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Biomedical subjects

D Siegel

Publications and source records attributed to D Siegel.

At least 73 records · Page 4Linked to original sources
PubMed1997

Trends in antihypertensive drug use in the United States: do the JNC V recommendations affect prescribing? Fifth Joint National Commission on the Detection, Evaluation, and Treatment of High Blood Pressure.

CONTEXT: The choice of pharmacological treatment for the approximately 50 million people in the United States with hypertension has important therapeutic and financial implications. OBJECTIVES: To describe national antihypertensive medication prescribing patterns for 1992 and 1995; to explore the influence of the Fifth Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure (JNC V), published in 1993, which recommended diuretics and beta-blockers as first-line antihypertensive therapy unless contraindicated; and to estimate the impact of these prescribing patterns on the cost of antihypertensive treatment. DESIGN: All prescriptions for drugs approved for the treatment of hypertension dispensed by 35000 retail pharmacies were tabulated for 1992 and 1995 (62% of all US retail pharmacies were surveyed). MAIN OUTCOME MEASURES: Number of prescriptions for each dosage form of medication and national cost estimates based on wholesale costs of medications dispensed. RESULTS: In 1992, of the 10 most frequently prescribed antihypertensive drugs, 3 were calcium antagonists, 3 were angiotensin-converting enzyme (ACE) inhibitors, 3 were beta-blockers, and 1 was the combination of triamterene and hydrochlorothiazide. In 1995, 4 were calcium antagonists, 3 were ACE inhibitors, 1 was a beta-blocker, 1 was the combination of triamterene and hydrochlorothiazide, and 1 an alpha-blocker. In 1992, calcium antagonists accounted for 33% of antihypertensive prescriptions compared with 38% in 1995, ACE inhibitor use went from 25% to 33%, beta-blocker use from 18% to 11%, and diuretic use from 16% to 8%. The estimated wholesale costs for calcium antagonists in 1995 dollars increased from $2.67 billion in 1992 to $2.86 billion in 1995; ACE inhibitor costs increased from $1.37 billion to $1.67 billion; costs for diuretics declined from $353 million to $168 million; and costs for beta-blockers declined from $763 million to $433 million. CONCLUSIONS: From 1992 to 1995 use of calcium antagonists and ACE inhibitors for treatment of hypertension increased and diuretics and beta-blockers declined, suggesting that the recommendations from JNC V had little effect on prescribing patterns. The cost implications of these practice patterns are enormous.

Antihypertensive Agents↗
PubMed1997

A model system for detection and isolation of a tumor cell surface antigen using antibody phage display.

To establish a screening procedure for tumor cell-surface reactive Fabs, we used a model antigen/antibody system including the epidermal growth factor receptor (EGF-R) and the anti-EGF-R monoclonal antibody 425. The 425 Fab was displayed on the surface of M13 filamentous phage. In a screening assay for 425 phage binding to tumor cell surfaces, biotinylated 425-phage bound specifically to EGF-R-positive A431 epidermoid carcinoma cells and not to K562 non-expressor erythroleukemia cells. With a model library, the sensitivity of phage enrichment by phage binding to cell surfaces was one 425-phage in 20,000 unrelated phages after 4 rounds of panning on A431 cells. In a phage tissue screening assay, 425-phage, but not unrelated phage, bound specifically to melanoma cells expressing EGF-R. Epitope and idiotope specificity of 425-phage was demonstrated in phage competition assays, using as targets A431 cells and anti-idiotypic antibodies to monoclonal antibody 425, respectively. Finally, the EGF-R protein was directly isolated from A431 cell extracts, using biotinylated 425-phage. The data obtained with the 425 model library system demonstrate the usefulness of antibody phage display for the rapid identification and isolation of tumor or other disease-related cell surface antigens.

Adenocarcinoma↗
PubMed1997

Cloning of anti-Gal Fabs from combinatorial phage display libraries: structural analysis and comparison of Fab expression in pComb3H and pComb8 phage.

