyperkeratinized lesions of the oral mucosa. Occasionally, however, the most basally positioned epithelial cells stained positive with AE1. The morphology of these cells was similar to stratum spinosum cells. Colloid bodies in the epithelium as well as in the connective tissue stained positive with AE1 and AE3, demonstrating their epithelial origin. Few bodies in the connective tissue staining positive with IgM were negative for keratin. These structures may be Russell bodies or may be derived from the basement membrane zone.
PERIODATE‐LYSINE‐PARAFORMALDEHYDE AS FIXATIVE FOR THE STUDY OF DUODENAL MUCOSA
Authors: RANTALA IMMO , MÄKI MARKKU , LAASONEN ANTERO , VISAKORPI JARMO K.
Published: August 2010

Methods are described which utilize periodate‐lysine‐paraformaldehyde (PLP) as the only fixative for the investigation of nonfrozen small‐bowel biopsy specimens by morphologic and immunohistochemical studies at both light and electron microscopic levels. Small‐bowel biopsy specimens were obtained from children suspected of coeliac disease. In light microscopy, there was good morphology and haematoxylineosin staining of the mucosa. Immunofluorescence and immunoperoxidase staining of paraffin‐embedded specimens enabled an accurate demonstration of immunoglobulins (IgA, IgM, IgG) in the duodenal mucosa. In conventional electron microscopy, PLP gave a reasonable preservation of ultrastructure. In immunoelectron microscopy, a pre‐embedding immunoperoxidase technique provided exact ultrastructural localization of immunoglobulins. The methods are easy to adapt and they give reliable light and electron microscopic results.
CHONDROMYXOID FIBROMA
Authors: KREICBERGS A. , LÖNNQUIST P. A. , WILLEMS J.
Published: August 2010

The present paper comprises a review of the literature on chondromyxoid fibroma (CMF) and a report on nine cases originally classified as CMF, found in a review of all curetted bone lesions at our department from 1955 to 1978. At histologic revaluation only two cases fulfilled the criteria for true CMF, whereas six were classified as other benign bone lesions and one proved to be a chondrosarcoma. The chondrosarcoma case after recurrence was subjected to more mutilating surgery than would have been necessary if correct diagnosis had been established initially. The other six benign cases were all well and without signs of recurrence 5–11 years after curettage. In one of the two true CMF cases, i.e. in a young boy, there were for 2 years postoperatively radiological signs of a progressive recurrence, which was left without treatment, since the patient was well. Interestingly, radiograms 2 and 11 years postoperatively essentially showed the same picture, indicating spontaneous cessation of the process. Chondromyxoid fibroma is an extremely rare lesion. Histologic misinterpretation is not uncommon. In sporadic cases this may have serious implications. It may be questioned whether surgical treatment of CMF in young patients, known to have a high recurrence rate, is mandatory.
S‐100 PROTEIN IN MALIGNANT MESOTHELIOMAS
Authors: Rasmussen Ole Ø. , Larsen Knud Erik
Published: August 2010

Recently, the presence of S‐100 protein has been described in a few tissues that are not of neuro‐ectodermal origin. Here we report the presence of S‐100 protein in epithelial and biphasic malignant mesotheliomas and one of seven reactively proliferating mesothelial lesions. Sarcomatous malignant mesotheliomas, six of seven reactive mesothelial lesions and normal mesothelium were without S‐100 protein. The presence of S‐100 protein in mesothelial cells may indicate intense proliferation.
RELEASE OF FIBRONECTIN, SULFATED GLYCOSAMINOGLYCANS AND β‐HEXOSAMINIDASE FROM INJURED SMOOTH MUSCLE CELLS AND FIBROBLASTS IN CULTURE ‐ POSSIBLE TRANSFERABLE EFFECTS ON NEW CULTURES
Authors: STAVENOW L. , HULTBERG B.
Published: August 2010

The effect of injury to the bovine arterial smooth muscle cellin vitrowas studied. Injury was caused by dimethylsulphoxide‐soluble particles from cigarette smoke. The release of fibronectin was studied with human skin fibroblasts, but all other experiments on bovine myocytes. Fibronectin release was increased from injured cells, while that of sulfated glycosaminoglycans was decreased. These changes in release were evident already during the first hour after injury, while the increased release of the lysosomal enzyme β‐hexosaminidase was manifest 1–24 hours after injury, but not during the first hour. Conditioned medium from injured cells was toxic to new cultures. This toxicity could be prevented by including the protease inhibitor α1‐antitrypsin to the cultures exposed to smoke particles. When α1‐antitrypsin was added first after the cells had been exposed to the smoke particles it was without effect. The free radical scavenger vitamin E was without effect. Cell detachment was a good index of cell death after exposure to cigarette smoke particles, as judged from the simultaneous measurement of DNA content and trypan blue uptake. During the period 24 hours after the toxic influence of cigarette smoke particles on original cultures, or 24 hours after the action of conditioned medium on new cultures, the injured cells revealed an augmented DNA synthesis compared to controls. The injured cells were, however, less responsive to growth‐stimulating activity from platelets.
GYNECOMASTY: ESTROGEN AND ANDROGEN RECEPTORS. A Clinical‐Pathological Investigation
Authors: POULSEN HANS SKOVGAARD , HERMANSEN CHRISTIAN , ANDERSEN JOHAN A. , ANDERSEN HANS U. , JENSEN JØRN
Published: August 2010

