摘要:

We have been studying hematopoietic effects by the tachykinins, which like many other neuropeptides can be expressed in neural and nonneural tissues. Substance P (SP) and neurokinin-A (NK-A), members of the tachykinins are immune and hematopoietic modulators. SP and NK-A are derived from the preprotachykinin-I gene (PPT-I) through alternate splicing and posttranslational modification. In the bone marrow (BM), nerve fibers provide a source of neural SP and the stroma provides a source of nonneural SP. The tachykinins interact with each of three cloned neurokinin (NK) receptors (NK-1R, NK-2R, NK-3R) with SP and NK-A exhibiting binding preferences for NK-1R and NK-2R, respectively. Proliferation of myeloid progenitors (CFU-GM) is differentially regulated by SP and NK-A. The former enhances the proliferation whereas the latter is inhibitory. The BM stroma mediates most of the hematopoietic effects exerted by SP and NK-A partly through the induction of cytokines. The proliferative effects of SP correlate with the induction of positive hematopoietic growth factors such as IL-3, IL-6, GM-CSF and c-kit ligand and the inhibitory effects by NK-A correlate with the induction of two negative hematopoietic regulators, MlP-lα and TGF-β. Intracellular signals mediated by NK-1R and NK-2R are part of the mechanism responsible for tachykinin-mediated regulation of hematopoiesis. The stimulatory effects on BM progenitors mediated by NK-1R can be partly inhibited by NK-2R activation. IL-1 and other cytokines induced by SP in BM stroma modulate NK-1R induction. Furthermore, SP can induce IL-1 type I receptor in stroma. Together, these data suggest that the tachykinins and the cytokines interact to regulate hematopoiesis. These interactions contribute to hematopoietic regulation by mechanisms that involve induction of: (1) tachykinins and cytokines by each other; (2) NK-1R by cytokines and (3) cytokine receptor by the tachykinins. These studies emphasize that in terms of hematopoiesis, the cytokines and neuropeptides are not mutually exclusive factors and thus, the hematopoietic regulatory network would be incomplete without the role of neuropeptides being considere

ISSN:0001-5792    

DOI:10.1159/000203593

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

In this paper we investigated the lymphoproliferative and cytotoxic responses of peripheral blood mononuclear cells (PBMC) of patients affected with lymphoproliferative disease of granular lymphocytes of T cell origin to mitogens and antigens. Most patients with lymphoproliferative disease of granular lymphocytes (LDGL) showed a severely impaired PBMC proliferative capacity in response to phytohemagglutinin, anti-CD3 and tetanus toxoid, an impairment that, in the case of anti-CD 3 response, appears to be related to a defect of phosphorylation in response to triggering. In contrast, at least 50% of the patients had normal proliferation in response to a mannoprotein fraction purified from Candida albicans. These data suggest that some CD3+ GL from LDGL patients, that usually respond poorly to proliferative stimuli in vitro, can be triggered to perform these functions by candidal antigens.

ISSN:0001-5792    

DOI:10.1159/000203594

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The distribution of lymphocyte subsets in blood, thymus, spleen, mesenteric lymph nodes, Peyer’s patches and bone marrow was evaluated in an experimental model of secondary hemochromatosis in rats. The values of CD2, CD4, CD 8, B and NK cells in these different lymphoid compartments did not differ between the control group and the experimental group. These results suggest that the abnormalities of lymphocyte subsets previously reported in patients with secondary hemochromatosis may be due to factors other than iron overloa

ISSN:0001-5792    

DOI:10.1159/000203595

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

We determined the in vivo ability of infused human recombinant hemoglobin 1.1 (hr-Hb) and erythropoietin to rescue the hematopoietic activity from the suppressive effects of AZT in normal and in a murine model of AIDS (MAIDS) mice. Mice were fed with AZT for 8 weeks with or without treatment in the last 4 weeks by administering various concentrations of hr-Hb and/or erythropoietin (Epo). Blood parameters, body weight (BW) and erythroid burst-forming units (BFU-E) for all mice were determined. AZT-treated normal and MAIDS mice showed a significant decrease in hematocrit (64 and 78.1%), hemoglobin (27.2 and 45.5%), BW (17.5 and 35.5%), number of white (66.9 and 42.1 %) and red blood cells (65.5 and 38%), and the number of BFU-E (73 and 59%), whereas the AZT-treated normal and MAIDS mice that received hr-Hb (5 mg/kg BW/day) and/or Epo (2 U/mouse/day) showed significant alleviation of AZT cytotoxicity. This was evident by the recovery in all blood indices examined, the number of BFU-E and the BW of mice treated. BFU-E recovery in MAIDS (97%) was greater than that in normal mice (63%) as compared to their controls. hr-Hb produced a similar response as the combination, however recovery was slightly better with the latter in some hematological parameters. Higher concentrations of hr-Hb (10-15 mg) did not result in a more significant increase in most blood indices. Our results indicate that infusion with hr-Hb can alleviate AZT toxicity in normal and in immunodeficient mice, and that hr-Hb may be clinically useful in preventing severe bone marrow depression brought about by various drugs or agents such as AZT.

