Patterns of Bone Marrow Micro Vessel Morphology in AML and High Risk MDS Predict Treatment Outcome Following Intensive Chemotherapy and Bevacizumab

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1555-1555 ◽  
Author(s):  
Alida C. Weidenaar ◽  
Arja ter Elst ◽  
Cees AGM van Montfort ◽  
Tiny G.J. Meeuwsen-de Boer ◽  
Stefano Rosati ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Reference Line ◽  
Bone Marrow Biopsies ◽  
Group Iii ◽  
Vascular Morphology ◽  
Thin Walls ◽  
Vessel Morphology ◽  
Group I ◽  
Bevacizumab Treatment ◽  
Vessel Count

Abstract Abstract 1555 An increase in micro vessel density has been shown in Acute Myeloid Leukemia (AML) bone marrow biopsies at diagnosis, correlating with increased expression of Vascular Endothelial Growth Factor (VEGFA) (de Bont et al, 2001, 2002; Padro et al, 2000; Aguayo et al, 1999). Previously we reported heterogeneity in AML bone marrow vessel patterns, and three subgroups can be distinguished: (a) low vessel count', (b) angiogenic sprouting' (biopsies exhibiting high vessel count with mainly a network of small vessels with thin walls, narrow lumen and branching) and (c) ‘vessel hyperplasia’ (biopsies displaying high number of vessels with predominantly a large lumen and thin walls) (Weidenaar et al, abstract ASH 2010; 2011). In this study we set out to confirm the previously defined morphology groups in a larger group of patients, and investigated the relationship between vascular morphology and clinical outcome in the HOVON81 study which is a multicenter phase II trial evaluating the additional value of Bevacizumab (Roche, Basel, Switzerland) (5 mg/kg to a maximum of 10 mg/kg) at day 1 and 15 of cycle I and II to standard intensive chemotherapy in elderly AML patients (>60 years). AML bone marrow biopsies at diagnosis (n=93) were immunohistochemical stained for FVIII (endothelial cell marker) and SMA (pericytes marker). The three previously reported AML vessel morphology patterns could be confirmed in this cohort (Fig 1A-B). The median percentage of vessels covered by pericytes was 50.1% (range 2.1–100.0, n=66), and was not significantly (P=.27) different between the three groups. In addition it was shown that patients with ‘angiogenic sprouting’ and ‘low vessel count’ (EFS 2 yr: 10%) have a decreased EFS as compared to patients with 'vessel hyperplasia' (EFS 2 yr 30%) (P=.017). For OS, a trend for unfavorable outcome was observed for the ‘angiogenic sprouting’ subgroup (P=.055). Interestingly, treatment with Bevacizumab significantly increased EFS and tended to be associated with a beneficial OS for patients displaying ‘low vessel count’ profile (P=.023 and P=.099 respectively). EFS and OS were not increased in patients with ‘angiogenic sprouting’ or ‘vessel hyperplasia’ upon Bevacizumab treatment. Multivariate analysis established vessel morphology (HR: 2.2 (95% CI 1.1–4.0)) as a prognostic indicator independent of other statistical significant risk factors (for EFS (P=.015)). In conclusion, our results demonstrate that different vasculature patterns in AML bone marrow biopsies are related to treatment outcome in AML patients. Patients displaying an ‘angiogenic sprouting’ profile seem to constitute an unfavorable subset of patients. In addition, AML patients with ‘low vessel count’ might be good candidates for Bevacizumab treatment. Our results show that AML vascular morphology provides prognostic information; therefore, it might be useful to study vessel patterns at diagnosis. Fig. 1. AML biopsies prior to treatment divided into three morphology groups. (A) Scatterplot representing the AML biopsies at diagnosis. Biopsies with a ‘low vessel count’ are displayed below the Y-axis reference line (13 microvessels/hpf, group I). The X-axis reference line divides AML biopsies at diagnosis with a ‘high vessel count’ into two subgroups according to the median Chalkley count of 5.4 in AML at diagnosis. Cut-off points are based on previously described results. Samples with a Chalkley count ≤5.4 were defined as ‘angiogenic sprouting’ (group II) and samples with a Chalkley count >5.4 as ‘vessel hyperplasia’ (group III). (B) A representative picture of the three groups is shown. Fig. 1. AML biopsies prior to treatment divided into three morphology groups. (A) Scatterplot representing the AML biopsies at diagnosis. Biopsies with a ‘low vessel count’ are displayed below the Y-axis reference line (13 microvessels/hpf, group I). The X-axis reference line divides AML biopsies at diagnosis with a ‘high vessel count’ into two subgroups according to the median Chalkley count of 5.4 in AML at diagnosis. Cut-off points are based on previously described results. Samples with a Chalkley count ≤5.4 were defined as ‘angiogenic sprouting’ (group II) and samples with a Chalkley count >5.4 as ‘vessel hyperplasia’ (group III). (B) A representative picture of the three groups is shown. Disclosures: No relevant conflicts of interest to declare.

