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Biomedical subjects

M F Fey

Publications and source records attributed to M F Fey.

140 records · Page 8Linked to original sources

DNA polymorphism 5' to the JH region of the human immunoglobulin heavy chain gene and immunoglobulin gene rearrangements in leukemia.

DNA samples of two patients with acute myeloblastic leukemia were noted to have a variant band on digestion with HindIII and hybridization to a probe for the joining region of the immunoglobulin (Ig) heavy chain gene (JH). Further analysis showed that the variant band represented a constitutional DNA polymorphism rather than an Ig gene rearrangement. The HindIII fragment detected by the JH probe includes a highly polymorphic region 5' to the Ig heavy chain locus, and hence variant germline bands may be seen on autoradiography that can be mistaken for Ig gene rearrangements. The use of several different restriction enzymes and the analysis of the constitutional DNA allows a clear distinction to be made between somatic gene rearrangements and DNA polymorphisms.

Acute Disease↗

Assessment of clonality in gastrointestinal cancer by DNA fingerprinting.

DNA fingerprinting with three different probes (33.15, 33.6, and alpha-globin 3'HVR) was investigated as a method for the determination of clonality in gastrointestinal tumors. In 29/44 carcinomas the tumor DNA showed clonal somatic mutations that were not seen in the corresponding peripheral blood and normal mucosa samples. The changes consisted of either novel fingerprint bands, losses of bands, or both. The probe 33.15 yielded the highest rate of abnormal DNA fingerprints (21/44 carcinomas). Sequential use of the probes increased the number of cases where clonal fingerprint markers could be detected. One out of five colorectal adenomas also showed a clonal loss of a fingerprint band. In two cases of gastric cancer, DNA from the metastatic tumor had a different DNA fingerprint from that found in the primary carcinoma. DNA fingerprinting offers a novel approach to determining clonality in tumors and may prove useful for the study of tumor progression.

Cloning, Molecular↗

Monitoring of heparin therapy with the activated partial thromboplastin time and chromogenic substrate assays.

Heparin therapy was monitored with the activated partial thromboplastin time (APTT) and with chromogenic substrate assays (factor Xa and factor IIa inhibition) in 100 plasma samples from 47 patients. Heparin concentrations were classified as being below, within or above a defined therapeutic range (TR; 0.2-0.55 units heparin/ml). In a first group of patients (A), all three assays allocated the plasma heparin levels to the same concentration interval with respect to the TR. The most frequent diagnoses in group A were uncomplicated arterial or venous thromboembolism, myocardial infarction with limited tissue necrosis, cardiac surgery without major complications and successfully treated infectious disease. In a second group of patients (B), the results of APTT suggested higher heparin concentrations with respect to the TR than the chromogenic assays. Predominant diagnoses were severe infectious diseases, severe liver disorders, extensive myocardial infarction and postoperative complications after cardiac surgery. The discrepancy between heparin concentrations determined by either APTT or the chromogenic substrate assays is most likely due to a non-heparin related prolongation of APTT caused by the underlying disease.

Chromogenic Compounds↗

[Hodgkin's disease in a Swiss family].

Hodgkin's disease was found in five members of the same generation in a large Swiss family. At presentation, the patients were between 20 and 30 years old. The histological diagnosis was confirmed in three patients. In one woman the differential diagnosis of histiocytic non-Hodgkin's lymphoma was considered. The patient history did not provide any conclusive evidence for environmental factors shared by all patients. Three siblings had grown up in the same household. They had never been in contact with the other pair of affected sisters. No clustering of cases in time occurred, as individual cases were diagnosed at least two years apart. Antibodies against Epstein-Barr viral capsid antigen were found in four patients (IgG: 1:10 to 1:160). There was no single HLA-haplotype common to all patients. However, two affected sisters were HLA-identical (paternal haplotype: Aw24(9), Bw62(15), DRw6; and maternal haplotype: A2, B7, DR2). Their brother with Hodgkin's disease was homozygous for A-, B- and DR-antigens. He shared all these antigens with his two affected sisters (A2, Bw62(15), DR2). A genetic predisposition in combination with environmental factors, in particular subclinical Epstein-Barr virus infection, may have been responsible for the development of Hodgkin's disease in this family.

Adult↗

Molecular diagnosis of haematological disorders using DNA from stored bone marrow slides.

