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K MacLennan

Publications and source records attributed to K MacLennan.

28 records · Page 2Linked to original sources
PubMed1992

Induction of transforming growth factor beta 1 in human breast cancer in vivo following tamoxifen treatment.

We have investigated the ability of tamoxifen to regulate members of the transforming growth factor beta (TGF-beta) family in human breast cancers in vivo. Using immunohistochemical techniques, we find that 3 months of tamoxifen treatment causes a consistent induction of extracellular TGF-beta 1 in breast cancer biopsies, compared with matched pretreatment samples from the same patient. The induced TGF-beta is localized between and around stromal fibroblasts and appears to be derived from these cells. Lower levels of TGF-beta 1,-beta 2, and -beta 3 seen in epithelial cells were not altered by tamoxifen treatment. The increased stromal staining of TGF-beta 1 occurred in estrogen receptor-negative as well as estrogen receptor-positive tumors. These results provide in vivo evidence for a novel, estrogen receptor-independent mechanism of action for tamoxifen, involving the stromal induction of a potent growth inhibitor for epithelial cells.

Biomarkers, Tumor↗
PubMed1992

Translocation t(11;14)(q13;q32) in chronic lymphoid disorders.

The translocation t(11;14)(q13;q32) has been described in a spectrum of B-lymphoproliferative diseases and involves a putative oncogene, BCL1, which maps to chromosome band 11q13. Recent evidence indicates that this abnormality may delineate particular subtypes of lymphoma, such as intermediate lymphocytic and centrocytic lymphomas. Thus the possible significance of the t(11;14) within B-cell disorders should be reexamined in the light of a more objective approach to classifying these diseases by morphology, histology, and immunophenotype. We describe 16 patients with t(11;14)(q13;q32) from a series of 90 patients with chronic lymphoid disorders in whom clonal chromosome abnormalities were detected. All the cases were leukemic: prolymphocytic (B-PLL; 4/15 cases), chronic lymphocytic leukemia (CLL) with increase in prolymphocytes (2/9 cases), or non-Hodgkin lymphoma in leukemic phase, intermediate (3/4 cases), lymphoplasmacytic (2/2 cases), splenic lymphoma with villous lymphocytes (4/18 cases), and follicular (1 case). None of the CLL (25) or hairy cell leukemia cases (15) had t(11;14). Our findings showed that t(11;14) occurred in leukemias of mature B cells with lymphoplasmacytic features as judged by morphology and immunophenotype.

Adult↗
PubMed1992

Massive abdominal lymphadenopathy in hairy cell leukaemia: a report of 12 cases.

Lymphadenopathy is an uncommon finding in hairy cell leukaemia (HCL). We report 12 HCL patients in whom relapse was associated with massive abdominal lymphadenopathy. All but one had long-standing HCL (range 3-25 years; median 10 years); in one it was discovered at presentation. Nine patients had been splenectomized and seven had previously been treated with 2'deoxycoformycin (DCF) and/or alpha-interferon (alpha IFN): three had achieved complete remission and four a partial response. The computerized tomography (CT) scan appearances were similar in all cases with a primary lymph node mass centred around the coeliac axis and involving upper para-aortic and retropancreatic regions. Histology and/or cytology confirmed nodal involvement by HCL in six patients. Large immature hairy cells were seen in both lymph nodes and bone marrow, suggesting a degree of transformation. Nine patients were treated with DCF: one had complete resolution, six responded with 50-90% reduction of the lymphadenopathy, one did not respond and one is still on treatment; alpha-IFN was used concomitantly or sequentially in two of the responders. One responding patient died of sepsis after four injections of DCF. Three patients received either alpha- or beta-IFN alone with no response. One elderly patient was not treated. Abdominal lymphadenopathy could be part of the natural history of HCL and/or may represent a transformation analogous to that seen in other low-grade lymphoproliferative disorders. Routine abdominal CT scanning should be part of the work up of all patients with HCL.

Adult↗
PubMed1992

Comparison of four immunochemical methods for the measurement of oestrogen receptor levels in breast cancer.

