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Biomedical subjects

J D Jackson

Publications and source records attributed to J D Jackson.

At least 55 records · Page 3Linked to original sources
PubMed1994

Differential recovery of polymorphonuclear neutrophils, B and T cell subpopulations in the thymus, bone marrow, spleen and blood of mice following split-dose polychemotherapy.

In these studies, we examined the effect of a maximum-tolerated, split-dose chemotherapy protocol of cyclophosphamide, cisplatin, and 1,3-bis(2-chloroethyl)-1-nitrosourea carmustine on neutrophil and lymphocyte, subpopulations in the peripheral blood (PBL), thymus, bone marrow and spleen. It was found that this protocol of polychemotherapy, modeled after the induction protocol used with autologous bone marrow transplantation for breast cancer, suppressed both B and T cell populations and T cell function at times when the absolute neutrophil count had returned to normal or supernormal numbers. In the peripheral blood, 7 days following initiation of chemotherapy, there was a twofold increase in the percentage of granulocytes as compared to the level in control animals on the basis of a differential count. The polymorphonuclear neutrophil (PMN) frequency in the bone marrow was increased on day 14 and statistically identical to that in control mice on all other days analyzed. In contrast to the bone marrow cells and PBL on day 7, the frequency of PMN in the spleen and thymus was depressed. B cells (B220+) were depressed in the pBL, spleen and bone marrow and took 18-32 days to return to their normal frequency, while the frequency of B cells in the thymus was increased owing to a loss of immature T cells. The percentage of CD3+ cells in the thymus, spleen and bone marrow was significantly increased and required 10-18 days to return to normal levels, while the absolute number of CD3+ cells in the blood varied around the normal value. The ratio of CD4+ to CD8+ cells in all the organs studied varied only slightly owing to a similar reconstitution of CD4+ and CD8+ cells. In contrast to the phenotypic recovery of the CD3+, CD4+, and CD8+ cells, the ability of the splenic lymphocytes to respond to concanavalin-A was depressed and remained depressed, despite the phenotypic reconstitution of the T cell subsets, on the basis of both percentage and absolute cell number. These results show a selective T and B cell depression following multi-drug, split-dose chemotherapy in tissue and blood leukocyte populations and a chronic depression in T cell function.

Animals↗
PubMed1994

The leukemic myeloid cell line OMA-AML-1: an in vitro model of hematopoietic cell differentiation.

The OMA-AML-1, acute myelogenous leukemia cell line is unique in that it spontaneously maintains both a CD34+ precursor cell compartment and a CD15+ differentiating cell compartment in vitro. A third transitional cell type with co-expression of CD34 and CD15 can also be identified in in vitro cultures. The cell line shows dynamic fluctuations in the relative sizes of these three cell compartments in suspension culture. In contrast, OMA-AML-1 fails to show phenotypic or morphologic evidence of differentiation when grown subcutaneously in immunodeficient mice. OMA-AML-1 responds to a number of hematopoietic cytokines. Delineation of cytokine responses on FACS isolated populations of CD34+ versus CD15+ cells demonstrated that proliferative responses occurred primarily at the level of the precursor cell (CD34+) while the production of endstage eosinophils occurred within the CD15+ compartment. OMA-AML-1 mimics a number of features of normal hematopoiesis and is proving to be a useful in vitro model for the study of hematopoietic differentiation.

Acute Disease↗
PubMed1994

After rehabilitation: meeting the long-term needs of persons with traumatic brain injury.

Many survivors of traumatic brain injury have significant needs for long-term support. The rehabilitation professions, including occupational therapy, have begun to recognize these needs more fully during the last decade. The literature describes various models of supported living that provide housing, support services, and vocational assistance; however, these programs are not widely available due to limitations in public funding and inadequate insurance coverage for long-term care. Occupational therapists can contribute a broad expertise to the provision of supported living services, and the profession is encouraged to provide leadership and advocacy with respect to the long-term care needs of survivors of traumatic brain injury.

Adult↗
PubMed1994

Effects of a multidrug chemotherapy regimen on the thymus.

