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J S Ross

Publications and source records attributed to J S Ross.

At least 19 recordsLinked to original sources

Deregulated alternative splicing of CD44 messenger RNA transcripts in neoplastic and nonneoplastic lesions of the human thyroid.

CD44 is a polymorphic family of immunologically related cell surface proteoglycans and glycoproteins implicated in cell-cell and cell-matrix adhesion interactions, lymphocyte activation and homing, cell migration, and tumor metastasis. CD44 exists as a standard form and as multiple isoforms, each generated by alternative splicing of up to 10 variant exons (termed v1-v10) encoding parts of the extracellular domain. Using semiquantitative reverse transcriptase-PCR and Southern hybridization, alternative CD44 mRNA splicing was examined in 10 papillary thyroid carcinomas, 8 nodular goiters, 9 adenomas, 2 cases of thyroiditis, and 3 histologically normal thyroid controls. The amount of input cDNA for the CD44 PCRs was standardized against an internal control gene (glyceraldehyde phosphate dehydrogenase). Four papillary carcinomas showed significant overexpression of CD44 transcripts migrating between 750 and 1000 bp. These cases demonstrated reduced levels of the 482-bp standard isoform transcript. In six papillary cancers, we found a prominent v6-containing isoform at 750 bp that was present in only trace amounts in normal thyroid tissue. It is of interest that similar findings were seen in the majority of the goiters and adenomas but not in the cases of thyroiditis. These results show that deregulation of alternative CD44 splicing is a common feature of disordered thyroid follicular cell growth, both in neoplastic and nonneoplastic lesions. The data imply an important role for CD44, including CD44v6, in the pathogenesis of various thyroid lesions.

Adenocarcinoma, Papillary

Interobserver and intraobserver variability in interpretation of lumbar disc abnormalities. A comparison of two nomenclatures.

STUDY DESIGN: A double-blind prospective study was used to measure interobserver and intraobserver variability when interpreting lumbar spine magnetic resonance imaging studies of disc abnormalities. OBJECTIVES: To evaluate reader consistency when interpreting disc extension beyond the interspace, and assess the effect of two distinct nomenclatures on reader consistency. SUMMARY OF BACKGROUND DATA: Interobserver and intraobserver variability in interpretation of lumbar disc abnormalities is an important consideration in analyzing the technical efficacy of an imaging modality. However, this has not been well measured (particularly for standardized nomenclature). METHODS: Magnetic resonance imaging studies of the lumbar spine performed prospectively in 98 asymptomatic volunteers, and an additional 27 selected studies from symptomatic patients, were read blindly by two experienced neuroradiologists, using two separate nomenclatures. Only the discs were evaluated (625 interspaces). Nomenclature I was normal, bulge, herniation. Nomenclature II was normal, bulge, protrusion, extrusion. Intraobserver and interobserver variation were measured with Kappa statistic analysis. RESULTS: Interobserver agreement was 80% for both nomenclatures with a Kappa statistic of 0.58. Intraobserver agreement was 86% for each reader, with a Kappa statistic of 0.71 and 0.69, respectively. The most common disagreement was for normal versus bulge. The next most common disagreement (5-6%) was for bulge versus herniation (or protrusion in Nomenclature II). Herniation was read in 23% of the asymptomatic subjects. Using Nomenclature II, protrusion was seen in 27% of these subjects. Extrusion was read in only two asymptomatic subjects. CONCLUSIONS: Experienced readers using standardized nomenclature showed moderate to substantial agreement with interpreting disc extension beyond the interspace on magnetic resonance imaging.

Adult

Three-dimensional magnetic resonance techniques for evaluating the cervical spine.

The general technique of three-dimensional magnetic resonance imaging is briefly described, as is a variety of specific three-dimensional sequences useful in the evaluation of spinal disease, particularly related to degenerative disc disease. Advantages of three-dimensional imaging include an increase in signal-to-noise ratio, thin contiguous slices, more accurate slice thickness, and a reduction in susceptibility artifacts. Computer post-processing allows reformatting of the data along any desired imaging plane, with minimal degradation in image quality.

