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Biomedical subjects

W H West

Publications and source records attributed to W H West.

16 recordsLinked to original sources
PubMed1991

Continuous interleukin-2 and lymphokine-activated killer cells for advanced cancer: a National Biotherapy Study Group trial.

We conducted a multicenter, phase II trial of continuous-infusion recombinant interleukin-2 (rIL-2) and lymphokine-activated killer (LAK) cells. Patients had advanced cancer, measurable disease, and a good performance level. Treatment included a 5-day continuous infusion of 18 x 10(6) IU/m2/d of rIL-2 followed by 1 day of rest, 4 days of leukapheresis to collect cells for in vitro augmentation of cellular cytotoxicity, and 5 more days of rIL-2 infusion with reinfusion of LAK cells for 3 successive days. Therapy was repeated after 2 weeks. There were 117 patients enrolled: 63% were males, with a median age of 51 years. Eighty-two percent were managed in oncology units, and 18% were in intensive care units. Six patients died within 1 month of initiating therapy. In renal cell carcinoma, the response rate was one of 31 patients (3%), with a median survival of 10.7 months. In melanoma, the response rate was four of 33 patients (12%), with a median survival of 6.1 months. For all other histologies, response rate was three of 53 patients (5%), with a median survival of 7.4 months. All responders were asymptomatic when therapy was initiated. This trial confirms the feasibility of administering continuous rIL-2 and LAK cells outside the intensive care unit environment. Antitumor activity in melanoma was similar to that seen in multicenter trials of bolus rIL-2 and LAK cells. Activity in renal cell cancer was disappointing.

Adolescent↗
PubMed1990

Recombinant interleukin-2 and adoptive immunotherapy alternated with dacarbazine therapy in melanoma: a National Biotherapy Study Group trial.

We evaluated adoptive cellular therapy with recombinant interleukin-2 (rIL-2) plus lymphokine-activated killer (LAK) cells alternating with sequential dacarbazine chemotherapy in 27 patients with metastatic melanoma. rIL-2 was given to the patients as a 5-day continuous-infusion priming cycle followed by 1 day of rest, 4 days of leukapheresis for in vitro LAK cell expansion, and then 4 1/2 days of continuous rIL-2 infusion in conjunction with reinfusion of LAK cells during the first 3 days of the continuous infusion. Two weeks later, patients received dacarbazine (1,200 mg/m2) chemotherapy. Two patients achieved complete remission, and five achieved a partial remission for a response rate of 26% (95% confidence interval = 12%-47%). Three patients had mixed responses. The partial and mixed responses were brief, ranging from 1 month to 6 months, whereas the two complete responses have been sustained for 13+ and 24+ months. There were no additive toxic effects except for thrombocytopenia, which delayed treatment in two patients. Alternating adoptive immunotherapy and dacarbazine chemotherapy appear to be reasonably tolerated by patients, but the response rate is not clearly better than that achieved with other rIL-2 regimens or with chemotherapy alone.

Adult↗
PubMed1990

Biodistribution and plasma survival in mice of anti-melanoma monoclonal antibody cross-linked to OKT3.

Anti-melanoma monoclonal antibody XMMME-001 was cross-linked to anti-CD3 monoclonal antibody OKT3 with succinimidyl 3(2-pyridyldithio)propionate (SPDP), and 2-iminothiolane. The dimer heteroconjugate was purified by HPLC gel filtration, labeled with 131I, and 10 micrograms was injected into each of 24 BALB/c mice. The dimeric heteroconjugate's blood survival in sequentially bled mice (n = 3) and its biodistribution in organs of sacrificed mice (n = 21) were studied. In plasma, the heteroconjugate showed an alpha phase with a half-life of 4 h, and a beta phase with a half-life of about 18 h. Electrophoretic analysis of labeled heteroconjugate in plasma showed that the half-life of disulfide bonds linking the monoclonal antibodies was approximately 7-8 h. Radioactive heteroconjugate accumulated primarily in the liver; significant uptake was also seen in white blood cells and spleen. Very little radioactivity accumulated in kidney, lung, or colon. As a comparison, SPDP-derivatized anti-melanoma antibody was studied by the same methods. It showed an average alpha-phase half-life of 12.5 h; its maximum accumulation in liver or white blood cells was less than 30% of that of the heteroconjugate. Very low levels accumulated in other tissues. The results imply that the shorter half-life in plasma of the heteroconjugate is primarily determined by clearance due to its larger size and conformation, not the lability of cross-linking disulfide bonds.

