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Biomedical subjects

T M Phillips

Publications and source records attributed to T M Phillips.

At least 109 records · Page 6Linked to original sources

Regression of canine mammary carcinoma after immunoadsorption therapy.

The plasma of dogs afflicted with mammary carcinoma was perfused through chambers bearing Staphylococcus aureus Cowan strain I in an attempt to remove tumor-promoting, immunosuppressive immune complexes from the peripheral blood of these animals. In this canine model of spontaneous mammary carcinoma, reduction of breast and/or soft-tissue tumor (posttreatment size equal to 0 to 50% of pretreatment tumor size) was observed in five of the ten animals so treated. Immune complexes capable of blocking lymphocytotoxicity were measured pre- and postimmunoadsorption; removal was more efficient in the five responders (four of six complexes) than in nonresponders (one of ten complexes), although statistical significance was not attained. The reduction of tumor size seen in soft-tissue sites was not always accompanied by a similar reduction of tumor size in visceral sites, and surgical resection of residual soft-tissue tumor nodules remaining after immunoadsorption treatment was required to achieve a complete response in two responding animals. No significant decrease in tumor size was observed in the control group, perfused without immunoadsorbent, nor in five additional tumor-bearing animals infused with normal dog plasma which had been passed through S. aureus Cowan strain I-containing chambers. These data indicate that immunoadsorption of tumor-bearing host plasma can result in reduction in size of canine mammary adenocarcinoma but that the response is dependent on the site of the tumor (s.c. versus visceral) and may require utilization of other modalities to achieve a complete disappearance of the tumor.

Adenocarcinoma↗

A defect in the formation of uropod-bearing lymphocytes (hand-mirror cells) in patients with the Wiskott-Aldrich syndrome.

The formation of a uropod by lymphocytes (hand-mirror cells) represents a morphologic stage of immune activation and motility in lymphocytes. Immune complexes have been previously shown to induce hand-mirror-cell (HMC) formation in human lymphocytes and have been associated with increased number of HMC in acute leukemia. We studied the ability of immune complexes to induce HMC in patients with Wiskott-Aldrich syndrome (WAS), a disease of cellular immune deficiency. Our findings indicate that lymphocytes from patients with WAS adhere to immune complexes but have a defect in their ability to form HMC when compared with normal human lymphocytes. These results support the concept that immune complexes induce HMC formation and that the HMC is related to the normal cellular immune response.

Antibodies, Viral↗

Acute lymphoblastic leukemia--hand mirror variant--viral immune interrelationship as demonstrated by ultrastructural studies.

Acute lymphoblastic leukemia--hand mirror variant--was extensively restudied in a 22-year-old white female who survived for 22 months without therapy. Immune complexes to the baboon endogenous virus (BaEV) were found in the bone marrow plasma of the relapse specimen in 1977, but not in the bone marrow plasma from the terminal state in 1979. Immunoperoxidase-tagged IgM antibody prepared from the patient's bone marrow plasma revealed BaEV antigen on the tip of the uropod of the HMC at the time immune complexes were found in the marrow. Absence of immune complexes in the marrow. Absence of immune complexes in the bone marrow in the terminal state suggested a failure of the patient's immune surveillance system and/or possible immune suppression by chemotherapy.

Adult↗

Immune complexes in transitional cell carcinoma.

Bladder cancer patients from 2 different medical centers were examined to establish whether such patients have circulating immune complexes. Four methods of analysis were used: 1) polyethylene glycol precipitation, 2) double crossed immunoelectrophoresis, 3) Raji cell and 4) Clq binding assays. In the first group of 24 patients 17 had positive results on cystoscopy for pathologically defined tumors at the time of the serum sample. Two tested positive for the presence of circulating immune complexes by all 4 techniques and an additional 1 tested positive by 3 of the 4 techniques. In the second group of 54 patients (41 of whom had pathologically definable tumors at sample date) 9 were judged possibly positive by the Raji cell assay, the polyethylene glycol and double crossed immunoelectrophoresis techniques. When tested by the Clq binding assay 8 of the 9 patients were positive, most being in the range of 260 to 320 microgram/ml. immune complex. Combining all data from the 78 patients with bladder cancer the results in 10 cases definitely were positive by all 4 techniques and an additional 2 were positive by 3 techniques. Our data indicate that a low percentage (13 to 15 per cent) of patients with bladder cancer has circulating immune complexes. Of interest is that the complexes, as judged by our assay procedures, bind Clq, contain aggregated IgG and can be dissociated into antigen and antibody. Thus, the immune complexes are similar to those found in immune complex diseases.

