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Biomedical subjects

P A Thompson

Publications and source records attributed to P A Thompson.

At least 19 recordsLinked to original sources
PubMed1999

Comparison of DNA adduct levels associated with exogenous and endogenous exposures in human pancreas in relation to metabolic genotype.

Recently, we examined normal human pancreas tissue for DNA adducts derived from either exogenous chemical exposure and/or endogenous agents. In an effort to explain the different types and levels of DNA adducts formed in the context of individual susceptibility to cancer, we have focused on gene-environment interactions. Here, we report on the levels of hydrophobic aromatic amines (AAs), specifically those derived from 4-aminobiphenyl (ABP), and DNA adducts associated with oxidative stress in human pancreas. Although these adducts have been reported in several human tissues by different laboratories, a comparison of the levels of these adducts in the same tissue samples has not been performed. Using the same DNA, the genotypes were determined for N-acetyltransferase 1 (NAT1), the glutathione S-transferase (GST) M1, GSTP1, GSTT1, and NAD(P)H quinone reductase-1 (NQO1) as possible modulators of adduct levels because their gene products are involved in the detoxification of AAs, lipid peroxidation products and in redox cycling. These results indicate that ABP-DNA adducts, malondialdehyde-DNA adducts, and 8-oxo-2'-deoxyguanosine (8-oxo-dG) adducts are present at similar levels. Of the metabolic genotypes examined, the presence of ABP-DNA adducts was strongly associated with the putative slow NAT1*4/*4 genotype, suggesting a role for this pathway in ABP detoxification.

Aminobiphenyl Compounds↗
PubMed1999

Manganese superoxide dismutase (MnSOD) genetic polymorphisms, dietary antioxidants, and risk of breast cancer.

Oxidative stress, resulting from the imbalance between prooxidant and antioxidant states, damages DNA, proteins, cell membranes, and mitochondria and seems to play a role in human breast carcinogenesis. Dietary sources of antioxidants (chemical) and endogenous antioxidants (enzymatic), including the polymorphic manganese superoxide dismutase (MnSOD), can act to reduce the load of oxidative stress. We hypothesized that the valine-to-alanine substitution that seems to alter transport of the enzyme into the mitochondrion, changing its efficacy in fighting oxidative stress, was associated with breast cancer risk and that a diet rich in sources of antioxidants could ameliorate the effects on risk. Data were collected in a case-control study of diet and breast cancer in western New York from 1986 to 1991. Caucasian women with incident, primary, histologically confirmed breast cancer were frequency-matched on age and county of residence to community controls. Blood specimens were collected and processed from a subset of participants in the study (266 cases and 295 controls). Using a RFLP that distinguishes a valine (V) to alanine (A) change in the -9 position in the signal sequence of the protein for MnSOD, we characterized MnSOD genotypes in relation to breast cancer risk. We also evaluated the effect of the polymorphism on risk among low and high consumers of fruits and vegetables. Premenopausal women who were homozygous for the A allele had a 4-fold increase in breast cancer risk in comparison to those with 1 or 2 V alleles (odds ratio, 4.3; 95% confidence interval, 1.7-10.8). Risk was most pronounced among women below the median consumption of fruits and vegetables and of dietary ascorbic acid and alpha-tocopherol, with little increased risk for those with diets rich in these foods. Relationships were weaker among postmenopausal women, although the MnSOD AA genotype was associated with an almost 2-fold increase in risk (odds ratio, 1.8; confidence interval, 0.9-3.6). No appreciable modification of risk by diet was detected for these older women. These data support the hypothesis that MnSOD and oxidative stress play a significant role in breast cancer risk, particularly in premenopausal women. The finding that risk was greatest among women who consumed lower amounts of dietary antioxidants and was minimal among high consumers indicates that a diet rich in sources of antioxidants may minimize the deleterious effects of the MnSOD polymorphism, thereby supporting public health recommendations for the consumption of diets rich in fruits and vegetables as a preventive measure against cancer.

Aged↗
PubMed1999

Lithium augmentation fails to reduce symptoms in poorly responsive schizophrenic outpatients.