Anti-Gal is the most abundant natural antibody in humans. It interacts specifically with the carbohydrate epitope Gal alpha1-3Galbeta1-4GlcNAc-R (termed the alpha-galactosyl epitope). In an attempt to characterize the Ig genes encoding anti-Gal, two combinatorial phage display libraries in phagemid pComb3H were screened for anti-Gal Fabs. For this purpose, phages were incubated with biotinylated BSA coupled with alpha-galactosyl epitopes (designated alpha-Gal-BSA). Subsequently, phages complexed with alpha-Gal-BSA were isolated by streptavidin-coupled magnetic beads. Because of the low affinity of this antibody, a characteristic shared with other anti-carbohydrate antibodies, only two clones displaying anti-Gal activity were isolated. Clone G9 contained the VH gene V3-43 and VL gene DPK15, whereas clone P19 contained the VH gene V3-15 and VL gene DPL16. Both clones contained between five and 14 mutations in their H and L chain V genes. The affinity of clone G9 was found to be higher than that of clone P19, as only the former could bind to solid-phase alpha-galactosyl epitopes in an enzyme-linked immunosorbent assay. This interaction could be increased by expressing Fabs in phagemid pComb8 grown in the presence of IPTG. Under such conditions, the IPTG-activated Lac-Z promoter induces an increased expression of Fabs that are linked to phage envelope protein VIII, resulting in multiple Fab display on the phage. The data suggest that screening combinatorial phage display libraries for anti-carbohydrate antibodies may be more effective with pComb8 phage grown in the presence of IPTG.

Amino Acid Sequence↗
PubMed1997

Multiple idiopathic arterial aneurysms in children: a case report and review of the literature.

A 6-year-old boy from China presented initially at 2 years of age with a pulsatile mass in his right antecubital fossa. He was not fully evaluated until the age of six years, when pan-angiography and computed axial tomography scan revealed multiple aneurysms of his right brachial artery, right radial artery aneurysms, an infrarenal aortic aneurysm, and a right internal carotid artery aneurysm in the region of the cavernous sinus. The patient underwent uneventful repairs of both the abdominal aortic aneurysm and the multiple aneurysms of the right arm. Pathologic evaluation was significant for medial fibrosis of the arterial wall with decreased and disordered elastin fibers. Review of the previously reported cases in children indicate the upper extremity arteries are involved in 92% of patients, the aortoiliac region in 92% of patients, and the renal/mesenteric vessels in 77% of cases. Lower extremity and cerebrovascular arteries are involved to a lesser extent. Children with peripheral aneurysms should have pan-angiography performed before treatment is begun. Surgical repair in these cases has been excellent.

Aneurysm↗
PubMed1997

Adolescent AIDS prevention in context: the impact of peer educator qualities and classroom environments on intervention efficacy.

Peer-led, school-based interventions show promise for preventing AIDS among adolescents, but little is known about the processes underlying effective peer education or the conditions that promote its efficacy. This study examined the implementation in one school of an effective, peer-led AIDS prevention program for inner-city 7th-grade participants (n = 123) and identified the qualities of peer educators (n = 15) and classroom environments (n = 5) that contributed to improvement in participants' postintervention AIDS-related attitudes. The Peer Educator Rating Scale was developed to assess two dimensions of participants' perceptions of peer educators: "positive regard" and "perceived similarity." Participants reported greater positive regard for more highly individuated and less shy peer educators, and participants' positive regard for peer educators in turn was associated with lowered AIDS risk as measured by perceptions of peer norms regarding sexual activity and self-efficacy for peer communication regarding sexual topics and condoms. Participants' perceived similarity was not associated with any postintervention improvements in AIDS-related knowledge and attitudes. Participants' classroom membership was associated with improvements in all 5 knowledge and attitude scales, and exploratory classroom-level findings indicated that classroom intervention environments perceived as more organized by participants showed slightly greater overall improvements across AIDS-related knowledge and attitudes scales. Consistent with individual-level findings regarding participants' positive regard for peer educators, the two classrooms with the greatest positive regard for their peer educator teams showed the most student improvement. Implications for further research and the design of future prevention and promotion programs for adolescents are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Characterization of a polymorphism in NAD(P)H: quinone oxidoreductase (DT-diaphorase).

