Controlling the window size in mesoporous SBA-16.

The structure of the mesoporous silica SBA-16 has been interrogated by careful elimination of the organic templating agent using ozone treatment. It is shown that the as-synthesised material consists of large cages connected by very narrow, ca. 7 Å, windows. These windows open up to about 20 Å following a calcination treatment that suggests that the functionality of SBA-16 could be changed markedly depending upon the post-synthesis treatment. The structure of SBA-16 is compared with surfaces of constant mean curvature. This illustrates that although most of the structure conforms to a surface of constant mean curvature the necks in the structure near the windows deviate strongly. This confirms that attractive forces in this region during synthesis play an important role in shaping the final structure. Following calcination the structure changes as the silica framework relaxes to a constant surface energy.

Intraneural perineurioma of the sciatic nerve: an under-recognized nerve neoplasm with characteristic MRI findings.

Intraneural perineurioma is a benign peripheral nerve neoplasm that typically affects teenagers and young adults and tends to result in a motor-predominant neuropathy. The lesion is rare, but has likely been underdiagnosed due to a lack of familiarity among both clinicians and radiologists. There have been few reports in the radiology literature despite the lesion having a fairly characteristic imaging appearance. We report a case of a 26-year-old woman with an intraneural perineurioma of the left sciatic nerve confirmed with excisional biopsy and pathologic analysis.

Lack of association of tumor-associated macrophages with clinical outcome in patients with classical Hodgkin's lymphoma.

BACKGROUND: A recent study demonstrated that an increased number of CD68+ macrophages were correlated with primary treatment failure, shortened progression-free survival (PFS) and disease-specific survival (DSS) in patients with classical Hodgkin's lymphoma (cHL). PATIENTS AND METHODS: The aim of the present study was to verify the relationship between the number of CD68+ and CD163+ macrophages with clinical outcomes in a cohort of 265 well-characterized patients with cHL treated uniformly with the standard doxorubicin, bleomycin, vinblastine and dacarbazine chemotherapy regimen. Two pairs of hematopathologists carried out independent pathological evaluations of tissue microarray slides. RESULTS: There were no associations between clinical characteristics and the expression of CD68 or CD163. However, higher levels of CD68 and CD163 expression were correlated with the presence of Epstein-Barr virus-positive Hodgkin tumor cells (P = 0.01 and 0.037, respectively). The expression of CD68 or CD163 was not associated with either the PFS or the DSS. CONCLUSION: CD68 and CD163 expression require further evaluation before their use can be recommended for prognostic stratification of patients with cHL.

A multi-site study using high-resolution HLA genotyping by next generation sequencing.

The high degree of polymorphism at human leukocyte antigen (HLA) class I and class II loci makes high-resolution HLA typing challenging. Current typing methods, including Sanger sequencing, yield ambiguous typing results because of incomplete genomic coverage and inability to set phase for HLA allele determination. The 454 Life Sciences Genome Sequencer (GS FLX) next generation sequencing system coupled with conexio atf software can provide very high-resolution HLA genotyping. High-throughput genotyping can be achieved by use of primers with multiplex identifier (MID) tags to allow pooling of the amplicons generated from different individuals prior to sequencing. We have conducted a double-blind study in which eight laboratory sites performed amplicon sequencing using GS FLX standard chemistry and genotyped the same 20 samples for HLA-A, -B, -C, DPB1, DQA1, DQB1, DRB1, DRB3, DRB4, and DRB5 (DRB3/4/5) in a single sequencing run. The average sequence read length was 250 base pairs and the average number of sequence reads per amplicon was 672, providing confidence in the allele assignments. Of the 1280 genotypes considered, assignment was possible in 95% of the cases. Failure to assign genotypes was the result of researcher procedural error or the presence of a novel allele rather than a failure of sequencing technology. Concordance with known genotypes, in cases where assignment was possible, ranged from 95.3% to 99.4% for the eight sites, with overall concordance of 97.2%. We conclude that clonal pyrosequencing using the GS FLX platform and CONEXIO ATF software allows reliable identification of HLA genotypes at high resolution.

Influence of fatty acid diets on gene expression in rat mammary epithelial cells.

