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Biomedical subjects

R S Fraser

Publications and source records attributed to R S Fraser.

At least 19 recordsLinked to original sources
PubMed1991

Primary pulmonary adenocarcinoma with enteric differentiation.

A pulmonary neoplasm with cytologic characteristics typical of differentiated small intestinal epithelium is reported. Individual cells showed features suggesting columnar absorptive, goblet, Paneth, and neuroendocrine cell differentiation. Thorough investigation and follow-up for 4 years did not identify a primary tumor other than in the lung. The occurrence of such a neoplasm at this site is evidence for the existence of a common stem cell in the lower respiratory and gastrointestinal tract mucosa.

Adenocarcinoma↗
PubMed1991

Fungal tracheobronchitis. Report of 9 cases and review of the literature.

Clinical, roentgenographic and pathologic findings are described in 9 patients with fungal tracheobronchitis and comparison is made with 25 additional cases in the literature. Two morphologic patterns were identified: the first appears as a pseudomembrane of necrotic tissue, exudate, and fungal hyphae involving more-or-less the entire circumference of the bronchial wall or as mucus/fungus plugs completely occluding the airway lumen; the second consists of single or multiple discrete plaques on the airway wall, sometimes associated with invasion of the adjacent lung parenchyma or pulmonary artery. As with more invasive forms of fungal infection, a compromise in host defenses is probably the most important factor leading to fungal colonization and subsequent local invasion. Malignancies of the hematologic and lymphoreticular systems, solid neoplasms, granulocytopenia, and a history of a protracted course of broad-spectrum antibiotics, corticosteroids, and chemotherapy were present in most of our patients and in those reported in the literature. Despite this, there is some evidence that tracheobronchitis may occur in individuals with a relatively lesser degree of host defense impairment. Local damage to the airway wall such as occurs with prolonged mechanical ventilatory support, neoplastic infiltration, or nonfungal infection may also be a factor predisposing to fungal colonization and invasion. In 4 of our patients, the fungal infection of the tracheobronchial tree probably contributed significantly to the development of terminal respiratory failure. Although recognition of the infection may not have altered the course of the underlying disease in some of our patients, in others identification and early treatment might have been life-saving. Thus, culture and histologic examination of bronchoscopically identified tracheobronchial mucus plugs and necrotic material should be performed in all immunocompromised individuals.

Adolescent↗
PubMed1991

Alpha-1 antitrypsin deficiency and systemic necrotizing vasculitis.

We describe a 42-year-old woman with polyarteritis nodosa characterized by polyarthritis, purpuric rash, mononeuritis multiplex, focal segmental glomerulonephritis and necrotizing arteritis. alpha-1 antitrypsin deficiency was diagnosed incidentally on a liver biopsy. This is the third reported case of systemic necrotizing vasculitis in association with alpha-1 antitrypsin deficiency of the PI ZZ type, and the first to show significant response to cyclophosphamide and steroids.

Adult↗
PubMed1991

Transthoracic needle aspiration. The benign diagnosis.

Transthoracic needle aspiration is a relatively innocuous procedure used extensively in the diagnosis of pulmonary disease. Although its sensitivity for malignancy is high, a negative (benign) diagnosis is obtained in 5% to 25% of all cases. Some of these aspirates represent the result of inadequate sampling of a malignant tumor; others, however, are derived from a truly benign process. This review briefly describes and illustrates the cytologic features of these latter aspirates in order to exemplify the wide range of benign diseases that can be identified or suspected by transthoracic needle aspiration. Familiarity with such features should help the interpreting pathologist to prevent needless respiration or thoracotomy in many patients.

Biopsy, Needle↗
PubMed1990

The use of biomarkers in the prediction of survival in patients with pulmonary carcinoma.