The histology, estrogen (ER)‐ and androgen (AR)‐ receptor content, s‐FSH, s‐LH, s‐17‐β‐estradiol, U‐17‐ketosteroid and U‐17‐ketogen steroid patterns were measured in a consecutive series of 20 patients operated on for gynecomasty. Two out of 22 specimens were ER‐positive, and 4 out of 22 were AR‐positive. No relationship was demonstrated between the histopathologic features, ie. active – intermediate – inactive gynecomasty, and the steroid receptor content in the present limited number of cases. In addition, there was no marked relationship between the histopathologic features and the hormone values.
INFLAMMATORY CELLS IN 256 WALKER TUMOUR GROWING IN THE STOMACHS OF RATS
Authors: BRØYN T. , STORVIK H. , SVENNEVIG J. L.
Published: August 2010

The present study was undetaken in order to determine the relative number of inflammatory cells in Walker 256 tumour implanted in the gastric mucosa of the rat. Inflammatory cells were found in all tumours, the relative content ranging from 5–21 (mean 12 %), which is comparable to findings in human intestinal tumours. Approximately 80 % of the inflammatory cells were mononuclear (lymphocytes, plasma cells and macrophages); less than 20 % were polymorphonucleated (neutrophils and eosiniphils). Both the number of inflammatory cells and the composition of the cell infiltrates changed during the tumour growth. The highest proportion was found on day 6 after implantation. In addition to the inflammatory cells within the tumor parenchyma, a large number of inflammatory cells were found in the tumour stroma. Possible mechanisms for the inflammatory cell reaction within and around the experimental tumours are discussed.
XENO‐ AND AUTO‐PERFUSION OF RABBIT KIDNEY.
Authors: JØRGENSEN KAJ ANKER , KEMP EJVIND , BARFORT PER , STARKLINT HENRIK , LARSEN SVEND , JACOBSEN IB ABILDGAARD , DIEPERINK HANS , FRIFELT JENS JØRGEN , MUNK‐ANDERSEN GEORG
Published: August 2010

Five rabbit kidneys were perfused with human blood and another five with their own blood in a re‐circulating oxygenated system at 37°C. The flow decreased to 2 ml/min. within 30 min. in all xenoperfusions, while none of the autoperfused had decreased to this level by 60 min. Endothelial damage, exudation, and IgG deposits along the basement membrane of the glomerular capillaries were the discrimininative features of the xenoperfusion. In these experiments, we were unable to demonstrate any major role of platelets in the process leading to decreased blood flow.
DISSEMINATED HISTIOCYTOSIS X
Authors: ØRNVOLD K. , NIELSEN M. H. , CLAUSEN N.
Published: August 2010

Fourteen cases of disseminated histiocytosis x (HX) from a 15 year period were studied clinicopathologically. Morbidity and mortality were comparable to that of previous reports on disseminated HX. S‐100 protein, recently established as a HX marker, was demonstrated immunohistochemically in the cytoplasm and the nuclei of the HX cells of 12 examined cases. Neuron specific enolase (NSE) positive material was found in a minority of the cells of 2 cases. Cytoplasmic lysozyme was present in the mononuclear cells accompanying the HX cells in all examined cases. These results show that immunohistochemical demonstration of S‐100 protein and lysozyme can be successfully applied to formalin‐fixed, paraffin embedded tissue after storage at room temperature for as long as 15 years. The presence of cytoplasmic NSE positivity in the lesions from 2 patients was surprising and has not previously been observed in HX. This finding suggests an antigenic heterogenicity between cases with the disease of unknown prognostic significance. Nor did the presence of lysozyme in the lesions from patients with acute as well as chronic disease yield any prognostic information.
STAINING PATTERNS OF HUMAN PRE‐MALIGNANT ORAL EPITHELIUM AND SQUAMOUS CELL CARCINOMAS BY MONOCLONAL ANTI‐KERATIN ANTIBODIES
Authors: REIBEL J. , CLAUSEN H. , DABELSTEEN E.
Published: August 2010

Formalin‐fixed, paraffin‐embedded biopsies of metaplastic keratinized oral mucosa (fibromas and leukoplakias), oral mucosa with epithelial dysplasia and oral squamous cell carcinomas were stained with two monoclonal anti‐keratin antibodies (AE1 and AE2). Intense suprabasal staining was seen with AE1 in metaplastic keratinized epithelium, whereas staining of adjacent normal unkeratinized epithelium generally was restricted to basal cells. In dysplastic epithelium and squamous cell carcinomas, staining with AE1 revealed a highly disturbed anti‐keratin staining pattern. AE2 stained metaplastic keratinized epithelium in a suprabasal pattern but adjacent unkeratinized epithelium did not stain. In dysplastic epithelium and squamous cell carcinomas, AE2 staining was variable and sometimes absent. Further studies are indicated to clarify whether changes in anti‐keratin staining patterns can be used for diagnostic and prognostic purposes.
INDUCTION BY PARACETAMOL OF BLADDER AND LIVER TUMOURS IN THE RAT
Authors: FLAKS BOJAN , FLAKS ANTONIA , SHAW ANDREW P. W.
Published: August 2010

