Cervical epithelial brightness by optical coherence tomography can determine histological grades of cervical neoplasia.

Objective: The study aimed to determine if the difference in cervical epithelium brightness, as measured by optical coherence tomography (OCT), has potential as a distinguishing characteristic of normal, low-grade, high-grade (cervical intraepithelial neoplasia 2+), and cancer histological findings.

Materials And Methods: Information from 476 women was available for analysis. Demographic information was collected through in-person interview.

Diagnostic efficacy of computer extracted image features in optical coherence tomography of the precancerous cervix.

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.

Study of the diagnostic efficacy of real-time optical coherence tomography as an adjunct to unaided visual inspection with acetic acid for the diagnosis of preinvasive and invasive neoplasia of the uterine cervix.

Objectives: 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.

Background: 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.

Diagnostic efficacy of real-time optical coherence tomography in the management of preinvasive and invasive neoplasia of the uterine cervix.

Objective: 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.

Background: Optical coherence tomography (OCT) uses infrared light similar to ultrasound pulse-echo imaging. Image resolution is optimal in the 1-to-3-mm range.

Optical coherence tomography as an adjunct to white light cystoscopy for intravesical real-time imaging and staging of bladder cancer.

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 microm). The purpose of this study was to examine the application of OCT in augmenting the diagnosis and staging of bladder lesions.

Images of spinal nerves and adjacent structures with optical coherence tomography: preliminary animal studies.

Unlabelled: Multiple complications have been reported with spinal intervertebral transforaminal injection procedures, despite the use of fluoroscopic needle-positioning measures. We explored an imaging technology (optical coherence tomography, or OCT) for its possible use in spine interventional procedures as a means of providing needle tip vision at the neuroforamen. Optical coherence tomography is the B-mode optical analog of ultrasound.

Optical coherence tomography as a diagnostic aid to visual inspection and colposcopy for preinvasive and invasive cancer of the uterine cervix.

The purpose of this study was to determine the sensitivity and specificity of optical coherence tomography (OCT) under two well-defined clinical settings. First, as an aid to cervical cancer screening, using visual inspection with acetic acid (VIA) in low-resource settings, and the second, as an adjunct to the traditional management of abnormal cervical cytology with colposcopy and biopsy. Patients referred for colposcopy with > or = atypical squamous cells of undetermined significance were accrued for the study.

Severity of neurodegeneration correlates with compromise of iron metabolism in mice with iron regulatory protein deficiencies.

In mammals, iron regulatory proteins 1 and 2 (IRP1 and IRP2) posttranscriptionally regulate expression of several iron metabolism proteins including ferritin and transferrin receptor. Genetically engineered mice that lack IRP2, but have the normal complement of IRP1, develop adult-onset neurodegenerative disease associated with inappropriately high expression of ferritin in degenerating neurons. Here, we report that mice that are homozygous for a targeted deletion of IRP2 and heterozygous for a targeted deletion of IRP1 (IRP1+/- IRP2-/-) develop a much more severe form of neurodegeneration, characterized by widespread axonopathy and eventually by subtle vacuolization in several areas, particularly in the substantia nigra.

Vascular endothelial growth factor is expressed in multiple sclerosis plaques and can induce inflammatory lesions in experimental allergic encephalomyelitis rats.

The active lesions in multiple sclerosis (MS) are characterized by blood-brain-barrier (BBB) breakdown, upregulation of adhesion molecules on capillary endothelial cells, and perivascular inflammation, suggesting that altered vessel permeability and activated endothelial cells are involved in the pathogenesis of the disease. Vascular endothelial growth factor (VEGF) mediates multiple aspects of blood vessel physiology, including regulation of growth, permeability, and inflammation. To investigate a possible relationship between VEGF expression and CNS autoimmune disease, we examined VEGF expression in MS plaques compared to normal white matter by immunohistochemistry and in situ hybridization.

Frontotemporal dementia: report of a familial case.

The authors describe a 49-year-old woman (R.K.) who presented with one year of progressive frontal lobe dysfunction, including signs of expressive aphasia.

Structural abnormalities develop in the brain after ablation of the gene encoding nonmuscle myosin II-B heavy chain.

