PubMed HealthSearch

Biomedical subjects

E Bruno

Publications and source records attributed to E Bruno.

At least 19 recordsLinked to original sources

Ex vivo expansion of autologous bone marrow CD34(+) cells with porcine microvascular endothelial cells results in a graft capable of rescuing lethally irradiated baboons.

Hematopoietic stem cell (HSC) self-renewal in vitro has been reported to result in a diminished proliferative capacity or acquisition of a homing defect that might compromise marrow repopulation. Our group has demonstrated that human HSC expanded ex vivo in the presence of porcine microvascular endothelial cells (PMVEC) retain the capacity to competitively repopulate human bone fragments implanted in severe combined immunodeficiency (SCID) mice. To further test the marrow repopulating capacity of expanded stem cells, our laboratory has established a myeloablative, fractionated total body irradiation conditioning protocol for autologous marrow transplantation in baboons. A control animal, which received no transplant, as well as two animals, which received a suboptimal number of marrow mononuclear cells, died 37, 43, and 59 days postirradiation, respectively. Immunomagnetically selected CD34(+) marrow cells from two baboons were placed in PMVEC coculture with exogenous human cytokines. After 10 days of expansion, the grafts represented a 14-fold to 22-fold increase in cell number, a 4-fold to 5-fold expansion of CD34(+) cells, a 3-fold to 4-fold increase of colony-forming unit-granulocyte-macrophage (CFU-GM), and a 12-fold to 17-fold increase of cobblestone area-forming cells (CAFC) over input. Both baboons became transfusion independent by day 23 posttransplant and achieved absolute neutrophil count (ANC) >500/microL by day 25 +/- 1 and platelets >20,000/microL by day 29 +/- 2. This hematopoietic recovery was delayed in comparison to two animals that received either a graft consisting of freshly isolated, unexpanded CD34(+) cells or 175 x 10(6)/kg unfractionated marrow mononuclear cells. Analysis of the proliferative status of cells in PMVEC expansion cultures demonstrated that by 10 days, 99.8% of CD34(+) cells present in the cultures had undergone cycling, and that the population of cells expressing a CD34(+) CD38(-) phenotype in the cultures was also the result of active cell division. These data indicate that isolated bone marrow CD34(+) cells may undergo cell division during ex vivo expansion in the presence of endothelial cells to provide a graft capable of rescuing a myeloablated autologous host.

Animals

Role of members of the Wnt gene family in human hematopoiesis.

The hematopoietic system is derived from ventral mesoderm. A number of genes that are important in mesoderm development have been identified including members of the transforming growth factor-beta (TGF-beta) superfamily, the fibroblast growth factor (FGF) family, and the Wnt gene family. Because TGF-beta plays a pleiotropic role in hematopoiesis, we wished to determine if other genes that are important in mesoderm development, specifically members of the Wnt gene family, may play a role in hematopoiesis. Three members of the Wnt gene family (Wnt-5A, Wnt-2B, and Wnt-10B) were identified and cloned from human fetal bone stromal cells. These genes are expressed to varying levels in hematopoietic cell lines derived from T cells, B cells, myeloid cells, and erythroid cells; however, only Wnt-5A was expressed in CD34(+)Lin- primitive progenitor cells. The in vitro biological activity of these Wnt genes on CD34(+)Lin- hematopoietic progenitors was determined in a feeder cell coculture system and assayed by quantitating progenitor cell numbers, CD34(+) cell numbers, and numbers of differentiated cell types. The number of hematopoietic progenitor cells was markedly affected by exposure to stromal cell layers expressing Wnt genes with 10- to 20-fold higher numbers of mixed colony-forming units (CFU-MIX), 1.5- to 2. 6-fold higher numbers of CFU-granulocyte macrophage (CFU-GM), and greater than 10-fold higher numbers of burst-forming units-erythroid (BFU-E) in the Wnt-expressing cocultures compared with the controls. Colony formation by cells expanded on the Wnt-expressing cocultures was similar for each of the three genes, indicating similar action on primitive progenitor cells; however, Wnt-10B showed differential activity on erythroid progenitors (BFU-E) compared with Wnt-5A and Wnt-2B. Cocultures containing Wnt-10B alone or in combination with all three Wnt genes had threefold to fourfold lower BFU-E colony numbers than the Wnt-5A- or Wnt-2B-expressing cocultures. The frequency of CD34(+) cells was higher in Wnt-expressing cocultures and cellular morphology indicated that coculture in the presence of Wnt genes resulted in higher numbers of less differentiated hematopoietic cells and fewer mature cells than controls. These data indicate that the gene products of the Wnt family function as hematopoietic growth factors, and that they may exhibit higher specificity for earlier progenitor cells.