NAD(P)H:quinone oxidoreductase (NQO1, EC 1.6.99.2) is an obligate two-electron reductase that can either bioactivate or detoxify quinones and has been proposed to play an important role in chemoprevention. We have previously characterized a homozygous point mutation in the BE human colon carcinoma cell line that leads to a loss of NQO1 activity. Sequence analysis showed that this mutation was at position 609 of the NQO1 cDNA, conferring a proline to serine substitution at position 187 of the NQO1 enzyme. Using polymerase chain reaction (PCR) analysis, we have found that the H596 human non-small-cell lung cancer (NSCLC) cell line has elevated NQO1 mRNA, but no detectable enzyme activity. Sequencing of the coding region of NQO1 from the H596 cells showed the presence of the identical homozygous point mutation present in the BE cell line. Expression and purification of recombinant wild-type and mutant protein from E. coli showed that mutant protein could be detected using immunoblot analysis and had 2% of the enzymatic activity of the wild-type protein. PCR and Northern blot analysis showed moderate to low levels of expression of the correctly sized transcript in the mutant cells. Immunoblot analysis also revealed that recombinant mutant protein was immunoreactive; however, the mutant protein was not detected in the cytosol of either BE or H596 cells, suggesting that the mutant proteins were either not translated or were rapidly degraded. The absence of any detectable, active protein, therefore, appears to be responsible for the lack of NQO1 activity in cells homozygous for the mutation. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis for the mutation at position 609 conducted on 90 human lung tissue samples (45 matched sets of tumour and uninvolved tissue) revealed a 7% incidence of individuals homozygous for the mutation, and 42% heterozygous for the mutation. These data suggest that the mutation at position 609 represents a polymorphism in an important xenobiotic metabolizing enzyme, which has implications for cancer therapy, chemoprevention and chemoprotection.

Adult↗
PubMed1997

High-dose chemotherapy with carboplatin, cyclophosphamide and etoposide and autologous transplantation for multiple myeloma relapsing after a previous transplant.

Eighteen extensively pre-treated patients (35-73 years, median 46) with relapsed multiple myeloma received salvage chemotherapy with 6 g/m2 cyclophosphamide, 800 mg/m2 carboplatin, and 1800 mg/m2 etoposide (CCV) as a 96-h continuous infusion followed by autologous peripheral blood stem cells. The median number of prior chemotherapy regimens was five (range 4-10), including at least one autograft. Four patients died of toxicity, and one developed dialysis-dependent renal failure, while the others tolerated CCV well. Three of six patients with pre-transplant creatinine of > 1 mg/dl died of toxicity compared with one of 12 with creatinine < or = 1 mg/dl (P = 0.083, Fisher's exact test). Three of four patients treated with four previous regimens showed > 50% reduction in tumor compared with one of 14 treated with > 4 regimens (P = 0.02, Fisher's exact test). At the last follow-up, five patients were alive at 8-24 months (median 13) with stable (n = 1) or progressive (n = 4) disease, and nine had died of progressive disease at 2.5-15 months (median 7). We conclude that CCV chemotherapy with autografting is tolerated well by extensively pre-treated myeloma patients provided the pre-transplant creatinine is normal, but toxicity in patients with abnormal renal function is high. The efficacy in multiply relapsed disease is poor, with response in only 22% of patients. CCV may deserve further evaluation early in the course of myeloma in patients with normal renal function.

Adult↗
PubMed1997

The utility of follow-up testing after curative cancer therapy. A critical review and economic analysis.

OBJECTIVE: To review (1) basic principles of follow-up in patients who are in complete remission following curative therapy for cancer; (2) evaluate the available data on follow-up strategies for testicular cancer, Hodgkin's disease, non-Hodgkin's lymphoma, breast cancer, colorectal cancer, small cell and non-small cell lung cancer, and prostate cancer; and (3) analyze the cost of follow-up strategies. METHODS: The English language literature was reviewed utilizing MEDLINE headings for the specific malignancies and the text word "follow-up." Bibliographies of relevant articles also were reviewed. Emphasis was placed on prospective, randomized trials of large retrospective studies in which all patients who potentially could have been evaluated were accounted. The cost of various testing strategies were analyzed utilizing data from the Health Care Finance Administration. DATA SYNTHESIS: Proper follow-up strategies should take into account patterns and time course of recurrence and should be obtained of detection of recurrence would allow meaningful therapeutic intervention. Testing also should be directed at early detection of malignant and nonmalignant complications known to be associated with the primary disease. Testicular cancer is a "model" malignancy in that sensitive tests for recurrence are available and early detection of recurrence allows for potentially curative therapy. CONCLUSIONS: According to the currently available literature, repetitive follow-up laboratory and radiologic testing, except for nonseminomatous germ cell tumors, does not detect the vast majority of cancer relapses, nor does it result in a greater chance of cure or prolonged survival. The majority of recurrences at all disease sites will first be recognized as symptomatic changes in the patient's condition or alterations in the physical examination. A limited panel of blood tests and radiographic studies to detect recurrences, metachronous disease, and complications of therapy (malignant and nonmalignant), will suffice for most cancers. Though data are limited, this more restrictive policy of follow-up testing does not appear to adversely impact patient quality of life and result in dramatic cost of savings to the health care system.

