Feasibility of performing treadmill walking test for patients with peripheral arterial occlusive disease by the advanced practice nurses.

AIM: The treadmill walking test with post-exercise pressure measurement can be used as a diagnostic test and could classify peripheral arterial disease of the lower limbs. It can also exclude the diagnosis allowing to raise the possibility of differential diagnoses. In this study, we assessed the feasibility of performing treadmill test by advanced practice nurse to assess suspected lower extremity peripheral artery disease patients. DESIGN AND METHOD: This is a longitudinal monocentric study to assess the feasibility of a treadmill walking test performed by an advanced practice nurse. The primary endpoint was the number of tests performed during this period. The secondary objectives were to evaluate the reasons for requesting the test, the main results obtained in terms of the test's contribution and diagnoses, and patients' clinical characteristics. RESULTS: From February to May 2023, amongst 31 patients who underwent the treadmill walking test, 4 tests were able to rule out peripheral arterial disease and to detect differential diagnoses. For the remaining 27 patients, 4 had stage IIa of the Leriche classification, 23 had stage IIb, 2 of which were associated with a narrow lumbar spine. In contrast to the usual report, the APN's report on the walking test included an identification of cardiovascular risk factors, as well as a possible medical reorientation linked to the correction of a detected cardiovascular risk factor. CONCLUSION: The treadmill walking test can be performed by an advanced practice nurse. He/She added a comprehensive/global patient management, with the detection of cardiovascular risk factors. This new profession led to an increase in the number of tests performed of more than 50% over the period and reduced the time to access the test.

Quantum Vacuum Excitation of a Quasinormal Mode in an Analog Model of Black Hole Spacetime.

Vacuum quantum fluctuations near horizons are known to yield correlated emission by the Hawking effect. We use a driven-dissipative quantum fluid of microcavity polaritons as an analog model of a quantum field theory on a black-hole spacetime and numerically calculate correlated emission. We show that, in addition to the Hawking effect at the sonic horizon, quantum fluctuations may result in a sizable stationary excitation of a quasinormal mode of the field theory. Observable signatures of the excitation of the quasinormal mode are found in the spatial density fluctuations as well as in the spectrum of Hawking emission. This suggests an intrinsic fluctuation-driven mechanism leading to the quantum excitation of quasinormal modes on black hole spacetimes.

Evaluation of socio-economic insecurity in peripheral artery disease patients.

The social and economic environment has become a major determinant of cardiovascular health. The objective of our study was to assess socio-economic insecurity in patients with symptomatic PAD. The PRECAR study was a non-interventional prospective cohort study. Patients were recruited from the Vascular Medicine and Surgery Departments of Grenoble-Alpes University Hospital or during a consultation as part of the therapeutic education program "On the move! Better understanding and better living with arterial disease". The analysis of socio-economic and environmental data was based on the EPICES score (a reliable index used to measure individual deprivation) and INSEE parameters (level of education and socio-professional category). Cardiovascular risk factors were also recorded. 150 patients with symptomatic PAD were included between November 2017 and June 2018. 84% were men. In our population 54% (CI95% 45.7 - 62.1) were in a precarious situation compared to 40% (CI95% 39.8 - 40.2) in the general population, according to the EPICES score (P<0.001). Levels of education were low and patients with a baccalaureate or higher education degree were under-represented. Executives, intellectuals and intermediate professions were also under-represented in the PAD population. This data opens new perspectives on the social characterisation of patients that may contribute to improving the outcomes of patients with peripheral vascular disease.

Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for the treatment of cancer-associated thrombosis (which agent for which patient).

