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At least 613 records · Page 34Linked to original sources
PubMed1989

Granulocyte-macrophage colony-stimulating factor may inhibit neutrophil migration in vivo.

Recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) was administered by constant intravenous infusion to eight patients with malignant disease prior to chemotherapy. rh GM-CSF was given at a dose of 15 to 25 micrograms m-2 h-1 for 1 or 2 h. Neutrophil migration into an inflammatory zone was monitored throughout this period using a micropore skin window technique. Neutrophil migration into the micropore membrane prior to the commencement of the rh GM-CSF infusion was almost identical to that in eight normal control individuals (leading front distance of migrating neutrophils in 20-min period 81.3 +/- 7 microns in the patients compared to 79.4 +/- 4 microns in the control individuals). During the rh GM-CSF infusions there was a significant fall compared to controls in the number of neutrophils entering the membrane and the leading front distance (P less than 0.05). In four out of nine patient studies (eight patients) there was a greater than 30% fall from the pre-infusion level. In the control individuals the largest fall recorded was less than 10% and overall there was a progressive rise in the number of neutrophils entering the membrane throughout the period of study. This study suggests that intravenous infusion of rh GM-CSF may impair the ability of neutrophils to infiltrate an inflammatory focus.

Colony-Stimulating Factors↗
PubMed1972

Somatic cell genetic assignment of peptidase C and the Rh linkage group to chromosome A-1 in man.

The segregation of the human peptidase-C phenotype in five different series of human-mouse hybrid clones was examined. The chromosome constitution of these hybrids was determined by quinacrine mustard fluorescence, Giemsa banding, and constitutive heterochromatin staining. That the clones could be classified without exception either as human peptidase C positive/ A-1 positive (14 clones), or as peptidase C negative/ A-1 negative (12 clones) indicates that peptidase C can be assigned to the human A-i chromosome. Data from an extensive series of human-mouse clones used provide support for the syntenic association between peptidase C and phosphoglucomutase-1 and by inference a linkage of both to Rh factor group.

Animals↗
PubMed1993

Human recombinant GM-CSF selectively primes receptor mediated respiratory burst of neutrophils in vitro.

The influence of human recombinant granulocyte-macrophage colony-stimulating factor (rH GM-CSF) on respiratory burst response of isolated human neutrophils was examined. Preincubation of cells with rH GM-CSF significantly increased the respiratory burst in response to formyl-methionyl-leucyl-phenylalanine (FMLP), measured by luminol-dependent chemiluminescence (CL) assay. This priming effect of rH GM-CSF was independent of extracellular Ca2+ and Mg2+. On the other hand, the pretreatment of cells with rH GM-CSF could not enhance the neutrophil CL responses to unopsonized, serum complement-opsonized or immunoglobulin G (IgG)-opsonized zymosan particles. rH GM-CSF directly induced a weak CL signal in neutrophils. This signal, however, was abolished when extracellular Ca2+ and Mg2+ were removed. Exposure to rH GM-CSF caused a divalent cation-dependent up-regulation of complement receptors (CR1 and CR3) on neutrophil cell surface, while the expression of IgG Fc-receptors (FcRII and FcRIII) was not markedly changed by rH GM-CSF. The results indicate that rH GM-CSF primes FMLP-induced CL but not zymosan particle-induced respiratory burst in human neutrophils. It is hypothesized that the reason for the different sensitivity of FMLP-receptors and receptors to zymosan particles to rH GM-CSF priming may lie in differences in the signal-transduction pathways of these receptor types.

Calcium↗
PubMedDate not supplied

[Multi-profile analysis of survival rate and cause of death in patients with non-Hodgkin's lymphoma].