Adult

The Smad5 gene is involved in the intracellular signaling pathways that mediate the inhibitory effects of transforming growth factor-beta on human hematopoiesis.

Signals from transforming growth factor-beta (TGF-beta), a bifunctional regulator of the proliferation of hematopoietic progenitor cells, have been recently shown to be transduced by five novel human genes related to a Drosophila gene termed MAD (mothers against the decapentaplegic gene). We showed by reverse transcriptase polymerase chain reaction that the RNA from one homologue gene, Smad5, was present in the immortalized myeloid leukemia cell lines, KG1 and HL60, in bone marrow mononuclear and polymorphonuclear cells, as well as in purified CD34+ bone marrow cells. Therefore, we studied the role of this gene in the regulation of human hematopoiesis by TGF-beta. TGF-beta1 and TGF-beta2 significantly inhibited myeloid, erythroid, megakaryocyte, and multilineage colony formation as assayed in semisolid culture systems. The levels of Smad5 mRNA in CD34+ cells were decreased by antisense but not sense oligonucleotides to Smad5. Preincubation of CD34+ marrow cells with two sense oligonucleotides to Smad5 did not reverse the inhibitory effects of TGF-beta on hematopoietic colony formation. However, preincubation with two antisense oligonucleotides to Smad5 reversed the inhibitory effects of TGF-beta. These data show that the Smad5 gene is involved in the signaling pathway by which TGF-beta inhibits primitive human hematopoietic progenitor cell proliferation and that Smad5 antisense oligonucleotides can interrupt this signal.

Cell Division

Somatostatin release in response to glucose is impaired in chronic renal failure.

In order to evaluate somatostatin (SRIH) secretion in uremia, plasma SRIH concentrations were determined in basal conditions and after an oral glucose tolerance test (OGTT) in 14 non-dialysed patients with chronic renal failure (CRF), seven of whom had normal glucose tolerance (NGT) and seven impaired glucose tolerance (IGT). Plasma insulin, C-peptide and glucagon and blood glucose concentrations were also evaluated. The results were compared with those obtained in a group of age- and sex-matched normal subjects. In CRF patients, plasma SRIH fasting values (8.6 +/- 0.6 and 7.8 +/- 0.6 pmol/L in NGT and IGT patients, respectively) were comparable to those recorded in controls (7.7 +/- 0.5 pmol/L). SRIH response to OGTT, evaluated as area under curves (AUC) above basal, was similar in both groups of CRF patients (412.9 +/- 84.5 and 415.6 +/- 51.9 pmol/L per min), and significantly lower than in controls (660.1 +/- 58.5 pmol/L per min). Data indicate that chronic uremia induces a loss of SRIH secretory cell responsiveness to glucose. A possible effect of impaired SRIH secretion on glucose metabolism in CRF is discussed.

Adult

[Postural stabilization after otolithic repositioning for posterior semicircular canal canalization].

