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Biomedical subjects

E P Lester

Publications and source records attributed to E P Lester.

At least 55 records · Page 3Linked to original sources

Sequential combination chemotherapy for advanced squamous cell carcinoma of the head and neck.

Thirty-four patients with advanced squamous cell carcinoma of the head and neck have been treated with sequential combination chemotherapy consisting of Cytoxan, methotrexate, oncovin, bleomycin and adriamycin, followed by Leucovorin (COMBAL). All patients had undergone extensive prior radiation and/or surgery. All the patients had recurrent cancer. Toxicity included two deaths from drug induced pancytophenia and one from sepsis. Treatment was well tolerated and could be given in the outpatient clinic. No bleomycin pulmonary or adriamycin cardiac toxicity was seen. Results include 4 patients who achieved complete remission, objective improvement in measurable lesions in 6 others, stabilization of disease for 1 to 3 mo. in 5, and progression of disease in 13. Survival has ranged from 1 to 19+ months with a median of 10.7 mo. for patients that were evaluated. We conclude that COMBAL produces objective evidence of improvement in approximately 45% of patients with far advanced, previously treated squamous cell carcinoma of the head and neck.

Adolescent↗

Heterogeneity of human alpha-fetoprotein as revealed by isoelectric focusing in urea-containing gels.

The heterogeneity of human alpha-fetoprotein has been studied by analytical isoelectric focusing in polyacrylamide gel slabs in the presence of 8 M urea. Six major isoelectric variants could be identified over a pH range of 6.0--6.2. Verification of their identity was achieved by crossed immunoelectrophoresis into agarose gel containing monospecific antiserum to human alpha-fetoprotein. Complete desialylation of the protein did not abolish the heterogeneity; a complex pattern of major alpha-fetoprotein bands persisted over a more alkaline pH range. We have been able to correlate the pattern of alpha-fetoprotein heterogeneity seen following extended agarose gel electrophoresis with that obtained during isoelectric focusing in the presence of urea. The quantity of certain alpha-fetoprotein charge isomers in various alpha-fetoprotein isolates may be important in considering certain biological functions of this protein.

Carcinoma, Hepatocellular↗

Human alpha-fetoprotein: immunosuppressive activity and microheterogeneity.

Purified human alpha-fetoprotein (HAFP) from five patients with hepatoma, one with gastric carcinoma, one with an embryonal cell tumor, and from fetal liver has demonstrated immunosuppressive potencies in vitro which vary over three orders of magnitude. A reversible association of HAFP with the cell surface and a predominant effect on T cells are suggested. No evidence of complex formation between HAFP and mitogen has been found. The microheterogeneity of HAFP has been detailed with crossed immunoelectrophoresis and isoelectric focusing in polyacrylamide gels containing 8M urea, and the immunosuppressive potency of HAFP isolated from a given source can be correlated with the proportion of certain HAFP species contained in it.

Dose-Response Relationship, Immunologic↗

Monoclonal gammopathy in hereditary spherocytosis: a possible pathogenetic relation.

Two cases of monoclonal gammopathy in patients with hereditary spherocytosis led us to consider the possible pathogenetic relation between these two disorders. Twelve adult patients with hereditary spherocytosis had significant hypergammaglobulinemia in comparison to normal subjects. Retrospective analysis of previous illness in 140 patients with multiple myeloma showed a significant association between IgA myeloma and previous gallbladder disease. We propose that the chronic reticuloendothelial stimulation due to extravascular hemolysis, possibly potentiated by the inflammation associated with cholelithiasis and cholecystitis, may foster neoplastic transformation of immunocytes in patients with hereditary spherocytosis, ultimately leading to the development of monoclonal gammopathy.

Aged↗

A postsynthetic modification of human alpha-fetoprotein controls its immunosuppressive potency.

In a previous study, we demonstrated three variants of human alphafetoprotein by crossed immunoelectrophoresis. In addition, we correlated the capacity of alpha-fetoprotein isolates from various hepatoma and fetal sources to suppress human lymphocyte transformation in vitro with the relative proportion of the electronegative variant, HAFP-3, present in each isolate. We have now isolated alpha-fetoprotein from the serum, ascitic fluid, and saline extract of tumor from a single hepatoma patient and from a homogenate of fetal livers. When tested for their capacity to inhibit human lymphocyte transformation in vitro, tumor and fetal liver alphafetoprotein were found to be extremely potent, serum alphafetoprotein had intermediate potency, and ascitic fluid alpha-fetoprotein was the least potent. Analysis of these isolates by crossed immunoelectrophoresis confirmed the correlation between the proportion of HAFP-3 and the immunosuppressive potency of each isolate. In addition, analysis of these isolates by isoelectric focusing in polyacrylamide gels containing 8 M urea revealed further evidence of microheterogeneity; at least six molecular variants were apparent. The proportion of one of these variants, termed HAFP-3a, in each isolate was correlated with the immunosupressive potency of the isolate. The sialic acid content of the various alpha-fetoprotein isolates did not vary significantly. Our data suggest that a postsynthetic modification of alphafetoprotein occurs, probably after secretion, which reduces immunosuppressive potency by converting the active electronegative species to an inactive electropositive form. This modification probably involves a charged moiety other than sialic acid on the molecule.