Aged↗

Antigen--antibody complexes related to the baboon endogenous virus in humans with acute lymphoblastic leukemia--hand mirror variant (ALL-HMC).

Hand mirror cells are a morphological configuration that are seen in immunologically stimulated lymphocytes and can be induced by antigen--antibody complexes. Therefore, the bone marrow and peripheral blood plasma of two patients with acute lymphoblastic leukemia--hand mirror variant were evaluated for the presence of antigen--antibody complexes. Both patients had antigen--antibody complexes in the bone marrow plasma and not in the peripheral blood plasma as determined by double counter-current immunoelectrophoresis. The antigen moiety of these complexes appears immunologically related to components of the baboon endogenous virus (BaEV), and the antibody moiety also appears related to structural components of the BaEV. Bone marrow plasmas from patients without leukemia were evaluated for the presence of antigen--antibody complexes and found to be negative. The antigen--antibody complexes may account for the presence of hand mirror cells in the bone marrow of patients with acute lymphoblastic leukemia--hand mirror variant.

Acute Disease↗

Unilateral megalencephaly, cerebral cortical dysplasia, neuronal hypertrophy, and heterotopia: cytomorphometric, fluorometric cytochemical, and biochemical analyses.

A 13-month-old boy with intractable seizures, left hemiparesis, and psychomotor retardation due to right unilateral megalencephaly, died in hypovolemic shock 1 day after hemispherectomy. The gyral pattern of the hypermegalic hemisphere was simplified and coarse. The cortical cytoarchitecture was disarrayed by a population of giant neurons. Hippocampus and calcarine cortex were cytoarchitectonically normal, as was the entire left cerebral hemisphere. Neuronal heterotopias were present in the right centrum semiovale and both cerebellar hemispheres. Cytomorphometric study of parietal cortex of each cerebral hemisphere revealed a 4-fold increase in neuronal nuclear, and 11-fold increase in neuronal nucleolar, volume in the hypermegalic hemisphere, whereas glial nuclear volume was only one-third as great, in part because of edema of the left hemisphere. Microfluorometric cytochemical analysis demonstrated a 16% increase in neuronal DNA, 40% increase in total neuronal RNA, 12% increase in glial DNA, and 15% increase in glial RNA on the right. Biochemical analysis of tissue extracts disclosed increases in the right hemisphere of 40%, 56%, and 66%, respectively, for DNA, RNA, and protein. The data suggest heteroploidy of chromosomal DNA and enhanced transcription and translation in the hypermegalic hemisphere. Thus, a defect in regulation of cell metabolism may account for the morphologic and clinical abnormalities.

Brain↗

Herpes simplex type 2 encephalitis concurrent with known cerebral metastases.

A 62-year-old woman developed neurologic deficits 7 months after pulmonary lobectomy for alveolar cell carcinoma of the lung. CT scan of the head demonstrated two metastases with marked peritumoral edema. Administration of Decadron, chemotherapy and 3,000 rad cranial radiation resulted in dramatic improvement of dysphasia and right hand paresis. Almost 2 months later, rhythmic, involuntary movements of the left hand developed. There was progression to multifocal seizures, grand mal seizures, postictal depression, status epilepticus, and coma, with death 9 days after onset of the movement disorder. Bronchoalveolar carcinoma was widely disseminated in lungs and bones, and as three metastases in brain. Bland "ischemic" necrosis in a pseudolaminar pattern was present in the neocortex. Innumerable Cowdry type A intranuclear inclusion bodies were seen in neurons, astrocytes, and oligodenodroglia. Immunofluorescence demonstrated Herpes simplex virus type 2 antigen and electron microscopy revealed virions with the morphology of the Herpes group. The case is significant for (1) the concurrence of intracranial metastases and Herpes simplex encephalitis, and (2) the causal agent, Herpes simplex virus type 2. The implication for the clinical neurocientist is the potential in a patient with systemic cancer, for the causation of neurologic complications by more than one factor or mechanism.

Adenocarcinoma, Bronchiolo-Alveolar↗

Ia antigens on indeterminate cells of the epidermis: immunoelectronmicroscopic studies of surface antigens.

An antiserum against human B-lymphoblastoid cell membrane alloantigens (Ia-like antigens) was used to study the presence of such antigens on dendritic cells in human epidermis. Only Langerhans cells and the majority (85%) of so-called indeterminate cells were positively stained, as shown by immuno-electron microscopy. Fifteen percent of the indeterminate cells were negative and were considered to be immature melanocytes. A relationship exists between the indeterminate cell and the Langerhans cell. A proposal is made concerning emigration of Langerhans cells in response to haptenic stimulation, and the immigration of indeterminate cells to restore the status quo.

