Department of Haematology
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Item Fetomaternal hemorrhage among pregnant women in Accra, Ghana(International Federation of Gynecology and Obstetrics, 2019-07-04) Akorsu, E.E.; Acquaye, J.K.; Benneh, A.A.; Oppong, S.A.; Olayemi, E.Objective: To determine the occurrence of and risk factors for fetomaternal hemorrhage (FMH) among pregnant women at Korle Bu Teaching Hospital in Accra, Ghana. Methods: A prospective study of FMH among pregnant women without hemoglobinopathies in the second trimester attending prenatal care between October 2015 and May 2016 performed using the Kleihauer-Betke test. Volume of FMH was estimated; ABO and Rh blood groups of participants were determined. A data extraction form and structured questionnaire were used to collect demographic and clinical information, and data on risk factors. Results: Of 151 participants, 32 (21.2%) had FMH. Almost 18% (n=27) had FMH at baseline (16–24 weeks), 10% (10/100) at 28–32 weeks, and 11.1% (11/99) at 34–37 weeks of pregnancy. Volume of FMH was less than 30 mL in 30 (19.9%) women, whereas it was greater than 30 mL in 2 (1.3%) women. No identifiable patient-specific factors were associated with occurrence of FMH. Conclusion: FMH is common among pregnant women in Ghana and can occur as early as 16 weeks, without identifiable risk factors. RhD negative women who may be pregnant with RhD positive fetuses should be screened early in pregnancy, not only at delivery, for occurrence of FMH.Item Prevalence of potentially zoonotic gastrointestinal parasites in canine faeces in Ibadan, Nigeria(Ghana Medical Journal, 2016-12) Ayinmode, A.B.; Obebe, O.; Olayemi, E.Background: Humans can get infected through direct or indirect contact with infective stages of zoonotic parasites shed to the environment through dog faeces. Objectives: This study was designed to investigate the presence of gastrointestinal parasites present in dog faeces shed on the street of Ibadan metropolis, one of the largest cities in Africa. Methods: Twenty-three locations were randomly selected using grid-sampling method. A total of 203 faecal samples collected from the streets of selected areas were processed for detection of helminth eggs and protozoan oocysts using flotation technique. Eggs/oocysts per gram of faeces was counted using modified McMaster technique. Results: The prevalence of gastrointestinal parasites was 43.3% (88/203). Single and multiple infections were 69 (78.4%) and 19 (21.6%) respectively. The parasites detected were Ancylostoma sp. 24.6% (50/88) Isospora sp. 14.2% (29/88), Toxocara sp. 9.8% (20/88), Uncinaria sp. 2.5% (5/88) and Strongyloides sp, 3.9% (8/88). Ancylostoma sp. (320 x 102 epg) and Uncinaria sp. (5 x 102 epg) had the highest and least intensity respectively. Streets within residential areas having markets had the highest number of positive samples. All the genera of parasites detected in this study have zoonotic potential. Conclusion: The high prevalence of zoonotic parasites detected in dog faeces from Ibadan metropolis showed that infected stray dogs roam the streets and constitute potential risk to human health. This study suggests the need for enforcement of laws restraining roaming or straying dogs and proper veterinary care of dogs.Item Sensorineural Hearing Loss in Ghanaians with Sickle Cell disease.(Ghana Medical Journal, 1989-01) Ankra-Badu, G.; Atsina, K.K.A study seeking to determine whether Sensorineural hearing loss occurs with similar prevalence in sickle cell haemoglobin (Hb) SS and SC disease patients was conducted on 200 subjects comprising 93 Hb SC patients, 55 Hb SS patient. and 52 Hb AA subjects serving as controls. Each subject was given haematological and pure tone audiological examinations. Three out of 93 Hb SC patient (3.2%) showed hearing losses ranging from 30 10 40 dB but 15 out of 55 Hb SS patients (27.3%) exhibited hearing loss ranging from 30 to 60 dB. All hearing losses were in the high frequency range of 4 to 8kHz, Further studies art required to determine why Sensorineural hearing loss is prevalent in Hb SS patients but not so common in Hb SC patients.Item Ten Years of Preoperative Autologous Blood Donation in Accra(Ghana Medical Journal, 