Venous thromboembolism (VTE) is a common complication among patients with cancer, associated with significant higher rate of mortality and morbidity. Low-molecular-weight heparin (LMWH) as a single therapeutic is considered as the standard of care for the treatment of acute cancer-associated thrombosis for many years, showing a significant 40% reduction of recurrent VTE (RR: 0.58; 95% CI, 0.43 - 0.77) without a significant increase of major bleeding complications compared to VKA (RR: 1.09; 95% CI 0.55 - 2.12). Based on results analysis studies only including patients with proximal DVT or PE the risk of recurrent VTE was similar in the DOAC and the LMWH (RR 0.68; 95% CI, 0.39 - 1.17) groups, without significantively increasing the risk of either major bleeding (RR = 1.32; 95% CI 0.7 - 2.47) or CRNMB (RR 1.6; 95% 0.99 - 2.6). Compared with LMWH, the risk of major bleeding and clinically relevant-non major bleeding was higher, although non-significantly, with DOACs than with LMWH, underlying that DOACs should be avoided in patients at high risk of bleeding. The higher risk of bleeding reported in DOACs-treated patients appears related to an excess of upper GI bleeding. In addition to GI cancer, other high-risk features associated with bleeding complications are an urothelial cancer, drug-drug interactions and use of anticancer drugs associated with GI toxicity. Overall, DOACs are an effective treatment option, and safe in most cancer patients with acute VTE. Nonetheless, DOACs should be used with caution in cancer patients at high risk for bleeding due to cancer site and stage per se or to cancer treatments.

Appendicular myxoglobulosis; a rare form of appendicular mucocele.

Myxoglobulosis is a particular, rare, form of appendicular mucocele, characterized by the presence of numerous, occasionally calcified, globules that are grouped together like grapes, and look like pearls or fish eggs, in the appendicular lumen. The diagnosis of myxoglobulosis is most often fortuitous, but sometimes, can be made in the face of acute appendicitis or another setting of abdominal pain. Imaging (sonography or computerized tomography (CT)) is highly suggestive when it shows a cystic, encapsulated, oblong, well-delineated mass, containing (heterogeneous, liquid, and viscous) mucus with calcified globules. In contrast to acute appendicitis, the wall of the appendix is thin (<6mm) and there is no peri-appendicular inflammation. Long-term complications are similar to other appendicular mucoceles, including invagination, bleeding, perforation, peritonitis and peritoneal pseudomyxoma.

EXPRESSION OF MENIN IN THE HUMAN THYROID GLAND.

INTRODUCTION: The expression of menin in the thyroid gland has long been debated. Animal models with targeted inactivation of menin in the thyroid gland have shown that its inactivation might play a role in the progression to a more aggressive type of cancer. Human studies are conflicting, some have identified mutations in the MEN1 gene in a sub-type of oncocytic thyroid carcinomas, while others have not identified a higher prevalence of thyroid cancer in MEN1 patients. OBJECTIVE: To analyze the immunohistochemical expression of menin in different types of thyroid carcinomas. MATERIALS AND METHODS: 48 thyroid tumours (12 papillary thyroid carcinomas (PTC), 6 anaplastic thyroid carcinomas (ATC), 12 poorly differentiated thyroid carcinomas (PDTC), 5 medullary thyroid carcinomas (MTC), 5 oncocytic follicular carcinomas (OC), 3 oncocytic adenomas (OA) and 5 goiters (G)) were tested for nuclear expression of menin using an anti-menin antibody. The expression was considered positive, negative or decreased. RESULTS: The expression of menin was positive, identical to normal tissue, in 39 cases (81.25%). The expression was decreased (n=8) or absent (n=1) in 9 tumours (18.75% - 2 PTC, 5 PDTC, 2 OC) accounting for 42% (5/12) of the PDTC and 40% (2/5) of the OC. CONCLUSIONS: Our results show that the expression of menin is generally preserved in human thyroid carcinomas, but it can be decreased or absent in certain types of thyroid cancer. Further molecular studies are needed to evaluate to potential of menin protein in tumorigenesis.

O6-Methylguanine-DNA methyltransferase status in neuroendocrine tumours: prognostic relevance and association with response to alkylating agents.

BACKGROUND: O(6)-Methylguanine-DNA methyltransferase (MGMT) loss of expression has been suggested to be predictive of response to temozolomide in neuroendocrine tumours (NETs), but so far, only limited data are available. We evaluated the prognostic and predictive value of MGMT status, assessed by two molecular methods and immunohistochemistry, in a large series of NETs of different origins. METHODS: A total of 107 patients, including 53 treated by alkylants (temozolomide, dacarbazine or streptozotocin), were retrospectively studied. In each case, we used methyl-specific PCR (MS-PCR) and pyrosequencing for evaluation of promoter methylation and immunohistochemistry for evaluation of protein status. RESULTS: MGMT promoter methylation was detected in 12 out of 99 (12%) interpretable cases by MS-PCR and in 24 out of 99 (24%) by pyrosequencing. O(6)-Methylguanine-DNA methyltransferase loss of expression was observed in 29 out of 89 (33%) interpretable cases. Status of MGMT was not correlated with overall survival (OS) from diagnosis. Progression-free survival and OS from first alkylant use (temozolomide, dacarbazine and streptozotocin) were higher in patients with MGMT protein loss (respectively, 20.2 vs 7.6 months, P<0.001 and 105 vs 34 months, P=0.006) or MGMT promoter methylation assessed by pyrosequencing (respectively, 26.4 vs 10.8 months, P=0.002 and 77 vs 43 months, P=0.026). CONCLUSIONS: Our results suggest that MGMT status is associated with response to alkylant-based chemotherapy in NETs.

