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Biomedical subjects

T M Phillips

Publications and source records attributed to T M Phillips.

At least 91 records · Page 5Linked to original sources
PubMed1986

Circulating immune complexes in malignant melanoma: serial studies in 130 patients.

We evaluated the ability of repeated measurements of circulating immune complexes (CIC) to predict for tumor recurrence in 130 patients with malignant melanoma. Twenty-two patients had level 2, 45 had level 3, and 51 had level 4/5, stage I disease in remission at the start of monitoring, while 12 had stage II disease. The polyethylene glycol precipitation assay was used for serial studies, based on an initial comparative evaluation with the Clq-binding and Raji assays. The study averaged 22 +/- 11 months (6-43 months) and an average of 22 +/- 5.3 assays were performed per patient (range 3-36), with a follow-up of 4 years. CIC were present in sera in recurrent, irregular 'bursts' of activity. Serial measurements doubled the incidence of CIC compared to single determinations. Only 23% of these bursts of activity were clearly related temporarily to documented recurrences, while 34% occurred with treatment events such as surgery or immunotherapy, and 42% occurred without correlation to either recurrence or treatment. CIC activity was greater and more closely related to recurrence in high-risk stage I (level 4,5) and stage II patients. Whether analyzed as positive sera or as bursts of elevated CIC activity, CIC assays predicted for recurrence at the 5% significance level. The assay was highly sensitive (97%), but with poor specificity (21%) with many false positives (79%). The assay was helpful at ruling out recurrences (95%), but poor at ruling them in (29%). The advantage was seen only in high-risk stage I and II patients, and there was no advantage to serial assays over random single determinations. Although generally, CIC in the sera of melanoma patients were found to predict for recurrence, the use of serial CIC measures monitoring of individual patients cannot be recommended.

Antigen-Antibody Complex↗
PubMed1986

Treatment of cancer-associated hemolytic uremic syndrome with staphylococcal protein A immunoperfusion.

Plasma perfusion over filters containing staphylococcal protein A (SPA) was used to treat 11 patients with adenocarcinoma who developed a hemolytic uremic syndrome. Immunoperfusion resulted in complete clearance of pretreatment elevated levels of circulating immune complexes in eight of the 11 patients with normalization of complement values depressed at the start of the therapy in seven. A significant rise in platelets and erythrocyte counts was achieved in nine patients, and stabilization of progressive renal impairment was achieved in six. The response was incomplete and short lived in three patients with clinically evident tumor recurrence, whereas long-term control of the syndrome was demonstrated in seven patients in complete tumor remission (no recurrence with median follow-up of 9 months). SPA immunoperfusion appears to be an effective form of therapy for this otherwise fatal syndrome.

Adenocarcinoma↗
PubMed1985

Isolation and quantitation of serum IgE levels by high-performance immunoaffinity chromatography.

High-performance immunoaffinity chromatography on monoclonal antibodies coupled to protein A-coated glass beads is a method for the rapid isolation and quantitation of immunoglobulin E (IgE) from the serum of both adult and pediatric patients. The technique is as sensitive as most immunoassays but takes less than an hour to perform. In addition to measuring total IgE in both plasma and serum, the technique provides biologically active, affinity-isolated IgE, which can be used for other clinical and research studies.

Animals↗
PubMed1985

Protein A-coated glass beads. Universal support medium for high-performance immunoaffinity chromatography.

High-performance immunoaffinity chromatography (HPIC) is a technique for the fast isolation and quantitation of both antibodies and antigens. Protein A-coated glass beads provide a stable general immobilization support for most immunoglobulin G (IgG) antibodies. In conjunction with the modern expanding repertoire of monoclonal antibodies, HPIC can be applied to the quantitation and isolation of any biological material, in an active form.

Binding Sites, Antibody↗
PubMed1985

Accelerated recovery from immune-mediated thrombocytopenia with plasmapheresis.