Vascular Morphology Differences In Acute Myeloid Leukemia Are Associated with Blast Derived VEGFA Levels

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2712-2712
Author(s):  
Alida C. weidenaar ◽  
Ajra ter Elst ◽  
Gineke Koopmans-Klein ◽  
Stefano Rosati ◽  
Wilfred F.A. den Dunnen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Point Group ◽  
Reference Line ◽  
Bone Marrow Biopsies ◽  
Protein Levels ◽  
Vascular Morphology ◽  
Thin Walls ◽  
Group I ◽  
Vessel Count ◽  
Group Ii

Abstract Abstract 2712 Acute Myeloid Leukemia (AML) bone marrow biopsies at diagnosis display an enhanced microvessel density (MVD), restoring to normal vessel counts when a complete remission has been achieved (de Bont et al, 2001; Padro et al, 2000). The enhanced MVD is correlated with increased expression of Vascular Endothelial Growth Factor (VEGFA), which is found to be a prognostic factor for therapeutic outcome in AML (de Bont et al, 2001, 2002; Aguayo et al, 1999). In the literature it has been described that the availability of VEGFA is related to different vascular morphology patterns in a xenograft mouse model (Lee et al., 2005). In this study we investigated the vascular morphology in AML bone marrow biopsies in relation to AML-derived VEGFA protein levels. Bone marrow biopsies (n=32) were stained for Factor VIII, a marker for Endothelial Cells, to enumerate the number of vessels. A significant (p<0.001) increased vessel count was demonstrated in AML at diagnosis compared with normal control bone marrow (NBM, n=14) and AML at remission (n=8). Based on the fact that >95% of the NBM and AML remission biopsies had a vessel count below 13 microvessels/hpf, this value was taken as cut-off point for categorization into ‘low vessel count’ (13 or less) and ‘high vessel count' (more than 13). A ‘high vessel count' was detected in 75% (24/32) of the AML bone marrow biopsies at diagnosis. Since vessel stabilization requires pericyte coverage of the vascular sprouts, we studied the number of vessels positive for Smooth Muscle Actin (SMA), a marker for pericytes. In AML bone marrow biopsies at diagnosis 35% of vessels were pericyte coated versus 55% of vessels in NBM and AML remission (p=0.02). Interestingly, the percentage vessels coated with pericytes was significantly (p=0.04) higher in the biopsies with a ‘low vessel count' (45%) compared with the biopsies showing a ‘high vessel count' (29%), indicating that a high vessel density in AML is related to a more immature vessel status. To quantify the vasculature morphology, the vessel count was combined with a method to measure the vessel surface area (Chalkley count; Sie et al., 2010) (Fig. 1A). Based on the Chalkley count the AML bone marrow biopsies at diagnosis with ‘high vessel count' could be divided into two groups with abnormal vessels. The first group (37.5%) had a normal Chalkley count (group I in Fig. 1A) and was defined as ‘vessel hyperplasia', characterized by vessels with a predominantly large lumen and thin walls (Fig 1B). The second group (37.5%) had a Chalkley count below normal (group II in Fig. 1A) and was defined as ‘angiogenic sprouting', displaying a network of small