Agonistic anti-DCIR antibody inhibits ITAM-mediated inflammatory signaling and promotes immune resolution.

DC inhibitory receptor (DCIR) is a C-type lectin receptor selectively expressed on myeloid cells, including monocytes, macrophages, DCs, and neutrophils. Its role in immune regulation has been implicated in murine models and human genome-wide association studies, suggesting defective DCIR function associates with increased susceptibility to autoimmune diseases such as rheumatoid arthritis, lupus, and Sjögren's syndrome. However, little is known about the mechanisms underlying DCIR activation to dampen inflammation. Here, we developed anti-DCIR agonistic antibodies that promote phosphorylation on DCIR's immunoreceptor tyrosine-based inhibitory motifs and recruitment of SH2 containing protein tyrosine phosphatase-2 for reducing inflammation. We also explored the inflammation resolution by depleting DCIR+ cells with antibodies. Utilizing a human DCIR-knock-in mouse model, we validated the antiinflammatory properties of the agonistic anti-DCIR antibody in experimental peritonitis and colitis. These findings provide critical evidence for targeting DCIR to develop transformative therapies for inflammatory diseases.

Natural Feedstock in Catalysis: A Sustainable Route Towards Organic Transformations.

Catalysts are the jewel in the crown of the chemical industry, accelerating reaction kinetics and augmenting the efficiency of desired reaction paths. Natural feedstock is a renewable resource capable of providing valuable functional products; in addition, it confers an opportunity to create catalysts. As an alternative to stoichiometric reagents, and as a part of a sustainable approach, the implications of using natural feedstocks as a source of new catalysts has attracted considerable interest. Natural feedstock-derived catalysts can promote chemical transformations more efficiently. Recent reports have highlighted the significant role of these biogenic, cost-effective, innocuous, biodegradable materials as catalysts in many biologically and pharmacologically important protocols. This review outlines the decisive organic transformations for which feedstock-derived catalysts have been employed effectively and successfully, along with their economic and environmental benefits over traditional catalytic systems.

Clinical, Etiological, Anatomical, and Bacteriological Study of "Diabetic Foot" Patients: Results of a Single Center Study.

OBJECTIVE: To examine the clinical pattern of foot-related complications in type 2 diabetes patients. MATERIAL AND METHODS: A cross-sectional study was conducted among indoor, adult type 2 diabetes patients with risk factors for diabetic foot complications. The diabetic neuropathy symptom score (DNSS), Doppler scanning, ankle brachial pressure index (ABPI) assessment, neuropathy assessment, neuropathic disability score (NDS), biothesiometry evaluation, and bacteriological examination was performed. Diabetic foot risk stratification was done using the NICE risk stratification system. Foot ulcer severity was assessed with the Lipsky severity grading system. RESULTS:  Ninety-one patients (mean age 59 years; male 65.9%) were included, of which 20 (22%) had a history of ulcer and 40 (44%) were smokers. Seventy-seven (83.5%) patients had a neuropathy symptom score between 4 and 9. Biothesiometry vibration perception threshold (VPT) was "severe" in 55 (60.4%) patients. Doppler assessment showed triphasic flow in 53 patients (58.2%). Out of 52 patients (57.1%) with neuropathy, 30 (57.7%) had a severe problem. Diabetic foot ulcer, cellulitis, and callus were present in 44 (48.3%), 29 (31.5%), and 11 (12.4%) patients, respectively. Foot ulcers were present on 21 (38%) metatarsal heads, 11 (20%) toes, 10 (18%) heels, 08 (15%) ankles, and 05 (09%) lateral foot borders. Of the 55 patients who underwent culture examination, 30 (33.3%) showed the presence of Staphylococcus aureus. As per NICE risk stratification, 55 patients (60%) were at "very high risk." CONCLUSION: A foot ulcer is the commonest complication in diabetic patients followed by cellulitis. Standardized simple noninvasive testing methods should be used to identify patients at risk for the diabetic foot. Multidisciplinary diabetic foot care could be useful to prevent diabetes-related amputation of the lower extremities.

Synergistic effect of natural chickpea leaf exudates acids in heterocyclization: a greener protocol for benzopyran synthesis.

