Threshold regulation and stochasticity from the MecA/ClpCP proteolytic system in Streptococcus mutans competence.

Many bacterial species use the MecA/ClpCP proteolytic system to block entry into genetic competence. In Streptococcus mutans, MecA/ClpCP degrades ComX (also called SigX), an alternative sigma factor for the comY operon and other late competence genes. Although the mechanism of MecA/ClpCP has been studied in multiple Streptococcus species, its role within noisy competence pathways is poorly understood. S. mutans competence can be triggered by two different peptides, CSP and XIP, but it is not known whether MecA/ClpCP acts similarly for both stimuli, how it affects competence heterogeneity, and how its regulation is overcome. We have studied the effect of MecA/ClpCP on the activation of comY in individual S. mutans cells. Our data show that MecA/ClpCP is active under both XIP and CSP stimulation, that it provides threshold control of comY, and that it adds noise in comY expression. Our data agree quantitatively with a model in which MecA/ClpCP prevents adventitious entry into competence by sequestering or intercepting low levels of ComX. Competence is permitted when ComX levels exceed a threshold, but cell-to-cell heterogeneity in MecA levels creates variability in that threshold. Therefore, MecA/ClpCP provides a stochastic switch, located downstream of the already noisy comX, that enhances phenotypic diversity.

Detection of clinically occult primary tumours in patients with cervical metastases of unknown primary tumours: comparison of three-dimensional THRIVE MRI, two-dimensional spin-echo MRI, and contrast-enhanced CT.

AIM: To evaluate and compare the utility of contrast-enhanced three-dimensional (3D) T1-weighted high-resolution isotropic volume examination (THRIVE), spin-echo (SE) T1-weighted magnetic resonance imaging (MRI), and computed tomography (CT) for detecting clinically occult primary tumours in patients with cervical lymph node metastases. MATERIALS AND METHODS: Seventy-three consecutive patients with tumours that went undetected during endoscopic or physical examinations underwent preoperative contrast-enhanced CT and MRI (SE and 3D THRIVE) after gadolinium injection. Guided biopsy results served as reference standards. The diagnostic performances of the imaging techniques were compared with McNemar's tests. RESULTS: Primary tumours were identified in 59 (80.8%) of the 73 patients after surgery. Of these, 36 were found in the palatine tonsil, 11 in the base of the tongue, seven in the nasopharynx, and five in the pyriform sinus. The sensitivity (72.9%) and accuracy (71.2%) of 3D THRIVE for detecting primary tumours were higher than were those of SE T1-weighted MRI (49.2% and 53.4%, p≤0.002) or CT (36.4% and 46.4%, p≤0.001). The specificities of these techniques did not differ. The diagnostic performance of 3D THRIVE (area under the curve [AUC]=0.681) for detecting tumours did not differ from that of SE T1-weighted MRI or CT (AUC=0.671 and 0.608, p>0.05). CONCLUSION: 3D THRIVE was more sensitive at detecting primary tumours than was SE T1-weighted MRI or CT in patients with cervical metastases of unknown primary tumours. This sequence may improve biopsy and therapeutic planning in these patients.

QTL analysis of body weight and carcass body length traits in an F2 intercross between Landrace and Korean native pigs.

Growth traits, such as body weight and carcass body length, directly affect productivity and economic efficiency in the livestock industry. We performed a genome-wide linkage analysis to detect the quantitative trait loci (QTL) that affect body weight, growth curve parameters and carcass body length in an F2 intercross between Landrace and Korean native pigs. Eight phenotypes related to growth were measured in approximately 1000 F2 progeny. All experimental animals were subjected to genotypic analysis using 173 microsatellite markers located throughout the pig genome. The least squares regression approach was used to conduct the QTL analysis. For body weight traits, we mapped 16 genome-wide significant QTL on SSC1, 3, 5, 6, 8, 9 and 12 as well as 22 suggestive QTL on SSC2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 17. On SSC12, we identified a major QTL affecting body weight at 140 days of age that accounted for 4.3% of the phenotypic variance, which was the highest test statistic (F-ratio = 45.6 under the additive model, nominal P = 2.4 × 10(-11) ) observed in this study. We also showed that there were significant QTL on SSC2, 5, 7, 8, 9 and 12 affecting carcass body length and growth curve parameters. Interestingly, the QTL on SSC2, 3, 5, 6, 8, 9, 10, 12 and 17 influencing the growth-related traits showed an obvious trend for co-localization. In conclusion, the identified QTL may play an important role in investigating the genetic structure underlying the phenotypic variation of growth in pigs.