Autoimmune thrombocytopenia unresponsive to corticosteroid therapy developed in a 16-year-old female with long-standing Sjögren's syndrome. Serial plasma exchange caused a linear decrease in platelet antibody titer associated with a concomitant rise in platelet count. Statistical analysis of sequential platelet counts revealed an increase with plasmapheresis and immunosuppression that was significantly greater than that achieved with immunosuppression alone (p less than 0.005).

Adolescent↗
PubMed1985

Thymic functions in uremic rats: evidence for thymosin alpha 1 deficiency.

Changes in the circulating lymphocyte populations and thymus glands were studied in rats with experimental chronic renal insufficiency (CRI). Compared to normal or sham-operated animals, rats with CRI had significant reduction in the percentages of circulating T and B lymphocytes. CRI was also associated with marked thymic atrophy and reduction in the numbers of small cortical and medullary thymic lymphocytes. Quantitative microfluorometry revealed a significant reduction in the intrathymic concentration of a potent immunomodulator, thymosin alpha 1 in all uremic animals. There was a significant positive correlation between the percentages of circulating T lymphocytes and the intrathymic concentrations of thymosin alpha 1.

Animals↗
PubMed1985

Anti-myelin basic protein antibody in experimental allergic optic neuritis and encephalomyelitis.

We produced demyelinating optic neuritis and encephalomyelitis in juvenile strain 13 guinea pigs by sensitization with optic nerve myelin. Three distinct clinical courses were noted: a severe, acute optic neuritis associated with a rapidly fatal encephalomyelitis; a mild, chronic optic neuritis with a nonfatal encephalomyelitis; and an initially mild disease followed by an acute exacerbation of optic neuritis and fatal encephalomyelitis. Clinically mild disease was associated with elevated levels of anti-myelin basic protein antibody, while severe disease was associated with extremely low antibody levels.

Animals↗
PubMed1985

Carcinoma-associated hemolytic-uremic syndrome: a complication of mitomycin C chemotherapy.

A thrombotic microangiopathy resembling the hemolytic uremic syndrome was diagnosed in 12 patients with adenocarcinoma, in whom the tumor was in complete or near-complete remission after treatment with mitomycin C-containing drug regimens. Microangiopathic hemolytic anemia, thrombocytopenia, and renal failure were initially present in all cases. All patients eventually developed pulmonary edema and systemic arterial hypertension, and three experienced neurologic complications. Blood transfusions exacerbated the syndrome in nine patients. High titers of platelet-aggregating plasma immune complexes were present in all six cases in which they were measured. The constituent antibody of each complex failed to react with mitomycin C antigen preparations, whereas in vitro reactivity to endodermally derived neoplasms was demonstrated. Plasmapheresis was associated with amelioration of the syndrome in only one patient. In patients receiving mitomycin C chemotherapy, the development of anemia and thrombocytopenia or azotemia may represent the initial manifestations of this newly defined thrombotic microangiopathy. A consistently effective form of management of this syndrome has not as yet been defined.

Acute Kidney Injury↗
PubMed1985

Recombinant leukocyte A interferon in B-cell chronic lymphocytic leukemia: in vivo effects on autologous antitumor immunity.

Eight previously treated and four untreated patients with B cell chronic lymphocytic leukemia (CLL) received 20 X 10(6) U/m2 recombinant leukocyte interferon clone A (rIFN-alpha A) intramuscularly three times a week for 8 weeks. None of the eight patients who had received prior chemotherapy exhibited objective evidence of tumor regression. Two of the four previously untreated patients responded with transient (90%) decreases in absolute lymphocyte counts lasting for 2 and 7 months. Toxicity was moderate, with all patients experiencing a flu-like syndrome requiring a 50% dose reduction. Half of the patients exhibited anorexia, weight loss, and a drop in performance status. The two responders had normal serum immunoglobulin levels prior to treatment, whereas 80% of non-responders had depressed levels. Treatment with rIFN-alpha A was associated with a depression of nonspecific and specific humoral immunity in assays employing cryopreserved autologous pretherapy CLL cells. No consistent effects were demonstrable in cytolytic assays with purified peripheral blood T cells as effector cells, including one that utilized autologous CLL target cells. rIFN-alpha A has limited antitumor activity in B cell CLL which is restricted to untreated patients with an early stage of disease. With the assays employed it was not possible to demonstrate that rIFN-alpha A could augment autologous antitumor immunity.