Today the canal/cupulolithiasic pathogenesis of benign paroxysmal positional vertigo (BPPV) appears well defined; what is less clear is the origin of the postural "instability" often associated with rotatory vertigo. This form is less marked but still resists all know treatments. The purpose of the present study was to determine the actual postural arrangement of subjects suffering from canalolithiasis (CL) of the posterior semicircular canal (PSC) both before and after the positioning maneuver. In this case a personal method of spectral frequency analysis was used in an attempt to clarify the origin of the residual "instability" following otolithic repositioning. Static posturographic testing was performed on 20 patients with CL of the PSC and another 20 normal subjects of comparable age. In the present study the repositioning maneuver leads to a reduction in latero-lateral oscillation without any anterior-posterior variation. Such stabilization covers all the frequencies if a visual input is also present while it is limited to the lower frequencies when the visual content is lacking. In fact, in the latter case the subject maintains his posture using only vestibular and proprioceptive input. On the other hand, the anterior-posterior oscillations increase in all frequency ranges and this increase remains essentially unchanged after the repositioning maneuver. The authors feel that the anterior-posterior destabilization seen in CL of the PSC may stem from a proprioceptive-macular alteration linked to otolitic detachment rather than abnormal ampullar stimulation. The persistence and residual postural alterations found could, therefore, explain the persistent sense of instability that CL patients often complain of, even after the maneuvers which have encountered such success in controlling BPPV.

Adult

Thrombopoietin mobilizes CD34+ cell subsets into peripheral blood and expands multilineage progenitors in bone marrow of cancer patients with normal hematopoiesis.

Thrombopoietin (TPO), the primary regulator of megakaryocytopoiesis, also mediates biologic effects in vitro on hematopoietic cells more primitive than those committed to the megakaryocyte (MK) lineage. To assess the spectrum of hematopoietic effects of recombinant human (rh)TPO in vivo, we evaluated its proliferative effect on bone marrow (BM) progenitor cells, its maturation effect on BM MKs, and its mobilizing effect on peripheral blood (PB) progenitor cells during a phase I clinical laboratory investigation in which rhTPO was administered to cancer patients with normal hematopoiesis. Twelve patients received a single dose of rhTPO (0.3, 0.6, 1.2, or 2.4 microg/kg of body weight) prior to chemotherapy. BM and PB samples from these patients were analyzed 1 to 2 days before (baseline) and 7 days after rhTPO administration. At higher doses (1.2-2.4 microg/kg), rhTPO produced increased concentrations of primitive CD34+Thy-1+Lin-cells (mean 2.1-fold), CD34+mpl+ cells (mean 5.2-fold), CD34+CD41+CD14- promegakaryoblasts (mean 2.9-fold), and myeloerythroid colony-forming cells (mean threefold) in BM. No significant increases in the frequency of BM colony-forming unit (CFU)-MK were observed. Elevated numbers of both immature (2N-8N) and more mature (64N and 128N) CD41+ MKs were detected in BM, with modal ploidy remaining at 16N. Higher doses of rhTPO (1.2-2.4 microg/kg) also induced increased concentrations of CD34+ cell subsets in PB, including both primitive CD34+Thy-1+Lin- (mean 8.8-fold) and MK lineage-committed CD34+CD41+CD14- cells (mean 14.6-fold) as well as various myeloerythroid colony-forming cells (mean 3.6- to 5.5-fold). These results demonstrate that rhTPO given as a single dose not only promotes proliferation and maturation of cells of the MK lineage, but also expands the pool of BM primitive hematopoietic cells. In addition, rhTPO induces mobilization of hematopoietic progenitors into peripheral circulation. The extent to which such multilineage effects on human progenitor cells will contribute to clinical efficacy remains to be determined.

Adolescent

Human megakaryocyte progenitor cells.