Multidrug chemotherapy regimens are commonly used in the treatment of cancer. The dose limiting tissue for chemotherapeutic treatment is often the bone marrow, as many chemotherapeutic agents selectively target rapidly proliferating cells. Bone marrow transplantation (BMT) has allowed an increase in chemotherapeutic dose; however, this type of therapy is associated with a prolonged suppression of immune function following the BMT. Although it may be possible to augment this immune function, animal models which can be used to test various cytokines have not been well described. We have developed a mouse model of multi-drug chemotherapy which, like the human, demonstrates long term immune suppression following BMT. In this report, we describe the specific effects of this chemotherapy regimen on T cell differentiation in the thymus of treated mice using three color FACS analysis. Results demonstrated that specific populations of thymocytes are extremely susceptible to chemotherapeutic insult. Both thymus cellularity and the immature CD3-CD4+CD8+ double positive population dropped to approximately 3% of their original values by 7 days after chemotherapy initiation. During the same time period, cells expressing both alpha beta and gamma delta T cell receptors demonstrated a 2-6 fold increase in frequency. Similar results were observed for the alpha beta+ CD4-CD8- population of natural suppressor cells. Long-term changes in the proportion of cells expressing the V beta 5 TCR were also observed following chemotherapy. These results demonstrate that chemotherapy regimens may directly influence T cell differentiation within the thymus, and also suggest that long term changes in the T cell V beta repertoire may occur following chemotherapy.

Animals↗
PubMed1994

Fatal eosinophilic disease following autologous bone marrow transplantation.

A 15-year-old girl developed massive, fatal eosinophilic disease following autologous bone marrow transplantation (BMT) for Hodgkin's disease (HD). Prior to autologous BMT, the erythrocyte sedimentation rate (ESR) was elevated, with active HD, but eosinophilia was absent. Post-autologous BMT, ESR and peripheral eosinophilia were observed to correlate with respiratory symptoms. Initial evaluation revealed no recurrent tumor, infection or other identifiable etiology. A diagnosis of chronic eosinophilic pneumonia was made following lung biopsy. A complete response was initially achieved with steroid therapy; however, when steroid therapy was tapered, the eosinophilia and elevated ESR recurred with worsening respiratory symptoms. Terminally, severe pulmonary disease developed and recurrent HD was found in lung, lymph nodes and bone marrow. During episodes of eosinophilia, the patient's serum stimulated her bone marrow as well as control marrow to produce predominantly eosinophilic colonies. Eosinophilic colony production was not observed with patient's sera obtained prior to or during autologous BMT or with control sera. This patient died of eosinophilic inflammatory disease following autologous BMT. The etiology of this disease was not definitely identified but appeared to be due to an eosinophilic-stimulating factor which developed after autologous BMT.

Adolescent↗
PubMed1993

T-cell reconstitution by molecular, phenotypic, and functional analysis in the thymus, bone marrow, spleen, and blood following split-dose polychemotherapy and therapeutic activity for metastatic breast cancer in mice.

We examined the effect of a maximum tolerated, split-dose chemotherapy protocol of cyclophosphamide, cisplatin, and 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) on neutrophil and lymphocyte subpopulations in the peripheral blood leukocytes (PBLs), thymus, bone marrow, and spleen. It was found that this protocol of polychemotherapy, modeled after the induction protocol used with autologous bone marrow transplantation (AuBMT) for breast cancer, suppressed both B- and T-cell populations and T-cell function at times when the absolute neutrophil count had returned to normal or supernormal numbers. We observed an organ- and phenotype-specific T- and B-cell recovery to normal levels following chemotherapy. However, despite normalization of cellularity and phenotype frequency, splenic lymphocytes remained unable to respond to normally concanavalin A (ConA). This polychemotherapy protocol in mice with an extensive experimental metastasis mammary tumor burden, was a dose lethal to 20% of the test group, which could be overcome with treatment by BMT and rHu interleukin (IL)-7. Furthermore, therapy with the T-cell augmenting agent rHu IL-7 had additive therapeutic activity and significantly prolonged survival beyond that of chemotherapy and BMT although it did not cure any mice with a heavy tumor burden. In summary, these studies demonstrate an organ-specific and selective polymorphonuclear neutrophil and T- and B-cell reconstitution following multidrug, split-dose chemotherapy on tissue and PBL populations, and a chronic depression in T-cell function, which when modified can result in significant therapeutic activity.

