Retraction Note: Imipenem-resistance in Serratia marcescens is mediated by plasmid expression of KPC-2.

The article "Imipenem-resistance in Serratia marcescens is mediated by plasmid expression of KPC-2", by W.-Q. Su, Y.-Q. Zhu, N.-M. Deng, L. Li, published in Eur Rev Med Pharmacol Sci 2017; 21 (7): 1690- 1694-PMID: 28429335 has been retracted by the Editor in Chief. Following some concerns raised on PubPeer (link: https://pubpeer.com/publications/F7E91E2863540C7CB030B86E16917F), the Editor in Chief has started an investigation to assess the validity of the results as well as possible figure and data manipulation. The authors were informed about the journal's investigation but have remained unresponsive and have not provided the manuscript's raw data. Therefore, the validity of the overall results could not be verified. The journal's investigation revealed that Figures 2 and 3 have been computer-generated. Additionally, Figure 1 was duplicated from a previously published article. Moreover, several terminology inaccuracies were identified within the manuscript. Consequently, the Editor in Chief mistrusts the results presented and has decided to retract the article. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/12540.

Investigation of cross-sectional image analysis method to determine the blending ratio of polyester/cotton yarn.

It has been considered as a great challenge to identify the blending ratio of polyester/cotton yarn in the field of textile industry. A new digital cross-sectional image processing method based on geometrical shape analysis is proposed to improve the measurement accuracy of polyester/cotton blend ratio. A self-developed microscope image capturing system is established to digitalise the cross-sectional images of polyester/cotton blended yarn. One set of image preprocessing algorithm is developed to conduct greyscale inversion, median filtering denoising and binarisation. The specially designed edge detection algorithm is used to identify the continuous profile of fibres. Finally, the roundness value of the cross-sectional fibre is calculated based on the proposed roundness algorithm, it can be used to identify the polyester/cotton fibres and calculate the blending ratio of them. Our experimental results show that the new digital analysis method proposed in this paper is feasible for the measurement of polyester/cotton blended ratio; therefore, it has a good application prospect in the field of textile quality control, including the development of new equipment, methods and standards.

[Effects of calcineurin gene silencing on the remodeling of transient outward potassium current ionic channel in hypertrophic ventricular myocytes from neonatal rats].

Objective: To investigate the effects of calcineurin gene silencing on the remodeling of transient outward potassium current (Ito) ionic channel and action potential duration (APD) in phenylephrine (PE)-induced hypertrophic ventricular myocytes from neonatal rats. Methods: The ventricular myocytes of 1-day-old Sprague-Dawley rats were isolated and cultured for 48 h. RNA interference mediated by adenovirus carrying short hairpin RNA was used to knock down the gene which encodes the beta subtype of calcineurin A subunit (CnAß) and the cells were divided into 4 groups as Ad-null group, Ad-null+ PE group, Ad-CnAßshRNA1(A1) group and A1+ PE group, and then cultured for 48 h. The gene expression of Kv4.2 was assayed by real-time reverse transcriptase-polymerase chain reaction. The protein expressions of CnAß and Kv4.2 were assayed by Western blot test. Whole cell patch clamp technique was used to record Ito and action potential. Results: Treatment of the neonatal rat ventricular myocytes with PE induced the cell hypertrophy, up-regulated the protein expression of CnAß, attenuated the gene and protein expressions of Kv4.2 and the Ito current density, and prolonged APD. Silencing of CnAß in the neonatal rat ventricular myocytes using Ad-CnAßshRNA1 inhibited the aforementioned ability of PE significantly. Conclusion: CnAß gene silencing inhibits the remodeling of transient outward potassium current ionic channel and change of APD in PE-induced hypertrophic ventricular myocytes from neonatal rats.

Identification of a TLR2-regulated gene signature associated with tumor cell growth in gastric cancer.

