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Biomedical subjects

J E Green

Publications and source records attributed to J E Green.

18 recordsLinked to original sources
PubMed1992

Adrenal medullary tumors and iris proliferation in a transgenic mouse model of neurofibromatosis.

The expression of the human T-cell lymphotropic virus type 1 (HTLV-1) tax gene in transgenic mice has been shown to result in the development of neurofibromas. Further characterization of these transgenic mice has revealed other significant pathologic similarities between this transgenic mouse model and human neurofibromatosis (NF). Pheochromocytomas of the adrenal medulla and hamartomas of the iris are well-recognized manifestations of human NF. Adrenal medullary tumors have been found in 68% of transgenic animals that were studied. They appear, however, not to be pheochromocytomas, but rather composed of undifferentiated spindle cells. Proliferation of fibroblastlike cells in the iris also occurs in one-half of the transgenic animals surviving more than 6 months. Melanocytes, however, have not been found in the transgenic iris lesion, although they are characteristically found in the Lisch nodules of human NF. The similarities between human neurofibromatosis and this transgenic mouse model (in which the overexpression of a single gene results in neoplasia) are discussed. This transgenic system may provide further insights into molecular mechanisms involved in the pathogenesis of neurofibromatosis.

Adrenal Gland Neoplasms↗
PubMed1991

trans activation of nerve growth factor in transgenic mice containing the human T-cell lymphotropic virus type I tax gene.

Three lines of transgenic mice containing the human T-cell lymphotropic virus type I (HTLV-I) tax gene develop neurofibromas composed of perineural fibroblasts (S. H. Hinrichs, M. Nerenberg, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1340-1343, 1987; M. Nerenberg, S. H. Hinrichs, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1324-1327, 1987). Tumors and tumor cell lines derived from these mice produce neurite outgrowth from PC-12 cells and nerve growth factor (NGF), as determined by RNA (Northern) blot analysis and enzyme-linked immunosorbent assays. In vitro cotransfection studies demonstrate that Tax is able to trans activate the NGF promoter in NIH 3T3 fibroblast cells. The major cis-acting tax-responsive element in the NGF promoter (AGGGTGTGACGA) has 92% homology with a tax-responsive element contained within the 21-bp repeats of the HTLV-I long terminal repeat. The receptor for NGF is also expressed in the transgenic tumor cells, suggesting that Tax may activate an autocrine mechanism through the upregulation of NGF.

Animals↗
PubMed1991

Cytotoxic T lymphocyte precursor (CTL-p) frequency analysis in unrelated donor bone marrow transplantation: two case studies.

HLA 'matched' unrelated donor bone marrow transplantation (BMT) is associated with an increased incidence and severity of acute graft-versus-host disease (GVHD) in comparison with HLA-identical sibling transplants. Using a limiting dilution analysis system for quantitating frequencies of alloreactive cytotoxic T lymphocyte precursors (CTL-p), we previously demonstrated a correlation between CTL-p frequency and HLA disparity between responder and stimulator, and between CTL-p frequency and the incidence of acute GVHD following HLA A, B, DR matched unrelated donor BMT. In this study we assayed CTL-p frequencies in two HLA 'matched' unrelated donor/patient pairs, with single HLA antigenic mismatches detected by allogenotyping or isoelectric focusing but not by HLA serology, and demonstrated that the CTL-ps were specifically directed at the mismatched antigen. Both class I and class II antigens were detected. These data, and our previous work, suggest that high CTL-p frequencies in HLA 'matched' unrelated pairs are indicative of HLA antigenic variants undetected by serology but recognized by molecular typing, and that these are responsible for the value of the assay in predicting acute GVHD after BMT. We propose that this assay system be used in aiding final donor selection before unrelated or mismatched related donor BMT.

Bone Marrow↗
PubMed1990

Hypertension and renal failure in a patient with tuberous sclerosis.

The cause of hypertension in this patient with tuberous sclerosis appeared to be the result of volume expansion due to renal failure. Renal insufficiency was presumably caused by extensive replacement of renal parenchyma with angiomyolipomas, resulting in compression and distortion of the renal parenchyma. Noninvasive imaging techniques were the most useful for characterizing the extent of the disease. It is clearly important to monitor renal function and blood pressure of patients with tuberous sclerosis as they grow older.

Adult↗
PubMed1989

Exocrinopathy resembling Sjögren's syndrome in HTLV-1 tax transgenic mice.

Human T-cell leukaemia virus 1 (HTLV-1) is a retrovirus aetiologically associated with adult T-cell leukaemia (ATL), tropical spastic paraparesis (TSP) and possibly multiple sclerosis (MS) in humans. Three founder lines of transgenic mice containing the HTLV-1 tax gene under the control of the viral long terminal repeat (LTR) have previously been shown to develop neurofibromas. Further analysis of these animals has now revealed that they also develop an exocrinopathy involving the salivary and lachrymal glands. This pathology resembles Sjögren's syndrome, a disease of presumed autoimmune aetiology, features of which are sometimes reported in HTLV-1 associated conditions. Mice with an HTLV-1 tax transgene might be a useful model for studying the development of Sjögren-syndrome-like pathology.

