Effects of iodinated contrast agents in MR imaging

At least two classes of mRNA for the GH receptor (GHR) and GH binding protein (GH BP) with different 5' untranslated first exons exist in the rat. One such class, the GHR1 is predominantly expressed in the liver of female rats. The hepatic expression of the GHR1 mRNA in normal and hypophsectomized rats of both sexes was studied by employing an RNase protection/solution hybridization assay. Normal females expressed 10-fold more GHR1 mRNA than males, hypophysectomy of female rats decreased the GHR1 level to that observed in male rats. Continuous GH treatment of hypophysectomized male and female rats for 6 days increased the expression of GHR1 mRNA to levels found in normal females, whereas intermittent GH treatment without effect. Bovine GH(bGH) induced the GHR1 expression in a time- and dose-dependent manner in primary cultures of adult rat hepatocytes as determined by solution hybridization. Maximal induction was achieved after 72 h of treatment with 50 ng bGH/ml medium. Female enriched expression of receptor and binding protein mRNAs raises the possibility that they participate in determining the ability of the liver to respond differently to the male and female GH secretory patterns. Our in vitro model utilizing cultures of primary adult rat hepatocytes could be used to address this issue as well as explore a hormonal interplay in regulation of GHR1 expression.     

Electron microscopic evidence for the mechanism of blood-retinal barrier breakdown in diabetic rabbits: comparison with magnetic resonance imaging

Diabetes leads to a breakdown of the blood-retinal barrier (BRB), which can be demonstrated in experimental models by immunocytochemistry and magnetic resonance imaging (MRI). The present study utilizes these methods to investigate the mechanism of BRB breakdown in diabetic rabbits, a model ideally suited to both procedures. Rabbits were treated with alloxan and examined 2 months, 1 year, and 1.5 years after the development of diabetes to assess BRB breakdown using MRI and immunocytochemical staining for endogenous albumin. Using MRI, an increased incidence of retinal vascular leakage is first evident at 1 year of diabetes. Electron microscopic immunolocalization of albumin suggests that BRB compromise is principally mediated by transendothelial transport of serum proteins in endocytic vesicle-like structures of approximately 0.4-1 micron diameter. Some additional retinal vascular leakage is occasionally demonstrated through the interendothelial cell tight junctions, but only when adjacent vascular endothelial cells show degenerative changes. The similarity of these findings to those previously reported for diabetic humans and rats supports the use of the diabetic rabbit as a model for studying BRB dysfunction. MRI and electron microscopic (EM) immunocytochemistry are complementary methods for evaluating BRB dysfunction. MRI can provide an overall picture of the entire eye without sacrificing the animal. EM immunocytochemistry can provide a more detailed picture of a limited area of interest to gain insight into the mechanisms of extravasation. Together, both methods provide a more complete understanding of BRB breakdown in diabetic rabbits.     

Hepatic lesion detection at MR imaging: a comparative study with four sequences

PURPOSE: To compare results with the following magnetic resonance (MR) imaging sequences in the detection of focal hepatic lesions: fast spin-echo (SE) before and after administration of superparamagnetic iron oxide (SPIO) particles, fat-suppressed T2-weighted SE, and dynamic gadolinium-enhanced fast low-angle shot (FLASH). MATERIALS AND METHODS: In 26 patients with known malignancy and documented focal liver lesions, 1.0-T MR imaging was performed prior to hepatic resection. All images were reviewed independently by four blinded observers. Sensitivity was calculated for each sequence and for each observer by means of alternative-free-response receiver operating characteristic (ROC) methods. RESULTS: The mean area under the alternative-free-response ROC curve with SPIO-enhanced fast SE (0.85) was significantly greater (P < .02) than that with all other sequences. Detection was significantly improved with SPIO-enhanced fast SE compared with dynamic gadolinium-enhanced FLASH (which was the best of the other three sequences) for all lesions (P < .002) and for malignant lesions (P < .0002). CONCLUSION: Findings with the SPIO-enhanced fast SE sequence improved detection of focal liver lesions and had the highest diagnostic accuracy.     