Groups of male and female inbred Leeds strain rats were fed diets containing either 0.5% or 1.0% paracetamol by weight for up to 18 months. At the 1.0% dosage level, 20% of rats of both sexes developed neoplastic nodules of the liver, a statistically significant incidence. These rats also showed gross enlargement of their livers and an increase in foci of cellular alteration, the latter also being observed in the low dosage male rats. Papillomas of the transitional epithelium of the bladder developed in all paracetamol‐treated groups, and three rats bore bladder carcinomas. However, significant yields of bladder tumours were only obtained from low dosage females and high dosage males. Additionally, 20 to 25% of paracetamol‐treated rats developed hyperplasia of the bladder epithelium, which was not coincident with the presence of bladder calculi. A low yield of tumours at various other sites also arose following paracetamol feeding. An electron microscope study of the livers of paracetamol‐treated rats revealed ultrastructural changes in the hepatocytes that resemble those that result from exposure to a variety of known hepatocarcinogens.
CEREBELLAR FOLIATION IN RATS
Authors: CONRADI NILS G.
Published: August 2010

The cerebellar cortices of foetal rats were examined for structural changes occurring prior to the formation of fissures. Female rats were mated overnight and the first day on which a sperm‐positive vaginal smear was found was designated as embryonic day 1 (E1). Birth of rats generally occurs on day E23. Foetuses from days E19 to 22 were fixed by perfusion followed by immersion, using a mixture of glutaraldehyde and paraformaldehyde, and their cerebella embedded in plastic. The cerebella of thirty‐five foetuses were sectioned sagittally at intervals of 100 μm, and those of five were sectioned coronally. A continuous Purkinje cell layer was formed during the examination period by fusion of four transverse bands. The study revealed formation of pre‐migratory granule cells in the EGL of foetal rats. The granule cells were orientated in the coronal plane and were seen only where Purkinje cells were present beneath the EGL. A local increase in pre‐migratory granule cells and indentation of the Purkinje cell layer were early signs of foliation and occurred prior to the formation of a fissure. The subsequent deepening of the fissures was due to the outward expansion of lobules, and the bottom of the different fissures retained their spatial relationship. The findings show that the expansion of the cerebellar surface is tangential before and after the formation of a fisure. In order to indent the surface, the direction of the expansion must change temporarily. This reorientation of the expansion appears to be related to the cortical changes which have been described and marks the onset of foliation.
LARGE, BUT NOT SMALL, ANTIGENS REQUIRE TIME‐AND TEMPERATURE‐DEPENDENT PROCESSING IN ACCESSORY CELLS BEFORE THEY CAN BE RECOGNIZED BY T CELLS
Authors: Buus SØREN , Werdelin OLE
Published: August 2010

We have studied if antigens of different size and structure all require processing in antigen‐presenting cells of guinea‐pigs before they can be recognized by T cells. The method of mild paraformaldehyde fixation was used to stop antigen‐processing in the antigen‐presenting cells. As a measure of antigen presentation we used the proliferative response of appropriately primed T cells during a co‐culture with the paraformaldehyde‐fixed and antigen‐exposed presenting cells. We demonstrate that the large synthetic polypeptide antigen, dinitrophenyl‐poly‐L‐lysine, requires processing. After an initial time‐lag of 30 min this antigen is fully processed within 2 to 4 of culture at 37°C. In contrast, the immunogenic heptapeptide, angiotensin III, can be presented by pre‐fixed accessory cells, viz. without any prior processing. Antigen processing was found to be temperature‐dependent and consequently energy‐requiring. Processing is strongly inhibited by the lysosomotrophic drug, chloroquine, suggesting a lysosomal involvement in antigen processing. The existence of a minor, non‐lysosomal pathway is suggested, since small amounts of antigen were processed even at 10°C, at which temperature no transport to and from the lysosomes can occur.
COMPARISON BETWEEN HOMOGENEOUS PHASE RADIO‐ASSAY AND ENZYME‐LINKED IMMUNOSORBENT ASSAY FOR MEASUREMENT OF ANTITHYROGLOBULIN ANTIBODY CONTENT IN SERUM
Authors: Feldt‐Rasmussen ULLA , HØIer‐Madsen MIMI , Hansen HANNE SAND , Blichert‐Toft MOGENS
Published: August 2010

The aim of the study was to test the influence of thyroglobulin in vitro and in vivo on two different principles for quantification of serum antithyroglobulin antibody content. The methods employed were a previously described homogeneous phase radioassay and a newly developed enzyme‐linked immunosorbent assay. Thyroglobulin inhibited the measurement of antithyroglobulin antibody content by both methods, not only by addition in vitro but also when present in vivo as a result of release from thyroid surgery. Both methods proved sufficiently sensitive as screening for presence of antithyroglobulin antibodies before measurement of thyroglobulin in serum. The study shows the importance of assessing the assay systems in each laboratory for interference before use, especially if intended for screening before quantifying serum thyroglobulin or for measurement of antithyroglobulin antibodies in other media (e.g. supernatants from lymphocyte cultures).
THE INDIRECT LEUCOCYTE MIGRATION INHIBITION ASSAY — AN ENDOTOXIN‐SENSITIVE CHEMOKINETIC ASSAY. PART II
Authors: Remvig L. , Baek L. , Kristensen E.
Published: August 2010

