Telemedicine visits in an established multidisciplinary central nervous system clinic for radiation oncology and neurosurgery (RADIANS) in a community hospital setting.

OBJECTIVE: To determine the impact of telemedicine visits, compared to in-person visits, on patient satisfaction in an established community hospital-based multidisciplinary central nervous system (CNS) clinic. METHODS: Telemedicine options - virtual visits and teleconferencing - were introduced in July 2020. Both radiation oncologist and neurosurgeon were simultaneously present for the telemedicine visit. Descriptive patient demographics, survey responses, and travel time and distance calculations were analyzed. Satisfaction score was compared to previously published data. RESULTS: A total of twenty-five telemedicine visits (n=22 video; n=3 phone) were completed since July 2020. Patient demographics are as follows: mean age was 59 years (range=22-81), women (9) and men (16), repeat telemedicine visits n=10, malignant CNS disease (17) and benign disease (5). Mean one-way distance traveled was 165.07 miles (median=114; range=0.8-358). Mean roundtrip travel time was estimated at 5h 5min. Mean telemedicine visit duration was 15.3 mins (range=4-46). Mean patient satisfaction score for telemedicine visits was 4.84. CONCLUSION: Patients who opted for the telemedicine visits found them just as effective as in-person visits, saving time and travel costs as well as ensuring patient safety during the current COVID-19 pandemic. The telemedicine visit platform facilitates the multidisciplinary clinic model and should be considered for more widespread utilization (Tab. 3, Fig. 1, Ref. 18).

Risk of persistent or recurrent cervical neoplasia in patients with 'pure' adenocarcinoma-in-situ (AIS) or mixed AIS and high-grade cervical squamous neoplasia (cervical intra-epithelial neoplasia grades 2 and 3 (CIN 2/3)): a population-based study.

OBJECTIVE: To compare outcomes of patients with pure adenocarcinoma-in-situ (AIS) and mixed AIS/CIN 2/3 lesions including the incidence of AIS persistence, recurrence and progression to adenocarcinoma. DESIGN: Retrospective cohort study. SETTING: Statewide population in Western Australia. POPULATION: Women diagnosed with AIS between 2001 and 2012. METHODS: We conducted a retrospective, population-based cohort study. MAIN OUTCOME MEASURES: De-identified linked data were utilised to ascertain the association between patient age at excisional treatment, margin status, lesion type, lesion size, and risk of persistent AIS (defined as the presence of AIS <12 months from treatment), recurrent AIS (≥12 months post-treatment), and adenocarcinoma. RESULTS: 636 patients were eligible for analysis. The mean age was 32.3 years and median follow-up interval was 2.5 years. Within the study cohort, 266 patients (41.8%) had pure AIS and 370 (58.2%) had mixed AIS/CIN 2/3. Overall, 47 patients (7.4%) had AIS persistence/recurrence and 12 (1.9%) had adenocarcinoma. Factors associated with persistence/recurrence were pure AIS (hazard ratio (HR) 2.3; 95%CI 1.28-3.94; P = 0.005), age >30 years (HR 2.1; 95%CI 1.16-3.81; P = 0.015), positive endocervical margins (HR 5.8; 95%CI 3.05-10.92; P = <0.001) and AIS lesions >8 mm (HR 2.5; 95%CI 1.00-6.20; P = 0.049). A histologically positive AIS ectocervical margin was not associated with persistence/recurrence. CONCLUSION: In this study, pure AIS was associated with greater risk of persistence/recurrence than was mixed AIS/CIN 2/3. AIS lesions >8 mm and positive endocervical margins were significant predictors for persistent or recurrent disease. TWEETABLE ABSTRACT: Pure cervical adenocarcinoma-in-situ (AIS) may have greater risk of recurrence than AIS co-existing with CIN 2/3.

Development of an In Vitro Model of Inflammatory Cytokine Influences on Intervertebral Disk Cells in 3D Cell Culture Using Activated Macrophage-Like THP-1 Cells.

We developed a new model for evaluation of the influence of proinflammatory cytokines on intervertebral disc cells in a 3D culture based on co-culturing of these cells with activated macrophage-like THP-1 cells. The levels of TNFα, IL-1ß, IL-6, IL-8, IL-10, and IL-12p70 production were assessed by flow cytofluorometry using microspheres. Considerable differences in the level of spontaneous cytokine secretion by normal and degenerated intervertebral disc cells were revealed. A significant increase in the level of IL-1ß and IL-8 was observed during co-culturing, which confirms consistency of the developed model.