Autotransplantation of mesiodens for missing maxillary lateral incisor with cone-beam CT-fabricated model and orthodontics.

AIM: Autotransplantation is a viable treatment option for a missing tooth when there is a suitable donor, especially in adolescents with remaining facial growth. This report presents the aesthetic restoration of a missing maxillary lateral incisor through orthodontic treatment and autotransplantation of a mesiodens using a CBCT-fabricated rapid-prototyping model. SUMMARY: A 14-year-old male patient with a congenitally missing maxillary lateral incisor was referred from the Department of Orthodontics. The teeth were moved orthodontically to regain space for the missing lateral incisor and to close the space of the mesiodens after transplantation. A replica of the donor tooth was fabricated from a cone-beam computed tomography scan through a rapid-prototyping machine before autotransplantation surgery. The model was used to create a socket for the graft tooth, thereby shortening the extra-oral time and minimizing the damage to the root surface. After transplantation and orthodontic tooth movement, the mesiodens was finally restored with an aesthetic laminate restoration. Over 3 years, the aesthetics remained excellent, and the transplant functioned normally without any signs or symptoms of root resorption. KEY LEARNING POINT: Missing anterior teeth may be replaced through a combination of orthodontics, autotransplantation with a rapid-prototyping model and prosthodontic restoration, in growing patients.

Cryopreservation induces macrophage colony stimulating factor from human periodontal ligament cells in vitro.

Cryopreservation is used to protect vital periodontal ligaments during the transplantation of teeth. We investigated which gene products implicated in root resorption are upregulated in human periodontal ligament cells by cryopreservation, and whether cryopreservation affects the expression of macrophage-colony stimulating factor (M-CSF) in human periodontal ligament cells. We used customized microarrays to compare gene expression in human periodontal ligament cells cultured from teeth immediately after extraction and from cryopreserved teeth. Based on the result of these assays, we examined M-CSF expression in periodontal ligament cells from the immediately extracted tooth and cryopreserved teeth by real-time PCR, enzyme-linked immunosorbent assay (ELISA), Western blot analysis, and immunofluorescence. We also investigated whether human bone marrow cells differentiate into tartrate-resistant acid phosphatase (TRAP) positive osteoclasts when stimulated with RANKL (Receptor Activator for Nuclear Factor κ B Ligand) together with any secreted M-CSF present in the supernatants of the periodontal ligament cells cultured from the various groups of teeth. M-CSF was twofold higher in the periodontal ligament cells from the rapid freezing teeth than in those from the immediately extracted group (p < 0.05). Cryopreservation increased M-CSF expression in the periodontal ligament cells when analyzed by real time PCR, ELISA, Western blotting, and immunofluorescence (p < 0.05). TRAP positive osteoclasts were formed in response to RANKL and the secreted M-CSF present in the supernatants of all the experimental groups except negative control. These results demonstrate that cryopreservation promotes the production of M-CSF, which plays an important role in root resorption by periodontal ligament cells.

BrpA is involved in regulation of cell envelope stress responses in Streptococcus mutans.

Previous studies have shown that BrpA plays a major role in acid and oxidative stress tolerance and biofilm formation by Streptococcus mutans. Mutant strains lacking BrpA also display increased autolysis and decreased viability, suggesting a role for BrpA in cell envelope integrity. In this study, we examined the impact of BrpA deficiency on cell envelope stresses induced by envelope-active antimicrobials. Compared to the wild-type strain UA159, the BrpA-deficient mutant (TW14D) was significantly more susceptible to antimicrobial agents, especially lipid II inhibitors. Several genes involved in peptidoglycan synthesis were identified by DNA microarray analysis as downregulated in TW14D. Luciferase reporter gene fusion assays also revealed that expression of brpA is regulated in response to environmental conditions and stresses induced by exposure to subinhibitory concentrations of cell envelope antimicrobials. In a Galleria mellonella (wax worm) model, BrpA deficiency was shown to diminish the virulence of S. mutans OMZ175, which, unlike S. mutans UA159, efficiently kills the worms. Collectively, these results suggest that BrpA plays a role in the regulation of cell envelope integrity and that deficiency of BrpA adversely affects the fitness and diminishes the virulence of OMZ175, a highly invasive strain of S. mutans.