Depletion of agarose for endotoxins resulted in a low spontaneous migration of polymorphnuclear cells (PMNC). Re‐addition of endotoxin, in casu lipopolysaccharide from E. coli 026:B6 (LPS), enhanced the spontaneous PMNC migration in a two‐phased dose‐response pattern, reaching maximum migration with LPS 1 times 10−7 g/ml. Thus, the migration of PMNC under agarose seems to be a chemokinesis. Leucocyte migration inhibition factor (LIF), induced by PPD 50 μg/ml at endotoxin‐free conditions, significantly reduced the PMNC migration compared to supernatants from control cultures, however not compared to the conventional limit of significance, MI = 0.80. With increasing PMNC migration there was an insignificant decrease in the MI. Addition of LPS, 1 times 10−9 g/ml, during LIF induction caused a significant increase in LIF production, an effect which overshadowed the effect of PPD. Thus, the application of the conventional limit of significance, MI = 0.80, may result in false‐negative or false‐positive conclusions, depending upon the endotoxin contamination. A standardization of the endotoxin content in both steps of the indirect leucocyte migration inhibition assay seems mandatory in order to obtain a reliable and reproducible bioassay.
RESTRICTED HETEROGENEITY OF THE EARLY ANTIBODY RESPONSE TO ALEUTIAN DISEASE VIRUS IN MINK KITS
Authors: Alexandersen SØREN , Aasted BENT
Published: August 2010

Mink kits born of Aleutian disease (AD) negative dams were infected neonatally with different isolates of Aleutian disease virus (ADV). They were then sacrified at different days after infection (10 — 45 days) and their sera were analysed by different techniques for concentrations of immunoglobulins and quality of the produced antibodies to ADV. The infected mink kits produced significantly higher concentrations of IgM and IgG immunoglobulins than non‐infected‐age matched control mink (p<0.001). Eight percent of the sera from the infected mink kits exhibited a restricted heterogeneous gammaglobulin profile as shown by serum electrophoresis. These findings were further investigated by other techniques such as SDS‐PAGE and crossed serum line immunoelectrophoresis. It is concluded that mink kits when infected neonatally with ADV start to develop hypergammaglobulinemia soon after infection, and that a small percentage of the mink react with a gammaglobulin response of restricted heterogeneity.
SECRETORY PRODUCTS FROM THROMBIN‐STIMULATED HUMAN PLATELETS EXERT AN INHIBITORY EFFECT ON NK‐CYTOTOXIC ACTIVITY
Authors: Madsen P. SKOV , Hokland P. , Hokland M.
Published: August 2010

We have investigated the interaction between human platelets and the NK‐system, with special emphasis on the action of secretory products from platelets in an NK assay with 51Cr‐labelled K562 as target cells. Supernatants from thrombin‐stimulated platelets added to the NK assay consistently decreased the NK‐cytotoxicity by 40% 4.3%, indicating the existence of secreted products from platelets as a source of NK‐inhibiting substances. In contrast, no direct cytotoxic effect of these secretory products on the target cells (K562) was seen. Thus, normal human platelets, when stimulated with thrombin, are capable of secreting different, yet undefined factors, which significantly inhibit NK activity in vitro. The results also suggest that the role of products from contaminating in vitro activated platelets should be borne in mind when performing conventional NK assays.
METABOLIC BONE DISEASE AND ALUMINIUM CONTAMINATION IN 38 UREMIC PATIENTS
Authors: PØDenphant J. , Heaf J. G. , Joffe P.
Published: August 2010

Iliac crest biopsies from 38 uremic patients, 26 hemodialysis, and 12 chronic uremics from a nephrology department with verified aluminium free dialysis water were investigated with histomorphometric method and aluminium‐specific staining. For both the uremic and the dialysed group the results showed a high incidence of both metabolic bone disease (75%, 69% respectively) and aluminium contamination (25%, 62%).
MAMMARY CARCINOMA: COMPARISON OF DNA‐CONTENT IN THE PRIMARY TUMOR AND THE CORRESPONDING AXILLARY LYMPHNODE METASTASES
Authors: Erhardt KERSTIN , Auer GERT
Published: August 2010

Twenty primary mammary carcinomas and their corresponding axillary lymphnode metastases were studied. The DNA‐content of individual tumor cells was measured in sections from the original paraffin embedded specimens. Comparison between the DNA‐patterns obtained from the primary tumor and the corresponding metastases showed very close agreement in all but one case. Both euploid and aneuploid tumors were represented. In spite of having lymphnode metastases at operation, 8 patients survived more than 10 years after operation. All of these patients had euploid tumors, in contrast to 11 patients who died within 2 years, in whom all but one of the tumors showed aneuploid DNA‐patterns. The results suggest that tumor progression in terms of lymphnode metastases is usually not associated with major changes in tumor nuclear DNA‐content.
IMMUNOHISTOCHEMICAL REACTIVITY OF MONOCLONAL ANTIBODIES TO HUMAN MILK FAT GLOBULE WITH BREAST CARCINOMA AND WITH OTHER NORMAL AND NEOPLASTIC TISSUES
Authors: Helle MARKKU , Krohn KAI
Published: August 2010

