Search tips
Search criteria

Results 1-5 (5)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  SPE-8, a protein-tyrosine kinase, localizes to the spermatid cell membrane through interaction with other members of the SPE-8 group spermatid activation signaling pathway in C. elegans 
BMC Genetics  2014;15:83.
The SPE-8 group gene products transduce the signal for spermatid activation initiated by extracellular zinc in C. elegans. Mutations in the spe-8 group genes result in hermaphrodite-derived spermatids that cannot activate to crawling spermatozoa, although spermatids from mutant males activate through a pathway induced by extracellular TRY-5 protease present in male seminal fluid.
Here, we identify SPE-8 as a member of a large family of sperm-expressed non-receptor-like protein-tyrosine kinases. A rescuing SPE-8::GFP translational fusion reporter localizes to the plasma membrane in all spermatogenic cells from the primary spermatocyte stage through spermatids. Once spermatids become activated to spermatozoa, the reporter moves from the plasma membrane to the cytoplasm. Mutations in the spe-8 group genes spe-12, spe-19, and spe-27 disrupt localization of the reporter to the plasma membrane, while localization appears near normal in a spe-29 mutant background.
These results suggest that the SPE-8 group proteins form a functional complex localized at the plasma membrane, and that SPE-8 is correctly positioned only when all members of the SPE-8 group are present, with the possible exception of SPE-29. Further, SPE-8 is released from the membrane when the activation signal is transduced into the spermatid.
PMCID: PMC4105102  PMID: 25022984
Caenorhabditis elegans; Spermatogenesis; Sperm activation; spe-8; Signal transduction
2.  Determination of Pesticide Residues in Cannabis Smoke 
Journal of Toxicology  2013;2013:378168.
The present study was conducted in order to quantify to what extent cannabis consumers may be exposed to pesticide and other chemical residues through inhaled mainstream cannabis smoke. Three different smoking devices were evaluated in order to provide a generalized data set representative of pesticide exposures possible for medical cannabis users. Three different pesticides, bifenthrin, diazinon, and permethrin, along with the plant growth regulator paclobutrazol, which are readily available to cultivators in commercial products, were investigated in the experiment. Smoke generated from the smoking devices was condensed in tandem chilled gas traps and analyzed with gas chromatography-mass spectrometry (GC-MS). Recoveries of residues were as high as 69.5% depending on the device used and the component investigated, suggesting that the potential of pesticide and chemical residue exposures to cannabis users is substantial and may pose a significant toxicological threat in the absence of adequate regulatory frameworks.
PMCID: PMC3666265  PMID: 23737769
3.  Ultraviolet Light B-Mediated Inhibition of Skin Catalase Activity Promotes Gr-1+CD11b+ Myeloid Cell Expansion 
Skin cancer incidence and mortality are higher in men compared to women, but the causes of this sex discrepancy remain largely unknown. Ultraviolet light exposure induces cutaneous inflammation and neutralizes cutaneous antioxidants. Gr-1+CD11b+ myeloid cells are heterogeneous bone marrow-derived cells that promote inflammation-associated carcinogenesis. Reduced activity of catalase, an antioxidant present within skin, has been associated with skin carcinogenesis. We utilized the outbred, immune competent Skh-1 hairless mouse model of ultraviolet light B (UVB)-induced inflammation and non-melanoma skin cancer to further define sex discrepancies in UVB-induced inflammation. Our results demonstrated that male skin had relatively lower baseline catalase activity, which was inhibited following acute UVB exposure in both sexes. Further analysis revealed that skin catalase activity inversely correlated with splenic Gr-1+CD11b+ myeloid cell percentage. Acute UVB exposure induced Gr-1+CD11b+ myeloid cell skin infiltration, which was inhibited to a greater extent in males by topical catalase treatment. In chronic UVB studies, we demonstrated that the percentage of splenic Gr-1+CD11b+ myeloid cells was 55% higher in male tumor-bearing mice compared to their female counterparts. Together, our findings indicate that lower skin catalase activity in male mice may at least in part contribute to increased UVB-induced Gr-1+CD11b+ myeloid cells and subsequent skin carcinogenesis.
PMCID: PMC3270125  PMID: 22030957
sex; ultraviolet light B; catalase; skin cancer; Gr-1+CD11b+ myeloid cells
4.  Routine Surveillance of Modular PFC TKA Shows Increasing Failures after 10 Years 
A 10-year survivorship of 100% was reported for patients with PFC cruciate-retaining prostheses. Beyond 10 years, we observed additional polyethylene wear likely related to thin liners gamma-irradiated in air and were concerned this wear might predispose to implant construct failure.
We therefore determined (1) the functional scores at a minimum of 15 years followup, (2) rates of radiographic failure, (3) overall revision rates, and (4) mode of failure after 10 years and the fate of the revised implants.
We retrospectively reviewed 75 patients with 101 press-fit condylar posterior cruciate-retaining prostheses. At a minimum followup of 15 years, 35 patients (47 knees) were living and evaluated clinically. No patients were lost to followup.
There were no revisions during the first 11 years and six reoperations subsequently were performed in five patients (6% overall rate of revision but 12.8% in patients who survived more than 15 years). Three of six revisions had concerning liner wear at 10 years and all six were revised for polyethylene wear. Polyethylene exchange was performed in four of the five patients who underwent revisions, all of whom were doing well at an average of 7.2 years (range, 4.7–9.1 years) after the revision procedure.
At long-term followup, the overall revision rate remained low (6%). For patients surviving 15 years or more, the rate of revision was 12.8% and all revisions were secondary to aseptic sequelae of polyethylene wear. All revisions occurred more than 10 years after the initial procedures.
Level of Evidence
Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC2919871  PMID: 20300900
5.  Prognostic significance of interleukin-6 single nucleotide polymorphism genotypes in neuroblastoma: rs1800795 (promoter) and rs8192284 (receptor) 
Neuroblastoma is a childhood cancer of the sympathetic nervous system and many patients present with high risk disease. Risk stratification, based on pathology and tumor-derived biomarkers, has improved prediction of clinical outcomes, but overall survival rates remain unfavorable and new therapeutic targets are needed. Some studies suggest a link between interleukin-6 and more aggressive behavior in neuroblastoma tumor cells. Therefore, we examined the impact of two IL-6 single nucleotide polymorphisms (SNP) on neuroblastoma disease progression.
Experimental design
DNA samples from 96 high risk neuroblastoma patients were screened for two SNP that are known to regulate the serum levels of IL-6 and the soluble IL-6 receptor (IL-6R), rs1800795 and rs8192284 respectively. The genotype for each SNP was determined in a blinded fashion and independent statistical analysis was performed to determine SNP-related event free survival (EFS) and overall survival (OS) rates.
The rs1800795 IL-6 promoter SNP is an independent prognostic factor for EFS and OS in -high risk neuroblastoma patients. In contrast, the rs8192284 IL-6 receptor SNP revealed no prognostic value.
The rs1800795 SNP (-174 IL-6 (G>C) represents a novel and independent prognostic marker for both EFS and OS in high risk neuroblastoma. Since the rs1800795 SNP (-174 IL-6 (G>C) has been shown to correlate with production of IL-6, this cytokine may represent a target for development of new therapies in neuroblastoma.
PMCID: PMC2740837  PMID: 19671870

Results 1-5 (5)