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Biomedical subjects

R R Miller

Publications and source records attributed to R R Miller.

At least 145 records · Page 8Linked to original sources

Primary anterior mediastinal tumours: "an investigational algorithm".

A review of 33 months' experience with primary anterior mediastinal masses in 31 patients disclosed that in 9 (29%) the tumour was benign. Nineteen (86%) of the 22 malignant tumours and only 2 of the 9 benign tumours were symptomatic. Diagnosis was established by histopathologic examination of a biopsy specimen or resected tissue and serum radioimmunoassay for alpha-fetoprotein or human chorionic gonadotropin, beta-subunit. The authors present an investigational algorithm, using modern procedures, to facilitate the diagnosis of this relatively uncommon and challenging condition.

Adolescent↗

Experimental osteoarthritic articular cartilage is enriched in guanidine soluble type VI collagen.

Experimental osteoarthritis was surgically induced in the right knee joint of dogs; the left knee served as a control. Articular cartilage was extracted with 4 M guanidinium chloride, 0.05 M sodium acetate, pH 6.0, containing proteinase inhibitors and the proteins purified by associative CsCl density gradient centrifugation. Equal quantities of protein were electrophoresed in agarose-acrylamide gradient gels and the high molecular weight type VI collagen bands detected in immunoblots with a polyclonal antiserum. Type VI collagen bands between 185 and 220 kDa were evident in the pathological specimens of dogs sacrificed 3, 5, and 7 months after surgery and were either absent or only very weakly visible in the controls. These results demonstrate that experimental osteoarthritic cartilage is enriched in 4 M guanidine-soluble type VI collagen.

Animals↗

Thrombospondin is present in articular cartilage and is synthesized by articular chondrocytes.

Thrombospondin, a multifunctional adhesive glycoprotein originally identified in platelets, was isolated and identified from an extract of ovine articular cartilage. Immunoreactive material from a cartilage extract comigrated on gel electrophoresis with purified human platelet thrombospondin. When articular chondrocytes were cultured in the presence of 35S-methionine, metabolically labeled thrombospondin was immunoprecipitated from the culture medium and cell layer extract. These results demonstrate that thrombospondin is present in articular cartilage and is synthesized by articular chondrocytes.

Animals↗

Glandular neoplasia of the lung. A proposed analogy to colonic tumors.

In 62 consecutive resections for adenocarcinoma of the lung, 50 cases (81%) had single adenocarcinomas and 12 (19%) had multiple adenocarcinomas. In seven of these 12 patients, two adenocarcinomas were found. In the other five patients, the specimen contained a dominant adenocarcinoma and several 0.1- to 1-cm nodules of similar histologic appearance. In four of the 50 single tumor patients and one of seven double tumor patients, 1- to 2-mm nodules were found along with adenocarcinomas that we interpreted as being bronchioloalveolar tumors of uncertain malignant potential. An analogy is drawn between these four types of findings and single tumors of the colon, double tumors of the colon, polyposis syndromes, and tubular adenomas of the colon, respectively.

Adenocarcinoma↗

Partial purification and characterization of detergent-solubilized N-sulfotransferase activity associated with calf brain microsomes.

Calf brain 3'-phosphoadenosine 5'-phosphosulfate (PAPS):proteoheparan sulfate (PHS) N-sulfotransferase activity is solubilized by extracting salt-washed microsomes with 1% Cutscum. A protocol is described for the partial purification of the sulfotransferase activity utilizing: (1) diethylaminoethyl (DEAE)-Sephacel, (2) heparin-Sepharose CL-6B, and (3) 3',5'-ADP-agarose as chromatographic supports. Sulfotransferase activity was followed by using 3'-phosphoadenosine 5'-phospho[35S]sulfate and endogenous acceptors in heat-inactivated microsomes as exogenous substrates. Two chromatographically distinct fractions (ST1 and ST2) of sulfotransferase activity are resolved on DEAE-Sephacel. Both sulfotransferase activities have been partially purified and characterized. An apparent purification of the two N-sulfotransferase fractions of 22- to 29-fold, relative to the microsomal activity, is achieved by this procedure. Since ST1 appears to represent approximately 24% of the total microsomal activity, a purification of 89-fold has been estimated for this fraction. Neither sulfotransferase activity was stimulated by MnCl2, MgCl2, or CaCl2 added at 10 mM, nor inhibited by the presence of 10 mM EDTA. ST1 and ST2 are optimally active at pH 7.5-8. Apparent Km values for PAPS of 2.3 microM and 0.9 microM have been determined for ST1 and ST2, respectively. ST1 exhibits N-sulfotransferase activity primarily and is inhibited by phosphatidylserine whereas the ST2 fraction contains a mixture of N- and O-sulfotransferase activity and is stimulated by phosphatidylserine, phosphatidylcholine, and lysophosphatidylcholine. The detection of two chromatographically distinct sulfotransferase activities raises the possibility that N-sulfation of proteoheparan sulfates could be catalyzed by more than one enzyme, and that N-sulfation and O-sulfation of proteoglycans are catalyzed by separate enzymes in nervous tissue.

