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K C Gatter

Publications and source records attributed to K C Gatter.

At least 181 records · Page 10Linked to original sources

Heterogeneity of the endothelial cell and its role in organ preference of tumour metastasis.

The vascular endothelium is a remarkably heterogeneous organ. In addition to well-characterized anatomical diversity in situ, specific differences are increasingly being recognized between surface antigens on endothelial cells from different tissues, including absence of the classic endothelial marker factor VIII-related antigen (von Willebrand factor) from many endothelial cells. Microvascular heterogeneity extends to properties of endothelial cells thought to be involved in tumour angiogenesis and metastasis, such as growth factor responsiveness and expression of cell adhesion molecules. These findings are not only of relevance to the unambiguous identification and characterization of cultured endothelial cells, but, as Roy Bicknell and colleagues discuss, may explain the phenomenon of preferential organ tumour metastasis and provide novel opportunities for antitumour therapy.

Cell Adhesion↗

Localization of the DMDL gene-encoded dystrophin-related protein using a panel of nineteen monoclonal antibodies: presence at neuromuscular junctions, in the sarcolemma of dystrophic skeletal muscle, in vascular and other smooth muscles, and in proliferating brain cell lines.

mAbs have been raised against different epitopes on the protein product of the DMDL gene, which is an autosomal homologue of the X-linked DMD gene for dystrophin. These antibodies provide direct evidence that DMDL protein is localized near acetylcholine receptors at neuromuscular junctions in normal and mdx mouse intercostal muscle. The primary location in tissues other than skeletal muscle is smooth muscle, especially in the vascular system, which may account for the wide tissue distribution previously demonstrated by Western blotting. The DMDL protein was undetectable in the nonjunctional sarcolemma of normal human muscle, but was observed in nonjunctional sarcolemma of Duchenne muscular dystrophy patients, where dystrophin itself is absent or greatly reduced. The expression of DMDL protein is not restricted to smooth and skeletal muscle, however, since relatively large amounts are present in transformed brain cell lines of both glial and Schwann cell origin. This contrasts with the low levels of DMDL protein in adult brain tissue.

Animals↗

The L1 antigen and squamous metaplasia in the bladder.

The L1 antigen was investigated as a marker of squamous differentiation in urothelium using a monoclonal antibody Mac387, and the results were compared with the expression of high molecular weight cytokeratins. L1 antigen was consistently demonstrated in all instances of partial and complete squamous metaplasia and in squamous carcinomas. In contrast, pure transitional cell carcinomas (except one with minor focal staining), adenocarcinomas and normal and hyperplastic urothelium did not label. In a few squamous carcinomas in situ, the pattern of labelling obtained with Mac387 was different from that seen in invasive squamous carcinomas and metaplasias. Compared with high molecular weight cytokeratins, the expression of L1 was more intense in areas of squamous differentiation. L1 expression, as identified by antibody Mac387, may therefore serve as a useful marker of squamous differentiation in urothelial lesions.

Antibodies, Monoclonal↗

CD30 expression in follicular lymphoma.

The CD30 antigen is a characteristic phenotypic feature of Sternberg-Reed and Hodgkin cells and is also found in a subset of large cell non-Hodgkin's lymphomas. The finding of CD30 positive cells in some centroblastic/centrocytic (cb/cc) follicular lymphomas prompted us to characterize the presence and distribution of CD30 positive cells in this type of lymphoma, using the monoclonal antibody BerH2. CD30 positive cells were present in 17/19 of the cases studied, located mainly at the edge of the neoplastic follicles, but also in some cases in perinodular or T-cell areas. This distribution resembles that found in reactive tonsils and lymph nodes. The majority of these CD30 positive cells in cb/cc lymphoma seem to be B-cells, as suggested by their reactivity with B-cell markers demonstrated by double immunostaining. The nature of these CD30 positive cells is unclear, but they should be taken into consideration in the differential diagnosis of cb/cc lymphoma with lymphocyte predominance Hodgkin's disease.

Antibodies, Monoclonal↗

Immunophenotyping of Nigerian cases of non-Hodgkin's lymphomas on paraffin sections.

