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)

Preclinical studies have shown that anti-CD3 antibodies can enhance the in vitro activation of human T lymphocytes in combination with low-dose interleukin-2 (IL-2) and induce the in vivo rejection of murine tumors. A Phase IA/IB trial combining a murine monoclonal antibody, anti-CD3 antibody (OKT3), with low-dose continuous-infusion IL-2 was conducted in cancer patients to define the toxicity and immunologic effects of this combination. OKT3 administered weekly as a 15-min infusion at dose levels of 10, 100, 200, 400, and 600 micrograms/m2 was followed 18 h later by a 100-h infusion of IL-2 at 3 MIU/m2/day for 3 consecutive weeks. When feasible, patients also received the IL-2 course without OKT3 to assess the effects of OKT3 on the IL-2 regimen within the same patient. Thirty patients were enrolled onto the study, with 24 completing the OKT3/IL-2 course and 18 completing both OKT3/IL-2 and IL-2 alone courses. OKT3 administration was associated with acute hypotension with fevers of > 40 degrees C and in two patients cerebral vascular infarcts. At 600 micrograms/m2 OKT3, these toxicities were dose limiting. In a dose-dependent manner, OKT3 induced the transient release of tumor necrosis factor (TNF) and IL-6 into the serum and a profound lymphopenia. OKT3 did not significantly enhance the toxicity of this schedule of IL-2 administration. All solid tumor patients treated at 100-600 micrograms/m2 OKT3 showed induction of a human anti-murine antibody response prior to the third week of treatment. A patient with renal cell cancer treated at the 600-micrograms/m2 OKT3 dose level experienced a 4-month partial remission, and two mixed responses were observed in a sarcoma and a melanoma patient treated at 100- and 400-micrograms/m2 OKT3 dose levels, respectively. Most importantly, we were unable to demonstrate that the addition of OKT3 enhanced immune activation within peripheral blood based upon the magnitude of rebound lymphocytosis, increase in CD56+ or CD3+, CD25+ lymphocytes, induction of natural killer, lymphokine activated killer, or cytolytic T lymphocyte cytotoxicity, or release of serum cytokines (TNF, IL-6) or soluble CD25 (as assayed 24 h following IL-2 infusion). Therefore, this approach was ineffective at enhancing the immunologic effects of a low-dose continuous-infusion IL-2 regimen and will not be pursued further in clinical trials.
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PMID:A phase IA/IB trial of anti-CD3 murine monoclonal antibody plus low-dose continuous-infusion interleukin-2 in advanced cancer patients. 761 43

Prospective studies were performed over a 28- to 77-month period (median, 66 months) on 5 cats with naturally acquired feline immunodeficiency virus (FIV) infection in an attempt to correlate hematologic and clinicopathologic changes with the emergence of clinical disease. On presentation, all cats were asymptomatic; free of opportunistic infections; and had normal complete blood counts, bone marrow morphologies, marrow progenitor frequencies, and progenitor in vitro growth characteristics. During study, 2 cats remained healthy, 2 cats showed mild clinical signs, and 1 cat developed a malignant neoplasm (ie, bronchiolar-alveolar adenocarcinoma). Although persistent hematologic abnormalities were not observed, intermittent peripheral leukopenias were common. In 3 of 5 FIV-seropositive cats, lymphopenia (< 1,500 lymphs/microL; normal reference range, 1,500 to 7,000 lymphs/microL) was a frequent finding and the absolute lymphocyte counts had a tendency to progressively decline. One of the other 2 cats had consistently low to low-normal absolute neutrophil counts (1,300 to 4,800 segs/microL; mean, 2,730 segs/microL; normal reference range, 2,500 to 12,500 segs/microL), and the remaining cat had consistently normal leukograms, except for a transient period (ie, 11 months) of benign lymphocytosis (7,200 to 13,430 lymphs/microL) early in the study. Periodic examinations of bone marrow aspirates revealed normal to slightly depressed myeloid-to-erythroid ratios with normal cellular morphology and maturation. Bone marrow abnormalities observed late in the study included mild dysmorphic changes (ie, megaloblastic features) in 2 cats, and a significant decrease (60% of controls, P < .001) in the frequencies of burst-forming units erythroid (BFU-E) in marrow cultures of FIV-seropositive cats compared with uninfected control cats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prospective hematologic and clinicopathologic study of asymptomatic cats with naturally acquired feline immunodeficiency virus infection. 767 14