BACKGROUND: Nearly one third of patients suffering from schizophrenia do not fully respond to antipsychotic medication. Safe, effective, and cost-efficient methods to reduce symptoms are clearly needed; therefore, lithium as an adjunct to fluphenazine decanoate was tested in a placebo-controlled trial in outpatients who were part of the Treatment Strategies of Schizophrenia (TSS) study. METHOD: Forty-one patients with DSM-III schizophrenia or schizoaffective disorder were assigned to either adjunctive lithium or placebo after at least 6 months of fluphenazine decanoate treatment to stabilize symptoms had failed. The trial was designed for 8 weeks of treatment, and patients assigned to placebo could afterward be administered lithium in an 8-week, open-label study. RESULTS: Assessment of the intent-to-treat analysis revealed no significant differences in demographic variables between the lithium and placebo groups. Although both groups showed significant (p = .00135) improvement as measured by total scores on the Brief Psychiatric Rating Scale (BPRS), there were no significant differences in response between the lithium and placebo groups. Patients originally treated with placebo added to neuroleptic did not have significantly greater improvement when receiving open-label adjunctive lithium. CONCLUSION: Although success with lithium augmentation therapy for persistent psychosis has been reported in the past, this study of well-characterized patients showed no benefit for this common strategy, thus indicating that care be used in utilizing lithium augmentation.

Ambulatory Care↗
PubMed1999

Development of an antipeptide antibody that binds to the C-terminal region of human CYP1B1.

An antipeptide antibody was raised against a 14-mer synthetic peptide (CDFRANPNEPA KMN) corresponding to the amino acid sequence from 491 to 504 of human cytochrome P-450 (CYP)1B1. Rabbit-derived antisera demonstrated the ability to induce moderately high antibody titers (>1:10(5)) as judged by enzyme-linked immunosorbent assay. In Western blot analysis, the purified antibody recognized a single protein band (estimated as 56 kDa) in microsomes prepared from human and rodent tissues. No significant cross-reactivity to either human CYP1A1 or human CYP1A2 protein was detected. Titration studies using recombinant human CYP1B1 and an enhanced chemiluminescence-based detection method demonstrated a minimal detection sensitivity for this antiserum at about 0.34 ng/band in 8 x 7-cm minigels. The immunoprecipitation and immunoinhibition results indicate that this antisera recognizes the nondenatured human CYP1B1 protein but does not inhibit its enzyme activity. Using this antibody, CYP1B1 protein was detected in nine different human tissues and in cultured cells induced by various chemicals. This highly specific, highly sensitive antibody provides an important tool to study tissue distribution and cellular expression levels of CYP1B1, with negligible cross-reactivity from the other members of the CYP1 family.

Amino Acid Sequence↗
PubMed1998

Comparison of DNA adduct levels associated with oxidative stress in human pancreas.

DNA adducts associated with oxidative stress are believed to involve the formation of endogenous reactive species generated by oxidative damage and lipid peroxidation. Although these adducts have been reported in several human tissues by different laboratories, a comparison of the levels of these adducts in the same tissue samples has not been carried out. In this study, we isolated DNA from the pancreas of 15 smokers and 15 non-smokers, and measured the levels of 1,N6-etheno(2'-deoxy)guanosine (edA), 3, N4-etheno(2'-deoxy)cytidine (edC), 8-oxo-2'-deoxyguanosine (8-oxo-dG), and pyrimido[1,2-alpha]purin-10(3H)-one (m1G). Using the same DNA, the glutathione S-transferase (GST) M1, GSTT1, and NAD(P)H quinone reductase-1 (NQO1) genotypes were determined in order to assess the role of their gene products in modulating adduct levels through their involvement in detoxification of lipid peroxidation products and redox cycling, respectively. The highest adduct levels observed were for m1G, followed by 8-oxo-dG, edA, and edC, but there were no differences in adduct levels between smokers and non-smokers and no correlation with the age, sex or body mass index of the subject. Moreover, there was no correlation in adduct levels between edA and eC, or between edA or edC and m1G or 8-oxo-dG. However, there was a significant correlation (r=0.76; p<0.01) between the levels of 8-oxo-dG and m1G in human pancreas DNA. Neither GSTM1 nor NQO1 genotypes were associated with differences in any of the adduct levels. Although the sample set was limited, the data suggest that endogenous DNA adduct formation in human pancreas is not clearly derived from cigarette smoking or from (NQO1)-mediated redox cycling. Further, it appears that neither GSTM1 nor GSTT1 appreciably protects against endogenous adduct formation. Together with the lack of correlation between m1G and edA or edC, these data indicate that the malondialdehyde derived from lipid peroxidation may not contribute significantly to m1G adduct formation. On the other hand, the apparent correlation between m1G and 8-oxo-dG and their comparable high levels are consistent with the hypothesis that m1G is formed primarily by reaction of DNA with a base propenal, which, like 8-oxo-dG, is thought to be derived from hydroxyl radical attack on the DNA.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1998

STAT6 is required for IL-4-induced germline Ig gene transcription and switch recombination.

