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Biomedical subjects

R Morgan

Publications and source records attributed to R Morgan.

At least 253 records · Page 14Linked to original sources

The Philadelphia (Ph) chromosome in leukemia. I. A new mechanism due to interstitial deletion and insertion in chronic myelocytic leukemia.

The Philadelphia (Ph) chromosome in leukemia is invariably derived from chromosome #22. A break occurs in the long (q) arm of chromosome #22 and, in every case observed until now, all of the material from that breakpoint through the telomere of chromosome #22 has been reciprocally translocated to another chromosome, most often chromosome #9. With the t(9;22) translocation, the oncogene c-sis moves from chromosome #22 onto 9q and the oncogene c-abl moves reciprocally from chromosome #9 onto 22q. We report a new mechanism for the genesis of the Ph chromosome in chronic myelocytic leukemia (CML) involving interstitial deletion of chromosome #22 with insertion of the deleted material into another chromosome: 46,XX,dir ins(11;22)(q13;q11q13). The distal portion of chromosome #22, including the telomere, appeared to have been retained in the Ph chromosome. There was no visible involvement of chromosome #9. This insertional deletion is of potential importance in evaluating the roles of oncogenes such as c-abl and c-sis in the Ph rearrangement in the origin of leukemia.

Bone Marrow↗

The Philadelphia (Ph) chromosome in leukemia. II. Variant Ph translocations in acute lymphoblastic leukemia.

Nearly 20 patients with a masked Philadelphia (Ph) translocation have been described in chronic myelocytic leukemia. We report two instances of acute lymphoblastic leukemia (ALL) with variant Ph translocations. One case, involving a 26-year-old male, was associated with a variant t(14;22)(q32;q11) translocation. The second case involved a 36-year-old male with a more complex translocation, t(9;15;22)(q12;q26;q11). In each case, cells with a masked Ph translocation were observed. These appear to be the first ALL cases reported with a masked Ph chromosome. The findings are discussed in relation to recent knowledge regarding the genesis of the Ph chromosome.

Adult↗

The Philadelphia (Ph) chromosome in leukemia. III. Complex Ph translocation plus inversion in chronic myelocytic leukemia.

Remarkable chromosome abnormalities were observed in bone marrow cells from a woman with chronic myelocytic leukemia and atypical tuberculosis due to Mycobacterium avium-intracellulare infection. Four chromosome breaks occurred at bands 1p13, 1q32, 11p15, and 22q11. These breaks resulted in a complex Philadelphia (Ph) translocation between chromosomes #1, #11, and #22 and in an inversion of chromosome #1. Oncogenes on these chromosomes include N-ras and c-sk on chromosome #1, c-H-ras on chromosome #11, and c-sis on chromosome #22. Complex chromosome rearrangements may facilitate multiple oncogene changes, thereby permitting several steps in cancer development to occur simultaneously.

Adult↗

Enhanced expression of chromosome fragile site 10q25 in chronic myelogenous leukemia.

Spontaneous expression of a BrdU-sensitive fragile site at 10q25 was observed in normal lymphocytes and malignant blood and bone marrow cells in chronic myelogenous leukemia (CML). The cells were marked by a Philadelphia chromosome rearrangement due to insertion of 22q11----q13 at 11q13. The fragile site at 10q25 was expressed in larger proportions of malignant than normal cells. Although this fragile site is not at a cancer chromosome breakpoint, malignancy enhanced its expression, consistent with a cascade effect.

Bone Marrow↗

Human chromosome variation with two Robertsonian translocations.

A woman was found to have 42 autosomes due to engagement of both chromosomes 14 in Robertsonian rearrangements, one with a chromosome 21 and the other with a chromosome 22: t(14q21q) and t(14q22q). The two translocations appear monocentric and by silver staining have no rRNA activity. The t(14q21q) translocation is familial and was ascertained through a nephew with Down syndrome, while the origin of the t(14q22q) translocation was not established. In addition to these two translocations, the woman had XX/XXX sex chromosome mosaicism. She has had two recognized pregnancies, each resulting in the birth of a child with one of the two translocations. Both children are phenotypically normal, as is their mother, the first normal liveborn individual identified with two Robertsonian translocations.