International collaborative study for the calibration of the Ph. Eur. somatropin chemical reference substance batches 3 and 4 (BSP108).

An international collaborative study was carried out for the establishment of replacement batches for the European Pharmacopoeia (Ph. Eur.) Somatropin Chemical Reference Substance (CRS) batch 2. The study was organised within the framework of the Biological Standardisation Programme (BSP) of the Council of Europe and the European Commission. Seventeen laboratories from Europe, North America, South America and Australia took part in the collaborative study. The study aimed at calibrating the somatropin content of 2 candidate preparations and demonstrating their suitability to serve as a reference substance in the tests for identification, for related proteins, for dimers and related substances of higher molecular mass (HMM), for charged variants distribution and for the assay of somatropin, as prescribed by the current Ph. Eur. monographs 0950 Somatropin bulk solution, 0951 Somatropin and 0952 Somatropin for injection. Based on the results summarised herein the Ph. Eur. Commission adopted in January 2012 candidate preparation b (cCRS-b, Sample D) as somatropin CRS batch 3 with an assigned content of 3.86 mg of somatropin monomer per vial, and candidate preparation a (cCRS-a, Sample C) as somatropin CRS batch 4 with an assigned content of 2.59 mg of somatropin monomer per vial.

Aligning research to meet policy objectives for migrant families: an example from Canada.

BACKGROUND: 'Evidence-based policy making' for immigrants is a complicated undertaking. In striving toward this goal, federal Canadian partners created the Metropolis Project in 1995 to optimize a two-way transfer of knowledge (researchers - policy makers) within five Canadian Centres of Excellence focused on migrants newly arrived in Canada. Most recently, Metropolis federal partners, including the Public Health Agency of Canada, defined one of six research priority areas as, immigrant 'families, children, and youth'. In order to build on previous work in the partnership, we sought to determine what has been studied within this research-policy partnership about immigrant 'families, children, and youth' since its inception. METHODS: Annual reports and working papers produced in the five Centres of Excellence between 1996-2006 were culled. Data on academic works were extracted, results coded according to eleven stated federal policy priority themes, and analyzed descriptively. RESULTS: 139 academic works were reviewed. All federal priority themes, but few specific policy questions were addressed. The greatest volume of policy relevant works were identified for Services (n = 42) and Education and Cultural Identity (n = 39) priority themes. CONCLUSION: Research conducted within the last 10 years is available to inform certain, not all, federal policy questions. Greater specificity in federal priorities can be expected to more clearly direct future research within this policy-research partnership.

Determination of somatropin charged variants by capillary zone electrophoresis - optimisation, verification and implementation of the European pharmacopoeia method.

Measurement of somatropin charged variants by isoelectric focusing was replaced with capillary zone electrophoresis in the January 2006 European Pharmacopoeia Supplement 5.3, based on results from an interlaboratory collaborative study. Due to incompatibilities and method-robustness issues encountered prior to verification, a number of method parameters required optimisation. As the use of a diode array detector at 195 nm or 200 nm led to a loss of resolution, a variable wavelength detector using a 200 nm filter was employed. Improved injection repeatability was obtained by increasing the injection time and pressure, and changing the sample diluent from water to running buffer. Finally, definition of capillary pre-treatment and rinse procedures resulted in more consistent separations over time. Method verification data are presented demonstrating linearity, specificity, repeatability, intermediate precision, limit of quantitation, sample stability, solution stability, and robustness. Based on these experiments, several modifications to the current method have been recommended and incorporated into the European Pharmacopoeia to help improve method performance across laboratories globally.

Alteration of cardiac and renal functions in transgenic mice overexpressing human mineralocorticoid receptor.

