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L F Skinnider

Publications and source records attributed to L F Skinnider.

At least 19 recordsLinked to original sources
PubMed2001

Non-Hodgkin's lymphoma and specific pesticide exposures in men: cross-Canada study of pesticides and health.

Our objective in the study was to investigate the putative associations of specific pesticides with non-Hodgkin's Lymphoma [NHL; International Classification of Diseases, version 9 (ICD-9) 200, 202]. We conducted a Canadian multicenter population-based incident, case (n = 517)-control (n = 1506) study among men in a diversity of occupations using an initial postal questionnaire followed by a telephone interview for those reporting pesticide exposure of 10 h/year or more, and a 15% random sample of the remainder. Adjusted odds ratios (ORs) were computed using conditional logistic regression stratified by the matching variables of age and province of residence, and subsequently adjusted for statistically significant medical variables (history of measles, mumps, cancer, allergy desensitization treatment, and a positive history of cancer in first-degree relatives). We found that among major chemical classes of herbicides, the risk of NHL was statistically significantly increased by exposure to phenoxyherbicides [OR, 1.38; 95% confidence interval (CI), 1.06-1.81] and to dicamba (OR, 1.88; 95% CI, 1.32-2.68). Exposure to carbamate (OR, 1.92; 95% CI, 1.22-3.04) and to organophosphorus insecticides (OR, 1.73; 95% CI, 1.27-2.36), amide fungicides, and the fumigant carbon tetrachloride (OR, 2.42; 95% CI, 1.19-5.14) statistically significantly increased risk. Among individual compounds, in multivariate analyses, the risk of NHL was statistically significantly increased by exposure to the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D; OR, 1.32; 95% CI, 1.01-1.73), mecoprop (OR, 2.33; 95% CI, 1.58-3.44), and dicamba (OR, 1.68; 95% CI, 1.00-2.81); to the insecticides malathion (OR, 1.83; 95% CI, 1.31-2.55), 1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane (DDT), carbaryl (OR, 2.11; 95% CI, 1.21-3.69), aldrin, and lindane; and to the fungicides captan and sulfur compounds. In additional multivariate models, which included exposure to other major chemical classes or individual pesticides, personal antecedent cancer, a history of cancer among first-degree relatives, and exposure to mixtures containing dicamba (OR, 1.96; 95% CI, 1.40-2.75) or to mecoprop (OR, 2.22; 95% CI, 1.49-3.29) and to aldrin (OR, 3.42; 95% CI, 1.18-9.95) were significant independent predictors of an increased risk for NHL, whereas a personal history of measles and of allergy desensitization treatments lowered the risk. We concluded that NHL was associated with specific pesticides after adjustment for other independent predictors.

Adult↗
PubMed1999

Molecular analysis of clonality of sporadic angiomyolipoma.

Angiomyolipoma, which consists of three intimately intermixed components, smooth muscle, blood vessels, and adipose tissue, is variably considered a hamartoma, a choristoma or a true neoplasm. This study has investigated the clonality of sporadic angiomyolipomas in seven women, each with a single lesion, by determining the pattern of X-chromosome inactivation. Polymerase chain reaction (PCR) amplification of the highly polymorphic human androgen receptor gene (HUMARA) was performed on the DNA extracted from the paraffin-embedded lesional tissue microdissected to sample the admixed smooth muscle and blood vessel component (SMC/BV) and the adipose tissue component. All seven patients were heterozygous for HUMARA polymorphism upon amplification of undigested DNA from non-lesional tissue and were therefore informative for further analysis. In all patients, lesional DNA, representative of the components, was predigested with HpaII restriction enzyme for amplification of the methylated allele. In six patients, the lesions were clonal, while in one, polyclonal. The polyclonal lesion was small and had less than 20 per cent SMC/BV component. Microdissected SMC/BV component was clonal in 6/7 lesions; the scanty SMC/BV in the remaining lesion did not yield amplifiable DNA. Microdissected adipose tissue was polyclonal in all seven lesions. Angiomyolipomas are three clonal lesions due to a clonal smooth muscle cell and blood vessel component, while the polyclonal adipose tissue is probably metaplastic or reactive.