A relationship has been established between the survival rate of 378 patients who had died of non-Hodgkin's lymphoma (NHL) and their sex, age, ABO- and Rh-factors of the blood, primary focus of the tumor lesion, morphological variant, diagnostic period duration, and the treatment intensity. A higher incidence rate and a higher mean survival were recorded in 222 males, as compared to 156 females. Favourable and unfavourable for survival age interval has been distinguished for NHL disease. Patients with Rh+ showed a higher survival rate, although the incidence rate among Rh+ and Rh- subjects was similar. Prognostically favourable and unfavourable sites of the primary tumor and morphological variants of NHL were specified. The time spent for detailed verification of the diagnosis has been justified, and the presence of a direct proportional relationship between the intensity of the treatment and the mean survival of patients with varying forms of NHL has been proved.

Adolescent↗
PubMed1977

A survey of blood groups.

A survey was conducted to investigate into the frequency of different blood groups in Punjab. A total of 1415 persons were included in this survey. The slide method was used for determination of ABO and AB blood groups as well as Rh factor. The frequency of blood group A was 21.20%; B, 36.16%; AB, 9.05% and O, 34.14%. Distribution of blood groups among various castes revealed the incidence of blood group A, 13.57% to 30%; B, 28.125% to 50%; O, 16.67% to 40%; and AB, zero to 25%. Only 2.76% cases were found to be Rh negative. Rh negative frequency was much higher in Baluchs, Awans and Gujjars than Rajputs, Jats and Arains.

ABO Blood-Group System↗
PubMed1975

Prognostic factors in Hodgkin's disease.

The clinical records and treatment results of 163 patients with Hodgkin's disease, who were seen at Ellis Fischel State Cancer Hospital (EFSCH) between 1940 and 1971, were reviewed and analyzed. More than 200 clinical and histological variables were recorded for each case of Hodgkin's disease, including details of radiotherapy and chemotherapy. Statistical studies were carried out in order to evaluate the independent prognosis significance of each of these factors. All of the lesions were reclassified according to the Lukes proposal which was modified and recommended at the 1965 Rye classification (except for hepatomegaly which was included in Stage IV). This is a retrospective study, and the modern techniques of staging were rarely used in pretreatment studies (since 1965, only ten patients have had an abdominal exploration). The basic work-up consisted of a complete blood count, urinalysis, blood type, chest X ray, and EKG. Lymphangiogram and radioisotope liver scans were used on less than 10% of the patients. About 30% of the patients had gastrointestinal X rays and 70% had IVP. Bone marrow biopsies -- the majority of which were done by needle aspiration -- were obtained for approximatley 50% of the patients. Clinical stage, histological type, and presence of absence of systemic symptoms appeared to be themost significant prognostic factors. The classification of systemic symptoms according to the criteria of either the Rye or Ann Arbor conferences showed no particular difference in determining the survival rate. Among the systemic symptoms, fever appeared to be the most important for survival rate. Survival rates were higher in nonanemic and nonlymphocytopenic patients. Eosinophilia, blood group, and Rh factor had no prognostic significance. The relapse-free interval was an important indicator of long-term prognosis. The unfavorable influence of relapse in ultimate prognosis was clearly seen; however, the extent of the relapse site was shown to have no significant influence on survival.

Adolescent↗
PubMed1990

Effect of N-methionine-free, bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor in a primate model.

We demonstrate the in vivo effects of bacterially synthesized, N-methionine-free recombinant human granulocyte-macrophage colony stimulating factor (rh GM-CSF) using a crab-eating monkey model. Monkeys were treated with cyclophosphamide (60 mg/kg) and administered with rh GM-CSF (30 micrograms/kg/d) subcutaneously (s.c.) for 7 days. Within 12 h, a transient increase of neutrophils (greater than 15.0 x 10(9)/l) was observed, and complete recovery of WBC counts was obtained by d 9 (d 16 in control monkeys). Neutrophils and eosinophils were absolutely increased (greater than 8 x 10(9)/l) on d 10. Readministration of rh GM-CSF (30 micrograms/kg/d, s.c.) for 3 d (including control monkeys) revealed absolute increases of neutrophils, eosinophils, monocytes and platelets. A two-fold increase of granulocyte/macrophage colony-forming units was also seen in the bone marrow, while the number of burst-forming units-erythroid was not affected. These data indicate that rh GM-CSF of this type stimulates granulopoiesis and thrombopoiesis in vivo.