Megakaryocytopoiesis is a complex biological process involving a series of cellular events that is initiated with the pluripotent hematopoietic stem cell and eventually results in the biogenesis of platelets shed by mature megakaryocytes (MK). A hierarchy of human MK progenitor cells has been defined by means of studies of in vitro megakaryocytopoiesis. A number of in vitro clonal assays have been established that have aided in the characterization of each of these MK progenitor cells which can be distinguished by their cellular phenotype, physical characteristics, chemosensitivity, kinetics of colony formation, the size of the colonies that each progenitor cell subclass is capable of producing, and the cytokines required to induce such progenitor-cell-derived colony formation. The kinetics of appearance of these various classes of MK colonies derived from MK progenitor cells of differing proliferative capacity are consistent with a sequential developmental relationship between these various cellular subpopulations. The most primitive lineage-restricted MK progenitor cell identified to date is termed the high proliferative potential cell-MK (HPPC-MK). The HPPC-MK can be assayed from fetal but not adult human marrow, and in vitro it forms large unifocal pure MK colonies consisting of more than 300 cells (300 to 1,000). The burst forming unit-megakaryocyte is the most primitive MK progenitor cell that can be assayed from a variety of adult hematopoietic tissues, while the colony forming unit-megakaryocyte is the most differentiated MK progenitor cell still capable of forming pure MK colonies in vitro. Furthermore, a number of multipotent progenitor cells have been identified that are capable of producing colonies composed of multiple hematopoietic lineages of which MKs represent a minority component. A bipotent erythromegakaryocytic progenitor cell in human marrow has been carefully characterized that has the unique ability to form colonies composed exclusively of MKs and erythroblasts. This bipotent progenitor cell has been termed the burst-forming unit erythroid/MK and is indicative of the close linkage between features of the erythroid and megakaryocytic lineages. Recently the ex vivo incubation of CD34+ cells in the presence of a combination of cytokines has resulted in the generation of cell populations enriched for MKs and MK progenitor cells. Such an ex vivo generated product may serve as a source of a new generation of transfusion products capable of supporting thrombocytopenic patients.

Adult

Laryngeal metastasis from a signet ring cell carcinoma of the colon. A case report and review of the literature.

Secondary involvement of the larynx and pharynx by malignant neoplasms arising in contiguous structures is well known, but metastases to the larynx from distant tumors are rare. In the present paper a case of signet ring cell carcinoma of the transverse colon metastatic to the left pyriform sinus is reported. A review of the literature identifies 7 other published cases of metastases to the larynx from a colon carcinoma.

Aged

[Nasal reactivity in systemic lupus erythematosus].

The present study was prompted by the fact that alterations in nasal respiration were observed in patients with active Systemic Lupus Erythematosus (SLE). These alterations were most likely of a disreactive nature and, thus, could not be attributed to pathology-induced vasculitic alterations. The study was performed using the case/control method. Patients with active SLE were selected on the basis of reference symptoms (difficulty in nasal breathing) and the absence of any significant alteration in the rhinological objectives. Basal, positioning and evoked (cold water, 5 degrees C) rhinomanometry was performed in line with the standards suggested by the "Committee Report on Standardization of Rhinomanometry". Positional testing of the SLE patients revealed "paradoxical response" (66% in the supine decubitus, 50% homolateral and 56% controlateral). In addition there was a statistically significant (p < 0.05) increase in resistance vs. the control group both in the positional testing and upon cold water stimulation. The authors recognized that the rhinomanometric values found in the SLE patients--index of nasal mucosa disreactivity--confirm the presence of the distonic-vegetative alterations characteristic of aspecific vasomotor rhinopathy. In conclusion, the authors hypothesize on the pathogenic mechanisms behind the clinical and instrumental conditions revealed in light of the documented autonomic neuropathy present in SLE patients.

Adult

Plasma somatostatin response to an oral test meal in liver transplant patients.

Ten liver transplant patients were studied in basal conditions and after ingestion of a standard mixed test meal. Control groups included 10 normal subjects, 10 patients with nonalcoholic liver cirrhosis, and seven kidney transplant patients. Plasma somatostatin, blood glucose, and plasma insulin, C-peptide, and glucagon were determined before and 15, 30, 45, 60, 90, 120, and 180 minutes after the start of the meal. In liver transplant patients, basal somatostatin and insulin levels were significantly lower than in cirrhotics and were comparable to those recorded in controls and in kidney transplant patients. The time course of the somatostatin secretory response after the meal was similar in any group, but the increase, evaluated as the incremental area above baseline, was significantly higher in liver transplant patients than in controls and cirrhotics and comparable to that recorded in kidney transplant patients. Insulin incremental areas were also lower than in cirrhotics and comparable to those recorded in controls and kidney transplant patients. The data suggest that in liver transplant patients an increased somatostatin response to a meal may be related to a relative beta-cell secretory defect, which in turn seems consequent to immunosuppressive treatment.