Actins↗
PubMed1998

Biologic and clinical significance of CD7 expression in acute myeloid leukemia.

CD7 antigen, a T-cell lineage associated antigen, is expressed in a minority of patients with acute myeloid leukemia (AML). The biologic and clinical significance of this finding is not clearly established. In this retrospective study of patients with de novo acute myeloid leukemia, we have identified CD7 expression and analyzed its association with markers expressed early in hemopoietic ontogeny and clinical parameters. Among 60 consecutive AML patients, we found six (10%) expressing CD7 on leukemic cells. There were five males and one female and the mean age was 59.6 years (age range: 32-76 years) with no demographic peculiarities. The FAB subtypes were: M0 (2), M1 (1), M2 (1), and M4 (2). CD7 expression was associated with immature antigens CD34, HLA-DR, and terminal deoxynucleotidyl transferase (TdT) and antigen receptor gene rearrangements (rearrangements of T-cell receptor gamma chain in 6/6 and immunoglobulin heavy chain in 2/6). Hepatomegaly was present in three and this was associated with splenomegaly with lymphadenopathy in one patient. Mediastinal or central nervous system involvement was absent. Complete remission was achieved in two patients with standard chemotherapy; one of these is in remission and alive (5 years later), while one died following relapse 9 months later. Three patients had significantly lower response to standard therapeutic regimen (two died during induction and one died 7 months later without ever achieving complete remission). One patient has been excluded in determining the prognostic significance of CD7 due to early death. Our results suggest origin of CD7+ AML from early hemopoietic precursors and indicate biologic aggressiveness in a significant proportion of patients. We suggest evaluation of CD7 in all patients with AML at the time of diagnosis in view of poor clinical outcome.

Acute Disease↗
PubMed1997

Characteristics of a cell line established from a case of acute megakaryoblastic leukemia.

Acute megakaryoblastic leukemia is uncommon and comprises about 5% of acute nonlymphoid leukemias in the French-American-British classification. Cell lines from such leukemias are relatively rare with only about 8 reported in the literature. We established a cell line from a case of acute megakaryoblastic leukemia arising in a 2-year-old child. Surface marker studies of the cells confirmed their megakaryoblastic nature, with 54% of the cells being CD61 positive and peroxidase and esterase negative. The cells had a doubling time of 72 h. Emperipolesis (a phenomenon in which a cell, usually a lymphocyte or neutrophil, enters another cell, moves about and leaves without undergoing phagocytosis) of one blast into another, larger one, was occasionally seen, and a review of the original bone marrow specimen also showed emperipolesis of neutrophils into the megakaryoblasts. The cells responded to interleukin 3 and were inhibited with all-trans-retinoic acid. The karyotype of the cells was the 46,XX,-16 with a marker chromosome. The marker chromosome is possibly chromosome 16 with a small segment of a chromosome translocated to the terminal portion of chromosome 16.

Antigens, CD↗
PubMed1996

Establishment of cell lines derived from chronic lymphocytic leukaemic cells by transfection with myc and ras.

Seventy-one samples from 37 cases of chronic lymphocytic leukaemia (CLL) were transfected with human c-myc and/or N-ras. In only three cases did the CLL cells further transform and four cell lines were established following transfection with myc plus ras. Surface marker profiles and immunoglobulin gene rearrangement studies confirm that all cell lines have arisen from the original CLL cells. The cell lines are EBNA positive but negative for EBV latent membrane protein (LMP). Karyotyping of the cell lines is as follows: SA4, 46,XY; SA4-2, 45,XY, 20; RK4, 48,XY,+ 5,+ 12; EHC4, 47,XY, t(14;18)(q32;q21), + 12. Although the majority of CLL cells appear resistant to transformation in vitro with myc and ras with the methods used, it does occur in a small percentage (about 8%). There appeared to be no correlation between the ability to transform in vitro and clinical behaviour.