ISSN:0001-5792    

DOI:10.1159/000203596

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The variation of natural killer (NK) cell activity and lymphocyte subsets 20 h after a single test dose of α-IFN, was studied in 17 thalassemic patients with chronic hepatitis C. All patients had suspended the α-IFN therapy at least 12 months before the study: 10 were considered responders and 7 nonresponders. Also NK cell cytotoxicity after in vitro incubation with α-IFN was studied. The administration of a single dose of α-IFN increased NK cell cytotoxic activity significantly in the group of responders and in non-responders; moreover the NK cell cytotoxic activity after α-IFN in vitro incubation increased both in responders and nonresponders, but to a lesser degree than in healthy controls. Absolute values of CD4+ and CD8+ lymphocytes decreased significantly only in responders. In conclusion, our data suggest that the variation of NK cytotoxic activity and lymphocyte subsets after a test dose of α-IFN can be considered a parameter related to IFN biological ef

ISSN:0001-5792    

DOI:10.1159/000203603

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Some lymphotropic viruses such as Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) have been proposed as causative agents of B cell non-Hodgkin’s lymphoma (NHL). More recently, the presence of hepatitis C virus (HCV), which is both a hepatotropic and lymphotropic virus, has been reported in one third of B cell NHL patients. The aim of this study was to investigate in a series of B cell NHL the prevalence of three lymphotropic viruses, i.e. EBV, HHV-6 and HCV, in peripheral blood mononuclear cells (PBMC

ISSN:0001-5792    

DOI:10.1159/000203597

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

As an approach to characterizing the molecules involved in the hematopoietic microenvironment provided by a murine clonal preadipose cell line MC3T3-G2/PA6 (PA6), we developed a unique system to detect the early phase of signal transduction caused by the direct cell-to-cell interaction using the reporter plasmid pfosluc2 with the c-fos enhancer/promoter linked with the Photinus pyralis luciferase gene. The plasmid pfosluc2 was genetically introduced into a mouse myeloid leukemia cell line NFS-60 which showed a growth dependency on contact with PA6 cells, and the mechanism by which stromal PA6 cells promote the proliferation of NFS-60 cells through the direct cell-to-cell interaction was analyzed. The direct cell-to-cell interaction with PA6 cells was found to cause a significant c-fos induction to NFS-60 cells within 1 h. Approximately 105 cDNA clones prepared from PA6 cells were screened for their activity to promote the c-fos expression in NFS-60 cells through the direct cell-to-cell interaction, and 13 positive clones were obtained. Of these positive clones, five clones encoded the stem cell factor, and the others encoded the hepatocyte growth factor (HGF). The c-fos induction caused by the contact with PA6 cells in NFS-60 was completely inhibited by addition of both antagonistic anti-c-kit and anti-HGF antibodies. These results represent direct evidence for the action of HGF on the proliferation of hematopoietic cells through direct cell-to-cell interaction with stromal cells. Thus, our developed reporter system can be useful in investigating the direct cell-to-cell interaction between stromal and hematopoietic cells.

ISSN:0001-5792    

DOI:10.1159/000203598

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

We report 2 cases of plasma cell dyscrasia presenting with significantly elevated serum CA125 levels. The serum levels of CA125 from these patients correlated well with their serum M-protein levels. One patient had an IgG-κ type extramedullary plasmacytoma with the culture supernatant from lymph node plasma cells showing a considerably high level of CA125 activity. The serum IgG fraction purified using a protein A column was devoid of any detectable CA125 activity, negating that the serum IgG M-protein from this patient might respond with a false-positive result in the CA125 immunoradiometric assay. The other patient had an IgG-λ type plasma cell leukemia with the culture supernatant from peripheral mononuclear cells also showing a high level of CA125 activity. These observations may suggest that in plasma cell dyscrasias the CA125 antigen is spontaneously produced by tumor cell

ISSN:0001-5792    

DOI:10.1159/000203599

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

We report a case of transient abnormal myelopoiesis (TAM) with Down’s syndrome. As the blast cells had additional chromosome abnormalities (50, XY,+12,+14,+21 × 2), a possibility of acute leukemia was considered from a cytogenetic point of view. But the abnormal clone gradually disappeared without antileukemic therapies. Viewing it together with previous reports of TAM with additional chromosome abnormalities in Down’s syndrome babies, its presence does not immediately indicate an aggressive clinical course as in acute leukemia and spontaneous complete hematological remission may beachieved. Thus, a careful follow-up should precede cytogenetic findings helping to determine the therapeutic interven

ISSN:0001-5792    

DOI:10.1159/000203600

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

A 61-year-old male with Epstein syndrome and chronic renal failure was admitted to our institution for kidney transplantation. He was asymptomatic at the time of evaluation. Physical examination revealed pallor and marked splenomegaly measuring approximately 12 × 10 cm below the left costal margin. Because of this finding, and a history of resected non-small lung cancer, a CT scan of the abdomen was obtained. This demonstrated massive, diffusely nodular splenomegaly. This article describes the histopathologic and immunohistochemical findings of littoral cell angioma, a novel splenic tumor. Also, we discuss the differential diagnosis and include a description of the imaging study performed. To our knowledge, this is the first case report of littoral cell angioma occurring in a patient with Epstein syndrome, and the first radiographic appearance of this rare tumor

ISSN:0001-5792    

DOI:10.1159/000203601

出版商:S. Karger AG    

年代:1997

数据来源: Karger