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Biomedical subjects

R R Miller

Publications and source records attributed to R R Miller.

At least 109 records · Page 6Linked to original sources

Thrombospondin in ligament, meniscus and intervertebral disc.

The presence of thrombospondin in extracts of ligament, meniscus and human nucleus pulposus was demonstrated by Western blot analysis using an anti-human thrombospondin antibody. Metabolic labeling of ligament fibroblast and meniscal fibrochondrocyte cultures followed by immunoprecipitation with anti-human thrombospondin revealed a single band corresponding to the molecular weight of thrombospondin when analyzed by SDS-PAGE and fluorography under reduced and non-reduced conditions. Thrombospondin, therefore, is a matrix constituent of ligament, knee joint meniscus and the nucleus pulposus and is synthesized by ligament fibroblasts and meniscal fibrochondrocytes in vitro.

Animals↗

A quantitative microwell assay for chondrocyte cell adhesion.

An assay for measuring the quantity of live articular chondrocytes attached to a substratum in microwell plates was established by measuring the absorbance of the blue formazan product generated from the dye 3-(4,5-dimethylthiazol-2-yl)-2,5-dypenyl tetrazolium bromide (MTT). Blue formazan production was optimal at an MTT concentration of 1 mg/ml (100 microliters per microwell) and an incubation period of 3 h. The absorbance of the dye was linearly related to the quantity of cells added per microwell. The number of live chondrocytes attached to adhesive proteins can be quantitated using this technique.

Animals↗

Hemolytic activity of ethylene glycol phenyl ether (EGPE) in rabbits.

Studies were conducted to characterize the hemolytic effects of EGPE in rabbits following oral and dermal exposure, and to evaluate the in vitro hemolytic potential of EGPE and its major metabolite using rabbit red blood cells (RBC). Gavage administration of EGPE to female New Zealand White rabbits at 100, 300, 600, or 1000 mg/kg/day for up to 10 consecutive days (one dose/day) resulted in a dose-related intravascular hemolytic anemia. The hemolytic anemia was characterized by decreased RBC count, hemoglobin concentration, packed cell volume, hemoglobinuria, splenic congestion, renal tubule damage, and a regenerative erythroid response in the bone marrow. The hemolytic anemia was observed without alterations in RBC glutathione or methemoglobin. Phenoxyacetic acid (PAA) was identified as a major blood metabolite of EGPE. In vitro exposure of female rabbit erythrocytes indicated EGPE to be considerably more hemolytic than PAA. In a 90-day dermal study in which EGPE was applied to the skin of male and female New Zealand White rabbits 6 hr/day, 5 days/week, at doses up to 500 mg/kg/day, there was no indication of a hemolytic response. The only treatment-related effects were sporadic occurrences of slight erythema and scaling of skin at the site of test material application in high dose group male and female rabbits. However, erythema and scaling were not associated with gross or histopathologic changes and were not considered toxicologically significant.

Anemia, Hemolytic↗

Proteoglycan synthesis by clonal skeletal muscle cells during in vitro myogenesis: differences detected in the types and patterns from primary cultures.

Proteoglycan synthesis by two clonal murine skeletal muscle cell lines, G8-1 and C2, was examined. Cultures of skeletal muscle cells at both the myoblast and myotube stages were radiolabeled using [35S]sulfate as a precursor. The proteoglycans of the cell layer and medium were separately extracted and isolated by ion exchange chromatography on DEAE-Sephacel followed by gel filtration chromatography on Sepharose CL-2B. The cell layer proteoglycans eluted from Sepharose CL-20 as a single peak with a Kav of 0.66 and contained glycosaminoglycan chains with an average molecular weight of 20,000. The glycosaminoglycan chains were composed of nearly equal mixtures of chondroitin sulfate and heparan sulfate with the exception that C2 myoblast cultures contained larger amounts of heparan sulfate. Of interest, this line differentiates more rapidly in our laboratory than G8-1. The medium proteoglycans also eluted from Sepharose CL-2B as a single peak with a Kav of 0.66 but contained glycosaminoglycan chains with an average molecular weight of 32,000. Based upon enzymatic and chemical analysis, the medium glycosaminoglycan chains were composed of a mixture of chondroitin sulfate (71-80%) and heparin sulfate (19-22%). Following chondroitinase ABC digestion, the predominant disaccharide released from all glycosaminoglycan fractions was chondroitin-4-sulfate. When the extracted cell layer proteoglycans were chromatographed on Sepharose CL-28 in the absence of detergent, a small but consistent proportion (14-18%) eluted in the void volume, suggesting the association of at least a portion of this proteoglycan with cellular lipid. These differences distinguish proteoglycan metabolism in fusing clonal lines from primary muscle cell cultures suggesting their utility in evaluating the contribution of these macromolecules in myogenesis.