2006-12) Ansah, J.K.; Acquaye, J.K.Background - Preoperative autologous blood donation (PABD) is utilized to circumvent the use of allogenic blood for various reasons. Objective - To describe the distribution in terms of demographic characteristic, trends in participation and result of screening test of the PABD programme of the Accra Area Blood Center from 1993-2003. Design and Setting Retrospective descriptive study of PABD in patients scheduled for a variety of elective surgical procedures. Setting- Different levels of institutional health care in Accra, Ghana. Methods Data from existing records of patients who had participated in PABD were collated and analyzed Results Five hundred and forty six (546) females and 89 males participated, with ages ranging between 14-74 years. Majority of the patients (76.7%) underwent gynaecological surgery. A total of 330 (52%) donated one unit only, and 299 (47.1%) donated two units. Majority of the patients (56.4%) had the surgery at the Korle-Bu Teaching Hospital (KBTH). Of the donations, 21 (3.3%), 1 (0.2%), 1 (0.3%) and nil were positive for HBV, HIV I & II, HCV and VDRL respectively. A total of 848 (89.4%) autologous crossmatched units were issued out. There was a steady progressive increase in participation. Conclusion Mainly adult females scheduled for gynaecological surgeries in KBTH participated, while almost equal proportions donated one or two units of blood which meets the blood needs of most elective surgeries. Therefore healthy patients going for elective surgeries in regions with limited blood supply must be encouraged to enter a PABD Programme. Further studies in this field should evaluate motivational factors for participationItem Presentation and survival of multiple myeloma patients in Ghana: a review of 169 cases(Ghana medical journal, 2019-03) Dei-Adomakoh, Y.; Acquah, M.E.; Hsing, A.W.; McGuire, V.; Wang, S.; Birmann, B.Background: Africans have an increased risk for multiple myeloma (MM) compared to other races. Reports from Africa are few and involve small cohorts, but suggest significant epidemiological and clinical differences from Caucasian patients. Objective: This report describes the clinic-pathological features of MM patients in Ghana at diagnosis, and the factors affecting their survival. Methods: A retrospective review of 169 MM cases diagnosed in a Ghanaian tertiary hospital from 2002-2016. Results: Median age was 58 years, with 29% ≤50 years. One-third presented >12 months after onset of symptoms, which included bone pain (96%), anaemia (67%), weight loss (55%) and fractures (44%). Myeloma-related tissue impairment included hypercalcaemia (36%), renal impairment (33%), severe anaemia (52%) and osteolytic lesions (76%); 51.3% of patients were diagnosed in ISS Stage III. Median survival was 33 months; 1-year and 5-year overall survival were 51.6% and 15.5%, respectively. Neither the age at diagnosis nor the duration of symptoms prior to diagnosis correlated with prognosis. Median survival improved with early ISS stage, haemoglobin >8g/dL, plasmacytosis <20%, and normal creatinine and calcium levels. Conclusion: Early onset and late stage presentation are common at diagnosis of MM patients in Ghana, but do not affect survival. Studies into genetic associations are recommended.Item Guidelines in lower-middle income countries(British Journal of Haematology, 2017-03) Olayemi, E.; Asare, E.V.; Benneh-Akwasi Kuma, A.A.Guidelines include recommendations intended to optimize patient care; used appropriately, they make healthcare consistent and efficient. In most lower-middle income countries (LMICs), there is a paucity of well-designed guidelines; as a result, healthcare workers depend on guidelines developed in Higher Income Countries (HICs). However, local guidelines are more likely to be implemented because they are applicable to the specific environment; and consider factors such as availability of resources, specialized skills and local culture. If guidelines developed in HICs are to be implemented in LMICs, developers need to incorporate local experts in their development. Involvement of local stakeholders may improve the rates of implementation by identifying and removing barriers to implementation in LMICs. Another option