vessels with thin walls, narrow lumen and branching (Fig.1C). Moreover, we found that high blast VEGFA protein levels were significantly (p=0.007) higher in the ‘vessel hyperplasia' group compared with the other defined groups. In conclusion, our study shows that heterogeneity in AML bone marrow vasculature exists and can be quantified using vessel count in combination with Chalkley count. Furthermore, the VEGFA protein levels excreted by AML blasts are related to the defined vessel morphology patterns. Clinical trials targeting the VEGF/VEGFR signaling pathway in patients with relapsed or refractory AML showed beneficial effects in only a subset of patients (Karp et al, 2004). It might be that adapting therapeutic approaches to bone marrow morphology will improve treatment outcome. Ongoing work investigating the response of anti-VEGFA therapies related to AML bone marrow vasculature will have to confirm this hypothesis. Fig.1. Morphology patterns in AML bone marrow biopsies. (A) Scatterplot representing the bone marrow vessel count and Chalkley count of AML at diagnosis, NBM and AML at remission. AML biopsies at diagnosis with a ‘low vessel count’ are displayed below the Y-axis reference line (13 microvessels/hpf), based on the fact that >95% of NBM and AML remission had a vessel count below 13 microvessels/hpf. The X-axis reference line divides AML biopsies at diagnosis with a ‘high vessel count' into two groups according to median Chalkley count of 5.4 in AML at diagnosis. The >95% Chalkley count of the NBM and AML remission biopsies sets an identical cut-off point. Group I, ‘vessel hyperplasia'>5.4; group II, ‘angiogenic sprouting' ≤5.4. Spearman's rho 0.15, p=0.42. (B) Representative picture of immunohistochemical staining for ‘vessel hyperplasia' and (C) ‘angiogenic sprouting'. Fig.1. Morphology patterns in AML bone marrow biopsies. (A) Scatterplot representing the bone marrow vessel count and Chalkley count of AML at diagnosis, NBM and AML at remission. AML biopsies at diagnosis with a ‘low vessel count’ are displayed below the Y-axis reference line (13 microvessels/hpf), based on the fact that >95% of NBM and AML remission had a vessel count below 13 microvessels/hpf. The X-axis reference line divides AML biopsies at diagnosis with a ‘high vessel count' into two groups according to median Chalkley count of 5.4 in AML at diagnosis. The >95% Chalkley count of the NBM and AML remission biopsies sets an identical cut-off point. Group I, ‘vessel hyperplasia'>5.4; group II, ‘angiogenic sprouting' ≤5.4. Spearman's rho 0.15, p=0.42. (B) Representative picture of immunohistochemical staining for ‘vessel hyperplasia' and (C) ‘angiogenic sprouting'. Disclosure: No relevant conflicts of interest to declare.

Evaluation of the rivastigmine role against botulinum toxin-A-induced osteoporosis in albino rats: A biochemical, histological, and immunohistochemical study

2018 ◽  
Vol 37 (12) ◽  
pp. 1323-1335 ◽  
Author(s):  
DM Ali ◽  
WY Abdelzaher ◽  
SMN Abdel-Hafez
Keyword(s):  
Bone Marrow ◽  
Botulinum Toxin ◽  
Botulinum Toxin A ◽  
Physiological Saline ◽  
Compact Bone ◽  
Albino Rats ◽  
Toxin A ◽  
Group Iii ◽  
Group I ◽  
Factor Α