Animals↗

Associative structure of differential inhibition: implications for models of conditioned inhibition.

Following A+/X- training (with A, X, and + being a light, tone, and footshock, respectively), rats received extinction of A and the training context, extinction of the training context alone, or no extinction. The inhibitory potential of X was then assessed with conditioned lick suppression in a neutral context using both summation and retardation tests. Extinction of the training context alone and extinction of A and the training context reduced the inhibitory potential of X appreciably and equally. Hence, what is traditionally called differential inhibition appears to depend not on the excitatory value of A but on the excitatory value of the training context. In conjunction with what is known about other inhibitory training procedures, these results suggest that a conditioned inhibitor is a stimulus that has been paired with little or no reinforcement in the presence of an accompanying stimulus that predicts greater reinforcement.

Animals↗

Solitary pulmonary nodule: high-resolution CT and radiologic-pathologic correlation.

Edge and internal characteristics of pulmonary nodules evaluated with high-resolution computed tomography (HRCT) were correlated with the pathologic specimens in 93 patients. Speculation correlated pathologically with irregular fibrosis, localized lymphatic spread of tumor, or an infiltrative tumor growth pattern and was observed in six of 11 benign nodules (55%) and 74 of 85 malignant nodules (87%). Pleural tags were observed in three benign nodules (27%) and 49 malignant lesions (58%); pathologically, these represented fibrotic bands usually associated with juxta-cicatricial pleural retraction. Bubblelike areas of low attenuation within the nodule were observed in 21 malignant lesions (25%) and only one benign nodule (9%). They were observed most commonly in bronchioloalveolar carcinomas (seven of 14) and were due either to patent small bronchi or small, cystic spaces within neoplastic glands. Malignant nodules as a group were larger than benign lesions (P = .02) and more commonly demonstrated a spiculated contour (P less than .05), lobulation (P less than .001), and inhomogeneous attenuation (P less than .05).

Adult↗

Intrathoracic complications following allogeneic bone marrow transplantation: CT findings.

The authors retrospectively reviewed computed tomographic (CT) scans of 18 patients who developed 21 episodes of intrathoracic complications after allogeneic bone marrow transplantation (BMT). Pathologic and/or microbiologic diagnoses were available for all patients. All patients were immunocompromised due to either graft-versus-host disease (GVHD), neutropenia, or recurrent malignancy after BMT. CT demonstrated diagnostically relevant findings that were not apparent at radiography in 12 of the 21 cases (57%). These included a ground-glass pattern in early pneumonia (n = 5); a peripheral distribution in GVHD, bronchiolitis obliterans organizing pneumonia, and eosinophilic drug reaction (n = 4); cavitating lesions in Pneumocystis carinii pneumonia (n = 1); hemorrhagic infarcts in aspergillosis (n = 1); and mediastinal adenopathy in recurrent Hodgkin disease (n = 1). The authors conclude that chest CT is superior to radiography in demonstrating the presence, distribution, and extent of intrathoracic complications developing in patients after allogeneic BMT. CT is useful in guiding procedures for tissue diagnosis.

Adult↗

Diffuse pulmonary hemorrhage.

Diffuse pulmonary hemorrhage is a syndrome consisting of hemoptysis, anemia, and air-space consolidation. The radiologic appearance is non-specific. Pulmonary hemorrhage may be due to a number of different causes. The differential diagnosis and the diagnostic approach are different in the immunologically intact host as compared with the immunocompromised host. This article reviews the main diagnostic considerations in diffuse pulmonary hemorrhage.

Anti-Glomerular Basement Membrane Disease↗

Bronchioloalveolar cell adenomas.

In a series of 247 consecutive resections for lung carcinoma, 23 (9.3%) patients had a total of 41 incidentally found nodules measuring 1-7 mm in diameter. These lesions were characterized histologically by lepidic growth and variable cellular atypia; they were interpreted as bronchioloalveolar adenomas. Five additional patients had dozens of such nodules in addition to their dominant tumor. One of these patients had this process bilaterally. It appears that these adenomas are an early, premalignant phase of glandular neoplasia with a potential for evolution to carcinoma. This phenomenon may help explain the relatively high incidence of multicentric synchronous and metachronous lung cancer cited in the literature.

Adenoma↗

Multicentric adenocarcinoma of the lung: CT-pathologic correlation.