Adult

The interaction between age and comorbidity contributes to predicting the mortality of geriatric patients in the acute-care hospital.

OBJECTIVE: To test the predictive power of comorbidity and of the interaction between age and comorbidity in geriatric patients with acute medical illness. DESIGN: Prospective observational study. SETTING: Medical and geriatric wards of an acute-care hospital. SUBJECTS: Three hundred and seventy patients over 70 years of age consecutively admitted in an 18-month period. MAIN OUTCOME MEASURE: In-hospital mortality. METHOD: On admission a multidimensional assessment was performed, and a comorbidity index and an age-comorbidity index developed on a comparable training population were calculated. The comorbidity index is based upon a scoring system that quantifies the prognostic weight of individual diseases, while the age-comorbidity index corrects the former for the age-related increase of the risk of death. The predictive power of variables univariately correlated with the outcome was tested by logistic regression. RESULTS: Death was independently predicted by clinical diagnosis of malnutrition (odds ratio = 1.87, confidence limits CL = 1.20-2.86), age-comorbidity index > 7 (odds ratio = 1.77, CL = 1.15-2.72), preadmission impairment in activities of daily living (odds ratio = 1.74, CL = 1.13-2.69), lymphocytopenia (odds ratio = 1.74, CL = 1.15-2.61). A weaker predictive model was obtained by substituting the comorbidity index for the index of age-comorbidity. Excluding comorbidity from the logistic regression greatly weakened the predictive model.

Acute Disease

Contribution of central neuropathy to postural instability in IDDM patients with peripheral neuropathy.

OBJECTIVE: To evaluate the contribution of central neuropathy on postural impairment observed in diabetic patients with peripheral neuropathy. RESEARCH DESIGN AND METHODS: Central sensory and motor nervous propagation, nerve conduction velocity, and static posturography were assessed in the following age-matched subjects: 7 IDDM patients with peripheral neuropathy (group DN), 18 IDDM patients without peripheral neuropathy (group D), and 31 control subjects (group C). Somatosensory-evoked potentials (SEPs) during tibial nerve stimulation were recorded, and the spine-to-scalp sensory central conduction time (SCCT) was evaluated. Motor-evoked potentials (MEPs) were recorded from leg muscles during magnetic transcranial brain stimulation, and the scalp-to-spine motor central conduction time (MCCT) was evaluated. The following posturographic parameters were calculated from the statokinesigram: trace length, trace surface, velocity of body sway with its standard deviation, and VFY (a parameter derived from the velocity variance and the anteroposterior mean position of the body). RESULTS: SCCT was significantly higher in the DN group than in the C and D groups (P < 0.001). MCCT was similar in all groups. Posturographic parameters were all significantly impaired in the DN group (P < 0.01). While posturographic parameters showed a direct relationship with some parameters of peripheral nerve conduction, no correlations were observed with SEP and MEP central conduction time. These results were also confirmed by logistic regression, which indicates peripheral neuropathy as the only implicating factor in postural instability (odds ratio 0.22, 95% CI 0.07-0.75) after data reduction by means of factor analysis. CONCLUSIONS: Although diabetic patients with peripheral neuropathy show a delay in central sensory conduction, postural instability may be fully explained by the presence of peripheral neuropathy.

Adult

[A rare case of angiolymphoid intramasseteric hyperplasia].

A white caucasian male 38-year-old has come to our Department with an intramasseterin neoformation. The histopathological report has been angiolymphoid hyperplasia. Surgical approach is discussed considering at the same time the peculiarity of this rare type of intervention.