Hepatic and adrenal changes in rabbits associated with hyperlipidemia caused by a semi-synthetic diet

Several investigators have reported that feeding a semi-synthetic diet of casein and dextrose to New Zealand White (NZW) rabbits will increase total serum cholesterol concentration, principally through an increase in the beta-lipoprotein fractions, thereby creating a useful model for atherosclerosis research. Although there is evidence to suggest that the dextrose/casein diet alters low-density lipoprotein receptor and bile acid clearance of cholesterol, the underlying mechanism is not completely understood. The effects of the diet on the overall physiology of the rabbit have received little attention. In this study feeding a diet of casein and dextrose of male NZW rabbits for 4 weeks resulted in changes in the serum lipid concentrations. During that time the rabbits fed the dextrose/casein diet gained less weight than did control rabbits. In the test diet rabbits, liver aspartate and alanine transaminase activities were increased from baseline values of 27 +/- 2 U/L and 89 +/- 9 U/L respectively to 112 +/- 21 U/L and 281 +/- 34 U/L respectively, then returned to the high end of the reference range. Necropsy findings included hepatomegaly caused by vacuolar hepatopathy in 19 or 20 experimental rabbits; rabbits fed the control diet had no hepatic lesions. Ultrastructural analysis revealed that enlargement of the liver cells was due to glycogen deposition. Adrenal glands from animals fed the experimental diet had a minimal change in the size of the adrenocortical cells consisting of slight ballooning and rarefaction of the cytoplasm. In a second study the level of dietary fiber was doubled. This resulted in a three-fold increase in lipid concentrations, compared with the fivefold increase in the first study. The liver enzyme activities were increased to the same extent as in the first study. Histologic changes were comparable to those in the first study. The activity of hepatic cholesterol 7alpha-hydroxylase was 3.7 +/- 0.4 pmol/min/mg of protein, compared with the control value of 7.7 +/- 1.1 pmol/min/mg of protein (P < 0.05) in the second study. The improved rate of weight gain and the lesser increase in total serum cholesterol concentration in the second study with increased dietary fiber suggest that two separate activities may be involved. Although the level of dietary fiber may be related to weight gain and total serum cholesterol values, the relation to the decrease in liver transaminase activities in study 1 was probably coincidental. It appears that the dextrose/casein diet causes decreased activity of hepatic cholesterol 7alpha-hydroxylase, which could cause a decrease in the biliary excretion of cholesterol.     

A new iodinated tropane derivative (beta-CDIT) for in vivo dopamine transporter exploration: comparison with beta-CIT

The expression of the human cytomegalovirus (HCMV) UL97 open reading frame in infected or transfected cells in the presence of the antiherpes compound ganciclovir (GCV) results in the intracellular phosphorylation of GCV. There are conventional kinase domains within the UL97-encoded protein (pUL97). However, the role of pUL97 in the HCMV replication cycle, and the mechanism by which it causes phosphorylation of GCV, are currently unknown. Herein, the biosynthesis and biogenesis of pUL97 was studied in HCMV-infected cells. pUL97 is expressed with early-late kinetics and is posttranslationally modified by phosphorylation. This phosphorylation occurs within 1 hr after synthesis, affects the electrophoretic mobility of pUL97, and is independent of the presence of other HCMV proteins. pUL97 was localized to the nucleus of infected cells and found in the HCMV virions. Thus, pUL97 is a virion phosphoprotein, and a likely tegument component.     

Doxycycline pleurodesis in rabbits: comparison of results with and without chest tube

We have reported previously that there is a high incidence of hemothorax and substantial mortality in rabbits that are given tetracycline derivatives intrapleurally. However, such complications have not been reported in humans when pleurodesis is attempted with tetracycline derivatives. One primary difference in the two situations is that a chest tube is placed only in humans. The objective of this study was to evaluate the hypothesis that chest tube placement would prevent the development of hemothoraces and lead to better pleurodesis in rabbits given doxycycline intrapleurally. Eighty New Zealand White male rabbits received doxycycline, 20 mg/kg, in a total volume of 2 mL. One half of the rabbits were randomized to receive a chest tube at the time of the injection and were subjected to pleural fluid aspiration twice daily. The remaining rabbits (control group) received no chest tube and no aspiration. Ten rabbits from each group were killed on days 4, 7, 14, and 28. The intrapleural injection of doxycycline induced the production of large exudative effusions. The insertion of chest tubes prevented the development of hemothorax (0/20 in chest tube group, 15/20 in control group, p<0.001). The insertion of chest tubes was also associated with a significant reduction in mortality and a significant improvement in pleurodesis. When pleurodesis is attempted in rabbits with intrapleural doxycycline, the insertion of a chest tube will prevent hemothorax and lead to a better pleurodesis.     

