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F Cotter

Publications and source records attributed to F Cotter.

31 records · Page 2Linked to original sources

Breakpoints at 11q23 in infant leukemias with the t(11;19)(q23;p13) are clustered.

We have analyzed a series of nine infant leukemias that carry a t(11;19)(q23;p13). They had the morphologic features of acute lymphoblastic leukemia (ALL) and expressed markers typical of B-cell progenitor ALL or pre-B ALL; one coexpressed myeloid markers in addition to lymphoid markers (biphenotypic). Two probes (P/S4 and 98.40) subcloned from a yeast artificial chromosome (YAC) known to span the breakpoint in the t(4;11) were used to investigate DNA isolated from the leukemic cells of these patients. A total of approximately 15 kb of genomic DNA in the vicinity of the probes was examined by conventional Southern blot analysis using a series of restriction enzymes. In eight of the nine cases, the breakpoint could be mapped to an approximately 10-kb BamHI fragment disclosed by hybridization to the P/S4 probe.

Antigens, CD↗

Myeloablative therapy with autologous bone marrow transplantation as consolidation of remission in patients with follicular lymphoma.

A study has been in progress since June 1985 to evaluate the use of myeloablative therapy (cyclophosphamide [60 mg/kg x 2] and total body irradiation [200 cGy x 6]) followed by reinfusion of autologous bone marrow in patients in second or subsequent remission of B-cell non-Hodgkin's lymphoma. The marrow mononuclear cell fraction is being treated in vitro with three cycles of the monoclonal antibody anti-CD20 (anti-B1, Coulter Immunology) and baby rabbit complement (Pel-Freez). Thirty-eight patients with follicular lymphoma (age range 29-61 years, median 43) have been treated to date. At the time of treatment, 28 patients were in second remission, 7 were in third, and 3 were in more than third remission. Twenty-three patients were in complete remission, 15 had residual disease (7 had lymph nodes less than 2 cm diameter, 4 had less than 10% bone marrow infiltration, 1 had involvement of lymph nodes and bone marrow, and 3 had involvement at other sites). Of the 38 study patients, 32 are alive; 6 have died, 4 in remission. Two of the deaths were treatment related: 1 resulted from cerebral haemorrhage at 29 days; 1 resulted from systemic fungal infection at three months). One patient died from secondary acute myelogenous leukaemia at four years, and another from an unrelated cause. Two patients died following relapse. The median time to engraftment was 28 days (range 15-45 days) for neutrophils greater than 0.5 x 10(9)/L and 28 days (range 15-46 days) for platelets greater than 20 x 10(9)/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Direct sequence analysis of the 14q+ and 18q- chromosome junctions in follicular lymphoma.

Although the t(14;18) chromosome translocation has been demonstrated to be a highly consistent feature of follicular lymphomas, the underlying mechanism generating this fusion has remained uncertain. To examine this question further, a polymerase chain reaction strategy has been devised to permit the amplification and direct sequencing of the resultant 14q+ and 18q- reciprocal junctions. Direct sequence analysis of amplified 14q+ junctions established that 7 of 11 tumors contained a bcl-2 (mbr) sequence fused to an immunoglobulin JH region (five were J6 and two were J5). One of these junctions had an unusual configuration with the bcl-2 and JH sequences separated by a recognizable DH region. This finding suggests that at least some of the junctional sequences, previously thought of as N insertions, may be fragments of unrecognized DH regions. It was also possible to amplify and sequence 18q- junctions using a primer based on the DH recombination signal sequences. Several 18q- junctions were shown to consist of DH/bcl-2 (either mbr or mcr) fusions. In two tumors the 14q+ and 18q- junctions were fully sequenced, and it was demonstrated that the bcl-2 sequence was conserved during mbr and mcr translocations. This contrasts with previous analyses that demonstrated either loss or duplication of several bases at the breakpoints in the bcl-2 gene.

Base Sequence↗

Gene mapping by enzymatic amplification from flow-sorted chromosomes.

A new approach to gene mapping which combines enzymatic amplification with high-resolution flow sorting of human chromosomes has been devised. Reliable amplification from as few as 200 chromosomes has been demonstrated. This method, with particular application to mapping the position of chromosomal translocations, has been used to show that the breakpoint for the constitutional translocation t(11;22)(q23;q11) lies proximal to the genes c-ets-1, Thy-1, and T3 delta and distal to the int-2 gene. The mapping was confirmed by Southern analysis to much larger numbers of chromosomes sorted from the same cell line. Control reactions for the bcl-2 gene on chromosome 18 and the C alpha gene of the IGH locus on chromosome 14 demonstrated the discrimination which can be achieved.

Base Sequence↗

Substance abuse units taught by four specialties in medical schools and residency programs.

