Improved approach to identify cancer-associated autoantigens

The failure to identify biomarkers of clinical significance for cancer diagnosis and prognosis generated a great deal of skepticism in regard to the usefulness of autoantibody-based methods. SEREX was a major advancement in immunoscreening that resulted in the identification of a large group of autoantigens recognized by cancer sera. However, few SEREX-defined autoantigens have proven to have definitive diagnostic value in clinical practice. Often, the identified antigens are patient-specific rather than tumor-specific and many tumor-associated antigens are rare in expression libraries made from non-autologous cells. Since autoantibodies are part of the normal immune response, it can be difficult to single out tumor-associated antibodies from the scores of irrelevant patient-specific responses. In our view, any practical approach for identifying cancer-related autoantigens must include an integral strategy for demonstrating tumor relevance early in the screening process. Care must also be taken not to exclude potentially important autoantibodies by pre-screening manipulations to patient sera. We have introduced substantial modifications in SEREX, designed to minimize confounding effects of unrelated autoantibodies and to eliminate steps that preclude the identification of cancer-related autoantigens commonly recognized by cancer sera. In addition, we incorporate methodology to identify candidate antigens that have potential diagnostic or prognostic value prior to their molecular cloning and characterization.     

Dopaminergic modulation of transcallosal activity of cat motor cortical neurons

The effects of dopamine (DA) and its antagonists on the transcallosal activity of pyramidal tract neurons (PTNs) and non-PTNs in the anesthetized cat motor cortex were studied with iontophoretic applications; dopamine, SCH 23390 (D1 antagonist), sulpiride (D2 antagonist) and haloperidol. Neuronal activity was recorded with a multi-barreled glass microelectrode. Transcallosal neuronal activity was evoked by stimulation of the contralateral motor cortex. The number of spikes thus activated was counted for the control and test conditions after application of each drug: (1) dopamine application decreased the number of spikes evoked by transcallosal stimulation; (2) application of SCH 23390, sulpiride and haloperidol restored these decreased spike numbers to the control level; (3) latency of neuronal response to transcallosal stimulation was not affected by the application of either DA, SCH 23390, sulpiride or haloperidol; and (4) there was no significant difference between PTNs and non-PTNs in the manner of response to DA and its antagonist applications. Our conclusion is that dopamine modulated the transcallosal neuronal response in the cat motor cortex in a suppressive manner. This fact suggested that interhemispheric neuronal communications could be subjected to suppressive modification by the dopaminergic system.     

View box luminance measurements and their effect on reader performance

RATIONALE AND OBJECTIVES: The purpose of this study was to investigate the importance of view box luminance and viewing conditions on low-contrast detection by readers. MATERIALS AND METHODS: Radiographs of a mammographic contrast-detail phantom were examined on 632 view box panels. The luminance of these panels was obtained by using a calibrated meter and ranged from 860 to 3,300 nit. Twelve radiologists reported the number of contrast-detail disks for each size (diameter, 0.3-7.0 mm) deemed to be visible on films with optical densities of 1.00-2.60. Radiologist performance in reading low-contrast phantom images was also studied as a function of room illuminance and image masking. RESULTS: Median luminance was 1,700 nit, with 25- and 75-percentile values of 1,450 and 2,150 nit, respectively. Low-contrast visibility generally was independent of view box luminance, regardless of film density or disk diameter. Low-contrast visibility deteriorated when masking around the image was removed and at normal room illuminance. The greatest deterioration in performance occurred at the highest film densities and with the smallest size disks. CONCLUSION: Detection of low-contrast features on radiographs is relatively independent of view box luminance, but it is degraded by the presence of stray light and by increased room illuminance.     

Gender-specific gene expression in post-mortem human brain: localization to sex chromosomes.

Gender differences in brain development and in the prevalence of neuropsychiatric disorders such as depression have been reported. Gender differences in human brain might be related to patterns of gene expression. Microarray technology is one useful method for investigation of gene expression in brain. We investigated gene expression, cell types, and regional expression patterns of differentially expressed sex chromosome genes in brain. We profiled gene expression in male and female dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum using the Affymetrix oligonucleotide microarray platform. Differentially expressed genes between males and females on the Y chromosome (DBY, SMCY, UTY, RPS4Y, and USP9Y) and X chromosome (XIST) were confirmed using real-time PCR measurements. In situ hybridization confirmed the differential expression of gender-specific genes and neuronal expression of XIST, RPS4Y, SMCY, and UTY in three brain regions examined. The XIST gene, which silences gene expression on regions of the X chromosome, is expressed in a subset of neurons. Since a subset of neurons express gender-specific genes, neural subpopulations may exhibit a subtle sexual dimorphism at the level of differences in gene regulation and function. The distinctive pattern of neuronal expression of XIST, RPS4Y, SMCY, and UTY and other sex chromosome genes in neuronal subpopulations may possibly contribute to gender differences in prevalence noted for some neuropsychiatric disorders. Studies of the protein expression of these sex-chromosome-linked genes in brain tissue are required to address the functional consequences of the observed gene expression differences.     

Radiation Exposure Time during MBSS: Influence of Swallowing Impairment Severity, Medical Diagnosis, Clinician Experience, and Standardized Protocol Use

Guidelines and preventive measures have been established to limit radiation exposure time during modified barium swallow studies (MBSS) but multiple variables may influence the duration of the exam. This study examined the influence of clinician experience, medical diagnosis category, swallowing impairment severity, and use of a standardized protocol on fluoroscopy time. A retrospective review of 739 MBSSs performed on 612 patients (342 males/270 females; age range = 18–96 years) completed in 1 year at the Medical University of South Carolina was performed with IRB approval. All studies were completed by speech-language pathologists trained in the data collection protocol, interpretation, and scoring of the MBSImP?^©. Medical diagnosis category, swallowing impairment severity (MBSImP?^© score), clinician experience, and fluoroscopy time were the variables recorded for analysis. Fluoroscopy time was not significantly associated with medical diagnosis category (p = 0.10). The severity of the MBSImP?^© Oral Total and Pharyngeal Total resulted in statistically significant increases in fluoroscopy time (p < 0.05). Studies by novice clinicians had longer exposure times when compared to those of experienced clinicians (p = 0.037). Average radiation exposure time using the MBSImP?^© approach was 2.9 min, with a 95 % confidence interval of 2.8–3.0 min, which was well within the range of exposure times reported in the literature. This study provides preliminary information regarding the impact of medical diagnosis category, swallowing impairment severity, and clinician experience on fluoroscopy time. These findings also suggest that a thorough, standardized protocol for MBSSs did not cause unnecessary radiation exposure time during the MBSS.     

Chronic pain related to first bite syndrome: report of two cases

First bite syndrome is the classic symptomatology of pain in the parotid region that occurs in response to the first bite of a meal. We report two cases of this syndrome in patients after operations to the parapharyngeal space.     

Synthesis,Tautomeric Structures,and Antitumor Activity of New Perimidines

New series of perimidine derivatives and fused perimidines were derived from the reaction of ketene aminals 1 and 2 with diazotized anilines or hydrazonoyl chlorides. In addition, 8,10‐disubstituted‐[1,2,4]triazolo[4,3‐a]perimidines ( 20a–m ) were prepared through the reaction of perimidine‐2‐thione ( 15 ) with hydrazonoyl chlorides. The structures of the newly synthesized compounds were established on the basis of spectral data and elemental analyses. Some products were investigated for their antitumor activities against the human breast cancer cell line MCF‐7 and the liver carcinoma cell line HEPG‐2, and the results of some derivatives showed promising activity.