One hundred cases of routinely fixed and processed non-Hodgkin's lymphoma from Nigeria were immunostained with a small panel of monoclonal antibodies against B-, T- and macrophage antigens. The aims of the study were to assess the suitability of stored material from a country like Nigeria for immunohistochemical examination and the ability of the antibody panel to evaluate the distribution of B- and T-cell neoplasms. Eighty-seven of the 100 cases gave interpretable immunostaining, with 75 being B-cell and 12 T-cell neoplasms. Eighty-seven of the 100 cases gave interpretable immunostaining, with 75 being B-cell and 12 T-cell neoplasms. There were no tumours of macrophage lineage. Four cases gave satisfactory staining of reactive lymphoid cells but no reactivity with malignant cells and thus were not phenotyped. The remaining nine cases gave no staining of neoplastic or reactive cells, suggesting that they were unsuitable for immunohistochemical study, presumably because of inappropriate fixation and handling. We concluded that a panel of three monoclonal antibodies is suitable for routine immunostaining of conventionally fixed and processed blocks in Third World countries and will give diagnostically useful information in approximately 95% of cases.

Antibodies, Monoclonal↗

Ki-67 immunostaining and survival in operable lung cancer.

One hundred and eighty-seven operable lung tumours were immunostained with the monoclonal antibody Ki-67 and divided into groups of high, moderate or low proliferation. Patients have been followed clinically for up to 7 years to ascertain whether this immunocytochemical measurement reflected tumour behaviour in terms of survival. The majority of the tumours were squamous cell carcinomas (104 cases) and adenocarcinomas (60 cases). These were divided into three groups of low, intermediate and high growth fraction, in which survival was better for tumours of lower proliferative rate up to approximately 2 years after operation. By 5 years these differences had largely disappeared and all tumours of a particular type showed a similar survival curve. Small cell carcinomas (13 cases) had high Ki-67 labelling indices, with more than 60% of patients deal in the first year, whereas carcinoid tumours (10 cases) had low labelling rates and all but one are still alive. We conclude that measurement of lung tumour growth rate with the monoclonal antibody Ki-67 shows promise as a possible indicator of short-term survival and perhaps as a means of choosing a group of patients with adenocarcinomas and squamous cell carcinomas for post-operative chemotherapy.

Adenocarcinoma↗

[Large cell anaplastic lymphomas in the immunocompromised host].

Large cell anaplastic (LCA) lymphomas are a newly defined tumor entity, which has recently been integrated in the updated Kiel classification. The occurrence of CD30+ LCA lymphoma in the setting of renal transplant patients has so far been reported only once. This report describes two LCA lymphomas of B-cell phenotype in renal transplant patients. The clonal evolution and possible etiologic role of Epstein-Barr Virus (EBV) in LCA lymphoma was studied. Our findings give further evidence that clonal evolution of B-cell populations is a second event in lymphomagenesis and is, at least in the cases studied, preceeded by either reactivated latent or primary EBV-infection with clonal EBV proliferation.

Antigens, CD↗

Malignant histiocytosis. A reassessment of cases previously reported in 1975 based on paraffin section immunophenotyping studies.

Malignant histiocytosis (MH) is a term that has been used to describe a syndrome in which there is a systemic proliferation of cells that have the cytologic appearance of atypical histiocytes. Biopsy materials from 15 patients with malignant lymphoma diagnosed as malignant histiocytosis in a previous study reported in 1975 were analyzed by a panel of antibodies and reclassified using current nosologic concepts of malignant lymphoma. The antibodies used comprised reagents detecting a formalin-resistant epitope on B-cells (L26), T-cells (anti-CD3, anti-leu 22 [CD43], and UCHL1 [CD45RO]), monocyte/macrophage-derived cells (KP1 [CD68]), as well as antibodies that detect leukocyte common antigen (PD7 [CD45RB]), and a formalin-resistant epitope of Ki-1 (Ber-H2 [CD30]). The authors found that nine lymphomas had a profile consistent with T-lineage, including six in which Ki-1 (CD30) was coexpressed, and two were B-lineage. Three lymphomas showed no specific lineage characteristics although two were Ki-1 (CD30) positive, and none had expression of KP1 (CD68). The 12 lymph node biopsy specimens showed a variety of patterns of involvement, including sinusoidal, paracortical, and diffuse; the spleens showed predominantly red pulp involvement. A 15th case was believed most consistent with a virus-associated hemophagocytic syndrome. These findings support previous suggestions that the majority of cases diagnosed as MH represent T-lineage-associated hematolymphoid neoplasms, and that only a rare case will be of monocyte/macrophage origin. It is suggested that the term MH be subsumed under the rubric of large cell lymphoma and unless there are compelling immunohistochemical data to support a histiocytic origin, that the term MH be abandoned in favor of a more accurate descriptive term, such as sinusoidal large cell lymphoma.