Four methods of assessing oestrogen receptor (ER) status were compared in 33 patients with operable primary breast cancer. The methods used to assess the ER status were immunocytochemical assay (ER-ICA) of frozen sections, fine needle aspirates and imprint material and enzyme immunoassay (ER-EIA) of tumour tissue. A mean overall ER positivity of 45% (15 out of 33), 41% (13 out of 32) and 21% (six out of 29) was obtained by immunocytochemical (ER-ICA) staining of frozen sections, fine needle aspirates and tumour imprints, respectively, and a mean overall ER positivity of 42% (14 out of 33) was obtained by ER-EIA. The concordance of ER positivity in pairs of data obtained from different method combinations was found to range between 72 and 91%. However, statistically there was no significant difference between the four methods on the basis of the data obtained. Good comparability has been shown between the three tissue analyses and therefore the method of choice is technically not immediately apparent.

Biopsy, Needle↗
PubMed1989

Haemangiopericytoma of the larynx.

Haemangiopericytoma is an uncommon vascular tumour which has rarely been recorded in the larynx. The diagnostic and histopathological difficulties are discussed. A total laryngectomy was performed because of the size and site of the tumour, the associated risk of local recurrence and the high metastatic rate.

Aged↗
PubMed1989

Intermediate filament-ubiquitin diseases: implications for cell sanitization.

The molecular pathology of chronic degenerative disease is not understood. Generally there must be two related, but opposing, processes: the direct deleterious effects of the pathogenic insult which can be chemical or viral and a cellular cytoprotective response to the insult. We have recently shown that there is a previously unsuspected link between the intracellular inclusions seen in some major chronic degenerative diseases: the inclusions contain ubiquitin immunoreactivity. The conditions include Parkinson's disease, motor neurone disease, Alzheimer's disease and alcoholic liver disease as well as astrocytomas and a myopathy. Protein ubiquitination is considered a signal for extra-lysosomal protein degradation although ubiquitin-protein conjugation may have several other important functions. Intermediate filaments are a component of some of the inclusions in diseased cells; we have previously reported that they are involved in protein sequestration for degradation by lysosomally mediated autophagy. Therefore, intermediate-filament-containing ubiquitinated inclusions may be hallmarks of cellular attempts to eliminate pathogenic insults by activating protein degradation mechanisms. Ubiquitinated inclusions could also be a hallmark of viral infections: they are in polio-virus-infected anterior horn neurones and Epstein-Barr-transformed lymphoblastoid cells. Some of the clinical observations can be reproduced experimentally in tissue culture cells. The implications of the combined clinical and experimental observations for cell sanitization and protein catabolism will be discussed.

Alzheimer Disease↗
PubMed1985

Hodgkin-cell leukaemia of B-cell origin.

A case of lymphocyte-depleted nodular sclerosing Hodgkin's disease with a terminal leukaemic phase is described. Circulating Hodgkin cells were shown to be of B-cell origin by immunological phenotyping and the demonstration of clonal immunoglobulin gene rearrangement.

Aged↗
PubMed1984

Homosexual men in London: lymphadenopathy, immune status, and Epstein-Barr virus infection.

By November 7, 1983, 24 cases of AIDS in the United Kingdom had been reported to the Communicable Disease Surveillance Centre. At the same time an increasing number of homosexual men with unexplained lymphadenopathy syndrome (LAS) have been seen in our department. Between December 1982 and July 1983, 14 homosexual men with LAS and 11 healthy homosexual men were studied. Patients with LAS had a high number of lifetime episodes of sexually transmitted diseases, a history of recent sexual activity in the United States (9 of 14), sexual contact with British AIDS patients or other persons with LAS (7 of 14), and hypergammaglobulinemia. Low T-helper/T-suppressor ratios (less than 0.8), due mainly to a decrease in T-helper cells, were found in both groups. Lymph node biopsies showed follicular hyperplasia and hypocellular pattern. All 25 patients studied had antibodies to Epstein-Barr virus capsid antigen (anti-VCA) and 11 had antibodies to early antigen (anti-EA); 13 of 17 were excreting the virus; and two showed no Epstein-Barr-virus-specific regression. Peripheral blood immunoglobulin-producing B-cells from six patients with hypergammaglobulinemia were negative for the Epstein-Barr virus nuclear antigen (EBNA). Five lymph node biopsies showed no EBNA-positive cells. Epstein-Barr virus reactivation is common in the patients with LAS and healthy homosexual men in London, but would not seem to be the cause of the polyclonal B-cell activation or lymphadenopathy.

Adult↗