Using biomarkers to allocate patients in a response-adaptive clinical trial.

In this paper, we discuss a response adaptive randomization method, and why it should be used in clinical trials for rare diseases compared to a randomized controlled trial with equal fixed randomization. The developed method uses a patient's biomarkers to alter the allocation probability to each treatment, in order to emphasize the benefit to the trial population. The method starts with an initial burn-in period of a small number of patients, who with equal probability, are allocated to each treatment. We then use a regression method to predict the best outcome of the next patient, using their biomarkers and the information from the previous patients. This estimated best treatment is assigned to the next patient with high probability. A completed clinical trial for the effect of catumaxomab on the survival of cancer patients is used as an example to demonstrate the use of the method and the differences to a controlled trial with equal allocation. Different regression procedures are investigated and compared to a randomized controlled trial, using efficacy and ethical measures.

How accurately is hospital acquired pneumonia documented for the correct assignment of a hospital acquired complication (HAC)?

BACKGROUND: In 2016, the Australian Commission on Safety and Quality in Healthcare (ACSQHC) released a list of 16 categories of potentially preventable, high impact hospital-acquired complications (HAC) identified by using administrative coded data (ACD). An important category are hospital-acquired infections (HAI). Within this category, hospital-acquired pneumonia (HAP) is among the most frequent complications documented. There are no published studies concerning the current ACSQHC approach to HAI surveillance using ACD and no pneumonia-specific ACD studies reported from Australia. Published work indicates that ACD detection of HAP has low a sensitivity and positive predictive value (PPV). The current study was designed to examine whether coders correctly reflected the documentation of HAP that was present in the medical record and also evaluated the medical documentation that was present. METHODS: One hundred patients with ACD encoded HAP were selected for review, drawn from admissions to 2 Hunter New England Health hospitals during 2017. Patient records and the eMR were reviewed by two medical officers to assess medical and radiological documentation of pneumonia. The district coding manager reviewed the accuracy of coding of a subset of 23 cases where medical review had not located documented evidence of HAP. RESULTS: Of the 100 reviewed cases, the median patient age was 75 years (range 0-95 years) with 3% under 16 years of age. Twenty one were intensive care-associated of which 13 were associated with ventilation. In 23 cases the documentation was disputed and a secondary review took place - the coding manager confirmed coding changes in 14 of these 23 cases. CONCLUSIONS: This study found that administrative coded data of HAP, utilizing the ACSQHC method reliably reflected the available documentation with a PPV of 86% (95% binomial exact confidence interval 77-92%), much higher than documented by previous ACD studies. The actual documentation of pneumonia by medical staff frequently used the non-specific term 'lower respiratory infection (LRTI)' which we recommend to be avoided. Radiological confirmation was absent in one third of cases. We recommend the adoption of a medical note template checklist for HAP to prompt clinicians with the accepted diagnostic criteria. We also recommend documenting a reason as to why any antibiotic has been commenced in a hospitalized patient in accord with the ACSQHC Antimicrobial Stewardship Clinical Care Standard.

Cancer--we're here to listen.

The National Cancer Forum (2006) recommended that high-quality efficient information resources should be made available to the public. In order to address the needs of the public, the Irish Cancer Society provide a national Cancer Information Service (CIS) incorporating a Prostate Cancer Information Service (PCIS). This audit was designed to explore the information and support needs of those who contacted the Irish Cancer Society's information services during 2007.

ER translocation intermediates are adjacent to a nonglycosylated 34-kD integral membrane protein.

We have used the homobifunctional cross-linking reagent disuccinimidyl suberate (DSS) to identify proteins that are adjacent to nascent polypeptides undergoing translocations across mammalian rough ER. Translocation intermediates were assembled by supplementing cell free translations of truncated mRNAs with the signal recognition particle (SRP) and microsomal membrane vesicles. Two prominent cross-linked products of 45 and 64 kD were detected. The 64-kD product was obtained when the cell free translation contained SRP, while formation of the 45-kD product required both SRP and translocation competent microsomal membrane vesicles. In agreement with previous investigators, we suggest that the 64-kD product arises by cross-linking of the nascent polypeptide to the 54-kD subunit of SRP. The 45-kD product resists alkaline extraction from the membrane, so we conclude that the 11-kD nascent polypeptide has been crosslinked to an integral membrane protein of approximately 34 kD (imp34). The cross-linked product does not bind to ConA Sepharose, nor is it sensitive to endoglycosidase H digestion; hence imp34 is not identical to the alpha or beta subunits of the signal sequence receptor (SSR). We propose that imp34 functions in concert with SSR to form a translocation site through which nascent polypeptides pass in traversing the membrane bilayer of the rough endoplasmic reticulum.

