Cytokine Gene Polymorphisms in Turkish Patients with Childhood Chronic Myeloid Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4368-4368
Author(s):  
Kursat Ozdilli ◽  
Fatma Oguz ◽  
Yeliz Duvarci ◽  
Hulya Bilgen ◽  
Sema Anak ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
The Other ◽  
Fine Tuning ◽  
Control Group ◽  
Cytokine Gene ◽  
Chi Square ◽  
Other Hand ◽  
Genotype Frequencies

Abstract Cytokines are necessary for normal hematopoiesis in the bone marrow and provide a means of fine-tuning bone marrow function in response to stimulation. Several of cytokines generated during both innate and adaptive immune responses stimulate the growth and differantiation of bone marrow progenitor cells. The vast majority of polymorphism found in cytokine genes and their reseptors are located in non coding regions. Cytokine gene polymorphism may be implicated in the pathogenesis of infections, autoimmun disease and malignancies via their effect on cytokine production and regulation. It is known that leukemic cells proliferate under the influence of cytokines. Our aim is to analyze cytokine gene profiles in patients with chronic myeloid leukemia (CML)in order to clarify the pathogenesis of CML. Genomic DNA from 26 CML patients were analysed. Genotyping was performed by polymerase chain reaction with sequence specific primers (PCR-SSP) using “ One lamda” kit in 26 childhood CML patients 60 unrelated healthy individuals. Genotype frequencies between CML patients and controls were compared using Chi-Square Yates, Fisher’s Exact Tests. In this study; 26 CML patients with a mean age of 15,6±5,3 and 60 healthy controls with a mean age of 18,2±5,4 were investigated. In CML patients the frequencies of TGF-b(TC/GG) genotype (in chi-square p=0,01,odds ratio(OR)=3,46, 95% confidence interval (CI) 1,3–9,04) and IL-10 (GCC/ATA) genotype (in chi-square p=0,04,OR=3,3, 95% CI 0,9–11,1 were found higher in patients with CML compared to the control group. On the other hand IL-6 (CC) genotype (in chi-square p=0,012,OR=0,17, 95% CI 0,4–0,76 frequency was found higher in the control group compared to the patients with CML. As a conclusion higher frequency in TGF-b(TC/GG) and IL-10(GCC/ATA) genotype polymorphism were significantly higher in the patients with CML so it may predispose to CML. On the other hand IL-6 (CC) genotype might be the preventive factor for CML. The present study is rather significant that it is the study which assessed the relation of the cytokines in patients with CML compared to the control group taken from the genetic pool of The Turkish population, we believe studies like this will eventually help to understand the pathogenesis of CML and the role cytokines play in CML,but larger groups of studies must be done in future.

Cytokine Gene Polymorphisms in Turkish Patients with Childhood Acute Lymphoblastic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4441-4441
Author(s):  
Kursat Ozdilli ◽  
Fatma Oguz ◽  
Hulya Bilgen ◽  
Yeliz Duvarci ◽  
Halim Issever ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Odds Ratio ◽  
Lymphoblastic Leukemia ◽  
The Other ◽  
Control Group ◽  
Target Cells ◽  
Cytokine Gene ◽  
Chi Square ◽  
Other Hand ◽  
Ifn Γ