Data on ten variables and 16 biomarkers were obtained on 119 patients with newly diagnosed pulmonary cancer. The prognostic value of 16 biomarkers (alpha-1-antitrypsin [AAT], adrenocorticotropic hormone [ACTH], alpha-fetoprotein [AFP], carcinoembryonic antigen [CEA], human chorionic gonadotropin [HCG], immune complexes, immunoglobulins, N-terminal peptide of proopiomelanocortin [NTERM], and tumor-associated antibody [TAA]) was tested by adding these to the model of age, gender, stage, morphology, Feinstein's classification of symptoms, Karnofsky scale, leukocyte count, recent weight loss, and liver enzymes. Using Cox's regression method and a forward stepwise procedure, seven biomarkers (ACTH, AAT, AFP, calcitonin, HCG, TAA, and prolactin) entered the model. Elevated levels of cortisol and TAA were associated with longer survival. The selection of biomarkers by stepwise regression needs to be interpreted with caution, especially since the Z scores were found to be dependent on the particular variables included in the model. Furthermore, when dichotomized on maximum of the normal laboratory values, HCG and AFP were infrequently (2%) elevated. The lack of correlation among the biomarkers supports the hypothesis of random derepression of the genome of cancer cells. Further studies in improved modeling and the formulation of a biomarker index could enhance our understanding of the biology of cancer.

Adenocarcinoma↗
PubMed1989

Long-term follow-up of drug abusers with intravenous talcosis.

Six patients who injected talc containing drugs intended for oral use were assessed over a period of ten or more years from the time of initiation of this habit. Despite discontinuation of the drug abuse, all developed severe respiratory disability and three died from their disease. An evolving spectrum of roentgenographic and functional patterns is considered to be virtually diagnostic of this disorder. Roentgenographically, an initial diffuse, pin-point micronodularity subsequently becomes associated with conglomerates, usually in the upper lobes, closely resembling the progressive massive fibrosis (PMF) of the pneumoconioses. The lower lobes, on the other hand, become relatively translucent, in some instances with bulla formation and the development of pneumothorax. Pulmonary function, initially with both restrictive and obstructive features, eventually becomes markedly obstructive with hyperinflation and air trapping. At this late stage, pathologic examination reveals emphysema in addition to the granulomatous inflammation and fibrosis surrounding the talc particles in the pulmonary interstitium.

Adult↗
PubMed1988

A beneficial effect of trypsin on the purification of turnip mosaic virus (TuMV) and other potyviruses.

The effects of treatment with trypsin during the purification of turnip mosaic virus (TuMV), on virus yield, infectivity and integrity of virus coat protein were examined. Trypsin increased yield markedly, and at a low concentration, increased infectivity. These effects were probably due to reduced aggregation of virus particles. At higher concentrations of trypsin, there was some degradation of virus coat protein, and infectivity was reduced. Treatment with trypsin at the optimum concentration can significantly improve purification of TuMV; more limited experiments suggest that it can also be applied to other potyviruses.

Capsid↗
PubMed1988

Lung perforation complicating tube thoracostomy: pathologic description of three cases.

Insertion of a chest tube into the pleural space is standard therapy for a variety of pleural abnormalities. Three cases are described of lung perforation secondary to this procedure. In all three cases the tube had been inserted with the use of a trocar, and in two there were pleural adhesions in the vicinity of the puncture; in none was the perforation suspected clinically or considered to contribute to patient death. Pathologic features included one or two pleural holes continuous with a parenchymal tract of variable length. In one case, there was early epithelialization of the inner surface of the tract, suggesting that some of these may remain patent and be seen as incidental findings long after their formation. Two of the cases were identified among 18 patients who had had chest tubes inserted and came to autopsy over a similar period, implying that the incidence of the complication is greater than is generally appreciated. Reasons for this under appreciation are the lack or nonspecificity of clinical and radiographic findings and the ease with which perforation can be overlooked at autopsy.

Aged↗
PubMed1987

Catheter-induced pulmonary artery perforation: pathologic and pathogenic features.

Perforation of the pulmonary artery due to insertion of a balloon-tipped, flow-directed (Swan-Ganz) catheter is described in four cases. These cases were found in a consecutive series of 270 autopsies done over a 1.5-year period and suggest that the incidence of this complication may be greater than the number of clinically reported cases implies. In three instances, a focal parenchymal hematoma or thrombotic nodule identified the site of rupture. Other pathologic features and the pathogenesis of the perforation are discussed. Difficulties in postmortem diagnosis include distinguishing perforation from hemorrhage due to trauma, thromboembolism, and coagulation abnormalities.

Aged↗
PubMed1987

Pulmonary involvement in giant cell arteritis.