Progress dissecting the oral microbiome in caries and health.

Recent rapid advances in "-omics" technologies have yielded new insights into the interaction of the oral microbiome with its host. Associations of species that are usually considered to be acid-tolerant with caries have been confirmed, while some recognized as health-associated are often present in greater proportions in the absence of caries. In addition, some newly identified bacteria have been suggested as potential contributors to the caries process. In spite of this progress, two major challenges remain. The first is that there is a great deal of heterogeneity in the phenotypic capabilities of individual species of oral bacteria. The second is that the most abundant taxa in oral biofilms display remarkable phenotypic plasticity, i.e., the bacteria associated most strongly with health or with caries can morph rapidly in response to alterations in environmental pH, carbohydrate availability and source, and oxygen tension and redox environment. However, new technologic advances coupled with "old-fashioned microbiology" are starting to erode the barriers to a more complete understanding of oral biofilm physiology and ecology, and in doing so are beginning to provide insights for the creation of novel cost-effective caries control therapies.

MRI-Visible Perivascular Spaces in the Centrum Semiovale Are Associated with Brain Amyloid Deposition in Patients with Alzheimer Disease-Related Cognitive Impairment.

BACKGROUND AND PURPOSE: The association of perivascular spaces in the centrum semiovale with amyloid accumulation among patients with Alzheimer disease-related cognitive impairment is unknown. We evaluated this association in patients with Alzheimer disease-related cognitive impairment and ß-amyloid deposition, assessed with [18F] florbetaben PET/CT. MATERIALS AND METHODS: MR imaging and [18F] florbetaben PET/CT images of 144 patients with Alzheimer disease-related cognitive impairment were retrospectively evaluated. MR imaging-visible perivascular spaces were rated on a 4-point visual scale: a score of ≥3 or <3 indicated a high or low degree of MR imaging-visible perivascular spaces, respectively. Amyloid deposition was evaluated using the brain ß-amyloid plaque load scoring system. RESULTS: Compared with patients negative for ß-amyloid, those positive for it were older and more likely to have lower cognitive function, a diagnosis of Alzheimer disease, white matter hyperintensity, the Apolipoprotein E ε4 allele, and a high degree of MR imaging-visible perivascular spaces in the centrum semiovale. Multivariable analysis, adjusted for age and Apolipoprotein E status, revealed that a high degree of MR imaging-visible perivascular spaces in the centrum semiovale was independently associated with ß-amyloid positivity (odds ratio, 2.307; 95% CI, 1.036-5.136; P = .041). CONCLUSIONS: A high degree of MR imaging-visible perivascular spaces in the centrum semiovale independently predicted ß-amyloid positivity in patients with Alzheimer disease-related cognitive impairment. Thus, MR imaging-visible perivascular spaces in the centrum semiovale are associated with amyloid pathology of the brain and could be an indirect imaging marker of amyloid burden in patients with Alzheimer disease-related cognitive impairment.

Diagnosis of Critical Illness Myopathy After Liver Transplantation and Muscle Condition Monitoring: A Case Report.