The mineralocorticoid receptor (MR), a ligand-dependent transcription factor, mediates aldosterone actions in a large variety of tissues. To explore the functional implication of MR in pathophysiology, transgenic mouse models were generated using the proximal human MR (hMR) promoter to drive expression of hMR in aldosterone target tissues. Tissue-specific analysis of transgene expression in two independent transgenic animal (TG) lines by ribonuclease protection assays revealed that hMR is expressed in all mineralocorticoid-sensitive tissues, most notably in the kidney and the heart. TG exhibit both renal and cardiac abnormalities. Enlarged kidneys were histologically associated with renal tubular dilation and cellular vacuolization whose prevalence increased with aging. Renal clearance studies also disclosed a significant decrease in urinary potassium excretion rate in TG. hMR-expressing animals had normal blood pressure but developed mild dilated cardiomyopathy (increased left ventricle diameters and decreased shortening fraction), which was accompanied by a significant increase in heart rate. Differential gene expression analysis revealed a 2- to 5-fold increase in cardiac expression of atrial natriuretic peptide, serum- and glucocorticoid-induced kinase, and early growth response gene 1 as detected by microarrays; renal serum- and glucocorticoid-induced kinase was also induced significantly. Altogether, TG exhibited specific alteration of renal and cardiac functions, thus providing useful pathophysiological models to gain new insights into the tissue-specific mineralocorticoid signaling pathways.

Haemodialysis with the biocompatible high permeability AN-69 membrane does not alter plasma insulin-like growth factor-I and insulin-like growth factor binding protein-3.

BACKGROUND: Insulin-like growth factor-I (IGF-I) bioactivity has been reported to be decreased in maintenance haemodialysis patients and this may affect their nutritional status. Clearances of IGF-I and its binding proteins (IGFBPs) during haemodialysis sessions using a high permeability biocompatible membrane are unknown. METHODS: Five well nourished, non-diabetic adult patients were studied during one 4-h morning haemodialysis treatment using the high permeability biocompatible AN-69 dialyser. Blood was collected at the arterial and venous ports of the dialyser at 0, 1, 2 and 4 h of dialysis for haematocrit, plasma IGF-I, IGFBP-3 and insulin measurements. IGF-I, IGFBP-3 and insulin concentrations were adjusted for haemoconcentration before comparisons were made. RESULTS: At the beginning of the dialysis session, plasma IGF-I, IGFBP-3 and insulin levels were within the normal range (297 +/- 47 ng/ml (mean+/-SEM), 4.3 +/- 0.6 microg/ml and 11.8 +/- 3.4 microIU/ml, respectively). During the session, insulin tended to be cleared through the dialyser, whereas plasma IGF-I and IGFBP-3 values did not vary significantly. CONCLUSION: Dialysis with the high permeability AN69 membrane did not alter the main blood compounds of the IGF system in well nourished chronic haemodialysis patients, and it is unlikely that the malnutrition frequently observed in such patients would result from alterations of the IGF system during haemodialysis.

Neurotrophin channeling of neural progenitor cell differentiation.

The act of defining neuropoietic progenitor/stem cells is still in its early phases. Epidermal growth factor (EGF) stimulates extended proliferation of aggregates of subventricular striatal cells, taken from E15 mouse striatum, termed neurospheres in liquid culture. We have shown here and in previous work, using either immunohistochemistry or RT-PCR, that neurosphere cells express 13 cytokines (32 tested) and 20 cytokine receptors (28 tested), with 11 potential paracrine and nine potential autocrine loops. The neurotrophin receptors, Trk A, B, and C, were all expressed. Using a newly developed FACS single cell deposition technique, we evaluated the capacity of single EGF stimulated neurosphere cells to respond to the ligands for Trk A and B, nerve growth factor (NGF), and brain-derived neurotrophin factor (BDNF). Addition of NGF or BDNF to EGF for 14 days had no effect, but removal of EGF at day 14 with subsequent addition of BDNF or NGF resulted in an increase in neuronal and astroglial, but not oligodendrocyte, colony cells at 21 and 28 days of culture for BDNF, and of both cell types at 28 days for NGF. Tri-lineage colonies increased at day 21 with BDNF and at day 28 for both NGF and BDNF. Gross colony morphology also showed changes with neurotrophin addition, forming multiple individual cell balls or filamentous spreads. When EGF was withdrawn, a threshold effect was observed, with small, but not large, colonies ceasing growth. BDNF and NGF showed no effects on cell proliferation when compared to EGF controls, as determined by 5'-bromo-2-deoxyuridine (BrdU) incorporation and thus, they appear to affect differentiation of progenitor cells. These data indicate a sequential action of cytokines with EGF maintaining viability and proliferation and blocking differentiation. Removal of EGF is then permissive for the differentiating effects of BDNF and NGF. These data further indicate that the majority of EGF neurosphere clones have neurotrophin dependent tri-lineage potential.