Aged↗
PubMed1984

High-performance affinity chromatography: a rapid technique for the isolation and quantitation of IgG from cerebral spinal fluid.

Standard techniques for the quantitative measurement of IgG in cerebral spinal fluid take up to 24 hs. This often delays diagnosis and treatment, critical in newborn infants. A high-performance affinity chromatography (HPAC) column, containing immobilized anti-IgG antibody, produced the same or better results in 1 h. The HPAC system gave a 98% correlation with the standard techniques at the normal-abnormal IgG level, but was more accurate at the extremely low IgG level.

Cephalometry↗
PubMed1984

Inverse correlation between age related abnormalities of T-cell immunity and circulating thymosin alpha 1 levels in haemophilia A.

T-cell immunity and serum levels of thymosin alpha 1, beta 2-microglobulin, circulating immune complexes, serum immunoglobulin levels, antibodies to hepatitis surface or core antigen, and to cytomegalovirus, and Epstein-Barr virus were investigated in 51 patients with haemophilia A ranging in age from 2 to 52 years. All patients had received commercial U.S. lyophilized concentrates of antihaemophilic factor (AHF). The mean helper/cytotoxic-suppressor (OKT4/OKT8) ratio of 11 pre-adolescents (1.6 +/- 0.4 SE) was not significantly different from that of age matched normal controls. In contrast, the mean OKT4/OKT8 ratios of 13 adolescent (1.2 +/- 0.2 SE) and 23 adult (0.8 +/- 0.1 SE) haemophiliacs were significantly reduced. Abnormalities of lymphocyte mitogenic responses were found only in adult haemophiliacs. Nine individuals treated with commercial U.S. prothrombin complex concentrates for antibodies directed against AHF or for haemophilia B had normal mean OKT4/OKT8 values. The mean serum thymosin alpha 1 levels for each age category was similar to that of age matched controls; however, regression analysis revealed a significant relationship between elevated thymosin alpha 1 levels and decreased OKT4/OKT8 ratios in adult haemophiliacs (P = 0.012). Although the mean serum level of beta 2-microglobulin was significantly increased in the adult haemophiliac group, there was no correlation between OKT4/OKT8 ratios and any of the other serologic parameters studied.

Adolescent↗
PubMed1984

Clinical experiences with extracorporeal immunoperfusion of plasma from cancer patients.

We have treated 11 patients having a variety of tumor types and three patients having mitomycin-C-associated thrombotic thrombocytopenic purpura (TTP) with extracorporeal plasma perfusion through filters containing immobilized protein A from Staphylococcus aureus. In performing more than 140 procedures we observed only minimal toxicity, of which fever, chills, nausea, and vomiting were the most common symptoms, occurring in 25% of the patients. Significant decrease in blood pressure and bronchospasm were rare complications. However, none of these side effects were severe enough to require therapeutic intervention. The antitumor effect of immunoperfusion was modest. In 10 adequately treated patients there was one measurable tumor reduction (40% decrease of original tumor mass). Two patients had correction of total small bowel obstruction, with return to normal food intake and restoration of normal bowel habits, lasting for 6 and 3 months; and two of the two adequately treated TTP patients had dramatic hematological improvement after four and five immunoperfusion treatments and are well at present. We found direct correlation between extent of complement activation and clinical toxicity. By temperature manipulation of the perfusion procedure we were able to control the above-mentioned side effects caused by complement activation.