Animals↗

Resectable stage III lung cancer: CT, surgical, and pathologic correlation.

The new International Staging System identifies a subset of patients with stage III lung cancer who have improved survival rates after surgical resection. The computed tomographic (CT), surgical, and pathologic findings in 26 patients with completely resected stage IIIa lung cancer were reviewed. Preoperative CT scans accurately demonstrated chest wall invasion in only two of ten patients with chest wall or diaphragmatic invasion. CT demonstrated pericardial involvement in only one of three patients. Tumor extension to within 2 cm of the tracheal carina was seen with CT in one of three patients. Eleven of 26 patients had limited ipsilateral mediastinal (N2) disease; eight of 11 had affected nodes greater then 10 mm on CT scans. As previously shown, CT is of limited value in the assessment of chest wall, mediastinal, pleural, or pericardial tumor extension; however, such extension does not preclude complete resection. Ipsilateral node involvement does not preclude surgery. Familiarity with the new staging system and awareness of what constitutes potentially resectable disease are necessary for an adequate assessment of CT findings.

Adult↗

Pulmonary lymphangitic carcinomatosis: CT and pathologic findings.

The authors retrospectively reviewed the computed tomographic (CT) scans, biopsy specimens, autopsy results, and lobectomy specimens of 21 patients who had lymphangitic carcinomatosis. Ten-millimeter collimation CT scans were obtained from all patients, and selected 1.5-mm CT scans were obtained from ten patients. In five patients, the diagnosis was established with open lung biopsy, lobectomy, or autopsy; in nine, with bronchial biopsy or transbronchial biopsy; and in seven, with clinical and radiologic criteria. Certain characteristic findings on CT scans were evident: uneven thickening of bronchovascular bundles, thickening of isolated interstitial lines, and the presence of polygonal lines. These findings may be seen on CT scans even if the findings on chest radiographs are normal or nonspecific. The pathologic basis for these characteristic CT findings may relate to tumor thrombi in lymphatic vessels rather than edema and fibrosis, at least in the early stages of disease.

Adult↗

Enterovenous fistula: unusual complication of Crohn disease.

An unusual complication in a patient with Crohn enterocolitis is presented. Ultrasound and computed tomographic studies showed stationary gas in the portal vein, and a presumptive diagnosis of septic ascending portal thrombophlebitis was made. Emergency laparotomy was performed and the terminal ileum was excised for recurrent Crohn disease. Pathologic examination showed a fistula from the lumen of the inflamed segment to the superior mesenteric venous system. Autopsy 1 month later showed organizing thrombi and fecal debris in the portal venules.

Crohn Disease↗

Mediastinal nodes in bronchogenic carcinoma: comparison between CT and mediastinoscopy.