Cervical Vertebrae

Fish oil, atherogenesis, and thrombogenesis.

Marine fish consumption is known to reduce mortality from ischemic heart disease. The use of fish oil as a dietary supplement, however, is not universally recommended. In large doses, fish oil reduces plasma cholesterol and triacylglycerol but increases low density lipoprotein (LDL) levels and the potential for free radical generation and bleeding. Moderate marine fish consumption is known to reduce mortality without altering commonly measured variables, i.e., plasma cholesterol levels, in vitro platelet aggregation, and bleeding times. In swine, we observed that monocyte adhesions and platelet clumps over the lesion surface of proximal left anterior descending (LAD) coronary arteries are markedly reduced when an atherogenic diet was supplemented with cod-liver oil, even when the cholesterol levels were equalized with the untreated group. These findings suggest that fish oil is hypothrombogenic. We developed an in vitro assay to delineate the mechanism whereby fish oil reduced monocyte-endothelial cell interactions in vivo. The effects of supplementing the culture medium with different fatty acids on adhesions between lipopolysaccharide (LPS) stimulated swine aortic endothelial cells (SAEC) and the human monocyte-like cell line, U937, was investigated in a 10 minute adhesion assay at 37 degrees C. Exposure of SAEC for 6 hours to media containing 50-200 microMs eicosapentaenoic (EPA), stearic, oleic, linoleic, and arachidonic acid, respectively, revealed that only EPA reduced U937-SAEC adhesion. Exposure of U937 to EPA also reduced adhesions. EPA was not effective when added to the SAEC more than 2 hours after they were stimulated with LPS. Exposure of human umbilical vein endothelial cells (HUVEC) to EPA reduced the expression of VCAM-1, ELAM-1, and ICAM-1 after 5 hours of stimulation with LPS. These results suggest that EPA may functionally impair the induction/expression of adhesion molecules.

Animals

E-cadherin expression in papillary transitional cell carcinoma of the urinary bladder.

E-cadherin (E-CD), a cell adhesion molecule that plays a diverse role in cell-cell and cell-matrix interaction, has recently been associated with tumor invasion and metastasis. We evaluated the E-CD expression in 55 cases of urinary bladder papillary transitional cell carcinoma using a double-linked immunoalkaline phosphatase procedure on formalin-fixed, paraffin-embedded specimens quantified as percentage positive staining area with the Roche RPW image analyzer (Roche Image Analysis Systems, Elon College, NC). The 10 grade I tumors stained intensely for E-CD (66%) and showed enhanced staining compared with normal transitional epithelium. The 20 grade II lesions stained moderately at 45%, and the 25 grade III lesions showed weak expression of E-CD with a 33% positive stain. This loss of expression for high-grade versus low-grade tumors was statistically significant (P < .02). There was a similar decrease in E-CD expression for high-stage versus low-stage specimens with 30 stage 0 and stage A cases having an average of 51% positive stain and 25 stage B, C, and D cases having an average stain of 33%. This difference was also statistically significant (P < .001). We conclude that loss of expression of E-CD in high-grade, high-stage urinary bladder transitional cell carcinoma is associated with significant bladder wall invasion, indicates potential for metastasis, and may be of clinical value in the assessment of prognosis and planning of therapy for patients with bladder tumors.

Adult

Quantitative immunohistochemical determination of cathepsin D levels in prostatic carcinoma biopsies. Correlation with tumor grade, stage, PSA level, and DNA ploidy status.