Abstract Cytokines are chemical mediators between cells and they bind on their own specific receptors on the target cells. Cytokine gene polymorphism may be implicated in the pathogenesis of infections autoimmun disease and malignancies via their effect on cytokine production and regulation. Leukemic cells proliferate under the influence of cytokines. It is known that acute lymphoblastic leukemia (ALL) which is sensitive to some cytokine gene is one of the hematological malignances derived from lymphoid tissue. Our aim is to determined frequencies of selected cytokines (TNF-α, TGF-β, IL-10, IL-6, IFN-γ) in childhood ALL patients and unrelated healthy control groups. We also investigated weather these polymorphism might contribute to the pathogenesis of ALL. Method: Genotyping was performed by polymerase chain reaction with sequence specific primers (PCR-SSP) using “ One lamda” kit in 44 ALL patients and 50 unrelated healthy individuals. Allelic frequencies were determined 24 polymorphism located within 16 cytokine genes. Genotype frequencies between ALL patients and controls were compared using Chi-Square Yates, Fisher’s Exact Tests and Stepwise Logistic Regression Analysis (SLRA). Results: The frequency of TGF-β(TT/GG) allel (29,5% versus 8%, respectively;in chi-square p=0,007,odds ratio=4,82, 95% confidence interval (CI) 1,49–16,16; in SLRA p=0,002, OR=15,26,95% CI 2,77–84,05), TGF-β(TC/GG) allel (36,4% versus 10%, respectively; in chi-square p=0,002,odds ratio=5,14, 95% CI 1,69–15,59; in SLRA p=0,005,OR=10,21, 95% CI 2,02–51,61), IL-6(GC) allel (38,6% versus 8%, respectively; in chi-square p<0,001; odds ratio 7,24; 95% CI 2,20–23,76; in SLRA p=0,02,OR=6,37, 95% CI 1,22–33,15), IL-10(GCC/ATA) allel (36,4% versus 8%, respectively; in chi-square p=0,001, odds ratio 6,57, 95% CI 1,99–21,64; in SLRA p=0,01,OR=8,04, 95% CI 1,40–46,04), IFN-γ(TA) allel (54,5% versus 10%, respectively; in chi-square p<0,001, odds ratio 10,8, 95% CI 3,60–32,40; in SLRA p<0,001,OR=29,43, 95% CI 5,47–158,35) frequencies were found higher in patients with ALL compared to the control group. On the other hand IFN-γ(TT) allel (20% versus 48%, respectively; p=0,005; odds ratio 0,27; 95% CI 0,11–0,70), IFN-γ(AT)(0% versus 22%, respectively; p=0,001; odds ratio 1,28; 95%CI 1,10–1,48; fisher’s exact=0,001) and IL-6(CA)(0% versus 22%, respectively; in chi-square p<0,001; odds ratio 1,28; 95% CI 1,10–1,28; fisher’s exact=0,001) allel frequencies were found higher in the control group compared to the patients with ALL.TNF-α(GG) allel frequency was higher both in patients with ALL and in the control group (72% versus 85%). As a conclusion higher frequency in TGF-b(TT/GG),TGF-b(TC/GG),IL-6(GC), IL-10(GCC/ATA) and IFN-g(TA) allels may predispose to ALL.On the other hand IFN-g(TT), IFN-g(AT) and IL-6(CA) allels might be the preventive factor for ALL The present study is rather significant that it is the study which assessed the relation of the cytokines in patients with ALL compared to the control group taken from the genetic pool of The Turkish population but larger groups of studies must be done in future.

scholarly journals Studying the Impact of Presence of Alpha Acid Glycoprotein and Protein Glycoprotein in Chronic Myeloid Leukemia Patients Treated with Imatinib Mesylate in State of Qatar

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4846-4846
Author(s):  
Nader I Al-Dewik ◽  
Andrew Jewell ◽  
Mohamed A. Yassin ◽  
Hisham Morsi
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
The Other ◽  
Control Group ◽  
Acid Glycoprotein ◽  
Other Hand ◽  
Significant Difference ◽  
Blast Cells ◽  
The Mean