Toll-like receptors (TLRs) are key regulators of innate immune responses, and their dysregulation is observed in numerous inflammation-associated malignancies, including gastric cancer (GC). However, the identity of specific TLRs and their molecular targets which promote the pathogenesis of human GC is ill-defined. Here, we sought to determine the clinical utility of TLR2 in human GC. TLR2 mRNA and protein expression levels were elevated in >50% of GC patient tumors across multiple ethnicities. TLR2 was also widely expressed among human GC cell lines, and DNA microarray-based expression profiling demonstrated that the TLR2-induced growth responsiveness of human GC cells corresponded with the up-regulation of six anti-apoptotic (BCL2A1, BCL2, BIRC3, CFLAR, IER3, TNFAIP3) and down-regulation of two tumor suppressor (PDCD4, TP53INP1) genes. The TLR2-mediated regulation of these anti-apoptotic and tumor suppressor genes was also supported by their increased and reduced expression, respectively, in two independent genetic GC mouse models (gp130F/F and Gan) characterized by high tumor TLR2 expression. Notably, enrichment of this TLR2-regulated gene signature also positively correlated with augmented TLR2 expression in human GC tumors, and served as an indicator of poor patient survival. Furthermore, treatment of gp130F/F and cell line-derived xenograft (MKN1) GC mouse models with a humanized anti-TLR2 antibody suppressed gastric tumor growth, which was coincident with alterations to the TLR2-driven gene signature. Collectively, our study demonstrates that in the majority of GC patients, elevated TLR2 expression is associated with a growth-potentiating gene signature which predicts poor patient outcomes, thus supporting TLR2 as a promising therapeutic target in GC.

Imipenem-resistance in Serratia marcescens is mediated by plasmid expression of KPC-2.

OBJECTIVE: Imipenem is a broad-spectrum carbapenem antibiotic with applications against severe bacterial infections. Here, we describe the identification of imipenem-resistant Serratia marcescens in our hospital and the role of plasmid-mediated KPC-2 expression in imipenem resistance. MATERIALS AND METHODS: We used the modified Hodge test to detect carbapenemase produced in imipenem-resistant strains. RESULTS: His resistance can be transferred to E. coli in co-culture tests, which implicates the plasmid in imipenem resistance. PCR amplification from the plasmid identified two products consistent with KPC-2 of 583 and 1050 bp that were also present in E. coli after co-culture. The restriction pattern for both plasmids was identical, supporting the transfer from the S. marcescens isolate to E. coli. Finally, gene sequencing confirmed KPC-2 in the plasmid. CONCLUSIONS: Due to the presence of KPC-2 in the imipenem-resistant S. marcescens, we propose that KPC-2 mediates antibiotic resistance in the S. marcescens isolate.

[Isolation of cariogenic Streptococcus mutans and the inhibitory effect of egg yolk antibody on caries].

Objective: To isolate the cariogenic Streptococcus mutans (Sm) strains and study the therapeutical effect of egg yolk antibody (IgY) of the Sm on dental caries development. Methods: Sm strains were isolated from the children's dental plaque samples. Morphological, biochemical and molecular biological methods were applied to identify the serotype, acid producing and adhesion abilities of isolated Sm strains. After inactivation one of the Sm strains was used as antigen to immune laying hens to collect and extract the specific anti-Sm IgY. The rats were infected with Sm (serotype e). After 16 weeks of infection, all the rats were found developing dental caries. The rats were then randomly divided into two groups. The rats in experimental group were supplied with diet containing anti-Sm IgY while the rats in control group with normal IgY. All rats were sacrificed after another 8 weeks' observation. The degree of caries for each rat was assessed using Keyes' method. Results: We isolated 7 Sm strains from the children's dental plaque samples in the present study. The numbers of serotype c, e, f, k were 3, 2, 0 and 2, respectively. All strains showed similar morphological and biochemical characters as standard UA159 Sm strain, and possessed strong capabilities of acid production and adherence. Interestingly, even the same serotypec strains, such as No.3 and No.7 strains, demonstrated significant difference on acid producing and adherence capabilities. After 16 weeks infection with serotype e strain, the rats' mandibular teeth were apparently decayed, and treatment with specific anti-Sm IgY obviously attenuated the development of caries in the experiment group rats (16.4±2.0) compared with that in the control group rats (30.2±9.3) (P<0.05) determined by Keyes' method. Conclusions: Seven cariogenic Sm strains of different serotypes were isolated, which possesses similar morphology and biochemical characters. Although belonging to the same serotype strains they always show significant difference in acid-producing and adherencec apabilities. Further experiment provides evidences that the serotype e strain could obviously induce caries independently, and employment of specific anti-Sm IgY as passive immunotherapy additive might effectively inhibit the further development of dental caries.

The effect of curcumin on bladder tumor in rat model.