Base Sequence↗
PubMed1996

Age-related prognostic factor analysis in non-Hodgkin's lymphoma.

BACKGROUND: Age is known to have an important influence on survival in non-Hodgkin's lymphoma (NHL). This observation and the relationship of age to other prognostic factors are of interest in designing treatment programs for these patients. This study was conducted to investigate the relationship of age to other known prognostic variables and survival in NHL. PATIENTS AND METHODS: Data on clinical features, treatment, response, survival and cause of death from 547 patients with NHL diagnosed between 1980 and 1989 were collected and analyzed by age group. Multivariate analysis of prognostic factors and a survival comparison to an age and sex matched control population were performed. RESULTS: Survival curves for 5-year age groups up to and including age 60-64 years were similar, after which a major effect of age upon survival was apparent. When groups aged < 65 years and > and = 65 years were compared, there were similar proportions of most known prognostic factors, except for a higher proportion with increased lactate dehydrogenase (LDH) levels and extranodal disease in older patients. When analyzed by age group, older patients had a lower response rate to initial therapy and salvage treatments. In younger patients, several recognized prognostic variables were found to lack significance. CONCLUSIONS: Prognostic variables differ between younger and older patients with NHL. Age, histology, LDH elevation and gender are less important in younger patients; only bulky disease is more important than in older patients. A lower response rate, poor response to salvage therapy and excess mortality, often due to concurrent diseases, were apparent in older patients. Age is a significant prognostic factor only in patients age > and = 65 years.

Age Factors↗
PubMed1994

Non-Hodgkin's lymphoma in Saskatchewan. A review of 10 years' experience.

BACKGROUND: The incidence and treatment of non-Hodgkin's lymphoma (NHL) have changed in recent years. This study was intended to compare current features with a previous study (1966-1975) and assess the impact of these changes in our jurisdiction. METHODS: Clinical features and treatment of 547 patients with NHL registered at our center from January 1980 through December 1989 were reviewed, including reassessment of histologic type in each patient. Multivariate analysis of potential pretreatment prognostic factors was performed using the Cox proportional hazards model, and survival was analyzed in relation to treatment outcome. RESULTS: This review includes virtually all incident cases of NHL in a defined geographic area, representing an average annual incidence of 11.3/100,000 population. The male-to-female ratio was 1.1:1, median age was 65 years (range, 4-92 years). Median survival time (MST) of 482 patients with disease diagnosed antemortem was 4.8 years (95% confidence interval [CI], 3.7-6.1 years), 52% of whom have died. Thirty-nine percent of patients with disease classified by the International Working Formulation (IWF) had low-grade disease (MST, 103 months); 27% had intermediate disease (MST, 62 months), and 30% had high-grade disease (MST, 35 months). Sixteen percent of patients had associated neoplasms: 4 acute leukemias, 35 skin cancers, and 37 miscellaneous solid tumors. Results of radiation therapy (RT), chemotherapy (CT), and combined CT/RT were analyzed. Survival correlated strongly with responsiveness to treatment. Considering all patients treated with CT, anthracycline-containing CT was associated with the highest response rate, and survival time (more than 48 months) may have been affected by the addition of this agent. A survival advantage for patients with bulky Stage I and II disease treated with consolidative RT after CT is suggested, but not for more advanced stage disease. The proportional hazards model identified histologic type, disease stage, patient age, hemoglobin level, lactate dehydrogenase (LDH) level, bulky abdominal disease, and systemic "B" symptoms as significant independent prognostic factors influencing survival. CONCLUSIONS: The incidence of NHL has increased, and the survival of patients with high-grade disease has improved significantly since the previous study. A high incidence of other associated malignancies was demonstrated in this group of patients with NHL. Recognition of prognostic factors should permit a rational application of innovative treatments for patients in unfavorable prognostic categories.

Adolescent↗
PubMed1994

Characteristics of a cell line established from a T cell acute leukemia by transfection with the bcl-2 gene.