Adult

[Oral cavity diseases in HIV and AIDS infections. Clinical, preventive and therapeutic aspects].

Few people with HIV infection fail to experience oral opportunistic lesions during the course of their disease. These are several oral mucosa and salivary gland manifestations that were not seen before the AIDS epidemic, while others are more severe in this population. Oral lesions reflect HIV status and the stage of immunosuppression are important clinical elements in HIV staging and classification schemes: these elements raise pertinent questions about mucosal aspects of immunosuppression and provide therapeutic challenges. Their pervasive nature and biological significance emphasize the importance of a careful oral examination as part of the general clinical evaluation. Prevention and treatment of oral diseases are required to maintain and improve the lifestyle of the patients infected with HIV. Odontoiatric and stomatologic managements require a team approach and a close collaboration with the appropriate responsible physicians and other health care workers are necessary.

AIDS-Related Opportunistic Infections

Thrombopoietin stimulates megakaryocytopoiesis, myelopoiesis, and expansion of CD34+ progenitor cells from single CD34+Thy-1+Lin- primitive progenitor cells.

Thrombopoietin (TPO) or MpI ligand is known to stimulate megakaryocyte (MK) proliferation and differentiation. To identify the earliest human hematopoietic cells on which TPO acts, we cultured single CD34+Thy-1+Lin- adult bone marrow cells in the presence of TPO alone, with TPO and interleukin-3 (IL-3), or with TPO and c-kit ligand (KL) in the presence of a murine stromal cell line (Sys1). Two distinct growth morphologies were observed: expansion of up to 200 blast cells with subsequent differentiation to large refractile CD41b+ MKs within 3 weeks or expansion to 200-10,000 blast cells, up to 25% of which expressed CD34. The latter blast cell expansions occurred over a 3- to 6-week period without obvious MK differentiation. Morphological staining, analysis of surface marker expression, and colony formation analysis revealed that these populations consisted predominantly of cells committed to the myelomonocytic lineage. The addition of IL-3 to TPO-containing cultures increased the extent of proliferation of single cells, whereas addition of KL increased the percentage of CD34+ cells among the expanding cell populations. Production of multiple colony-forming unit-MK from single CD34+Thy-1+Lin- cells in the presence of TPO was also demonstrated. In limiting dilution assays of CD34+Lin- cells, TPO was found to increase the size and frequency of cobblestone areas at 4 weeks in stromal cultures in the presence of leukemia inhibitory factor and IL-6. In stroma-free cultures, TPO activated a quiescent CD34+Lin-Rhodamine 123lo subset of primitive hematopoietic progenitor cells into cycle, without loss of CD34 expression. These data demonstrate that TPO acts directly on and supports division of cells more primitive than those committed to the MK lineage.

Adult

Nutritional assessment: a primary component of multidimensional geriatric assessment in the acute care setting.

OBJECTIVE: To test the prognostic role of nutritional variables as a component of geriatric multidimensional assessment and to study the effect of hospitalization on nutritional status. DESIGN: Validation cohort study: multidimensional assessment on admission and at discharge and a weekly nutritional assessment. SETTING: General Medicine and Geriatrics wards in an acute-care university hospital. PATIENTS: A consecutive sample of 302 patients aged 79 +/- 6 years, range 70-96 years. MAIN OUTCOME MEASURES: Mortality, longstay (> 29 days), loss of lean body mass as expressed by a negative change in mid-arm muscle circumference (MAMC). RESULTS: Incidence of mortality, longstay, and decreased MAMC was 6.9%, 24.8%, and 64.2%, respectively. According to logistic regression analysis, mortality was independently predicted by preadmission dependency in at least one Activity of Daily Living (odds ratio = 2.08, confidence limits = 1.19-3.65), clinical diagnosis of malnutrition (OR = 1.89, CL = 1.11-3.21), serum albumin < 3.5 g/dL (OR = 1.82, CL = 1.06-3.14). This predictive model allowed us to recognize 75% of the patients at risk of death by targeting 23% of the population. Longstay was independently predicted by stroke (OR = 1.54, CL = 1.01-2.35), clinical diagnosis of malnutrition (OR = 1.41, CL = 1.04-1.93), and more than five comorbid diseases (OR = 1.39, CL = 1.01-1.94). Dependency in at least one ADL was the only independent predictor of decreased MAMC (OR = 1.71, CL = 1.27-2.30). CONCLUSIONS: Nutrition variables are a cardinal component of multidimensional assessment in the acute-care setting. Nutritional status deteriorates during the hospital stay, mostly in physically dependent patients.