Adult↗

Evidence for opiate receptor involvement in the consumption of a high palatability diet in nondeprived rats.

Nondeprived adult rats were familiarized with a highly palatable diet (powdered small animal diet mixed with sweetened condensed milk and water). The palatability of food was such that it induced vigorous feeding responses, 15-20 g food consumed within the first 30 min of access. In partially-satiated male rats, the kappa receptor agonists EKC and U-50,488 (subcutaneously administered) produced large increases in food consumption in the first 30 min of access, post-injection. In experiments with naloxone and WIN 44,441-3, we found that the effects of naloxone (0.01-10 mg/kg; S.C.) were crucially dependent on the sex and dietary history of the animals. Male, obese rats were most sensitive to naloxone's anorectic effect. Lean females were completely insensitive. WIN 44,441-3 (0.01-10 mg/kg, S.C.) had no effect on food intake in any group of animals.

Animals↗

Translocation (1;7)(p11;p11): a new myeloproliferative hematologic entity.

Four cases with myeloproliferative syndromes or acute nonlymphocytic leukemia associated with t(1;7)(p11;p11) are presented. In each case, as in all cases published in the literature, the karyotypes of the affected cells contained two normal chromosomes #1, but only one chromosome #7, with the result that the basic karyotype was 46, -7, +t(1;7). This chromosome change is not geographically restricted, and appears to characterize a group of patients with myeloproliferative disorders and acute nonlymphocytic leukemia, including myeloproliferative syndromes, in whom exposure to previous chemotherapy, x-rays, or drugs is in the background history. The t(1;7) in secondary leukemia and myeloproliferative syndromes serves to duplicate the long arm of a chromosome #1 and to rescue the short arm of a chromosome #7.

Acute Disease↗

Deletion of chromosome band 13q14: a primary event in preleukemia and leukemia.

Chromosome abnormalities were analyzed in 200 consecutive patients with preleukemia and leukemia, and four patients were found with a deletion of 13q14 for an incidence of 2%. Together with data on chromosome aberrations in cancer from the literature, our results indicate clearly that deletion of band 13q14 is a nonrandom chromosome anomaly in premalignant and malignant blood disorders. Deletion of 13q14 appears specifically to constitute a primary event in the initiation of preleukemia. An additional rearrangement involving another chromosome must occur for progression of the preleukemia to acute nonlymphocytic leukemia.

Acute Disease↗

Unexpected lambda chain expression in lymphocytic malignancy.

Specific chromosome changes occur in the initiation and progression of cancer. A translocation between chromosomes 14 and 18 arises as a primary cytogenetic event in the formation of non-Hodgkin, non-Burkitt lymphomas (BL), while a translocation between chromosomes 2 and 8 is seen in BL and BL-type acute lymphocytic leukemia (ALL-L3) with expression of kappa (kappa) light immunoglobulin chains. These two translocations were detected in a lymphocytic malignancy expressing not kappa, but lambda (lambda) light chains. The anomalous light chain expression, it appears, provides the key clue indicating that the translocation between chromosomes 14 and 18 arose first during lymphoma formation in a cell committed to lambda chain synthesis and the translocation between chromosomes 2 and 8 occurred in the transformation to ALL. This sequence of cytogenetic events is consistent with the clinical course from lymphocytic lymphoma to ALL, the immunologic phenotype of the malignancy, and the concept of a cascade of chromosome changes eventuating in aggressive cancer.

Breast Neoplasms↗

Too many chronic mentally disabled patients are too fat.

In a survey of 190 chronic mentally disabled patients we found a significantly higher prevalence of overweight and obesity in both sexes, especially women, compared with the general population. The apparent causes were overeating, underactivity, ignorance of correct dietary principles and the differential effects of various psychotropic drugs which we were able to measure. Some preventive ideas are suggested.

Adult↗

Leukemia with Down's syndrome: translocation between chromosomes 1 and 19 in acute myelomonocytic leukemia following transient congenital myeloproliferative syndrome.