BACKGROUND: This study examines the impact of dietary fatty acids on regulation of gene expression in mammary epithelial cells before and during puberty. METHODS: Diets primarily consisted of n-9 monounsaturated fatty acids (olive oil), n-6 polyunsaturated fatty acids (safflower), saturated acids (butter), and the reference AIN-93G diet (soy oil). The dietary regimen mimics the repetitive nature of fatty acid exposure in Western diets. Diet-induced changes in gene expression were examined in laser capture microdissected mammary ductal epithelial cells at day of weaning and end of puberty. PCNA immunohistochemistry analysis compared proliferation rates between diets. RESULTS: Genes differentially expressed between each test diets and the reference diet were significantly enriched by cell cycle genes. Some of these genes were involved in activation of the cell cycle pathway or the G2/M check point pathway. Although there were some differences in the level of differential expression, all diets showed qualitatively the same pattern of differential expression compared to the reference diet. Cluster analysis identified an expanded set of cell cycle as well as immunity and sterol metabolism related clusters of differentially expressed genes. CONCLUSION: Fatty acid-enriched diets significantly upregulated proliferation above normal physiological levels during puberty. Higher cellular proliferation during puberty caused by enriched fatty acid diets poses a potential increase risk of mammary cancer in later life. The human homologs of 27 of 62 cell cycle rat genes are included in a human breast cancer cluster of 45 cell cycle genes, further emphasizing the importance of our findings in the rat model.

Zeolitisation of diatoms.

The development of low cost hierarchical porous materials based upon the zeolitisation of diatomaceous earth for fluid waste benification is described. Two preparative approaches invole: first, using the diatom as a support for zeolite nanocrystals; second, direct pseudomorphic transformation of the diatom into a zeolite. These hierarchical porous materials are potentially useful for important industrial processes in ion-exchange, catalysis and waste benefication.

Apoptosis in the regenerate produced by mandibular osteodistraction in the mature rat.

UNLABELLED: AUTHORS: Liu ZJ, Anderson MW, Gu GM, King GJ. OBJECTIVE: Little is known about the contribution of apoptosis to the formation of the regenerate in distraction osteogenesis. This study investigated the role of apoptosis in the regulation of osteogenesis in relation to mandibular distraction rate and recovery time. METHODS: One hundred and twenty-nine 3-month rats received unilateral mandibular ramus osteotomy and distraction device placement. After 3-day latency, these were distracted for 5 days. The slow group was distracted a total of 1 mm (0.2 mm/day), the moderate 2 mm (0.4 mm/day), the rapid 3 mm (0.6 mm/day), and the sham was not distracted (0.0 mm/day). Eight to nine rats from each group were killed at 6 (mid-distraction), 10 (early-consolidation), 24 (mid-consolidation) and 38 (late-consolidation) days following device placement. Baseline data were obtained from an additional eight rats killed at day 3 (end of latency). Sagittal sections (7 mum) of the harvested hemi-mandibles were embedded in paraffin, double-stained with the DeadEnd(TM) Colorimetric TUNEL system for apoptotic cells and tartrate-resistant acid phosphatase for osteoclasts. Cell counts of apoptotic cells and osteoclasts (apoptotic or otherwise) were preformed at 40x magnification using a calibrated grid at the middle regions of the caudal, central and rostral parts of the distraction gap. Counting reproducibility was verified as <13%. RESULTS: Counts from all three regions were combined because no significant regional difference was found. The majority of the fibrous matrix regenerate was seen at days 6 and 10 while osseous regenerate occurred mainly at days 24 and 38. Significantly higher levels of apoptotic activity were seen at day 24. Apoptotic osteoclasts also peaked at day 24. Apoptotic cell numbers in the slow and moderate groups most closely followed the pattern of the sham in which the apoptosis activity peaked at days 10 or 24. However, those in the rapid group showed delayed peaks at days 24 or 38. CONCLUSIONS: Chalmers Street, Surry Hill, NSW 2010, Australia. gshe6437@mail.usyd.edu.au The transition from fibrous to osseous regenerate during mandibular distraction osteogenesis is accompanied by an increase in cell clearance via apoptosis. A slow to moderate distraction rate allows for the most typical pattern of bone healing while a rapid rate prolongs the healing process.

In situ NMR and XRD studies of the growth mechanism of SBA-1.

In situ 17O, 14N and 29Si nuclear magnetic resonance (NMR) coupled with in situ energy dispersive X-ray diffraction (EDXRD) have been used to investigate the growth of the siliceous mesoporous material, SBA-1, synthesised under acidic conditions from a micellar solution of the surfactant hexadecyltriethylammonium bromide (HTEAB) and tetraethylorthosilicate (TEOS). For the last decade, the mechanism of growth of such materials has been thought to be driven by electrostatic interactions described as a co-assembly process between the silica species (I+) and the micelles (S(+)X(-)). However, this postulated model referred to as the "charge density matching model" has never been fully supported by experimental data for the acidic syntheses. We have carried out a detailed in situ study which challenges the so-called S(+)X(-)I(+) pathway and instead suggests that a salting-out effect coupled with a drastic change in the water activity are responsible for the composite I(1)3 (SBA-1 space group Pm3n) mesophase precipitation. Substantial reorganisation of the precipitated phase then results in the final structure.