Computed tomography (CT) and mediastinoscopy were compared in 151 patients with bronchogenic carcinoma. In all patients in whom findings at mediastinoscopy were negative, all accessible nodes were either removed or sampled at thoracotomy. Several size criteria for identifying nodes as enlarged on CT scans were compared. The long axis greater than or equal to 15 mm and short axis greater than 10 mm had very low sensitivity (61%), and the long axis greater than 5 mm had a low specificity (23%). CT (long axis greater than 10 mm) allowed sensitivity equal to that of mediastinoscopy (79%) in the detection of mediastinal metastases, but the specificity with CT was lower (65% vs. 100%). In seven of 44 patients with nodes greater than 10 mm on CT scans and with positive findings at mediastinoscopy, tumor was present not in the enlarged nodes but rather in normal-sized nodes in a different nodal station. The sensitivity of CT for actual nodal stations involved with tumor was only 66%. Eighty-three percent of patients with false-negative findings at mediastinoscopy but only 33% of patients with false-negative findings at CT had surgically resectable stage IIIa disease.

Carcinoma, Bronchogenic↗

Desquamative interstitial pneumonia. Computed tomographic findings before and after treatment with corticosteroids.

Noninvasive methods for diagnosis, assessing prognosis, and following response to treatment in idiopathic pulmonary fibrosis (IPF) have yet to prove their usefulness. We report a patient with desquamative interstitial pneumonia (DIP) in whom computed tomography (CT) suggested the diagnosis by the presence of patchy areas of haziness predominantly in a peripheral distribution. The chest x-ray and physical examinations, and the arterial blood gases showed normal findings after one month of treatment with corticosteroids, at which time the CT scan and lung volumes were still abnormal. At three months, lung volumes and the CT scan were normal. Hazy densities in a peripheral distribution on CT may indicate active IPF associated with a good prognosis.

Adult↗

"Density mask". An objective method to quantitate emphysema using computed tomography.

We used a computed tomography (CT) scanner program ("density mask") that highlights voxels within a given density range to quantitate emphysema by defining areas of abnormally low attenuation. We compared different density masks, mean lung attenuation, visual assessment of emphysema and the pathologic grade of emphysema in 28 patients undergoing lung resection for tumor. In each patient, a single representative CT image was compared with corresponding pathologic specimens of tissue. There was good correlation between the extent of emphysema as assessed by the density mask and the pathologic grade of emphysema. The optimal attenuation level to define areas of emphysema may vary in different scanners, but, once determined for a particular scanner, the density mask accurately assesses the extent of emphysema and eliminates interobserver and intraobserver variability. It has the added advantage of determining the exact percentage of lung parenchyma showing changes consistent with emphysema.

Adult↗

Testing response generation rules.

Robbins (1988) reported data that he viewed as inconsistent with Miller and Schachtman's (1985a) comparator hypothesis of conditioned response generation. Here we explain why we do not find his experiments a compelling test of the comparator hypothesis. We also briefly review other studies that tested the same predictions of the comparator hypothesis that Robbins examined. We conclude that there is considerable evidence that following excitatory or inhibitory conditioning with a target conditioned stimulus (CS) and unconditioned stimulus (US), extinction of other cues that were present during CS training ordinarily increases excitatory responding and decreases inhibitory responding to the CS. However, consistent with Robbins's conclusion, there is scant evidence that after CS-US training, enhancing the associative value of other cues that were present during CS training influences excitatory or inhibitory responding to the CS. The implications of these conclusions for the comparator hypothesis as an explanation of differences in acquired behavior and as a heuristic tool are considered.

Animals↗

Proteoglycan synthesis by primary chick skeletal muscle during in vitro myogenesis.

The proteoglycans synthesized by primary chick skeletal muscle during in vitro myogenesis were compared with those of muscle-specific fibroblasts. Cultures of skeletal muscle cells and muscle fibroblasts were separately labeled 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. Two cell layer-associated proteoglycans synthesized both by skeletal muscle cells and muscle fibroblasts were identified. The first, a high molecular weight proteoglycan, eluted from Sepharose CL-2B with a Kav of 0.07 and contained exclusively chondroitin sulfate chains with an average molecular weight greater than 50,000. The second, a relatively smaller proteoglycan, eluted from Sepharose CL-2B with a Kav of 0.61 and contained primarily heparan sulfate chains with an average molecular weight of 16,000. Two labeled proteoglycans were also found in the medium of both skeletal muscle and muscle fibroblasts. A high molecular weight proteoglycan was found with virtually identical properties to that of the high molecular weight chondroitin sulfate proteoglycan of the cell layer. A second, smaller proteoglycan had a similar monomer size (Kav of 0.63) to the cell layer heparan sulfate proteoglycan, but differed from it in that this molecule contained primarily chondroitin sulfate chains with an average molecular weight of 32,000. Studies on the distribution of these proteoglycans in muscle cells during in vitro myogenesis demonstrated that a parallel increase in the relative amounts of the smaller proteoglycans occurred in both the cell layer and medium compared to the large chondroitin sulfate proteoglycan in each compartment. In contrast, muscle-derived fibroblasts displayed a constant ratio of the small proteoglycans of the cell layer and medium fractions, compared to the larger chondroitin sulfate proteoglycan of the respective fraction as a function of cell density. Our results support the concept that proteoglycan synthesis is under developmental regulation during skeletal myogenesis.

