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Biomedical subjects

E P Lester

Publications and source records attributed to E P Lester.

At least 37 records · Page 2Linked to original sources

Psychopathology in the offspring of parents with bipolar affective disorders.

Thirty-nine children from intact families with a manic-depressive parent were evaluated by a semi-structured clinical interview and a number of rating scales for the presence or absence of psychopathology. This sample represents a larger one than in an earlier study, which showed minimal offspring psychopathology compared with reports of other investigators. The current study also examines the inter-relationships between the presence or absence of offspring psychopathology with both genetic loading and a number of psychosocial variables including measures of parental marital adjustment, severity and chronicity of proband parent illness and early exposure of children to parental illness. Nine of the thirty-nine children, (23%) received a positive DSM-III diagnosis, with depression of the dysthymic type being the most common. There was no significant correlation between genetic loading and offspring psychopathology. However, there were significant associations between children with psychopathology and paternal marital dissatisfaction and the age and chronicity of illness of the proband parent as compared with the children with no psychopathology.

Adolescent↗

The female analyst and the erotized transference.

The concept of erotized transference is discussed from Freud's original writings on the subject to those of recent contributors. It is noted that there exists an almost complete absence of reports in the literature of male patients developing an erotized transference to their female analysts. The question of how significant the gender of the analyst is in the unfolding of the transference and its vicissitudes is raised. It is maintained that the four possible analyst/analysand dyads differ qualitatively in that resistance and identification in the transference may be enhanced or inhibited by the gender of the analyst and/or the homosexual or heterosexual nature of the dyad. The erotized transference to the female analyst is focused upon as a vehicle to the study of such qualitative differences. It is hypothesized that the expression of strong erotic urges to the female analyst by the male patient is somewhat inhibited by the fantasy of the overwhelming pre-oedipal mother. In contrast, such erotic feelings are freely expressed by the female patient. Two cases, a male and a female, are described to support the above hypothesis.

Adult↗

Separation-individuation and cognition.

Through direct observation of infants and mothers in an "experimental" nursery, Mahler and her associates have accumulated data which when analyzed point to distinct phases (stages) during the long process of the development of the concepts of self and object. These phases, autism, symbiosis, and separation-individuation (itself subdivided into four subphases, differentiation, practicing, rapprochement, and consolidation of individuation) correspond well with the stages described by Piaget as constituting the period of cognitive growth described as sensorimotor intelligence. The intercorrelation of the phasic development along these two separate lines (objectal-affective and cognitive), expectable as it may be, is of considerable interest as it underlines the intrinsic strength of the psychoanalytic concept of the object. Furthermore, this intercorrelation enhances and enlarges our understanding of the process of consolidation of self and object during the first years of life.

Autistic Disorder↗

Effect of interferons on protein synthesis in human lymphocytes: enhanced synthesis of eight specific peptides in T cells and activation-dependent inhibition of overall protein synthesis.

Lymphoblastoid and fibroblast IFN inhibited PHA stimulation of overall protein synthesis in human lymphocytes by ca. 30%. Inhibition occurred within the first 6 hr of PHA treatment and was not progressive. DNA synthesis at 48 hr was inhibited to the same extent. Overall protein synthesis in resting lymphocytes was not detectably inhibited by IFN concentrations up to 1000 U/ml. Thus, inhibition of protein synthesis and subsequent reduction of cell proliferation by IFN require certain early events in mitogen activation. Resting lymphocytes were not unresponsive to IFN treatment, however. Two-dimensional electrophoretic analysis of newly synthesized proteins after IFN treatment showed enhanced synthesis of a specific set of eight peptides (I-peptides), which were shown to be synthesized in T lymphocytes. This enhancement was produced by both IFN-alpha and IFN-beta after 4 to 6 hr of exposure and was identical for all lymphocyte donors studied. After growth stimulation, IFN treatment produced no enhancements of additional peptides, although the original eight I-peptides were enhanced as usual. It is concluded that the biochemical activities of the I-peptides, which remain to be determined, cannot inhibit protein synthesis in resting lymphocytes, but may do so after mitogen activation, when the major physiologic restriction of lymphocyte protein synthesis is released. Alternatively, the I-peptides may be unrelated to regulation of protein synthesis but may be involved in viral protection or enhancement of NK activity.