Transcription of the germline C gamma1 and C epsilon Ig genes is believed to be a necessary prerequisite for isotype switching to IgG1 and IgE, respectively. IL-4 stimulation and ligation of CD40 can each independently induce low level germline gamma1 and epsilon transcription in murine B cells. Together these signals act synergistically to promote high level germline transcription and are normally required for T-dependent isotype switching to IgG1 and IgE. The STAT6 transcription factor has been suggested to play a critical role in IL-4-induced activation of germline C gamma1 and C epsilon genes. To directly assess the role of STAT6 in IL-4R- and CD40-mediated germline transcription and switching, we have analyzed these events in splenic B cells from STAT6-deficient mice. Our results demonstrate that IL-4 does not induce detectable levels of germline gamma1 or epsilon transcripts in STAT6-deficient B cells. Germline transcript expression induced by CD40 stimulation alone is unaffected, but synergism between CD40- and IL-4R-mediated signals is completely ablated. Switch recombination to S gamma1, as measured by digestion-circularization PCR, is dramatically reduced in STAT6-deficient B cells stimulated with CD40 ligand plus IL-4. Similarly, germline gamma1 transcript expression and switch recombination to S gamma1 are also impaired in STAT6-deficient B cells stimulated with IL-4, IL-5, and anti-IgD Abs conjugated to dextran, a model for T-independent type II responses. These results directly demonstrate a critical role for STAT6 in the IL-4-mediated activation of germline Ig gene transcription and switch recombination in nontransformed B cells.

Animals↗
PubMed1998

Genetic polymorphisms in catechol-O-methyltransferase, menopausal status, and breast cancer risk.

Polymorphic catechol-O-methyltransferase (COMT) catalyzes the O-methylation of estrogen catechols. In a case-control study, we evaluated the association of the low-activity allele (COMT(Met)) with breast cancer risk. Compared to women with COMT(Val/Val), COMT(Met/Met) was associated with an increased risk among premenopausal women [odds ratio (OR), 2.1; confidence interval (CI), 1.4-4.3] but was inversely associated with postmenopausal risk (OR, 0.4; CI, 0.2-0.7). The association of risk with at least one low-activity COMT(Met) allele was strongest among the heaviest premenopausal women (OR, 5.7; CI, 1.1-30.1) and among the leanest postmenopausal women (OR, 0.3; CI, 0.1-0.7), suggesting that COMT, mediated by body mass index, may be playing differential roles in human breast carcinogenesis, dependent upon menopausal status.

Body Mass Index↗
PubMed1998

Lymphoid hyperplasia, CD45RBhigh to CD45RBlow T-cell imbalance, and suppression of Type I diabetes mellitus result from TNF blockade in NOD-->NOD-scid adoptive T cell transfer.

Sustained antibody-mediated inhibition of tumor necrosis factor (TNF) activity offers protection against Type I (insulin-dependent) diabetes mellitus in non-obese diabetic (NOD) mice. The mechanism of this effect, however, has remained obscure: TNFalpha might be required for the development of specific immune responses to islet antigens or it could directly participate in destruction of beta cells. In this study, autoimmune destruction of beta cells was initiated in NOD-severe combined immunodeficient (scid) mice by transfer of NOD splenic T-cells to induce diabetes. The blockade of TNFalpha activity was achieved during a narrow window of time after transfer. Transient inhibition of TNFalpha greatly reduced the number of islet lymphocytes and the incidence of diabetes in recipients of prediabetic NOD spleen cells. Protection extended beyond the interval of effective TNF blockade. Furthermore, the protective effect was only observed if cells were obtained from 6-week-old donors. The suppression of autoimmunity was reversible in the context of adoptive transfer as indicated by the transfer of splenocytes from the primary recipient to a second NOD-scid host led to a diabetic outcome. The blockade of TNFalpha was accompanied by a considerable increase in spleen size and doubling of the total splenocyte count, suggesting that TNFalpha might normally eliminate a transplanted T-cell subset within the recipients. Further analysis showed an increase in the absolute count of CD4 + T cells and pronounced distortion of the CD45RBhigh to CD45RBlow ratio, with a relative augmentation in the CD45RBlow count in the spleen. TNFalpha appears to regulate the number and subtype distribution of a transplanted T cell population.