Abstract Background Despite the efficacy of Imatinib Mesylate (IM) in treating Chronic Myeloid Leukemia (CML), a high degree of resistance has already been noted. Alpha acid glycoprotein (AGP) may reduce drug efficacy through its ability to interact with IM and blocks it from reaching its target while Protein glycoprotein (PGP) may reduce the intracellular concentration of the drug via an active pump mechanism. In our cohort of patients with the highest rate of resistance to IM globally, we investigated if the level of AGP and PGP could be correlated with CML resistance/response to IM? and if so, could they be employed as biological markers for CML resistance to treatment? Methods To answer these questions, the 26 CML patients who were enrolled into our previous study between November 2006 and December 2011 were investigated for AGP and PGP levels at diagnosis and during treatment. Serum samples were analyzed to determine AGP level via an Immunoturbidimetric assay and up-regulation of PGP level was determined via Flow cytometry analysis of Peripheral Blood (PB) and Bone Marrow (BM) samples. Results A total of 100 serum, 40 BM & 100 PB samples were collected from the 26 CML patients (22 CP & 4 AP) treated at the National Center for Cancer Care and Research (NCCCR) in Qatar. Samples from 10 healthy volunteers were collected as a control. AGP results At Diagnosis 11/22 CP patients had elevated AGP (mean 1.5 ±0.11 g/l) while 3/4 AP patients had elevated AGP (mean 1.8 ±0.3 g/l). During follow-up The mean AGP values among the 14/26 patients who failed IM treatment were (1.05 ±0.09 g/l) while the values for the 12 patients who responded to the treatment were not significantly different (1.1 ±0.06 g/l) (p =) > 0.05. The 10/14 resistant patients who were previously reported to have mutations/Additional Chromosomal Abnormalities (ACAs) as underlying mechanisms of resistance, showed a mean AGP level of 1.06 (±0. 09) while the 4/14 patients with no mutations/ACAs showed no significant difference (AGP leve1.04 ±0.08) (p =) > 0.05. The mean value of the 10 healthy individuals who were enrolled as a control group was 0.71 ±0.04 g/l. The mean AGP levels were 1.2 (±0.12), 1.61 (±0.38), 1.05 (±0.09), 1.1 (±0.06), and 0.71(±0.04) g/l for 22/26 CP, 4/26 AP, 14/26 failed treatment, 12/26 optimal responders and controls respectively and the differences between patients groups and the control group on other hand were significant (p) 0.001, 0.03, 0.003, and 0.005 respectively. There was no a significant difference or correlation between AGP levels amongst the different groups of patients and there was no significant correlation between AGP and other biomarkers such as Platelets (PLTs), White Blood Cells (WBCs), Absolute Basophils (Abs. Baso) and Lactate Dehydrogenase (LDH) of CML patients in the responders group. However, the group who failed treatment showed a strong correlation between elevated AGP and LDH (p = 0.0001), WBCs (p=0.002) and Abs. Baso (p=0.03) PGP results On the other hand, the mean PGP level was 1.25 (±0.06), 1.17 (±0.02), 1.21 (±0.03), 1.2 (±0.04) for AP, CP, responders and resistant patients respectively. Flow cytometric analysis showed no significant difference in the fluorescence intensities of the blast cells incubated with CD 243 and the blast cells incubated with isotypic control among the different groups of patients. Discussion and Conclusion With a significant difference in AGP levels between patients and controls in our cohort of CML cases, combining AGP with others markers showed significant correlations during different disease stages that may be employed as a warning sign for resistance of CML to Tyrosine Kinase Inhibitors (TKIs). PGP expression, on the other hand did not differ in patients presenting in chronic phase or accelerated phase and showed no specific pattern for those who resist or respond to IM treatment. However, neither AGP nor PGP could be employed as an independent marker for disease progression as the noticed resistance in our CML patients could not be correlated to AGP or PGP levels and regardless of response or resistance to treatment, there was no significant pattern of AGP or PGP expression. Disclosures Al-Dewik: Qatar National Research Fund (QNRF): Other: sponsorship.

scholarly journals Depletion of Neoplastic CD11b Positive Cells in Jak2V617F Mutant Mice Reduced Fibrocytes in Bone Marrow and Improved Myelofibrosis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 310-310
Author(s):  
Yoshinori Ozono ◽  
Kotaro Shide ◽  
Takuro Kameda ◽  
Ayako Kamiunten ◽  
Yuki Tahira ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Blood Cells ◽  
Diphtheria Toxin ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasms ◽  
The Other ◽  
Immunofluorescent Staining ◽  
Control Group ◽  
Other Hand