Without using any toxic or hazardous reagent, ligand, acid, transition metal catalyst, additives/promoters and organic solvent, green Knoevenagel condensation and tandem Knoevenagel-Michael reactions have been successfully carried out by using chickpea leaf exudates as a naturally sourced Bronsted acid type bio-catalyst. The reaction proceeds in neat chickpea leaf exudates at room temperature in aqueous conditions in very short reaction times, and therefore, it is an evergreen and environmentally sound alternative to the existing protocols for benzopyran synthesis. In comparison to the conventional methods, this synthetic pathway complies with several key requirements of green chemistry principles such as the utilization of biodegradable catalyst obtained from renewable feedstock, auxiliary aqueous conditions, along with waste prevention. The same protocol was also extended to the synthesis of 2H-xanthene-1,8-diones by condensation of aromatic aldehydes with dimedone achieving excellent yields. Thus, the reported protocol offers an attractive option because of its ecological safety, environmental acceptance, sustainability, low-cost straightforward work-up procedure and with excellent values of green chemistry metrics as compared with other reported methods.

Porous Femoral Fixation in Total Hip Arthroplasty with Short Anatomical Stem: Radiographic Evaluation.

BACKGROUND: Hip prostheses with short anatomical stems were designed for metaphyseal fixation and to spare bone stock. We present a study of a short anatomical femoral stem used in all age groups of patients with Dorr A and B type of femora. METHODS: We reviewed radiographs of 85 hips in 74 patients who had a cementless total hip arthroplasty with a short anatomical 80 mm femoral stem designed to achieve pure metaphyseal fixation. A ream-only technique was used for femoral canal preparation in all patients. At each follow-up, radiological evaluation was performed for stem alignment, proximal metaphyseal fill, subsidence, status of biological fixation of the femoral stem, heterotrophic ossification, radiolucency, osteolysis, and limb length discrepancy of the stem. Acetabular components were evaluated for positioning, acetabular bone coverage, and radiolucent and osteolytic lesions. RESULTS: The final mean alignment of femoral stem was 2° valgus. The average intramedullary fill by the stem at the proximal level of the lesser trochanter was 93% in the coronal plane and 88% in the sagittal plane. No components were considered to be undersized. Thirteen hips (15.2%) presented radiolucent lines (10 hips < 1 mm in width and 3 hips [3.5%] 2 mm in width) and 100% of them were not progressive with respect to the last follow-up radiograph. All of the stems had excellent fixation by demonstrating bone ingrowth at the latest follow-up. At the last follow-up, heterotopic ossification was noted in 5 hips. The mean preoperative limb length discrepancy was 9.3 mm and the mean postoperative discrepancy was 3.8 mm. The mean acetabular component angle of the 85 components was 41.2° with a mean anteversion of 22.1°. At the last follow-up, there were no revisions of the femoral component. One patient, 25 months after the index operation, required an acetabular component revision because of recurrent hip dislocation. There were no radiological signs of loosening in any of the short-stem prostheses at the last examination. CONCLUSIONS: The short, metaphyseal-fitting anatomic cementless femoral stem provided stable fixation without relying on diaphyseal fixation.

Characterization of phytotoxin producing Alternaria species isolatedfrom sesame leavesand their toxicity.

Sesame (Sesamum indicum L.), is an important oilseed crop in the tropics and subtropics, referred as "Queen of Oilseeds" owing to its high cooking quality and medicinal value. Sesame production, particularly in India, has been declining since last decade and 'Leaf blight' caused by Alternaria spp. is reported to cause yield loss up to 30-40%. Here, we investigated the fungal toxin produced by Alternaria and its pathogenicity. A total of 164 Alternaria strainswere isolated on potato dextrose agar media from the infected sesame leaves showing circular concentric rings with dark brown spots symptoms. All the isolates were screened for cultural and morphological characters. Colour of the fungus was grey to dark brown, formed smooth, raised, fluffy, and regular to irregular margins. Among 164 isolates, 43 isolates were moderately growing and 121 were fast in growth. The DNA of the isolate was amplified with ITS primers and sequence of BLAST results confirmed seven different species of Alternaria of NCBI database. Further, toxigenic potentiality of the isolates was tested with dilutions of culture filtrate (1:1 to 1:5) on sesame leaves. Among 164 isolates, 23 showed toxigenicity, varied from highly toxigenic to least toxigenic. Pathogenicity of the isolates showed that they were highly virulent to less virulent when tested by the detached leaf method. Based on the toxigenicity, the toxin was partially purified and brown coloured paste was recovered. Chemistry of the toxin was confirmed based on the IR, UV, NMR and mass spectra analyses, and it resembled the structure of alternariol mono methyl ether and altenuene which are mycotoxins in nature. Further, bioassay of toxin was carried out at different concentrations (50 to 2000 ppm) on seeds and seedlings of sesame. Maximum inhibition of seed germination of 81.1% was observed at 2000 ppm and the least was 6.67% at 50 ppm. With the increase in the concentration of toxin, the manifestation of the symptom was conspicuous and quick such as marginal, veinal necrosis, drooping and yellowing with lesion formation. From the present study, it is found that the species of Alternaria are responsible for the cause of blight disease symptoms and the toxicity of toxin produced by the pathogen was very high. The Alternaria toxin could inhibit the growth of the plant as well as seed germination rate.