Adoptive Transfer↗
PubMed1998

Exfoliated ductal epithelial cells in human breast milk: a source of target tissue DNA for molecular epidemiologic studies of breast cancer.

Studies of biomarkers of putative breast carcinogens, such as DNA adducts, have been limited by the difficulty in obtaining representative ductal epithelial cells (DECs) from breast tissue. In this feasibility study, we sought to ascertain if exfoliated DECs in breast milk could be a source of DNA for biomarker studies. Specimens (n = 38) were collected over 24 h from nursing women, and a questionnaire was administered. Cell pellets were isolated by repeated centrifugation and washing. Pellets were resuspended and incubated for 2 h, with glass adherence used to remove monocytes, resulting in an enrichment of DECs of >80%. Nonadherent cells were removed, washed, and homogenized for DNA isolation. Accurate DNA quantification was performed by 32P-postlabeling of normal nucleotides under conditions of excess ATP. Although there was wide variability in the amounts of DNA recovered, DNA yield was significantly associated with the number of weeks postpartum (P < 0.01), with optimal yield between 6 and 8 weeks after birth. There were no significant associations (P < 0.05) between the number of cells recovered and milk volume, method of collection, or the number of samples in a 24-h period per individual. This study demonstrates that breast milk can be used as a source of DECs for biomarker studies of gene-environment interaction and that sufficient DNA can be recovered to evaluate carcinogen-DNA adducts and to perform genotyping assays. Using this approach, exfoliated DECs may serve as a source of representative cells for studies of breast carcinogenesis and biomarkers of exposure, susceptibility, and effect.

Biomarkers, Tumor↗
PubMed1997

Folding dynamics and mechanism of beta-hairpin formation.

Protein chains coil into alpha-helices and beta-sheet structures. Knowing the timescales and mechanism of formation of these basic structural elements is essential for understanding how proteins fold. For the past 40 years, alpha-helix formation has been extensively investigated in synthetic and natural peptides, including by nanosecond kinetic studies. In contrast, the mechanism of formation of beta structures has not been studied experimentally. The minimal beta-structure element is the beta-hairpin, which is also the basic component of antiparallel beta-sheets. Here we use a nanosecond laser temperature-jump apparatus to study the kinetics of folding a beta-hairpin consisting of 16 amino-acid residues. Folding of the hairpin occurs in 6 micros at room temperature, which is about 30 times slower than the rate of alpha-helix formation. We have developed a simple statistical mechanical model that provides a structural explanation for this result. Our analysis also shows that folding of a beta-hairpin captures much of the basic physics of protein folding, including stabilization by hydrogen bonding and hydrophobic interactions, two-state behaviour, and a funnel-like, partially rugged energy landscape.

Kinetics↗
PubMed1997

Dendritic cell ontogeny: a human dendritic cell lineage of myeloid origin.

Dendritic cells (DC) have been thought to represent a family of closely related cells with similar functions and developmental pathways. The best-characterized precursors are the epidermal Langerhans cells, which migrate to lymphoid organs and become activated DC in response to inflammatory stimuli. Here, we demonstrate that a large subset of DC in the T cell-dependent areas of human lymphoid organs are nonactivated cells and belong to a separate lineage that can be identified by high levels of the interleukin 3 receptor alpha chain (IL-3Ralphahi). The CD34+IL-3Ralphahi DC progenitors are of myeloid origin and are distinct from those that give rise to Langerhans cells in vitro. The IL-3Ralphahi DC furthermore appear to migrate to lymphoid organs independently of inflammatory stimuli or foreign antigens. Thus, DC are heterogeneous with regard to function and ontogeny.

Cell Lineage↗
PubMed1997

Laser temperature jump study of the helix<==>coil kinetics of an alanine peptide interpreted with a 'kinetic zipper' model.

