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Biomedical subjects

R Morgan

Publications and source records attributed to R Morgan.

At least 235 records · Page 13Linked to original sources

Common mechanism of chromosome inversion in B- and T-cell tumors: relevance to lymphoid development.

An inversion of chromosome 14 present in the tumor cells of a patient with childhood acute lymphoblastic leukemia of B-cell lineage was shown to be the result of a site-specific recombination event between an immunoglobulin heavy-chain variable gene and the joining segment of a T-cell receptor alpha chain. This rearrangement resulted in the formation of a hybrid gene, part immunoglobulin and part T-cell receptor. Furthermore, this hybrid gene was transcribed into messenger RNA with a completely open reading frame. Thus, two loci felt to be normally activated at distinct and disparate points in lymphocyte development were unified and expressed in this tumor.

B-Lymphocytes↗

Chromosome clues to acute leukemia in Down's syndrome.

Surprisingly few cases of Down's syndrome with acute leukemia have been documented by chromosome banding studies of the leukemia cells. We studied a Down's syndrome child with acute myelomonocytic leukemia and found that, including this case, only 24 cases of Down's syndrome and acute leukemia have been reported with chromosome banding analysis. Twenty-three of the patients had a trisomy 21 chromosome complement, whereas, one had a translocation. The types of acute leukemia included acute myeloblastic leukemia, acute myelomonocytic leukemia, acute monoblastic leukemia, acute lymphoblastic leukemia, and erythroleukemia. Only three cases had chromosomes missing from the leukemic cells. Sixteen of the 24 patients had extra chromosomes in their malignant cells. Chromosomes #8 and #21 were extra in six cases each and chromosomes #19 and #22 were extra in four cases each. Chromosome rearrangements were observed in nine cases. Three of the nine cases had partial deletion of the long arm of chromosome #6. Cases of Down's syndrome with acute leukemia need to be reported with high-resolution chromosome banding of the leukemia cells. There is as yet no clear chromosome clue as to the precise basis of the etiologic association between Down's syndrome and acute leukemia.

Acute Disease↗

Fragile sites: overview, occurrence in acute nonlymphocytic leukemia and effects of caffeine on expression.

Interest has recently grown in the possible role of chromosomal fragile sites as factors predisposing to chromosome rearrangements characteristic of specific human cancers. Data from two series of experiments relating to this hypothesis are presented. First, the effects of caffeine and theophylline on expression of the fragile X and common fragile sites was studied in lymphocytes from three subjects. Caffeine and theophylline did not enhance fragile X expression under the conditions employed but did greatly enhance expression of the common fragile sites. Second, three patients with acute nonlymphocytic leukemia-M4 and inv(16)(p13q22) in leukemic cells were tested for the presence of fra(16)(q22) in normal cells. The fragile site was not seen in any of the patients in this study.

Acute Disease↗

Telomeric fusion in pre-T-cell acute lymphoblastic leukemia.

Telomeric fusion, a rare phenomenon, was observed in malignant cells from the peripheral blood of an 18-year-old male with rapidly progressive pre-T-cell acute lymphoblastic leukemia (ALL). Only two comparable cases, both with B-cell ALL, have been reported with telomeric fusion in neoplasia. All of the leukemic cells examined from our patient had two chromosome abnormalities consisting of partial triplication (trp) of chromosome 2 and a derivative chromosome 3. Approximately a third of the leukemic cells showed in addition telomere-telomere fusions. These involved the telomeric regions of 1p, 2p, 4q, 5q, 7q, 10q, 11q, 12p, 15p, 21p, and Xq and 3p of the derivative (3). The findings in this case suggest that telomeric fusion may function as a mechanism for the development of chromosome rearrangements that may play a role, albeit rarely, in human neoplasia.

Adolescent↗

Pathways of sympathetic innervation to the superior and inferior (Müller's) tarsal muscles.

Fluorescent staining and fluorescent microscopy were used to evaluate the pathways which the sympathetic nerves followed to reach the smooth muscles of the eyelids. Selected structures from fresh orbits were removed, sectioned, and fluorescently stained utilizing glyoxylic acid. Photographic results from the fresh orbits showed fluorescence accompanying the oculomotor, trochlear, and abducent nerves and branches of the ophthalmic division of the trigeminal (lacrimal, supraorbital, and nasociliary) nerves. The eyelids exhibited intense fluorescence within the tarsus and throughout adjacent connective tissue. The principal paths of the sympathetic nerves are the sensory (first dimension of the trigeminal) and the motor nerves to the orbit. The arteries (in contrast to previous descriptions) do not appear to be a major pathway.

Eyelids↗

13-cis retinoic acid treatment for myelodysplastic syndromes.

