Search PubMed⌕ Search

Biomedical subjects

J Boileau

Publications and source records attributed to J Boileau.

At least 19 recordsLinked to original sources

An exactly solvable Ogston model of gel electrophoresis. VI. Towards a theory for macromolecules.

In this article, we present a generalized version of our lattice model of low-field gel electrophoresis that allows us to treat the case of macromolecules such as short linear or circular oligomers and semi-flexible rods. We show that free-solution electrophoresis problems can be seen as random walks in the conformational space of the analyte. For sufficiently small molecules, our mathematical approach provides exact mobilities. In a quenched gel-like environment, however, both conformational and positional degrees of freedom must be used, but exact solutions can also be obtained. As an example, we then investigate several two-dimensional model gels, as well as a simple channel system where we see evidence of entropic effects that cannot be captured by the traditional Ogston concept of free volume.

Electrophoresis, Agar Gel↗

Allogeneic transplantation for multiple myeloma: further evidence for a GVHD-associated graft-versus-myeloma effect.

We report a series of 37 consecutive patients with multiple myeloma (MM) who received an allograft between 1990 and 2000 at our institution. Median age was 47 years, and nearly 70% of patients were Durie-Salmon stage III. A median of five cycles of chemotherapy were given before transplant, with a median interval between diagnosis and transplant of 9.3 months. We report a nonrelapse mortality rate of 22% with a median follow-up period of 40 months, whereas complete remission (CR) rate at 12 months is estimated at 57%. Treatment failure rate and overall survival at 40 months are estimated at 52% and 32%, respectively. The number of chemotherapy cycles prior to allotransplantation achieved borderline statistical significance as a poor prognosis factor for overall survival (P = 0.05), while the presence of chronic graft-versus-host disease (cGVHD) was significantly correlated with CR achievement (P = 0.036). Our study confirms that early allografting in MM can yield toxicity rates significantly lower than those associated with historical cohorts, and supports the hypothesis that cumulative chemotoxicity has a negative influence on mortality and survival rates. More importantly, our study clearly demonstrates an association between cGVHD and CR and brings further evidence in favor of a graft-versus-myeloma effect.

Adult↗

Theory of DNA electrophoresis: a look at some current challenges.

Although electrophoresis is one of the basic methods of the modern molecular biology laboratory, new ideas are being suggested at an accelerated rate, in large part because of the pressing demands of the biomedical community. Although we now have, at least for some methods, a fairly good theoretical understanding of the physical mechanisms that lead to the observed peak spacings, widths and shapes, this knowledge is often too qualitative to be used to guide further technical developments and improvements. In this article, we review some selected elements of the current state of our theoretical ignorance, focusing mostly on DNA electrophoresis, and we offer several suggestions for further theoretical investigations.

Animals↗

Acute graft-versus-host disease prophylaxis with methotrexate and cyclosporine after busulfan and cyclophosphamide in patients with hematologic malignancies.

The combination of two powerful immunosuppressive agents, methotrexate (MTX) and cyclosporine (CSP), has resulted in a significant decrease in the morbidity and mortality after allogeneic bone marrow transplantation (BMT). However, the additive toxicities from ablative preparative regimens may lead to suboptimal use of this combined immunoprophylaxis. We evaluated the efficacy and feasibility of administering MTX/CSP with busulfan (4 mg/kg/d for 4 days) and cyclophosphamide (50 mg/kg/d for 4 days) (BuCy4) in 101 consecutive patients with hematologic malignancies categorized into high- and low-risk groups receiving HLA-matched marrow grafts. Postgrafting immunosuppression consisted of MTX short course (15 mg/m2 on day 1 and 10 mg/m2 on days 3, 6, and 11) and intravenous CSP (1.5 mg/kg every 12 hours). Eighty-three patients (82.1%) received 100% of MTX calculated dose and 87 (86.1%) achieved a CSP therapeutic level (250 to 600 ng/mL) within a median of 16 days. Seventy-three patients (72.2%) received optimal immunosuppressive therapy comprising a full MTX course and achieving CSP therapeutic concentrations. The Kaplan-Meier estimated incidence of grade II to IV acute graft-versus-host disease (GVHD) was 9.2% for all patients and 5.5% in patients receiving optimal GVHD prophylaxis. Eighty-nine patients (88.2%) survived > or = 100 days posttransplant and 43 (48.3%) developed chronic GVHD, the majority of which were de novo (31 of 43). The estimated incidence of relapse was 28.9% for all patients and 14.8% in the low-risk group, with a median follow-up of 24.5 months. High-risk features and the absence of chronic GVHD were significantly associated with relapse (P = .002 and .036, respectively) in multivariate analyses. Projected disease-free survival at 2 years was 52.3% for all patients and 65.2% in low-risk patients. Disease-free survival was significantly improved in optimally treated patients (P = .03) due to a lower incidence of early deaths from acute GVHD and infectious episodes. In conclusion, optimal delivery of MTX/CSP in association with BuCy4 resulted in a near complete abrogation of acute GVHD in HLA-matched transplants and a significantly improved disease-free survival.

