Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

E rosette-forming (T) lymphocytes and surface immunoglobulin-bearing lymphocytes were estimated in 85 patients with malignant melanoma. The melanoma patient group had lower mean levels of T lymphocytes and higher mean levels of immunoglobulin-bearing (? B) lymphocytes than did normal subjects. The absolute and percentage depressions of T-cell levels in the melanoma patients were stage-related, as was the depression of total lymphocyte and B-lymphocyte levels. The T lymphopenia in the melanoma patients could, in vitro, be partially abolished by fetal calf serum (as used in many E rosetting methods), and could be totally abolished by thymosin fraction 5 (Hoffmann-La Roche) at optimum concentration. In view of the ability of thymosin to restore T cells to normal levels in all of the T-lymphopenic patients, a clinical trial of this hormone in selected melanoma patients of all stages appears to be warranted.
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PMID:Thymosin-inducible lymphocytes in the peripheral blood of patients with malignant melanoma. 31 Mar 43

Twenty-two patients with cutaneous metastases of malignant melanoma were treated with intralesional injections of the methanol extraction residue of bacillus Calmette-Guerin (MER). The local reaction consisted of erythema and pustule formation followed by ulceration and tumor necrosis. Side effects included fever, chills, headache and malaise in the majority of patients; nausea, vomiting, cyanosis and hypotension occurred infrequently. Hypersensitivity reactions were not observed. Temporary abnormalities in liver function were seen in 11 of 19 patients tested. Reversible lymphopenia and thrombocytopenia developed in 7 of 17 and 7 of 18 patients, respectively. Immune function, as measured by skin tests for delayed hypersensitivity and the in vitro response of isolated lymphocytes to mitogens and microbial antigens, was not influenced by treatment with MER. Transient increases were observed in total hemolytic complement, complement components and the reduction of nitroblue-tetrazolium by neutrophils. Eight of eighteen evaluable patients showed a complete disappearance of all injected lesions. We conclude that intratumoral injection of MER is effective treatment for cutaneous metastases of malignant melanoma, with a complete response rate comparable to that observed after intralesional injection of BCG.
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PMID:Intralesional injection of the methanol extraction residue of Bacillus Calmette-Guerin (MER) into cutaneous metastases of malignant melanoma. 72 66

One hundred thirty two patients with disseminated malignant melanoma were treated using a combination of BCNU, vincristine and imidazole carboxamide. A response rate of 23% was observed, while 16% had stable disease. The patients' median survival was 42 months from diagnosis and 5.3 months from the onset of treatment. These results are not significantly different from therapy with imidazole carboxamide alone. Patients on this study were observed to have a significant reduction in the number of lymphocytes in their peripheral blood (mean 1800/mm3, median 1550/mm3). Patients with lymphopenia prior to the onset of therapy (86%) had a similar response rate but a shorter median survival (4.4 months vs. 7.8 months, P = .03) than patients with normal lymphocyte levels. These findings are compatible with recent observations on the importance of host immunocompetence in patients with malignant melanoma. Eosinophil levels were not closely correlated with response, although among patients with eosinophil counts of greater than 300/mm3 (22%), a slightly higher response rate (29%) was observed (P = .13). Eosinophilia did not influence patient survival.
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PMID:Combination chemotherapy with bis chloroethyl nitrosourea (BCNU), vincristine and dimethyl triazeno imidazole carboxamide (DTIC) in disseminated malignant melanoma. 83 24

Using a microassay for cellular immunity, tumour specific cytotoxicity was detected in 2/5 cases of ocular melanoma and 1/3 cases of primary cutaneous melanoma before treatment. Reactivity was measured against allogeneic skin melanoma target cells in short or long term in vitro culture. Lymphoid cells from patients with disseminated cutaneous melanoma were either non-reactive (4/8 cases) or gave a nonspecific cytotoxicity on target cells of diverse histogenic origins. Among tumour-free patients tested after surgery, 0/2 patients with ocular tumour were non-reactive 3-4 months post surgery. After sugical excision of cutaneous melanoma 2/2 patients gave tumour specific reactions during the first month after surgery. After longer time intervals, from 5 months to 3 years, only 1/8 patients were reactive. Preoperative radiotherapy in a total skin dose of 10,000 rad produ-ed a transient tumour specific reaction 24 h after therapy in a single case. Following local tumour excision in patients given preoperative irradiation, 2 cases which had previously demonstrated tumour specific CMI lost reactivity. Among 14 tumour-free individuals tested only after preoperative radiotherapy and surgery, at intervals from 5 day to 13 years, a single case gave tumour specific CMI. Palliative irradiation in doses 4000-4960 rad to the inguinal or axillary lymph nodes was found to induce a generalized lymphopenia within 48 h after treatment. Lymphoid cell preparations from patients with localized melanoma contained significantly increased numbers of immature cells (lymphoblasts and myeloblasts) and myeloid precursor elements. Those prepared from patients with disseminated disease had in addition elevated levels of eosinophils but reduced numbers of recoverable lymphocytes.
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PMID:The influence of tumour burden and therapy on cellular cytotoxicity responses in patients with ocular and skin melanoma. 115 16