The present study aimed to evaluate the role of rivastigmine against the effect of a single unilateral botulinum toxin-A (BTX-A) injection on the bone and bone marrow of adult albino rats 4 weeks after injection. Twenty-four Wistar albino rats were divided into four equal groups: group I, which received distilled water; group II, which received rivastigmine (0.3 mg/kg daily, intraperitoneally for 4 weeks); group III, which received BTX-A (4 IU in 0.2 mL physiological saline) single dose, intramuscularly; and group IV, which received BTX-A + rivastigmine. The results revealed that BTX-A induced a significant decrease in the calcium level with a significant increase in the phosphorus, alkaline phosphatase, C-reactive protein, and tumor necrosis factor α levels in serum. Furthermore, a significant increase in malondialdehyde with a significant decrease in reduced glutathione activities in both bone and bone marrow. Histologically, a distortion and thinning out of the compact bone and trabeculae of cancellous bone of the rat femur in the BTX-A group with an increase in adipocytes in adjacent bone marrow were detected. Immunohistochemically, Cluster of Differentiation 68 (CD68) showed a significant increase in both osteoclasts and bone marrow macrophage. Rivastigmine treatment could relieve the toxic effects induced by BTX-A. In conclusion, rivastigmine has a protective effect against the hazardous effects of BTX-A on bone and bone marrow.

scholarly journals Assessment the Genotoxic Potential of Fluoxetine and Amitriptyline at Maximum Therapeutic Doses for Four-Week Treatment in Experimental Male Rats

2021 ◽  
Vol 30 (1) ◽  
pp. 81-90
Author(s):  
Imad A. Al-Obaidi ◽  
Nada N. Al-Shawi
Keyword(s):  
Bone Marrow ◽  
Dna Damage ◽  
Adult Male ◽  
Negative Control Group ◽  
Negative Control ◽  
Male Rats ◽  
Control Group ◽  
Group Iii ◽  
Group I ◽  
Hydrochloride Solution

Abstract At any moment, the continuous usage of medications can accompanied by DNA damage and the accumulation of such damages can cause serious consequences. Antidepressants are long-term used drugs and the incidence of their genotoxic impacts cannot be excluded. Therefore, this work was designed to investigate the possible genotoxic effects of the commonly used antidepressants (fluoxetine and amitriptyline) in adult male rats. Detection of DNA damage in individual cells was assessed by comet and micronucleus assays in three different cell populations i.e. liver, testis and bone marrow tissues of 24 swiss albino adult male rats. The animals were randomly allocated into three groups of 8 rats each: Group I - rats orally-administered distilled water via gavage tube for four weeks as a negative control. Group II - rats orally-treated with fluoxetine hydrochloride solution (7.2mg/kg/day) via gavage tube for four weeks. Group III - rats orally-treated with amitriptyline hydrochloride solution (27mg/kg/day) via gavage tube for four weeks. The results showed that both drugs (Group II and Group III) induced the same extent of DNA damage, as evidenced by a significantly higher DNA fragmentation in liver and testis tissues with increased frequencies of micronuclei formation in bone marrow tissues as compared with the negative control (Group I). These findings indicates that both Fluoxetine and Amitriptyline have genotoxic potentials and can induce the same extent of cytogenetic damage in rats. Special precautions and medical supervision should be taken in consideration with their uses.

scholarly journals Establishment and Evaluation of Gvhd Mouse Model for Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5681-5681
Author(s):  
Mei Xie ◽  
Weihong Chen ◽  
Qiaoxia Zhang ◽  
Xin Du
Keyword(s):  
Bone Marrow ◽  
Conditioning Regimen ◽  
Group Iv ◽  
Spleen Cells ◽  
Hematopoietic Stem ◽  
Group Iii ◽  
Group I ◽  
Significant Difference ◽  
Leukocyte Counts ◽  
Group Ii