A major lung cancer susceptibility locus maps to chromosome 6q23-25.

Lung cancer is a major cause of death in the United States and other countries. The risk of lung cancer is greatly increased by cigarette smoking and by certain occupational exposures, but familial factors also clearly play a major role. To identify susceptibility genes for familial lung cancer, we conducted a genomewide linkage analysis of 52 extended pedigrees ascertained through probands with lung cancer who had several first-degree relatives with the same disease. Multipoint linkage analysis, under a simple autosomal dominant model, of all 52 families with three or more individuals affected by lung, throat, or laryngeal cancer, yielded a maximum heterogeneity LOD score (HLOD) of 2.79 at 155 cM on chromosome 6q (marker D6S2436). A subset of 38 pedigrees with four or more affected individuals yielded a multipoint HLOD of 3.47 at 155 cM. Analysis of a further subset of 23 multigenerational pedigrees with five or more affected individuals yielded a multipoint HLOD score of 4.26 at the same position. The 14 families with only three affected relatives yielded negative LOD scores in this region. A predivided samples test for heterogeneity comparing the LOD scores from the 23 multigenerational families with those from the remaining families was significant (P=.007). The 1-HLOD multipoint support interval from the multigenerational families extends from C6S1848 at 146 cM to 164 cM near D6S1035, overlapping a genomic region that is deleted in sporadic lung cancers as well as numerous other cancer types. Parametric linkage and variance-components analysis that incorporated effects of age and personal smoking also supported linkage in this region, but with somewhat diminished support. These results localize a major susceptibility locus influencing lung cancer risk to 6q23-25.

Macro-cellular silica foams: synthesis during the natural creaming process of an oil-in-water emulsion.

The room-temperature synthesis of a macro-mesoporous silica material during the natural creaming process of an oil-in-water emulsion is reported. The material has 3-dimensional interconnected macropores with a strut-like structure similar to meso-cellular silica foams with mesoporous walls of worm-hole structure. The material has very high surface area (approximately 800 m2 g(-1)) with narrow mesopore size distribution.

Wildtype Kras2 can inhibit lung carcinogenesis in mice.

Although the ras genes have long been established as proto-oncogenes, the dominant role of activated ras in cell transformation has been questioned. Previous studies have shown frequent loss of the wildtype Kras2 allele in both mouse and human lung adenocarcinomas. To address the possible tumor suppressor role of wildtype Kras2 in lung tumorigenesis, we have carried out a lung tumor bioassay in heterozygous Kras2-deficient mice. Mice with a heterozygous Kras2 deficiency were highly susceptible to the chemical induction of lung tumors when compared to wildtype mice. Activating Kras2 mutations were detected in all chemically induced lung tumors obtained from both wildtype and heterozygous Kras2-deficient mice. Furthermore, wildtype Kras2 inhibited colony formation and tumor development by transformed NIH/3T3 cells and a mouse lung tumor cell line containing an activated Kras2 allele. Allelic loss of wildtype Kras2 was found in 67% to 100% of chemically induced mouse lung adenocarcinomas that harbor a mutant Kras2 allele. Finally, an inverse correlation between the level of wildtype Kras2 expression and extracellular signal-regulated kinase (ERK) activity was observed in these cells. These data strongly suggest that wildtype Kras2 has tumor suppressor activity and is frequently lost during lung tumor progression.

Adductor insertion avulsion syndrome (thigh splints): spectrum of MR imaging features.

OBJECTIVE: "Thigh splints," also known as the adductor insertion avulsion syndrome, is a painful condition affecting the proximal to mid femur at the insertion of the adductor muscles of the thigh. Scintigraphic findings in this syndrome have been described; we report a spectrum of MR imaging abnormalities involving this portion of the femur in a group of patients presenting with hip, groin, or thigh pain. CONCLUSION: Symptoms of vague hip, groin, or thigh pain may be associated with stress-related changes in the proximal to mid femoral shaft (thigh splints). When interpreting MR imaging studies of the pelvis in patients presenting with these symptoms, careful attention should be directed to this portion of the femur. This is especially important because the findings may be subtle, and this region is often at the distal edge of most MR imaging studies of the pelvis and hip.

