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PubMed1991

Identification of colony-stimulating factor activity in patients with malignant tumors associated with excessive leukocytosis.

We have tried to demonstrate and identify colony-stimulating factor (CSF) activity in the plasma, pleural fluid, ascites or culture supernatant of tumor cells in 11 patients with malignant tumors associated with unexplained persistent leukocytosis. The specimens were treated with anti-granulocyte (G)-CSF or anti-granulocyte/macrophage (GM)-CSF monoclonal antibodies, then added to GM-progenitor (CFU-GM) cultures without exogenous CSFs. In all patients, untreated specimens generated CFU-GM-derived colonies, and colony formation was clearly inhibited by only one of the two antibodies, indicating the presence of either G-CSF or GM-CSF in the specimens. Furthermore, we measured the concentrations of G-CSF or GM-CSF in the specimens using an enzyme-linked immunosorbent assay, and confirmed the results by CFU-GM assay. Two patients were shown to have GM-CSF-producing tumors, while the other patients were G-CSF-producing. These assays are useful in identifying CSF activity in patients with CSF-producing tumors.

Aged↗

PubMed1991

Hepatocellular carcinoma presenting with pyrexia and leukocytosis: report of five cases.

In the past 26 years we have encountered five patients with primary liver malignancy clinically characterized by high remittent fever and leukocytosis mimicking liver abscess. Two patients underwent exploratory laparotomy, and drainage was carried out in another. The clinical courses went rapidly downhill. The liver was cirrhotic in two patients. The interior of the main mass was almost totally necrotic in four cases. Histologically, the malignant cells in the main portion resembled sarcoma, but in some areas cells appeared epithelial with eosinophilic cytoplasm and were in a trabecular arrangement, except for one case not subjected to autopsy in which histological study was inadequate because of extensive necrosis. It seems that these neoplasms were very poorly differentiated hepatocellular carcinomas rather than combinations of sarcoma and hepatocellular carcinoma. These patients, therefore, may represent a distinct clinicopathological type of hepatocellular carcinoma that is very rare in Japan but perhaps more common in South Africa, where similar cases have been clinically described in larger numbers.

Adult↗

PubMed1990

[Rheological analysis of suppressed leukocytosis in patients with pregnancy induced hypertension (PIH)].

It is documented that the number of leukocytes in peripheral blood increases considerably during pregnancy. We observed that the range of leukocytosis differs in normal pregnancy differs from that in cases with severe pregnancy induced hypertension (PIH). The data obtained in our university hospital, for example, give the number of leukocytes after twenty-four weeks of gestation as 9,000 +/- 1,600/mm3 (mean +/- SD) for normal cases (93 measurements in 37 cases) and 6,600 +/- 1,100/mm3 for PIH (72 measurements in 18 cases; p less than 0.001). To elucidate the cause and relation to PIH, we studied changes in the activity of leukocytes during pregnancy by means of a modified Nuclepore filtration method (Kikuchi et al., 1983). The time required for leukocytes to squeeze through filter pores under constant suction varies greatly depending on their active states; more active cells show greater resistance to pore passage, which can be clearly shown by exposing cells to various stimuli. The filtration time for 0.5ml blood containing 5,000/mm3 leukocytes minus that of leukocyte poor blood with the same hematocrit was taken as an index of the activity, which we called the rheological activity of leukocytes (RAL). RAL values for blood taken at delivery were 3.4 +/- 1.5 sec for normal cases and 5.0 +/- 2.1 sec for PIH (N.S.). RAL values obtained after the addition of a chemotactic stimulant FMLP (formyl-methionyl-leucyl-phenylalanine) (10nM) to the same samples were 21 +/- 10 sec for normal cases and 405 +/- 265 sec for PIH (p less than 0.001). Leukocyte activity, particularly, response to chemotactic stimulation, was the before thought to be considerably increased in PIH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

Ranitidine and leukocytosis.

Ranitidine has been used extensively in a variety of gastrointestinal illnesses. To date only scattered reports of hematological side effects have appeared in the literature. We present a case report of leukocytosis and eosinophilia occurring in a patient receiving ranitidine therapy.

Adult↗

PubMed1985

Neutrophilic leukocytosis associated with metastatic fibrosarcoma in a dog.