Abstract Objective: To study the feasibility of using cyclophosphamide alone without total body irradiation (TBI) as conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) and establish a graft-versus-host disease (GVHD) mouse model. Methods: Single cell suspension of spleen and bone marrow were prepared from donor C57/BL/6 mice (B6 mice) . The recipient B6D2F1 mice (F1 mice) were signed into 4 groups with 12 mice per each group. Groups I~III mice were conditioned with peritoneal injection of cyclophosphamide (300 mg/m 2/d) on day -5, -4 and -3 of allo-HSCT, and group IV mice were used as control with saline injection. On day 0, group I mice were injected through tail vein with a mixture of 2×107 spleen cells, 5×106 bone marrow cells and 1×104 P815 cells; group II with 5×106 bone marrow cells and 1×104 P815 cells; group III with 1×104 P815 cells and group IV with RPMI1640 culture medium. The blood leukocyte counts were analyzed, GVHD score and the pathological leukemia infiltration of skin, liver and colon were evaluated and compared on day 30 after allo-HSCT. Results: (1) The GVHD scores of group I mice were 2 to 4 on day 14 post allo-HSCT, and mice started to die on day 15, eight (8) mice survived and the GVHD scores of them were 1 to 6 with a survival rate of 66.7% on day 30. Group II mice began to die on day 6 and only one survived on day 30 with a survival rate of 8.3%. All of group III mice died on day 18. Group IV mice survived (Figure 1). (2) The leukocyte counts in group I and group II were significantly increased on day 7 post allo-HSCT(p<0.05). There was also a significant difference in total leukocyte counts between groups I/II and group IV (p<0.05). The leukocyte counts in mice of groups I~III were significantly decreased, and there were a significant difference between group I and groups II/III/IV respectively (p<0.05) on day 14 post allo-HSCT. On day 21 after allo-HSCT, the leukocyte count of Group I and II mice were ≥1×109/L, which means that allo-HSCT were successful. The leukocyte counts in group I mice were again increased on day 28 post allo-HSCT. There was no significant difference between Group I and Group IV (p>0.05). (3) Pathological observation: The cell atrophy and necrosis in the hepatic portal area and slight infiltration of the leukemia cells in central vein were observed in group I recipient mice. The number of hepatocytes of the mice decreased, and the infiltration of the leukemia cells in the liver sinus were observed in group II. The liver was heavily infiltrated by leukemic cells in group III mice. The mouse livers were normal in group IV mice. Conclusion: It is feasible to establish GVHD model of the leukemia mice with cyclophosphamide conditioning regimen of allo-HSCT, and simple to operate. This is less harmful to people, animals and the environment. Discussion: The traditional animal model of GVHD is based on TBI conditioning regimen prior to allo-HSCT. However, the process can lead to systemic adverse reactions such as myelosuppression, radiation gastroenteritis, endocrine disorders and systemic function disorders, etc. in both the operators and animals. Therefore, the radiotherapy doses have to be low. At the same time, it is difficult to establish animal models of GVHD due to the uneven distribution of the doses. Cyclophosphamide was selected for the conditioning regimen of allo-HSCT in the study. Cyclophosphamide had the effect direct on killing tumor cells, induced recipients to tolerate the immune of donors, enabled to implant donor cells into recipients smoothly. The stable chimeras were obtained. There are a large number of T and B lymphocytes in donor's spleen cells. By injecting donor spleen cells and active immune cells derived from proliferation and differentiation of hematopoietic stem cells, the effects of graft-anti-leukemia are availably activated in recipients. Acknowledgments We thank Dr Zhifu Xiang very much for his great helpful revisions. Disclosures No relevant conflicts of interest to declare.

scholarly journals Study of Humoral Factors Regulating the Production of Leukocytes. I. Demonstration of a "Neutropoietin" in the Plasma after Administration of Triamcinolone to Rats

Blood ◽  
1961 ◽  
Vol 17 (4) ◽  
pp. 434-443 ◽  
Author(s):  
SHU CHU SHEN ◽  
TAKASHI HOSHINO
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Wistar Rats ◽  
Significant Alteration ◽  
Humoral Factors ◽  
Group Iii ◽  
Group I ◽  
Male Wistar Rats ◽  
Group Ii ◽  
Blood Elements

Abstract Male Wistar rats were divided into 3 groups: Group I. Rats given the triamcinolone daily by gastric catheter all developed neutrophilia accompanied by lymphopenia. Group II. Rats given daily intraperitoneal injections of plasma from normal rats manifested no significant alteration in the peripheral blood elements. Group III. Rats given daily intraperitoneal injections of plasma from rats given triamcinolone invariably developed neutrophilia without lymphopenia. Studies of the bone marrow of these groups at the end of the experiments revealed increased myeloid:erythroid ratios in Groups I and III but not II. It is therefore believed that this experiment suggests the existence of a neutrophilia-promoting factor in the plasma following the administration of triamcinolone.