Animals↗
PubMed1987

Enhancement of neutrophil-mediated phagocytosis by human granulocyte-macrophage colony-stimulating factor demonstrated using a novel mathematical model.

A mathematical model is presented which may be applied to describe and analyse data from microscopic phagocytosis assays. The method has been used to investigate the phagocytosis of opsonized yeast by peripheral blood neutrophils treated with purified recombinant human granulocyte-macrophage colony-stimulating factor (rH GM-CSF) in vitro. Under limiting conditions of serum opsonization, rH GM-CSF decreased the proportion of non-phagocytic cells and increased the mean number of ingested yeast per cell. Stimulation of phagocytosis was dose-dependent and occurred with concentrations of rH GM-CSF in the range 10-320 units/ml. The effect was dependent on a heat-labile component in serum and was not attributable to endotoxin contamination of the preparation.

Colony-Stimulating Factors↗
PubMed1993

Effects of recombinant human granulocyte-macrophage colony stimulating factor on hematopoiesis in normal cynomolgus monkeys.

The in vivo efficacy of nonglycosylated recombinant human granulocyte-macrophage colony stimulating factor (rh GM-CSF) expressed in Escherichia coli was studied in cynomolgus monkeys (Macaca fascicularis). A single intravenous (IV) administration of rh GM-CSF (100 micrograms/kg) resulted in a two-fold increase in peripheral white blood cell (WBC) count with a predominance of neutrophils after 12 hr. The increased WBC count returned to the initial level within 48 hr after administration. In a study with consecutive IV administrations for 10 days, animals treated with 20 micrograms/kg/day rh GM-CSF underwent marked leukocytosis (four fold) and thrombocytosis (two fold). The increase in WBC count was due to increased number of neutrophils, eosinophils, lymphocytes, monocytes and basophils. Red blood cell count was unaffected. The leukocytosis resolved within one week after the termination of administration. A lower mean platelet volume compared to the pre-treatment level was observed in rh GM-CSF treated animals receiving 20 micrograms/kg/day for 20 days. This coincided with the elevation in platelet count.

Animals↗
PubMed1988

Phase I study of recombinant human granulocyte-macrophage colony-stimulating factor in patients with bone marrow failure and malignancy.

Twenty-five patients with malignancy and/or bone marrow failure were treated with recombinant human granulocyte macrophage colony-stimulating factor (rh GM-CSF) (specific activity 5 x 10(7) units/mg, purity greater than 95%) given by continuous intravenous infusion at various fixed dose levels (15-500 micrograms/m2/day), as part of a phase I study. Treatment was associated with marked increases in white blood cell counts (2-70 fold), consisting mainly of neutrophilic granulocytes. Significant increases were also observed in eosinophils, monocytes and lymphocytes. In addition six patients had multilineage responses characterized by increases in platelet counts (greater than 2 fold and greater than 100,000/mm3) and reticulocyte counts (greater than 2 fold). Three of these 6 patients did not require red cell or platelet transfusion for 17 to 37 weeks. Treatment also resulted in an increase in bone marrow cellularity and myeloid: erythroid cell ratio. The common side effects were constitutional symptoms and bone pain. These findings demonstrate that rh GM-CSF is well tolerated when given by continuous IV infusion and is a potent stimulator of hematopoiesis in vivo.

Bone Marrow↗
PubMed1987

Efficacy of recombinant human granulocyte-macrophage colony-stimulating factor in rhesus monkeys.