Blood Proteins↗

A two-dimensional gel analysis of autologous T and B lymphoblastoid cell lines.

We sought polypeptide markers of pathways of lymphoid differentiation by comparing the protein-synthesis patterns of a pair of autologous human lymphoblastoid cell lines: the B-cell line CCRF-SB and the T-cell line CCRF-HSB-2. Cells were cultured in standard medium for 24 or 120 h, then biosynthetically radiolabeled with [3H]leucine. Whole cell lysates were subjected to two-dimensional gel electrophoresis and patterns of protein synthesis were made visible by fluorography. Replicate cultures showed highly reproducible patterns, but differing culture durations produced alterations in the relative synthetic rates of some proteins. Protein synthetic patterns were analyzed visually and with the GELLAB system for computer analysis of two-dimensional gel images. Qualitative and quantitative differences were found between the T- and B-cell patterns. GELLAB detected and accurately paired most of the well-defined spots in each image and constructed a unified data base from data on our initial gels. Statistical analysis of this data revealed several marker proteins, the relative synthetic rates serving to distinguish the T-cell line from the B-cell line. Such computerized analysis of protein synthetic patterns of malignant cells appears likely ultimately to provide important diagnostic information regarding human malignancies.

B-Lymphocytes↗

Some extensions to the GELLAB two-dimensional electrophoretic gel analysis system.

Several important extensions to the GELLAB 2D electrophoresis gel analysis system are discussed, including concepts that lead to the generation of consistent gel maps for a particular cell line, as illustrated by some recent results for the P388D1 cell system, GELLAB is an interactive graphics computer system that facilitates (a) image accessioning, (b) spot-data extraction from the image with position and density quantitation, (c) pairing of corresponding spots between gels, and (d) spot analysis for a large number of corresponding spots (over 3000 per gel) for up to 128 gels. Multiple gels are accessioned into the system used to create a composite gel data base. These then may be partitioned into multiple classes of gels and searched for statistically significant interclass spot differences, which can be visualized in reference map images of selected spot sets as well as mosaic images of particular spots in all gels. In addition to the visual feedback that is available during the gel analysis, various statistical, numerical, and other displays may be generated in the CGELP interactive program of the GELLAB system.

Animals↗

Polyamines as physiological substrates for transglutaminases.

When normal human blood lymphocytes are treated with mitogen in the presence of [3H]putrescine, label is incorporated into a few cellular proteins. Labeled N-(gamma-glutamyl) putrescine, N1-(gamma-glutamyl)spermidine, and N8-(gamma-glutamyl)spermidine were identified in exhaustive proteolytic digests of the cellular protein fraction. The enzyme-mediated clotting of rat seminal plasma to which 14C-labeled spermidine and spermine are added is accompanied by incorporation of the polyamines into a number of seminal plasma proteins. Proteolytic digests of the protein fraction from this clotted seminal plasma contain labeled N1-(gamma-glutamyl)spermidine, N8-(gamma-glutamyl)spermidine, N1,N8-bis(gamma-glutamyl)spermidine, N1-(gamma-glutamyl)spermine, and N1,N12-bis(gamma-glutamyl)spermine. These findings support a proposal that polyamines serve as substrates for transglutaminases both in cells and in an extracellular fluid. They show differences in cellular and extracellular substrate properties of the polyamines and indicate cross-linking through these amines in the extracellular system, but provide no evidence for such cross-linking in the cells.

Humans↗

Cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (COMLA) combination sequential chemotherapy for advanced diffuse histiocytic lymphoma.

A program of combination sequential chemotherapy using cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (COMLA) was administered to 42 previously untreated patients with advanced diffuse histiocytic lymphoma. Twenty-three patients achieved a complete remission as determined by strict clinical restaging criteria. The observed median duration of survival for the complete responders is longer than 33 months. Eight patients achieved a partial response, with a median survival longer than 21 months. Eleven patients showed no response, with a median survival of 5 months. Toxicity was acceptable. None of the responders have shown central nervous system relapse. There was no difference in response rates between patients with stage III or IV lymphoma or between asymptomatic or symptomatic patients. The COMLA program produces a high rate of complete and durable remissions and should be considered as an initial form of management of patients with advanced diffuse histiocytic lymphoma.