OBJECTIVE: Bladder cancer is the most commonly malignant tumor in the urogenital tract, only next to prostate cancer with a higher incidence in China. Curcumin is the major component of curcuma longa and has multiple biological effects including anti-tumor. This study aimed to investigate the effect of curcumin on bladder cancer. MATERIALS AND METHODS: SPF-grade Wistar rats were used for establishing bladder cancer model through injection of N-methyl-N-nitrosourea (MNU). Rats were then randomly divided into experimental, model and control group. 160 µmol/L curcumin were applied in the experimental group while model group received an equal volume of saline. General condition, morphology changes and cell cycle of bladder cancer cells were examined. Meanwhile, apoptotic proteins including Bcl-2, Bax and surviving were also measured by Western blot. RESULTS: Model rats displayed fever, hematuria, decreased food and water intake, dispersed fur, lower body mass and decreased activity. Under microscopy, the bladder wall was thickened with the cauliflower-like lesion, in which significant necrotic and hemorrhagic lesions were found. Experimental group rats improved general condition without decrease of body mass. The only minor lesion was found without significant necrosis or hemorrhage without invasion into the muscular layer. The number of G1 phase cells was increased while S phase cell number was decreased after drug intervention, suggesting suppression of G1/S transition (p < 0.05). In curcumin-treated rats, the expression of Bcl-2 and Survivin were significantly decreased while Bax protein expression was significantly elevated (p < 0.05). CONCLUSIONS: Curcumin can inhibit the growth and invasion of rat bladder cancer cells, possibly through the arresting of G1/S transition and subsequently increased apoptosis.

FOXC1 is involved in ERα silencing by counteracting GATA3 binding and is implicated in endocrine resistance.

Estrogen receptor-α (ERα) mediates the essential biological function of estrogen in breast development and tumorigenesis. Multiple mechanisms, including pioneer factors, coregulators and epigenetic modifications have been identified as regulators of ERα signaling in breast cancer. However, previous studies of ERα regulation have focused on luminal and HER2-positive subtypes rather than basal-like breast cancer (BLBC), in which ERα is underexpressed. In addition, mechanisms that account for the decrease or loss of ER expression in recurrent tumors after endocrine therapy remain elusive. Here, we demonstrate a novel FOXC1-driven mechanism that suppresses ERα expression in breast cancer. We find that FOXC1 competes with GATA-binding protein 3 (GATA3) for the same binding regions in the cis-regulatory elements upstream of the ERα gene and thereby downregulates ERα expression and consequently its transcriptional activity. The forkhead domain of FOXC1 is essential for the competition with GATA3 for DNA binding. Counteracting the action of GATA3 at the ERα promoter region, overexpression of FOXC1 hinders recruitment of RNA polymerase II and increases histone H3K9 trimethylation at ERα promoters. Importantly, ectopic FOXC1 expression in luminal breast cancer cells reduces sensitivity to estrogen and tamoxifen. Furthermore, in breast cancer patients with ER-positive primary tumors who received adjuvant tamoxifen treatment, FOXC1 expression is associated with decreased or undetectable ER expression in recurrent tumors. Our findings highlight a clinically relevant mechanism that contributes to the low or absent ERα expression in BLBC. This study suggests a new paradigm to study ERα regulation during breast cancer progression and indicates a role of FOXC1 in the modulation of cellular response to endocrine treatment.

ASCT2/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer.

Alanine, serine, cysteine-preferring transporter 2 (ASCT2; SLC1A5) mediates uptake of glutamine, a conditionally essential amino acid in rapidly proliferating tumour cells. Uptake of glutamine and subsequent glutaminolysis is critical for activation of the mTORC1 nutrient-sensing pathway, which regulates cell growth and protein translation in cancer cells. This is of particular interest in breast cancer, as glutamine dependence is increased in high-risk breast cancer subtypes. Pharmacological inhibitors of ASCT2-mediated transport significantly reduced glutamine uptake in human breast cancer cell lines, leading to the suppression of mTORC1 signalling, cell growth and cell cycle progression. Notably, these effects were subtype-dependent, with ASCT2 transport critical only for triple-negative (TN) basal-like breast cancer cell growth compared with minimal effects in luminal breast cancer cells. Both stable and inducible shRNA-mediated ASCT2 knockdown confirmed that inhibiting ASCT2 function was sufficient to prevent cellular proliferation and induce rapid cell death in TN basal-like breast cancer cells, but not in luminal cells. Using a bioluminescent orthotopic xenograft mouse model, ASCT2 expression was then shown to be necessary for both successful engraftment and growth of HCC1806 TN breast cancer cells in vivo. Lower tumoral expression of ASCT2 conferred a significant survival advantage in xenografted mice. These responses remained intact in primary breast cancers, where gene expression analysis showed high expression of ASCT2 and glutamine metabolism-related genes, including GLUL and GLS, in a cohort of 90 TN breast cancer patients, as well as correlations with the transcriptional regulators, MYC and ATF4. This study provides preclinical evidence for the feasibility of novel therapies exploiting ASCT2 transporter activity in breast cancer, particularly in the high-risk basal-like subgroup of TN breast cancer where there is not only high expression of ASCT2, but also a marked reliance on its activity for sustained cellular proliferation.