Adult↗

Allogeneic bone marrow transplantation following busulfan-cyclophosphamide with or without etoposide conditioning regimen for patients with acute lymphoblastic leukaemia.

We have investigated the feasibility and efficacy of administering a radiation-free preparative regimen in the setting of allogeneic bone marrow transplantation (BMT) in 40 consecutive patients with acute lymphoblastic leukaemia (ALL). Busulfan (4 mg/kg/d x 4 d) and cyclophosphamide (50 mg/kg/d x 4 d) (BuCy4) were given in 29 patients and 11 received busulfan (4 mg/kg/d x 4 d), etoposide (60 mg/kg) and cyclophosphamide (60 mg/kg/d x 2 d) (BuCy+VP - 16). Median age was 22 years (range 1-50); 11 patients were children < or = 15 years of age. All children and 20 adults were at high risk of relapse pretransplant. Nine adults and one child died from transplant-related toxicity. 11 patients relapsed at a median of 11 months post-transplant (range 2-27). The 3-year Kaplan-Meier estimated probability of relapse was 42.1% and found to be significantly lower in patients with chronic GVHD (P = 0.03). 19 patients are leukaemia-free survivors with a median follow-up of 33 months (range 7-59). The Kaplan-Meier actuarial probability of disease-free survival at 3 years was 43% for all patients. 63.6% for children versus 30.2% for adults (P = 0.24) and 51.6% for patients transplanted in first remission versus 30.2% for those transplanted in subsequent remissions (P = 0.20).

Adolescent↗

Cytogenic characterization of primary refractory anemia.

Refractory anemia (RA) is the only myelodysplastic syndrome (MDS) devoid of quantitative marrow diagnostic criteria. The diagnosis rests mainly on the subjective identification of qualitative abnormalities according to the French-American-British criteria (FAB) involving one or more bone marrow hematopoietic cell lineages. The occurrence of nonrandom chromosome abnormalities remains the hallmark of the disease and the only means of investigation which confirms the disease objectively. With the purpose in mind to further characterize RA among MDS, we have undertaken a prospective high resolution banding chromosome analyses of bone marrow cells in patients with primary refractory anemia (PRA) with the aim of defining a cytogenetic phenotype and of assessing the clinical relevance of clonal abnormalities at initial diagnosis. Of 39 patients consecutively referred for chromosome analyses with a diagnosis of RA according to the FAB criteria, 27 patients had PRA and fulfilled our criteria for adequate chromosome analyses. Median age was 68 years. Fourteen of 27 patients (52%) had clonal chromosomal abnormalities at diagnosis. None of the patients showed a complex karyotype; 9/14 (64%) had a mixture of normal and abnormal cells. Interstitial or terminal deletions, involving chromosomes 5, 6, 7, 9, 11, 12, and 20, were found in 11/14 (79%) of the patients. Comparison of survival between patients with and without abnormalities showed no difference. The presence of clonal abnormalities did not predict transformation to acute myeloblastic leukemia (AML) nor was it associated with poor survival. In this study, patients with PRA were found to have a predominant pseudodiploid karyotypic pattern characterized by interstitial and/or terminal deletions as opposed to derivatives, specific and non-specific balanced translocations, or other structural and numerical abnormalities. We were unable to reveal any prognostic significance to the presence of these clonal abnormalities at initial diagnosis.

Adult↗

Chronic B-cell lymphocytosis.

Persistent elevation of lymphocyte counts is usually associated with a malignant monoclonal lymphoproliferative disease. Over the last 8 years, amongst patients investigated in our center for undetermined persistent lymphocytosis, a diagnosis of malignant lymphoproliferation was excluded in 6 cases as studies of surface membrane immunoglobulin light chains showed that they presented a polyclonal expansion of their B-lymphocyte pool. All patients were young-to-middle aged women presenting peculiar immunohematologic findings characterized by 1) persistent (2-7 yr) elevation of lymphocyte counts (4-14 x 10(9)/l), 2) presence of characteristic binucleated B cells on peripheral blood smears, 3) a normal bone marrow histology, 4) a polyclonal increase of serum IgM with low-to-normal IgG and IgA levels. Histologic examination of the spleen in 2 patients and lymph nodes in 1 showed a benign follicular lymphoid hyperplasia. The evolution was benign in every case. We suggest that chronic polyclonal B-cell lymphocytosis is a distinct clinicopathologic entity that should not be confused with malignant lymphoproliferative disorders.