Breast Neoplasms↗
PubMed1997

Combinatorial antibodies against human malignant melanoma.

The general responsiveness of human melanoma to immunotherapy has been well established, but active immunotherapy of melanoma has been hampered by insufficient information on the immunogenicity of melanoma antigens in patients. We have attempted to identify melanoma-associated antigens recognized by patients' B cells using an antibody phage display approach. Antibody display on filamentous phages allows direct screening of cDNA libraries for expression of cell-surface-reactive antibodies, without the need for antibody production and purification using bacteria or eukaryotic cell systems. This approach was used to identify melanoma-associated cell-surface antigens recognized by patients' B cells. Antibodies produced by the B cells of a melanoma patient (in remission for > 7 years following periodic vaccination with allogeneic melanoma cell vaccine) were displayed as Fabs on the surfaces of filamentous phages. A library of 10(8) phages was absorbed to normal melanocytes, followed by phage binding to and elution from melanoma cells (human lymphocyte antigen nonmatched and vaccine melanoma cells). Phages were further selected for reactivities with tunicamycin-treated melanoma cells. These procedures resulted in a > 10(6)-fold enrichment of tumor-specific phages from the original phage library. One phage-Fab bound to melanoma cells, other tumor cells, and a few normal cells in cultured cell lines and in tissue sections.

Antibodies, Neoplasm↗
PubMed1997

The reduction of alpha-tocopherolquinone by human NAD(P)H: quinone oxidoreductase: the role of alpha-tocopherolhydroquinone as a cellular antioxidant.

alpha-Tocopherolquinone (TQ), a product of alpha-tocopherol oxidation, can function as an antioxidant after reduction to alpha-tocopherolhydroquinone (TQH2). We examined the ability of human NAD(P)H:quinone oxidoreductase (NQO1) to catalyze the reduction of TQ to TQH2 in cell-free and cellular systems. In reactions with purified human NQO1, TQ was reduced to TQH2. Kinetic parameters for the reduction of TQ by NQO1 (Km = 370 microM; k(cat) = 5.6 x 10(3) min(-1); k(cat)/Km = 15 min(-1) x microM(-1)) indicate that NQO1 can efficiently reduce TQ to TQH2. A comparison of the rate of reduction of TQ and coenzyme Q10 by NQO1 showed that TQ is reduced more efficiently than coenzyme Q10. Experiments with either Chinese hamster ovary (CHO) cells stably transfected with human NQO1 or CHO cell sonicates demonstrated a correlation between NQO1 activity and TQ reduction to TQH2. CHO cells with elevated NQO1 generated and maintained higher levels of TQH2 after treatment with TQ relative to NQO1-deficient CHO cells. TQH2 generated from NQO1-mediated reduction of TQ prevented cumene hydroperoxide-induced lipid peroxidation in rat liver microsomes. In addition, cumene hydroperoxide-induced lipid peroxidation was inhibited more efficiently by TQ in CHO cell lines with elevated NQO1 activity. These data demonstrate that NQO1 can reduce TQ to TQH2 and that TQH2 can function as an efficient antioxidant. This work suggests that one of the physiological functions of NQO1 may be to regenerate antioxidant forms of alpha-tocopherol.

Animals↗
PubMed1997

Unique role of cytogenetics in the prognosis of patients with myeloma receiving high-dose therapy and autotransplants.