Nuclear factor-kappaB activation in mouse lung lavage cells in response to Streptococcus pneumoniae pulmonary infection.

OBJECTIVES: To assess the state and activation kinetics of the nuclear transcription regulatory protein nuclear factor-kappB (NF-kappaB) in lung lavage cells in a murine pneumococcal pneumonia model and to determine how the virulence of the infecting organisms altered the activation state of NF-kappaB. DESIGN: Experimental, comparative study of three Streptococcus pneumoniae strains that induced three distinct pulmonary diseases. SETTING: Experimental laboratory in a university-based medical center. SUBJECTS: Female BALB/cby mice, 8-10 wks of age. INTERVENTIONS: We randomly divided the mice into the following five groups: a) the control group; b) animals infected by virulent encapsulated S. pneumoniae P4241 strain; c) animals infected by avirulent encapsulated S. pneumoniae P15986 strain; d) animals infected by avirulent unencapsulated S. pneumoniae R6 strain; e) animals infected by virulent lysed S. pneumoniae P4241 strain. Animals were anesthetized and infected by intratracheal delivery of 4 x 10(5) colony-forming units (CFU) of S. pneumoniae per mouse or bacterial components equivalent to 4 x 10(5) CFU for lysed S. pneumoniae challenge. After intratracheal challenge with virulent encapsulated strain P4241, mice developed acute pneumonia, became bacteremic, and died within 3 to 5 days. None of the mice infected with the avirulent encapsulated strain P15986 or the avirulent unencapsulated strain R6 died. After collection of lung lavage cells and nuclear extraction, NF-kappaB activation was determined 1 hr, 4 hrs, 6 hrs and 24 hrs after pneumococcal infection. At the same time, pulmonary and blood clearance, bronchoalveolar lavage cells population, and tumor necrosis factor-alpha production were assessed (six mice per time point). MEASUREMENTS AND MAIN RESULTS: NF-kappaB was constitutively expressed within nuclear extracts of lung lavage cells from uninfected control mice. A significant increase in NF-kappaB activation was detected within 1 hr after injection of virulent lysed S. pneumoniae P4241 strain (bacterial components equivalent to 4 x 10(5) CFU), and was still present 24 hrs after the injection. After live pneumococcal challenge, significant NF-kappaB activation was detected within 4 hrs with a peak at 24 hrs. Responses to all three strains (P4241, P15986 and R6) were time-dependent (p < .0001), as NF-kappaB activation gradually increased during the first 24 hrs. Moreover, compared with the control uninfected mice, the intensity of the retarded KB oligonucleotide, as determined by densitometry, was increased approximately four- to five-fold and seven-fold in reactions containing nuclear extracts isolated 24 hrs after infection with the avirulent strains P15986 or R6 and the virulent strain P4241, respectively. With the virulent strain P4241, responses were significantly stronger than with the avirulent strains P15986 and R6 (p < .01). Responses were of similar order with avirulent strains P15986 and R6 (p > .05). CONCLUSION: Pulmonary infection by S. pneumoniae induced delayed and time-dependent activation of NF-kappaB in mouse lung lavage cells. The degree of NF-kappaB activation in lung lavage cells correlated with the virulence of the infecting organisms. Our results suggest that the more severe the infection, the higher the rise in NF-kappaB.

Relationship between capsular type, penicillin susceptibility, and virulence of human Streptococcus pneumoniae isolates in mice.