The kinetics of the helix<==>coil transition of an alanine-based peptide following a laser-induced temperature jump were monitored by the fluorescence of an N-terminal probe, 4-(methylamino)benzoic acid (MABA). This probe forms a peptide hydrogen bond to the helix backbone, which changes its fluorescence quantum yield. The MABA fluorescence intensity decreases in a single exponential relaxation, with relaxation times that are weakly temperature dependent, exhibiting a maximum value of approximately 20 ns near the midpoint of the melting transition. We have developed a new model, the kinetic version of the equilibrium 'zipper' model for helix<==>coil transitions to explain these results. In this 'kinetic zipper' model, an enormous reduction in the number of possible species results from the assumption that each molecule contains either no helical residues or a single contiguous region of helix (the single-sequence approximation). The decay of the fraction of N-terminal residues that are helical, calculated from numerical solutions of the kinetic equations which describe the model, can be approximately described by two exponential relaxations having comparable amplitudes. The shorter relaxation time results from rapid unzipping (and zipping) of the helix ends in response to the temperature jump, while the longer relaxation time results from equilibration of helix-containing and non-helix-containing structures by passage over the nucleation free energy barrier. The decay of the average helix content is dominated by the slower process. The model therefore explains the experimental observation that relaxation for the N-terminal fluorescent probe is approximately 8-fold faster than that for the infrared probe of Williams et al. [(1996) Biochemistry 35, 691-697], which measures the average helix content, but does not account for the absence of observable amplitude for the slow relaxation in the fluorescence experiments (<10% slow phase). If we assume that the activation barrier for the coil-->helix rate is purely entropic, the model can also explain the maximum in the temperature dependence of the relaxation time for the fluorescent probe. Parameters that best reproduce the melting curves and the ratio of relaxation times predict a value of the cooperativity parameter sigma which is approximately 3-fold larger than previously reported values obtained from fitting equilibrium data only. The helix growth rate of approximately 10(8) s-1 that reproduces the experimental relaxation times is approximately 100-fold slower than those observed in molecular dynamics simulations. These parameters can be used to simulate the kinetically cooperative formation of a helix from the all-coil state.

Alanine↗
PubMed1997

Serotonin receptors in suicide victims with major depression.

Serotonin1A (5-HT1A) and serotonin2A (5-HT2A) receptors in the brain have been implicated in the pathophysiology of suicide. Brain samples were collected at autopsy from suicide victims with a current episode of major depression and matched comparison subjects who died of natural or accidental causes. Retrospective psychiatric assessments were collected from knowledgeable informants for all suicide victims and most of the comparison subjects. Psychiatric diagnoses were determined according to DSM-III-R criteria. Any subjects with current psychoactive substance use disorders were excluded. Quantitative receptor autoradiography was used in serial sections of the right prefrontal cortex (area 10) and hippocampus to measure the binding of [3H]8-hydroxy-2-(di-n-propyl)-aminotetralin ([3H]8-OH-DPAT) to 5-HT1A receptors and [3H]ketanserin to 5-HT2A receptors. Analysis of covariance was used to compare control subjects and suicide victims with major depression. The age of subjects, the time from death to freezing the tissue (postmortem interval), and the storage time of tissues in the freezer were used as covariates in the analyses. There were no significant differences between suicide victims with major depression and comparison subjects in 5-HT1A or 5-HT2A receptors in area 10 of the right prefrontal cortex or the hippocampus. The current results suggest that the number of 5-HT1A and 5-HT2A receptors in the right prefrontal cortex (area 10) or hippocampus are not different in suicide victims with major depression.

Adult↗
PubMed1997

Submillisecond kinetics of protein folding.

New experimental methods permit observation of protein folding and unfolding on the previously inaccessible nanosecond-microsecond timescale. These studies are beginning to establish times for the elementary motions in protein folding - secondary structure and loop formation, local hydrophobic collapse, and global collapse to the compact denatured state. They permit an estimate of about one microsecond for the shortest time in which a protein can possibly fold.

Humans↗
PubMed1997

Correlates of psychological distress among mothers of children and adolescents with hemophilia and HIV infection.

