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Biomedical subjects

M A Silverman

Publications and source records attributed to M A Silverman.

48 records · Page 3Linked to original sources

Maximizing differences in the concanavalin A-induced blastogenic responses of lymphocytes from breast cancer patients and controls by the use of alpha-methyl-D-mannoside.

In an attempt to magnify differences in the immune responses of potentially immunosuppressed cancer patients and normal controls, an assessment was made on the effects of the competitive inhibitor alpha-methyl-D-mannoside on the concanavalin A (Con A)-induced blastogenic responses of lymphocytes from each of these populations. Lymphocytes from breast cancer patients with metastatic disease were significantly deficient in their capability to undergo blast transformation regardless of whether the monosaccharide inhibitor was added to the assay cultures. In contrast, lymphocytes from breast cancer patients who did not display metastatic disease were capable of normal blastogenic responses to Con A. The addition of alpha-methyl-D-mannoside to lymphocyte cultures caused a significantly greater inhibition of the blastogenic responses of these patients' cells as compared to cells of normal controls. Thus the monosaccharide seems to serve as a useful reagent for optimizing differences between lymphocyte blastogenic responses of normal donors and those of immunodepressed donors. The results suggest that lymphocytes from breast cancer patients without clinically evident metastases possess some modification of their cell membrane. One possibility discussed was that the number or distribution of receptors for Con A on the membrane of lymphocytes of these patients is deficient.

Binding, Competitive↗

The voice of conscience and the sounds of the analytic hour.

Two patients reacted to sudden, unexpected, adventitious sounds during an analytic session as though they had been warmed that they would be punished for their misdeeds. One promptly confessed to wrongdoings which she had been denying or keeping secret. It was as though a "voice of conscience" had spoken to them to remind them of their obligations, demand compliance with the rules, and threaten them with dire punishments should they fail to obey. The sounds seemed to be experienced as a re-externalized admonishing parental voice that had been incompletely internalized in the course of superego development. Conflicts involving guilt over objectionable fantasies and acts, in part connected with primal scene experiences, appeared to be involved.

Adult↗

Cognitive development and female psychology.

Freud was an astute observer, but his understanding of female psychology was distorted by centration on biological forces, the adult neurosis, libido theory, the Oedipus complex, and male psychology. His views on the role of penis envy, narcissism, and masochism in women, and on the female superego, currently are being updated on the basis of new data emerging out of psychoanalytic investigation and direct observational studies. It has become clear, for example, that core feminine gender identity develops very early and that it is mediated in large part by cognitive development and learning rather than by the impact of the observation of genital differences between the sexes. The little girl's level of cognitive organization does not permit her at first to construct logical, consistent categories of female and male, predicated or coordination of criteria of inclusion and exclusion. She puts girls and women into one group out of intuitive recognition that they "go together" and builds up a view of herself as female on the basis of what she feels as her mother's daughter and what she perceives of the way her parents and other significant object see her. Her mother's feelings about her, about herself, and about females in general influence her greatly, and her father's responses to and expectations of her have an important impact on her self-image and self-esteem. Her representation of herself as female at first does not necessarily take genital differences between the sexes into account. The discovery, some time in the second or third year, that the genitals of boys and girls are different from one another presents the girl with a number of problems, however. Her cognitive organization makes it extremely difficult for her to apprehend her complex, incompletely demarcated, and to a large extent internal, unobservable, and impalpable sexual organs. Her initial conclusion is that she lacks desirable body parts which are possessed by other beings. Because of the narcissistic-exhibitionistic libidinal organization of that period of life, this represents a painful narcissistic injury. The intensity of the girl's castration reaction and the degree to which she will be able to overcome it in the course of further development are determined by multiple internal and external developmental factors. Masochism, narcissistic vulnerability, and penis envy are neither limited to the female sex nor normal outcomes of female development. Where they are prominent features in the psychopathology of female patients, it is insufficient to interpret them as emanating from penis envy as a bedrock, primal cause. Detailed clinical examples are presented to illustrate the thesis that through exploration and explication of the multiple sources of such symptomatology in a female analysand is the most effective way of relieving the symptomatology and releasing the potential for emotional growth.