We examined the relationship between penicillin susceptibility, peritoneal virulence in Swiss mice, and capsular type in a selection of 122 clinical Streptococcus pneumoniae isolates belonging to 24 serotypes. Regardless of the serotype, all 32 virulent strains were susceptible to penicillin, and all 41 strains with diminished susceptibility or resistance to penicillin were avirulent. The remaining 49 strains were both susceptible to penicillin and avirulent, irrespective of the serotype. On the basis of their capsular type and pathogenic behavior, strains fell into one of four groups. In the group consisting of serotypes 1, 3, and 4 (n = 16), strains were predominantly virulent (81.3%), and all were penicillin susceptible. In the serotype 6 group (n = 32), the frequency of virulence was significantly lower (34.4 versus 81.3%, P = 0.002), and strains were predominantly penicillin susceptible (71.9%). In the group composed of serotypes 9, 14, 19, and 23 (n = 50), all strains were avirulent, and 56% had decreased susceptibility (n = 12) or resistance to (n = 16) penicillin. The fourth group was heterogenous, as it pooled 24 strains of 15 different serotypes; in this group the frequency of virulence was 33.3%, and strains were predominantly penicillin susceptible (83.3%). These data point to a complex relationship between penicillin susceptibility and virulence in mice but do not entirely separate these characteristics from the role of the capsular type. The possibility that the mechanisms conferring penicillin resistance are related to those leading to a loss of virulence is supported by these findings.

Evolution of GH secretion in urine during an in-patient slimming course in obese children.

OBJECTIVE: To estimate the change in GH excretion in urine (GH-U) during a slimming course, and if increased, to assess the components of the course related to the increase in obese children. DESIGN: Observational follow-up study of patients admitted for primary obesity to an in-patient slimming course lasting at least 10 weeks. SUBJECTS: 48 complete observations out of 54 consecutive pre-pubertal patients admitted to a paediatric centre for treatment of primary obesity (BMI greater than the 90th percentile of the national reference curves). MEASUREMENTS: GH excretion in urine by immunoradiometric assay, at entry and after 10 weeks, various anthropometric measurements, nutritional intake and departure from the prescribed diet, time spent in physical activity, sleep duration. RESULTS: A mean decrease of 0.90 standard deviations for BMI was accompanied by a 34% increase of GH-U. Time spent in physical activity was the only component of the course found to be related to the magnitude of GH-U increase. CONCLUSION: The results of this observational study confirm that GH-U is increased after a slimming course in children, and suggest that physical activity is a major contributor to the restoration of normal GH-U levels.

Prospective study of CD8+ lymphocyte activation in relation to viral load in HIV-infected patients with > or = 400 CD4+ lymphocytes per microliter.

To investigate the temporal relationship between CD8+ lymphocyte phenotypic alterations, the CD4+ T cell decline, and plasma HIV RNA levels during the natural history of HIV infection, 33 treatment-naive HIV-infected patients with > or =400 CD4+ cells/microl were studied prospectively for 3 years. During the study period, 20 patients remained untreated, and only 6 received more than 6 months of therapy. A significant relationship was found between changes in plasma HIV RNA and changes in the proportion of CD38+CD8+ cells. Conversely, the number of CD4+ T cells lost per year was strongly related to the increase in the proportion of CD28-CD8+ T cells. A strong relationship between mean yearly changes in CD4+ T cell numbers and changes in HIV RNA was also observed. CD4+ T cell changes were associated with changes in both viral load and CD8+ T cell activation. These results provide support for the use of both virologic and immunologic parameters for prognosis and management during HIV infection.

Correlates between hematopoiesis and neuropoiesis: neural stem cells.

There are many parallels between the neuropoietic and lymphohematopoietic systems. The lymphohematopoietic stem/progenitor cell system has been extensively characterized, but there are still major questions relating to the definitive stem cell assay, the structure of the system (i.e., hierarchical versus cell cycle-based), and the nature of differentiation (i.e., stochastic versus deterministic). Recent data have established the existence of an epidermal growth factor (EGF)-responsive neural stem cell in adult mice. We have studied these neural progenitor/stem cells in fetal (day 15) and 2-day postnatal mice and established a single-cell progenitor assay and a variety of putative uni-, bi-, and tripotential stem cells that form in response to EGF. Neurospheres are the EGF-responsive neural units that grow in liquid culture, and we have found that cells derived from these neurospheres express a wide array of cytokines and their receptors. This will provide a window on the hemopoietic progenitor system analogous to that created by the description of in vitro growth of clonal hematopoietic progenitors.