The glycosylated and the non-glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) expressed in Chinese hamster ovary cells and E. coli, respectively, were administered in rhesus monkeys either by the subcutaneous (three times daily) or intravenous route (6-hr infusions) for seven consecutive days. Within 24 hr peripheral white blood cells (WBC) increased 2-3 fold over normal values. Thereafter, the WBC increased steadily in a dose-dependent manner to reach maximum levels on the last day of or one day after the treatment period. The differential counts showed that neutrophils contributed to 50-80%, eosinophils to 10-20%, monocytes to 2-7%, and lymphocytes to 15-30% of the WBC rise. No effect was found on platelets and erythrocytes. After termination of treatment, WBC counts returned to normal levels within one week. Subcutaneously administered CSF was more effective in inducing leukocytosis than that injected intravenously In addition to the rise in WBC, the administered rh GM-CSF also enhanced the oxidative metabolism and bactericidal activity of the circulating mature granulocytes isolated from the blood of monkeys treated with rh GM-CSF. These results show that glycosylated or non-glycosylated rh GM-CSF is both an effective stimulator of leukocytosis and a potent activator of the functional activity of mature granulocytes in vivo.

Animals↗
PubMed1988

Functional properties of hemoglobin in human red cells: II. Determination of the Bohr effect.

Parameters of the Bohr effect (delta log P50/delta pHi) for human normal red blood cell suspensions have been calculated between intracellular pH (pHi) 5.5 and 8.5, in order to test how these quantities compare with those measured in dilute human hemoglobin solution (Hb). For a precise comparison between red cell and Hb solutions data, the cells were fractionated to reduce cellular heterogeneity and depleted of their 2,3-diphosphoglycerate (DPG) content. The P50 values were related to pHi. From the value of the Donnan equilibrium factor rH+ and the cellular water content at each extracellular pH (pHe), the variations of the intracellular chloride concentration were calculated. This quantity exhibited a three fold change between pHi 5.5 and 8.5, with extracellular chloride concentration [Cl-]e fixed at 140 mM. In the absence of DPG, chloride is the main allosteric effector of Hb and increases the alkaline Bohr effect. When all these interacting factors are accounted for, the oxygen affinity and Bohr parameters for red cell suspensions become identical to those observed for dilute Hb solutions. These results indicate that the hydration of the Hb molecules in the highly concentrated red cell milieu is not much different from that of nearly ideal solutions.

2,3-Diphosphoglycerate↗
PubMed1988

Phase I/II study of recombinant human granulocyte colony-stimulating factor in patients receiving intensive chemotherapy for small cell lung cancer.

Twelve patients with advanced small cell carcinoma of the bronchus were treated by continuous infusion of recombinant human granulocyte colony-stimulating factor (rh G-CSF) at the following dose levels: 1 microgram, 5 micrograms, 10 micrograms, 20 micrograms and 40 micrograms/kg/day for 5 days. No toxicities resulted from the treatment and in all 12 patients the number of peripheral neutrophils increased rapidly to a maximum of 100 x 10(9)/l in one patient at 10 micrograms/kg/day. The neutrophils were shown to be functionally normal in tests of their mobility and bactericidal activity. During the Phase II part of the patients were treated using a combination of i.v. Adriamycin, Ifosfamide and Etoposide. The chemotherapy was repeated every 3 weeks. rh G-CSF was given to each patient for 14 days on alternate cycles of chemotherapy and reduced the period of absolute neutropenia considerably (median of 80%), with a return to normal, or above normal, neutrophil counts within 2 weeks after day 1 of chemotherapy. Ten severe infective episodes were observed during the 20 cycles of chemotherapy which did not include rh G-CSF, while only one infective episode occurred in 20 courses when treated with rh G-CSF. These results demonstrate the utility of rh G-CSF in restoring functional neutrophils to patients undergoing intensive chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Donor factors in cadaveric renal transplantation.