Antigens, Surface↗

Immune derangement in patients with malignant melanoma.

The interaction between immune system and growing tumor can be expressed differently at different stages of the disease. This presentation covers three facets of these reactions in melanoma patients. A. The Primary Tumor. Time-lapse cinematography, with an analysis of lymphocyte movement demonstrated positive and negative chemotaxis against tumor tissues which correlated with their histological presence or absence within the primary tumor. B. The Regional Lymph Nodes. Histological examination of regional lymph nodes showed an increase in germinal center activity and B cell number, with a decrease in sinus histiocytosis and monocyte count as the tumor progressively invaded the node. This correlated with the elution studies, wherein the antimembrane antibody decreased and the anti-cytoplasmic antibody increased during the same period of progression. C. Humoral Immunity and Metastasis. Clinical metastasis heralded the decrease of anti-membrane antibodies with a rise in anti-immunoglobulins, especially anti-idiotypic antibodies and immune complexes containing tumor-directed antibody and either antigen or anti-immunoglobulin. This triad of anti-immunoglobulin, immune complexes and anergy as seen in other diseases with persistent antigenic stimulation, results in abnormal regulation and derangement.

Antibodies, Neoplasm↗

Target role of Langerhans cells in mycosis fungoides: transmission and immuno-electron microscopic studies.

Langerhans cells of the epidermis are "special" macrophages, as indicated by their expression of Fc and C3 receptors and Ia antigen. Functionally, they can replace macrophages in presentation of antigens to T cells and in the MLR. Ultrastructural and immunologic studies were carried out on epidermal samples of mycosis fungoides. As in contact allergy, apposition of lymphocytes to Langerhans cells was noted. Destruction of Langerhans cells appeared to act as the focus for the development of Pautrier microabscesses. This destruction was accompanied by ingress of histocytic cells, probably related to the stem cell population for Langerhans cells. The target cell role of Langerhans cells appears to be similar in contact allergy and mycosis fungoides.

Antigens↗

Immune reactions in patients with bladder and prostatic cancer.

Although there are many reports of cellular immune reactions in bladder and prostatic carcinoma patients, few have demonstrated the presence of humoral reactivity. The use of microtechniques, especially the enzyme-linked immunosorbent assay (ELISA), has made sequential studies possible on patients with early or small tumours. Using this assay, the presence of serum antibodies has been demonstrated in both bladder and prostate patients, the specificities of these reactions being checked against a battery of different tumours and normal tissues. In many of the patients, with low or transient antibody levels, the presence of circulating immune complexes was shown by the Raji cell assay and analysed by double counter-current immunoelectrophoresis (DCIE). The content of these complexes appeared to be either antibody and tumour antigen or antibody and antiimmunoglobulin. In a small series of cryosurgically treated prostatic carcinoma patients, the course of these antibodies was monitored over several weeks, and the fluctuations in antibody levels were related to the presence of these different types of complexes.

Antibodies, Neoplasm↗

Specificity of tumor-associated antibodies in sera of patients with uveal melanoma.

We have identified antibodies against cytoplasmic components of allogeneic uveal melanoma cells in the sera of 16 of 31 patients with proven intraocular melanoma. Similar antibodies were found in 27% of controls and in 24% of patients with uveal nevi. The antibodies in these 3 groups of subjects were absorbed by components of uveal and cutaneous melanoma cells but not by those of normal choroidal melanocytes, normal uvea and retinal pigment epithelium, dermal nevus, pigmented skin or fetal cells. We found that specificity of the antibodies was also demonstrated by absence of reactivity with normal choroidal melanocytes, loss of reactivity after immune blocking, and absence of reactivity of melanoma antigen with conjugated antihuman immunoglobulin alone. Attempted absorption of the conjugated antihuman immunoglobulin by components of uveal melanoma cells did not alter the reactivity of the conjugated antihuman immunoglobulin.

Antibodies↗

[The influence of humoral immune mechanisms on metastasizing tumors in humans (author's transl)].

Long-continued stimulation of the immune system by chronic infections or tumors leads to dysfunction of the immunoregulation. Different types of antibody, anti-antibody and immunocomplex point to the fact that it is not a matter of the weakening of the patient's immune defense but that these antibodies are important regulating mechanisms for the immune system. While antibodies directed against a tumor have a useful function for the patient with dissemination of metastasizing tumors, the anti-antibodies and antigenotypic antibodies represent a counterregulation which, in the advanced stage of the disease, eliminates the initial control.

Antibodies, Anti-Idiotypic↗