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The effect of thrombopoietin on the proliferation and differentiation of murine hematopoietic stem cells 总被引:15,自引:16,他引:15
Sitnicka E; Lin N; Priestley GV; Fox N; Broudy VC; Wolf NS; Kaushansky K 《Blood》1996,87(12):4998-5005
In this study, we explored whether thrombopoietin (Tpo) has a direct in vitro effect on the proliferation and differentiation of long-term repopulating hematopoietic stem cells (LTR-HSC). We previously reported a cell separation method that uses the fluorescence-activated cell sorter selection of low Hoescht 33342/low Rhodamine 123 (low Ho/low Rh) fluorescence cell fractions that are highly enriched for LTR-HSC and can reconstitute lethally irradiated recipients with fewer than 20 cells. Low Ho/low Rh cells clone with high proliferative potential in vitro in the presence of stem cell factor (SCF) + interleukin-3 (IL-3) + IL-6 (90% to 100% HPP-CFC). Tpo alone did not induce proliferation of these low Ho/low Rh cells. However, in combination with SCF or IL-3, Tpo had several synergistic effects on cell proliferation. When Tpo was added to single growth factors (either SCF or IL-3 or the combination of both), the time required for the first cell division of low Ho/low Rh cells was significantly shortened and their cloning efficiency increased substantially. Moreover, the subsequent clonal expansion at the early time points of culture was significantly augmented by Tpo. Low Ho/low Rh cells, when assayed in agar directly after sorting, did not form megakaryocyte colonies in any growth condition tested. Several days of culture in the presence of multiple cytokines were required to obtain colony-forming units-megakaryocyte (CFU-Mk). In contrast, more differentiated, low Ho/high Rh cells, previously shown to contain short- term repopulating hematopoietic stem cells (STR-HSC), were able to form megakaryocyte colonies in agar when cultured in Tpo alone directly after sorting. These data establish that Tpo acts directly on primitive hematopoietic stem cells selected using the Ho/Rh method, but this effect is dependent on the presence of pluripotent cytokines. These cells subsequently differentiate into CFU-Mk, which are capable of responding to Tpo alone. Together with the results of previous reports of its effects on erythroid progenitors, these results suggest that the effects of Tpo on hematopoiesis are greater than initially anticipated. 相似文献
4.
Merlin Sobia Poomani Iyyadurai Mariappan Ramachandran Perumal Rathika Regurajan Krishnaveni Muthan Venkatesh Subramanian 《Global Heart》2022,17(1)
Although tremendous progress has been made in conventional treatment for ischemic heart disease, it still remains a major cause of death and disability. Cell-based therapeutics holds an exciting frontier of research for complete cardiac recuperation. The capacity of diverse stem and progenitor cells to stimulate cardiac renewal has been analysed, with promising results in both pre-clinical and clinical trials. Mesenchymal stem cells have been ascertained to have regenerative ability via a variety of mechanisms, including differentiation from the mesoderm lineage, immunomodulatory properties, and paracrine effects. Also, their availability, maintenance, and ability to replenish endogenous stem cell niches have rendered them suitable for front-line research. This review schemes to outline the use of mesenchymal stem cell therapeutics for ischemic heart disease, their characteristics, the potent mechanisms of mesenchymal stem cell-based heart regeneration, and highlight preclinical data. Additionally, we discuss the results of the clinical trials to date as well as ongoing clinical trials on ischemic heart disease. 相似文献
5.