Age-related changes in auditory nerve-inner hair cell connections, hair cell numbers, auditory brain stem response and gap detection in UM-HET4 mice.

This study compared the timing of appearance of three components of age-related hearing loss that determine the pattern and severity of presbycusis: the functional and structural pathologies of sensory cells and neurons and changes in gap detection (GD), the latter as an indicator of auditory temporal processing. Using UM-HET4 mice, genetically heterogeneous mice derived from four inbred strains, we studied the integrity of inner and outer hair cells by position along the cochlear spiral, inner hair cell-auditory nerve connections, spiral ganglion neurons (SGN), and determined auditory thresholds, as well as pre-pulse and gap inhibition of the acoustic startle reflex (ASR). Comparisons were made between mice of 5-7, 22-24 and 27-29 months of age. There was individual variability among mice in the onset and extent of age-related auditory pathology. At 22-24 months of age a moderate to large loss of outer hair cells was restricted to the apical third of the cochlea and threshold shifts in the auditory brain stem response were minimal. There was also a large and significant loss of inner hair cell-auditory nerve connections and a significant reduction in GD. The expression of Ntf3 in the cochlea was significantly reduced. At 27-29 months of age there was no further change in the mean number of synaptic connections per inner hair cell or in GD, but a moderate to large loss of outer hair cells was found across all cochlear turns as well as significantly increased ABR threshold shifts at 4, 12, 24 and 48 kHz. A statistical analysis of correlations on an individual animal basis revealed that neither the hair cell loss nor the ABR threshold shifts correlated with loss of GD or with the loss of connections, consistent with independent pathological mechanisms.

Transfection of hBMP-2 into mesenchymal stem cells derived from human umbilical cord blood and bone marrow induces cell differentiation into chondrocytes.

AIM: Objective of the study was to compare the liposome-mediated transfection efficiency of the recombinant plasmid pIRES2-EGFP-hBMP-2 into mesenchymal stem cells (MSCs) derived from human umbilical cord blood (UCB-MSCs) and bone marrow (BM-MSCs). METHODS: UCB-MSCs and BM-MSCs were isolated using density gradient centrifugation followed by adherent cultures. The plasmid (pIRES2-EGFP-hBMP-2) was transfected into MSCs by using X-treme GENE transfection kit. Successful transfection was determined by both the protein expression of EGFP observed by fluorescence microscopy and the mRNA expression of human bone morphogenetic protein-2 (hBMP-2) detected using RT-PCR. Cell surface marker and morphological changes were examined by immunohistochemistry (IHC) after two weeks of transfection. RESULTS: Both UCB-MSCs and BM-MSCs were isolated and expanded successfully for multiple passages and demonstrated slight growth and morphological differences. The recombinant plasmid (pIRES2-EGFP-hBMP-2) was successfully transfected into both UCB-MSCs and BM-MSCs with an efficiency of 27.7 ± 7.6% and 18.4 ± 5.9%, respectively. The mRNA expression of hBMP-2 correlated with increased staining for collagen type II in the transfected cells. CONCLUSION: Transfection of hBMP-2 in UCB-MSCs and BM-MSCs increases the expression of collagen type II. These results indicate that increased BMP-2 levels induce multipotent stem cell differentiation into chondrocytes.

Collective nature of the reentrant integer quantum Hall states in the second Landau level.

We report an unexpected sharp peak in the temperature dependence of the magnetoresistance of the reentrant integer quantum Hall states in the second Landau level. This peak defines the onset temperature of these states. We find that in different spin branches the onset temperatures of the reentrant states scale with the Coulomb energy. This scaling provides direct evidence that Coulomb interactions play an important role in the formation of these reentrant states evincing their collective nature.

Photodegradation of 17alpha-ethynylestradiol in aqueous solution exposed to a high-pressure mercury lamp (250 W).