Urethrography and cavernosography imaging in a small series of penile fractures: a comparison with surgical findings

OBJECTIVES: To compare our results of preoperative corporal cavernosography and retrograde urethrography in penile fractures with the clinical and intraoperative findings. METHODS: From January to October 1996, 7 cases of penile fracture were diagnosed at our inner city trauma center. All cases were associated with sexual activity and patients underwent preoperative retrograde urethrography and corpus cavernosography with immediate surgical intervention. RESULTS: We found that 2 patients who presented with blood at the meatus had intact urethras, whereas 2 of the 3 patients who had urethral lacerations did not have a bloody meatus. In 2 cases the urethrogram and cavernosogram revealed lacerations that were not initially detected surgically. However, in another 2 cases, the urethrogram and cavernosogram were falsely negative. Two of the seven corporal fractures were bilateral and five were unilateral. CONCLUSIONS: On the basis of this small sample, it appears that preoperative cavernosography and retrograde urethrography may show additional sites of tears in the corpora and urethra because hematoma formation may mask some ruptures. However, the presence or absence of a bloody meatus may not necessarily correlate with the status of the urethra, and the urologist also should be wary of a false-negative imaging study. We suggest that all cases of penile fracture be explored surgically, but preferably by a subcoronal degloving incision that allows careful examination of the urethra and corpora. Results of a larger series may determine if the routine use of these imaging modalities is justified intraoperatively.     

Evaluation of breast tumors with color Doppler imaging: a comparison with image-directed Doppler ultrasound

Preclinical experience has shown that it is possible to maintain and expand hematopoietic cells in liquid culture systems by provision of optimal combinations of colony-stimulating factors (CSF). Ex vivo hematopoietic cell expansion (HCE) would be expected to reduce harvesting time and effort and could also decrease the infusion dose necessary for hematopoietic reconstitution after bone marrow transplantation. In addition, ex vivo expanded cells might be of value for therapeutic gene transfer. The central question in ex vivo HCE is whether the CSF combinations employed provide not only amplification of the late progenitor pools, but also maintenance or expansion of the stem cell compartment to ensure long term engraftment. Choice of CSF and experimental parameters in the culture system appear to be the most critical factors influencing the outcome of strategies for ex vivo HCE. Moreover, it is essential to define the goal of HCE and to adapt the experimental conditions to obtain the required cell populations. In future work, it remains to test the potential applicability of ex vivo expanded cells and to carefully monitor the possibility of the expansion of tumoral cells in ex vivo proliferation systems.     

Dietary L-arginine reduces the progression of atherosclerosis in cholesterol-fed rabbits: comparison with lovastatin

BACKGROUND: We investigated whether L-arginine induces regression of preexisting atheromatous lesions and reversal of endothelial dysfunction in hypercholesterolemic rabbits, whether similar effects can be obtained by cholesterol-lowering therapy with lovastatin, and which mechanism leads to these effects. METHODS AND RESULTS: Rabbits were fed 1% cholesterol for 4 weeks and 0.5% cholesterol for an additional 12 weeks. Two groups of cholesterol-fed rabbits were treated with L-arginine (2.0% in drinking water) or lovastatin (10 mg/d) during weeks 5 through 16. Systemic nitric oxide (NO) formation was assessed as the urinary excretion rates of nitrate and cGMP in weekly intervals. Cholesterol feeding progressively reduced urinary nitrate excretion to approximately 40% of baseline (P<.05) and increased plasma concentrations of asymmetrical dimethylarginine (ADMA), an endogenous NO synthesis inhibitor. Dietary L-arginine reversed the reduction in plasma L-arginine/ADMA ratio and partly restored urinary excretion of nitrate and cGMP (each P<.05 vs cholesterol) but did not change plasma cholesterol levels. L-Arginine completely blocked the progression of carotid intimal plaques, reduced aortic intimal thickening, and preserved endothelium-dependent vasodilator function. Lovastatin treatment reduced plasma cholesterol by 32% but did not improve urinary nitrate or cGMP excretion or endothelium-dependent vasodilation. Lovastatin had a weaker inhibitory effect on carotid plaque formation and aortic intimal thickening than L-arginine. L-Arginine inhibited but lovastatin potentiated superoxide radical generation in the atherosclerotic vascular wall. CONCLUSIONS: Dietary L-arginine improves NO-dependent vasodilator function in cholesterol-fed rabbits and completely blocks the progression of plaques via restoration of NO synthase substrate availability and reduction of vascular oxidative stress. Lovastatin treatment has a weaker inhibitory effect on the progression of atherosclerosis and no effect on vascular NO elaboration, which may be due to its stimulatory effect on vascular superoxide radical generation.     