Animals↗
PubMed1989

Linkage analysis of multiple endocrine neoplasia type 1 with INT2 and other markers on chromosome 11.

We evaluated linkage between the locus for multiple endocrine neoplasia type 1 (MEN1) and several polymorphic DNA markers on chromosome 11 in a single large pedigree. On the basis of the finding of a basic fibroblast growth factor (bFGF)-like substance circulating in plasma of MEN1 patients, we chose a bFGF-related gene known to be localized to 11q13 as one of the markers. This gene locus, INT2, was found to be closely linked to the MEN1 gene. Pairwise and multipoint analyses with INT2 confirm the recent finding by C. Larsson et al. (1988, Nature (London) 332: 85-87) of MEN1 linkage to another marker, skeletal muscle glycogen phosphorylase, at 11q13.

Chromosomes, Human, Pair 11↗
PubMed1989

Variant nucleolus organizing regions and the risk of Down syndrome.

In order to determine whether nucleolus organizing region (NOR) heteromorphisms of the acrocentric chromosomes could identify individuals at risk for having offspring with trisomy 21, a comparison was made between 43 parents of individuals with Down syndrome and 39 controls. NORs, as visualized by silver staining, were analyzed by mean number per cell, average size, total NOR "mass" per cell (designated mean score per cell) and by mean number of acrocentric chromosome satellite associations per cell. No "double NOR" variants (dNOR) were found in either the control or study group in contrast to observations of others (Jackson-Cook et al. 1985). The risk for having a child with trisomy correlated with a higher frequency of associations and number of NORs per cell, but slightly lower average NOR size. Although these group differences were statistically significant, specific types of NOR variants such as enlarged or dNORs were not associated with the risk of having trisomy 21 offspring. The constancy of NOR mass per cell in our control and study groups indicates that NOR activity remains constant, even though distribution of the rRNA genes (variation in number and size of NORs on the 10 acrocentrics) may vary.

Adult↗
PubMed1989

trans activation of granulocyte-macrophage colony-stimulating factor and the interleukin-2 receptor in transgenic mice carrying the human T-lymphotropic virus type 1 tax gene.

Three lines of transgenic mice carrying the human T-cell lymphotropic virus type 1 tax gene have previously been reported to develop neurofibromas composed of perineural fibroblasts (S. H. Hinrichs, M. Nerenberg, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1340-1343, 1987; M. Nerenberg, S. H. Hinrichs, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1324-1329, 1987). Tumors from these mice and tumor cell lines derived from them expressed high levels of tax RNA and protein. They also expressed high levels of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene as measured by proliferative responses of FD-CP1 target cells using conditioned media from tumor cells and by Northern (RNA) blot analysis of RNA from tumors and tumor cell lines. Although other tissues, such as salivary glands and muscles, in the transgenic mice also expressed high levels of tax, they did not express the gene for GM-CSF. This indicates that tissue-specific cellular factors, in addition to tax, are required for GM-CSF gene expression. Systemic effects of excessive GM-CSF production were demonstrated by infiltration of polymorphonuclear leukocytes into tumor tissues which are not necrotic, by peripheral granulocytosis, and by splenomegaly resulting from myeloid hyperplasia. The interleukin-2 (IL-2) receptor was also found to be expressed by the tumors and tumor cell lines as measured by IL-2-binding and cross-linking studies. This is the first demonstration that the IL-2 receptor can be activated by tax in a nonlymphoid cell type. These in vivo findings are consistent with other reports which have demonstrated in vitro cis-regulatory elements within the 5'-flanking regions of the genes for GM-CSF and the IL-2 receptor which are responsive to trans activation by the tax gene.

Animals↗
PubMed1988

Chorionic villus sampling: experience with an initial 940 cases.

Of over 1000 patients referred to the Genetics & IVF Institute for chorionic villus sampling, 10% had an abnormal gestational sac at the time of initial presentation. Villus sampling could not be performed in 0.6% of cases, usually because of fibroids. Chorioamnionitis, probably related to the procedure, occurred in two patients (0.2%). The total fetal loss was 2.4%, which is not significantly different from the background fetal loss rate reported in normal pregnancies after eight weeks of gestation. The procedure-related loss was estimated as approximately 0.6%. The cytogenetic analysis routinely used was "direct" trophoblast karyotyping. There were no false-negative diagnoses. Trophoblastic mosaicism was observed in 1.3% of samples. Amniocentesis was performed in 3.5% of cases because of chorionic villus sampling failure, chorionic mosaicism, or elevated maternal serum alpha-fetoprotein (MSAFP) concentrations. Chorionic villus sampling was not associated with falsely elevated MSAFP levels at 15-18 weeks' gestation. Chorionic villus sampling has proved a safe and accurate prenatal diagnostic method associated with relatively low risk when performed by an experienced team, although additional amniocentesis will be necessary in a small percentage of pregnancies.