Adolescent↗

Lymphoproliferative responses to mouse mammary tumor virus in lymphocyte subsets of breast cancer patients.

Altered immunologic reactions were observed in breast cancer patients as compared to those in normal subjects. Lymphoproliferative responses to murine mammary tumor virus (MuMTV) were significantly enhanced in peripheral blood mononuclear cells from patients with metastatic disease. These reactivities occurred with mammary tumor virus purified from either mouse milk or infected feline kidney cells but not with Rauscher murine leukemia virus. For the assessment of the role of peripheral blood mononuclear leukocyte subpopulations in the responsiveness to MuMTV, the cell preparations were fractionated according to their ability to form spontaneous rosettes with sheep red blood cells (E-rosettes). The effectiveness of the separation was ascertained by means of cell surface markers, i.e., presence of surface immunoglobulins or a T-cell marker. Leu-1 antigen, and mitogen-induced blastogenesis. The responsiveness to the MuMTV antigen(s) was associated with the T-cell subset, identified as the E-rosetting. Leu-1-positive, and surface immunoglobulin-negative population. Although some subjects with the normal population gave positive reactions, the results reveal an apparent association between high levels of responsiveness to MuMTV within the T-lymphocyte subset and breast cancer disease.

Antigens, Viral↗

Mechanisms of levamisole-induced granulocytopenia in breast cancer patients.

Five of 39 (13%) women treated with adjuvant combination chemotherapy plus levamisole immunotherapy after mastectomy for Stage II or III breast cancer developed levamisole-induced granulocytopenia. This complication occurred in each of the women between six and ten weeks after the completion of six months of combination chemoimmunotherapy when they were taking levamisole alone. Although none of the patients had an HLA B-27 locus and leukoagglutinins could not be demonstrated, complement-dependent, IgM mediated, peripheral destruction of granulocytes was documented using a microgranulocytotoxicity assay. In addition, a factor(s) present in serum from patients developing levamisole-induced granulocytopenia caused suppression of bone marrow granulocyte progenitor cells (CFU-C). The possible relationships between levamisole-induced peripheral granulocyte destruction and bone marrow CFU-C suppression are discussed.

Acute Disease↗

Studies on levamisole--induced agranulocytosis.

Widespread clinical trials of leavo-tetramisole (levamisole) as an immunopotentiating agent in rheumatoid arthritis, metastatic carcinoma, and immunodeficiency states have been complicated by agranulocytosis (AGC) in 2.5%-13% of patients. Other than a relationship with prolonged high dosage, very little is known regarding the pathogenesis of levamisole-induced AGC. Whereas leukoagglutination was negative, fluorochromatic microgranulocytotoxicity (GCY) tests were positive with serum from 10 of 10 acutely neutropenic patients. The antibody was IgM, reacted with 100% of unrelated granulocytes, but not with T or B lymphocytes. Some sera also reacted with monocytes and the myeloid cell line, K-562. Tests for antigen-antibody complexes or cold autoantibodies were negative. Although clinical evidence strongly suggests a haptene (drug) mechanism, in vitro mixing experiments were also negative. An alternative choice parallels the model of aldomet-induced Coombs'-positive hemolytic anemia. Finally, GCY first became positive 2-3 mo prior to the onset of AGC on two patients, suggesting the possibility of identifying those at risk well before the onset of neutropenia.

Agranulocytosis↗

Phase I clinical trial of weekly iv 2,3-dihydro-1H-imidazo[1,2-b]pyrazole (IMPY).

In a phase I trial, 2,3-dihydro-1H-imidazo[1,2-b]pyrazole was administered iv weekly at doses ranging from 0.1 to 3.0 g/m2/wk to patients with refractory metastatic solid tumors. Although gastrointestinal toxicity was tolerable and neither granulocyte nor platelet toxicity was seen, significant dose-limiting hemolysis was encountered at doses of 1.5 g/m2/wk. While no definite tumor regressions were seen in the 32 patients evaluable for response, two patients (squamous cell carcinoma of lung and tonsil) had clinically useful improvement.

Antineoplastic Agents↗