is to encourage local experts to adapt them for use in LMICs; these guidelines may recommend strategies different from those used in HICs, but will be aimed at achieving the best practicable standard of care. Infrastructural deficits in LMICs could be improved by learning from and building on the successful response to the human immunodeficiency virus/acquired immunodeficiency syndrome pandemic through interactions between HICs and LMICs. Similarly, collaborations between postgraduate medical colleges in both HICs and LMICs may help specialist doctors training in LMICs develop skills required for guideline development and implementation. © 2017 John Wiley & Sons LtdItem Implementation of multidisciplinary care reduces maternal mortality in women with sickle cell disease living in low-resource setting(Social Science Journal, 2017-05) Asare, E.V.; Olayemi, E.; Boafor, T.; Dei-Adomakoh, Y.; Mensah, E.; Ghansah, H.; Osei-Bonsu, Y.; Crabbe, S.; Musah, L.; Hayfron-Benjamin, C.; Covert, B.; Kassim, A.A.; James, A.Sickle cell disease (SCD) is associated with adverse pregnancy outcome. In women with SCD living in low-resource settings, pregnancy is associated with significantly increased maternal and perinatal mortality rates. We tested the hypothesis that implementing a multidisciplinary obstetric and hematology care team in a low-resource setting would significantly reduce maternal and perinatal mortality rates. We conducted a before-and-after study, at the Korle-Bu Teaching Hospital in Accra, Ghana, to evaluate the effect of a multidisciplinary obstetric-hematology care team for women with SCD in a combined SCD-Obstetric Clinic. The pre-intervention period was assessed through a retrospective chart review to identify every death and the post-intervention period was assessed prospectively. Interventions consisted of joint obstetrician and hematologist outpatient and acute inpatient reviews, close maternal and fetal surveillance, and simple protocols for management of acute chest syndrome and acute pain episodes. Primary outcomes included maternal and perinatal mortality rates before and after the study period. A total of 158 and 90 pregnant women with SCD were evaluated in the pre- and post- intervention periods, respectively. The maternal mortality rate decreased from 10 791 per 100 000 live births at pre-intervention to 1176 per 100 000 at postintervention, representing a risk reduction of 89.1% (P50.007). Perinatal mortality decreased from 60.8 per 1000 total births at pre-intervention to 23.0 per 1000 at post-intervention, representing a risk reduction of 62.2% (P50.20). A multidisciplinary obstetric and hematology team approach can dramatically reduce maternal and perinatal mortality in a low-resource setting.© 2017 Wiley Periodicals, Inc.Item Sjögren's and plasma cell variant Castleman disease: a case report(Ghana medical journal, 2018-04) Dei-Adomakoh, Y.A.; Quarcoopome, L.; Abrahams, A.D.; Segbefia, C.I.; Dey, D.I.Castleman disease is a rare cause of lymphoid hyperplasia and may result in localized symptoms or an aggressive, multisystem disorder. It can mimic other diseases like lymphoma or tuberculosis. It classically presents as a mediastinal mass that involves the lymphatic tissue primarily but can also affect extra lymphatic sites including the lungs, larynx, parotid glands, pancreas, meninges, and muscles. In HIV and HHV8-negative patients with idiopathic multi-centric Castleman disease, pathogenesis may involve autoimmune mechanisms. We highlight and report a case of a 34-year-old Ghanaian female who was successfully diagnosed and managed for Sjögren's as well as plasma cell variant Castleman disease with combination chemotherapy and rituximab followed by eighteen months maintenance therapy with pulse chlorambucil and prednisolone and three monthly rituximab.Item Augmented NRF2 activation protects adult sickle mice from lethal acute chest syndrome(British Journal of Haematology, 2018-06) Ghosh, S.; Hazra, R.; Ihunnah, C.A.; Weidert, F.; Flage, B.; Ofori-Acquah, S.F.Acute chest syndrome (ACS) mortality in sickle cell disease (SCD) rises sharply in young adult patients and mechanism-based prophylaxis is lacking. In SCD, haem oxygenase-1 (HO-1) declines with age and ACS is associated