To test the biologic activity of 13-cis retinoic acid (13-CRA) in patients with myelodysplastic states (MDS), we administered 13-CRA orally (2.5 mg/kg/d initially, escalated to 4 mg/kg/d) for 8 weeks to 15 consecutive patients. Eight of 15 patients (53%) experienced an increase in peripheral granulocyte counts of greater than 20% (range, 22% to 700%). In five patients, the absolute increase in peripheral granulocyte count was greater than 500 cells/microL. Two of 15 patients experienced a decrease in the circulating granulocyte count of greater than or equal to 20%. Comparable values for peripheral platelet counts were 27% (4/15 patients) greater than 20% increase and 33% (5/15 patients) greater than 20% decrease. No patient experienced a major change in erythrocyte transfusion requirement while receiving 13-CRA in comparison with pretreatment status. Thirteen patients had morphologic and cytogenetic evaluation of marrow cells before 13-CRA treatment, and with one exception, marrow morphologic and cytogenetic abnormalities persisted following 13-CRA administration. The exception occurred in the patient with the most dramatic response, whose granulocyte count increased from 400 to 2,800 cells/microL along with a normalization of the leukocyte alkaline phosphatase score, a morphologic improvement in granulocyte maturation, and a disappearance of the initial chromosome abnormality. These changes did not persist after cessation of 13-CRA administration, but were reproduced following drug readministration. No patients experienced serious decrements in peripheral blood counts or leukemic transformation while receiving 13-CRA. All patients had mild to marked dermatologic toxicity (cheilosis, skin dryness). No other major toxicity was encountered. We conclude that 13-CRA may be safely administered and may increase peripheral granulocyte counts in a proportion of patients with MDS.

Adult↗

Cytogenetic and immunophenotypic analysis of cell lines established from patients with T cell leukemia/lymphoma.

Cell lines were established from five patients with T cell malignancies. Two patients had T cell lymphoblastic lymphoma (T-LL), whereas three patients had T cell acute lymphoblastic leukemia (T-ALL). Both T-LL cell lines expressed cell surface antigens characteristic of midthymocytes (Leu 2, 3, 6+). One T-ALL cell line also expressed this immunophenotype, one expressed suppressor/cytotoxic antigens (Leu 2+; Leu 3, 6-), and one expressed antigens of a mature but uncommitted T cell (Leu 4+; Leu 2, 3, 6-). Cytogenetic analysis showed that each cell line had 46 chromosomes with pseudodiploidy. The three T-ALL cell lines had only a few chromosome changes; one cell line had one deletion, another had two deletions, and the third had a translocation and two deletions (including loss of part of 9p). In comparison, both T-LL cell lines had complex chromosome changes, including most notably a rearrangement of band 14q11.2. The immunophenotypes and chromosome breakpoints showed patterns of interlock between the T-LL and T-ALL cell lines because common abnormalities occurred at six distinct chromosome sites. Cell lines with limited and specific chromosomal abnormalities are important because they can provide the basic material for molecular genetic studies that could elucidate the genetic mechanisms involved in neoplasia.

Adolescent↗

Responses of hemopoietic precursors to 13-cis retinoic acid and 1,25 dihydroxyvitamin D3 in the myelodysplastic syndromes.

To determine the effects of the "maturation-inducing" agents 13-cis retinoic acid and 1,25 dihydroxyvitamin D3 on marrow cells from normal individuals and patients with myelodysplastic syndromes (MDS), we assessed marrow hemopoietic clonogenicity and differentiation response patterns to these agents. These vitamins caused increased proliferation in vitro of normal clonogenic marrow myeloid precursor cells (CFU-GM), decreased erythroid precursors (BFU-E), and no change in multipotent stem cells (CFU-GEMM). Marrow hemopoietic colony-forming cell incidence was generally subnormal in the 22 MDS patients evaluated. In vitro exposure to both agents caused various patterns of alteration of MDS hemopoietic colony and cluster formation, with similar but more pronounced effects evoked by retinoic acid. In the vast majority of MDS patients, enhanced marrow clonal granulocyte-monocyte differentiation and decreased BFU-E growth were noted after in vitro exposure to these vitamins. Correlation of biological effects was demonstrated between in vivo changes of peripheral neutrophil counts and in vitro responses of myeloid precursors for ten MDS patients treated with an eight-week therapeutic course of retinoic acid. Cytogenetic analyses indicated persisting aneuploidy or coexisting normal and aneuploid karyotypes in the cultured MDS myeloid cells and (with one exception) in native marrow cells from the treated patients. The varying responses of the MDS cells may monitor differing proportions of normal versus leukemic marrow cells susceptible to proliferative and differentiative expression on exposure to these agents.

Adult↗

Mechanisms of global support and posttraumatic enophthalmos: I. The anatomy of the ligament sling and its relation to intramuscular cone orbital fat.

The mechanisms of posttraumatic enophthalmos were evaluated to determine the interrelation between fat and ligaments in globe support. Anatomic studies demonstrate that the ligaments form an essential "sling" framework for the globe but are alone insufficient to maintain the globe's full forward position. Removal of extramuscular fat in cadavers and in patients undergoing blepharoplasty did not significantly change globe position. Loss of intramuscular cone fat (atrophy or displacement) in cadavers and patients produced enophthalmos. Fat atrophy is not a prominent feature in most patients with posttraumatic enophthalmos. Some loss of intramuscular cone fat from displacement outside the muscle cone is frequently present. The principal mechanism, however, of posttraumatic enophthalmos involves a displacement and change in the shape of orbital soft tissue. Loss of bone and ligament support permits posterior displacement and a reshaping of orbital soft tissue under the influence of gravity and the remodeling forces of fibrous scar contracture. The shape of the retrobulbar orbital contents changes from a modified cone to a sphere, and the globe sinks backward and downward. Given that the volume of orbital soft tissue is constant following trauma, procedures to restore the shape and position of the orbital soft tissue by mobilization and bone reconstruction will correct or significantly improve enophthalmos.

Adipose Tissue↗