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Biomedical subjects

C R Taylor

Publications and source records attributed to C R Taylor.

At least 109 records · Page 6Linked to original sources
PubMed1995

Characterization of focal hepatic lesions with duplex sonography: findings in 198 patients.

OBJECTIVE: The purpose of this study was to determine the value of duplex Doppler sonography in the characterization of focal hepatic lesions. SUBJECTS AND METHODS: Duplex Doppler sonography with a 3-MHz transducer was performed prospectively on 198 patients with focal hepatic lesions. One hundred thirty-two patients had pathologically proved diagnoses, confirming 46 hepatomas and 86 metastatic lesions. Twenty-three hemangiomas were confirmed either with tissue, tagged RBC study, MR imaging, or hemangioma CT protocol. Forty-three patients with no history of cancer had benign lesions that were established on the basis of follow-up imaging and at least a 2-year clinical history with no evidence of cancer. RESULTS: Thirty-two hepatomas and four metastatic lesions had Doppler shifts of 4.5 kHz or more, giving a 70% sensitivity, 95% specificity, and 89% positive predictive value in distinguishing hepatomas from metastatic lesions. Forty-three hepatomas, 47 metastatic lesions, one hemangioma, and three benign lesions had Doppler shifts of 1.75 kHz or more, giving a 68% sensitivity, 94% specificity, and 96% positive predictive value in distinguishing malignant from benign lesions. Doppler shifts (mean +/- SD) were as follows: hepatomas, 4.72 +/- 1.72 kHz; metastases, 1.99 +/- 1.63 kHz; and hemangiomas, 0.53 +/- 0.75 kHz. These differences in mean Doppler shifts were statistically significant (p < .0001). CONCLUSION: Duplex Doppler sonography aids in distinguishing hepatomas from metastases and malignant from benign hepatic lesions with a high degree of specificity but low sensitivity.

Adult↗
PubMed1994

"Metabolic switch" for desert survival.

Food, like water, is in short supply in the desert. We report a specialized mechanism used by a desert mouse for surviving prolonged food shortages. The key element of this adaptation is a large reduction in resting metabolism. After about 2 weeks of restricted food intake (50% of normal), the desert mouse "switched down" its resting metabolism and was able to survive and maintain its weight indefinitely on these limited rations. When food was again freely available, resting metabolism "switched up," returning to normal levels in a single day. The reduced metabolism occurred without a decrease in body temperature or in levels of activity. In marked contrast, metabolism of the laboratory white mouse increased during food restriction, and the experiments had to be terminated to avoid starvation. We think this "metabolic switch" is common among desert mammals. It may be an amplification of a general metabolic response for coping with food scarcity common to all mammals, including humans.

Adaptation, Physiological↗
PubMed1994

Strategies for improving the immunohistochemical staining of various intranuclear prognostic markers in formalin-paraffin sections: androgen receptor, estrogen receptor, progesterone receptor, p53 protein, proliferating cell nuclear antigen, and Ki-67 antigen revealed by antigen retrieval techniques.

Different variations of the antigen retrieval technique using different retrieval solutions have been evaluated for their effectiveness in restoring the antigenicity of six intranuclear antigens, each of which is a potentially valuable prognostic indicator in formalin-fixed, paraffin-embedded tissue sections. The results of immunohistochemical staining for estrogen receptor, progesterone receptor, androgen receptor, p53 protein, proliferating cell nuclear antigen, and Ki-67 antigen were compared following the different antigen retrieval approaches. The strongest immunostaining signal with the clearest background was obtained by microwave heating of dewaxed paraffin sections for 10 minutes in 0.05 mol/L glycine HCl (pH 3.5) or in citrate buffer solution (pH 6). Urea solution, distilled water, and lead thiocyanate solution yielded improvements with some antigens, but less consistently and less impressively than glycine HCl buffer or citrate buffer. Following antigen retrieval nuclear staining was sharply defined and could be achieved consistently in a variety of tissues after formalin fixation for as long as 7 days. The duration of fixation, however, was an important variable; generally, the longer the fixation time the more vigorous the retrieval procedure required. This study demonstrates the ability to stain a variety of intranuclear antigens, which are not readily demonstrable otherwise, in formalin-paraffin sections with a high degree of consistency and reproducibility. The availability of methods that are effective in paraffin sections may facilitate studies of the possible value of these markers as prognostic indicators for predicting the response of major tumors to different forms of therapy. This study also provided insight into the basic principles of the antigen retrieval method, which may be helpful in attempts to develop a more uniformly standardized technique applicable to many different antigen systems.