Adult↗
PubMed1979

A practical application of computer pattern recognition research: the Abbott ADC-500 differential classifier.

The ADC-500 is a new blood cell differential classifier manufactured by Abbott Laboratories. It performs 500-cell leukocyte differentials on both normal and abnormal cells, evaluates red cell morphology and estimates platelet sufficiency at a rate of 40 to 50 samples per hour in stand-alone operation. The ADC-500 system consists of a spinner which prepares a uniform blood monolayer on a slide, a stainer which reproducibly stains the slide with Wright's stain, an encoder which attaches an instrument and human readable identification to the slide and an analyzer which accepts a stack of up to 50 slides, evaluates these slides and prints the results and the slide identification on report forms. The system's analysis rate, which represents a 5- to 10-fold increase over other commercially available differential counters, requires a number of specialized techniques for its realization. One key to this performance is the development of a high speed X-Y slide positioning stage which can move to a new cell and settle in 50 msec. Another is the high degree of parallelism used in the system structure and the pipelining of the data processing. A third is the development of uniform and repeatable sample preparation modules. Within the analyzer module, the autofocus, white cell acquisition and high resolution cell analysis systems are independent and operate in parallel. At the same time within the high resolution cell analysis system, one cell is acquired; the digitized image of a second processed; and a third is classified using pattern recognition techniques. All of these tasks, except focus, are under the control of a minicomputer system. Tests of the system reveal good accuracy and an improvement in precision due to the increase in the number of counted cells.

Blood Cells↗
PubMed1979

Rapid analysis of hematology image data: the ADC-500 preprocessor.

A sequential, pipeline processor (that we have named the ADC-500 preprocessor) has been developed which scene segments the three color image data from the ADC-500 optics one image element at a time, groups together image elements from each object in the scene and extracts features from each object. The processing occurs at television frame rates, requiring 16.7 msec to process the entire image. This speed was instrumental in allowing the ADC-500 automated differential analyzer to perform routine 500-cell differentials. The preprocessor also contains hardware which simplifies compilation of the three color histograms. The segmentation algorithms implemented in the preprocessor are multicolor extensions of the classical monochrome density histogram threshold method. For most cell image analysis tasks, a sequential pipeline processor of this type should be more economical and as fast or faster than a parallel processor.

Blood Cells↗
PubMed1973

Feasibility of computer screening of blood films for the detection of malaria parasites.

This paper considers the feasibility of automatic screening procedures for detecting malaria parasites in blood smears prepared in the field. A simple programme for pattern recognition by computer has been developed for thin blood films that identifies parasites as densely stained particles within an erythrocyte. The parasites are detected correctly, but platelets falling accidentally within the outline of an erythrocyte and perhaps reticulocytes may be wrongly classified as parasites. The results indicate that automated detection of parasites is technically feasible but that the technique needs to be refined to reduce the incidence of false positives. A substantial increase in processing speed is required if the automatic procedure is to be economically feasible in screening programmes. The complexity of the equipment and the need for well prepared blood smears point to a possible use of the technique in laboratory checks but not under usual field conditions.

Bacteriological Techniques↗
PubMedDate not supplied

Sample preparation variation and its effects on automated blood cell differential analysis.

Uniform and reproducible sample preparation is an indispensable ingredient in automated instruments for cell analysis. Differences in measured cell morphology resulting from nonuniform sample preparation are indistinguishable to the instrument from differences reflecting different cell types or functions. As a result, as sample preparation becomes more variable, subtle cell distinctions are first confused and then completely obscured. As part of the development of the Abbott ADC-500 differential analysis system, automatic blood film spinner and stainer modules were developed to provide uniform sample preparation. These modules were tested to quantitate the effects of variations in the spinning and staining conditions on the measured ADC-500 parameters and observed cell morphology. The previously reported increase in spin time with increasing hematocrits was confirmed for the ADC-500 spinner. Moderate variations in spin speed, acceleration, deceleration and spin chamber configuration were found to have little or not effect. Postspinning air flow over the slide had a dramatic effect on morphology distortion. Variations of the staining temperature, staining time or rinse volume were found to have very little effect on measured leukocyte parameters although staining temperature had a dramatic effect on observed erythrocyte morphology and staining. Stain:buffer ratio variations were found to alter measured leukocyte parameters, with the measured density increasing as the fraction of stain increased up to a 1:2 stain:buffer ratio. Because the operational limits for the spinning and staining parameters are much tighter than the range of variables investigated, it was concluded that the ADC-500 sample preparation modules do not introduce variations in the analyzer results.

Autoanalysis↗