GV Ramesh Prasad Marcel Ruzicka Kevin D Burns Sheldon W Tobe Marcel Lebel 《The Canadian journal of cardiology》2009,25(5):309-314
For the first time, the Canadian Hypertension Education Program has studied the evidence supporting blood pressure control in people requiring renal replacement therapy for end-stage kidney disease, including those on dialysis and with renal transplants. According to the Canadian Organ Replacement Registry’s 2008 annual report, there were an estimated 33,832 people with end-stage renal disease in Canada at the end of 2006, an increase of 69.7% since 1997. Of these, 20,465 were on dialysis and 13,367 were living with a functioning kidney transplant. Thus, it is becoming more likely that primary care practitioners will be helping to care for these complex patients. With the lack of large controlled clinical trials, the consensus recommendation based on interpretation of the existing literature is that blood pressure should be lowered to below 140/90 mmHg in hypertensive patients on renal replacement therapy and to below 130/80 mmHg for renal transplant patients with diabetes or chronic kidney disease. 相似文献
6.
The coeliac iceberg in Italy. A multicentre antigliadin antibodies screening for coeliac disease in school-age subjects 总被引:8,自引:0,他引:8
C Catassi E Fabiani IM Rätsch GV Coppa PL Giorgi R Pierdomenico S Alessandrini G Iwanejko R Domenici E Mei A Miano M Marani G Bottaro M Spina M Dotti A Montanelli M Barbato F Viola R Lazzari M Vallini G Guariso M Plebani F Cataldo G Traverso C Ughi G Chiaravalloti M Baldassarre P Scarcella F Bascietto L Ceglie A Valenti P Paolucci M Caradonna E Bravi A Ventura 《Acta paediatrica (Oslo, Norway : 1992)》1996,85(S412):29-35
Background : Recent studies suggest that coeliac disease (CD) is one of the commonest, life-long disorders in Italy. The aims of this multicentre work were: (a) to establish the prevalence of CD on a nationwide basis; and (b) to characterize the CD clinical spectrum in Italy. Patients and methods : Fifteen centres screened 17201 students aged 6–15 years (68.6% of the eligible population) by the combined determination of serum IgG- and IgA-antigliadin antibody (AGA) test; 1289 (7.5%) were IgG and/or IgA-AGA positive and were recalled for the second-level investigation; 111 of them met the criteria for the intestinal biopsy: IgA-AGA positivity and/or AEA positivity or IgG-AGA positivity plus serum IgA deficiency. Results : Intestinal biopsy was performed on 98 of the 111 subjects. CD was diagnosed in 82 subjects (75 biopsy proven, 7 not biopsied but with associated AGA and AEA positivity). Most of the screening-detected coeliac patients showed low-grade intensity illness often associated with decreased psychophysical well-being. There were two AEA negative cases with associated CD and IgA deficiency. The prevalence of undiagnosed CD was 4.77 × 1000 (95% CI 3.79–5.91), 1 in 210 subjects. The overall prevalence of CD, including known CD cases, was 5.44 × 1000 (95% CI 4.57–6.44), 1 in 184 subjects. The ratio of known to undiagnosed CD cases was 1 in 7. Conclusions : These findings confirm that, in Italy, CD is one of the most common chronic disorders showing a wide and heterogeneous clinical spectrum. Most CD cases remain undiagnosed unless actively searched. 相似文献
7.
Hill JC Krishnaveni GV Annamma I Leary SD Fall CH 《Acta obstetricia et gynecologica Scandinavica》2005,84(2):159-165
BACKGROUND: The incidence of type 2 diabetes is increasing worldwide, most rapidly in developing countries such as India. Exposure as a fetus to maternal gestational diabetes is thought to be a risk factor for developing the disease. This study was set up to determine the incidence of gestational diabetes mellitus in one urban maternity unit in South India and to examine its effect on the offspring's neonatal anthropometry, childhood growth, and glucose/insulin metabolism. This paper reports neonatal outcomes. METHODS: Seven hundred and eighty five women were recruited consecutively from the antenatal clinic of the Holdsworth Memorial Hospital, Mysore and underwent a 100 g, 3-hr oral glucose tolerance test at 30 +/- 2 weeks gestation. Gestational diabetes was defined using Carpenter and Coustan criteria. The babies were measured in detail at birth. RESULTS: Mean maternal age and body mass index were 23.6 years and 23.1 kg/m(2). The incidence of gestational diabetes was 6.2%. Mothers with gestational diabetes had babies that were heavier (3339 g compared with 2956 g for non-diabetic mothers) and larger in measurements of fat, muscle, and skeleton. Even in non-diabetic pregnancies, neonatal weight, head circumference, and ponderal index were positively related to maternal fasting glucose concentrations (P < or = 0.05 for all). CONCLUSIONS: The incidence of gestational diabetes was high in this unselected sample of mothers booking into one urban Indian maternity unit. Community-based studies are required to confirm this. The effect of maternal glucose concentrations on neonatal anthropometry is continuous and extends into the "normal" glycemic range. 相似文献
8.