Pedicle screw placement with O-arm and stealth navigation.

Various navigation systems are available to aid pedicle screw placement. The O-arm replaces the need for fluoroscopy and generates a 3-dimensional volumetric dataset that can be viewed as transverse, coronal, and sagittal images of the spine, similar to computed tomography (CT) scanning. The dataset can be downloaded to the Stealth system (Medtronic Navigation, Louisville, Colorado) for real-time intraoperative navigation.The main objectives of the current study were to assess (1) accuracy of pedicle screw placement using the O-arm/Stealth system, and (2) time for draping, positioning of the O-arm, and screw placement. Of 188 screws (25 patients), 116 had adequate images for analysis. The average time for O-arm draping was 3.5 minutes. Initial O-arm positioning was 6.1 minutes, and final positioning was 4.9 minutes. Mean time for screw placement, including O-arm draping and positioning and array attachment, was 8.1 minutes per screw. Mean time for screw placement alone was 5.9 minutes per screw. Screw placements on final O-arm images were on average 3.14 mm deeper than on the snapshot navigation images. Three screws (2.6%) breached the medial cortex, and 3 screws (2.6%) were misaligned and did not follow the pilot hole trajectory.The use of the O-arm/Stealth system was associated with a low rate of pedicle screw misalignment. The time to place screws was less than previously reported with CT navigation, but longer than conventional techniques. It is important to be aware of the potential discrepancy between snapshot navigation images and actual screw placement on final O-arm images. Our findings suggest that final screw positions may be deeper than awl positions appear on navigation images.

Intramedullary rod and cement static spacer construct in chronically infected total knee arthroplasty.

Two-stage reimplantation, with interval antibiotic-impregnated cement spacer, is the preferred treatment of prosthetic knee joint infections. In medically compromised hosts with prior failed surgeries, the outcomes are poor. Articulating spacers in such patients render the knee unstable; static spacers have risks of dislocation and extensor mechanism injury. We examined 58 infected total knee arthroplasties with extensive bone and soft tissue loss, treated with resection arthroplasty and intramedullary tibiofemoral rod and antibiotic-laden cement spacer. Thirty-seven patients underwent delayed reimplantation. Most patients (83.8%) were free from recurrent infection at mean follow-up of 29.4 months. Reinfection occurred in 16.2%, which required debridement. Twenty-one patients with poor operative risks remained with the spacer for 11.4 months. All patients, during spacer phase, had brace-free ambulation with simulated tibiofemoral fusion, without bone loss or loss of limb length.

Expression and functional roles of caspase-5 in inflammatory responses of human retinal pigment epithelial cells.

PURPOSE: To investigate the expression, activation, and functional involvement of caspase-5 in human retinal pigment epithelial (hRPE) cells. METHODS: Expression and activation of caspase-5 in primary cultured hRPE cells, telomerase-immortalized hTERT-RPE1 cells (hTERT-RPE1), or both, were measured after stimulation with proinflammatory agents IL-1ß, TNF-α, lipopolysaccharide (LPS), interferon-γ, monocyte coculture, adenosine triphosphate (ATP), or endoplasmic reticulum (ER) stress inducers. Immunomodulating agents dexamethasone (Dex), IL-10, and triamcinolone acetonide (TA) were used to antagonize proinflammatory stimulation. Cell death ELISA and TUNEL staining assays were used to assess apoptosis. RESULTS: Caspase-5 mRNA expression and protein activation were induced by LPS and monocyte-hRPE coculture. Caspase-5 activation appeared as early as 2 hours after challenge by LPS and consistently increased to 24 hours. Meanwhile, caspase-1 expression and protein activation were induced by LPS. Activation of caspase-5 was blocked or reduced by Dex, IL-10, and TA. Activation of caspase-5 and -1 was also enhanced by ATP and ER stress inducers. Expression and activation of caspase-5 were inhibited by a caspase-1-specific inhibitor. Caspase-5 knockdown reduced caspase-1 protein expression and activation and inhibited TNF-α-induced IL-8 and MCP-1. In contrast to caspase-4, the contribution of caspase-5 to stress-induced apoptosis was moderate. CONCLUSIONS: Caspase-5 mRNA synthesis, protein expression, and catalytic activation were highly regulated in response to various proinflammatory stimuli, ATP, and ER stress inducers. Mutual activation between caspase-5 and -1 suggests caspase-5 may work predominantly in concert with caspase-1 in modulating hRPE inflammatory responses.