Lymphocyte subpopulations in peripheral blood and bronchoalveolar lavage fluid (BAL) were examined in 29 patients with AIDS (26 men, three women; median age 32 [16-55] years). Patients in group 1 (n = 12) had no lung disease, in group 2 (n = 11) had Pneumocystis carinii pneumonia, in group 3 (n = 6) had other lung disease. There were 13 men and two women (median age 48 [21-80]) in the control group (bronchoscoped for mild pulmonary symptoms: no abnormal findings in the BAL). Compared with the control group, patients with AIDS had a significant deficiency in helper cells, both in blood (7-23% vs 50%; P < 0.01) as well as in the BAL (7-24% vs 52%; P < 0.001). There was a correlation of the percentage helper cell proportion in peripheral blood and BAL (for both group 1 and 2, rs = 0.75; P < 0.05). The proportion of helper cells in peripheral blood and BAL in AIDS patients was significantly lower in those with than without lung disease (group 1: 23% blood, 24% BAL vs group 2: 9% blood, 7% BAL; group 3: 7% blood, 7% BAL; P < 0.02 blood, P < 0.004 BAL). The percentage proportion of suppressor cells was greater in both blood and BAL in AIDS patients (group 1: blood 47%, BAL 63%; group 2: blood 44%, BAL 76%; group 3: blood 52%, BAL 75%) than in the controls (blood 28%, BAL 33% [P < 0.01], but there was no correlation between peripheral blood and BAL. In addition, the absolute number of suppressor cells in the lavage (30 cells/microliters in group 1 and 3, 65 cells/microliters in group 2) was significantly higher than in the controls (8 cells/microliters).--In AIDS patients there occurs a lymphocytosis in the BAL, while in blood there is a lymphopenia. The concordant decrease in helper cells in blood and BAL is decisive for the severity of any pulmonary infections.
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PMID:[Lymphocyte subpopulations in bronchoalveolar lavage fluid in AIDS]. 811 8

Recombinant human interleukin-2 (IL-2) was administered by the intravenous (i.v.) or intralymphatic (i.l.) route to 14 patients with advanced malignancy. IL-2 was given in doses of 600,000 IU/kg or 1,050,000 IU/kg daily x 5. Thoracic duct (TD) catheters were placed, and both TD lymphocytes (TDL) and peripheral blood lymphocytes (PBL) were studied. Five of eight patients at the 600,000 IU/kg dose experienced grade III toxicity as did five of six patients at the 1,050,000 IU/kg dose. Two episodes of grade IV toxicity were seen at the higher dose. The i.l. and i.v. routes had a similar toxicity profile excepting lymphangitis/pedal infection, seen only with i.l. administration. One partial response was seen in a patient with renal cell carcinoma. Lymphopenia was seen early in therapy, with lymphocytosis by day 6. Lymphoid yield of the TD catheter fell early in therapy, then increased over baseline by the end of treatment. Intralymphatic administration resulted in a prolonged serum t1/2 and lower serum levels than did i.v. administration, but resulted in higher TD levels. Antibodies against IL-2 were ubiquitous but had no clear effects. Lymphocyte trafficking studies suggested that IL-2 affected lymphocyte redistribution to liver, spleen, bone marrow, and lymph nodes. NK activity and phenotype and LAK activity increased in response to IL-2, with no advantage for TDL. Tumor necrosis factor-alpha and gamma-interferon levels increased sporadically with treatment. The i.l. route offered no advantage over the i.v. route, and TDL offered no advantage over PBL.
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PMID:A comparative study of intravenous versus intralymphatic interleukin-2, with assessment of effects of interleukin-2 on both peripheral blood and thoracic-duct lymph. 813 47