The immunohistochemical reactivity of three monoclonal antibodies, generated against human milk fat globule membranes (HMFG), were studied using peroxidase conjugated secondary antibody or avidin‐biotin‐peroxidase complex method. Two of the antibodies, III E 8 and III H 2 showed rather broad reactivity, staining all mammary, ovarian, endometrial, cervical and bronchial adenocarcinomas. They also stained all pancreatic adenocarcinomas but only 30% of the carcinomas of the colon. Reaction with prostatic and renal adenocarcinomas varied. No reaction was seen with squamous or transitional cell carcinomas. Antibody III D 5, which previously has been shown to recognize an estrogen receptor activation associated antigen in mammary carcinomas, stained 60% of mammary or gynegological adenocarcinomas. This antibody had a more limited reactivity with other tissues as well, as all intestinal carcinomas were negative. It stained all bronchial adenocarcinomas, however, and 50% of the prostatic carcinomas. The three monoclonal antibodies, althought not specific, show a more restricted reactivity than the so far described HMFG antibodies and they may therefore be of value in histopathological diagnosis.
PRECANCEROUS CHANGES IN THE ANAL CANAL EPITHELIUM IN RESECTION SPECIMENS
Authors: Fenger CLAUS , Nielsen VIBEKE THUE
Published: August 2010

Systematic histological examination for precancerous changes was carried out on 139 anal canals resected for anal or colo‐rectal tumours or for inflammatory bowel disease. Severe squamous dysplasia or carcinoma in situ were found in 13 of 16 anal canals harbouring variants of squamous carcinoma but not in others. The lesions were mainly or totally located to the anal transitional zone (ATZ) in 11 cases and only in 2 cases exclusively to the squamous zone below the dentate line. Dysplastic areas separate from the tumour were found in 6 of the 13 cases. Junctional melanocytic activity and atypical melanocytic hyperplasia located in the ATZ as well as the squamous zone were present in 1 of 3 cases of malignant melanoma. The findings underline the close relationship between dysplasia and invasive carcinoma in the anal canal. Further they support the concept that basaloid, mucoepidermoid and some ordinary squamous carcinomas arise in the ATZ, and that this may also be the point of origin for malignant melanoma. A search for precancerous changes for anal canal tumours should therefore include the whole ATZ, i.e. in some cases up to 2 cm above the dentate line and it should be borne in mind that the lesions may be spotty.
LACK OF HISTOLOGICAL SIGNS IN RATS DYING DURING THE ACUTE PHASE OF EXPERIMENTAL AUTO‐IMMUNE ENCEPHALOMYELITIS
Authors: KÄLlÉN Bengt , Nilsson Olle
Published: August 2010

Rats dying acutely of experimental auto‐immune encephalomyelitis show very meagre histological signs of the disease in routine histology sections. This cannot be explained by postmortal changes. It is suggested that the infiltrating lymphoid cells seen in the central nervous system of surviving rats are involved in the normally occurring self‐limitation of the disease.
ENTEROCYTE‐LABELLING INDEX IN THE DUODENAL MUCOSA OF PATIENTS WITH PROGRESSIVE SYSTEMIC SCLEROSIS (PSS)
Authors: Hendel LENE , AmmitzbØLl THORKIL , Petri M.
Published: August 2010

Ten patients with progressive systemic sclerosis (PSS), 4 patients with other gastro‐intestinal diseases and 5 normal controls, underwent small intestinal biopsy procedure. The biopsy material was incubated with tritiated thymidine and processed for auto‐radiography. The labelling index (LI) in the small intestinal mucosa was estimated. The LI in PSS patients with duodenal involvement was significantly higher than the LI in PSS patients without duodenal involvement. In the latter group, the LI was at the same level as in normal controls. The LI in patients with other gastro‐intestinal diseases, with diarrhoea as a main symptom, was not significantly different from the LI found in duodenal PSS.
OCCURRENCE OF BENIGN HEPATOCELLULAR TUMORS IN ALCOHOLIC MEN
Authors: Karhunen PEKKA J. , PenttilÄ ANTTI , Liesto KIMMO , MÄNnikkÖ ANTTI , MÖTtÖNen MATTI M.
Published: August 2010

Focal nodular hyperplasia (FNH) and liver cell adenoma (LCA) are benign hepatocellular tumors, found mainly in females in association with the use of oral contraceptives. In adult male clinical patients and in retrospective male autopsy cases, both tumors were often found in association with chronic abuse of alcohol. This association was also found (p< 0.025) in a prospective autopsy series on alcoholic and non‐alcoholic males, in which a family member or close friends of the deceased were interviewed for estimating the consumption of alcohol. Nine of the 12 tumors found in males were FNH and three were LCA. In the average males with FNH were as old (51.0 years) as those with LCA (48.7 years). In two of the FNH cases two tumors were found. In the prospective autopsy series the weight of the liver of males with FNH was significantly (p < 0.001) higher than that of non‐alcoholic controls. A correlation (p <0.05), independent of age or liver weight, was found between the size of cavernous hemangioma, another hepatic tumor suggested to respond to estrogens, and daily alcohol dose. It is suggested that alcohol‐induced liver cell hypertrophy or the feminizing effect of chronic use of alcohol on male sex hormone metabolism might contribute to the growth of pre‐existing benign hepatocellular tumors in males.
THE SIGNIFICANCE OF HANDMIRROR CELLS IN ACUTE MYELOCYTIC LEUKAEMIA TYPE M1 AND M2 AFTER WEAK CYTOSTATIC TREATMENT
Authors: Norberg BO , Wredhammar ULF , Wahlin ANDERS , Eriksson STURE , Rudolphi OLLE
Published: August 2010