Functional analysis of retinitis pigmentosa 2 (RP2) protein reveals variable pathogenic potential of disease-associated missense variants.

Genetic mutations are frequently associated with diverse phenotypic consequences, which limits the interpretation of the consequence of a variation in patients. Mutations in the retinitis pigmentosa 2 (RP2) gene are associated with X-linked RP, which is a phenotypically heterogenic form of retinal degeneration. The purpose of this study was to assess the functional consequence of disease-associated mutations in the RP2 gene using an in vivo assay. Morpholino-mediated depletion of rp2 in zebrafish resulted in perturbations in photoreceptor development and microphthalmia (small eye). Ultrastructural and immunofluorescence analyses revealed defective photoreceptor outer segment development and lack of expression of photoreceptor-specific proteins. The retinopathy phenotype could be rescued by expressing the wild-type human RP2 protein. Notably, the tested RP2 mutants exhibited variable degrees of rescue of rod versus cone photoreceptor development as well as microphthalmia. Our results suggest that RP2 plays a key role in photoreceptor development and maintenance in zebrafish and that the clinical heterogeneity associated with RP2 mutations may, in part, result from its potentially distinct functional relevance in rod versus cone photoreceptors.

Accumulation of the Raf-1 kinase inhibitory protein (Rkip) is associated with Cep290-mediated photoreceptor degeneration in ciliopathies.

Primary cilia regulate polarized protein trafficking in photoreceptors, which are dynamic and highly compartmentalized sensory neurons of retina. The ciliary protein Cep290 modulates cilia formation and is frequently mutated in syndromic and non-syndromic photoreceptor degeneration. However, the underlying mechanism of associated retinopathy is unclear. Using the Cep290 mutant mouse rd16 (retinal degeneration 16), we show that Cep290-mediated photoreceptor degeneration is associated with aberrant accumulation of its novel interacting partner Rkip (Raf-1 kinase inhibitory protein). This effect is phenocopied by morpholino-mediated depletion of cep290 in zebrafish. We further demonstrate that ectopic accumulation of Rkip leads to defective cilia formation in zebrafish and cultured cells, an effect mediated by its interaction with the ciliary GTPase Rab8A. Our data suggest that Rkip prevents cilia formation and is associated with Cep290-mediated photoreceptor degeneration. Furthermore, our results indicate that preventing accumulation of Rkip could potentially ameliorate such degeneration.

TOPORS, implicated in retinal degeneration, is a cilia-centrosomal protein.

We recently reported that mutations in the widely expressed nuclear protein TOPORS (topoisomerase I-binding arginine/serine rich) are associated with autosomal dominant retinal degeneration. However, the precise localization and a functional role of TOPORS in the retina remain unknown. Here, we demonstrate that TOPORS is a novel component of the photoreceptor sensory cilium, which is a modified primary cilium involved with polarized trafficking of proteins. In photoreceptors, TOPORS localizes primarily to the basal bodies of connecting cilium and in the centrosomes of cultured cells. Morpholino-mediated silencing of topors in zebrafish embryos demonstrates in another species a comparable retinal problem as seen in humans, resulting in defective retinal development and failure to form outer segments. These defects can be rescued by mRNA encoding human TOPORS. Taken together, our data suggest that TOPORS may play a key role in regulating primary cilia-dependent photoreceptor development and function. Additionally, it is well known that mutations in other ciliary proteins cause retinal degeneration, which may explain why mutations in TOPORS result in the same phenotype.

Clinical and radiological outcomes of axial lumbar interbody fusion.