Patients with advanced renal cell carcinoma, previously failed maximal treatment with standard chemo-hormonal-radiation therapies, were treated with plant lectin phytohemagglutinin (PHA)-stimulated autologous peripheral blood lymphocytes in a 10-year study with a 16-year follow up period. In a phase I-II setting, 52 patients were given subcutaneously 40-80 x 10(6) PHA-stimulated lymphocytes weekly for 3 weeks and then escalated to a maximum number of 80 x 10(9) lymphocytes over the next 9 weeks at 3 week intervals. In vitro blastogenesis under study conditions (10 micrograms/ml PHA for 72 hr) measured by [3H]thymidine uptake was optimal with lymphocyte stimulating indexes approaching 300. Lymphocytes obtained from patients with breast cancer, melanoma and renal cell carcinoma responded to PHA similarly to those from normal volunteers. All patients that responded developed erythematous reactions at the sites of injection; malaise, joint paint and chill-fever for 24-48 hr. The patients that responded the best were those with at least 1 positive reaction out of 4 skin tests (tuberculosis, yeast, dermatophytin, mumps) prior to therapy. All toxicity was transient and did not exceed Grade I based on criteria of the Southwest Oncology Group. The majority of patients developed a lymphopenia in the first 24 hr followed by a lymphocytosis 48-72 hr later. For some patients the lymphocytosis was as much as 30% atypical lymphocytes. Of 41 evaluable patients, there were 5 complete responses, 8 partial responses, 3 stable diseases, and 25 progressive disease. The overall response rate was 32% and the median survival was 2.8 years.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adoptive immunotherapy of advanced renal cell cancer using PHA-stimulated autologous lymphocytes. 826 79

West African Dwarf (WAD) and Red Sokoto (RS) goats were experimentally infected with the Kafanchan strain of Trypanosoma congolense and the course of the infection was monitored. The organism was pathogenic and produced fatal disease in the goats, which was characterized by rapid progressive anaemia, leucocytosis, weight loss and death. All RS goats died within 11 days of infection, and had a mean reduction in packed cell volume (PCV) of 11%. In West African Dwarf goats, one death occurred on Day 13 post-infection with a mean drop in PCV of 9%. Statistically significant (P < 0.05) mean reductions in values of PCV, haemoglobin and red blood cell counts were observed between the infected and control animals of both breeds, and also between the infected WAD and infected RS goats. The anaemia produced was macrocytic. Leucocytosis characterized by neutropenia and lymphocytosis was observed among infected WAD goats, but leucopenia characterized by neutrophilia and lymphopenia was observed in infected RS goats. Infected WAD goats recorded some positive unit weight gain in spite of the infection. It was concluded that the RS breed of goats is more susceptible to T. congolense infection than the WAD breed.
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PMID:Susceptibility of Nigerian west African dwarf and red Sokoto goats to a strain of Trypanosoma congolense. 833 25

T cells and their sub-populations were evaluated with respect to reactive, intermediate and unreactive forms of tuberculosis as classified by Lenzini. Significant CD4 lymphopenia and a reduction of CD4/CD8 ratios were found in patients with reactive tuberculosis. It was observed that there was a B lymphocytosis, CD8 lymphocytosis and a reduction of CD4/CD8 ratio in patients with intermediate and unreactive forms of tuberculosis. The T lymphocytes and CD4 subset were unchanged. There was no significant difference in the lymphocytes and sub-populations among the intermediate and unreactive groups.
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PMID:T lymphocytes in pulmonary tuberculosis. 848 3

The case of a 7-year-old boy with virus-associated hemophagocytic syndrome (VAHS) and serologically proven parvovirus B-19 infection is described. The patient with VAHS presented with fever, hepatosplenomegaly, pancytopenia, and hyperlipidemia type IV. After induction therapy with VP-16 and prednisone, partial remission was achieved. Despite maintenance therapy, reinductions, and the addition of cyclosporine A for 3 months, several relapses occurred. The therapy was stopped because of life-threatening complications (Klebsiella sepsis, neutropenic enterocolitis, and stercoral peritonitis). The complications were treated successfully. The patient status was stabilized after splenectomy. However, hepatomegaly progressed slowly and the hyperlipidemia endured. Ten months after the diagnosis leukocytosis with absolute T lymphocytosis appeared. Reactivation of VAHS was suspected and intravenous immunoglobin and then antilymphocyte immunoglobulin ALG therapy were started. The resultant decrease in leukocytosis was prompt, but lymphopenia did not occur. Virostatic treatment with foscarnet was introduced based on human herpesvirus-6 seroconversion. Twenty-six months after the diagnosis, the patient is well, without any sign of VAHS or lymphoproliferation.
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PMID:Infection-associated hemophagocytic syndrome complicated by infectious lymphoproliferation: a case report. 872 Oct 28