Evaluated the correlates of mood state (psychological distress) in a multisite study of two groups: (a) mothers of HIV-positive children and adolescents with hemophilia (n = 91), and (b) mothers of HIV-negative children and adolescents with hemophilia (n = 92). Socioeconomic status, quality of family relationship support, and frequency of negative life events accounted for significant variance in Total Mood Disturbance (psychological distress) as measured by the Profile of Mood States in the overall sample. Severity of hemophilia was unrelated to distress. A significant interaction between HIV status and frequency of stressful life events indicated that this variable related more strongly to distress among mothers of HIV-infected children and adolescents with hemophilia than among mothers of HIV-negative children with hemophilia. Findings suggest that the presence of HIV infection in their children and adolescents may heighten the impact of negative life events on the psychological distress experienced by these mothers.

Adolescent↗
PubMed1997

Age at onset and gender of schizophrenic patients in relation to neuroleptic resistance.

OBJECTIVE: The age at onset of schizophrenia for males has usually but not always been reported to be less than that for females. Early onset has also been associated with poor response to neuroleptic treatment and worse long-term outcome. The authors compared age at onset in neuroleptic-resistant and -responsive schizophrenic patients to determine whether the gender difference in age at onset is related to response to neuroleptic treatment. METHOD: The subjects were 322 patients with schizophrenia or schizoaffective disorder who were consecutively admitted to a university hospital-based research program. RESULTS: Analysis of variance showed significant relationship between age at onset and both gender and longterm responsivity to neuroleptic drugs. The mean ages at onset in the neuroleptic-responsive men (mean = 21.2 years, SD = 6.1, N = 75), neuroleptic-resistant men (mean = 19.4 years, SD = 4.7, N = 119), and neuroleptic-resistant women (mean = 20.1 years, SD = 6.3, N = 77) were fairly similar, whereas that of the neuroleptic-responsive women (mean = 24.2 years, SD = 8.7, N = 51) was significantly greater than for all other groups. A simple effects model indicated that male and female neuroleptic-resistant patients did not differ significantly in mean age at onset, whereas male and female neuroleptic-responsive patients did. The effect of gender and neuroleptic responsivity on age at onset was related to schizophrenic subtype. CONCLUSIONS: These results confirm previous data indicating neuroleptic resistance is associated with early onset. The finding that the difference in age at onset between males and females is smaller in neuroleptic-resistant patients than in neuroleptic-responsive patients suggests that neuroleptic-resistant patients differ premorbidly as well as after onset of illness.

Adolescent↗
PubMed1996

Granulocytic and monocytic differentiation of CD34hi cells is associated with distinct changes in the expression of the PU.1-regulated molecules, CD64 and macrophage colony-stimulating factor receptor.

The present study investigated the possibility that macrophage colony-stimulating factor (M-CSF) responsiveness of hematopoietic progenitor cells is regulated at the level of receptor expression and that M-CSF receptor (M-CSFR) may be used as an early marker of monocyte lineage commitment. Immunofluorescence measurements with an anti-M-CSFR antibody showed that 44% +/- 5% of CD34hi cells expressed the receptor. The M-CSFR was present on progenitor cells that were positive for the granulo-monocytic marker CD64, but not on primitive, erythroid, or lymphoid progenitors. The CD34hiCD64+ population could be divided into subsets of M-CSFRhi and M-CSFRlo cells. In addition, a subset of CD34hiCD64-M-CSFRhi cells was found. CD34+ cells that were positive for M-CSFR, CD64, or both gave rise exclusively to granulo-monocytic cells, and 65% of the granulomonocytic colony-forming cells in the CD34+ population were recovered from these cells. Approximately 70% of the colony-forming cells (CFCs) derived from CD34hiM-CSFRhi cells were macrophage colony-forming units (CFU-M), whereas 91% of the CFCs in the CD34hiCD64+M-CSFRlo population were granulocyte colony-forming units (CFU-G). The M-CSFRhi cells with the highest frequency of colony-forming and bipotent cells and largest average colony size were found in the CD64- subset, indicating that M-CSFR appears earlier than CD64 during monocyte development. After 60 hours in culture, a subset of the CD34hiM-CSFRhi cells had downmodulated M-CSFR (29% to 38%). This population gave rise almost exclusively to granulocytes, whereas the cells that remained M-CSFRhi gave rise exclusively to monocytes. In all experiments, the M-CSFRhi population responded to M-CSF, whereas minimal responses were observed among M-CSFRlo cells. These results suggest that M-CSF target specificity among human hematopoietic progenitor cells is determined by lineage-specific regulation of the M-CSFR and show that M-CSFR is a useful marker to discriminate between monocytic and granulocytic progenitor cells.

Animals↗