with low HO-1. To test if enhanced HO-1 can reduce ACS mortality, young SCD mice were treated with D3T (3H-1,2-dithiole-3-thione), an activator of nuclear-factor erythroid 2 like 2, which controls HO-1 expression, for 3 months. Following haem-induced ACS, all vehicle-treated mice succumbed to severe lung injury, while D3T-treated mice had significantly improved survival. Blocking HO-1 activity abrogated the D3T effect. Thus HO-1 may be targeted to reduce ACS severity in adult patients.Item Lung Function Abnormalities in Sickle Cell Anaemia(Advances in Hematology, 2019-04) Dei-Adomakoh, Y.A.; Afriyie-Mensah, J.S.; Forson, A.; Adadey, M.; Ndanu, T.A.; Acquaye, J.K.Background. Abnormalities in lung function tests have been shown to commonly occur in a majority of patients with sickle cell disease (SCD) even at steady state. The prevalence and pattern of these lung function abnormalities have been described in other populations but this is unknown among our sickle cell cohort. There is generally little information available on risk factors associated with the lung function abnormalities and its relevance in patient care. Method. This was an analytical cross-sectional study involving 76 clinically stable, hydroxyurea-naive adult Hb-SS participants and 76 nonsickle cell disease (non-SCD) controls. A structured questionnaire was used to obtain sociodemographic data and clinical history of the participants. Investigations performed included spirometry, pulse oximetry, tricuspid regurgitant jet velocity (TRV) measurements via echocardiogram, complete blood counts, free plasma haemoglobin, serum urea, and creatinine. Results. Weight, BMI, mean FVC, and FEV1% predicted values were comparatively lower among the Hb-SS patients (p < 0.001). Abnormal spirometry outcome occurred in 70.4% of Hb-SS patients, predominantly restrictive defects (p < 0.001), and showed no significant association with steady-state Hb, WBC count, free plasma haemoglobin, frequency of sickling crisis, chronic leg ulcers, and TRV measurements (p > 0.05). The mean oxygen saturation was comparatively lower among Hb-SS patients (p < 0.001). Conclusion. Measured lung volumes were significantly lower in Hb-SS patients when compared to non-SCD controls and this difference was not influenced by anthropometric variance. Lung function abnormalities, particularly restrictive defects, are prevalent in Hb-SS patients but showed no significant association with recognized markers of disease severity.Item Mismatch in body-chair dimensions and the associated musculoskeletal pain among selected undergraduate students in Ghana(Journal of Musculoskeletal Research, 2013-09) Bello, A.I.; Sepenu, A.S.Purpose: To assess the misfit in body-chair dimensions ith regard to the occurrence of musculoskeletal pain among undergraduates. Methods: Selected undergraduate students of School of Allied Health Sciences University of Ghana, participated in this study. The popliteal height, buttock-popliteal length and the hip breadth of the students ere measured in sitting using retractable tape measure. The corresponding seat height, seat depth and seat idth of three fixed-style lecture hall chairs ere similarly measured and the average scores ere determined. Mismatch or fit in body-chair dimension ere calculated through a standard rule. The associated musculoskeletal pain as reported by the participants as assessed using numerical rating scale. Data ere analyzed ith percentage, mean, standard deviation and Krukas-allis test at p < 0.05. Results: A total of 126 students ith mean age 22 ± 01 years ere recruited. The mean popliteal height, buttock-popliteal length and hip breadth of the students ere 40.8(4.5), 46.8(4.6) and 35.3(3.3) cm, respectively hile the corresponding average chair dimensions for seat height, seat depth and seat idth ere 52.0, 51.0 and 53.0 cm, respectively. Appreciable number of the students mismatched the lecture hall chair at the three levels of study. About 114 (90.5%) of the students attributed their pain to the study chairs in hich 40 (31.7%) and 38 (30.2%) ere in their fourth and second years of study, respectively. Loer back pain as the most prevalent (38.6%) among the sampled students. Conclusion: The large proportion of the