Ventilation and perfusion imaging by electrical impedance tomography: a comparison with radionuclide scanning

Cytokine gene transfer into tumor cells has been shown to mediate tumor regression and antimetastatic effects in several animal models via immunomodulation. Therefore, clinical protocols have been developed to treat cancer patients with cytokine gene-modified tumor cells. We inserted the genes coding for the p35 and p40 chain of interleukin-12 (IL-12) in two independent eukaryotic expression vectors and transduced melanoma cells of 15 different primary tumor cultures with both plasmids by a ballistic gene transfer approach. Secreted IL-12 demonstrated strong bioactivity by inducing interferon-gamma release from peripheral blood lymphocytes upon coculture with cell culture supernatants after IL-12 gene transfer which could at least partly be blocked by IL-12-specific antisera. Further enrichment of transduced tumor cells by magnetic separation directly after gene transfer increased cytokine secretion from a mean of 119 pg in the unsorted to 507 pg IL-12 (24 h/10(8) cells) in the magnetically enriched cell fraction. Irradiation of these cells led to a further elevation of secreted IL-12 (mean 987 pg). Elevated IL-12 levels were detected over 7 days after irradiation in vitro. In a subsequent first clinical phase I study six patients with metastatic melanoma were vaccinated with autologous, interleukin-12 gene-modified tumor cells. Melanoma cells were expanded in vitro from surgically removed metastases, transduced by ballistic gene transfer, irradiated and were then injected subcutaneously (s.c.) at weekly intervals. Clinically, there was no major toxicity except for mild fever. All patients completed more than four s.c. vaccinations over 6 weeks and were eligible for immunological evaluation. Post-vaccination, peripheral mononuclear cells were found to contain an increased number of tumor-reactive proliferative as well as cytolytic cells as determined by a limiting dilution analysis in two patients. Two patients developed DTH reactivity against autologous melanoma cells and one had a minor clinical response. Biopsies taken from that patient's metastases revealed a heavy infiltration of CD4+ and CD8+ T lymphocytes. In conclusion, vaccination induced immunological changes even in a group of advanced, terminally ill patients. These changes can be interpreted as an increased antitumor immune response.     

Hepatic and splenic sarcoidosis: ultrasound and MR imaging

Two polypeptide antigens with molecular sizes of 34,000 daltons (34 kDa) and 38 kDa were separated from heated cells of a human clinical treponeme strain G7201 and Treponema denticola ATCC 35404, respectively. The rabbit polyclonal antisera against these antigens were produced and examined for their immunological reactions with the two heated antigens or intact spirochetal cells. Immunoblot analysis showed that the 34-kDa protein was also detected in T. denticola ATCC 35404 and ATCC 33520, and the 38-kDa protein was detected only in the two ATCC strains. Immunoelectron microscopy using the two rabbit antisera and protein A-gold complexes demonstrated that the 38-kDa protein antigen was present on the axial flagella of two T. denticola strains, and that the 34-kDa protein was located in the axial flagella of the G7201 cell, but neither in axial flagella nor on outer envelopes of the two ATCC strains cells, suggesting that the native 34-kDa axial flagellar protein of the G7201 strain may be different from that of T. denticola in terms of immunological reactivity.     

Indirect computed tomography lymphography of subdiaphragmatic lymph nodes using iodinated nanoparticles in normal dogs

RATIONALE AND OBJECTIVES: We evaluated the imaging characteristics of an iodinated particulate contrast agent for indirect computed tomography (CT) lymphography of normal subdiaphragmatic lymph nodes in dogs. METHODS: Four milliliters of a 15% (wt/vol) iodinated nanoparticle suspension was injected into the gastric, colonic, rectal, or cervical submucosa, loose paraprostatic fascia, or metatarsal subcutaneous tissues in 10 healthy beagles. Endoscopic, CT, or ultrasound guidance was used when necessary to facilitate contrast agent delivery. CT and radiographic images were obtained prior to contrast administration and at 4 hr, 24 hr, and 7 days postcontrast injection. Postmortem examinations were then conducted. RESULTS: CT images showed enhancement of regional lymph nodes draining the various injection sites. The mean attenuation of opacified nodes was 678 +/- 463 Hounsfield units 24 hr after injection and remained elevated 7 days later. Lymph node opacification on CT images correlated well with the node location observed on postmortem examinations. CONCLUSION: Subdiaphragmatic lymph nodes can be effectively opacified using an iodinated nanoparticle contrast agent for indirect CT lymphography.     