Antigens, Neoplasm↗
PubMed1994

Treatment of nevus of Ota by Q-switched ruby laser.

BACKGROUND: There are few reports on therapy for nevus of Ota. Moreover, traditional treatments are largely palliative or risk permanent pigmentary changes and/or scarring. OBJECTIVE: The efficacy of the Q-switched ruby laser (694 nm, 40 nsec) as a therapy for nevus of Ota was investigated. METHODS: Nine nevi or portions thereof were irradiated up to six times with 4.5 and/or 7.5 J/cm2 at a mean exposure interval of 3 weeks. Sequential skin biopsy specimens were processed for light microscopy, immunohistochemistry, and electron microscopy. RESULTS: Cosmetic improvement occurred at both doses in the irradiated parts of the six nevi available for follow-up. No appreciable difference was noted between single and multiple treatments. There was no gross scarring. Light microscopy revealed dose-related immediate injury with more melanophages and fewer dermal melanocytes after irradiation in comparison with control areas. Electron microscopic distinction between dermal melanocytes and melanin-laden macrophages was difficult. A monoclonal antibody to human melanosome-specific antigen type 1 (HMSA-1) was used to distinguish between the two cell populations. CONCLUSION: Our findings suggest that the Q-switched ruby laser is useful for treating nevus of Ota.

Adult↗
PubMed1994

Identification of a cell-surface glycoprotein associated with normal mammary and extramammary epithelial cells.

The goal of the study was to identify any normal genes that may become inactivated in malignant cells, with associated modifications or loss of gene products. Consequently, attempts were made to identify such products by generating monoclonal antibodies using an immune tolerisation-immunisation procedure. Using such a technique, a plasma membrane-associated glycoprotein with an apparent molecular weight of 92 kDa was identified. The glycoprotein was termed luminal epithelial antigen (LEA.92). The pattern of expression of LEA.92 was demonstrated by an indirect immunostaining technique. Using an in vitro model system representing various stages of breast oncogenesis, LEA.92 was detected on normal or immortalised mammary epithelial cell (MEC) lines which were dependent on epidermal growth factor (EGF) and anchorage formation for growth and non-tumorigenic in nude mice. In contrast, LEA.92 was undetectable on oncogenically transformed or established lines of mammary carcinoma cell lines which were independent of EGF or anchorage formation for growth and were highly tumorigenic. The results appear to suggest a correlation between the down-regulation of LEA.92 and the development of tumorigenicity in malignant MEC lines. Furthermore, the patterns of expression of LEA.92 on breast cells in tissue mirrored those of breast epithelial cells in cell cultures. LEA.92 was detected on the surface of normal but not malignant epithelial cells, which included breast, cervix, colon, lung, pancreas and stomach. LEA.92 appeared to be distinct from receptor for epidermal growth factor, antigens associated with milk fat globule membrane and the family of epithelium-specific keratins.

Adult↗
PubMed1994

Ineffective treatment of refractory melasma and postinflammatory hyperpigmentation by Q-switched ruby laser.