Adolescent↗

Computer-assisted analysis of two-dimensional electrophoreses of human lymphoid cells.

Two-dimensional electrophoresis in polyacrylamide gel provides a highly reproducible display of biosynthetically pulse-labeled cellular polypeptides, whose relative rates of synthesis can be judged from the relative spot densities they produce in fluorographic images of the electrophoreses. When experimental and control cell populations synthesize protein at differing rates, either the sample load per gel or the duration of exposure of gel to film may be adjusted to produce comparable experimental and control images with no alteration in the rank order of relative spot density. However, variation in the duration of pulse-labeling may significantly alter relative spot density. Film density saturation and nonlinear response to radiation may also alter relative spot density for polypeptides with very large or very small amounts of radioactivity. Stimulation of human peripheral blood lymphocytes with phytohemagglutinin alters the relative synthesis rates of certain polypeptides visualized on the gels. These can be quantitated by using an automated series of computer algorithms to analyze the images. Data from this analysis confirm statistically significant alterations in the relative densities produced by certain polypeptides. Various human lymphoblastoid cell lines may also be distinguished from each other by this technique.

Cells, Cultured↗

Imagery and transference in the analytic process.

The structural and formal aspects of free association have not received adequate attention in the psychoanalytic literature partly because of the methodological problems involved in their objective study. Visual imagery aroused considerable interest during Freud's concentration technique but, following this, interest in imagery has declined and has remained low despite the "primacy" retained by the dreams in the analytic practice and theory. Visual imagery, an integral part of conscious thought, is enhanced during free association by the regression, the altered states of consciousness, the suspension of censorship and the shift in figure ground relationships of ordinary awareness of the analytic setting as the analysis progresses and, despite the deepening of regression, the development of transference and the establishment of the analyst as the focal figure of the patient's experience produce a shift from the visual to the verbal and a decrease in the sensory elements of free association. The predominantly verbal nature of the analytic exchange once transference is established is underscored by the analyst's interpretations which, by their emphasis on ordered verbal thought, reinforce the dialectical elements of analysis. The above shift from the visual to the verbal during free association was well illustrated in a case where the development of transference signalled the decrease of the abundant visual element present at the beginning in the material of the patient. Interestingly, the patient's dreams became equally more verbal as the analysis progressed, a phenomenon which was also observed by Anzieu in Freud's dreams in his study of the latter's self-analysis. The possible mechanism for this shift and its significance are discussed.

Adult↗

Necrotizing myelopathy complicating Hodgkin's disease.

A case of necrotizing myelopathy is presented as a complication of Hodgkin's disease. The distinctive pathologic feature of this case was severe acute vasculitis involving only the vessels of the spinal cord that was considered to have been the cause of the segmental necrosis.

Aged↗

Pathologic stage I and II Hodgkin's disease, 1968--1975: relapse and results of retreatment.

Sixty-seven previously untreated patients with Hodgkin's disease, pathologic stages I and II, seen during a 7-year period were evaluted with respect to initial staging and treatment, as well as relapse and retreatment results. The initial treatment consisted of radiation therapy (RT) to an involved field (IF) or an extended field (EF) for patients with stages IA and IIA, or RT and, in recent cases, combination chemotherapy [cyclophosphamide, Oncovin, procarbazine, and prednisone (COPP)] for patients with stages IB and IIB. Nineteen of the 67 patients relapsed (28%), including 11 of 56 patients with stages IA and IIA (20%) and 8 of 11 patients with stages IB and IIB (73%). Seventeen of the 19 relapses occurred within 24 months after completion of the initial therapy (89%). The relapse-free survival at 5 years was 75% for the A patients and 25% for the B patients. The actuarial survival of stage IA and stage IIA patients at 5 years was 91%; there was no significant difference between patients treated initially with either IF or EF. The actuarial survival at 5 years for the patients with stages IB and IIB was 88%, as most responded to a second program of induction therapy. No correlation could be found between the pattern of relapse and the initial pathologic stage or the mode of treatment.

Adolescent↗