Animals↗

Laser treatment of obstructive endobronchial tumors: factors which determine response.

To investigate whether computerized tomography (CT) and radionuclide quantitative ventilation-perfusion lung scan add any useful information to a carefully performed endoscopic examination in determining the response of patients with obstructive endobronchial tumors to laser treatment, the findings in 40 patients treated with photodynamic therapy (PDT) or the Nd:YAG laser were analysed. Endoscopic laser treatment was found to be most effective when the tumor was polypoid in appearance bronchoscopically, with little or no submucosal invasion or peribronchial extension seen on CT. When bronchoscopy and CT showed increasing submucosal and/or peribronchial disease, the immediate and long-term response to treatment was poorer. CT provided valuable information regarding the extent of the peribronchial involvement and airway distortion which were often underestimated by bronchoscopy alone. Reduction of regional perfusion out of proportion to ventilation on scintigraphy in the involved lung zone was found to be associated with extensive peribronchial involvement. We conclude that the addition of CT and radionuclide quantitative ventilation-perfusion lung scan to bronchoscopic examination is useful in predicting the response of patients with obstructive endobronchial tumors to laser treatment. Whether PDT or YAG laser is more effective in relieving endobronchial obstruction by tumor awaits a randomized controlled trial.

Aged↗

Recruitment time of conditioned opioid analgesia.

Three experiments examined the development of conditioned analgesia in rats exposed to stimuli that had previously been paired with footshock. In Experiment 1, tailflick latencies increased if the tailflick test for analgesia was immediately preceded by 90 sec of exposure to a context in which unsignaled shock had previously been administered. This analgesia was blocked by the opiate antagonist naloxone administered prior to exposure to the context on the test day. Experiment 2 determined that 90 and 300 sec of exposure to the conditioning context immediately prior to testing evoked comparable analgesia as indexed by increased latencies to pawlick in response to thermal stimulation (hotplate). However, no analgesia was evident in animals exposed to the aversive context for 5 sec immediately prior to the hotplate test relative to animals not exposed to that context. In Experiment 3, a 5-sec exposure to the aversive context produced analgesia comparable to a 90-sec exposure if an 85-sec delay intervened between the 5-sec exposure and the hotplate test. These results suggest that brief exposure to stimuli previously paired with shock can activate the endogenous opioid system, but the analgesic action of these opioids is delayed. Implications for the role of endogenous opioids in learning are discussed.

Analgesia↗

Lingular and right middle lobe biopsy in the assessment of diffuse lung disease.

It has been said that the lingula and right middle lobe should be avoided for open-lung biopsy because of nonspecific fibrosis and vascular changes. To determine if the diagnostic yields of lingular or right middle lobe biopsy specimens were unsatisfactory, we reviewed the results of open-lung biopsy in 73 adult patients; 26 were immunocompromised and 47, nonimmunocompromised. We found no evidence to suggest that these two sites were inherently inferior. In 20 of the nonimmunocompromised patients, computed tomography was performed prior to biopsy, and demonstrated no particular tendency for greater involvement of the lingula or right middle lobe. We conclude that lingular and right middle lobe biopsy is useful in the diagnosis of parenchymal lung disease and that these sites should not necessarily be avoided. Computed tomographic scanning prior to biopsy is helpful in guiding the surgeon to the appropriate sites from which to obtain biopsy specimens.

Adult↗