The photodegradation of 17alpha-ethynylestradiol (EE(2)) induced by high-pressure mercury lamp (lambda> or =313, 250 W) in aqueous solution of EE(2) was investigated initially. The affecting factors on the photodegradation were studied and described in details, such as EE(2) initial concentration, Fe(3+), algae, exposure time, and so on. The concentration of EE(2) in distilled water was mainly determined using fluorescence spectrophotometer. The photodegradation of EE(2) in aqueous solution exposed to high-pressure mercury lamp was evident and could be accelerated by Fe(3+) or algae (e.g. Anabaena cylindrica) in general. With the algae concentration increasing, photodegradation rate increased. In this paper, the mechanism of photocatalytic degradation of EE(2) by Fe(3+) or algae is discussed primarily.

[Correlation of asymptomatic bronchial hyperresponsiveness with serum specific IgE and eosinophilic cation protein].

OBJECTIVE: To explore the correlation of asymptomatic bronchial hyperresponsiveness with serum specific IgE(sIgE) and eosinophilic cation protein(ECP). METHODS: Histamine inhalation provoking test (quantitative method) was used in a survey for bronchial responsiveress in 1,123 students aged between 11 to 14 years old, 41 individuals with asymptomatic bronchial hyperresponsiveness received further test for sIgE and ECP. 31 students with normal bronchial responsiveness were randomly selected as the control. RESULTS: 4%(41/1,123) of the students showed bronchial hyperresponsiveness. The incidence of bronchial hyperresponsiveness with family history of asthma (11/14, 79%) was higher than that without a family history (30/1,109, 3%), with statistical significance (P < 0.005). The positive rates for sigE (90%, 37/41, P < 0.01) and ECP (17%, 7/41, P < 0.05), sIgE q value (14.3 +/- 12.1) micrograms/L, (P < 0.01) and ECP value (44.3 +/- 60.2) micrograms/L, (P < 0.01) in asymptomatic bronchial hyperresponsiveness group were higher than those of the control with statistical significance. His PD20-FEV1 was negatively related to aIgE q value (P < 0.05) and not related to ECP (P > 0.05). CONCLUSION: The asymptomatic bronchial hyperresponsiveness was closely related to allergy but not to ECP. Those with a family history of asthma, or with positive sIgE should be followed.

Identification and functional analysis of novel human melanocortin-4 receptor variants.

Inactivation of the melanocortin-4 receptor (MC4-R) by gene-targeting results in mice that develop maturity-onset obesity, hyperinsulinemia, and hyperglycemia. These phenotypes resemble common forms of human obesity, which are late-onset and frequently accompanied by NIDDM. It is not clear whether sequence variation of the MC4-R gene contributes to obesity in humans. Therefore, we examined the human MC4-R gene polymorphism in 190 individuals ascertained on obesity status. Three allelic variants were identified, including two novel ones, Thr112Met and Ile137Thr. To analyze possible functional alterations, the variants were cloned and expressed in vitro and compared with the wild-type receptor. One of the novel variants, Ile137Thr, identified in an extremely obese proband (BMI 57), was found to be severely impaired in ligand binding and signaling, raising the possibility that it may contribute to development of obesity. Furthermore, our results also suggest that sequence polymorphism in the MC4-R coding region is unlikely to be a common cause of obesity in the population studied, given the low frequency of functionally significant mutations.

Cloning and characterization of an uncoupling protein homolog: a potential molecular mediator of human thermogenesis.

We have identified a novel cDNA encoding a protein highly homologous to the mammalian brown fat uncoupling protein (UCP). Unlike the known UCP, which is expressed specifically in brown adipose tissue, the UCP homolog (UCPH) mRNA is expressed in a variety of tissues, with predominant expression in human white adipose tissue and skeletal muscle. In the white adipose tissue of ob/ob and db/db mice, the UCPH transcript is induced approximately fivefold relative to lean littermate controls. Expression of murine UCPH in yeast results in growth inhibition under conditions that require aerobic respiration, but does not affect growth under anaerobic conditions. Furthermore, UCPH expression in yeast causes a decrease in the mitochondrial membrane potential, as judged by staining with the potential-sensitive dye DiOC6. These observations suggest that UCPH, like UCP, uncouples oxidative phosphorylation. The possibility that the UCPH protein is an important mediator of human thermogenesis is discussed.

Identification and localization of polycystin, the PKD1 gene product.