Polyinosinic-polycytidylic acid (PIC), a synthetic polyribonucleotide, inhibits the growth of B16 malignant melanoma in C57BL/6 mice. Since PIC has been reported to augment immune responses, we tested the hypothesis that the antitumor effect of PIC against B16 melanoma is via immune stimulation. Mice were neonatally thymectomized or neonatally thymectomized and subsequently irradiated to suppress their immune reactivity. In such animals PIC retained its ability to inhibit the growth of B16 melanoma, in the face of profound leukopenia and lymphopenia, suggesting that its antimelanoma effect is probably not mediated by augmentation of the host's immune antitumor response.
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PMID:Retention of antimelanoma effect of polyinosinic-polycytidylic acid in neonatally thymectomized, irradiated, leukopenic mice. 115 15

Cell mediated immunocompetence was measured serially in 35 patients with malignant melanoma in order to determine the effect of extent of disease and prognosis as well as the influence of BCG immunotherapy on immune reactivity. Compared with normal adult controls, statistically significant lymphopenia occurred only in patients with widespread disease. Seventeen of 21 patients with negative pre-therapy PPD skin test converted to skin test positivity. PHA blastogenesis was depressed only in patients in the pre-terminal stages of their disease using optimal mitogen concentrations for stimulation. Threshold concentrations of this mitogen more clearly demonstrated a depressed responsiveness which correlated in severity with extent of disease. PPD induced blastogenesis was normal or increased in the majority of patients; however, the degree of stimulation by PPD was less in the BCG induced convertors than in those patients who were skin test positive before BCG treatment. Comparison of the pre- and post BCG assessments reveals no significant differences except in relation to PPD conversion. We conclude that using threshold concentrations of PHA, impaired responses are regularly associated with disease beyond the regional lymph nodes. Routine assessment of lymphocyte function by these parameters did not provide information that was not available from clinical evaluation.
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PMID:Cellular immunocompetence in melanoma: effect of extent of disease and immunotherapy. 123 77

R24 is a mouse IgG3 monoclonal antibody that reacts with the ganglioside GD3 expressed by melanoma cells and other cells of neuroectodermal origin (e.g. adrenal medulla). Antitumour activity of R24 was demonstrated in initial phase I and pilot trials, but treatment was limited by urticaria at cumulative doses of 400 mg/m2. A trial exploring intensification of the dose of R24 was conducted in eight patients. Planned doses of R24 antibody were 800 and 1200 mg/m2 over 6-8 days by continuous i.v. infusion. All patients received concomitant therapy with hydroxyzine hydrochloride and cimetidine to minimize urticaria. One patient developed anaphylaxis, after which no further therapy was given. All patients developed peripheral blood lymphopenia and marked decreases in serum complement values during treatment, suggesting depletion of two possible effector mechanisms of the antitumour effects of R24. A vascular leak syndrome, manifested by weight gain, oedema and hypotension, was evident in seven patients during the initial 24-36 h of treatment. Serum sickness syndrome was observed in six of seven evaluable patients between days 5 and 8, coincident with the onset of the human anti-globulin response to R24. One patient given 1200 mg/m2 had a minor response (38% reduction in pelvic nodes) lasting 12 months. There was no detectable increase (by immunohistochemical staining) in deposition of R24 within tumour sites at doses used in this trial compared to that observed at doses of 240 and 400 mg/m2. The maximum tolerated dose was 800 mg/m2. Dose-limiting toxicity was manifest as reversible hypertension with end-organ symptoms (chest pain or visual field defects) in patients treated with a dose of 1200 mg/m2.(ABSTRACT TRUNCATED AT 250 WORDS)
Melanoma Res 1992 Dec
PMID:Treatment with high dose mouse monoclonal (anti-GD3) antibody R24 in patients with metastatic melanoma. 129 83