The handmirror shape is a cell configuration assumed by mononuclear leucocytes and leucocyte precursors during locomotion. A fraction of fixed tumour cells in bone‐marrow smears from patients with acute leukaemia have this handmirror shape. The incidence of handmirror cells has been reported to correlate positively with length of patient survival in some previous studies, but not in others. This controversy was elucidated by examination of bone‐marrow smears of a retrospective material, consisting of smears from 32 patients with acute myelocytic leukaemia of the M1 and M2 type from 1971–1974. During this period, cytostatic treatment of acute myelocytic leukaemia was so weak that it can be considered almost negligible for the patient group studied. There was a positive but statistically non‐significant correlation between incidence of handmirror cells and length of patient survival (Rs=+0.28, p=0.11). It is reasonable to assume that incidence of handmirror cells is a minor prognostic sign, the effect of which is not detectable in all materials.
A PITFALL IN THE INTERPRETATION OF INTESTINAL METAPLASIA OF THE STOMACH
Authors: Rubio C. , Kato Y. , Kitagawa T. , Sugano H.
Published: August 2010

Four cases having vacuolated gastric (pyloric) cells resembling the goblet cells of intestinal metaplasia are presented. Contrary to goblet cells of intestinal metaplasia, the vacuolated pyloric cells in the four cases herein reported were negative for mucus stains. Although the nature of these mucus‐free vacuolated gastric cells remains obscure, their occurrence should be considered in studies of intestinal metaplasia of the stomach.
RELIABILITY OF ENDOMETRIAL CANCER DIAGNOSES IN A SWEDISH CANCER REGISTRY – WITH SPECIAL REFERENCE TO CLASSIFICATION BIAS RELATED TO EXOGENOUS ESTROGENS
Authors: Persson INGEMAR , Adami HANS‐OLOV , Lindgren ANDERS , Nordlinder HANS , Pettersson BIRGITTA , Silverberg STEVEN
Published: August 2010

In this study, various qualitative aspects of endometrial cancer diagnoses were critically evaluated regarding cases included in the Swedish Cancer Registry from the Uppsala Health Care Region. By comparing the number of such cases in the registry with cases reported directly from the departments of pathology and of gynecological oncology in the same region, it was found that approximately 5% of all incident cases had not been notified to the registry. An independent histopathological review of the original specimens showed that almost 9% of the cases did not represent an endometrial neoplastic lesion, the majority of these being reclassified as uterine sarcoma. The review also revealed the problem of a diagnostic bias that might arise in connection with estrogen exposure, in that a significantly higher proportion of the cases observed in a cohort of women who had received estrogen prescriptions were reclassified as a premalignant endometrial lesion than of the cases from the background population without estrogen exposure (33% versus 10%). Additional independent reviews of cases showing discordant diagnoses in the primary review indicated variability in diagnostic criteria among pathologists. It is concluded that when cancer registry data are employed in epidemiological studies of endometrial cancer, the use of additional sources of case recruitment is desirable in order to obtain a complete material; also that an independent histopathological review is necessary to standardize diagnostic criteria and thereby to avoid a classification bias.
LECTIN‐BINDING SITES IN NORMAL, HYPERPLASTIC, ADENOMATOUS AND CARCINOMATOUS HUMAN COLORECTAL MUCOSA
Authors: Kellokumpu1 I. , Karhi K. , Andersson L. C.
Published: August 2010

The carbohydrate structures of cellular glycoconjugates in normal, hyperplastic, adenomatous and carcinomatous human colorectal mucosa were analysed with six fluorescein isothiocyanate‐conjugated lectins. In normal, hyperplastic and adenomatous colorectal mucosa showing mild or moderate dysplasia Concanavalin A (Con A), Lens culinaris (LCA), and wheat germ (WGA) agglutinins stained goblet cell glycoconjugates (actual mucin goblet ifself) while peanut (PNA), Vicia villosa (VVA), and Griffonia simplicifolia‐II (GSA‐II) agglutinins showed a supranuclear staining of goblet cell glycoconjugates. After neuraminidase treatment of tissue sections PNA and VVA stained mucin goblets of mature cells in normal mucosa, while less differentiated cells in the lower crypt displayed a supranuclear staining with VVA. The mucin goblets in adenomatous mucosa with mild or moderate dysplasia did not stain with PNA and VVA, neither before nor after neuraminidase treatment. Areas of in situ cancer in adenomas and carcinomas displayed a strong and direct binding of ConA, LCA, WGA and PNA in an apical linear distribution, while the binding of VVA and GSA‐II was heterogeneous. We conclude that there are alterations in the carbohydrate structures of cellular glycoconjugates, which can be related to goblet cell differentiation in normal colorectal mucosa and to the degree of dysplasia in adenomas. Heterogeneous and incompletely glycosylated glycoconjugates appear to be synthesized by the majority of colorectal carcinomas.
SIALYLATED LEWISa DETERMINANT CA 19‐9 IN BENIGN AND MALIGNANT GASTRIC TISSUE
Authors: Sipponen PENTTI , Lindgren JAN
Published: August 2010