Animals↗
PubMed1992

OMA-AML-1: a leukemic myeloid cell line with CD34+ progenitor and CD15+ spontaneously differentiating cell compartments.

OMA-AML-1 was established from a patient with acute myelomonocytic (M4) leukemia at fifth relapse when blasts were greater than 85% CD34+, CD15-. Leukemic cells were established in suspension culture and independently grown as subcutaneous tumors in SCID mice. Cells growing in suspension culture underwent differentiation by phenotypic and morphologic criteria. In contrast, cells grown as subcutaneous solid tumors in SCID mice maintained progenitor cell characteristics with high-density CD34 expression and lack of morphologic differentiation. A tendency toward differentiation to CD15+, CD34- cells in vitro and self-renewal of CD34+, CD15- cells in vivo was consistently demonstrated regardless of whether cells were initially grown in vitro or in vivo. The cell line maintains both a CD34+, CD15- progentitor cell pool and a non-overlapping, CD15+, CD34- differentiating cell compartment after more than 1 year in continuous culture. Cell cycle analysis and cloning experiments were consistent with terminal differentiation occurring in the CD15+, CD34- population. The cell line shows concentration-dependent proliferative responses to interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-6, but not to granulocyte CSF (G-CSF). OMA-AML-1 appears to mimic several features of normal myeloid hematopoiesis and should prove useful for the study of normal and malignant myeloid differentiation.

Animals↗
PubMed1992

DNA methylation inhibits transcription of procollagen alpha 2(I) promoters.

Our previous studies have demonstrated that a 2-[N-(acetoxyacetyl)amino]fluorene-transformed rat epithelial-like cell line, W8, contains a transcriptionally inactive alpha 2(I) gene with a hypermethylated promoter/first-exon region. We have cloned the rat promoter/first-exon region (-211 to +207) from W8 cells and their parent cell line, K16, which expresses alpha 2(I) collagen. There were no sequence differences between the clones from the two cell lines, indicating that a mutation was not responsible for transcriptional inhibition. The alpha 2(I) rat promoters were cloned upstream of the chloramphenicol acetyltransferase gene. Both constructs were equally active in both cell lines, suggesting that trans-activating factors for alpha 2(I) transcription are present in W8 cells. Finally, methylation of plasmids at all CpG sites with SssI methylase completely inhibited transcription using alpha 2(I) promoters, but methylation did not inhibit simian-virus-40 promoter-driven transcription. Certain methylation sites partially inhibit promoter activity. An HhaI methylation site inhibited transcriptional activity of the alpha 2(I) promoter 8-fold, whereas methylation at the HpaII site in the rat alpha 2(I) promoter did not decrease transcriptional activity. This provides further evidence that methylation at specific sites in the collagen alpha 2(I) promoter is responsible for the inactivation of transcription in W8 cells.

Animals↗
PubMed1992

Are the stray 60-Hz electromagnetic fields associated with the distribution and use of electric power a significant cause of cancer?

The putative causal relation between ambient low-frequency (50 or 60 Hz) electromagnetic fields (necessarily present in living and working environments because of our ever increasing use of electrical devices) and cancer, especially leukemia, can be tested on the large scale by examining historical data on the growth of the generation and consumption of electric power since 1900 and corresponding data on cancer death and incidence rates. The United States per capita generation and residential consumption of electric power have grown roughly exponentially since 1900; total per capita generation has increased by a factor of 10 since 1940, and per capita residential consumption has increased by a factor of 20 in the same period. The ubiquitous stray fields from power distribution lines and internal and external wiring in buildings have grown in the same proportions. In contrast to the explosive increase in the generation and use of electricity, the age-adjusted cancer death rate for the population as a whole shows only a slight rise since 1900. When respiratory cancers (largely caused by tobacco use) are subtracted, the remaining death rate has actually fallen since 1940. That the death rate may have fallen because of better diagnosis and treatment, despite a rising incidence rate, is not substantiated, especially for leukemia, including childhood leukemia, where the incidence rate has been constant or declining slightly for the past 25 yr. The absence of any appreciable change in the national cancer incidence rates during a period in which residential use of electric power has increased dramatically shows that the associated stray 50- or 60-Hz electromagnetic fields pose no significant hazard to the average individual.

Child↗