National screening programs resulting in an increased detection rate of prostatic adenocarcinoma have prompted the search for new methods of predicting disease outcome that can be applied to the initial narrow bore needle biopsy specimens. Cathepsin D, a lysosomal aspartyl protease and autocrine mitogen, has been studied in a wide variety of human neoplasms as an invasion and metastasis marker. Prostatic carcinoma needle biopsy tumor cell cathepsin D content was measured in 61 men using a semiquantitative image analysis assisted immunohistochemical procedure. Results were compared with preoperative serum prostatic specific antigen levels, tumor grade, DNA ploidy status, pathologic stage after radical prostatectomy and disease recurrence during a median 2.6 year follow-up. Biopsy cathepsin D levels significantly correlated with tumor grade (P = .022) and DNA ploidy status (P = .028) by logistic regression analysis. Post-prostatectomy pathologic stage and disease recurrence did not correlate with tumor cathepsin D levels. Final prostatectomy grade and DNA ploidy status independently predicted metastasis and post-operative disease recurrence (P < .001). Although this study did not find independent prognostic status for cathepsin D in prostate cancer, the correlation with tumor grade and DNA ploidy status is noteworthy and the inter-relationship of outcome variables may prove of interest and warrant further evaluation of this potential predictor or CO-predictor of disease outcome.

Adenocarcinoma

Contact and photocontact sensitization in chronic actinic dermatitis: sesquiterpene lactone mix is an important allergen.

Eighty-nine patients with chronic actinic dermatitis (CAD) were retrospectively studied: 69 (78%) male and 20 (22%) female, with mean ages of 66 and 64 years, respectively; nine (10%) were dark skinned. Eight (9%) were abnormally sensitive to UVB wavelengths alone, 74 (83%) to UVB and UVA, and seven (8%) to UVB, UVA and visible radiation. Eighty-six patients were patch tested to an extended standard European series of contact allergens, including in 80 cases a 0.1% mix of three sesquiterpene lactones, and photopatch tested to a standard photopatch series. Sixty-four of these 86 patients (74%) had positive patch or photopatch tests; 36% (29 of 80) were sensitive to the sesquiterpene lactone mix, 21% (18 of 86) to fragrance compounds, 20% (17 of 86) to colophony, and 14% (12 of 86) to rubber chemicals. Ten (12%) had positive photopatch tests; five (6%) to musk ambrette, six (7%) to sunscreens and one to both. Fourteen of the eighty-nine patients with CAD (16%) had preceding endogenous eczema. In 18 of 86 patients (21%), CAD occurred alone, with neither detectable contact nor photocontact allergy, nor a preceding history of endogenous eczema. This study confirms the association between Compositae (sesquiterpene lactone) dermatitis and CAD.

Aged

Contrast-enhanced MR imaging in acute lumbar radiculopathy: a pilot study of the natural history.

PURPOSE: To prospectively study clinical findings and contrast material-enhanced magnetic resonance (MR) images over time in patients with acute lumbar radiculopathy. MATERIALS AND METHODS: Twenty-five patients underwent physical examination and MR imaging at presentation, 6 weeks, and 6 months. Initial symptoms and clinical course were correlated with type, size, location, and enhancement of disk herniations. RESULTS: Eighteen patients had a herniated nucleus pulposus (HNP) at one or more levels, two had synovial cysts and stenosis, and five had normal findings. Patients with an HNP had marginally more severe neurologic symptoms than did patients without an HNP (P = .07) at presentation. Twenty-two patients completed the 6-week examinations and 14 patients the 6-month examinations; three patients were eliminated from the study after surgical treatment. Among HNPs larger than 6 mm, substantial reduction in size was noted in 36% at 6 weeks and in more than 60% at 6 months after presentation. CONCLUSION: Agreement between clinical and MR findings for level and side of HNP and radicular symptoms was excellent. There was no correlation of pain and disability with disk size, behavior, or type.

Acute Disease

Hyperintense disks on T1-weighted MR images: correlation with calcification.