A girl with Down's syndrome was born with a myeloproliferative disorder. The child had spontaneous regression of the myeloproliferation, with acute leukemia developing at a later date. Morphologic, cytochemical, immunologic, and immunoglobulin gene configuration studies all supported the diagnosis of acute nonlymphocytic leukemia. High-resolution chromosome studies revealed that the leukemic cells consistently contained a translocation between chromosomes 1 and 19: der(19)t(1;19)(q25;p13). Spontaneous regression of the transient myeloproliferative syndrome of the newborn with Down's syndrome may not always be permanent, and the transient myeloproliferative syndrome may sometimes represent an early sign of acute nonlymphocytic leukemia.

Antibodies, Monoclonal↗

Chronic schizophrenia.

When I was an SHO at the old Observation Ward at the North Middlesex Hospital in 1954, my immediate boss walked in one day and handed me a piece of paper on which was typed "Largactil 50 mg tds" and said "Try that on the next schizophrenic we get in". What follows is what I have learnt since then.

Antipsychotic Agents↗

Common region on chromosome 14 in T-cell leukemia and lymphoma.

Chromosome 14 breakpoints in malignant human lymphocytes cluster on the long (q) arm near bands q11 and q32. An inversion of chromosome 14 due to breaks in q11.2 and q32.3 has now been found in a newly established childhood T-cell lymphoma cell line and confirmed in T-cell chronic lymphocytic leukemia. A translocation was also found between chromosomes 10 and 14 with a breakpoint at 14q11.2 in another T-cell lymphoma cell line. It is proposed that a proximal region on chromosome 14 in or near sub-band q11.2 is related to T-cell function. Rearrangements in this region may affect the growth of T lymphocytes and be involved in the development of T-cell malignancies.

Cell Line↗

Decrease of vasoactive intestinal polypeptide (VIP) in the penises from impotent men.

Vasoactive intestinal polypeptide (VIP)-containing nerves were depleted in the penises of 28 impotent men. The extent of the decrease in VIP-containing nerves broadly reflected the severity of erectile dysfunction. VIP-immunoreactive nerves were most depleted in those men with complete erectile impotence, irrespective of the aetiology of the dysfunction, whereas in those men in whom some erectile function persisted, loss of VIP-immunoreactive nerves was more variable and less complete. Conventional histology demonstrated only mild changes (muscle atrophy and occasional thickening of blood vessel walls). VIP levels, measured by radioimmunoassay of tissue extracts, were depleted by more than 80% in penises from impotent diabetics (43.4 +/- 9.9 pmol/g wet weight [mean +/- SEM]), when compared with 6 controls (189.9 +/- 45.9 pmol/g). These findings not only support the contention that VIP may be the principal neurotransmitter involved in penile erection, but also suggest that depletion of this powerful vasodilatory peptide may play a key role in the development of penile impotence.

Adult↗

Chromosome analysis in hematologic disorders. The leukemias.

For two decades, cytogenetic studies have been used to rule in (or out) the Philadelphia (Ph1) chromosome associated with chronic myeloid leukemia. Beyond this single purpose, chromosome studies have generally not been utilized in or applied to the practice of hematology-oncology. This report presents male and female patients, teens to 70s in age, with representative hematologic disorders, in whom the cytogenetic findings were useful clinically. These cases illustrate the following principles: (1) hematologic disorders can be characterized by chromosome analysis; (2) chromosome findings help in the diagnosis, prognosis, and treatment of blood diseases; (3) blood and bone marrow samples can be processed routinely for cytogenetic analysis; (4) these samples can be transported long distances from clinic to laboratory; and (5) the contemporary practice of hematology and oncology requires chromosome analysis for fuller evaluation and understanding of hematologic conditions.

Adult↗

Cloning of the vaccinia virus telomere in a yeast plasmid vector.

The vaccinia virus DNA telomere, which contains a covalently closed hairpin structure, has been cloned in a yeast plasmid vector. Restriction mapping indicates that the cloned vaccinia telomere is maintained in yeast not in its native hairpin configuration but as an inverted repeat structure, within a circular plasmid, with the sequences of the viral hairpin now at the axis of symmetry of an imperfect palindrome. As such, the cloned telomere resembles the telomeric replicative intermediate observed during vaccinia virus DNA replication. Small deletions and duplications in the viral inverted repeats of different clones suggest a model in which the observed circular plasmids were generated in yeast by the replication of hybrid linear DNA molecules consisting of the linearized yeast vector flanked by two hairpin-containing vaccinia termini.

Cloning, Molecular↗