To evaluate the sensitivity of computed tomography (CT) in detecting multicentric primary bronchogenic adenocarcinoma manifesting as a pulmonary nodule, the authors reviewed CT scans and pathologic specimens of 158 consecutive patients who underwent resection of a pulmonary nodule. Two independent observers assessed the scans without knowledge of the pathologic findings. Lung specimens were fixed in inflation and sectioned transversely, analogous to the plane of the CT scans. In 88 patients the nodule represented adenocarcinoma. Multicentric adenocarcinoma was present in 19 of these patients (22%). The sensitivity of CT in correctly detecting the presence and location of two or more lesions was 0.63 and 0.68 for two observers, with a specificity of 0.86 for both. The CT appearance of multicentric disease varied from well-defined nodules to ill-defined hazy opacities simulating pneumonitis. The data indicate that (a) multicentric adenocarcinomas are more common than generally reported in the literature and (b) meticulous evaluation of CT images enables detection of multicentricity in a high percentage of cases.

Adenocarcinoma↗

Pulmonary capillary blood volume in emphysema.

We determined single breath diffusing capacity (DLCO) and pulmonary capillary blood volume (Vc) in a total of 110 patients, who were being evaluated for resectional lung surgery for a localized tumor or lesion. Pathologic assessment of emphysema was obtained in 55 cases who had resection of a lung or an upper lobe, based on a standard reference panel for emphysema grading. In 86 cases, the extent of emphysema was quantitated by computed tomography (CT) of the chest. There was a significant negative correlation between Vc and emphysema assessed by either pathology or CT (r = about -0.5, p less than 0.001) similar to the correlation between DLCO and the extent of emphysema. Results of Vc were significantly lower in cases with moderate emphysema (pathologic grade greater than or equal to 30) than those with no emphysema (grade less than or equal to 5) (p less than 0.001) or mild emphysema (grade 10 to 25) (p less than 0.05), and they were significantly lower (p less than 0.05) in the group with mild emphysema compared with the group with no emphysema on pathologic assessment similar to DLCO results. Although Vc was reduced in emphysema, determination of Vc did not result in improved discrimination in separating cases with emphysema from those without emphysema when compared with DLCO.

Adult↗

CT in differential diagnosis of diffuse pleural disease.

The CT features of benign and malignant pleural diseases have been described. However, the accuracy of these features in the differential diagnosis of diffuse pleural disease has not been assessed before. Without knowledge of clinical or pathologic data, we reviewed the CT findings in 74 consecutive patients with proved diffuse pleural disease (39 malignant and 35 benign). The patients included 53 men and 21 women 23-78 years old. Features that were helpful in distinguishing malignant from benign pleural disease were (1) circumferential pleural thickening, (2) nodular pleural thickening, (3) parietal pleural thickening greater than 1 cm, and (4) mediastinal pleural involvement. The specificities of these findings were 100%, 94%, 94%, and 88%, respectively. The sensitivities were 41%, 51%, 36%, and 56%, respectively. Twenty-eight of 39 malignant cases (sensitivity, 72%; specificity, 83%) were identified correctly by the presence of one or more of these criteria. Malignant mesothelioma (n = 11) could not be reliably differentiated from pleural metastases (n = 24). We conclude that CT is helpful in the differential diagnosis of diffuse pleural disease, particularly in differentiation of malignant from benign conditions.

Actinomycosis↗

Bronchiolitis obliterans organizing pneumonia: CT features in 14 patients.

Bronchiolitis obliterans organizing pneumonia is a disease characterized by the presence of granulation tissue within small airways and the presence of areas of organizing pneumonia. We retrospectively reviewed the chest radiographs, CT scans, and biopsy specimens in 14 consecutive patients with proved bronchiolitis obliterans organizing pneumonia. Six patients were immunocompromised because of leukemia or bone-marrow transplantation. In all patients, 10-mm collimation CT scans were available. In 11 of the 14 patients, select 1.5-mm scans were obtained. The CT findings included patchy unilateral (n = 1) or bilateral air-space consolidation (n = 9), small nodular opacities (n = 7), irregular linear opacities (n = 2), bronchial wall thickening and dilatation (n = 6), and small pleural effusions (n = 4). All patients had areas of air-space consolidation, small nodules, or both. A predominantly subpleural distribution of the air-space consolidation was apparent on the radiographs of two patients and on CT scans of six. Pathologically, the nodules and the consolidation represented different degrees of inflammation in bronchioles, alveolar ducts, and alveoli. Although most of the findings were apparent on the radiographs, the CT scans depicted the anatomic distribution and extent of bronchiolitis obliterans organizing pneumonia more accurately than did the plain chest radiographs.

Adult↗