Myelofibrosis (MF) associated with myeloproliferative neoplasms (MPN) has been considered to be a reactive phenomenon caused by mesenchymal stromal cells (MSCs) stimulated by cytokines such as TGFb-1 overproduced by neoplastic megakaryocytes (MKs) and platelets. TGFb-1 stimulates non-neoplastic mesenchymal cells to produce collagen and fibronectin and to induces bone marrow (BM) fibrosis. However, the involvement of neoplastic fibrocyte in MF has recently been reported (Verstovsek et al. JEM 2016), and among blood cells, monocytes in particular are considered to be the main source of neoplastic fibrocytes. In this study, we assesed the role of neoplastic fibrocytes using a mouse model of MPN induced by Jak2V617F (Shide et al. Leukemia 2008). First, the distribution of neoplastic fibrocyte in the BM of Jak2V617F transgenic (TG) mice was examined. We transplanted wild-type (WT) or Jak2V617F TG cells (B6-CD45.2), together with WT BM cells (B6-CD45.1) into irradiated WT recipient mice (B6-CD45.1). Only recipient mice transplanted with a mixture of Jak2V617F cells and WT cells developed BM fibrosis. In immunofluorescent staining of fibrotic BM, cells expressing the fibrocyte marker CD45/Collagen-1(Col-1) were observed much more than cells expressing the fibroblast marker CD90(usually positive for MSCs)/Col-1. As for CD45/Col-1 positive cells, cells expressing CD45.2/Col-1 were much more than cells expressing CD45.1/Col-1, clearly indicating that these cells were derived from Jak2V617F mutant blood cells. On the other hand, in the BM of recipient mice transplanted with control WT cells, few cells expressing CD45/Col-1 or CD90/Col-1 were present. To examine the differentiation ability of Jak2V617F blood cells to fibrocytes directly, peripheral blood (PB) mononuclear cells (MNC) of Jak2V617F mice or WT mice were cultured in vitro. After 5 days of culture, PB MNCs from Jak2V617F mice differentiated into mature fibrocytes exhibiting a long spindle shape with Col-1 expression. On the other hand, there were very few fibrocytes differentiated from PB MNC from WT mice. Next, we depleted monocytes, the main source of fibrocytes, and observed its effects on BM fibrosis in vivo. Jak2V617F TG mice were mated with CD11b-diphtheria toxin receptor (DTR) TG mice (Duffield et al. JCI 2005) to obtain Jak2V617F/CD11b-DTR double TG mice. Mice transplanted with BM cells from Jak2V617F/CD11b-DTR double TG mice (hereinafter called Jak2V617F/CD11b-DTR mice) exhibit leukocytosis, thrombocytosis, anemia, splenomegaly, and BM fibrosis with increased megakaryocytes. Jak2V617F/CD11b-DTR mice was administered diphtheria toxin (DT) intraperitoneally to deplete monocytes. One day after DT administration, the number of PB monocytes (CD11b+/F4/80+) drastically decreased in Jak2V617F/CD11b-DTR mice, and the reduction of monocyte was maintained by every-other-day DT administration. After 8 weeks DT treatment, mice were sacrificed and analyzed. As a control group, Jak2V617F/CD11b-DTR mice treated with PBS were examined. DT treatment drastically decreased the number of neoplastic fibrocytes expressing CD45.2/Col-1 in BM and spleen of Jak2V617F/CD11b-DTR mice compared with control mice treated with PBS. Consistently, reticulin fibers were eliminated almost completely and collagen fibers almost fully disappeared in BM, which led to a reversal of the decrease in BM cellularity, although the number of MKs was not affected. Similar findings were observed in the spleen, although not completely. Plasma TGF-b1 level were about 2-fold higher in Jak2V617F/CD11b-DTR mice than in WT mice. Neoplastic monocyte depletion significantly decreased TGF-b1 level. Since MK numbers did not change, this indicates that fibrocytes are one of the main sources of TGF-b1. In other features of MF in Jak2V617F/CD11b-DTR mice, splenomegaly was ameliorated by DT treatment. Microscopic analysis revealed an improvement in the damaged spleen architecture and the disappearance of splenic fibrosis. In summary, most collagen-producing cells in BM were neoplastic fibrocytes in Jak2V617F-induced MPN, indicating that neoplastic fibrocytes played an essential role and mesenchymal fibroblasts had a minor contribution in fibrosis in MPN. Depletion of neoplastic monocytes also improved splenomegaly as well as BM fibrosis in mice, and this cell fraction could be a promising therapeutic target. Disclosures No relevant conflicts of interest to declare.

scholarly journals Proteomics Analysis Reveals Protein Panels That Are Associated with Prediction to Tyrosine Kinase Inhibitors Response, Bone Marrow Transplant, Survival and Disease Outcome of Chronic Myeloid Leukemia Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5434-5434
Author(s):  
Ayodele Alaiya ◽  
Mahmoud Aljurf ◽  
Zakia Shinwari ◽  
Fahad Z. Alsharif ◽  
Hazza A. Alzahrani ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Personalized Medicine ◽  
Tyrosine Kinase ◽  
Treatment Response ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
The Other ◽  
Disease Outcome