PURPOSE: To determine if calcification in the intervertebral disk is associated with hyperintensity on T1-weighted spin-echo magnetic resonance (MR) images. MATERIALS AND METHODS: Sagittal T1-weighted MR images that showed one or more hyperintense intervertebral disks and correlative computed tomographic (CT) scans, plain radiographs, or both, were obtained in 11 patients retrospectively and in 43 patients prospectively. Six patients underwent MR imaging with a fat-suppression technique. Histologic analysis of two disks was performed. RESULTS: Absence of calcification was associated with disks that were isointense relative to normal disks (P < .001), mild to moderate calcification was associated with hyperintense disks (P < .001 and P = .004 [two readers]), and both mild to moderate and marked calcifications were associated with hypointense disks (P < .001). Fat suppression resulted in a decrease in hyperintense signal in two patients. CONCLUSION: The results indicate that hyperintensity is associated with calcification. In the absence of clinical findings that suggest other causes, hyperintense disks are suggestive of degenerative disk disease.

Adult

Image analysis quantification in hormone receptor assay of mucinous carcinoma of the breast. Comparison with biochemical analysis.

Mucinous carcinoma (MC) of the breast is characterized by abundant extracellular mucin and by variable epithelial cellularity. Since some MCs are extremely hypocellular, we questioned the validity of biochemical (BIO) assays in these tumors. We analyzed paraffin-embedded tissue from 34 cases of MC of the breast for quantitative estrogen receptor (ER) and progesterone receptor (PR) using immunohistochemistry (IHC) on the Cell Analysis System CAS-200. Of the 34 cases, 31 (91%) were positive for ER, whereas 18 (53%) were positive for PR. In 21 cases the quantitative ER and PR were assayed biochemically by a dextran-coated charcoal method. Using the BIO results as the "true" values, the sensitivity of IHC for ER and PR was 100% and 78%, and the specificity was 13% and 64%, respectively. The low specificity of the values obtained by IHC was attributed to the fact that eight cases were "falsely" false positive (negative by BIO and positive by IHC) for ER and/or PR. Review of the histologic patterns of all 21 cases showed that 7 of the 8 falsely false positive cases were significantly hypocellular (epithelial cellularity 5-20%) as compared to the remaining cases (epithelial cellularity 20-75%). We conclude that immunohistochemical analysis of ER/PR status using image analysis in MC is a sensitive method, with the ability to detect receptor content when their concentration might be too low to be demonstrated by the conventional method as a result of sparse cellularity.

Adenocarcinoma, Mucinous

Myelopathy.

Myelitis and myelopathy may be caused by numerous ideologies, such as neoplastic, inflammatory, metabolic, infectious, and physical agents. Cervical spondylitic myelopathy, a spectrum of degenerative change occurring in the cervical spine, is the most common cause of cord dysfunction in patients more than 50 years of age. A variety of ideologies of myelopathy and imaging features are presented in this article.

Humans

p53 gene status in endometrial carcinomas showing diffuse positivity for p53 protein by immunohistochemical analysis.

Although detection of p53 protein by immunohistochemical testing was originally thought to indicate p53 gene mutation, recent analyses of human malignancies have shown that high expression of p53 protein may occur without detectable gene mutation. Several explanations have been proposed for this phenomenon, including mutation out of "hot spot" regions, overexpression of wild-type protein, sampling error in molecular analyses, and conformational changes of wild-type p53 protein. As discussed, it is unlikely that the first two possibilities contribute significantly to the occurrence of this phenomenon, and the current study examined the possibility that sampling error in molecular analyses might account for a lack of concordance between immunohistochemical and molecular analyses. Such a possibility exists because immunohistochemical studies frequently report high expression when staining is only focal or regional and molecular analyses are based on the polymerase chain reaction, which is highly exponential in nature and may not detect mutation if the target gene segment is not amplified early in the chain reaction. In the current report, p53 protein expression was examined by immunohistochemical testing in 45 cases of endometrioid carcinoma, and all cases showing diffuse positivity were then examined by polymerase chain reaction in combination with single-strand conformational analysis for exons 4 to 9 with the use of a microdissection technique to separate malignant from benign cells. Of the 45 cases, diffuse staining was found in four cases, and only two of the four were found to show evidence of gene mutation.(ABSTRACT TRUNCATED AT 250 WORDS)

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