In multiple sclerosis (MS) patients, a coordinated attack of the immune system against the primary constituents of oligodendrocytes and/or the myelin sheath of oligodendrocytes results in the ...formation of lesions in the brain and spinal cord. Thus far, however, a limited number of genes that potentially contribute to lesion pathology have been identified. Using cDNA microarray technology, we have performed experiments on MS tissue monitoring the expression pattern of over 5,000 genes and compared the gene expression profile of normal white matter with that found in acute lesions from the brain of a single MS patient. Sixty‐two differentially expressed genes were identified, including the Duffy chemokine receptor, interferon regulatory factor‐2, and tumor necrosis factor alpha receptor‐2 among others. Thus, cDNA microarray technology represents a powerful new tool for the identification of genes not previously associated with the MS disease process.
Objectives Optical coherence tomography (OCT) is a novel, real-time endoscopic imaging modality that permits delineation of microarchitectural features of bladder lesions. It may provide an extension ...of conventional cystoscopy by allowing noninvasive examination of bladder tissue at microscopic resolution (10 to 20 μm). The purpose of this study was to examine the application of OCT in augmenting the diagnosis and staging of bladder lesions. Methods We conducted a retrospective institutional review board–approved, single-institution, single-user review on the use of OCT as an adjunct to conventional cystoscopy in 32 patients with a history of bladder cancer (24), primary tumor (6), prostate cancer (1), or hematuria (1). We obtained OCT images of suspicious areas before biopsy or resection, interpreted them in real time, and subsequently compared them with pathology results. Results We obtained 94 images in 32 patients undergoing bladder biopsy or transurethral resection of bladder tumor. Age of the patients ranged from 49 to 84 years (mean, 59 years), with 25 men (78%) and 7 women (22%). We correlated 38 suspicious areas with biopsy findings. OCT imaging correctly identified tumors confined to the mucosa with a sensitivity and specificity of 90% and 89%, respectively. Muscle-invasive tumors were detected in 7 of 7 lesions with 100% sensitivity, 90% specificity, and 92% accuracy. Conclusions Optical coherence tomography is a rapid, easy-to-use tool that can help differentiate Ta and T1 tumors and identify muscle-invasive bladder tumors. It provides real-time microarchitectural information that can aid in the evaluation of bladder tumors and adjacent and remote urothelium.
Purpose:
To determine the diagnostic efficacy of optical coherence tomography (OCT) to identify cervical intraepithelial neoplasia (CIN) grade 2 or higher by computer-aided diagnosis (CADx).
Methods:
...OCT has been investigated as a screening/diagnostic tool in the management of preinvasive and early invasive cancers of the uterine cervix. In this study, an automated algorithm was developed to extract OCT image features and identify CIN 2 or higher. First, the cervical epithelium was detected by a combined watershed and active contour method. Second, four features were calculated: The thickness of the epithelium and its standard deviation and the contrast between the epithelium and the stroma and its standard deviation. Finally, linear discriminant analysis was applied to classify images into two categories: Normal/inflammation/CIN 1 and CIN 2/CIN 3. The algorithm was applied to 152 images (74 patients) obtained from an international study.
Results:
The numbers of normal/inflammatory/CIN 1/CIN 2/CIN 3 images are 74, 29, 14, 24, and 11, respectively. Tenfold cross-validation predicted the algorithm achieved a sensitivity of 51% (95% CI: 36%–67%) and a specificity of 92% (95% CI: 86%–96%) with an empirical two-category prior probability estimated from the data set. Receiver operating characteristic analysis yielded an area under the curve of 0.86.
Conclusions:
The diagnostic efficacy of CADx in OCT imaging to differentiate high-grade CIN from normal/low grade CIN is demonstrated. The high specificity of OCT with CADx suggests further investigation as an effective secondary screening tool when combined with a highly sensitive primary screening tool.
Determine the sensitivity and specificity of optical coherence tomography (OCT) as an adjunct to colposcopy in the detection of cervical intraepithelial neoplasia (CIN) grade 2 or higher in a ...real-time clinical evaluation.
Optical coherence tomography (OCT) uses infrared light similar to ultrasound pulse-echo imaging. Image resolution is optimal in the 1-to-3-mm range. This study is the third in our series of OCT investigations and our first real-time clinical trial. The study was conducted at the Peking University Shenzhen Hospital, Shenzhen, China.
Nonpregnant women 18 years or older with abnormal cervical cytologic findings or a positive high-risk human papillomavirus test result were recruited. Women were assessed; and diagnoses, recorded by cervical quadrant first with colposcopy, followed by colposcopic directed OCT. A biopsy of the abnormal areas was performed. In normal quadrants, biopsy specimens were obtained at the 2-, 4-, 8-, and 10-o'clock positions at the squamocolumnar junction depending on the quadrant. An endocervical curettage was also done. Individual OCT diagnoses were paired with colposcopic impressions and biopsy specimens to assess its role as a paired secondary screen. Data were analyzed using generalized estimating equations to control for correlation within a woman.
One thousand two hundred thirty-seven paired diagnoses from 299 women were analyzed. Median age was 36 years. Ninety-six women (8%) had a diagnosis of CIN 2 or higher. Evaluation by quadrant showed that the sensitivity for CIN 2 or higher decreased by adding OCT to colposcopy, but the specificity increased from 83% to 93%.