BACKGROUND: Intensive care unit-acquired weakness (ICUAW) can occur after liver transplantation. Early diagnosis of ICUAW and monitoring of muscle condition during rehabilitation are helpful in improving functional recovery. METHODS AND MATERIALS: A 47-year-old man with liver cirrhosis developed limb weakness after liver transplantation. The patient had a Medical Research Council sum score of 2 weeks post-liver transplantation with marked proximal limb weakness. Direct muscle stimulation was performed on the right tibialis anterior muscle; the nerve-to-muscle ratio of compound muscle action potentials was 0.96, which indicated critical illness myopathy. Fatigue analysis using surface electromyography was performed 4 times after liver transplantation. RESULTS AND CONCLUSIONS: The maximal voluntary contraction tended to increase during rehabilitation, whereas the percentage of maximal voluntary contraction tended to decrease, indicating that muscle strength was increased. The fatigue index gradually decreased, showing that muscle endurance had improved along with strength. Muscle fatigue can be evaluated during rehabilitation using surface electromyography to prevent damage of the impaired muscle and to control exercise intensity. Early diagnosis of ICUAW and evaluation of muscle fatigue during rehabilitation will ensure a better prognosis for patients with ICUAW.

Diffusion-Weighted Imaging of Brain Metastasis from Lung Cancer: Correlation of MRI Parameters with the Histologic Type and Gene Mutation Status.

BACKGROUND AND PURPOSE: Development of noninvasive imaging biomarkers indicating the histology and the gene mutation status of brain metastasis from lung cancer is important. We aimed to investigate diffusion-weighted imaging parameters as predictors of the histology and gene mutations of brain metastasis from lung cancer. MATERIALS AND METHODS: DWI data for 74 patients with brain metastasis from lung cancer were retrospectively reviewed. The patients were first grouped according to the primary tumor histology (adenocarcinoma, small-cell lung cancer, squamous cell carcinoma), and those with adenocarcinoma were further divided into epidermal growth factor receptor (EFGR) mutation-positive and wild type groups. Sex; age; number, size, and location of brain metastasis; DWI visual scores; the minimum ADC; and the normalized ADC ratio were compared among groups using χ2 and ANOVA. Multiple logistic regression analysis was performed to determine independent predictors of the EGFR mutation. RESULTS: The minimum ADC was lower in the small-cell lung cancer group than in the other 2 groups, though the difference was not significant. Furthermore, minimum ADC and the normalized ADC ratio were significantly lower in the EGFR mutation-positive group than in the wild type group (P = .021 and .014, respectively). Multivariate analysis revealed that minimum ADC and the normalized ADC ratio were independently associated with the EGFR mutation status (P = .028 and .021, respectively). CONCLUSIONS: Our results suggest that DWI parameters (minimum ADC and normalized ADC ratio) for the solid components of brain metastasis from lung cancer are not correlated with their histology, whereas they can predict the EGFR mutation status in brain metastasis from lung adenocarcinoma.

Diagnostic Performance of Multidetector Computerized Tomography in the Detection of Abdominal Complications Early and Late After Liver Transplantation: A 10-Year Experience.

BACKGROUND: Multidetector computerized tomography (MDCT) is considered to be a fast noninvasive diagnostic technique for the evaluation of postoperative complications in patients with liver transplantation (LT). However, its role has not been fully established in the diagnosis for detecting complications after liver transplantation. The aim of this work was to evaluate the diagnostic performance of MDCT for detecting abdominal complications in the early and late periods after LT. METHODS: We retrospectively enrolled 75 patients who had undergone LT from March 2006 to January 2010, followed by MDCT from March 2006 to November 2017. Patients were divided into 2 groups according to the timing after LT: within the first 3 months (early period) or ≥3 months after LT (late period). We evaluated vascular, biliary, and other complications on MDCT. Angiography, endoscopic retrograde cholangiography, and percutaneous transhepatic cholangiography were used as reference standards. RESULTS: We initially found 77 complications in 45 patients (60.0%) with the use of MDCT. After comparison with the reference standards, 83 complications were diagnosed in 49 patients (65.3%). Forty-seven complications (34 vascular, 10 biliary, 3 other complications) were diagnosed in 33 patients (44.0%) during the early period, and 36 complications (6 vascular, 20 biliary, 10 other complications) were detected in 27 patients (36.0%) in the late period. The sensitivity, specificity, and diagnostic accuracy of MDCT for diagnosing overall complications were, respectively, 93.6%, 90.2%, and 92.0% in the early period (for vascular complications: 97.1%, 92.6%, and 94.3%,; for biliary complications: 80.0%, 100%, and 97.7%) and 77.8%, 98.1%, and 89.8% in the late period (for vascular complications: 83.3%, 100%, and 98.9%; for biliary complications: 65.0%, 98.6%, and 90.9%). CONCLUSIONS: Although MDCT in the late period should be interpreted with caution in patients with suspected biliary complication, MDCT is a reliable diagnostic technique for the identification of early and late abdominal complications after LT.