Detrital nonprotein amino acids are the key to rapid growth of tilapia in lake valencia, Venezuela.

The detritivorous cichlid Sarotherodon mossambicus grows rapidly on a low-protein diet by assimilating detrital nonprotein amino acids. Differences in the quantity of detrital amino acids in different lakes may account for the variable success of S. mossambicus introductions around the world.

Very low density lipoproteins stimulate surfactant lipid synthesis in vitro.

Surfactant synthesis is critically dependent on the availability of fatty acids. One fatty acid source may be circulating triglycerides that are transported in VLDL, and hydrolyzed to free fatty acids by lipoprotein lipase (LPL). To evaluate this hypothesis, we incubated immortalized or primary rat alveolar pre-type II epithelial cells with VLDL. The cells were observed to surface bind, internalize, and degrade VLDL, a process that was induced by exogenous LPL. LPL induction of lipoprotein uptake significantly increased the rates of choline incorporation into phosphatidylcholine (PC) and disaturated PC, and these effects were associated with a three-fold increase in the activity of the rate-regulatory enzyme for PC synthesis, cytidylyltransferase. Compared with native LPL, a fusion protein of glutathione S-transferase with the catalytically inactive carboxy-terminal domain of LPL did not activate CT despite inducing VLDL uptake. A variant of the fusion protein of glutathione S-transferase with the catalytically inactive carboxy-terminal domain of LPL that partially blocked LPL-induced catabolism of VLDL via LDL receptors also partially blocked the induction of surfactant synthesis by VLDL. Taken together, these observations suggest that both the lipolytic actions of LPL and LPL-induced VLDL catabolism via lipoprotein receptors might play an integral role in providing the fatty acid substrates used in surfactant phospholipid synthesis.

Region-dependent alterations in glutamate and GABA measured by high-resolution magnetic resonance spectroscopy following acute binge inhalation of toluene in juvenile rats.

Little is known about the neurochemical effects accompanying the high-concentration inhalant exposures characteristic of binge solvent abuse. In adult animals, prior studies with other patterns of exposure indicate that toluene, a commonly abused household and industrial solvent, has significant effects on the glutamatergic and GABAergic neurotransmitter systems and on other neurotransmitter systems as well. In the current investigation, high-resolution "magic angle" spinning proton magnetic resonance spectroscopy (HR-MAS (1)H-MRS) was used to assess the effect of acute binge toluene inhalation on regional brain concentrations of various neurochemicals including glutamate (GLU), GABA, and glutamine (GLN) in juvenile male and female rats. Acute toluene (8000 ppm or 12,000 ppm) significantly reduced levels of hippocampal GABA (-12%) and GLU (-8%), and the GLU/GLN ratio, an index of glutamatergic tone, was significantly reduced (-22%) in the dorsal anterior striatum, driven largely by a 28% increase in GLN. Significant increases in alanine and lactate in several brain regions after acute toluene may be indicative of altered oxygen-dependent metabolism associated with the inhalation of higher concentrations of toluene (e.g., >5000 ppm). Other components of the MR-visible neurochemical profile, such as N-acetylaspartate (NAA), myo-inositol, creatine, and various choline containing compounds, were unchanged by acute toluene. The results are consistent with the notion that binge toluene exposure affects juvenile neurochemistry in systems mediating the rewarding and emotional aspects of substance abuse. Moreover the results provide a framework to understand further (1)H-MRS studies in clinical populations.

Prenatal toluene exposure impairs performance in the Morris Water Maze in adolescent rats.