We continue to try to improve sensitivity by improving the near-infrared light source, decreasing the scan time to 8 frames per second, and using a larger diameter (5 mm) fiberoptic probe with a newly designed application specific probe sheath.
To determine the sensitivity and specificity of optical coherence tomography (OCT) as an adjunct to unaided visual inspection using acetic acid (VIA) in the detection of cervical intraepithelial ...neoplasia 2 (CIN 2) in a real-time clinical evaluation.
This clinical study was a prospective cross-sectional comparative trial that screened 1000 patients (aged 30-50 years) in a low-resource setting. Women with abnormal cervical cytology or positive human papillomavirus (HPV) tests were referred for further evaluation including VIA, OCT imaging, colposcopy, and cervical biopsies.
The VIA diagnoses were coded by quadrant. The OCT was then performed in all VIA-positive areas and at the squamocolumnar junction in all 4 quadrants. All patients were colposcoped; assessed by quadrant with biopsies at 2, 4, 8, and 10 o'clock; all abnormal areas were biopsied; and endocervical curettage was performed. Data were analyzed using generalized estimating equations and logistic regression.
Of the 1000 patients, 175 (17.5%) were HPV positive, 93 (9.3%) had abnormal cervical cytology greater than or equal to atypical squamous cells of undetermined significance, and 211 (21.1%) were either HPV positive or had abnormal cytology. The VIA, OCT, colposcopy, and biopsies were completed on 183 (86.7%) of 211 women. For VIA alone, the sensitivity and specificity in detecting lesions greater than or equal to CIN 2 was 43% and 96%. With the addition of OCT, the sensitivity increases to 62% with a specificity of 80%.
With the addition of OCT, the sensitivity of VIA increased in all analyses for the detection of greater than or equal to CIN II, with a loss in specificity. We hope that the potential of this technology will be realized when a computer algorithm is generated to aid in image interpretation.
Sympathetic neurons innervating sweat glands undergo a target-directed developmental switch in neurotransmitter properties. Using cultured sympathetic neurons as a bioassay for cholinergic ...differentiation factors, we and others found that extracts containing soluble proteins from developing and adult footpads caused the same changes in transmitter properties in sympathetic neurons
in vitro that the target does
in vivo. In the present studies, using footpads from
Tabby mutant mice that lack sweat glands, we found that the presence of sweat glands is correlated with the presence of cholinergic differentiation activity in footpad extracts. We examined the conditions necessary for secretion of differentiation activity from primary cultures of sweat gland cells. Surprisingly, sweat gland cells cultured alone do not produce or secrete cholinergic differentiation activity. When grown in the presence of sympathetic neurons, however, gland cells induce cholinergic function, increase vasoactive intestinal peptide content, and reduce catecholamine production in the neurons. Medium conditioned by sweat gland/neuron cocultures has a similar effect on the transmitter properties of cultured sympathetic neurons, indicating that the target influence on phenotype is mediated by a secreted factor(s). The innervation-dependence of cholinergic differentiation factor production provides evidence that reciprocal interactions between neurons and sweat glands are necessary for acquisition of the mature transmitter phenotype.
Sympathetic neurons innervate the heart early in postnatal development, an event that is crucial for proper modulation of blood pressure and cardiac function. However, the axon guidance cues that ...direct sympathetic neurons to the heart, and the neuronal receptors that recognize those cues, are poorly understood. Here we present evidence that interactions between the alpha4beta1 integrin on sympathetic neurons and vascular cell adhesion molecule-1 (VCAM-1) in the heart plays a role in cardiac innervation. The alpha4 subunit was detected on postnatal rat superior cervical ganglion (SCG) neurons in culture and in cryosections of SCG and heart. VCAM-1 immunoreactivity was detected on cardiac myocytes that associate with invading sympathetic neurons. Purified recombinant soluble VCAM-1 (rsVCAM-1) stimulated SCG neurite outgrowth at levels comparable with laminin 2/4 and fibronectin (Fn), and outgrowth on rs-VCAM-1 and Fn was blocked by antibodies specific for the alpha4 and beta1 integrin subunits. Intrathoracic injection of function-blocking antibodies to alpha4 and VCAM-1, as well as a small molecule inhibitor of alpha4 integrins, significantly reduced sympathetic innervation of the heart. These results indicate that the interaction between alpha4 integrin and VCAM-1 is important for sympathetic innervation of the heart.
Experimental allergic encephalomyelitis (EAE) was induced in the NIH minipig to create a large animal model of multiple sclerosis with a well-characterized immune system. Sixteen NIH minipigs were ...inoculated with minipig spinal cord homogenate (SCH). The clinical course was primarily monophasic, but re-induction was possible. CNS and blood lymphocytes specifically proliferated to SCH. Flow cytometry of CNS-isolated cells and SCH-stimulated PBMC revealed a shift to CD4
+ CD8
+ cells. Pathology demonstrated demyelination in the CNS white matter with perivascular mononuclear cell infiltrates of CD3
+CD4
+CD45
+ lymphocytes with a subset CD8
+. Pathology and in vitro SCH responses implicate a central role of CD4
+ lymphocytes in swine EAE.
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