Prevalence of Intracranial Aneurysms in Patients with Aortic Dissection.

BACKGROUND AND PURPOSE: There is an uncertainty about the association between intracranial aneurysms and aortic dissection. We aimed to determine the prevalence of intracranial aneurysms in patients with aortic dissection and evaluate the independent risk factors for the presence of intracranial aneurysms in these patients. MATERIALS AND METHODS: Seventy-one patients with a confirmed aortic dissection who underwent additional brain imaging were enrolled as the aortic dissection group, and 2118 healthy individuals with brain imaging, as controls. Demographic data were obtained from their medical records, including age, sex, comorbidities, and arch vessel involvement of aortic dissection. Two readers reviewed all brain images independently regarding the presence, morphology, size, and location of intracranial aneurysms. Baseline characteristics were compared between the aortic dissection group and controls by propensity score matching, and logistic regression analysis was performed for independent risk factors for the presence of intracranial aneurysms. RESULTS: The prevalence of intracranial aneurysms was 12.96% in the aortic dissection group and 1.85% in controls (P = .022). The mean diameter of intracranial aneurysms was significantly larger in the aortic dissection group (5.79 ± 3.26 mm in aortic dissection versus 3.04 ± 1.57 mm in controls; P = .008), and intracranial aneurysms of >7 mm were also more common in the aortic dissection group (28.6% in aortic dissection versus 5.3% in controls, P = .003). On multivariate analysis, arch vessel involvement of aortic dissection was an independent risk factor for the presence of intracranial aneurysms (odds ratio, 6.246; 95% confidence interval, 1.472-26.50; P = .013). CONCLUSIONS: Patients with aortic dissection have a high prevalence of intracranial aneurysms, and selective screening for brain vessels could be considered in these patients with arch vessel involvement. A further prospective study is needed to demonstrate a substantial prevalence of intracranial aneurysms.

Reduction of Oxygen-Induced CSF Hyperintensity on FLAIR MR Images in Sedated Children: Usefulness of Magnetization-Prepared FLAIR Imaging.

BACKGROUND AND PURPOSE: Oxygen-induced CSF hyperintensity on FLAIR MR imaging is often observed in sedated children. This phenomenon can mimic leptomeningeal pathology and lead to a misdiagnosis. The purpose of this study was to investigate whether magnetization-prepared FLAIR MR imaging can reduce oxygen-induced CSF hyperintensity and improve image quality compared with conventional (non-magnetization-prepared) FLAIR MR imaging. MATERIALS AND METHODS: Bloch simulation for magnetization-prepared and non-magnetization-prepared FLAIR sequences was performed for tissue contrast. We retrospectively reviewed 85 children with epilepsy who underwent MR imaging under general anesthesia with supplemental oxygen (41 with non-magnetization-prepared FLAIR and 44 with magnetization-prepared FLAIR). CSF hyperintensity was scored from 0 to 3 points according to the degree of CSF signal intensity and was compared between the 2 sequences. The contrast-to-noise ratios among GM, WM, and CSF were evaluated to assess general image quality from both sequences. To assess the diagnostic accuracy for hemorrhage, we reviewed an additional 25 patients with hemorrhage. RESULTS: Bloch simulation demonstrated that CSF hyperintensity can be reduced on magnetization-prepared FLAIR compared with non-magnetization-prepared FLAIR. CSF hyperintensity scores were significantly lower in magnetization-prepared FLAIR than in non-magnetization-prepared FLAIR (P < .01). The contrast-to-noise ratios for GM-WM, GM-CSF, and WM-CSF were significantly higher in magnetization-prepared FLAIR than in non-magnetization-prepared FLAIR (P < .05). Hemorrhage was clearly demarcated from CSF hyperintensity in the magnetization-prepared group (100%, 12/12) and non-magnetization-prepared group (38%, 5/13). CONCLUSIONS: Magnetization-prepared 3D-FLAIR MR imaging can significantly reduce oxygen-induced CSF artifacts and increase the tissue contrast-to-noise ratio beyond the levels achieved with conventional non-magnetization-prepared 3D-FLAIR MR imaging.