The Application of a New Composite in Large Bone Defects using Fibrillar Collagen and HA/TCP

1987 ◽  
Vol 110 ◽  
Author(s):  
Masaaki Uratsuji ◽  
T. W. Bauer ◽  
S. I. Reger
Keyword(s):  
Bone Marrow ◽  
Biological Response ◽  
Volume Ratio ◽  
Bone Defects ◽  
Autogenous Bone ◽  
Fibrillar Collagen ◽  
Group Iii ◽  
Group I ◽  
Large Bone ◽  
Large Bone Defects

The handling property and short term biological response to a new composite of fibrillar collagen (FC) and porous calcium phosphate (HA/TCP) were studied. A 4 mm by 20 mm defect was created in the femora of rabbits. The rabbits were divided into four treatment groups and sacrificed from each group at 4, 8 and 12 weeks. In each group, the defect was treated as follows: in Group I with autogenous bone marrow; in Group II with FC and HA/TCP; and in Group III with FC and HA/TCP with bone marrow in volume ratio of 3:1. In the fourth group, the defect was unfilled. The femora were excised and studied by microradiography or histology or both. The FC could improve the handling property of the HA/TCP granules. Although the composite of FC and HA/TCP was not osteoinductive, the defects in Groups II and III showed good healing at 12 weeks without signs of inflammation. The results showed the composite of FC and HA/TCP to be an effective filler for large bone defects especially when mixed with autogenous bone marrow.

Different Response Patterns to Inactivated, Subunit or Live Attenuated Vaccines in Children after Treatment for Malignancies and Bone Marrow Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5478-5478
Author(s):  
Sema S Anak ◽  
Elif Erdem Ozcan ◽  
Ayse Kilic ◽  
Mustafa Onel ◽  
Ayhan Ozguven ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Hepatitis B ◽  
Solid Tumors ◽  
Marrow Transplantation ◽  
Hepatitis A ◽  
Live Attenuated Vaccines ◽  
Group Iii ◽  
Group I