incompatibility indicated that the school chairs ere not designed based on anthropometric dimensions, thus giving insight into the source of the pain. © World Scientific Publishing Company.Item Plasma levels of some coagulation parameters in Steady State HBSC disease patients(Pan African Medical Journal, 2014-11) Ajuwon, M.D.; Olayemi, E.; Benneh, A.A.Introduction: sickle cell disease is a collection of autosomal recessive genetic disorders. It includes homozygous HbSS and double heterozygote combinations such as HbSC. Central and West Africa bears a significant burden of HbSC disease.Methods: prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen concentration (FC) and platelet count (PC) weredetermined in 41HbSC and HbSS patientsin steady state along with 40 apparently healthy HbAA controls. One way ANOVA test was used to compare means;p values < 0.05 were considered statistically significant.Results: there was no significant difference in mean PT for the study groups (p = 0.192). Mean PC was highest in HbSS patients: 445.7 +/- 128.3 X 10 9/ L compared to HbSC: 330.0 +/- 97.7 X 10 9/ L andHbAA:245 +/- 77.7 X 10 9/ L (p= 0.000).Mean APTT was 28.1 +/- 3.8 seconds in controls,24.1+/- 66 seconds in HbSS patients and 21.8 +/- 3.8 seconds in HbSC patients (p = 0.000). Mean FCin HbSS was 1.6 +/- 0.7 g/L , 3.2 +/- 0.6 g/L in HbSC and 2.9 +/- 0.4 g/L in HbAA (p =0.000).Conclusion: a significant difference exists in PC, APTT and FC in HbSC patients compared to HbSS patients and HbAA controls. Elevated FC and shortened APTT may play a role in complications more characteristic of HbSC such as retinopathy and osteonecrosis. These suggestHbSC is not merely a milder form of HbSS; both diseases should be seen as different entities with regards to approaches for management. © 2014, Mauryne Debola Ajuwon et al.Item Haematological Aspects of Tropical Diseases(Postgraduate Haematology, Sixth edition, 2010-11) Bates, I.; Ekem, I.Rapid increases in worldwide travel mean that haematologists need to keep up to date with tropical diseases that can cause haematological abnormalities. This chapter covers tropical diseases associated with organisms in the blood or bone marrow (e.g. malaria, filariasis, sleeping sickness, Chagas disease, leishmaniasis) and diseases which alter the blood count or coagulation systems. This chapter not only describes the haematological abnormalities associated with these conditions but also provides an overview of disease epidemiology, clinical presentation, diagnosis and the haematological complications of treatment.Item Managing healthcare quality in ghana: A necessity of patient satisfaction(2011) Atinga, R.A.; Abeka-Nkrumah, G.; Domfeh, K.A.Purpose – The study aims to examine how communication, provider courtesy, support/care, environment of the facility and waiting time significantly predict patients’ satisfaction with quality of healthcare in two hospitals located in northern Ghana. Design/methodology/approach – An exploratory study of which 324 respondents were selected using stratified and convenient sampling techniques. Results are presented using a multiple regression model. Findings – The results revealed that of the five-factor model, support/care, environment of the facility and waiting time determine patients’ satisfaction with quality of healthcare delivery. The explanatory power of the dependent variable was explained by 51 percent. Originality/value – The findings suggest that internal and external health sector stakeholders may possibly use this study.Item Microvessels in health and disease.(2012-04) Inal, J.M.; Ansa-Addo, E.A.; Stratton, D.; Kholia, S.; Antwi-Baffour, S.; Jorfi, S.; Lange, S.Microvesicles (or MVs) are plasma membrane-derived vesicles released from most eukaryotic cells constitutively during early apoptosis or at higher levels after chemical or physical stress conditions. This review looks at some of the functions of MVs in terms of intercellular communication and ensuant signal transduction, including the transport of proteins (unconventional protein export) as well as of mRNA and microRNA. MVs also have roles in membrane repair, the removal of misfolded proteins, and in the control of apoptosis. We also discuss the role MVs have been shown to have in invasive growth and metastasis as well as in hypoxia in tumours and cerebral ischaemia. The association of MVs in infectious and autoimmune disease is also summarised together with their possible use as therapeutic agents.Item Red cell PMVs, plasma membrane-derived vesicles calling out for standards.