Activities of Daily Living

Postural rearrangement in IDDM patients with peripheral neuropathy.

OBJECTIVE: To evaluate the influence of diabetic peripheral neuropathy on postural strategy. RESEARCH DESIGN AND METHODS: Static posturography and nerve conduction velocity were performed in the following age-matched subjects: 10 IDDM patients with peripheral neuropathy, 23 IDDM patients without peripheral neuropathy, and 21 control subjects. All subjects with signs or symptoms of postural instability were excluded from the study. The following posturographic parameters were drawn: 1) velocity of body sway, expressed as mean velocity and average of the SDs, 2) VFY, the parameter derived from the velocity variance and the anteroposterior mean position of the body (this parameter monitors the postural strategy pursued by the subject), and 3) fast Fourier transformation on the x (FFTX) and y (FFTY) planes, spectral analysis of the frequencies of body oscillation on frontal (x) and anteroposterior (y) planes. RESULTS: Mean velocity and its SD were higher in IDDM patients with peripheral neuropathy than in control subjects and IDDM patients without peripheral neuropathy (P < 0.001). VFY was increased in IDDM patients with peripheral neuropathy versus control subjects and IDDM patients without peripheral neuropathy (P < 0.01). A direct relationship was found between parameters of posturography and some parameters of nerve conduction tests. CONCLUSIONS: Diabetic patients with peripheral neuropathy demonstrate a shift from physiological ankle control to hip postural control as monitored by specific posturography analysis.

Adult

Detection of a primitive megakaryocyte progenitor cell in human fetal bone marrow.

Ontogeny-related changes in megakaryocyte (MK) progenitor cells were a analyzed to further define the cellular hierarchy occurring during human MK development. CD34+ cells were selected from human low-density adult bone marrow (ABM) or unfractionated fetal bone marrow (FBM) and assayed for MK colony formation in a serum-depleted fibrin clot assay system. At days 3, 7, 12, 16, 21, and 28 of incubation, MK colonies were analyzed for colony number, size and number of foci of development. Unifocal CFU-MK-derived colonies cloned from FBM formed after fewer days of in vitro culture and were 2.6-fold larger than those colonies cloned from ABM, However, the frequency of CFU-MK derived colonies cloned from ABM was significantly greater. the MK colonies cloned from FBM morphologically consisted of both pure MK colonies and mixed MK-containing colonies, in which a core of CD41- cells were surrounded by CD41+MKs. Large colonies resembling the primitive burst-forming unit-MK (BFU-MK) also were assayable from both FBM and ABM. These BFU-MK-derived colonies appeared after fewer days of incubation when FBM was assayed compared to ABM, but at a significantly lower frequency. In addition, large unifocal MK colonies consisting of >300 cells (300-1000) appeared from cells cloned from FBM but not ABM. This type of colony, which appears to represent a unique type of MK progenitor cell, was termed a high proliferative potential cell-MK (HPPC-MK). such colonies represent a relatively rare MK progenitor. We conclude that there are a significant ontologic changes in human MK progenitor cell development. The kinetics of MK colony formation from ABM differs significantly from that of FBM. Furthermore, the proliferative capacity of fetal MK progenitor cells appear to be far greater than that of ABM. In addition, a more primitive lineage-restricted MK progenitor cell with extensive proliferative capacity, the HPPC-MK, was assayable exclusively from FBM.

Adult