Ablation of nonmuscle myosin heavy chain II-B (NMHC-B) in mice results in severe hydrocephalus with enlargement of the lateral and third ventricles. All B(-)/B(-) mice died either during embryonic development or on the day of birth (PO). Neurons cultured from superior cervical ganglia of B(-)/B(-) mice between embryonic day (E) 18 and P0 showed decreased rates of neurite outgrowth, and their growth cones had a distinctive narrow morphology compared with those from normal mice.

Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice.

In mammalian cells, regulation of the expression of proteins involved in iron metabolism is achieved through interactions of iron-sensing proteins known as iron regulatory proteins (IRPs), with transcripts that contain RNA stem-loop structures referred to as iron responsive elements (IREs). Two distinct but highly homologous proteins, IRP1 and IRP2, bind IREs with high affinity when cells are depleted of iron, inhibiting translation of some transcripts, such as ferritin, or turnover of others, such as the transferrin receptor (TFRC). IRPs sense cytosolic iron levels and modify expression of proteins involved in iron uptake, export and sequestration according to the needs of individual cells.

Effective antigen-specific immunotherapy in the marmoset model of multiple sclerosis.

Mature T cells initially respond to Ag by activation and expansion, but high and repeated doses of Ag cause programmed cell death and can suppress T cell-mediated diseases in rodents. We evaluated repeated systemic Ag administration in a marmoset model of experimental allergic encephalomyelitis that closely resembles the human disease multiple sclerosis. We found that treatment with MP4, a chimeric, recombinant polypeptide containing human myelin basic protein and human proteolipid protein epitopes, prevented clinical symptoms and did not exacerbate disease.

Targeting dipeptidyl peptidase IV (CD26) suppresses autoimmune encephalomyelitis and up-regulates TGF-beta 1 secretion in vivo.

CD26 or dipeptidyl peptidase IV (DP IV) is expressed on various cell types, including T cells. Although T cells can receive activating signals via CD26, the physiological role of CD26/DP IV is largely unknown. We used the reversible DP IV inhibitor Lys[Z(NO(2))]-pyrrolidide (I40) to dissect the role of DP IV in experimental autoimmune encephalomyelitis (EAE) and to explore the therapeutic potential of DP IV inhibition for autoimmunity.

Dipeptidyl peptidase IV in inflammatory CNS disease.

Current pathogenic concepts of inflammatory demyelinating disorders such as multiple sclerosis (MS) are based on the hypothesis that a T cell-mediated autoimmune response is involved in the disease process. One of the primary goals in the in the development of immunotherapies for autoimmune diseases has been to achieve inactivation of disease-inducing lymphocytes either by direct inhibition or suppression through regulatory cells and/or cytokines. The CD26 antigen is identical with the cell surface ectopeptidase dipeptidyl peptidase IV (DP IV, EC 3.

Biophysical characterization of gp41 aggregates suggests a model for the molecular mechanism of HIV-associated neurological damage and dementia.

In human immunodeficiency virus (HIV)-infected individuals, the level of the HIV envelope protein gp41 in brain tissue is correlated with neurological damage and dementia. In this paper we show by biochemical methods and electron microscopy that the extracellular ectodomain of purified HIV and simian immunodeficiency virus gp41 (e-gp41) forms a mixture of soluble high molecular weight aggregate and native trimer at physiological pH. The e-gp41 aggregate is shown to be largely alpha-helical and relatively stable to denaturants.

Induction of experimental allergic encephalomyelitis in the NIH minipig.

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.

Gene dosage affects the cardiac and brain phenotype in nonmuscle myosin II-B-depleted mice.

Complete ablation of nonmuscle myosin heavy chain II-B (NMHC-B) in mice resulted in cardiac and brain defects that were lethal during embryonic development or on the day of birth. In this paper, we report on the generation of mice with decreased amounts of NMHC-B. First, we generated B(DeltaI)/B(DeltaI) mice by replacing a neural-specific alternative exon with the PGK-Neo cassette.

Analysis of gene expression in mutiple sclerosis lesions using cDNA microarrays.

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.

Serial MR imaging of experimental autoimmune encephalomyelitis induced by human white matter or by chimeric myelin-basic and proteolipid protein in the common marmoset.