MR imaging in pelvic inflammatory disease: comparison with laparoscopy and US

PURPOSE: To assess the value of magnetic resonance (MR) imaging in the diagnosis of pelvic inflammatory disease (PID) and to compare MR imaging with transvaginal ultrasonography (US) and laparoscopy. MATERIALS AND METHODS: Thirty consecutive patients hospitalized because they were clinically suspected of having PID underwent transvaginal US and T1-weighted spin-echo, T2-weighted turbo spin-echo, and inversion-recovery MR imaging at 1.5 T. All patients underwent laparoscopy after MR imaging. RESULTS: PID was laparoscopically proved in 21 (70%) patients. The MR imaging diagnosis agreed with that obtained with laparoscopy in 20 (95%) of the 21 patients with PID. The imaging findings for PID were as follows: fluid-filled tube, pyosalpinx, tubo-ovarian abscess, or polycystic-like ovaries and free pelvic fluid. Findings at transvaginal US agreed with those at laparoscopy in 17 (81%) of the 21 patients with PID. The sensitivity of MR imaging in the diagnosis of PID was 95%, the specificity was 89%, and the overall accuracy was 93%. For transvaginal US, the corresponding values were 81%, 78%, and 80%. CONCLUSION: MR imaging is more accurate than transvaginal US in the diagnosis of PID and provides information about the differential diagnosis of PID. MR imaging may reduce the need for diagnostic laparoscopy.     

Hepatic parenchymal hyperperfusion abnormalities detected with multisection dynamic MR imaging: appearance and interpretation

On arterial-dominant-phase images in multisection dynamic MR imaging, early-enhancing areas that are perfusion abnormalities rather than tumor deposit are sometimes encountered. The purpose of this article was to determine the frequency, location, and appearance of these hepatic parenchymal hyperperfusion abnormalities and to discuss possible causes of these abnormalities. Multisection dynamic MR images obtained in 415 patients with suspected hepatobiliary diseases were reviewed for the presence of hyperperfusion abnormalities. A total of 96 hyperperfusion abnormalities were identified in 88 (21%) of 415 patients. They were characterised from their shape, distribution, or location as lobar or segmental (n = 36 [38%]), subsegmental (n = 32 [33%]), or subcapsular (n = 28 [29%]) hyperperfusion abnormalities. Presumable etiologies were considered as follows: (a) compression, obstruction, or ligation of the portal vein; (b) siphoning effect by tumor; (c) aberrant cystic venous drainage; (d) percutaneous ethanol injection; (e) percutaneous needle biopsy; (f) rapid drainage by the subcapsular vein; or (g) cirrhosis or unknown. A significant percentage of patients had hepatic hyperperfusion abnormalities. Familiarity with these hyperperfusion abnormalities on multisection dynamic MR images is important to prevent false-positive diagnoses.     

Edge detection in brain SPET perfusion imaging: a comparison of several methods

Four methods of brain edge detection on brain SPET perfusion (99Tcm-hexamethylpropylene amine oxime) images were compared: ellipse adaptation, simple thresholding (four threshold values), a low threshold (40%) followed by 1, 2 or 3 pixel erosion, and the Deriche 3D adaptive cut-off frequency method (four filter widths: alpha = 1, 2, 3 or 4). The SPET data of six patients were reconstructed to obtain 10 axial slices, each 10 mm thick, covering the whole brain. On the 60 axial slices, the methods were compared based on automaticity, computation time and accuracy of edge detection compared with morphological edges drawn manually on the patients' 3D co-registered magnetic resonance imaging (MRI) scans. The proportion of pixels inside the contour defined by the MRI scan but outside the SPET edge (p(i)), and the proportion of pixels inside the contour defined by the SPET image but outside the MRI contour (pe), were calculated. The thresholding methods provided interesting results, particularly the application of a low threshold value (40%), followed by a 2 pixel erosion, which required a computation time of 12 s (p(i) = 5.7 +/- 2.2%; pe = 2.7 +/- 0.9%). Because of adjustments to each slice of the ellipse axis, the processing time of this method was about 3 min (p(i) = 1.5 +/- 1.4%; pe = 11.3 +/- 3.4%). The Deriche 3D filter was time-consuming (6 min for 10 slices on a NXT workstation, SMV International). With this method, the best edge fitting was found with a filter width of 3 and 4 (p(i) = 9.6 +/- 11.1%; pe = 14.1 +/- 23.2%; alpha = 3). Three-dimensional filtering methods must be refined to reduce the computation time and to improve brain edge fitting accuracy when compared with the eroded thresholding method.     