Abstract Clinical and molecular diagnosis of most hematological malignancies including Chronic Myeloid Leukemia (CML) can be accurately made. However, prediction of treatment response and estimation of disease survival period eludes the currently available tools for patient care. Quantitative expression proteomics can potentially be developed as effective tool to monitor therapy response towards achieving personalized medicine for CML patients. We have over 10 years follow up period for some of the CML patients, and the majorities of them are alive and doing well on Imatinib. On the other hand, a small fraction of the patients were switched to alternative Tyrosine Kinase Inhibitors (TKI) and some underwent bone marrow transplants (BMT). Our follow up results stratified all 37 analyzed newly diagnosed CP-CML patients into 5 distinct cohorts including 52% on Imatinib, 12% on Nilotinib, 9% on Dasatinib, and 15% BMT, while 12% of the patients had disease-related mortality. Kaplan-Meier survival curve showed no significant difference between all patients on TKI and BMT that were alive under a follow up period of 4-11 years compared. On the other hand 3 of 4 patients had disease related deaths less than 2 years of diagnosis. Only one patient survived for almost 10 years (Figure 1). Besides survival analysis, peripheral blood samples obtained from the patients at time of diagnosis were subjected to expression proteome analysis using label-free quantitative liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). A subset of significantly differentially expressed proteins was able to distinctively discriminate samples into their respective treatment response and disease outcome groups based on unique protein expression signatures (P<0.05 and > 2- ∞- fold change, (Figure 2). Some of the identified proteins were implicated in hematological diseases including CML as potential biomarkers using Ingenuity Pathway Analysis. These protein signatures once validated in larger sample cohorts might be capable of prediction of molecular response, choice of therapy and disease outcome for CML patients. Therefore; allowing for identification of would be high risk patients that might potentially benefit from aggressive treatment at point of diagnosis pre initiation of conventional therapy. Altogether our findings indicate that analysis of panel of protein markers have the potential of clinical utility for prediction of response to therapy, disease survival and objective prognostication of disease outcome, thus bringing personalized medicine closer to CML patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Distinct Osteogenic Potentials of BMP-2 and FGF-2 in Extramedullary and Medullary Microenvironments

2020 ◽  
Vol 21 (21) ◽  
pp. 7967
Author(s):  
Shuji Nosho ◽  
Ikue Tosa ◽  
Mitsuaki Ono ◽  
Emilio Satoshi Hara ◽  
Kei Ishibashi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factors ◽  
Bone Resorption ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Marrow Cells ◽  
The Other ◽  
Bone Morphogenetic Protein 2 ◽  
Control Group ◽  
Other Hand

Bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-2 (FGF-2) have been regarded as the major cytokines promoting bone formation, however, several studies have reported unexpected results with failure of bone formation or bone resorption of these growth factors. In this study, BMP-2 and FGF-2 adsorbed into atellocollagen sponges were transplanted into bone defects in the bone marrow-scarce calvaria (extramedullary environment) and bone marrow-abundant femur (medullary environment) for analysis of their in vivo effects not only on osteoblasts, osteoclasts but also on bone marrow cells. The results showed that BMP-2 induced high bone formation in the bone marrow-scarce calvaria, but induced bone resorption in the bone marrow-abundant femurs. On the other hand, FGF-2 showed opposite effects compared to those of BMP-2. Analysis of cellular dynamics revealed numerous osteoblasts and osteoclasts present in the newly-formed bone induced by BMP-2 in calvaria, but none were seen in either control or FGF-2-transplanted groups. On the other hand, in the femur, numerous osteoclasts were observed in the vicinity of the BMP-2 pellet, while a great number of osteoblasts were seen near the FGF-2 pellets or in the control group. Of note, FCM analysis showed that both BMP-2 and FGF-2 administrated in the femur did not significantly affect the hematopoietic cell population, indicating a relatively safe application of the two growth factors. Together, these results indicate that BMP-2 could be suitable for application in extramedullary bone regeneration, whereas FGF-2 could be suitable for application in medullary bone regeneration.

Effect of Dasatinib on Genes Related to Mitotic Catastrophe Pathway in Chronic Myeloid Leukemia Cells

2020 ◽  
Vol 20 ◽  
Author(s):  
Sezgi Kipcak ◽  
Buket Ozel ◽  
Cigir B. Avci ◽  
Leila S. Takanlou ◽  
Maryam S. Takanlou ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Fusion Gene ◽  
Philadelphia Chromosome ◽  
K562 Cells ◽  
Mitotic Catastrophe ◽  
Control Group ◽  
Cancer Therapies ◽  
Apoptosis Pathways