The bcl-2 gene product inhibits apoptosis and thus its over-expression may promote development of the malignant phenotype under certain circumstances. We have introduced the bcl-2 alpha and bcl-2 beta genetic elements into T cell acute lymphoblastic leukemic blasts. These transfectants were able to survive and grow in liquid culture with the establishment of cell lines while the untransfected blast cells died off. Thus transfection of the bcl-2 genes appears to give additional survival advantages to already malignant cells. Although the original leukemic blasts did not have cytoplasmic granules, the established transfectants have a morphology and surface marker profile compatible with large granular lymphoid cells.

Apoptosis↗
PubMed1993

Interferon instillation for malignant pleural effusions.

BACKGROUND: Malignant pleural effusions can be managed in various ways including instillation of antineoplastic agents. Instillations of alfa interferon-2b (IFN-alpha 2b) have been utilized with success in various loco-regional malignancies suggesting a possible role in management of pleural effusions. This trial was designed to evaluate the tolerability and efficacy of intrapleural IFN-alpha 2b instillations in this situation. PATIENTS AND METHODS: Twenty-three patients with cytologically proven malignant pleural effusions were given IFN-alpha 2b 50 x 10(6) units in 50 ml normal saline (NS) by intrapleural instillation after partial or complete clearance of effusions by percutaneous aspiration or chest tube drainage. For persistent or recurrent effusions, instillations were repeated with dose escalation to 75 x 10(6) units. Patients were assessed and monitored by regular clinical examinations, chest radiographs, biochemical and hematological parameters and assays of lymphocyte subpopulations until relapse or death in each case. RESULTS: Fourteen of 20 evaluable patients (70%) had responses lasting for a median of 6 months; there were 8 complete responses (CR) and 6 partial responses (PR). In 6 CR patients the effusions did not recur after the first instillation. In 2 of 6 other patients, the second instillation was successful in inducing CR. Intrapleural instillation of IFN-alpha 2b was well tolerated, no grade 4 toxicities were encountered. There were no significant effects on any of the studied parameters at the initial dose level; however, grade 3 neutropenia occurred with the escalated dose. The most common toxicity was flu-like syndrome, after 70% of the instillations. CONCLUSIONS: Intrapleural instillation of IFN-alpha 2b produced an encouraging response rate without significant toxicities. This approach may warrant additional phase II or phase III comparative clinical studies.

Aged↗
PubMed1992

Transfection of chronic lymphocytic leukemic cells with myc and ras.

Thirty samples of cells from twenty-one cases of chronic lymphocytic leukemia (CLL) were transfected with myc and/or ras. Transformation, as assessed by growth in liquid culture and change in morphology, occurred in only one case. Colony culture in semi-solid media, however, does not occur with these cells. It would appear that the neoplastic genotype of CLL cells does not predispose the cells to readily transform, even with transfection with these two oncogenes.

Cell Transformation, Neoplastic↗
PubMed1985

Characterisation of a new cell line (CJ18) from a patient with 'hairy' cell leukaemia.

A cell line (CJ18) has been established from the peripheral blood of a patient with hairy cell leukaemia (HCL) in a leukaemic phase. They grow slowly in large clumps with a doubling time of 3-4 d. 8% show positivity for surface immunoglobulin G and a small percentage (5%) are positive for intracytoplasmic immunoglobulin. They are B1,Ia1 positive and CALL, TdT and OKM1 negative. Although they are Epstein Barr Virus Nuclear Antigen (EBNA) positive they have several features not found in other EBNA positive B lymphoblastoid cell lines which suggest they may be derived from the patient's leukaemic hairy cells. They are strongly positive for tartrate resistant acid phosphatase, esterase positive, contain numerous lysosomes and are able to phagocytose sheep red blood cells after exposure to tetradecanoyl-12, 13-phorbol acetate (TPA). Following exposure to retinoic acid and TPA they adhere to plastic with numerous slender processes, a feature seen in HCL cells.

Antibodies, Monoclonal↗
PubMed1985

Lymphoid colony growth with phorbol myristate acetate and lymphocyte-conditioned media in chronic lymphocytic leukemia and malignant lymphomas.