A method is described for the extraction of high molecular weight DNA from bone marrow slides which have been stored at room temperature for more than 10 years. This technique widens the scope of molecular analysis of haematological malignancies to include the investigation of cases where the original malignant cells are not otherwise available.

Bone Marrow↗

[Monitoring heparin therapy by thrombin time and activated partial thromboplastin time--a comparison].

In 106 plasma samples obtained from patients on heparin therapy, monitoring by 2 methods (activated partial thromboplastin time and thrombin clotting time--APTT and TT) was compared. All patients in whom APTT indicated markedly higher plasma heparin concentrations than the TT were critically ill (group B): their main diagnoses included severe infectious disease, severe liver disease and extensive myocardial infarction. Patients with lesser discrepancies between the results of APTT and TT did not suffer from such severe conditions (group A). Cardiac surgery without major postoperative problems, limited myocardial infarction and uncomplicated thromboembolism were the main diagnoses in this group. In group B, non-heparin related prolongation of APTT was thought to be the main factor responsible for the overestimation of plasma heparin concentrations by this test. We conclude that in patients with severe infectious disease, liver disease or extensive tissue necroses (i.e. myocardial infarction), APTT cannot be recommended for laboratory monitoring of heparin therapy.

Blood Coagulation Tests↗

Hereditary leaky red cell syndrome in a Swiss family.

A Swiss family was found to have a hereditary hemolytic disorder associated with excessively leaky red cell membranes. Hemolysis was mild and fully compensated. Membrane lipid analysis revealed an increased phosphatidylcholine:phosphatidylethanolamine ratio. Membrane leaks included an increased permeability to sodium, potassium, calcium and, possibly, creatine. It is suggested that in hemolytic states, the combined finding of reticulocytosis and normal red cell creatine might be an easily obtainable clue to the presence of a leaky red cell syndrome.

Adult↗

Psychogenic purpura, idiopathic thrombocytopenic purpura, and platelet dysfunction in the same patient.

A patient whose peculiar and painful purpura seemed to be strongly related to psychogenic factors is described. The skin bleeding pattern in this patient was consistent with the diagnosis of psychogenic purpura (autoerythrocyte sensitization). In addition, idiopathic thrombocytopenic purpura and platelet storage pool deficiency were present. These somatic conditions are considered to be of minor importance in the pathogenesis of this hemorrhagic syndrome. The association of these various types of bleeding disorders in the same patient has not been previously described.

Adult↗

Prognostic factors in metastatic breast cancer.

Modern polychemotherapy has decisively changed the spontaneous course and median survival in metastatic stages of breast cancer. The prognosis for patients with the rather unfavorable type of visceral metastatic spread is definitely better now than 10 years ago. The influence of modern polychemotherapy on the survival and course of cases with mainly osseous metastases, however, is more limited. It seems that, in contrast to hormonal therapy, modern polychemotherapy alters the course of more aggressive types of metastases with a poor prognosis into a more favorable form of disease.

Breast Neoplasms↗

Different p16INK4a and p14ARF expression patterns in acute myeloid leukaemia and normal blood leukocytes.

The p16INK4a gene is often disrupted or transcriptionally silenced by CpG island methylation in human cancers. However, in acute myeloid leukaemia (AML) alterations of the INK4a-ARF tumour suppressor locus are rarely found despite the noted variable p16INK4a mRNA and protein levels. The p14ARF, an alternative reading frame protein encoded from the same INK4a-ARF locus, is a potent tumour suppressor functionally linked to p53. There is little known regarding the role of p14ARF in primary human tumours. Therefore, we analysed the expression patterns of these two tumour suppressors in 37 cases of AML. The relative expression of p16INK4a and p14ARF mRNA in AML blasts, measured by a specific p16INK4a/p14ARF multiplex RT-PCR, was significantly shifted towards p14ARF whereas relatively lower levels of p16INK4a were detected. Quantitative RT-PCR revealed significantly higher expression of both transcripts in AML blasts when compared to normal differentiated myeloid cells or CD34+ progenitor cells. Furthermore, a good correlation between p16INK4a protein and mRNA was observed, whereas no correlation was found with p14ARF. Our results suggest: a) increased levels of both p16INK4a and p14ARF may participate in the pathogenesis of AML, b) that high p14ARF mRNA expression might influence p16INK4a transcription and c) that post-transcriptional regulatory mechanisms are important for p14ARF expression.

Acute Disease↗