A 3 1/2-year-old dog with extensive tumor metastases to the lungs was found to have neutrophilic leukocytosis termed a leukemoid reaction. The term leukemoid reaction describes an absolute increase in the blood leukocyte concentration without regard to a predominant cell type or to the degree of cell immaturity. These types of reactions are extremely difficult to differentiate from leukemia. Leukemoid reactions can be acute or chronic and they may have an infectious, inflammatory, toxic, or neoplastic origin. Those reactions attributable to neoplasia have been documented in medical literature, but the mechanism causing the granulocytosis has not always been clearly understood. A granulopoietin capable of stimulating a leukemoid reaction may be elaborated by certain types of tumors, tumors with extensive metastasis, or tumors involving the lungs, liver, or stomach.

Animals↗

PubMedDate not supplied

Secondary amyloidosis and the serum amyloid precursor in leprosy: geographical variation and association with leukocytosis.

The prevalence of the amyloid-related serum component, protein SAA, was investigated in two groups of leprosy patients from different areas of Papua New Guinea. Protein SAA was more prevalent in coastal leprosy patients (49% positive) than in highland patients (21% positive). Paradoxically, many more cases of amyloidosis were diagnosed in the highland group (17 of 199) than in the coastal group (3 of 112). In the highland patient group, SAA was found to correlate with the leprosy disease spectrum, being more prevalent in patients toward the lepromatous pole. Borderline and tuberculoid patients who had detectable SAA usually had neurotrophic ulcers. No such relationships were observed in the coastal patient group, probably because other infections, more common on the coast, were also responsible for causing increased concentrations of SAA which is known to behave as an acute phase reactant. A correlation was observed between SAA positivity and neutrophil leukocytosis. This suggests that various inflammatory stimuli such as erythema nodosum leprosum reactions, neurotrophic ulcers and intercurrent infections, all contribute to the prevalence of SAA in leprosy patients.

Amyloid↗

PubMed1977

Leukocytosis and artifactual hypoglycemia.

Two patients are described with asymptomatic low blood glucose and excessive in vitro consumption of glucose by leukocytes before separation of the serum for assay. This may be a more common problem than is appreciated and need not be associated with leukemia or extreme leukocytosis. The circumstances that allow this avoidable type of artifactual hypoglycemia may also produce factitious euglycemia during evaluation of suspected diabetes mellitus.

Blood Glucose↗

PubMed1984

Stimulation of human and murine bone marrow cell colony formation by colony-stimulating factors obtained from the urine of mice bearing leukocytosis-inducing fibrosarcoma.

Dialyzed urine of mice bearing leukocytosis-inducing fibrosarcoma stimulated granulocyte colony formation in semisolid agar culture of human bone marrow cells. Removal of phagocytic cells prior to stimulation did not interfere with the formation of these colonies in the culture. On the other hand, macrophage colonies were predominantly produced when murine bone marrow cells were stimulated by the dialyzed mouse urine. The activity of colony-stimulating factor (CSF) in the urine of normal mice was less than 1/100 of that in the urine of tumor-bearing mice. DEAE-cellulose column chromatography separated the activity stimulating human granulocyte colony formation from that stimulating murine macrophage colony formation. Further purification showed that a sialoglycoprotein with an apparent molecular weight of 80,000 corresponded to the macrophage CSF, which was devoid of activity toward human cells. The molecular properties of the human-active granulocyte CSF could not be studied further, because it was quite unstable.

Animals↗

PubMed1983

Effect of Bordetella pertussis leukocytosis (lymphocytosis)-promoting factor (LPF) on the physical lymphoepithelial-cell association studied with the use of an in vitro model of mouse thymus.