Efficacy and safety of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. Multicenter phase III clinical trials. Efficacy of early imaging.

The efficacy of contrast-enhanced magnetic resonance imaging (MRI) for detecting and characterizing, or excluding, hepatic masses was assessed in 404 patients, following the intravenous administration of mangafodipir trisodium (MnDPDP) injection, a hepatic MRI contrast agent. An initial contrast-enhanced computed tomography (CT) examination was followed by unenhanced MRI, injection of MnDPDP (5 micromol/kg IV), and enhanced MRI at 15 minutes post injection. Agreement of the radiologic diagnoses with the patients' final diagnoses was higher for enhanced MRI and for the combined unenhanced and enhanced MRI evaluations than for unenhanced MRI alone or enhanced CT using the clinical diagnosis as the gold standard. Mangafodipir-enhanced MRI uniquely provided additional diagnostic information in 48% of the patients, and patient management was consequently altered in 6% of the patients. MnDPDP-enhanced MRI was comparable or superior to unenhanced MRI and enhanced CT for the detection, classification, and diagnosis of focal liver lesions in patients with known or suspected focal liver disease.

Association of posterior tibial tendon abnormalities with abnormal signal intensity in the sinus tarsi on MR imaging.

OBJECTIVE: To evaluate the association of abnormal signal intensity within the sinus tarsi with abnormalities of the posterior tibial tendon (PTT) on MR imaging. DESIGN AND PATIENTS: Sinus tarsi abnormalities were identified on 30 ankle MR examinations in 29 patients. The PTT and anterior talofibular ligament were retrospectively analyzed for abnormalities in these same patients. RESULTS AND CONCLUSIONS: Tears of the anterior talofibular ligament were found in 13 of 30 (43%) ankles. PTT abnormalities (complete tear, partial tear or dislocation) were seen in 14 of 30 (47%) studies, and were distributed relatively equally between those patients with and without lateral ligament tears. Our results provide evidence of an association between abnormalities of the PTT and the sinus tarsi. The finding of abnormal signal intensity within the sinus tarsi on MR imaging should alert the radiologist to potential abnormalities of the PTT.

Magnetic resonance imaging of denervated muscle: comparison to electromyography.

The purpose of the study is to further assess the usefulness of short TI (time to inversion) recovery (STIR) magnetic resonance imaging (MRI) in detecting denervation of skeletal muscle compared to needle electromyography (EMG). Ninety subjects with clinical evidence of peripheral nerve injury or radiculopathy underwent STIR MRI and EMG of the affected limb. In 74 (82%) of these subjects, a positive correlation was found between STIR MRI and EMG (P < 0.009). STIR MRI has a relative sensitivity of 84% and specificity of 100% for detecting denervation. A subset of 28 subjects underwent quantitative assessments of signal intensity ratio (SIR) from the STIR MRI. The rank order correlation coefficient between the SIR and abnormal spontaneous activity on EMG was 0.70 (P < 0.001). Increased signal intensity on STIR MRI corresponds closely with spontaneous activity on EMG in denervated muscle. Although less sensitive than EMG in detecting muscle denervation, STIR MRI may be a useful adjunctive diagnostic tool in this setting.

Safety and efficacy of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. multicenter phase III clinical trials (safety).

The short-term safety of mangafodipir trisodium (MnDPDP) injection was studied in 546 adults with known or suspected focal liver lesions. An initial contrast-enhanced computed tomography examination was followed by unenhanced magnetic resonance imaging (MRI), injection of MnDPDP (5 micromol/kg), and enhanced MRI. Adverse events were reported for 23% of the patients; most were mild to moderate in intensity, did not require treatment, and were not drug related. The most commonly reported adverse events were nausea (7%) and headache (4%). The incidence of serious adverse events was low (nine events in six patients) and not drug related. Injection-associated discomfort was reported for 69% of the patients, and the most commonly reported discomforts included heat (49%) and flushing (33%). Changes in laboratory values and vital signs were generally transient, were not clinically significant, and did not require treatment. There were no clinically significant short-term risks from exposure to MnDPDP.

A germ-line p53 mutation accelerates pulmonary tumorigenesis: p53-independent efficacy of chemopreventive agents green tea or dexamethasone/myo-inositol and chemotherapeutic agents taxol or adriamycin.