While clinically suspected in some cases, pulmonary lesions in giant cell arteritis have rarely been described pathologically. We report the findings at autopsy in an elderly woman with typical giant cell arteritis. In addition to inflammation of temporal and other major systemic vessels, large- and medium-sized pulmonary arteries showed focal necrosis as well as medial granulomatous inflammation. These findings, as well as a review of previous clinical and pathologic reports, emphasize that the disease can affect the lungs and may rarely be a significant cause of morbidity.

Aged↗
PubMed1985

A new physical assay method for tobacco mosaic virus using a radioactive virus recovery standard and the first derivative of the ultraviolet absorption spectrum.

A new physical assay method for tobacco mosaic virus is described which incorporates two improvements on previous procedures. Losses of up to 75% of virus during extraction are corrected by adding a trace of radioactive virus to leaf samples before homogenization, and determining percentage recovery of radioactivity in final virus preparations. Estimation of virus concentration in partially purified preparations is from the first derivative (dA/d lambda) of the ultraviolet absorption spectrum, using a pronounced signal from the tryptophan fine-structure absorption band at 285-293 nm. This method is highly insensitive to ultraviolet-absorbing contaminants, which cause errors and increase variation between replicates, when estimation of virus concentration is by normal measurement of ultraviolet absorption (A260). The method can be applied to at least some other viruses.

RNA, Viral↗
PubMed1984

Long-term effects of pulmonary shrapnel injury. Report of a case with carcinoma and residual shrapnel tract.

Bullets and shrapnel fragments may occasionally lead to intrathoracic complications many years after their initial penetration. We report a case of pulmonary carcinoma arising in relation to pleural scarring from a shrapnel wound received 38 years earlier. An incidental finding was a patent, epithelialized tract running from the upper lobe pleural scar deep into the lower lobe, interpreted as a residue of the shrapnel's path through the lung.

Adenocarcinoma, Papillary↗
PubMed1983

Theoretical analysis of a method for determining the pattern of macromolecular synthesis during the cell cycle.

The dual-labelling centrifugal-elutriation method has been extensively used to study patterns of macromolecular synthesis and accumulation in the yeast cell cycle. Cells are long-term labelled with a radioactive precursor for about 1.5 cycles (a measure of macromolecular mass), then pulse-labelled with a precursor containing a different radioactive isotope for the final 0.1 cycle (a measure of rate of synthesis). Harvested cells are fractionated into cell cycle stages by centrifugal elutriation, and changes in pulse : long-term labelling during the cycle determined. This pattern of change is compared with theoretical changes in rate : mass calculated for various patterns of synthesis. Using this method, it has been suggested that rates of synthesis and accumulation of several types of RNA and protein all increase exponentially through the cycle. In contrast, experiments using synchronous cultures or zonal centrifugation for cell cycle analysis have suggested other synthetic patterns, including periodic doubling in rate in each cycle. In this paper we analyse whether the dual-labelling, centrifugal-elutriation method is capable of discriminating between exponential and periodic rate-doubling patterns. Three possible sources of imprecision in the method and its application are examined. (1) Theoretical rate : mass curves have been simulated for macromolecules with a wider range of properties than previously considered. It is shown that for some important classes, such as messenger RNAs, with turnover rates in the range measured experimentally, and proteins, differences between rate : mass curves for exponential and periodic rate-doubling models are considerably smaller than previously suggested. (2) Long-term labelling is shown to be an accurate measure of macromolecular mass, but pulse-labelling can be inadequate as a measure of rate of synthesis. The error is greater with RNAs with faster turnover, and again reduces the ability of the method to discriminate exponential and periodic rate-doubling models of synthesis. The error is greater with RNAs with faster turnover, and again reduces the ability of the method to discriminate exponential and periodic rate-doubling models of synthesis. (3) Imperfections in cell cycle fractionation by centrifugal elutriation are examined, and by computer simulation it is shown that these also reduce the ability of the method to distinguish between the two models of synthesis. The three sources of imprecision are cumulative. It is concluded from simulation analyses that the differences between exponential and periodic rate-doubling patterns analysed by the method would be so small as to be almost impossible to establish against the background of error in experimental measurement. We therefore suggest that in practice, the dual-labelling centrifugal-elutriation method is unable to discriminate between the exponentially increasing and periodic rate-doubling models. The mathematical treatment developed in this paper should be applicable to analysis of other methods and cell cycle events.