The effect of highly purified leukocytosis (lymphocytosis)-promoting factor (LPF) of Bordetella pertussis on physical lymphocyte and reticuloepithelial (RE) cell association was studied in an in vitro thymus model. First, a simplified in vitro system to assess the lympho-RE-cell association was developed. A completely confluent layer of thymic RE cells was formed by cultivating trypsinized thymus cell suspensions from 2- to 7-day-old mice. When thymic lymphoid cells were seeded on this cell layer and cultivated overnight, a significant proportion of them were found underneath the RE cell layer. This physical lympho-RE-cell association was quantitated by counting the lymphoid cells underneath the RE cell layers. Second, the effect of LPF on this physical lympho-RE-cell association phenomenon was investigated. Addition of LPF to the culture markedly inhibited the formation of the lympho-RE-cell complex; that is, it inhibited the infiltration of lymphoid cells under the RE cell layer. LPF rendered a nearly maximal level of inhibitory effect at a dose of 0.1 ng/ml. Furthermore, LPF enhanced the liberation of lymphoid cells from preformed lympho-RE-cell complexes. On the other hand, LPF had no direct cytotoxic effect on lymphoid cells at doses below 1 microgram/ml. In order to investigate whether LPF produced the effect by acting on lymphoid cells, RE cells, or both, the following experiments were performed. When lymphoid cells were pretreated with LPF and added to normal RE cell layers, the lympho-RE-cell association was maximally inhibited above the dose of 1 ng/ml. Treatment of these LPF-treated lymphoid cells with anti-LPF antibodies failed to abrogate the effect of LPF. When RE cell layers were similarly pretreated with LPF and were cultivated with normal lymphoid cells, however, much higher doses of LPF, above 100 ng/ml, were required for maximal inhibition. Furthermore, treatment of these LPF-treated RE cells with anti-LPF antibodies abrogated the effect of LPF. Therefore, the apparent effect of LPF on RE cells was considered to be due to the carry-over by RE cells of LPF, which should directly act on lymphoid cells at extremely low doses. On the basis of these results, it was concluded that LPF acted directly on lymphoid cells without mediation of RE cells. These in vitro results appear to parallel the effects of LPF in vivo, where it induces a depletion of cells in the thymus. The model may be useful to study this phenomenon and the concomitant accumulation of blood lymphocytes.

Animals↗

PubMed1982

Granulopoietic inhibitors excreted in the urine of a patient with uterine cancer and marked leukocytosis.

An inhibitor of colony stimulating factor (CSF) was found in normal human urine and in the urine of a patient with uterine cancer and leukocytosis. The amount of inhibitor excreted in the patient's urine was inversely related to the amount of CSF excreted. Since the patient's urine contained the inhibitor in large amounts, it was used for further characterization of the inhibitor. The inhibitor was separated from CSF by DEAE-cellulose column chromatography, and precipitated by ammonium sulfate and 30-80% saturation. The result of centrifugation of the inhibitor in a NaBr solution of d = 1.21 and extraction of its solution by chloroform suggested that it is not a lipoprotein. Furthermore, it was inactivated by heating at 60 degree C. Isoelectrofocusing resolved in into two peaks of pI 6.7-8.4 (pI-7 inhibitor) and pI 4.7-5.4 (pI-5 inhibitor), both of which showed an apparent molecular weight of 80,000-90,000 upon Sephadex G-100 chromatography. Dose-response relation for CSF in the presence of the inhibitor(s) showed that the action of the inhibitor(s) was not due to specific inactivation of CSF. Both pI-05 and pI-7 inhibitor fractions showed mitogenic activity to mouse spleen cells in culture, and only slightly inhibited [3H]thymidine uptake in the PHA or LPS stimulated spleen lymphocytes. The result suggests that the granulopoietic inhibitor(s) obtained above is not a non-specifically cytotoxic substance(s).

Aged↗

PubMed1996

[Chronic myelomonocytic leukemia with repeated respiratory failure associated with leukocytosis following splenic arterial embolization and splenectomy].

A 32-year-old female was admitted due to splenomegaly and leukocytosis in September, 1993. The leukocyte count was 26,900/microliter with 29% monocytes (7,800/microliter). A diagnosis of the chronic phase of chronic myelomonocytic leukemia was made. On November 19, 1993, splenic arterial embolization was performed. After the embolization, the leukocyte count rapidly increased, and acute respiratory failure developed. The respiratory condition was improved by methylprednisolone (m-PRED) pulse therapy. Subsequently, the effectiveness of chemotherapy gradually decreased, and there was an increase in the leukocyte count. Respiratory failure developed again but was successfully treated with m-PRED pulse therapy in addition to aclarubicin. On July 4, 1995, splenectomy was performed. The leukocyte count rapidly increased, and acute respiratory failure again developed. She did not respond to m-PRED pulse therapy, but the respiratory condition was markedly improved by leukoplasmapheresis. The respiratory failure in this patient may be associated with capillary leak syndrome due to neutrophilia. In addition, stasis of increased monocytes in the pulmonary capillaries and their infiltration into the pulmonary parenchyma and alveoli was thought to have occurred.