The Revascularization Scales Dilemma: Is It Right to Apply the Treatment in Cerebral Ischemia Scale in Posterior Circulation Stroke?

BACKGROUND AND PURPOSE: Although various revascularization scales are used in the angiographic evaluation of acute ischemic stroke, observer reliability tests of these scales have been rarely performed for posterior circulation stroke. We aimed to evaluate inter- and intraobserver variability of 2 scales, the modified Treatment in Cerebral Ischemia and the Arterial Occlusive Lesion, in posterior circulation stroke. MATERIALS AND METHODS: Three independent readers interpreted pre- and postthrombolytic angiographies of 62 patients with posterior circulation stroke by using the modified Treatment in Cerebral Ischemia and Arterial Occlusive Lesion scales. The κ statistic was used to measure observer agreement for both scales, and κ > 0.6 was considered substantial agreement. RESULTS: For the Arterial Occlusive Lesion scale, inter- and intraobserver agreement was >0.6. While intraobserver agreement of the modified Treatment in Cerebral Ischemia scale was >0.6 except for 1 reader, interobserver agreement was lower in dichotomized and original scales. In 49 cases with solely basilar artery occlusion, inter- and intraobserver agreement of both scales was similar to that in all 62 patients with posterior circulation stroke. In 2 consecutive readings, there was a significant decrease in the proportion of mTICI 2a reads (22.58% in the first versus 13.44% in the second session, P < .03) and a reciprocal increase in the sum of proportions for modified Treatment in Cerebral Ischemia 2b and modified Treatment in Cerebral Ischemia 3 reads (62.37% in the first versus 72.58% in the second session, P < .046). CONCLUSIONS: In angiographic assessment of posterior circulation stroke, inter- and intraobserver agreement for the Arterial Occlusive Lesion scale was reliable, while the modified Treatment in Cerebral Ischemia failed to achieve substantial interobserver agreement. The clinical impact of this result needs to be validated in future studies.

Efficacy of skull plain films in follow-up evaluation of cerebral aneurysms treated with detachable coils: quantitative assessment of coil mass.

BACKGROUND AND PURPOSE: Skull plain films of coiled aneurysms have been used in a limited role, including morphologic comparison of the coil mass. We aimed to evaluate the efficacy of skull plain films in patients treated with detachable coils by using quantitative assessment. MATERIALS AND METHODS: In this retrospective study, 78 pairs of the initial and follow-up skull anteroposterior and lateral images were reviewed independently by 2 neuroradiologists. The largest diameter, the perpendicular diameter, and area of the coil mass were measured separately on plain film, and quantitative changes of parameters were compared between subgroups, which were determined by consensus, depending on the need for retreatment. Subgroup analysis was also performed according to aneurysm size, packing attenuation, and ruptured status. RESULTS: On skull lateral images, mean quantitative changes of the largest diameter (0.53 ± 0.43 mm versus 1.17 ± 0.91 mm, P < .01), the perpendicular diameter (0.56 ± 0.48 mm versus 1.20 ± 1.05 mm, P < .01), and the area of the coil mass (5.21 ± 7.51 mm(2) versus 10.55 ± 10.93 mm(2), P < .02) differed significantly between subgroups. Receiver operating characteristic analysis showed quantitative change of the largest diameter (>1.1 mm; sensitivity, 50.0%; specificity, 90.3%), the perpendicular diameter (>.9 mm; sensitivity, 62.5%; specificity, 85.5%), and the area (>8.5 mm(2); sensitivity, 50.0%; specificity, 83.9%) on skull lateral films to be indicative of aneurysm recurrence, and the diagnostic accuracy of these parameters increased significantly in the high-packing-attenuation group. CONCLUSIONS: Quantitative measurement of the coil mass by using skull plain lateral images has the potential to predict aneurysm recurrence in follow-up evaluations of intracranial aneurysms with coiling.