Carcinoembryonic Antigen↗
PubMed1984

Autoantibodies in minimal change nephrotic syndrome.

The presence of low level antibody (AAb) activity and circulating immune complexes (CIC) were studied in 17 patients with minimal change nephrotic syndrome (MCNS). Study groups include 12 MCNS without mesangial deposits (Group I) and 5 MCNS with mesangial deposits (Group II). In Group I reactivity against normal tissue antigens was demonstrated (kidney tubular microsomal antigen - 8, smooth muscle - 5, gastric cell - 5). In Group II reactivity against kidney basement membrane was demonstrated in all five patients. CIC were detected in eight (Group I - 6, Group II - 2). Dissociation of the CIC showed that they all contained antibodies with a corresponding autoantibody activity which could be removed by prior incubation with their complexed antigen. The presence of these AAb's and their formation of CIC may indicate their role in initiating a primary immunological insult to the kidney.

Adolescent↗
PubMed1983

Acute myelomonocytic leukemia associated with nephrotic syndrome. A case report with immunological studies.

A patient with acute myelomonocytic leukemia (AML) developed nephrotic syndrome. The renal biopsy showed focal glomerulosclerosis by light microscopy. Electron microscopy and immunofluorescence revealed electrondense deposits, IgG and C'3 in the glomerular mesangium. A 21S circulating immune complex (CIC) present in the patient's serum and the renal biopsy eluate contained immunochemically identical materials. The isolated antibodies from the 21S CIC and the eluate showed restricted reactivity against autologous AML cells. Immunodiffusion studies demonstrated common antigenicity between the 21S CIC antigen, the eluted antigen and between autologous AML cell membrane antigens.

Antigen-Antibody Complex↗
PubMed1982

Gastric carcinoma and thrombotic thrombocytopenic purpura: association with plasma immune complex concentrations.

A patient with metastatic adenocarcinoma of the stomach developed microangiopathic haemolytic anaemia, thrombocytopenia, renal insufficiency, and fluctuating neurological abnormalities in association with appreciably raised plasma concentrations of immune complexes. This syndrome, similar to thrombotic thrombocytopenic purpura, occurred while the tumour was in sustained objective remission after successful treatment with fluorouracil, doxorubicin, and mitomycin. Reversal of the syndrome was achieved with plasmapheresis, azathioprine, corticosteroids, and antiplatelet treatment; this response was paralleled by a reduction in immune complex concentration, suggesting an immune aetiology for the syndrome. Antibodies eluted from the immune complexes reacted with 50% of cells from the gastric cancer but less than 10% of cells from normal gastric mucosa. There was no reactivity with either carcinoembryonic antigen or mitomycin. A 17S immune complex reacted with a glycoprotein from the patient's autologous platelets and produced platelet aggregation. It is postulated that reducing the tumour and the pre-existing state of antigen excess by chemotherapy allowed soluble antigen-antibody complexes to form and the syndrome to develop.

Adenocarcinoma↗
PubMed1982

Acute myeloid leukemia with hand-mirror cells.

A retrospective analysis of 37 cases of acute myeloid leukemia (AML) seen during five years was undertaken to evaluate the presence in the bone marrow of hand-mirror cells (HMCs). Three cases with greater than 5% HMC were investigated by light and electron microscopy, cytochemistry, levels of terminal-deoxy-nucleotidyl-transferase, study of histologic aspects of bone marrow clot and biopsy specimens, and bone marrow immune complexes for numerous viruses. The findings supported the myeloid nature of the HMC; however, immune complexes associated with the baboon endogenous virus was absent, a finding that has been observed in all cases of acute lymphoblastic leukemia (ALL) with HMCs so studied. In light of this finding, it was suggested that HMCs are produced in ALL and AML by different mechanisms. In addition, the patients with AML-HMC did not survive longer than those without HMCs in the bone marrow. Further studies in larger groups are needed to clarify the phenomenon of HMC formation in AML and its relation to survival.

Adult↗