Adult↗

PubMed1997

Evaluation of leukocytosis, bacteremia, and portal vein partial oxygen tension in clinically normal dogs and dogs with portosystemic shunts.

OBJECTIVE: To assess the relationship of WBC counts and partial oxygen tension in the portal vein and caudal vena cava with portal bacteremia, bacteria in the liver, and postoperative morbidity and mortality in dogs with portosystemic shunts. DESIGN: Prospective study. ANIMALS: 12 clinically normal dogs and 15 dogs with single congenital portosystemic shunts. PROCEDURE: Blood was collected from the portal vein and caudal vena cava for aerobic and anaerobic bacterial culture, WBC count, and measurement of partial oxygen tension. Samples of liver tissue, indwelling catheters, and fluids administered IV were also obtained for bacterial culture. RESULTS: Bacteria were cultured from samples obtained from the portal vein and caudal vena cava of 1 dog with a shunt and from the caudal vena cava of 1 clinically normal dog; neither dog had postoperative complications. In dogs with shunts and in clinically normal dogs, partial oxygen tension in the portal vein was significantly greater than that in the caudal vena cava. Postoperative complications were identified in 33% of dogs with shunts. Partial oxygen tensions of dogs with shunts with postoperative complications did not significantly differ from those of all dogs with shunts or dogs with shunts without complications. Significant differences in WBC counts were not found when comparing dogs with shunts with and without complications. Anaerobic bacteria were not cultured from the liver of any dog. CLINICAL IMPLICATIONS: Leukocytosis, portal bacteremia, and portal hypoxemia were not notable findings in dogs with shunts and were not correlated with postoperative morbidity or mortality.

Animals↗

PubMed1996

[G-CSF and all-trans retinoic acid-induced leukocytosis].

During the treatment with all-trans retinoic acid (ATRA) for acute promyelocytic leukemia (APL), leukocytosis occured in 33%-75% of the treated cases. ELISA method was used in detecting levels of serum granulocyle colony-stimulating factor (G-CSF) in 47 cases of APL during treatment with ATRA. It was found that the peak of increased serum G-CSF level occurred on the 9th day, and WBC number was highest on the 11th day. After ATRA treatment, both serum G-CSF level and WBC number increased in 68.1% of the cases. In 19.2% of the cases treated, serum G-CSF level was increased but without obvious change in WBC number, and the reverse was true in 12.7% of the cases. Serum G-CSF level was statistically correlated to the number of WBC, promyelocytes and its late stage by Spearman rank correlation analysis.

Adolescent↗

PubMed2002

"Cecal gangrene": a rare cause of right-sided inferior abdominal quadrant pain, fever, and leukocytosis.

We report on a 58-year-old man with known diabetes, congestive heart failure, and need for chronic hemodialysis presenting with right lower abdominal quadrant pain, fever, and leukocytosis. Although initial clinical findings were highly suggestive of acute appendicitis, CT revealed marked circumferential wall thickening of the cecum, which was interpreted as cecal infarction by the radiologist. Intraoperatively, cecal necrosis was confirmed, but the ileocecal valve and, especially, the appendix showed no ischemia. No vascular occlusions were found. Histopathologic analysis of the resected cecum demonstrated isolated transmural cecal necrosis with marked infiltration of the cecal wall by numerous bacteria and neutrophils. We present the CT features and histopathologic findings of isolated cecal gangrene, review the pathogenesis of occlusive and nonocclusive cecal ischemia or infarction, and discuss the role of bacterial superinfection as a potential cofactor in the pathogenesis of isolated cecal necrosis which should be included in the differential diagnosis of right-sided inferior abdominal quadrant pain.

Journal Article↗

PubMed1995

Effects of defibrotide on leukocytosis in rabbits with diet-induced atherosclerosis.