Volatile organic solvent abuse continues to be a worldwide health problem, including the neurobehavioral teratogenic sequelae of toluene abuse during pregnancy. Although abuse levels of prenatal toluene exposure can lead to a Fetal Solvent Syndrome, there is little research examining these effects on memory. Consumption of toluene can have detrimental effects on the developing hippocampus which could lead to specific spatial learning and memory deficits. This study used a rat model to determine how prenatal exposure to abuse levels of toluene would affect performance in a spatial learning and memory task, the Morris Water Maze (MWM). Pregnant Sprague-Dawley rats were exposed to 0, 8000 or 12,000ppm (ppm) of toluene for 15min twice daily from gestation day 8 (GD8) through GD20. Male and female offspring (N=104) were observed in the MWM for 5days beginning on postnatal day (PN) 28 and again on PN44. While prenatal toluene-exposed animals did not differ in initial acquisition in the MWM, rats prenatally exposed to 12,000ppm toluene displayed performance deficits during a probe trial and in reversal learning on PN44. Overall, this study indicates that prenatal exposure to repeated inhaled abuse patterns of high concentrations of toluene can impair spatial memory function that persists into adolescence.

Changes in developmental body weight as a function of toluene exposure: A meta-analysis of animal studies.

Inhalant abuse is a globally prevalent health issue with particular concerns about substance-abusing pregnant women. In both animal models and clinical case reports of toluene exposure, the primary physiological outcome measure of prenatal inhalant exposure is low birth weight (BW). However, the effect of prenatal toluene exposure on animal BW varies widely in the literature. To clarify this effect and investigate possible design moderators of pup BW, a systematic review and meta-analytic techniques were applied to the existing peer-reviewed animal literature of prenatal and postnatal exposure models to the inhaled solvent toluene. Of 288 studies screened, 24 studies satisfied the inclusion criteria. Evaluation of these studies indicated that toluene exposure was negatively associated with pup BW (d = -0.39), with external inhaled concentration, route of administration, day of weighing, and toluene exposure magnitude moderating this association. Investigators doing animal studies should be cognizant of these factors before investigating the reproductive and developmental outcomes associated with prenatal and postnatal toluene exposure.

Artemia hemoglobins. Increase in net synthesis of the beta-polypeptide (relative to the alpha-polypeptide) in hypoxia.

Previous studies have shown that in the brine shrimp there are three dimeric hemoglobins with polypeptide composition alpha 2, alpha beta, beta 2. Concentrations of the alpha- and beta-polypeptides increase in hypoxia. We now report a two-dimensional electrophoretic method for assay of radiolabelled polypeptides in each hemoglobin. Net synthesis (synthesis minus degradation) of the beta-chain, relative to that of the alpha-chain, increases more than 3-fold (in male and female adults) within 3 days following a downshift in oxygen concentration from 0.2 to 0.1 mM in the culture medium. 3 days after downshift (2 days after in vivo incorporation of radiolabelled leucine), the beta-homodimer contained 10-20% of the radiolabel in the three hemoglobins although beta 2 was usually not detectable in the protein stain of an overloaded gel. The amount of radioactive leucine incorporated per unit amount of protein was more than 300-times greater in the beta 2 homodimer than in the beta-subunit of the heterodimer, suggesting that beta 2 does not dissociate rapidly during electrophoresis on the first dimension non-denaturing gel. This evidence for stable association of the two beta-monomers and the 5-8 heme-binding domains within each monomer (in vivo and during electrophoresis on non-denaturing gels) allows us to exclude one of two alternative interpretations of genetic data published previously. We present an independent line of evidence for the dimer model of the native hemoglobins (which states that each polypeptide has many heme-binding domains).

Dehydroepiandrosterone sulfate and beta-cell function: enhanced glucose-induced insulin secretion and altered gene expression in rodent pancreatic beta-cells.

Administration of dehydroepiandrosterone (DHEA), or its sulfated form (DHEAS), controls hyperglycemia in diabetic rodents without directly altering insulin sensitivity. We show that DHEAS enhanced glucose-stimulated insulin secretion when administered in vivo to rats or in vitro to beta-cell lines, without changing cellular insulin content. Insulin secretion increased from 3 days of steroid exposure in vitro, suggesting that DHEAS did not directly activate the secretory processes. DHEAS selectively increased the beta-cell mRNA expression of acyl CoA synthetase-2 and peroxisomal acyl CoA oxidase in a time-dependent manner. Although DHEAS is a peroxisomal proliferator, it did not alter the mRNA expression of peroxisomal proliferator-activated receptor (PPAR) alpha or beta, or enhance the activity of transfected PPAR alpha, beta, or gamma in vitro. Thus, DHEAS directly affected the beta-cell to enhance glucose-stimulated insulin secretion and increased the mRNA expression of specific beta-cell mitochondrial and peroxisomal lipid metabolic enzymes. This effect of DHEAS on insulin secretion may contribute to the amelioration of hyperglycemia seen in various rodent models of diabetes.