1. Donor kidney side (left/right) had no significant effect on cadaveric renal allograft survival. 2. Kidneys from male donors had an 83% one-year graft survival rate, compared with 78% for those from female donors. 3. Donor race did not have an effect on renal allograft survival. 4. One-year survival rates for kidneys from very young (< 5 years old) donors and older (> 50 years old) cadaver donors (74%) were significantly poorer than those for kidneys from donors age 6-50 (84%). 5. Donor ABO blood type and Rh factor had no significant effect on renal allograft survival. 6. Cause of death (trauma/nontrauma) had a pronounced effect on cadaveric renal allograft survival. Kidneys from trauma donors (motor vehicle accident, gunshot wound, head injury, etc.) had a significantly higher one-year graft survival rate (84%) than that of kidneys from nontrauma donors (77%). This effect was found to be independent of donor age. 7. Donor past medical history had a significant effect on renal allograft survival. Kidneys from donors with histories of hypertension had slightly poorer graft survival (75%) than those from "normal" donors (80%). Donors with histories of diabetes had significantly lower graft survival; 54.8% at one-year posttransplant. 8. Donor lifestyle factors, including smoking, drinking, drug use, and sexual history, had no significant effect on renal allograft survival. 9. The duration of donor hospitalization (from admission to the time of procurement) had no effect on renal allograft survival. 10. Donor cardiac arrest (in either the field, hospital, or operating room) had no significant effect on renal allograft survival.(ABSTRACT TRUNCATED AT 250 WORDS)

ABO Blood-Group System↗
PubMed1992

[Use of anti-D (Rh) IgG or intramuscular polyvalent human immunoglobulin in the treatment of chronic autoimmune thrombocytopenic purpura].

The present study compares the effect of the intramuscular injection of low doses of IgG anti-D or human polyvalent immunoglobulin (Ig) on the platelet count of patients with CATP. Forty patients (14 children, 26 adults), 11 who had undergone splenectomy, were divided in the following groups of treatment: 20 patients received a single injection of 300 micrograms of IgG anti-D, 6 patients received the same dose as above plus 0.5 mg/kg daily of prednisone v.o and 14 patients received 640 mg of polyvalent Ig. Each patient was sequentially studied by measuring peripheral blood parameters, reticulocyte index, direct Coombs' test and C3-C4 determinations. Their blood group and Rh factor had been previously determined. The platelet response was evaluated as refractory (no response) and favorable (platelet increment over 50,000/microliters compared with initial platelet count). Patients with a favorable response over a month were considered as a prolonged remission. The results showed a favorable platelet response in 74% of the patients that received a single injection of IgG anti-D alone (one of the patients was Rh negative) or associated to prednisone, and 42.8% of the cases when polyvalent Ig was used. The patients who had not undergone splenectomy obtained better results than the group with splenectomy (62% vs 45%) and children showed a better response than adults (78.5% vs 46.1%). Forty five percent of prolonged remissions (including the Rh negative patient) were obtained with both schemes of IgG anti-D administration and only 28.5% when polyvalent Ig was used. The remissions were significantly longer with IgG anti-D (p < 0.01). The hematological and serological parameters did not show any significant modifications in all the cases and there was no adverse effects with the treatment. In conclusion, the intramuscular injection of immunoglobulins, especially IgG anti-D, produce an increase in the platelet count in some patients with CATP, several of them can obtain prolonged remissions, particularly children and patients that had not received immunoglobulins previously. This treatment is safe, ambulatory, easy to administer, and relatively inexpensive.

Adolescent↗
PubMed1999

Use of granulocyte colony-stimulating factor for treatment of aplastic anemia.

Over the last ten years, recombinant human granulocyte colony-stimulating factor (rh G-CSF) has been widely used in the treatment of aplastic anemia (AA). It has been shown to facilitate the recovery of neutrophil count and useful for complicated bacterial or fungal infections. However, recent randomized clinical trials showed that the addition of rh G-CSF to immunosuppressive therapy had no clinical benefit for the prophylaxis of severe infections. These results suggested that rh G-CSF should be used for the treatment of infectious complications, not for the prophylaxis of infections in patients with AA.

Anemia, Aplastic↗
PubMed1989

Dose escalation study of recombinant human granulocyte-colony-stimulating factor (KRN8601) in patients with advanced malignancy.