BACKGROUND: Melasma and postinflammatory pigmentation are cosmetic problems with limited options for treatment. OBJECTIVE: To determine whether selective photothermolysis of pigmented cells by Q-switched ruby laser treatment would produce clinical benefit in these disorders. METHODS: Eight subjects with melasma or postinflammatory hyperpigmentation refractory to traditional treatments were treated with Q-switched ruby laser pulses (694 nm, 40 nanoseconds) at fluences of 15-7.5 J/cm2, and followed. Histology was obtained before and after treatment. RESULTS: Regardless of fluence, no permanent improvement and, in some cases, darkening was seen in each type of lesion. Except for small depression at high fluences in black patients, there were no textural changes after healing. Immediately after treatment, there was epidermal and dermal injury, with extracellular melanin. Several months later, epidermal pigmentation had returned to baseline and dermal macrophages were apparently focally increased. CONCLUSIONS: The Q-switched ruby laser by itself does not provide an effective treatment for refractory melasma or postinflammatory hyperpigmentation.

Adult↗
PubMed1994

Increased capacity for circulatory fatty acid transport in a highly aerobic mammal.

Plasma fatty acid (FA) and albumin concentrations, cardiac output, and hematocrit of dogs and goats [dog-to-goat ratio of maximal oxygen consumption (VO2max) = 2.2] were measured to determine rates of circulatory FA delivery during exercise. Our goals were 1) to characterize the mechanism(s) used by the endurance-adapted species (dog) to support higher rates of FA delivery to working muscles than the sedentary species (goat) and 2) to determine whether circulatory transport is scaled with VO2max. Lipid oxidation was 2.5 times higher in dogs than in goats. Dogs had higher cardiac outputs than goats, but this positive effect on their FA delivery was canceled by higher hematocrit. Dogs always had higher plasma FA concentrations than goats. In contrast, albumin was steady and identical in both species, showing that dogs transport FA at higher rates than goats only because they load more FA on their albumin. Average dog-to-goat ratios for FA delivery (1.5-2.0) were lower than would be expected if this rate were scaled with VO2max. In vitro experiments showed that dog albumin is designed for high rates of FA transport because it can bind 50% more FA than goat albumin. All endurance-adapted species may possess such "aerobic albumins" to supply more circulating FA to their working muscles than sedentary species.

Aerobiosis↗
PubMed1994

Generation of a murine monoclonal antibody to normal mammary epithelium using mice rendered immune-tolerant to malignant mammary epithelium.

A monoclonal antibody (MAb) that distinguishes normal from malignant mammary epithelia in tissue or cell lines was generated using a procedure that involved immune-tolerization before immunization. Immune-tolerance to two transformed mammary epithelial cell lines (MCF.7 and MDA.MB.231 cell lines combined) was induced in neonatal mice within 24 hr of birth. Successful induction of immune-tolerance was determined by an indirect immunohistological method, testing sera from mice against the tolerogen (i.e., the MCF.7 and MDA.MB.231 cell lines). Mice lacking antibodies in their sera against the immune-tolerogen were subsequently immunized with an extract of normal breast epithelium. One mouse was selected for hybridoma production based on evidence of serum antibody that showed reactivity with normal mammary epithelial cells (MEC) but not with invasive breast carcinoma cells, as determined by an indirect immunohistological method. Spleen cells from the selected mouse were fused with a mouse myeloma cell line to generate MAb. After extensive screening, one MAb was further studied on the basis of reactivity with normal MEC in tissue and absence of staining of malignant MEC in tissue or tumorigenic MEC lines. This test of specificity of reactivity revealed that the antigen detected by the specific antibody was expressed on the apical plasma membrane of normal glandular epithelia that included breast, cervix, colon, lung, pancreas, and stomach, but not on their malignant counterparts in tissue sections. The antigen recognized by the MAb was termed luminal epithelial antigen with an apparent MW of 92 KD (LEA.92). This study illustrates the practical usefulness of the immune-tolerization/immunization approach in the generation of antibodies with particular specificity requirements, as in the identification of an antigen that is differentially expressed in two tissues (e.g., normal and malignant) which otherwise have a multiplicity of antigens in common.

Adult↗
PubMed1994

Capillary blood transit time in muscles in relation to body size and aerobic capacity.