PURPOSE: Although important predictors of survival in myeloma patients have been identified, it is well recognized that better prognostic factors for this disease are needed. Because cytogenetics play a dominant role in the outcome of patients with acute leukemia, their prognostic value was evaluated in a large group of newly diagnosed and previously treated myeloma patients receiving autotransplants. METHODS: A total of 427 either newly diagnosed (26%) or previously treated patients (74%) received tandem transplants, supported by mobilized peripheral-blood stem cells. Numerous variables, including cytogenetics, were analyzed for their impact on complete remission, event-free survival (EFS), and overall survival (OS). RESULTS: Abnormal karyotypes were detected in 37% of our patients and were very complex, irrespective of the duration of standard therapy before the first autotransplant. In addition to previously recognized unfavorable implications of partial or complete deletion of chromosome 13 and 11q abnormalities, we now observed that the presence of any translocation likewise portended poor outcome (unfavorable karyotypes). On multivariate analysis, the absence of an unfavorable karyotype was the most favorable variable for both EFS (P = .0001) and OS (P = .0001). Other favorable factors were duration of standard therapy and a low beta-2 microglobulin (B2M) level before the first autotransplant. A risk-based classification system was developed according to the number of these favorable variables present, showing highly significant differences in event-free and overall survival. CONCLUSION: Cytogenetics play a dominant role in myeloma and were independent of previously recognized important prognostic factors, such as B2M and duration of prior standard therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Incidence and impact of light chain associated (AL) amyloidosis on the prognosis of patients with multiple myeloma treated with autologous transplantation.

Little is known about the incidence of clinically occult AL amyloid in patients with multiple myeloma and its impact on prognosis of these patients. To address these issues, subcutaneous fat pad aspirates (SAFA) and bone marrow biopsies were evaluated for the presence of amyloid in a cohort of newly diagnosed patients with multiple myeloma prior to enrollment on a phase II study including tandem transplants. Organ directed biopsies were performed when clinically indicated. Presence of amyloid at > or = 1 site was noted in 32 patients (38%). SAFA was positive in 25 (31%), bone marrow in 8 patients (10%) and other organ sites in 7 patients. Patients with and without amyloid did not differ in disease characteristics, in particular no lambda predominance was observed in patients with amyloid. Event free survival (59+ vs 52 months; p = .9) and overall survival (59+ vs 66+ months; p = .9) were similar in both groups. Even the seven patients with symptomatic organ involvement with AL amyloid had a median overall survival of 38+ months. In conclusion, AL amyloidosis occurs more often than previously reported, but its presence does not influence the outcome of these patients after transplantation.

Amyloidosis↗
PubMed1997

Biology and therapy of multiple myeloma in 1996.

Since the introduction of melphalan-prednisone for the treatment of multiple myeloma (MM) three decades ago, the prognosis of patients has not been improved by the addition of other agents, probably due to marked resistance of tumor cells, even at diagnosis, to commonly employed cytotoxic drugs. The biological basis for drug resistance is reviewed and current methods of diagnosis and staging delineated. The overview on treatment focuses on recurrent advances with myeloablative therapy demonstrating, in randomized and historically controlled trials, that high-dose therapy increases the incidence of true complete remission (CR) from 5% to approximately 40%, with an extension of median event-free (EFS) and overall (OS) survival durations to 3.5 and > or = 5 years, respectively. It is concluded that high-dose therapy should be offered to all patients with symptomatic meyloma, and current therapeutic research explores posttransplant immunotherapy.

Antineoplastic Agents↗
PubMed1996

Autotransplants in multiple myeloma: what have we learned?