Recent evidence indicates that individuals with a p53 germ-line mutation (Li-Fraumeni syndrome) have a 50% risk of developing lung cancer by age 60. In this study, p53 heterozygous knockout mice and p53 transgenic mice carrying a dominant negative mutant were crossed with the A/J mouse, which is highly susceptible to lung tumor induction, to investigate whether a p53 germ-line mutation is a predisposing gene for carcinogen-induced pulmonary adenomas in mice. The number of lung tumors was not significantly increased in (TSG-p53 x A/J)F1 p53 heterozygous knockout mice as compared with that in (TSG-p53 x A/J)F1 wt mice 16 weeks after exposure to N-nitrosomethylurea (MNU). In contrast, an average of 22 lung tumors were observed in (UL53-3 x A/J)F1 mice carrying a mutant p53 transgene (135Valp53) compared with an average of 7 lung tumors seen in (UL53-3 x A/J)F1 wt mice after treatment with N-nitrosomethylurea. Similar enhancement of lung tumor multiplicity (approximately 3-fold) was seen when mutant versus wt mice were treated with the tobacco-related carcinogens benzo[a]pyrene or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. These results suggest that the mutant p53 transgene may have a dominant negative effect on the wt p53. The potential usefulness of this new mouse model in lung cancer chemoprevention and chemotherapy was examined. The chemopreventive efficacy of the green tea or a combination of dietary dexamethasone and myoinositol and the chemotherapeutic efficacy of Taxol or Adriamycin was examined in wt mice or mice with a mutation in the p53 gene. Mice treated with dexamethasone/myo-inositol and green tea displayed an average of 70 and 50% inhibition of lung tumors, respectively, regardless of p53 status. Similarly, when mice bearing established lung adenomas were treated with Taxol or Adriamycin, a decrease in tumor volume of approximately 70% was observed independent of p53 mutation status. Thus, the (UL53-3 x A/J)F1 p53 transgenic mouse seems to be an excellent model for human carriers of p53 germ-line mutations (Li-Fraumeni syndrome). Furthermore, the lung adenomas generated in this model possess mutations in both the K-ras proto-oncogene and the p53 tumor suppressor gene. This model should prove directly useful for chemoprevention and chemotherapy studies.

Fluoroscopy-guided sacroiliac joint injections.

The authors performed fluoroscopy-guided sacroiliac (SI) joint injections. With the patient prone and the x-ray tube perpendicular to the fluoroscopic table, the skin was marked over the distal 1 cm of the SI joint. With the tube angled 20 degrees - 25 degrees cephalad, a 22-gauge needle was inserted at the skin mark and advanced perpendicular to the fluoroscopic table toward the posterior joint. Nonionic contrast material was injected to confirm the intraarticular position of the needle. Of 31 SI joint injections, 30 (97%) were intraarticular. Mean procedure time was 108 seconds. This technique is safe, rapid, and reproducible.

Pedicle marrow signal intensity changes in the lumbar spine: a manifestation of facet degenerative joint disease.

OBJECTIVE: Signal intensity changes in lumbar pedicles, similar to those described in vertebral body endplates adjacent to degenerated discs, have been described as an ancillary sign of spondylolysis on MRI. The purpose of this study was to determine whether pedicle marrow signal intensity changes also occur in association with facet degenerative joint disease. DESIGN: Eighty-nine lumbar spine MRI examinations without spondylolysis were reviewed for marrow signal intensity changes in pedicles and vertebral bodies as well as for facet degenerative joint disease. RESULTS: Five percent (46/890) of lumbar pedicles in 23 patients had marrow signal intensity changes. Ninety-one percent (42/46) of the abnormal pedicles had adjacent degenerative joint disease of the facets, while only 21% (189/890) of normal pedicles had adjacent facet degenerative joint disease (p<0.001). Eighty-nine percent (41/46) of the pedicles with marrow signal intensity changes had adjacent degenerative disc disease. CONCLUSIONS: Pedicle marrow signal intensity changes are not a specific sign of spondylolysis; they are commonly seen with adjacent facet degenerative joint disease in the absence of spondylolysis. Pedicle marrow signal intensity changes are probably a response to abnormal stresses related to abnormal motion or loading caused by the degenerative changes in the spinal segment.

Compartmental anatomy: relevance to staging and biopsy of musculoskeletal tumors.

A thorough understanding of compartmental anatomy is essential for accurate staging of a suspected musculoskeletal tumor with MR imaging and for avoiding potentially devastating biopsy-related complications. Imaging-guided, percutaneous needle biopsy is a safe and cost-effective technique but requires careful planning in conjunction with the surgeon who will perform the definitive surgery because it constitutes the final step in the staging process and the first step in surgical therapy.