Adolescent↗

Peripheral T-cell lymphoma associated with hemophagocytic syndrome.

Nine patients with an acute disease characterized by high fever, loss of weight, prominent hepatosplenomegaly, slight or no lymphadenopathy, abnormal liver function tests, and profound pancytopenia are reported. In all cases, the disease presented in the absence of any pre-existing disease or immunosuppressive therapy. In seven of the nine patients, survival was very short (mean = 7 weeks). Two patients are still alive: one had a relapse 24 months after the initial diagnosis, while the other is in complete remission. The main pathological feature was the infiltration of the marrow, spleen and liver by neoplastic T cells, accompanied by an exuberant hyperplasia of benign-looking, hemophagocytizing histiocytes. The term "peripheral T-cell lymphoma with hemophagocytic syndrome" is proposed for this condition. Retrospective analysis of stored paraffin material (1949 to 1965) from the Radcliffe Infirmary files suggests that at least some of the cases designated as "histiocytic medullary reticulosis" by Scott and Robb-Smith were examples of the syndrome herein described.

Autopsy↗

The 14;18 translocation in European cases of follicular lymphoma: comparison of Southern blotting and the polymerase chain reaction.

The 14;18 chromosomal translocation is widely recognized as a cytogenetic abnormality associated with follicular lymphomas, but estimates of its frequency in this type of lymphoma vary widely from less than 50% to almost 90%. Furthermore, no extensive data have been published on the frequency of t(14;18) in European cases of follicular lymphoma. Lymph nodes from 51 patients with follicular lymphomas obtained from two European centres (Oxford and Copenhagen) were examined for the presence of this translocation. Southern blotting and the polymerase chain reaction (PCR) were used in 26 cases and the PCR alone in 25 cases (from which only degraded DNA or formalin fixed samples were available). DNA probes capable of detecting rearrangement at both the major and the minor breakpoint regions were employed. We could detect t(14;18) in only 21 out of 51 cases (41%). However, a review of the literature showed that comparable results have been obtained previously using both cytogenetic and molecular biological techniques and our results support the view that the global incidence of t(14;18) in follicular lymphoma is no greater than 70%. Furthermore, this study has indicated that the PCR is a reliable method for identifying t(14;18) when only formalin-fixed paraffin-embedded tissue or degraded DNA is available.

Base Sequence↗

Megakaryocytes in myelodysplasia: an immunohistochemical study on bone marrow trephines.

Megakaryocytes in 63 bone marrow trephine biopsies were examined for their staining characteristics, location and size distribution using the monoclonal antibody Y2/51 directed against platelet glycoprotein IIIa (CD61). Megakaryocytes in normal bone marrow were evenly distributed and demonstrated homogeneous staining with Y2/51. In addition, there was little variation in their size or shape. In contrast, myelodysplastic and myeloproliferative bone marrow trephines showed considerable dysmegakaryopoiesis demonstrated by heterogeneity of staining, an altered architectural distribution with a predominantly paratrabecular location and considerable variation in size and shape. Furthermore, in myelodysplasia 25% of the CD61 positive cells were micromegakaryocytes as opposed to less than 10% in normal or reactive marrows. Such dysmegakaryopoiesis is believed to be a clinically important feature of myelodysplasia, although until now it has only been possible to assess it subjectively. The availability of the monoclonal antibody Y2/51 provides a rapid and reproducible means of studying megakaryocyte size, shape and distribution in routine trephine specimens and may help to overcome some of the diagnostic problems currently associated with myelodysplasia and other intrinsic bone marrow neoplasias.

Antibodies, Monoclonal↗

CD30 expression in non-Hodgkin's lymphoma.

The CD30 antigen has been reported as the immunophenotypic hallmark of a recently described category of non-Hodgkin's lymphoma, termed anaplastic large cell lymphoma. From a series of approximately 500 lymphomas, 17 cases showing typical anaplastic features have been identified. They were strongly labelled by monoclonal antibodies recognizing CD30 (Ki-1 or BerH2). However, 36 other lymphomas, mainly high-grade, of non-anaplastic cytology also expressed CD30, either diffusely or focally, with a staining pattern identical to that seen in anaplastic large cell lymphomas. This clearly suggests that such lymphomas cannot be identified solely on the basis of being high-grade non-Hodgkin's lymphomas showing CD30 positivity. From the present results, the distinction between the anaplastic and non-anaplastic types would be better made with antibodies to epithelial membrane antigen than to CD30. Clinical data, available for 48 of the patients (16 with anaplastic large cell lymphomas and 32 with non-anaplastic) revealed no significant differences with regard to age at presentation, sex or clinical signs. A short-term follow-up study of 25 patients revealed that for the first 2 years after diagnosis there were no significant differences in patient survival between anaplastic large cell lymphoma, other CD30+ high-grade lymphomas and all high-grade non-Hodgkin's lymphomas considered together. These findings, which must be confirmed by larger studies, suggest that in a general lymphoma clinic there is probably little justification for differentiating anaplastic large cell lymphomas or CD30+ lymphomas from other high-grade non-Hodgkin's lymphomas.