Axial lumbar interbody fusion is a novel percutaneous alternative to common open techniques, such as anterior, posterior, and transforaminal lumbar interbody fusion. This minimally invasive technique uses the presacral space to access the L5-S1 and L4-L5 disk space. The goal of this study was to examine outcomes following axial lumbar interbody fusion. The charts of all patients who underwent axial lumbar interbody fusion surgery at our institution between 2006 and 2008 were reviewed. Clinical outcomes included visual analog scale (VAS) and Oswestry Disability Index (ODI). Radiographs were also evaluated for disk space height, L4-L5 and/or L5-S1 Cobb angle, and fusion. Of the 50 patients (32 women, 18 men; mean age, 49.29 years) treated with axial lumbar interbody fusion, 48 had preoperative VAS scores and 16 had preoperative ODI scores available. Complete radiographic data were available at the preoperative, initial postoperative, and final postoperative time points for 46 patients (92%). At last follow-up (average, 12 months), ODI scores were reduced from 46 to 22, and VAS scores were lowered from 8.1 to 3.6. Of the 49 patients with postoperative radiographs, 47 (96%) went on to a solid fusion. There were no significant differences between pre- and postoperative disk space height and lumbar lordosis angle. The most common complications were superficial infection and pseudoarthrosis. Other complications were rectal injury, hematoma, and irritation of a nerve root by a screw. Overall, we found the axial lumbar interbody fusion procedure in combination with pedicle screw placement to have good clinical and radiological outcomes.

Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy.

Nephronophthisis-related ciliopathies (NPHP-RC) are recessive disorders that feature dysplasia or degeneration occurring preferentially in the kidney, retina and cerebellum. Here we combined homozygosity mapping with candidate gene analysis by performing 'ciliopathy candidate exome capture' followed by massively parallel sequencing. We identified 12 different truncating mutations of SDCCAG8 (serologically defined colon cancer antigen 8, also known as CCCAP) in 10 families affected by NPHP-RC. We show that SDCCAG8 is localized at both centrioles and interacts directly with OFD1 (oral-facial-digital syndrome 1), which is associated with NPHP-RC. Depletion of sdccag8 causes kidney cysts and a body axis defect in zebrafish and induces cell polarity defects in three-dimensional renal cell cultures. This work identifies loss of SDCCAG8 function as a cause of a retinal-renal ciliopathy and validates exome capture analysis for broadly heterogeneous single-gene disorders.

RhoA- and PKC-alpha-mediated phosphorylation of MYPT and its association with HSP27 in colonic smooth muscle cells.

Agonist-induced activation of the RhoA/Rho kinase (ROCK) pathway results in inhibition of myosin phosphatase and maintenance of myosin light chain (MLC20) phosphorylation. We have shown that RhoA/ROCKII translocates and associates with heat shock protein (HSP)27 in the particulate fraction. We hypothesize that inhibition of the 130-kDa regulatory myosin-binding subunit (MYPT) requires its association with HSP27 in the particulate fraction. Furthermore, it is not certain whether regulation of MYPT by CPI-17 or by ROCKII is due to cross talk between RhoA and PKC-alpha. Presently, we examined the cross talk between RhoA and PKC-alpha in the regulation of MYPT phosphorylation in rabbit colon smooth muscle cells. Acetylcholine induced 1) sustained phosphorylation of PKC-alpha, CPI-17, and MYPT; 2) an increase in the association of phospho-MYPT with HSP27 in the particulate fraction; 3) a decrease in myosin phosphatase activity (66.21+/-3.52 and 42.19+/-3.85% nM/ml lysate at 30 s and 4 min); and 4) an increase in PKC activity (298.12+/-46.60% and 290.59+/-22.07% at 30 s and 4 min). Inhibition of RhoA/ROCKII by Y-27632 inhibited phosphorylation of MYPT and its association with HSP27. Both Y27632 and a negative dominant construct of RhoA inhibited phosphorylation of MYPT and CPI-17. Inhibition of PKCs or calphostin C or selective inhibition of PKC-alpha by negative dominant constructs inhibited phosphorylation of MYPT and CPI-17. The results suggest that 1) acetylcholine induces activation of both RhoA and/or PKC-alpha pathways, suggesting cross talk between RhoA and PKC-alpha resulting in phosphorylation of MYPT, inhibition of myosin phosphatase activity, and maintenance of MLC phosphorylation; and 2) phosphorylated MYPT is associated with HSP27 and translocated to the particulate fraction, suggesting a scaffolding role for HSP27 in mediating the association of the complex MYPT/RhoA-ROCKII. Thus both pathways (PKC and RhoA) converge on the regulation of myosin phosphatase activities and modulate sustained phosphorylation of MLC20.