To evaluate the toxicity and efficacy of recombinant human granulocyte-colony-stimulating factor (rh G-CSF) administered with intensive chemotherapy, 39 patients with advanced pulmonary cancers were enrolled in a dose escalation trial of rh G-CSF. Three days after initiation of chemotherapy rh G-CSF was administered i.v. for 14 consecutive days at five dose levels (50-800 micrograms/m2). Absolute neutrophil counts showed a dose-dependent increase with an increasing dose of rh G-CSF and the durations of neutropenia (less than 1000/mm3) shortened significantly at doses of 200, 400, and 800 micrograms/m2 compared to those at 50 micrograms/m2 (P less than 0.01). The duration of neutropenia was shortened significantly at all five dose levels following treatment with rh G-CSF compared to treatment without rh G-CSF (P less than 0.05). Adverse side effects associated with rh G-CSF administration were fever higher than 38 degrees C (21%), chest pain, and low back pain (13%). No intolerable side effects were experienced. It can be concluded that rh G-CSF is effective in shortening the duration of neutropenia following intensive chemotherapy at a dose level of 100 to 200 micrograms/m2 i.v. a 400-micrograms/m2 dose of rh G-CSF is recommended in patients with prior treatment because of the possibility of a lower bone marrow response.

Adult↗
PubMed1997

The effects of recombinant human granulocyte-colony stimulating factor on vascular dysfunction and splanchnic ischaemia-reperfusion injury.

1. The aim of our study was to investigate the effects of recombinant human granulocyte-colony stimulating factor in a rat model of splanchnic ischaemia-reperfusion injury. 2. Male anaesthetized rats were subjected to clamping of the splanchnic arteries for 45 min. This surgical procedure resulted in an irreversible state of shock (splanchnic artery occlusion shock. SAO shock). Sham operated animals were used as controls. Survival rate, serum tumour necrosis factor-alpha (TNF-alpha), neutrophil count, bone marrow myeloid precursor cells, myeloperoxidase activity (MPO; studied as a quantitative means to assess leukocyte accumulation), mean arterial blood pressure and the responsiveness of aortic rings to phenylephrine (PE, 1 nM-10 microM) were studied. 3. SAO shocked rats had a decreased survival rate (0% at 4 h of reperfusion, while sham shocked rats survived more than 4 h), increased serum levels of TNF-alpha (201 +/- 10 u ml-1; sham shocked rats = undetectable), neutropenia, enhanced MPO activity in the ileum (0.11 +/- 0.06 u x 10(-3) g-1 tissue; sham shocked rats = 0.02 +/- 0.001 u x 10(-3) g-1 tissue) and in the lung (1.5 +/- 0.2 u x 10(-3) g-1 tissue; sham shocked rats = 0.19 +/- 0.05 u x 10(-3) g-1 tissue) and unchanged bone marrow myeloid precursor cells. Furthermore aortic rings from shocked rats showed a marked hyporeactivity to PE. 4. Administration of recombinant human granulocyte colony stimulating factor (rh G-CSF; 5, 10 and 20 micrograms kg-1 5 min following the release of occlusion) increased in a dose-dependent manner survival rate (90% at 4 h of reperfusion with the dose of 20 u x 10(-3) g kg-1), reduced serum TNF-alpha (13 +/- 5 u ml-1) and MPO activity in the ileum (0.065 +/- 0.002 u x 10(-3) g-1 tissue) and in the lung (0.7 +/- 0.03 microgram kg-1 tissue), improved neutropenia and mean arterial blood pressure but did not modify bone marrow myeloid progenitor cells. Furthermore rh G-CSF, either in vivo or in vitro (200 nM for 1 h in the organ bath), restored to control values the hyporeactivity to PE. Finally rh G-CSF potently inhibited the activity of inducible nitric oxide synthase in peritoneal macrophages activated with endotoxin. 5. Our results suggest that rh G-CSF protects against splanchnic ischaemia reperfusion injury by a mechanism(s) that does not depend upon its haematopoietic effects.

Animals↗