Abstract Objective: In pediatric patients treated for malignancies with chemotherapy or bone marrow transplantation (BMT), the disease and the treatment lead to impaired immunity and loss of immunity continues for a time period after the completion of therapy. Therefore, revaccination of these children is necessary. The aim of this study was to examine the differences between different treatment groups, namely solid tumors, leukemias and BMT patients, for their response to inactivated or subunit or live attenuated vaccines at least 6 months after the cessation of the of treatment. Materials and Method: The study was performed prospectivly in 35 patients with solid tumors (Group I), 32 patients with leukemia (28 ALL, 4 AML) (Group II) and 13 patients after BMT (Group III). Inactivated (Diphtheria, tetanus), subunit (acellular pertussis, hepatitis B, hepatitis A) and live attenuated (measles-mumps-rubella (MMR), varicella) vaccines were applied to patients. Blood samples taken from the all patients before vaccination and 1 month after vaccination. IgG antibodies against measles-mumps-rubella and varicella were evaluated in vitro. Results: For inactivated vaccines, the level of anti diphteria antigen was highly positive in Group I and II, 80% and 71.8% respectively, but only 53.8% of Group III patients were positive before vaccination. After one dose all of these levels became 100%. For tetanus it was the same pattern (84.4% 88.6% and 46.2%, low in Group III). They all reached 100% after vaccination with one dose. Anti pertussis IgGs were low in all 3 groups, 54.3%, 46.9%, 38.5% respectively. These levels were 66.7%, 66.7%, 50% after the vaccination and the differences were meaningful for Groups I and II (p : 0.02 and 0.002), but not for Group III (p : 0.068). In subunit (purified antigen) vaccines, for Hapatitis B, Anti HBs levels were low in all groups (60%, 37.5%, 46.2%) before vaccination. After one dose, 55.6%, 64.3%, 50% became positive, but only after the second dosage 100% of the patients were positive. For Hepatitis A, positive levels of antiHAV IgG before vaccination were 28.6%, 37.5%, 53.8% for the 3 groups. Except for one patient in the BMT group 100% became positive with one dose. Among live, attenuated viruses, measles, rubella, mumps vaccinations were applied. Anti-rubeola IgG levels were positive in 45.7%, 34.4% 15.4% of patients in 3 groups before vaccination. After one dose they all became positive except for one patient in each group, who responded after one more dose. For rubella, 85.7%, 78.1% and 61.5% of patients were positive for anti-rubella IgG before vaccination in respective groups and they all became 100% positive after one dose. Before mumps vaccination, 82.9%, 71.9% and 46.2% of patients were positive for anti-mumps IgG before first dose. 83.3%, 100% and 50% became also positive after one dose, but after the second dosage 100% were positive. 65.7%, 59.4% and 53.8% of the patients were seropositive for antiVZV IgG respectively before vaccination. Except for four cases in Group I, the rest achieved seropositivity after one dose. Conclusion: In our study, after one booster dose of vaccine, all patients had very good antibody response against to diphtheria, tetanus, hepatitis A, rubella vaccines at least 6 months after the cessation of therapy for leukemia and solid tumors and 12 months after BMT. Protection after mumps vaccine was in moderate levels in leukemia and solid tumor groups, but not in BMT group. All groups responded moderately for measles, varicella, pertussis, hepatitis B, some needing one more booster. BMT group seems to be the maximum looser and the least responder after vaccination. The groups showed differences in antibody responses to vaccines, according to age, the time passed after the cessation of treatment and their primary vaccination status. To evaluate the response obtained, following antibody levels for response to vaccination is necessary and a booster should be considered when there is a decrease or loss in these levels. Disclosures Karakas: Novartis: Research Funding.

Ultrastructural Lesions Produced by Alcohol and Sucrose in the Heart and Liver of C57BL Mice

1970 ◽  
Vol 28 ◽  
pp. 208-209
Author(s):  
K.K. SEKHRI ◽  
C.S. ALEXANDER ◽  
H.T. NAGASAWA
Keyword(s):  
Osmium Tetroxide ◽  
Male Mice ◽  
Alcohol Group ◽  
Group Iii ◽  
Group I ◽  
C57bl Mice ◽  
Group Ii

C57BL male mice (Jackson Lab., Bar Harbor, Maine) weighing about 18 gms were randomly divided into three groups: group I was fed sweetened liquid alcohol diet (modified Schenkl) in which 36% of the calories were derived from alcohol; group II was maintained on a similar diet but alcohol was isocalorically substituted by sucrose; group III was fed regular mouse chow ad lib for five months. Liver and heart tissues were fixed in 2.5% cacodylate buffered glutaraldehyde, post-fixed in 2% osmium tetroxide and embedded in Epon-araldite.

The Quantitative Ultrastructure of the Heart Muscle of Japanese Quail by Hypergravitation, Hypodynamy and Combination

1990 ◽  
Vol 48 (3) ◽  
pp. 188-189
Author(s):  
Anton Bózner ◽  
Mikuláš Gažo ◽  
Jozef Dostál
Keyword(s):  
Japanese Quail ◽  
Heart Muscle ◽  
Relative Size ◽  
Combination Group ◽  
Control Group ◽  
Group V ◽  
Group Iii ◽  
Space Flights ◽  
Group I ◽  
Quantitative Ultrastructure