Animals↗
PubMed1979

Necrolytic migratory erythema, presenting as candidiasis, due to a pancreatic glucagonoma.

A 54-year-old male with diabetes, weight loss, glossitis and Candidiasis presented with the typical cutaneous eruption of necrolytic migratory erythema. The suspicion of pancreatic glucagonoma was confirmed by an elevated plasma glucagon level. Surgical removal of the pancreatic alpha cell tumor resulted in a complete disappearance of all symptoms. The importance of the recognition of the skin eruption of necrolytic migratory erythema as a clue to the presence of pancreatic glucagonoma is emphasized.

Candidiasis↗
PubMed1978

Low affinity E-rosette formation by the human K cell.

Human T lymphocytes were separated into two subsets on the basis of relative affinity for sheep red blood cells (E), and these T cell fractions were examined for cytotoxic reactivity against antibody-sensitized Change liver cells (ADCC). High affinity E-rosette-forming cells (E-RFC) (55 +/- 6% of peripheral blood mononuclear cells), capable of rosette formation despite elevated temperatures of incubation (29 degrees C) and a limited concentration of E, contained few antibody-dependent cytotoxic cells (K cells). In contrast, low affinity E-RFC (23+/-7% of mononuclear cell suspensions) requiring cool temperatures of incubation (4 degrees C) and an excess of E to form rosettes, were highly enriched for ADCC activity. The majority of K cells exhibited low affinity interactions with E. T cells in thymus, tonsil, and lymph node formed high affinity E-rosettes and exhibited little reactivity in ADCC. Only peripheral blood and spleen contained easily identified low affinity E-RFC and anti-body-dependent cytotoxic cells. The proportion of low affinity E-RFC in the peripheral blood of normal subjects correlated closely with reactivity in ADCC, making it possible to predict cytotoxic potential for the E-rosette pattern. These data indicate that the human K cell may belong to a previously unappreciated but functionally important subset of thymic dependent mononuclear cells.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1978

Role of interferon in augmentation of natural and antibody-dependent cell-mediated cytotoxicity.

Natural killer (NK) activity in rats and NK and antibody-dependent cell-mediated cytotoxicity in mice have been shown to be rapidly augmented by in vivo treatment with a variety of viruses and immune adjuvants. Poly I:C and other interferon inducers also caused boosting in NK-cell activity, with peak levels occurring at about the time of peak interferon levels. Crude and purified virus-induced interferon itself had strong boosting effects in mice, both when inoculated in vivo and when incubated briefly with normal spleen cells. The in vitro activation by interferon or by poly I:C was completely abrogated by anti-interferon. Interferon also appears to play a central role in augmentation of human NK-cell activity. Inoculation of normal volunteers with influenza virus or of a patient with poly I:C produced rapid boosting. In vitro incubation of peripheral blood mononuclear cells with various interferon preparations for 1 hour or overnight usually produced an appreciable increase in lytic activity.

Animals↗
PubMed1977

Relationship of human natural lymphocyte-mediated cytotoxicity to cytotoxicity of breast-cancer-derived target cells.

Mononuclear cells from 115 individuals were tested in a 4-h chromium release assay against two breast-cancer-derived cell lines, G11 and MCF-7, and a myeloid line, K-562, shown previously to be sensitive to natural cytotoxicity. These data were analyzed in a manner designed to detect hyperreactivity against the breast cell lines relative to the level of reactivity against K-562. A high proportion of breast cancer patients were found to be relatively hyperreactive against G11 (12/18 or 67%) and against MCF-7 (10/18 or 56%). Fibroadenoma patients were very similar to the normal females, with 0/11 hyperreactive to G11 and 1/11 (9%) to MCF-7. However, several normal males (7/17 or 41%) were hyperreactive to G11 but not to MCF-7 (2/17 or 12%). Colon cancer and lung cancer patients were also more hyperreactive to G11, 4/8 or 50% and 4/6 or 67%, respectively, than they were to MCF-7, 1/8 or 13% and 1/6 or 17%, respectively. Only fibrocystic patients resembled the breast cancer patients, with some but not as many individuals being hyperreactive to G11 (3/8 or 38%) and to MCF-7 (2/8 or 25%). With another group of individuals reproducibility of the method was demonstrated, with only 1/14 or 7% of normal females and 12/17 or 70% of breast cancer patients being hyperreactive to G11. Thus, natural cytotoxicity toward K-562 can be related to breast cancer-associated cytotoxicity toward MCF-7 in a way that distinguishes a majority of breast cancer patients specifically from other groups of individuals.