The mean minimal transit time for blood in muscle capillaries (tc) was estimated in six species, spanning two orders of magnitude in body mass and aerobic capacity: horse, steer, dog, goat, fox and agouti. Arterial (CaO2) and mixed venous (CvO2) blood O2 concentrations, blood hemoglobin concentrations ([Hb]) and oxygen uptake rates were measured while the animals ran on a treadmill at a speed that elicited the maximal oxygen consumption rate (VO2max) from each animal. Blood flow to the muscles (Qm) was assumed to be 85% of cardiac output, which was calculated using the Fick relationship. Total muscle capillary blood volume (Vc) and total muscle mitochondrial volume were estimated by morphometry, using a whole-body muscle sampling scheme. The tc was computed as Vc/Qm. The tc was 0.3-0.5 s in the 4 kg foxes and agoutis, 0.7-0.8 s in the 25 kg dogs and goats, and 0.8-1.0 s in the 400 kg horses and steers. The tc was positively correlated with body mass and negatively correlated with transcapillary O2 release rate per unit capillary length. Mitochondrial content was positively correlated with VO2max and with the product of Qm and [Hb]. These data suggested that Qm, Vc, maximal hemoglobin flux, and consequently tc, are co-adjusted to result in muscle O2 supply conditions that are matched to the O2 demands of the muscles at VO2max.

Aerobiosis↗
PubMed1994

Antigen retrieval using pH 3.5 glycine-HCl buffer or urea solution for immunohistochemical localization of Ki-67.

A new antibody (MIB-1) has been described, permitting the demonstration of Ki-67 proliferation antigen in paraffin sections. However, satisfactory results were obtained only after subjecting tissue sections to microwave based antigen retrieval in citrate buffer solution. Other buffer solutions produce equivalent or better results and also permit use of the original Ki-67 antibody, which hitherto has been considered ineffective for paraffin sections.

Buffers↗
PubMed1994

Immunocytochemical detection of cyclin A and cyclin D in formalin-fixed, paraffin-embedded tissues: novel, pertinent markers of cell proliferation.

Cyclin proteins in association with cyclin-dependent protein kinase subunits represent a new class of potentially oncogenic serine/threonine protein kinases that function to execute critical cell cycle transitions in all eukaryotic cells. Characterized by dramatic fluctuations in abundance, which occur in accordance with the periodicity of the cell cycle, the expression patterns of specific cyclins provide a unique and relevant indicator of cellular activation and cell cycle progression. In this study, we introduce a series of monospecific antibodies that are selective for human cyclin A and cyclin D, respectively, and we assess the feasibility of utilizing these reagents for immunocytochemical analyses. Conditions were optimized for detecting cyclin A and cyclin D in formalin-fixed, paraffin-embedded sections of the postnatal human palatine tonsil, in which normal cell proliferation is well characterized. Subsequent studies demonstrated the performance of these antibodies in the examination of pediatric bone tumors, in which decalcification methods are additionally performed. In both cases, the proliferative status of individual cells was monitored with an exceedingly high degree of resolution. Taken together with the available biochemical data, the results of these studies reveal a novel means of characterizing the proliferative status of normal as well as neoplastic tissues. The demonstrated utility of these immunochemical reagents will potentially facilitate retrospective studies aimed at examining cell proliferation in a wide variety of archival histopathologic specimens.

Antibodies↗
PubMed1994

To approve or not to approve? That is the question. Ethical concerns over the regulation of immunohistochemical stains.