It is anticipated that Japanese quail /Coturnix coturnix japonica/ will provide animal proteins in long term space flights. Consequently this species of birds is of research interest of international space program INTERCOSMOS. In the year 1987 we reported on an experiment /2/ in which the effect of chronic acceleration of 2 G hypergravitation, the hypodynamy and the simultaneous effect of chronic acceleration and the location in the centre of the turntable of the centrifuge on the protein fractions in skeletal muscles was studied. The ultrastructure of the heart muscle was now in this experiments examined as well.Japanese quail cockerels, aged 48 days were exposed to 2 G hypergravitation /group IV/ in a 6,4 m diameter centrifuge, to hypodynamy /group III/ and their combination /group V/, respectively for 6 days / Fig.1/. The hypodynamy in group III was achieved by suspending the birds in jackets without contact the floor. The group II was located in the centre ofthe turntable of the centrifuge. The control group I. was kept under normal conditions. The quantitative ultrastructure of myocard was evaluated by the methods of Weibel/3/ - this enables to determine the number, relative size and volume of mitochondria volume of single mitochondria, defficiency of mitochondrial cristae and volume of myofibrils.

Heterogeneity and Immunochemical Properties of Anti-β2-glycoprotein I Autoantibodies

1998 ◽  
Vol 80 (09) ◽  
pp. 393-398 ◽  
Author(s):  
V. Regnault ◽  
E. Hachulla ◽  
L. Darnige ◽  
B. Roussel ◽  
J. C. Bensa ◽  
...  
Keyword(s):  
Fluid Phase ◽  
Anticardiolipin Antibodies ◽  
Dual Reactivity ◽  
Group Iii ◽  
Important Group ◽  
Epitope Specificity ◽  
Glycoprotein I ◽  
Group I ◽  
Group Ii ◽  
Sufficient Concentration

SummaryMost anticardiolipin antibodies (ACA) associated with antiphospholipid syndrome (APS) are directed against epitopes expressed on β2-glycoprotein I (β2GPI). Despite a good correlation between standard ACA assays and those using purified human β2GPI as the sole antigen, some sera from APS patients only react in the latter. This is indicative of heterogeneity in anti-β2GPI antibodies. To characterize their reactivity profiles, human and bovine β2GPI were immobilized on γ-irradiated plates (β2GPI-ELISA), plain polystyrene precoated with increasing cardiolipin concentrations (CL/β2GPI-ELISA), and affinity columns. Fluid-phase inhibition experiments were also carried out with both proteins. Of 56 selected sera, restricted recognition of bovine or human β2GPI occurred respectively in 10/29 IgA-positive and 9/22 IgM-positive samples, and most of the latter (8/9) were missed by the standard ACA assay, as expected from a previous study. Based on species specificity and ACA results, IgG-positive samples (53/56) were categorized into three groups: antibodies reactive to bovine β2GPI only (group I) or to bovine and human β2GPI, group II being ACA-negative, and group III being ACA-positive. The most important group, group III (n = 33) was characterized by (i) binding when β2GPI was immobilized on γ-irradiated polystyrene or cardiolipin at sufficient concentration (regardless of β2GPI density, as assessed using 125I-β2GPI); (ii) and low avidity binding to fluid-phase β2GPI (Kd in the range 10–5 M). In contrast, all six group II samples showed (i) ability to bind human and bovine β2GPI immobilized on non-irradiated plates; (ii) concentration-dependent blockade of binding by cardiolipin, suggesting epitope location in the vicinity of the phospholipid binding site on native β2GPI; (iii) and relative avidities approximately 100-fold higher than in group III. Group I patients were heterogeneous with respect to CL/β2GPI-ELISA and ACA results (6/14 scored negative), possibly reflecting antibody differences in terms of avidity and epitope specificity. Affinity fractionation of 23 sera showed the existence, in individual patients, of various combinations of antibody subsets solely reactive to human or bovine β2GPI, together with cross-species reactive subsets present in all samples with dual reactivity namely groups III and II, although the latter antibodies were poorly purified on either column. Therefore, the mode of presentation of β2GPI greatly influences its recognition by anti-β2GPI antibodies with marked inter-individual heterogeneity, in relation to ACA quantitation and, possibly, disease presentation and pathogenesis.

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