Breast Neoplasms↗
PubMed1977

Natural cytotoxic reactivity of human lymphocytes against a myeloid cell line: characterization of effector cells.

Using a series of techniques to identify and deplete various peripheral blood lymphocyte subpopulations, we studied the cytotoxic reactivity of normal individuals against the myeloid cell line K-562 in a 4-hr 51chromium-release assay. Depletion of lymphocytes bearing complement receptors had a variable, usually negligible effect on cytotoxicity. In contrast, depletion of lymphocytes bearing Fc receptors abrogated target cell lysis. Separation of lymphocytes with high-affinity binding of sheep red blood cells (SRBC) evidenced by rosette formation at 29 degrees C yielded a population of rosette-forming cells containing few cytotoxic cells, whereas separation of total E-RFC under optimal rosetting conditions produced a rosette fraction containing a major proportion of the effector cells. These data indicate that the cytotoxic lymphocyte in this system is Fc receptor positive, largely complement receptor negative, and may possess low density or low affinity receptors for SRBC.

Antigen-Antibody Complex↗
PubMed1977

Fc receptors on mouse effector cells mediating natural cytotoxicity against tumor cells.

Mouse effector cells mediating natural cytotoxicity against tumor cells have been previously thought to be lymphocytes that lack any detectable cell surface markers. The present study presents evidence for receptors for the Fc portion of IgG on these cells. By adsorption of cytotoxic spleen cells on monolayers of sheep erythrocytes (E) plus IgG antibodies to sheep erythrocytes (EA), 50 to 96% of the total cytotoxic reactivity could be removed. Parallel adsorption of cells on E monolayers or on EA monolayers coated with protein A, to block the Fc portion of IgG, resulted in little or no depletion of cytotoxic activity. The presence of Fc receptors on the NK cells was confirmed by combining EA rosette formation with velocity sedimentation at unit gravity. Peak cytotoxicity occurred at the same sedimentation velocity as the peak of Fc-positive cells. After EA rosette formation, there was a shift to a higher sedimentation velocity in the Fc-positive cells and in the natural cytotoxic activity. The increase in sedimentation velocity of NK activity that was observed in these experiments indicated that most of the cells had only bound a small number (three or four) of antibody-coated erythrocytes. Together, these data indicate that cells with Fc receptors account for most of the total lytic activity of normal mouse spleen cells.

Animals↗
PubMed1976

Lymphocytes forming rosettes with sheep erythrocytes in metastatic pleural effusions.

Percentages of lymphocytes forming rosettes with sheep erythrocytes at 29 degrees C were determined in 10 cancer patients with metastases to the pleural cavity. Compared with normal controls, the patients showed a decreased proportion of rosette-forming cells (RFC) in the peripheral blood. The same patients had elevated levels of RFC in their metastatic pleural effusions. However, 2 patients with benign diseases had normal levels of RFC in their peripheral blood and pleural transudates. These observations suggested that in cancer patients some T-cells might migrate from the peripheral blood and accumulate in sites of tumor infiltration such as the pleural cavity.

Adult↗
PubMed1975

Effect of steroidogenesis on ascorbic acid content and uptake in isolated adrenal cells.

Isolated adrenal cell preparation was used to investigate the relationship between ascorbic acid and steroidogenesis by two methods: (1) in vivo incorporation of exogenous [1-14C]ascorbic acid into endogenous ascorbic acid of adrenal by intraperitoneal injection of labeled ascorbic acid into rats and studying the depletion of labeled ascorbic acid under a variety of experimental conditions; and (2) study of the uptake of [14C]ascorbic acid by IAC in response to steroidogenic stimuli and various steroids. These studies demonstrate that: 1. IAC preparation by the trypsin digestion method results in almost total depletion of ascorbic acid from adrenal cells, i.e., ascorbic acid content of the cell preparation was less than 1% of the original ascorbic acid in quartered adrenal gland. 2. In spite of such a severe depletion of ascorbic acid, steroidogenesis in response to ACTH and dibutyryl cyclic AMP (dcAMP) is quite pronounced. 3. ACTH and dcAMP affect depletion of endogenously labeled ascorbic acid in IAC by a process that is both concentration- and time-dependent, but is independent of steroidogenic processes. 4. ACTH and dcAMP both inhibit the uptake of exogenous [1-14C]ascorbic acid, which is time-dependent but independent of the steroidogenic phenomenon. 5. The uptake of [14C]ascorbic acid by IAC is independent of extra-to-intracellular gradient of glucocorticoids or mineralocorticoids.

Adrenal Glands↗