The expression of the carbohydrate antigen CA 19‐9 in human gastric mucosa was studied by using the monoclonal 1116 NS 19‐9 antibody, immunohistochemical ABC staining technique and formalin‐fixed, paraffin‐embedded biopsy specimens. Among 26 gastric carcinoma (GCA) patients CA 19‐9 antigen was found in 16 patients (62%). The antigen was also found in 10 (48%) out of 21 non‐cancer patients who had benign gastric ulcer and in 9 (12%) out of 74 non‐ulcer, non‐cancer patients. In non‐cancerous mucosa, the CA 19‐9 antigen was localized in the surface epithelium (foveolar type of staining) and/or in goblet cells and sometimes in absorptive epithelium of metaplastic intestinal glands (goblet cell type). The foveolar type but not the goblet cell type was related to the nonsecretor status of the subject, to Lea positivity and to anti‐H negativity of the gastric surface epithelium. It is concluded that, although being commonly present in GCA tissue, the expression of the antigen in benign gastric tissue is too common to advocate the practical value of CA 19‐9 in predicting malignant gastric lesions in immunohistochemistry.
ULTRASTRUCTURE OF HYALINE CARTILAGE
Authors: Engfeldt BENGT , Hultenby KJELL , MÜLler MARTIN
Published: August 2010

Important progress in the cryofixation of tissues has recently been made with the introduction of a new technique which permits a great reduction in the rates of ice‐crystal growth and nucleation by rapid freezing under a pressure of 2 100 bar. Tissue pieces up to 0.5 mm in thickness can now be processed at a freezing rate sufficient to prevent the formation of detectable ice crystals at the ultrastructural level. In the present investigation this technique, in combination with freeze substitution and low temperature embedding was applied for ultrastructural and immunocytochemical studies of hyaline cartilage. No extraction of matrix proteoglycans was observed during the substitution procedure, and there are good reasons to believe that in preparations obtained by this technique the native state of the matrix components is preserved, since, for example, the collapse temperature of the macromolecules is not exceeded. Furthermore, no chemical fixatives or cryoprotectants are required. Ultrastructural differences in the hyaline cartilage of the growth‐plate between normal rats and mice were observed, and also differences between cartilage at different locations, such as tracheal cartilage and growth‐plate. Using this technique, further comparative ultrastructural studies enable us to obtain information about the macromolecular organisation of cartilage matrix under various normal and pathological conditions in vivo. In addition, using monoclonal antibodies to the main macromolecules of the matrix, it was found that this technique not only provides excellent tissue preservation but is also well suited for immunocytochemistry with colloidal gold as a marker.
COMPARISON OF CHARACTERISTICS OF HUMAN SMALL CELL CARCINOMA OF THE LUNG IN PATIENTS, IN VITRO AND TRANSPLANTED INTO NUDE MICE
Authors: Engelholm S. AA. , Spang‐Thomsen M. , VindelØV L. L. , BrÜNner N. , Nielsen M. H. , Hirsch F. , Nielsen A. , Hansen H. H.
Published: August 2010

Specimens from 24 patients with metastatic small cell carcinoma of the lung were explanted in vitro as well as transplanted directly into nude mice. A method to obtain fibroblast‐free cultures is described. This method resulted in cell lines which could be grown for more than one year in 79% of the cases. Fifty‐four % of the tumours could be established as serially transplantable tumours in nude mice. The tumours were characterized by histology, electron microscopy, DNA index, and cell cycle distribution. The in vitro cell lines were furthermore characterized by the plating efficiency and by doubling time. The macroscopic growth of the heterotransplanted tumours was ascribed to a transformed Gompertz function. The tumour cells preserved their light microscopic constitution of small cell carcinoma of the lung in the model systems. The heterogeneity of the original tumours was reflected in vitro and in nude mice and the model systems thus allows an expression of the inherent heterogeneity and instability. The panel of transplantable tumours and the in vitro cell lines offer the study of biology inclusive of tumour progression of SCCL.
PHENOTYPIC IN SITU CHARACTERIZATION OF LYMPHOCYTES IN MILD ALCOHOLIC LIVER DISEASE
Authors: Bergroth V. , Konttinen Y. T. , Segerberg‐Konttinen M. , Ollikainen V. , Salaspuro M.
Published: August 2010

The subsets and expression of activation markers of inflammatory mononuclear cells in mild alcoholic liver disease were studied using monoclonal antibodies and an avidin‐biotin‐peroxidase complex (ABC) method. There were few B cells and monocytes in situ. Most of the mononuclear cells were of T cell origin, T4 and T8 positive cells being evenly distributed in a ratio of 2 to 1. This contrasts with the present and earlier findings on autoimmune liver diseases. The frequency of Ia (HLA‐DR) positive cells varied between 15 and 30% of all mononuclear cells, which indicates activation of the local T cells. This implies that T cells in alcoholic fatty liver are not innocent bystanders but actively participate in the local inflammatory process. Staining for Tac, 4F2 and T9 was completely negative, however. These findings suggest that the local T cell activation may be incomplete and that it is not as extensive as in autoimmune liver diseases.
POLYCYTAEMIA VERA ASSOCIATED WITH THYMOMA
Authors: Voigt SØREN
Published: August 2010