Adult↗

Extramedullary plasmacytoma associated with angiofollicular lymph node hyperplasia.

We report a case of hyaline-vascular type of angiofollicular lymph node hyperplasia involving the left pulmonary lymph nodes and lung. It clinically presented as an obstruction of the left lower lobe main bronchus secondary to the development of an extramedullary plasmacytoma in the lesion. An immunoperoxidase stain revealed a monoclonal IgG-lambda pattern of the tumor, contrasting with the polyclonal plasma cell population of the angiofollicular lymph node hyperplasia. This case demonstrates the neoplastic potential of angiofollicular lymph node hyperplasia.

Antibodies, Monoclonal↗

Lymphoid interstitial pneumonia after allogeneic bone marrow transplantation. A possible manifestation of chronic graft-versus-host disease.

Interstitial pneumonia (IP) is a frequent and serious complication of bone marrow transplantation with a median time of onset about 2 months posttransplant. Most cases result either from toxicity of radiation and chemotherapy or from infection with pathogens such as cytomegalovirus. Described are two patients with chronic graft-versus-host disease (GVHD) who presented with late-onset IP 242 and 632 days posttransplant. Histologic examination of lung biopsy specimens disclosed a lymphoid interstitial pneumonia (LIP) in both cases. The major lymphocyte subset found in bronchoalveolar lavages and lung tissue was OKT8(+) and showed a positive dot staining for acid phosphatase. Contrary to peripheral blood mononuclear cells, most OKT8(+) lymphocytes in the lungs were OKT3(-). Since acute GVHD lesions are mediated mainly by cytotoxic T-lymphocytes, our data suggest that LIP in marrow-grafted patients may be a manifestation of chronic GVHD. It should be distinguished from the more common types of IP encountered following bone marrow transplantation.

Acid Phosphatase↗

Serum immunoglobulin levels following allogeneic bone marrow transplantation.

In order to study the posttransplant evolution of serum immunoglobulin levels, we measured serum IgG, IgA and IgM levels in 50 recipients of allogeneic bone marrow before transplantation and at different intervals thereafter (days 39, 120, 365 and 730). IgG and IgM levels were depressed for 1 year and IgA levels for 2 years posttransplant. Immunoglobulin deficiency was more severe and prolonged in patients with graft versus-host-disease. Hypogammaglobulinemia may contribute to the frequent infections observed in these patients, especially those with chronic graft-versus-host disease.

Adolescent↗

Persistence of host Langerhans cells following allogeneic bone marrow transplantation: possible relationship with acute graft-versus-host disease.

Langerhans cells (LC) are bone marrow-derived dendritic antigen-presenting cells found in the epidermis. In an effort to determine the origin (host versus donor) of LC at different intervals following bone marrow transplantation, we performed skin biopsies in 16 recipients of sex-mismatched marrow. LC were identified using monoclonal antibody OKT6 in an indirect immunoperoxidase assay and their donor or host origin determined according to the presence or absence of Y body. The presence of Y-positive (donor) LC could be demonstrated in all (6/6) skin biopsies of female recipients of male marrow tested between days 39 and 730 post-transplant. Persistence of host LC in male recipients of female marrow was documented in all (6/6) recipients studied on day 39 and in two out of seven patients tested on day 120 post-transplant. From day 365 onward, no residual host LC could be detected, suggesting that by this time all epidermal LC are donor-derived. Our study demonstrates that host LC usually persist for 39 and up to 120 d following bone marrow transplantation. The relevance of this observation to the possible role of LC and other host dendritic antigen-presenting cells in the graft-versus-host reaction is discussed.

Acute Disease↗

Treatment of therapy-induced preleukemic syndrome.

Two young adult patients with therapy-induced preleukemic syndrome and Hodgkin's disease as primary malignancy were treated with aggressive antileukemic regimens before the establishment of leukemic conversion. Pretreatment clinical staging procedures did not reveal recurrence of Hodgkin's disease. One of the regimens consisted of an HLA-identical allogeneic bone marrow transplant and the other of high dose cytosine arabinoside. Both therapeutic approaches have proved successful in restoring normal hematopoiesis with reversal to normal karyotypes and unmaintained remissions 556 and 192 days post-treatment. The rationale for such a therapeutic approach in the preleukemic stage of therapy-induced leukemogenesis is discussed.

Adult↗

Brain abscess due to Petriellidium boydii.

A 22 year-old man died from multiple cerebral abscesses due to Petriellidium boydii 4 1/2 months after an episode of near drowning. The autopsy showed dissemination to heart and kidney. This patient had no immunocompromising disease but was treated with corticosteroids. The treatment of this condition with ventricular shunting and amphotericin B is discussed and compared with the experience of ten other cases reported in the literature.

Adult↗