Carcinoma, Hepatocellular↗

Inhibition of human lymphocyte transformation by human alpha-fetoprotein (HAFP); HAFP monomers and multimers and a resistant lymphocyte subpopulation.

We have previously shown that human alpha-fetoprotein (HAFP) inhibits the response in vitro of human lymphocytes to a variety of mitogenic stimuli. In this report we present evidence that HAFP preparations containing dimeric and trimeric forms are no more inhibitory than HAFP monomeric isolates. HAFP isolates of low inhibitory potency cannot impede the capacity of high-potency HAFP to inhibit lymphocyte transformation. Since lymphocyte responses to phytomitogens or anti-human thymocyte antiserum cannot be totally suppressed by increasing doses of HAFP, we conclude that human lymphocyte preparations contain a population of lymphocytes resistant to the inhibitory action of HAFP.

Antilymphocyte Serum↗

Prognostic classification of Hodgkin disease in pathologic stage III, based on anatomic considerations.

Fifty-two patients with pathologic stage III Hodgkin disease were studied in an effort to determine whether location of involved abdominal nodes influenced survival. Treatment consisted of total nodal radiotherapy with or without subsequent combination chemotherapy. Th initial radiation field was the "extended mantle," which included supradiaphragmatic nodes, the splenic hilar area, and paraaortic nodes to the level of L2-L4. Subsequently, lower paraaortic and iliac regions were treated ("lower inverted Y"). Patients with disease limited to the spleen and/or splenic, celiac, or portal nodes ("anatomic substage" III1) had a more favorable 5-yr survival than did patients with involvement of paraaortic, iliac, or mesenteric nodes ("anatomic substage" III2): 93% versus 57%, respectively (p less than 0.05). The addition of combination chemotherapy to total nodal irradiation was associated with improved survival of patients in stage III2, but not of those in stage III1.

Hodgkin Disease↗

Disseminated intravascular coagulation in pregnancy.

The DIC syndrome is the most common cause of an abnormal hemorrhage tendency during pregnancy and the puerperium and reflects systemic activation of the coagulation cascade by circulating thromboplastic material, with secondary activation of the fibrinolytic system. Its presence in a pregnant patient almost invariably is evidence of an underlying obstetric disorder such as abruptio placentae, eclampsia, retention of a dead fetus, amniotic fluid embolism, placental retention or bacterial sepsis. Diagnosis of the DIC syndrome rests on the demonstration of reduced levels of fibrinogen and platelets, prolongation of the thrombin, prothrombin and partial thromboplastin times, and the presence of fibrin/fibrinogen degradation products (FDP) in the serum. Therapy consists of prompt removal of the source of procoagulant material, replacement of depleted clotting factors and, in some cases, anti-coagulation with heparin.

Blood Coagulation Tests↗

Human alpha-fetoprotein as a modulator of human lymphocyte transformation: correlation of biological potency with electrophoretic variants.

Human alpha-fetoprotein (HAFP) isolated by immunoadsorbent column was shown to suppress the mitogenic response of human lymphocytes to phytomitogens, antihuman thymocyte antiserum, and the mixed lymphocyte culture. HAFP isolated from the sera and ascitic fluid of five hepatoma patients, and from fetal liver, varied in biological potency over three orders of magnitude. Extended agarose gel electrophoresis and crossed immunoelectrophoresis demonstrated three molecular species of HAFP. Quantitation of the three species revealed a correlation between the relative amount of the most negatively charged species and biological potency. Treatment of HAFP with neuraminidase to remove completely sialic acid residues did not alter the biological potency, but converted the three species to two species having slower electrophoretic mobilities. We conclude that differences in sialic acid content are only partly responsible for the microheterogeneity demonstrated by HAFP, and that variability in another charged moiety is also present. Variation in the relative proportions of the different molecular species of HAFP may be important in the regulation of its immunosuppressive properties.

Carcinoma, Hepatocellular↗

Language behaviour and child psychotherapy.

The dichotomy between non-verbal or play therapy for the younger and verbal psychotherapy for the older child is questionable in view of the fact that lexical representation begins in the second year of life. It is equally doubtful whether, in the absence of certain communications expressed in verbal symbols, any type of interaction between therapist and child may be called psychotherapy. Language, in varying forms of syntactical and semantic complexity, constitutes the matrix which connects and makes coherent all interactive processes in psychotherapy. This paper attempts to relate some notions of language development to current concepts of child psychotherapy. Linguistic growth is characterized by a fixed gross developmental schedule as well as a specific and universal sequence of acquisition. For the preschooler, still lacking a flexible grammer and syntax to express intricate relationships of perceived events, the value of "interpretations" is doubted; simple statements concerning expression of affect are seen as a rudimentary psychotherapeutic intervention. For the latency child the play situation, with its familiar concrete activity, fuels the child's linguistic competence. Not the play itself but the resulting language becomes the major element of psychotherapy. In late childhood distancing devices and role playing may correct the sociolinguistic asymmetry (adult-child) which inhibits verbal behaviour.

Adolescent↗