Of 496 consecutive patients with multiple myeloma (MM) enrolled in clinical trials of tandem transplants with peripheral blood stem cells support, 470 (95%) completed the first autotransplant with melphalan 200 mg/m2 (MEL 200) and 363 (73%) completed the second transplant with either MEL 200 (40%), MEL 140 mg/m2 (MEL 140) with total-body irradiation (17%), or a combination of alkylating agents (16%), depending on the response status prior to the second transplant; 31 patients up to age 60 years received an allograft as the second transplant. The median interval from first to second transplant was 5 months. Treatment-related mortality during the first year after transplantation was 7%, and complete remission (CR) was obtained in 36%; the median durations of event-free survival (EFS) and overall survival (OS) after transplant were 26 and 41 months, respectively. Low beta 2-microglobulin ([B2M] < or = 2.5 mg/L) and C-reactive protein ([CRP] < or = 0.4 mg/dL) were the most significant standard parameters associated with both prolonged EFS and OS. Median OS exceeded 5.5 years in the one third of patients with both low B2M and CRP. When cytogenetics were included in the analysis, the presence of 11q abnormalities and/or complete or partial deletion of chromosome 13 ("unfavorable karyotype") became a dominant negative feature for both EFS and OS. In addition to these pretransplant parameters, attainment of CR and application of two transplants within 6 months both significantly extended EFS and OS. The group of patients (7%) with high B2M and CRP with either IgA isotype or unfavorable karyotype had the worst prognosis (EFS, < or = 10 months; median OS, < or = 12 months) and will require novel therapy. We conclude that tandem transplants are feasible in the majority of patients up to age 70 years, effecting CR in one third of all patients. Median OS was greater than 5.5 years, regardless of pretransplant features, if the first transplant was applied within 12 months of initial treatment and the second transplant no more than 6 months later.

Adult↗
PubMed1996

Role of NAD(P)H:quinone oxidoreductase (DT-diaphorase) in cytotoxicity and induction of DNA damage by streptonigrin.

The metabolism, cytotoxicity, and genotoxicity of streptonigrin (SN) w ere determined in two human colon carcinoma cell lines: HT-29 with high NAD(P)H:quinone oxidoreductase (EC 1.6.99.2, DTD) activity and BE with undetectable DTD activity. Dicumarol-sensitive oxidation of NADH was observed with HT-29 cytosol, but not with BE cytosol. Oxygen consumption was also observed using HT-29 cytosol, but was absent with BE cytosol. Dicumarol inhibited oxygen consumption with HT-29 cytosol, but deferoxamine had no effect, suggesting that divalent metal cations were not necessary for efficient auto-oxidation of SN hydroquinone. In cytotoxicity studies, SN was much more toxic to the DTD-rich HT-29 cells than to the DTD-deficient BE cells. Deferoxamine decreased toxicity in both cell lines, implicating hydroxyl radicals produced during Fenton-type reactions as the toxic species. In the genotoxicity assay, SN induced a much higher incidence of DNA strand breaks in HT-29 cells than in BE cells, and deferoxamine protected against DNA strand breaks in both cell lines. Some evidence of DNA repair was also observed in the two cell lines. These results support an important role for DTD in the cytotoxicity of SN in the high DTD HT-29 colon carcinoma cell line.

Antibiotics, Antineoplastic↗
PubMed1996

Cell-specific activation and detoxification of benzene metabolites in mouse and human bone marrow: identification of target cells and a potential role for modulation of apoptosis in benzene toxicity.

The role of cell-specific metabolism in benzene toxicity was examined in both murine and human bone marrow. Hemopoietic progenitor cells and stromal cells are important control points for regulation of hemopoiesis. We show that the selective toxicity of hydroquinone at the level of the macrophage in murine bone marrow stroma may be explained by a high peroxidase/nicotanimide adenine dinucleotide phosphate, reduced [NAD(P)H]:quinone oxidoreductase (NQO1) ratio. Peroxidases metabolize hydroquinone to the reactive 1,4-benzoquinone, whereas NQO1 reduces the quinones formed, resulting in detoxification. Peroxidase and NQO1 activity in human stromal cultures vary as a function of time in culture, with peroxidase activity decreasing and NQO1 activity increasing with time. Peroxidase activity and, more specifically, myeloperoxidase, which had previously been considered to be expressed at the promyelocyte level, was detected in murine lineage-negative and human CD34+ progenitor cells. This provides a metabolic mechanism whereby phenolic metabolites of benzene can be bioactivated in progenitor cells, which are considered initial target cells for the development of leukemias. Consequences of a high peroxidase/NQO1 ratio in HL-60 cells were shown to include hydroquinone-induced apoptosis. Hydroquinone can also inhibit proteases known to play a role in induction of apoptosis, suggesting that it may be able to inhibit apoptosis induced by other stimuli. Modulation of apoptosis may lead to aberrant hemopoiesis and neoplastic progression. This enzyme-directed approach has identified target cells of the phenolic metabolites of benzene in bone marrow and provided a metabolic basis for benzene-induced toxicity at the level of the progenitor cell in both murine and human bone marrow.

Animals↗