Paltiel HJ; O'Gorman AM; Meagher-Villemure K; Rosenblatt B; Silver K; Watters GV 《Radiology》1987,162(1):115
9.
Prevalence and characteristics of brittle diabetes in Britain 总被引:3,自引:0,他引:3
Gill GV; Lucas S; Kent LA 《QJM : monthly journal of the Association of Physicians》1996,89(11):839-843
We investigated the prevalence and characteristics of 'brittle diabetes',
defined as insulin-dependent diabetes mellitus associated with glycaemic
instability of any type, leading to life disruption with recurrent and/or
prolonged hospitalizations. A questionnaire was sent to all physicians and
paediatricians running diabetic clinics in the UK, from lists held at the
British Diabetic Association. A total of 414 brittle patients were reported
(72% questionnaire return). Most were young (mean age +/- SD was 26 +/- 15
years), though there was a small peak at ages 60-70 years. There was an
excess of females (66%) and overall clinic prevalence was 1.2 per 1000
diabetic patients and 2.9 per 1000 insulin-treated diabetic patients. On
average, there was 1.0 brittle patient per diabetic clinic. The most common
form of brittleness was recurrent ketoacidosis (59%), with 17% having
predominant hypoglycaemia, and 24% mixed instability. Female excess was
highest and mean age lowest in the recurrent ketoacidosis group, whilst the
reverse was true for those with recurrent hypoglycaemia. Causes of
brittleness were offered by 58% of consultants, and most (93%) considered
various psychosocial problems as likely underlying factors. We conclude
that brittle diabetes is a small but significant problem, currently
affecting about 1 per 1000 diabetic patients. Most, but by no means all,
are young females--often with recurrent ketoacidosis. Older age groups are
more likely to have recurrent hypoglycaemic or mixed types of brittleness.
Perceived causes of brittleness are usually psychosocial.
相似文献
10.
SUMMARY Analysis of the age of onset of diabetes amongst insulin-treatedpatients in a large African diabetic clinic revealed a bimodaltype of distribution, 23 per cent having an age of onset before30 years and 77 per cent with onset at 30 years of age. All66 of the young insulin-treated group (21.7±4.8 years(mean±1 SD)), and a random selection of 50 older insulin-treatedpatients (49.7±10 years), were studied. The older groupwere better controlled (HbA1 8.4±1.7 per cent vs. 10.8±2.6per cent, p<0.001), on lower doses of insulin (49±23vs. 71±23 u/day, p<0.001) and had higher body massindex (26.0±5.6 vs. 21.8±3.5, p<0.001). SerumC-peptide (0.24±0.15 vs. 0.07±0.10 nmol/l, p<0.0001),and C-peptide/glucose ratio (2.57±2.65 vs. 0.56+0.98nmol/mmolx 102, p<0.001) were very significantly higher inolder patients. Patients with later onset disease thus had betterpreservation of pancreatic function, higher body mass indexand better glycaemic control on lower doses of insulin. Thesefeatures suggest that older insulin-treated patients could infact be Type 2 or non-insulin dependent patients,and the condition may be controllable with diet and/or oralhypoglycaemic agents, at least in some. 相似文献