(2010-09) Hind, E.; Heugh, S.; Ansa-Addo, E.A.; Antwi-Baffour, S.; Lange, S.; Inal, J.Plasma membrane-derived vesicles (PMVs) or microparticles are vesicles (0.1-1mum in diameter) released from the plasma membrane of all blood cell types under a variety of biochemical and pathological conditions. PMVs contain cytoskeletal elements and some surface markers from the parent cell but lack a nucleus and are unable to synthesise macromolecules. They are also defined on the basis that in most cases PMVs express varying amounts of the cytosolic leaflet lipid phosphatidylserine, which is externalised during activation on their surface. This marks the PMV as a biologically distinct entity from that of its parent cell, despite containing surface markers from the original cell, and also explains its role in events such as phagocytosis and thrombosis. There is currently a large amount of variation between investigators with regard to the pre-analytical steps employed in isolating red cell PMVs or RPMVs (which are slightly smaller than most PMVs), with key differences being centrifugation and sample storage conditions, which often leads to result variability. Unfortunately, standardization of preparation and detection methods has not yet been achieved. This review highlights and critically discusses the variables contributing to differences in results obtained by investigators, bringing to light numerous studies of which RPMVs have been analysed but have not yet been the subject of a review.Item A filtration-based protocol to isolate human plasma membrane-derived vesicles and exosomes from blood plasma.(2011-08-31) Grant, R.; Ansa-Addo, E.; Stratton, D.; Antwi-Baffour, S.; Jorfi, S.; Kholia, S.; Krige, L.; Lange, S.; Inal, J.The methods of Plasma Membrane-derived Vesicle (PMV) isolation and quantification vary considerably in the literature and a new standard needs to be defined. This study describes a novel filtration method to isolate PMVs in plasma, which avoids high speed centrifugation, and to quantify them using a Becton Dickinson (BD) FACS Calibur™ flow cytometer, as annexin V-positive vesicles, larger than 0.2 μm in diameter. Essentially microvesicles (which comprise a mixture of PMVs and exosomes) from citrate plasma were sonicated to break up clumped exosomes, and filtered using Millipore 0.1 μm pore size Hydrophilic Durapore membranes in Swinnex 13 mm filter holders. Phosphatidylserine-positive PMVs detected with annexin V-PE were quantified using combined labelling and gating strategies in conjunction with Polysciences Polybead Microspheres (0.2 μm) and BDTrucount tubes. The PMV absolute count was calculated on the analysis template using the Trucount tube lot number information and expressed in PMV count/ml. Having estimated a normal reference range (0.51×10(5)-2.82×10(5) PMVs/ml) from a small sample of human donors, using the developed method, the effect of certain variables was investigated. Variations such as freezing of samples and gender status did not significantly alter the PMV absolute count, and with age plasma PMV levels were only marginally reduced. Smokers appeared to have reduced PMV levels. Nicotine, as for calpeptin was shown to dose-dependently (from 10 up to 50 μM) reduce levels of early apoptosis in THP-1 monocytes and to decrease the level of PMV release. Fasting individuals had 2-3 fold higher PMV absolute counts compared to non-fasting subjects.Item Human plasma membrane-derived vesicles inhibit the phagocytosis of apoptotic cells - possible role in SLE.