The antithrombotic drug Defibrotide (DFT) (a polydeoxyribonucleotide with a mean MW of 20,000 Daltons) reduces the number of leukocytes and platelets in thrombi. Because leukocytes and platelets are of importance in the genesis of endothelial lesions leading to atherosclerosis, DFT was given to challenge leukocytosis in rabbits with diet-induced atherosclerosis (0.25% cholesterol for 16 weeks). After 9 weeks of cholesterol feeding and at the end of experiment, oral DFT (60 mg/Kg per day) had decreased the leukocyte count raised by the cholesterol diet. Leukocyte stickiness and leukocyte differential counts were not modified by either oral cholesterol or by oral cholesterol plus oral DFT. At the end of experiment, oral DFT had normalized the platelet count increased by cholesterol diet. The red blood cell count decreased by oral cholesterol at 9 weeks and at the end of experiment was normalized by DFT. The % of aortae endothelial surface involved in the atherosclerotic process was decreased by oral DFT. The frequencies of intimal thickening in blood vessels of kidneys and hearts and in cardiac valves were reduced by oral DFT by 47%, 29% and 17%, although these reductions were not statistically significant. It is suggested that DFT, by preventing the increase in the number of leukocytes and platelets and deactivating them, as demonstrated in papers already published, was able to counteract against the atherosclerotic process.

Animals↗

PubMed2002

Leukocytosis and hypoalbuminemia in mixed bipolar states: evidence for immune activation.

OBJECTIVE: Although activation of an immune response during major depressive episodes has been reported, less is known about changes during manic and mixed bipolar episodes. METHOD: Albumin and leukocyte levels were compared between subjects in manic and mixed bipolar episodes. Neutrophil, lymphocyte and monocyte levels were compared between the two groups. RESULTS: Albumin levels were lower in mixed manic subjects as opposed to pure manic subjects and in the combined groups levels were lower in females than in males. Leukocyte levels were higher in mixed manic patients compare with pure manic patients. Both neutrophil and monocyte levels were higher in the mixed manic patients but lymphocyte levels were no different. CONCLUSION: Leukocytosis and hypoalbuminemia during mixed manic states suggest immune activation in mixed mania similar to depression. This finding also tends to support the recognition of mixed mania as a distinct bipolar state.

Albumins↗

PubMed2002

Physiological leukocytosis during pregnancy is associated with changes in glucose transporter expression of maternal peripheral blood granulocytes and monocytes.

PROBLEM: The scarce data on glucose transporter expression of leukocytes are contradictory and nothing is known about changes accompanying physiological leukocytosis during pregnancy, which imposes acute metabolic demands on the cells. METHOD OF STUDY: Cytospin preparations of intravascular leukocytes were searched immunocytochemically for the high affinity glucose transporters GLUT1, 3 and 4. Pregnancy-associated quantitative changes in transporter expression were assessed by flow cytometry. RESULTS: Granulocytes and monocytes stained for GLUT1, 3 and 4. Major changes in cell surface transporter expression during pregnancy were a 36% (P < 0.05) down-regulation of granulocyte GLUT1 at term, and an increase in monocyte GLUT3 levels to 137% (P < 0.05), paralleled by a 24% (P < 0.05) decrease in GLUT4 content in second trimester. Apart from a minor subpopulation, lymphocytes were negative for these carriers. CONCLUSION: GLUT1, 3 and 4 are abundantly expressed in granulocytes and monocytes. The particular isoforms are differentially regulated during pregnancy, suggesting an individual functional significance.

Female↗

PubMed1982

Erythrocytosis and marked leukocytosis in overlapping myeloproliferative diseases.

We describe two patients who had similar features of erythrocytosis and marked leukocytosis but who were subsequently classified as having chronic myelogenous leukemia and polycythemia vera, respectively, using leukocyte alkaline phosphatase scores and cytogenetic studies to detect the Philadelphia chromosome. The patient diagnosed as having polycythemia vera had a leukocyte count of 164,000/cu mm, which remained at similar levels when the patient was not in remission. We believe this is the first well documented case of PV with a leukocyte count above 150,000/cu mm.

Adult↗