Polycystin, the product of autosomal dominant polycystic kidney disease (ADPKD) 1 gene (PKD1) is the cardinal member of a novel class of proteins. As a first step towards elucidating the function of polycystin and the pathogenesis of ADPKD, three types of information were collected in the current study: the subcellular localization of polycystin, the spatial and temporal distribution of the protein within normal tissues and the effects of ADPKD mutations on the pattern of expression in affected tissues. Antisera directed against a synthetic peptide and two recombinant proteins of different domains of polycystin revealed the presence of an approximately 400-kD protein (polycystin) in the membrane fractions of normal fetal, adult, and ADPKD kidneys. Immunohistological studies localized polycystin to renal tubular epithelia, hepatic bile ductules, and pancreatic ducts, all sites of cystic changes in ADPKD, as well as in tissues such as skin that are not known to be affected in ADPKD. By electron microscopy, polycystin was predominantly associated with plasma membranes. Polycystin was significantly less abundant in adult than in fetal epithelia. In contrast, polycystin was overexpressed in most, but not all, cysts in ADPKD kidneys.

Identification and expression cloning of a leptin receptor, OB-R.

The ob gene product, leptin, is an important circulating signal for the regulation of body weight. To identify high affinity leptin-binding sites, we generated a series of leptin-alkaline phosphatase (AP) fusion proteins as well as [125I]leptin. After a binding survey of cell lines and tissues, we identified leptin-binding sites in the mouse choroid plexus. A cDNA expression library was prepared from mouse choroid plexus and screened with a leptin-AP fusion protein to identify a leptin receptor (OB-R). OB-R is a single membrane-spanning receptor most related to the gp130 signal-transducing component of the IL-6 receptor, the G-CSF receptor, and the LIF receptor. OB-R mRNA is expressed not only in choroid plexus, but also in several other tissues, including hypothalamus. Genetic mapping of the gene encoding OB-R shows that it is within the 5.1 cM interval of mouse chromosome 4 that contains the db locus.

Macrophage colony-stimulating factor (CSF-1) enhances invasiveness in CSF-1 receptor-positive carcinoma cell lines.

We have identified two lung carcinoma cell lines, A549 and Calu-1, expressing low levels of the macrophage colony-stimulating factor (CSF-1) receptor (CSF-1R), encoded by the c-fms oncogene. The effect of CSF-1 on the invasive potential of these CSF-1R-positive tumor cell lines and on two other CSF-1R-bearing cell lines, the BT-20 breast carcinoma cell line and the CSF-1 growth-dependent murine macrophage cell line BAC1.2F5, was examined using a human amnionic basement membrane invasion model. Culture of A549, Calu-1, and BAC1.2F5 cells with CSF-1 (250 ng/ml) resulted in a maximal 12-, 5-, and 12-fold enhancement of invasion, respectively, compared to control cells cultured in medium alone. Larger concentrations of CSF-1 (750 ng/ml) reduced A549 and Calu-1 invasiveness compared to the effect of the 250-ng/ml dose. Maximal enhancement in invasion of A549 and Calu-1 cells occurred after a 24- and 48-h exposure to CSF-1, respectively. CSF-1 increased invasiveness 6-fold in BT-20 cells induced by glucocorticoids to express high levels of CSF-1R, in comparison to control cells not exposed to glucocorticoids or CSF-1. In contrast, CSF-1 had no effect on invasion in the CSF-1R-negative MCF-7 cell line. Culture of A549 and Calu-1 cells with other cytokines and growth factors including GM-CSF (500 units/ml), IL-3 (1 ng/ml), interferon-gamma (500 units/ml), and tumor necrosis factor (50 units/ml) had no significant effect on invasiveness. Thus, CSF-1 increases invasiveness in CSF-1R-positive tumor cell lines, suggesting a role in enhancing the metastatic potential of tumor cells expressing the CSF-1R.

Prediction of N-acetylprocainamide disposition kinetics in rat by combination of gamma variate and physiological pharmacokinetic model.

Clearances and tissue/blood drug concentration ratios of N-acetylprocainamide (NAPA) in rats were determined. The clearances of NAPA in rat blood, liver, and kidney were 13.1, 4.88, and 8.24 ml.kg-1.min-1, respectively. Disposition kinetics of NAPA in rats was predicted with combination of gamma variate and physiological pharmacokinetic model. Equation for estimating the concentration of NAPA in rat blood following iv NAPA 40 mg.kg-1 was C = 55.06t(-0.220) exp(-0.00713t). Using r2 value as a criterion, we found a good agreement between predicted and observed concentrations in blood, lung, small intestine, heart, brain, and skin.