Hyperintense Vessels on T2-PROPELLER-FLAIR in Patients with Acute MCA Stroke: Prediction of Arterial Stenosis and Perfusion Abnormality.

BACKGROUND AND PURPOSE: Fluid-attenuated inversion recovery hyperintense vessels in stroke represent leptomeningeal collateral flow. We presumed that FLAIR hyperintense vessels would be more closely associated with arterial stenosis and perfusion abnormality in ischemic stroke on T2-PROPELLER-FLAIR than on T2-FLAIR. MATERIALS AND METHODS: We retrospectively reviewed 35 patients with middle cerebral territorial infarction who underwent MR imaging. FLAIR hyperintense vessel scores were graded according to the number of segments with FLAIR hyperintense vessels in the MCA ASPECTS areas. We compared the predictability of FLAIR hyperintense vessels between T2-PROPELLER-FLAIR and T2-FLAIR for large-artery stenosis. The interagreement between perfusion abnormality and FLAIR hyperintense vessels was assessed. In subgroup analysis (9 patients with MCA horizontal segment occlusion), the association of FLAIR hyperintense vessels with ischemic lesion volume and perfusion abnormality volume was evaluated. RESULTS: FLAIR hyperintense vessel scores were significantly higher on T2-PROPELLER-FLAIR than on T2-FLAIR (3.50 ± 2.79 versus 1.21 ± 1.47, P < .01), and the sensitivity for large-artery stenosis was significantly improved on T2-PROPELLER-FLAIR (93% versus 68%, P = .03). FLAIR hyperintense vessels on T2-PROPELLER-FLAIR were more closely associated with perfusion abnormalities than they were on T2-FLAIR (κ = 0.64 and κ = 0.27, respectively). In subgroup analysis, FLAIR hyperintense vessels were positively correlated with ischemic lesion volume on T2-FLAIR, while the mismatch of FLAIR hyperintense vessels between the 2 sequences was negatively correlated with ischemic lesion volume (P = .01). CONCLUSIONS: In MCA stroke, FLAIR hyperintense vessels were more prominent on T2-PROPELLER-FLAIR compared with T2-FLAIR. In addition, FLAIR hyperintense vessels on T2-PROPELLER-FLAIR have a significantly higher sensitivity for predicting large-artery stenosis than they do on T2-FLAIR. Moreover, the areas showing FLAIR hyperintense vessels on T2-PROPELLER-FLAIR were more closely associated with perfusion abnormality than those on T2-FLAIR.

Apoptosis and bcl-2 expression as predictors of survival in radiation-treated non-small-cell lung cancer.

OBJECTIVES: We assessed the role of apoptosis and the expression of bcl-2, p53, and c-myc oncoproteins in pretreatment histologic specimens as a predictor of response to radiation therapy and survival in non-small-cell lung cancer (NSCLC) patients. METHODS: Pretreatment biopsy specimens of 68 patients with NSCLC (62 squamous cell carcinoma, 6 adenocarcinoma) were stained with hematoxylin and eosin. From 5 high-powered fields, the apoptotic index (AI) was calculated as the ratio of apoptotic tumor cells to the total number of tumor cells. Bcl-2, p53, and c-myc oncoprotein expression was detected by immunohistochemical staining. RESULTS: Twenty-nine cases showed partial or complete remission, whereas 39 showed no response. AI ranged from 0.2 to 12.0% (mean +/- SD; 4.3 +/- 2.6%, median 4.0%). There was no difference in AI between responders (4.0 +/- 2.3) and nonresponders (4.5 +/- 2.8, p > 0.05). However, in the responders, AI was correlated with the degree of change in tumor volume (r = 0.41, p < 0.05). In an analysis of 53 subjects who survived more than 1 month after the completion of radiation therapy, the patients with a higher AI (n = 27, MST = 22.8 m) survived longer than those with a lower AI (n = 26, MST = 9.2, log-rank, p = 0.03). Patients expressing bcl-2 had poorer survival (n = 22, MST = 6.0 m) than patients without bcl-2 (n = 31, 22.8 m, p < 0.003). According to multivariate analysis, three variables, bcl-2 expression, AI, and response to radiation, were independent prognostic factors for survival. CONCLUSION: A low level of spontaneous apoptosis and expression of apoptosis blocking bcl-2 protein in pretreatment histology predict a poor prognosis for radiation-treated NSCLC patients.