Adolescent↗

Monoclonal antibody Ki-67: its use in histopathology.

Monoclonal antibody Ki-67 is a reliable and easy means of accurately assessing the growth fraction of human neoplasms. Although the number of long-term follow-up studies is limited, it does appear to provide valuable prognostic information particularly in lymphoproliferative disease. Since the estimation of growth fraction is only one factor influencing tumour behaviour it would be naive to believe that measurement of this parameter alone, no matter how accurately, would provide the clinician with definitive prognostic information for all tumours. The antibody is also of use in research, providing a means of measuring proliferative activity in a variety of conditions besides malignancy, and may prove of value in monitoring tumour response to established and trial therapies.

Antibodies, Monoclonal↗

Immunosuppression and thrombosis in renal transplantation: an immunohistological study.

Renal biopsies were taken from 42 patients at seven and 21 days after renal transplantation. Paraffin sections from these specimens were examined immunocytochemically for the presence of platelet microthrombi in glomerular capillaries using the monoclonal antibody Y2/51. Patients were treated by one of four different immunosuppressive regimes, three of which included cyclosporin A, either alone or in combination with steroids and azathioprine. Microthrombi were detected in approximately 30% of biopsies and were much commoner in patients receiving multi-drug therapy. We conclude that, contrary to previous suggestions, glomerular capillary thromboses are not frequent in patients on cyclosporin A alone. They are found mainly in patients on multiple drug therapy, particularly when steroids are included. The detection of microthrombi is unlikely to be of assistance in the earlier detection of cyclosporin toxicity.

Azathioprine↗

Crypt cell proliferation and HLA-DR expression in pelvic ileal pouches.

To investigate the nature of the morphological changes that occur in ileal pouches, 26 biopsy specimens from patients with functioning ileo-anal pouches (eight with pouchitis) were studied. Normal ileum (n = 10) was used as a control. Mucosal morphometry (using linear measurements), crypt cell proliferation (CCP) (using the monoclonal antibody Ki67), and epithelial HLA-DR expression (monoclonal antibody CR3/43) were assessed. CCP (expressed as the percentage of Ki67 positive nuclei for each crypt) was significantly higher in pouches with pouchitis, compared with those without, and in pouches without pouchitis compared with normal ileum. CCP values in some pouches without pouchitis approached values found in those with pouchitis. CCP was related inversely to villous height and an index of villous atrophy (VH/TMT), and directly to crypt depth. In the presence of pouchitis there was intense epithelial HLA-DR expression that extended into the crypts. In some pouches with high CCP values, but without clinically important inflammation, surface epithelial HLA-DR expression was weak and patchy. It is concluded that villous atrophy and crypt hyperplasia in ileal pouches are associated with high CCP values. These may be increased even in the absence of active inflammation, and this increase may occur as a response to the new luminal environment.

Adenomatous Polyposis Coli↗

Proliferation in non-Hodgkin's lymphoma: a comparison of Ki-67 staining on fine needle aspiration and cryostat sections.

Assessment of the growth fraction of non-Hodgkin's lymphomas may provide useful additional prognostic information to that obtained with conventional histological criteria. The monoclonal antibody Ki-67 has been reported to provide such information immunocytochemically in tissue biopsy specimens from lymphoma as well as other tumours. This study was undertaken to assess whether this approach could be extended to fine needle aspiration (FNA) biopsy specimens which are becoming increasingly important in the diagnosis of lymphoma. In 21 cases of non-Hodgkin's lymphoma the rate of tumour proliferation estimated by Ki-67 immunostaining of FNA material, obtained from surgically removed specimens, was compared with that obtained on tissue biopsy. The correlation between both preparations was excellent, indicating that FNA biopsy material is suitable for the immunocytochemical assessment of the growth fraction of non-Hodgkin's lymphoma.

Antibodies, Monoclonal↗