This study examined a temporal relationship between exercise-induced changes in blood cortisol levels and circulating leukocyte and lymphocyte subset counts during and after exercise. Twenty-one young male, sedentary subjects [mean age, 20.8 +/- 2.4 (SD) yr; mean VO2max, 48.0 +/- 7.9 (SD) ml/kg/min] underwent a cycle ergometer exercise for 60 min at 60% VO2max. Peripheral blood samples, collected every 30 min during exercise and at 30, 60 min, 2.5 and 6 h of recovery, were used for the determination of serum cortisol and plasma catecholamines; lymphocyte subsets were analyzed by flow-cytometry. Based on the analysis of serum cortisol levels in response to exercise, the subjects can be identified as two groups: cortisol-responder (n = 13) and non-responder (n = 8) groups. Other than the cortisol response, the two groups showed no significant differences in terms of age, physical build, aerobic fitness, maximal heart rate, and pre-exercise blood leukocyte and lymphocyte subset counts. The two groups also did not differ significantly in their relative work rate and catecholamine response to the exercise. Both cortisol responder and non-responder groups displayed a granulocytosis, lymphocytosis and monocytosis during exercise, and a further granulocytosis after exercise. Changes in lymphocyte count and distribution during recovery, however, differed significantly between the two groups. In the circulation of the cortisol non-responder group, total lymphocyte counts returned to the baseline level shortly after exercise, whereas a significant lymphopenia occurred at 2.5 h of recovery in the cortisol responder group: the CD4+ cells showed the greatest decrease in cell count, followed by the CD8+ cells. In both groups, the CD16+ cell-counts tended to decline below the pre-exercise values at 30 and 60 min of recovery and returned to the baseline values by 2.5 h of recovery. The CD19+ cell-count was not suppressed in both groups after exercise. These results suggest that exercise-induced secretion of blood cortisol may contribute to post-exercise suppression of the helper- and cytotoxic-T cell counts, but does not seem to be involved in post-exercise changes in the NK-cell and B-cell counts as well as in post-exercise granulocytosis.
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PMID:Cortisol response to exercise and post-exercise suppression of blood lymphocyte subset counts. 897 81

Recent investigation has suggested there is an adrenergically-driven efflux of beta 2-receptor rich lymphocyte subsets into the circulation with altered function following either exercise or infusion of exogenous catecholamines. Myocardial ischemia, like exercise, is associated with generalized sympathoadrenal activation. To determine whether ischemia influences immunoregulatory cell traffic and function in a manner comparable to beta 2-adrenergic stimulation via isoproterenol, rats underwent thoracotomy with or without coronary ligation. Another group of rats received either isoproterenol (1 mg/kg) or vehicle (10 mM HCl) intraperitoneally. Thoracotomy, regardless of whether or not myocardial ischemia was induced, led to lymphocytosis, reflected primarily by an increase in Thelper (Th) cells and, to a lesser degree, in Tsuppressor/cytotoxic (Ts/c) and natural killer (NK) cells, with a tendency toward an increased Th/Ts/c ratio. To the contrary, isoproterenol injection resulted in a relative lymphopenia characterized by diminished B and Th cell numbers, preserved Ts/c and increased NK cell numbers leading to a significant decrease in the Th/Ts/c ratio. With respect to splenic composition, 60 but not 15 min of myocardial ischemia led to diminished Th and B cell numbers compared to sham operated controls, whereas isoproterenol appeared to stimulate an efflux of only NK cells. Both ischemia and isoproterenol enhanced basal splenocyte function; however, only ischemia significantly boosted splenocyte responsiveness to the mitogen Concanavalin A. Surgically induced myocardial ischemia leads to alterations in immunoregulatory cell migration and function which are distinct from those found with beta 2-adrenergic stimulation via isoproterenol.
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PMID:Myocardial ischemia alters immunoregulatory cell traffic and function in the rat independent of exogenous catecholamine administration. 898 9


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