Cell preparations from 49 cases of lymphoid malignancy were cultured to determine optimal culture conditions (in semisolid media). Colony growth was obtained in the majority of cases (73%) using the combination of phorbol myristate acetate (PMA) and lymphocyte-conditioned medium (L-CM). Cell surface marker studies of plated cells in 36 cases identified 31 to be B-cell type, 1 to be T-cell type, and 4 null-cell type. The morphology and markers of harvested cells were similar to plated cells, suggesting proliferation of neoplastic cells predominantly. A relationship was found between the degree of colony growth and the clinical course of the disease in lymphomas but not in chronic lymphocytic leukemia (CLL). The use of PMA in combination with other mitogens deserves further investigation as a colony growth stimulator in hemopoietic malignancies.

Cell Division↗
PubMed1984

Growth of malignant histiocytic cells induced by phorbol myristate acetate.

Cells from the spleen of a patient with malignant histiocytosis were cultured in methyl cellulose with and without 100 ng/mL of phorbol myristate acetate (PMA). Colony growth occurred only with PMA; comparing surface marker studies of the cells before and after culture, it was evident that proliferation had occurred among the histiocytic cells as well as the lymphocytes. After exposure to PMA in organ culture for ten days, the histiocytes appeared to be differentiated and showed evidence of continuing phagocytosis by electron microscopy. This suggests that PMA is a mitogen for the histiocytes in this condition and maintains differentiation of the cells.

Adult↗
PubMed1984

Orbital involvement in chronic lymphocytic leukemia.

In a 68-year-old man with chronic lymphocytic leukemia diagnosed on the basis of peripheral lymphocytosis, marked bilateral exophthalmos developed owing to massive orbital involvement by the disease. At the time there was no lymphadenopathy or evidence of organ infiltration. The response to radiotherapy was excellent. Orbital involvement is rare as an early clinical feature of chronic lymphocytic leukemia but should be considered in the differential diagnosis of bilateral exophthalmos in adults.

Aged↗
PubMed1983

Chronic immune thrombocytopenic purpura in hemophilia A.

Chronic immune thrombocytopenic purpura resistant to steroid therapy occurred in a 30-year-old patient with severe hemophilia A. This association has recently been reported in other patients, and a possible relation to the acquired immune deficiency syndrome (AIDS) has been suggested. Although this patient had been treated with factor VIII concentrate for 4 years, the proportions of helper and suppressor T cells were normal, and there was no evidence of AIDS. An uncomplicated splenectomy gave excellent results. All patients with hemophilia should have their platelet counts monitored closely and should report any unusual pattern of bleeding.

Adult↗
PubMed1983

Waldenström macroglobulinemia terminating in acute leukemia: a report of three cases.

Acute leukemia was observed to develop in three patients with Waldenstöm macroglobulinemia. Each patient had been treated with cytotoxic drug therapy. Pancytopenia preceded the onset of the terminal leukemia in two of the three cases. The acute leukemias were all of acute myelogenous type. All of the patients died soon after the development of the terminal leukemia. A number of recent reports have documented acute terminal leukemia in patients with macroglobulinemias and multiple myeloma, as well as other malignant and nonmalignant diseases. The role of the cytotoxic drugs, especially chlorambucil, cyclophosphamide, and melphalan, in leukemogenesis has been raised by these recent reports.

Aged↗
PubMed1983

Phorbol myristate acetate induced colony growth in Hodgkin's disease.

Discrete pleomorphic colonies were cultured from a lymph node of a patient with Hodgkin's disease using phorbol myristate acetate in semi-solid media. A mean of 216 colonies were counted after 10 days incubation. No colonies were noted after similar incubation with pokeweed mitogen or lymphocyte conditioned medium. A gradation in morphology from small lymphoid cells to giant multinucleated cells was noted. The majority (80%) of the cultured cells bore T lymphoid surface markers. The use of phorbol myristate acetate as a stimulant for colony growth of cells from the lymph nodes of Hodgkin's disease patients would appear to be of value.

Cell Division↗