Even though the coexistence of rare clinical conditions may be conincidental, an association between thymoma and autoimmune diseases appears well‐established, possibly mediated via T‐lymphocytes. An unusual case of initial polycytaemia vera and the later diagnosis of a thymoma, and with this known associated diseases is presented.
MONOCLONAL ANTIBODIES TO GFAP EPITOPES AVAILABLE IN FORMALDEHYDE FIXED TISSUE
Authors: Jie ZHENG , Ivarsson BIRGITTA , Collins V. PETER
Published: August 2010

We have recently demonstrated that one of our monoclonal antibodies (MAB's) to glial fibrillary acidic protein (GFAP) recognizes an epitope on this molecule which is to a large degree blocked during fixation with formaldehyde or crosslinking with Dithiobis (Succinimidyl) Propionate (DTSP). This was shown to be due to the crossbinding of a single or a number of proteins to the GFAP and is not due to a change in the epitope on GFAP induced by the fixation itself. In an attempt to produce further MAB's capable of recognizing epitopes on the GFAP molecule available following formaldehyde fixation, we immunized BALB‐C mice with cytoskeletal preparations of human glioma cells which contain GFAP where the blocking protein or proteins were crossbound by DTSP or formaldehyde to the GFAP. Following fusion of the spleen Iymphocytes to Sp 2/0 myeloma cells we have cloned hybridomas which produce antibodies that recognize GFAP in formaldehyde fixed tissues. This method presents the antigen in its native “fixed” state for the mouse's immune system and avoids the production of MAB's which (although excellent for immunochemical studies) do not recognize any epitopes available on the molecule in question in formaldehyde fixed tissues. Antibodies so produced are of great interest in routine pathology where most tissues are still, unfortunately, undiscriminately fixed in formalin. The results also show that GFAP varies immunologically in different species (i.e. human v. rat/mouse) and confirm that the GFAP of the PNS is immunologically distinct and/or associated with different proteins from that found in the CNS.
MORPHOLOGICAL FEATURES OF ESTABLISHED CULTURES OF HUMAN SQUAMOUS LUNG CARCINOMA CELLS AND THE CELLULAR DISTRIBUTION OF TUMOR‐SPECIFIC GLYCOPROTEINS
Authors: Klokker M. , Jessen H. , Olsson L. , Behnke O.
Published: August 2010

Phenotypic characteristics of a cloned cell line, RH‐SLC‐L11, established from a human squamous lung carcinoma, were studied. The line has maintained its morphologically characteristic growth pattern for over 3 years. Settling cells exhibited extensive surface blebbing during spreading and established small cell islands that eventually expanded by mitosis to confluent cultures. Cell islands and confluent cultures presented three cell types: (i) small, polygonal cells, (ii) polygonal cells of intermediary size and (iii) very large, extremely flattened, degenerating cells. Mitotic activity was present predominantly in type (i) and the sequence (i) ‐ (iii) is presumed to represent the lines' cycle. Previous work has demonstrated that the SLC‐L11 line releases tumor‐associated glycoproteins and glycolipids. These could be identified with a murine Mab (43‐9F). The specific epitope was determined by carbohydrate residues and was shown to have growth factor‐like properties. Mab 43‐9F bound heterogeneously to the surface of SLC‐L11 cells: Most large cells were unreactive while both type (i) and (ii) cells showed conspicuous differences in immunostaining intensity. Immunocytochemical analysis also indicated redistribution, shedding and internalization of antigen‐Mab complexes, which may have significant impact on the use of the epitope as tumor marker in diagnosis and therapy. No definite clue was obtained as to the release of the antigenic carbohydrate epitope itself.
VACCINATION‐INDUCED ACTIVATION OF HUMAN BLOOD T CELLS SUPPRESSING PNEUMOCOCCAL POLYSACCHARIDE‐SPECIFIC B CELLS
Authors: Heilmann Carsten
Published: August 2010

In order to study the regulation of the human B cell response to pneumococcal polysaccharides (PPS), anti‐PPS‐secreting cells (SC) and Ig‐SC were quantitated in unstimulated and EBV‐stimulated cultures of blood mononuclear cells (MNC) established before and one and two weeks after vaccination. In unstimulated cultures established one week after vaccination, significant numbers of anti‐PPS‐SC were detected; however, they were observed only in cultures depleted of T cells (mean: 62/106), suggesting the presence of T cells suppressing in vivo‐activated PPS‐specific B cells. In EBV‐stimulated cultures depleted of T cells, low numbers of anti‐PPS‐SC were observed before the vaccination, and the numbers of these cells increased significantly two weeks after the immunization (from 28 to 48/106). In contrast, the numbers of anti‐PPS‐SC and total Ig‐SC decreased in EBV‐stimulated cultures of unseparated MNC established after the vaccination, suggesting T cell‐mediated suppression. The findings were not explained by changes in the numbers of blood T helper (Leu 3+) or T suppressor (Leu 2+) cells following the vaccination. Possibly the vaccination induces the appearance in the blood of activated suppressor cells responsible for the suppression of B cells in unstimulated and EBV‐stimulated cultures.