A 67-year-old man with xeroderma pigmentosum (XP) originally presented with malignant melanoma at the age of 28 years. This recurred 22 years later and subsequently numerous primary and secondary melanomas developed on the skin, several of which underwent spontaneous regression. Despite a marked lymphopenia, the proportion of natural killer cells was elevated and it is proposed that this led to the regression of the melanomas. Skin-derived fibroblasts from the patient were more sensitive to UVC (D10 approximately 3 J/m-2) than those from normal individuals (D10 approximately 15 J/m-2). The fibroblast culture was shown to be defective in excision repair with less than 10% of residual activity compared with controls. No assignment to a complementation group has yet been made. There was an elevated frequency of mutants resistant to 6-thioguanine in the circulating T lymphocytes.
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PMID:Long-term survival and preservation of natural killer cell activity in a xeroderma pigmentosum patient with spontaneous regression and multiple deposits of malignant melanoma. 191 21

Recombinant human interleukin 1 beta (IL 1 beta) inhibits growth of B16 melanoma in syngeneic C57BL/6 mice in a dose-dependent manner when given intratumorally, intradermally, or intramuscularly over a period of 5 to 7 days. Inhibition of tumor growth was rapid and measurable within 3 days after the initial injection and occurred regardless of the route of injection. However, only intratumoral (ITU) injections of IL 1 beta resulted in greater than 90% inhibition in tumor growth. This enhanced inhibition of tumor growth was not dependent on T or NK cells since inhibition of tumor growth occurred in nude and Beige mice. Also, a profound lymphopenia occurred in mice receiving IL 1 beta. Inhibition of tumor growth did correlate with an increase in the number of polymorphonuclear leukocytes (PMN's) in the circulation. However, only ITU injections of IL 1 beta increased the number of PMN's within the tumors. IM injections of IL 1 beta, while increasing the number of PMN's in the circulation, did not increase the influx of PMN's into the tumors. Furthermore, the transfer of PMN's directly into B16 tumors caused a 49% reduction in tumor growth without the presence of IL 1 beta. These results suggest that in vivo, PMN's may effectively control the growth of tumors and that IL 1 beta may increase this effectiveness by increasing the number of PMN's in the circulation and by locally stimulating the production of chemotactic factors for PMN's within the tumor.
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PMID:In vivo inhibition of tumor growth of B16 melanoma by recombinant interleukin 1 beta. II. Mechanism of inhibition: the role of polymorphonuclear leukocytes. 196 51

The effects of gallium arsenide (GaAs) exposure on immunocompetence of B6C3F1 female mice were investigated. GaAs was administered as a single intratracheal instillation at doses of 50, 100, and 200 mg/kg. Fourteen days after exposure, various cellular and humoral immune parameters were assessed. GaAs exposure increased spleen cellularity in a dose-dependent manner. However, the percentages of Thy 1.2 positive and Ig positive cells were decreased and that of F4/80 positive cells was increased dose dependently. The IgM and IgG antibody-forming cell response of the spleen to the T-dependent antigen sheep erythrocytes was reduced by 66 and 48%, respectively, at 200 mg/kg. Levels of the serum complement protein, C3, were increased by as much as 16% with no significant change in CH50 levels. The mitogenic response of splenic T cells to Con A and PHA was unaffected by GaAs, but that of B cells to LPS was increased by 52%. The delayed hypersensitivity response to keyhole limpet hemocyanin and mixed lymphocyte response were significantly reduced in a dose-dependent manner by GaAs exposure. Natural killer cell activity against the YAC-1 mouse lymphoma was enhanced in treated mice. Analysis of peritoneal exudate cells (PEC) revealed a dose-dependent decrease in number and a shift in the composition of PECs. The percentage of PEC monocytes increased from 53% of the population to 81%, while the lymphocytes decreased from 46 to 20%. The adherent PEC population demonstrated decreased phagocytosis of covaspheres and increased phagocytosis of chicken erythrocytes (CRBC). GaAs exposure had no effect on host resistance to Plasmodium yoelii or Streptococcus pneumoniae, but dose dependently increased resistance of the mouse to Listeria monocytogenes. Treated mice demonstrated a significantly decreased resistance to the B16F10 melanoma with a sevenfold increase in tumor burden at 200 mg/kg. GaAs affects both humoral and cellular immune parameters in mice and impairs the ability of the immune system to protect against B16F10 tumor challenge.
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PMID:Immunotoxicity of the semiconductor gallium arsenide in female B6C3F1 mice. 269 79


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