Cell Cycle↗
PubMed1981

Scoring technique for diagnosis of ventricular hypertrophy from three orthogonal lead electrocardiogram.

A prospective study for the development of scoring techniques for the diagnosis of ventricular hypertrophy from the three orthogonal lead electrocardiogram was undertaken. A total of 51 hearts was examined at necropsy in a training group on which the scoring techniques were developed and a test group of a further 82 hearts was studied to assess the sensitivity and specificity of the method. The hearts were classified as being normal or having left ventricular hypertrophy, right ventricular hypertrophy, biventricular hypertrophy, or were placed in a borderline category. These classifications were based on the measurement of the weight of the left ventricular free wall, the interventricular septum, and the right ventricular free wall. Classical electrocardiographic variables were selected and assigned a point score on the basis of their diagnostic value. The electrocardiographic diagnosis of left ventricular hypertrophy, right ventricular hypertrophy, and biventricular hypertrophy was then made when the relevant score exceeded four points. After excluding 25 cases which showed conduction defects or were regarded as borderline at necropsy, 57 cases remained in the test group for assessing the technique. The sensitivity and specificity for left ventricular hypertrophy were 65 per cent and 91 per cent, respectively. For right ventricular hypertrophy corresponding results were 53 and 90 per cent. For biventricular hypertrophy the sensitivity was lower at 42 per cent, with a corresponding specificity of 93 per cent. These results represent a considerable improvement over older techniques, with up to a tenfold increase in sensitivity being obtained. The technique can be applied with or without computer assistance.

Adult↗
PubMed1979

Altered patterns of ribonucleic acid synthesis during the cell cycle: a mechanism compensating for variation in gene concentration.

In the fission yeast Schizosaccharomyces pombe, a series of diploid mutants divides at smaller cell sizes than wild type. In these smaller strains, the mean gene concentration (defined by previous authors as the DNA to protein ratio) is higher than in wild type. Such an increase in gene concentration should also increase the concentration of those components such as messenger and ribosomal RNA, whose rate of synthesis is determined by gene dosage. We show that the mean concentrations of these 2 RNA species in the small cells are not increased, but are the same as in wild type. The small mutant cells are thus able to compensate for changes in gene concentration. This compensation is shown to operate through differences in the patterns of synthesis of RNA during the cell cycle. In all the strains of the diploid series, the rates of synthesis of messenger and ribosomal RNA double as steps once in each cell cycle. The timings of the steps in the cell cycle appear to be cell-size related, since the smaller the cell at division, the later are the steps in the cell cycle. In contrast, there is comparatively little variation in the timing of DNA replication in the cycles of cells of different sizes. We propose that after DNA replication, there is a delay before doubling in the rate of transcription. Such a cell mass-related delay is all that is required to compensate for increased gene concentration, and results in the same mean functional DNA concentration in all strains. This mechanism will maintain the same mean messenger and ribosomal RNA concentrations in cells dividing at different sizes. Ways in which the cell size-related control over transcription may operate are discussed.

Adenine↗
PubMed1979

Analysis of the significance of a periodic, cell size-controlled doubling in rates of macromolecular synthesis for the control of balanced exponential growth of fission yeast cells.

Mutant strains of the fission yeast Schizosaccharomyces pombe are available which divide at smaller mean sizes than wild type. Earlier work by the present authors has shown that all these strains double their rates of polyadenylated messenger RNA synthesis as a step once in each cell cycle. The smaller the cell, the later in the cycle is the doubling in rate of synthesis. Strains of all sizes, however, double their synthetic rate when at the same threshold size. We show here that the differences in cell cycle stage of doubling in rate of polyadenylated messenger RNA synthesis are enough to explain the reduced mean steady state polyadenylated messenger RNA contents of the smaller strains. The cell size-related control over doubling in rate of synthesis is also shown to maintain the mean polyadenylated messenger RNA content as a constant proportion of cell mass, irrespective of cell size. This control thus allows cells to maintain balanced exponential growth, even when absolute growth rate per cell is altered by mutation. It is also shown that the concentration of polyadenylated messenger RNA itself could act as a monitor of the threshold size triggering the doubling in rate of synthesis in each cell cycle.

Ascomycota↗