(2010-07-23) Antwi-Baffour, S.; Kholia, S.; Aryee, Y.K.; Ansa-Addo, E.A.; Stratton, D.; Lange, S.; Inal, J.M.Plasma membrane-derived vesicles (PMVs) also known as microparticles, are small membrane-bound vesicles released from the cell membrane via blebbing and shedding. PMVs have been linked with various physiological functions as well as pathological conditions such as inflammation, autoimmune disease and cardiovascular disease. PMVs are characterised by the expression of phosphatidylserine (PS) on the plasma membrane. PS, also expressed on apoptotic cells (ACs) enables macrophages to phagocytose ACs. As it is widely known that PMV production is increased during apoptosis, we were able to show that PMVs could compete dose dependently with ACs for the PS receptor on macrophages, so reducing phagocytosis of ACs. In a clinical setting this may result in secondary necrosis and further pathological conditions. In SLE in which there are raised PMV levels, there is an anti-phospholipid-mediated increase in PMV release, which can be abrogated by depletion of IgG. Our work provides an insight into how PMVs may play a role in the aetiology of autoimmune disease, in particular SLE.Item Human plasma membrane-derived vesicles halt proliferation and induce differentiation of THP-1 acute monocytic leukemia cells.(2010) Ansa-Addo, E.A.; Lange, S.; Stratton, D.; Antwi-Baffour, S.; Cestari, I.; Ramirez, M.I.; McCrossan, M.V.; Inal, J.M.Plasma membrane-derived vesicles (PMVs) are small intact vesicles released from the cell surface that play a role in intercellular communication. We have examined the role of PMVs in the terminal differentiation of monocytes. The myeloid-differentiating agents all-trans retinoic acid/PMA and histamine, the inflammatory mediator that inhibits promonocyte proliferation, induced an intracellular Ca2+-mediated PMV (as opposed to exosome) release from THP-1 promonocytes. These PMVs cause THP-1 cells to enter G0–G1 cell cycle arrest and induce terminal monocyte-to-macrophage differentiation. Use of the TGF-β receptor antagonist SB-431542 and anti–TGF-β1 Ab showed that this was due to TGF-β1 carried on PMVs. Although TGF-β1 levels have been shown to increase in cell culture supernatants during macrophage differentiation and dendritic cell maturation, the presence of TGF-β1 in PMVs is yet to be reported. In this study, to our knowledge we show for the first time that TGF-β1 is carried on the surface of PMVs, and we confirm the presence within PMVs of certain leaderless proteins, with reported roles in myeloid cell differentiation. Our in vitro findings support a model in which TGF-β1–bearing PMVs, released from promonocytic leukemia cells (THP-1) or primary peripheral blood monocytes on exposure to sublytic complement or after treatment with a differentiation therapy agent, such as all-trans retinoic acid, significantly reduce proliferation of THP-1 cells. Such PMVs also induce the terminal differentiation of primary peripheral blood monocytes as well as THP-1 monocytes.Item Plasma levels of Th1 and Th2 cytokines in Ghanaian children with vaccine-modified measles.(2003) Tetteh, J.K.A.; Addae, M.M.; Commey, J.O.O.; Ishiwada, N.; Yempewu, S.M.; Yamaguchi, S.; Ofori-Adjei, D.To understand the pathogenesis of vaccine-modified measles (VMM), we measured plasma levels of IFN-gamma and IL-2 (Th1 cytokines), IL-4 and IL-10 (Th2 cytokines), IL-12, TNF-alpha and TGF-beta1 in children with uncomplicated measles, who had anti-measles IgG antibodies and with a history of immunization on admission (day 0), day 14 and day 60. We compared these to levels in healthy, age-matched, immunized children. Plasma levels of IFN-gamma, IL-2 and IL-12 were significantly higher in VMM patients on day 0 compared to healthy controls (p = 0.023; p = 0.018; p = 0.001) respectively. In contrast, plasma IL-4 was lower in VMM patients on day 0 when compared to the controls (p = 0.009). Plasma levels of IL-12 remained consistently high on days 14 and 60 (p = 0.001; p = 0.04), whilst IL-10 levels fell significantly on the same days (p = 0.002; p = 0.001) respectively. Kinetically, IFN-gamma and IL-10 levels decreased consistently from day 0 to days 14 and 60 in VMM patients. In contrast, IL-4 levels increased from day 0 to day 14 and day 60. Our results therefore suggest that VMM is associated with an early up-regulation of Th1 cytokine production and a down-regulation of Th2 cytokine production. The strong Th1 response may be associated with the induction of IL-12 and memory cells, thus contributing to the early resolution of the infection and lack of complications.
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