Radionuclide imaging and ultrasound in liver/spleen trauma: a prospective comparison

In a prospective blind study of liver/spleen trauma, 32 consecutive patients were evaluated by radionuclide imaging (99mTc-sulfur colloid) and gray-scale ultrasound. Six patients (19%) had inadequate sonograms due to injuries and pain. Thirteen (41%) were normal, 13 (41%) were abnormal with one technique or the other, and there was a discrepancy in 2 (6%). Of the 13 abnormal patients, 1 had a lacerated spleen, 2 had angiographic confirmation of a subcapsular hematoma, and 10 showed resolution on follow-up. Two patients with left-sided trauma had abnormal radionuclide scans of the liver; sonograms were initially normal in one of them, but subsequent imaging confirmed the abnormality. The authors feel that imaging with 99mTc-sulfur colloid should be the primary screening examination for liver/spleen trauma.     

Magnetic resonance imaging of bone destruction in rheumatoid arthritis: comparison with radiography

Bony changes in forty-four knees of patients with clinically established rheumatoid arthritis (RA) were examined using magnetic resonance imaging (MRI) and plain film radiography. In all cases MRI was clearly superior to radiographs, demonstrating 25 marginal erosions and 42 subchondral cysts, while the number seen on radiographs was 3 and 8, respectively. These results emphasize the problems in visualizing bone erosions in large joints using plain films. MRI is the method of choice for detecting early changes in RA, not only because of its high sensitivity, but also because of the ability of contrast-enhanced MRI to provide physiological characterization of these lesions.     

Pharmacokinetics and hypotensive effect of diltiazem in rabbits: comparison of diltiazem with its major metabolites

To assess the contribution of its metabolites to the antihypertensive effects of diltiazem, a previously established rabbit model has been used to compare the pharmacokinetics and haemodynamic effects of the drug with those of its major metabolites deacetyldiltiazem (M1) and deacetyl-N-monodemethyldiltiazem (M2). Diltiazem, M1 and M2 were administered separately to each animal (n = 5 or 6 per study group) as a single 5 mg kg(-1) intravenous dose. Blood samples, systolic and diastolic blood pressure (SBP and DBP) and heart rate were recorded for each rabbit up to 8 h, and urine samples were collected for 48 h post-dose. Plasma concentrations of diltiazem and its major metabolites were determined by HPLC. The results showed that systemic clearance (CL) and volume of distribution at steady state (Vdss) were smaller for diltiazem than for the metabolites. Diltiazem and the metabolites reduced both SBP and DBP, the effects of diltiazem being most potent. Their effects on heart rate were highly variable and not statistically different between treatment groups (P > 0.05). These results indicate that diltiazem is a more potent hypotensive agent than M1 or M2, possibly because of the higher plasma concentrations secondary to the smaller CL and Vdss of diltiazem compared with the metabolites. The effects of the metabolites might, however, be more sustained.     

Iodination of mouse EGF with chloramine T at 4 degrees C: characterization of the iodinated peptide and comparison with other labelling methods

The BP-1/6C3 molecule expressed by early B lineage cells and some stromal cells has been identified as aminopeptidase A (APA). We have previously demonstrated that IL-7 selectively induces BP-1/APA expression by pre-B cells coincident with their growth. Here we directly demonstrate that BP-1 is preferentially expressed by the proliferating subpopulation of normal B cell progenitors. Furthermore, when non-adherent BALB/c bone marrow cells were incubated with IL-7 in the presence of purified BP-1 antibody, B cell precursor proliferation was markedly inhibited. Modulation of the BP-1/6C3 antigen did not occur in the presence of the BP-1 antibody, but APA enzymatic activity was significantly inhibited. The 6C3 antibody, which recognizes a different epitope on the APA molecule, had no effect on either B cell precursor proliferation or APA enzyme activity. We hypothesized that neutralization of APA by the BP-1 antibody results in inhibition of IL-7 driven B cell precursor proliferation. However, when isolated 14.8+ bone marrow cells were cultured with IL-7 in the presence of the BP-1 antibody, no inhibition of proliferation occurred. This data suggested that the effect of the BP-1 antibody might be related to the action of APA on peptides in the marrow microenvironment which are not present in cultures of isolated B cell precursors. The addition of irradiated non-adherent bone marrow cells to the 14.8+ cell cultures restored the inhibitory effect of the BP-1 antibody. Based on these observations, we propose that APA cleaves a small peptide which serves as a natural inhibitor of B cell precursor proliferation.