Aging and gastrointestinal smooth muscle.

The present review is an attempt to put into perspective the available information on the putative changes in cellular mechanisms of the contractile properties of the aging gastrointestinal (GI) smooth muscle. Information on smooth muscle of the GI tract is scanty. Smooth muscle cells from old rats (32 months old) exhibit limited cell length distribution and diminished contractility. The observed reduced contractile response may be due to the effect of aging on signal transduction pathways, especially an inhibition of the tyrosine kinase-Src kinase pathway, a reduced activation of the PKCalpha pathway, a reduced association of contractile proteins (HSP27-tropomyosin, HSP27-actin, and actin-myosin). Levels of HSP27-phosphorylation are also reduced compared to adult rats. Regulation of GI motility is a complex mechanism of signal transduction and interaction of signaling and contractile proteins. It is suggested that further studies to elucidate the role of HSP27 in aging smooth muscle of the GI tract are needed.

Translocation and association of ROCK-II with RhoA and HSP27 during contraction of rabbit colon smooth muscle cells.

The focus of the paper is to understand the role of HSP27 in mediating the association of RhoA with ROCK-II in sustained contraction of smooth muscle cells from the rabbit colon. In circular smooth muscle cells; acetylcholine-induced contraction (10(-7)M) was associated with translocation of ROCK-II to the particulate fraction, which remained sustained at 4 min after stimulation (135.1+/-8.1% increase, P

Direct association and translocation of PKC-alpha with calponin.

Calponin has been implicated in the regulation of smooth muscle contraction through its interaction with F-actin and inhibition of the actin-activated MgATPase activity of phosphorylated myosin. Calponin has also been shown to interact with PKC. We have studied the interaction of calponin with PKC-alpha and with the low molecular weight heat-shock protein (HSP)27 in contraction of colonic smooth muscle cells. Particulate fractions from isolated smooth muscle cells were immunoprecipitated with antibodies to calponin and Western blot analyzed with antibodies to HSP27 and to PKC-alpha. Acetylcholine induced a sustained increase in the immunocomplexing of calponin with HSP27 and of calponin with PKC-alpha in the particulate fraction, indicating an association of the translocated proteins in the membrane. To examine whether the observed interaction in vivo is due to a direct interaction of calponin with PKC-alpha, a cDNA of 1.3 kb of human calponin gene was PCR amplified. PCR product encoding 622 nt of calponin cDNA (nt 351-972 corresponding to amino acids 92-229) was expressed as fusion glutathione S-transferase (GST) protein in the vector pGEX-KT. We have studied the direct association of GST-calponin fusion protein with recombinant PKC-alpha in vitro. Western blot analysis of the fractions collected after elution with reduced glutathione buffer (pH 8.0) show a coelution of GST-calponin with PKC-alpha, indicating a direct association of GST-calponin with PKC-alpha. These data suggest that there is a direct association of translocated calponin and PKC-alpha in the membrane and a role for the complex calponin-PKC-alpha-HSP27, in contraction of colonic smooth muscle cells.

Inhibitory effects of phaseolotoxin on proliferation of leukemia cells HL-60, K-562 and L1210 and pancreatic cells RIN-m5F.

Phaseolotoxin (PT) is a non-host specific phytotoxin produced by the plant pathogenic bacterium Pseudomonas syringae (P.s.) pv. phaseolicola. In the present study, the inhibitory effect of PT on the proliferation of leukemia cells was studied. After 4 days of treatment, PT decreased cell growth of leukemia cell lines HL-60, K-562 and L1210 in a dose-dependent manner. In addition, PT also reduced cell growth of the insulinoma pancreatic cell line RIN-m5F. IC50 values were 2.1 +/- 1.0 microM (HL-60), 13.3 +/- 3.7 microM (K-562), 2.5 +/- 0.4 microM (L1210) and 5.5 +/- 0.3 microM (RIN-m5F). Although the exact mechanism by which PT inhibits cell growth in these cells is currently not known, we present first evidence that PT may in part be active via inhibition of ornithine decarboxylase (ODC). Based on our findings, PT presents a lead compound with potential for further development into a new anti-cancer agent.