The recombinant rat glucagon-like peptide-1 receptor, expressed in an alpha-cell line, is coupled to adenylyl cyclase activation and intracellular calcium release.

The glucagon-like peptide-1 (GLP-1) receptor is expressed on alpha-cells, though its functional significance is unknown. The endogenous beta-cell GLP-1 receptor is coupled to adenylyl cyclase, cell depolarization, activation of voltage-dependent Ca2+ channels (VDCC) and extracellular Ca2+ influx (Lu et al., 1993 b). In contrast, the signaling pathways of the GLP-1 receptor in alpha-cells are poorly understood. To determine the signaling mechanisms of the alpha-cell GLP-1 receptor, we established a stable pancreatic islet alpha-cell line expressing the recombinant rat GLP-1 receptor (INR1-SF2), using INRl-G9 cells. These INRl-G9 cells do not express endogenous GLP-1 receptor. In INR1-SF2 cells, GLP-1 bound to the recombinant receptor (Kd = 0.9 nM) and increased cAMP (ED50 = 0.6 nM). GLP-1 increased the free cytosolic Ca2+ ([Ca2+]i) (ED50 = 50 nM) by release from intracellular stores, but did not affect INR1-SF2 cell phosphoinositol turnover. Despite expressing VDCC, the INR1-SF2 cells were not depolarized by GLP-1, even in the presence of glucose. This contrasts with the depolarizing action of GLP-1 in beta-cells in the presence of glucose (Lu et al., 1993 b). This study establishes that a single GLP-1 receptor species can mediate the effects of GLP-1 through multiple signaling pathways, including the adenylyl cyclase system and intracellular Ca2+ release, in an alpha-cell type. Furthermore, since GLP-1 is unable to cause cellular depolarization or activate VDCC in INR1-SF2 cells, these data suggest that glucose-induced membrane depolarization may be crucial for GLP-1 to further activate VDCC and potentiate glucose-stimulated insulin release in beta-cells. Finally this study describes a cell line that can be used as a model system for evaluation of GLP-1 signaling in alpha-cells.

Relationship between molecular mass and duration of activity of polyethylene glycol conjugated granulocyte colony-stimulating factor mutein.

Proteins conjugated with polyethylene glycol (PEG) have increased in vivo activity compared to native proteins. We examined the activity of a variety of PEG conjugates prepared with a recombinant mutein of granulocyte colony-stimulating factor (nartograstim [NTG], KW-2228). The total PEG mass was varied by the number and size of the PEG molecules conjugated. In vitro activity, determined using a proliferation assay with G-NFS-60 cells, demonstrated an inverse relationship between PEG mass and concentration required for half-maximal proliferation. In vivo activity was examined by injecting compounds subcutaneously into normal mice and determining neutrophil counts at various times. Initial experiments in C57BL/6J mice indicated that neutrophil levels were significantly elevated 5 days after a single injection of 25 micrograms/mouse of each PEG-NTG preparation. More detailed experiments were performed with several of the preparations in C3H/HeJ mice lacking endotoxin receptors. The results demonstrated that the time after injection at which neutrophil numbers reached a maximum increased with increasing size of PEG. Similar results were obtained with purified preparations containing 1, 2, or 3 units of 20-kDa PEG per molecule of NTG, showing that increasing the extent of PEGylation also increases in vivo activity. Dose-response studies with the 20-kDa PEG-NTG demonstrated a plateau at doses > 2.7 micrograms/mouse at day 3. The plateau dose increased to 8.4 micrograms/mouse at day 5, and no plateau was evident at the highest dose tested (50 micrograms/mL) at days 7 and 10. These results demonstrate that elevated neutrophil levels can be maintained for extended periods following single administration of high-molecular-weight PEG-NTG.

Imaging and dosimetric errors in 4D PET/CT-guided radiotherapy from patient-specific respiratory patterns: a dynamic motion phantom end-to-end study.