Four medical specialty organizations conducted a survey of 294 departments in 98 medical schools and 1,124 residency programs to identify the number and type of curriculum units on substance abuse offered by these specialties. A curriculum unit was defined as a formal block of teaching on substance abuse. A total of 251 (85 percent) of the medical school departments and 828 (74 percent) of the residency programs responded. Of those, 175 (70 percent) of the medical school departments and 479 (58 percent) of the residency programs reported offering at least one curriculum unit on substance abuse. There was considerable variation among the four specialties in the number and percentage of departments or programs reporting such units. Overall, a majority of the units addressed both alcohol and other drugs, were required, and included a clinical component. Evaluations of content and teaching strategies are needed to examine the quality and adequacy of substance abuse training.

Curriculum↗

Detection of somatic changes in human cancer DNA by DNA fingerprint analysis.

Minisatellite DNA probes which can detect a large number of autosomal loci dispersed throughout the human genome were used to examine the constitutional and tumour DNA of 35 patients with a variety of cancers of which eight were of gastrointestinal origin. Somatic changes were seen in the tumour DNA in ten of the 35 cases. The changes included alterations in the relative intensities of hybridising DNA fragments, and, in three cases of cancers of gastrointestinal origin, the appearance of novel minisatellite fragments not seen in the corresponding constitutional DNA. The results of this preliminary study suggests that DNA fingerprint analysis provides a useful technique for identifying somatic changes in cancers.

Breast Neoplasms↗

Increased platelet and red cell counts, blood viscosity, and plasma cholesterol levels during heat stress, and mortality from coronary and cerebral thrombosis.

Recorded deaths from coronary and cerebral thrombosis rise markedly in heat waves. In a British heat wave with little or no distortion due to air-conditioning, outside temperatures of 34.6 degrees C (maximum) and 20.8 degrees C (minimum) were followed by peak mortalities from coronary and cerebral thrombosis one to two days later. Experimental exposure of volunteers to moving air at 41 degrees C for six hours caused core temperature to rise 0.84 degree C, weight to fall 1.83 kg with sweating despite access to water, heart rate to increase 32 beats per minute, and arterial pressure to fall, particularly on standing. The red blood cell count increased 9 percent, and blood viscosity increased 24 percent, mostly after the first hour. The platelet count rose 18 percent, and the platelet volume fell, mostly in the first hour. The plasma cholesterol level increased 14 percent without a change in distribution among lipoprotein fractions. The changes seem able to explain the increased mortality from arterial thrombosis in hot weather.

Adult↗

Increases in platelet and red cell counts, blood viscosity, and arterial pressure during mild surface cooling: factors in mortality from coronary and cerebral thrombosis in winter.

Six hours of mild surface cooling in moving air at 24 degrees C with little fall in core temperature (0.4 degree C) increased the packed cell volume by 7% and increased the platelet count and usually the mean platelet volume to produce a 15% increase in the fraction of plasma volume occupied by platelets. Little of these increases occurred in the first hour. Whole blood viscosity increased by 21%; plasma viscosity usually increased, and arterial pressure rose on average from 126/69 to 138/87 mm Hg. Plasma cholesterol concentration increased, in both high and low density lipoprotein fractions, but values of total lipoprotein and lipoprotein fractions were unchanged. The increases in platelets, red cells, and viscosity associated with normal thermoregulatory adjustments to mild surface cooling provide a probable explanation for rapid increases in coronary and cerebral thrombosis in cold weather. The raised arterial pressure and possibly cholesterol concentration may contribute to slower components of the increased thrombosis.

Adolescent↗

Angiotropic large cell lymphoma (ALCL): morphological, immunohistochemical and genotypic studies with analysis of previous reports.

The entity 'angioendotheliomatosis proliferans systemisata' was first described 28 years ago as a cutaneous small vessel neoplasm of presumed endothelial origin. Since then, 101 similar cases have been reported under a variety of different names, most with systemic as well as cutaneous lesions, and a lymphoid histogenesis of the tumour cell is now favoured. Review of these cases has shown a characteristic clinical presentation with predominant neurological and dermatological features, although the diagnosis was made at autopsy in 53 per cent of patients. Most therapeutic regimens have proved ineffective with a median survival of 5 months from date of clinical presentation. Aggressive combination chemotherapy can produce complete and lasting remission and a partial response to steroids is sometimes seen. We have examined a case of this condition showing unusual clinical features. Immunohistochemical studies confirm the lymphoid origin of the tumour cells with B cell phenotype. Antigen receptor gene rearrangement studies indicate the presence of the same clonal population of B cells in multiple sites. We suggest that the term 'angioendotheliomatosis proliferans systemisata' should be dropped and support the use of 'angiotropic large cell lymphoma' to describe this unusual condition.

B-Lymphocytes↗

Faculty development and curriculum change in substance abuse.

What approaches can be used to upgrade nursing education and clinical skills in alcohol and drug abuse? The authors discuss the development of faculty and curricula in three schools of nursing. The programs described are part of a national initiative to ensure that health care professionals have basic knowledge and clinical skills in screening, assessment, intervention, and the appropriate use of referral systems for clients with substance abuse problems.

Curriculum↗