Background: Chronic myeloid leukemia (CML), is characterized by a reciprocal translocation t(9;22) and forms the BCR/ABL1 fusion gene, which is called the Philadelphia chromosome. The therapeutic targets for CML patients which are mediated with BCR/ABL1 oncogenic are tyrosine kinase inhibitors such as imatinib, dasatinib, and nilotinib. The latter two of which have been approved for the treatment of imatinib-resistant or intolerance CML patients. Mitotic catastrophe (MC) is one of the non-apoptotic mechanisms which frequently initiated in types of cancer cells in response to anti-cancer therapies; pharmacological inhibitors of G2 checkpoint members or genetic suppression of PLK1, PLK2, ATR, ATM, CHK1, and CHK2 can trigger DNA-damage-stimulated mitotic catastrophe. PLK1, AURKA/B anomalously expressed in CML cells, that phosphorylation and activation of PLK1 occur by AURKB at centromeres and kinetochores. Objective: The purpose of this study was to investigate the effect of dasatinib on the expression of genes in MC and apoptosis pathways in K562 cells. Methods: Total RNA was isolated from K-562 cells treated with the IC50 value of dasatinib and untreated cells as a control group. The expression of MC and apoptosis-related genes were analyzed by the qRT-PCR system. Results: The array-data demonstrated that dasatinib-treated K562 cells significantly caused the decrease of several genes (AURKA, AURKB, PLK, CHEK1, MYC, XPC, BCL2, and XRCC2). Conclusion: The evidence supply a basis to support clinical researches for the suppression of oncogenes such as PLKs with AURKs in the treatment of types of cancer especially chronic myeloid leukemia.

scholarly journals Ghrelin and orexin levels in infertile male: evaluation of effects on varicocele pathophysiology, relationship seminal and hormonal parameter

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Üçler Kısa ◽  
M. Murad Başar ◽  
Timuçin Şipal ◽  
Özlem Doğan Ceylan
Keyword(s):  
The Other ◽  
Control Group ◽  
Infertile Male ◽  
Seminal Parameters ◽  
Other Hand ◽  
Healthy Control ◽  
Regulatory Effects ◽  
Serum Ghrelin ◽  
Infertile Patients ◽  
Group 1

AbstractObjectiveThe aim of the present study was to investigate serum ghrelin and orexin levels in patients with varicocele and compare these levels with idiopathic infertile male and healthy control cases.MethodsThis study enrolled 24 men with varicocele, 24 males having idiopathic infertility, and 21 fertile men as the control group. Hormonal analyses, ghrelin and orexin levels were measured samples. Semen was analyzed after 3 and 5 days of sexual abstinence.ResultsSerum ghrelin levels were statistically different among the three groups (p=0.015), and it was due to a statistically lower level in group-1 than the level in the control cases (p=0.012). On the other hand, serum orexin levels were lower than healthy subjects in infertile groups with/without varicocele, but there was no difference (p=0.685) among three groups. Serum ghrelin level showed a negative and significant correlation only with sperm motility (r=−0.646, p=0.022), there was no correlation with other parameters. On the other hand, serum orexin levels did not show a significant correlation with seminal parameters.ConclusionBoth new investigated peptides ghrelin and orexin have regulatory effects on testicular function. However, ghrelin has a more obvious and complex effect on spermatogenesis. Impaired seminal parameters, especially motility was associated with increased serum ghrelin levels in infertile patients, especially with varicocele.

scholarly journals Molecular analysis of relapse in chronic myeloid leukemia after allogeneic bone marrow transplantation

Blood ◽  
1987 ◽  
Vol 70 (3) ◽  
pp. 873-876 ◽  
Author(s):  
TS Ganesan ◽  
GL Min ◽  
JM Goldman ◽  
BD Young
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Chronic Myeloid Leukemia ◽  
Marrow Transplantation ◽  
Myeloid Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone Marrow ◽  
Leukemic Cells ◽  
Allogeneic Bone ◽  
Leukemic Clone

Abstract Four patients with Philadelphia (Ph′) positive chronic myeloid leukemia (CML) were studied before, after, and on relapse following allogeneic bone marrow transplantation (BMT). Southern analysis of DNA from cells collected before and at relapse after BMT was performed in order to investigate the origin of the leukemia at relapse. Using minisatellite probes we showed that the relapse occurred in cells of host origin in all four patients and this was confirmed with a Y chromosome specific probe in two male patients who had a female donor. Furthermore, using two probes for the breakpoint cluster region (bcr) on chromosome 22, we showed that leukemic cells at relapse bore identical rearrangements to those in the disease at time of presentation of each patient. We conclude that relapse in all four patients is due to re-emergence of the original leukemic clone.

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