Effective positron emission tomography / computed tomography (PET/CT) guidance in radiotherapy of lung cancer requires estimation and mitigation of errors due to respiratory motion. An end-to-end workflow was developed to measure patient-specific motion-induced uncertainties in imaging, treatment planning, and radiation delivery with respiratory motion phantoms and dosimeters. A custom torso phantom with inserts mimicking normal lung tissue and lung lesion was filled with [(18)F]FDG. The lung lesion insert was driven by six different patient-specific respiratory patterns or kept stationary. PET/CT images were acquired under motionless ground truth, tidal breathing motion-averaged (3D), and respiratory phase-correlated (4D) conditions. Target volumes were estimated by standardized uptake value (SUV) thresholds that accurately defined the ground-truth lesion volume. Non-uniform dose-painting plans using volumetrically modulated arc therapy were optimized for fixed normal lung and spinal cord objectives and variable PET-based target objectives. Resulting plans were delivered to a cylindrical diode array at rest, in motion on a platform driven by the same respiratory patterns (3D), or motion-compensated by a robotic couch with an infrared camera tracking system (4D). Errors were estimated relative to the static ground truth condition for mean target-to-background (T/Bmean) ratios, target volumes, planned equivalent uniform target doses, and 2%-2 mm gamma delivery passing rates. Relative to motionless ground truth conditions, PET/CT imaging errors were on the order of 10-20%, treatment planning errors were 5-10%, and treatment delivery errors were 5-30% without motion compensation. Errors from residual motion following compensation methods were reduced to 5-10% in PET/CT imaging, <5% in treatment planning, and <2% in treatment delivery. We have demonstrated that estimation of respiratory motion uncertainty and its propagation from PET/CT imaging to RT planning, and RT delivery under a dose painting paradigm is feasible within an integrated respiratory motion phantom workflow. For a limited set of cases, the magnitude of errors was comparable during PET/CT imaging and treatment delivery without motion compensation. Errors were moderately mitigated during PET/CT imaging and significantly mitigated during RT delivery with motion compensation. This dynamic motion phantom end-to-end workflow provides a method for quality assurance of 4D PET/CT-guided radiotherapy, including evaluation of respiratory motion compensation methods during imaging and treatment delivery.

Vitamin A excess alters membrane flow in rat liver.

Pulse-chase methodology with [35S]methionine as label was employed to determine flow kinetics through the endoplasmic reticulum-Golgi apparatus-(lysosome-) secretory vesicle-plasma membrane export route in livers of animals receiving vitamin A excess by gavage. Overall fraction composition determined by morphometry and by analyses of marker enzymes was unchanged by vitamin administration. The vitamin modified the pattern of flow of proteins through the Golgi apparatus to the cell surface and to lysosomes. Altered flux was evidenced by a markedly reduced rate of labeling of lysosomes and a slightly increased rate of labeling of both total membrane proteins of the plasma membrane and of a specific membrane glycoprotein GP80. Also reduced was overall labeling of the Golgi apparatus. Differences in the rate or routes of trafficking of glycoproteins through the Golgi apparatus together with altered opportunities for processing might account for some of the alterations in glycoconjugate glycosylation associated with excess vitamin A administration.

Administration of recombinant interleukin-12 to mice suppresses hematopoiesis in the bone marrow but enhances hematopoiesis in the spleen.

Although IL-12 has been reported to synergize with c-kit ligand (KL) in promoting hematopoietic stem cell proliferation in vitro, administration of recombinant mouse IL-12 (rIL-12) to normal mice caused a dose- and time-dependent anemia, leukopenia, and thrombocytopenia in vivo. Decreased numbers of bone marrow cells were recovered from the tibiae of IL-12-treated mice, and histologic examination of the marrow revealed a loss of mature neutrophils and red blood cell precursors. However, simultaneously with the suppression of hematopoiesis in the bone marrow, the IL-12-treated mice developed splenomegaly, which was largely caused by a marked enhancement of splenic extramedullary hematopoiesis of the erythroid, myeloid, and megakaryocytic lineages. These histologic observations were confirmed by colony-forming cell assays in which administration of IL-12 was shown to cause a time-dependent decrease in bone marrow CFU-GM, CFU-E, and BFU-E hematopoietic colony-forming cells while causing an increase in splenic CFU-GM and BFU-E colony-forming cells. All these effects were reversible upon cessation of IL-12 treatment. The observation that in IL-12-treated mice hematopoiesis was suppressed in the marrow but enhanced in the spleen suggests that myelosuppression was not caused by a direct effect of IL-12 on hematopoietic progenitors. It seems likely that myelosuppression was caused instead by an IL-12-induced alteration in the local environment of the marrow.