Overexpression of phospholipase D1 in human breast cancer tissues.

Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine (PC) to produce phosphatidic acid (PA) and choline. PLD is a major enzyme implicated in important cellular processes, such as cell proliferation. We designed this study to investigate the expression of PLD in human breast carcinomas and non-malignant tissues using RT-PCR, Western blot analysis, immunohistochemistry and an Arf-dependent PLD activity assay. We examined about 550 bp of PCR product and 120 kDa of PLD protein. Our results showed that PLD protein and mRNA levels were overexpressed in 14 of 17 breast cancer tissues. We also observed increased expression by immunohistochemistry and Arf-dependent PLD activity in microsomes of human breast tumors, which correlated well with PLD expression. PLD expression was elevated in human breast tumors compared with normal breast tissues. These results implicate a possible role of PLD in human breast tumorigenesis and suggest that PLD may be useful as a marker for malignant disease in the breast.

Effect of pentoxifylline on radiation response of non-small cell lung cancer: a phase III randomized multicenter trial.

PURPOSES: The objectives of this prospective clinical trial were to determine whether pentoxifylline improves the radiation response and survival in patients with non-small cell lung cancer. MATERIALS AND METHODS: From July 1993 through October 1994, 64 patients with histologically confirmed Stage I, II and III non-small cell lung cancer were randomly divided into pentoxifylline (Pento)+Radiotherapy (RT) group and RT alone group. Out of the 64 patients, only 47 patients who had measurable tumors on chest X-ray views were analyzed and divided into Pento+RT group (n=27) and RT alone group (n=20). Total tumor dose of 65-70 Gy was delivered as conventional fractionated radiation schedules. Pento was given to the patients 3 x 400 mg/day with a daily dose of 1200 mg during RT. RESULTS: Complete response (CR), partial response (PR), and stable in Pento+RT group were three (11%), 13 (48%), and 11 (41%), respectively, as compared with corresponding values of three (15%), 13 (65%), and four (20%) in the RT alone group. The median time to relapse in the Pento+RT group was 11 months which was 2 months longer than for the RT alone group (P>0.05). All the patients in both groups showed lower than or equal to grade 2 dysphagia, odynophagia, pulmonary fibrosis, and pneumonitis. The median survival was 18 months in the Pento+RT group and 7 months in the RT alone group. The 1-year survival rate was 60% in the Pento+RT group and 35% in the RT alone group, the 2-year survival rate was 18% in the Pento+RT group and 12% in the RT alone group. But these differences were not statistically significant (P>0.05). CONCLUSION: We concluded that Pento is a modestly effective radiation response modifier and provide benefit in the treatment of non-small cell lung cancer.

Roles of salivary proteins in the adherence of oral streptococci to various orthodontic brackets.

Knowledge of salivary pellicles on orthodontic brackets provides a better understanding of microbial adherence. The aim of this study was to analyze the effects of bracket pellicles on the adherence of Streptococcus gordonii and Streptococcus mutans. Bracket pellicles were formed by the incubation of 4 kinds of orthodontic brackets with unstimulated whole saliva for 2 hrs, and analyzed by electrophoresis, immunodetection, and amino acid analysis. Binding assays were then performed by the incubation of tritium-labeled streptococci with the pellicle-transfer blots and orthodontic brackets. The results showed that low-molecular-weight mucin, alpha-amylase, secretory IgA, acidic proline-rich proteins, and cystatins adhered to all kinds of brackets, though the amino acid composition of pellicles differed between bracket types. Some of these proteins increased the binding of S. gordonii to saliva-coated brackets. However, salivary pellicles decreased the binding of S. mutans. Collectively, salivary pellicles were found to play a significant role in the initial adhesion of oral streptococci to orthodontic brackets.