Over the past two decades, immunohistochemical stains have evolved to become an essential part of the practice of surgical pathology. An extensive literature documents significant diagnostic and prognostic applications, and the pathology journals add new applications and new tests almost on a daily basis. The antibodies that provide the basis of immunohistochemical stains fall under the purview of the Food and Drug Administration (FDA). The vast majority of these antibodies have not been submitted for FDA approval or clearance, but nonetheless are widely employed in practice. The FDA, therefore, faces a major dilemma in attempting to fulfill its legislative mandate. Lack of adequate regulation may permit the use of unproven or poor quality reagents. On the other hand, overzealous regulation will preclude the use of large numbers of stains that are now integral to the diagnostic process. If ethical considerations truly are governed by following the course that leads to the greatest good for the greatest number, then the evidence suggests that overzealous regulation should be avoided. The argument is presented that immunohistochemical stains should be treated no differently from other special stains already in use in surgical pathology. With all tissue stains, including immunohistochemical stains, the pathologist makes the diagnosis by interpreting morphologic features and staining patterns: the stain alone is of no value to clinician or patient, rather it is the pathologist's report that establishes the diagnosis. It is suggested that a certification process that ensures quality and technical validity, somewhat analogous to that already in existence for biological stains, would be sufficient to meet the needs of the pathologist, providing ongoing benefits to patient care, with minimal risk.

Drug and Narcotic Control↗
PubMed1993

Identification of a cell-surface antigen (LEA.135) associated with favorable prognosis in human breast cancer.

The present study was undertaken with a rationale that loss of certain "normal tissue" antigens might have prognostic significance, reflecting inactivation of the corresponding genes during neoplastic progression. An attempt was made to identify such antigens by means of generating monoclonal antibodies using a tolerization/immunization procedure. A monoclonal antibody generated by immunization of BALB/c mice with normal breast tissue extract, following prior tolerization with mammary carcinoma cells, recognized a cell-surface glycoprotein, luminal epithelial antigen, with an apparent molecular weight of 135,000 (LEA.135). The pattern of expression on LEA.135 was determined by immunohistochemical-staining techniques on frozen and formalin-fixed and paraffin-embedded tissue sections. LEA.135 was demonstrable on the apical plasma membrane of normal and nonneoplastic epithelial cells in breast and other tissues. Studies have shown that LEA.135 is distinct from receptors for epidermal growth factor and from known antigens associated with epithelial cells, including the family of keratins. In a retrospective study, with a follow-up ranging from 5 to 15 years, patients whose breast tumor cells expressed LEA.135 had a superior overall survival rate (78 0.139% at > 5 years; P = 0.025). Furthermore, in patients with histologically poorly differentiated tumors, LEA.135-positive cases had a better prognosis (80 0.179% at > 5 years; P = 0.013) compared with LEA.135-negative cases. In addition, in patients with aneuploid tumors, LEA.135-positive cases again showed an improved survival (90 0.001% at > 5 years; P = 0.039) compared with those that were with LEA.135 negative. The results suggest that the expression of LEA.135 provides a useful indication of clinical outcome in patients with breast carcinomas.

Antibodies, Neoplasm↗
PubMed1993

Technology assessment in diagnostic imaging. A proposal for a phased approach to evaluating radiology research.

RATIONALE AND OBJECTIVES: The authors propose an objective basis for critical evaluation of research trends and define and analyze a sample of radiology studies according to research phase. METHODS: A random sample of 146 original diagnostic studies from two radiology journals was categorized according to phase, modality, and design by three physician reviewers, collated with a microcomputer database, and analyzed using an SAS program. RESULTS: Phase 1 studies (technical evaluation) constituted 18.5% of publications: phase 2 (standardization and tissue characterization), 10.3%; phase 3 (spectrum of appearances), 40.4%; phase 4 (diagnostic efficacy), 21.2%; and phase 5 (clinical evaluation), 9.6%. Of 48 diagnostic efficacy studies, 42% were prospective (versus 35% for the total sample), 38% were controlled (median sample size, 53 [versus 30 for the total sample]). Only 27% of the 48 diagnostic efficacy studies were externally funded. Research in magnetic resonance imaging (MRI), which comprised 45% of all publications, was oriented toward phase 1 (32%) rather than phase 5 studies (0%). Phase 5 studies were the focus of 18% and 8% of ultrasound (US) and computed tomography (CT) studies, respectively. There were more prospective, controlled efficacy studies in US than in MRI or CT. CONCLUSIONS: Analyses of research trends will be facilitated by use of a standard taxonomy which adopts a modality-based, phased approach.

Diagnostic Imaging↗