Background And Purpose: Experimental autoimmune encephalomyelitis (EAE) in the marmoset was monitored by serial MR imaging to determine correlates to the natural-history MR studies in multiple sclerosis (MS). The relationships of MR-revealed lesions to clinical status and histopathologic findings were also explored.

Methods: We induced EAE by subcutaneous inoculation in two marmosets by human white matter (HWM) and in seven marmosets by MP4 (a chimeric recombinant fusion protein of myelin-basic and proteolipid protein) in adjuvant along with intravenous inactivated pertussis vaccine to facilitate the disease process.

Costimulatory markers in muscle of patients with idiopathic inflammatory myopathies and in cultured muscle cells.

In an attempt to understand the mechanisms of cell injury in the inflammatory myopathies, we analyzed the expression of costimulatory molecules, CTLA4, CD28, CD86, CD40, and CD154 as well as HLA class I, HLA class II, and ICAM-I in normal muscle and in muscle biopsies from patients with polymyositis (PM) or dermatomyositis (DM). By immunohistochemical staining, DM and PM biopsies showed the presence of CTLA4, CD28, CD86, and CD40 on inflammatory cells. More strikingly, however, low levels of CTLA4 and CD28 were observed on muscle cells.

Extrapituitary parasellar microadenoma in Cushing's disease.

Negative sellar exploration (despite the results of endocrine evaluation indicating Cushing's disease), the high incidence of failure of total hypophysectomy, and remission of Cushing's syndrome after unsuccessful hypophysectomy and sellar irradiation suggest that the etiology of refractory Cushing's disease, in some patients, lies near the sella but not in the pituitary gland. We present 5 patients, out of 626 who received surgery for Cushing's disease, in whom an ACTH-secreting extrapituitary parasellar adenoma was identified: 2 after unsuccessful total hypophysectomy for the treatment of refractory Cushing's disease, 2 after unsuccessful hemihypophysectomy (the first, 2 yr before treatment at the NIH for Nelson's syndrome; and the second, with recurrent Cushing's disease 5 yr after negative transsphenoidal exploration), and 1 with a preoperative diagnosis of an intraclival microadenoma, which was cured by resection of the tumor. In all cases, an extrapituitary parasellar microadenoma was confirmed unequivocally as the cause of the disease, by negative pathology of the resected pituitary gland (patients 1, 2, 3, and 5), and/or the remission of the disease after selective resection of the extrasellar adenoma (patients 3, 4, and 5).

Determinant spreading associated with demyelination in a nonhuman primate model of multiple sclerosis.

Definition of the immune process that causes demyelination in multiple sclerosis is essential to determine the feasibility of Ag-directed immunotherapy. Using the nonhuman primate, Callithrix jacchus jacchus (common marmoset), we show that immunization with myelin basic protein and proteolipid protein determinants results in clinical disease with significant demyelination. Demyelination was associated with spreading to myelin oligodendrocyte glycoprotein (MOG) determinants that generated anti-MOG serum Abs and Ig deposition in central nervous system white matter lesions.

The effect of interferon and anti-CD44 antibody on mouse glioma invasiveness in vitro.

In this study the effect of interferon and anti-CD44 antibody on the invasiveness of mouse glioma G-26 cells was evaluated. We confirmed the glial nature of G-26 glioma cells (G-26) in vitro and in vivo using immunohistochemistry: G-26 stained strongly for S-100 and stained weakly for glial fibrillary acidic protein (GFAP). Immunohistochemical evaluation for CD44 adhesion molecule showed that G-26 was positive both in vitro and in vivo.

Alpha synuclein is present in Lewy bodies in sporadic Parkinson's disease.

A missense mutation in the human alpha synuclein gene was recently identified in some cases of familial Parkinson's disease (FPD). We have developed an antibody that recognizes the C-terminal 12 amino acids of the human alpha synuclein protein and have demonstrated that alpha synuclein is an abundant component of the Lewy bodies found within the degenerating neurons of patients with Parkinson's disease (PD). The presence of alpha synuclein in Lewy bodies of sporadic PD patients suggests a central role for alpha synuclein in the pathogenesis of PD.