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W F Coulson

Publications and source records attributed to W F Coulson.

At least 19 recordsLinked to original sources
PubMed2002

Deep-seated mycosis as a complication in bone marrow transplantation patients.

Achieving control of opportunistic fungal infections which occur during the course of immunosuppressive therapy is one of the key factors deciding the success or failure of bone marrow transplantation (BMT). A review was conducted of autopsied patients who had undergone BMT at the University of California at Los Angeles Medical Center in the USA between 1985 and 1994. The incidence of complication by deep-seated mycoses was determined, and the causative fungal species and invaded organs were elucidated. Deep fungal infections were found to have occurred in 31.5% (47/149 cases) of the BMT patients, and disseminated disease was found in approximately one-quarter of the infected cases. The findings suggest that BMT patients, who require the use of potent immunosuppressive agents, show increased susceptibility to the development of more serious, and widespread diffuse fungal infections. The most commonly detected causative fungi were Aspergillus species and Candida species. In addition, it was found that the incidence of candidosis had decreased markedly in recent years; conversely, aspergillosis had increased. It was surmised that these findings reflect the development of antifungal agents which are effective against candidosis and have enabled a reduction in the incidence of this disease even in BMT patients, whereas aspergillosis remains difficult to treat. In consideration of these findings regarding the manifestation of deep-seated mycosis in BMT patients, we conclude that in order to increase the success rate of BMT it will be essential to establish safe and effective methods for the prevention and treatment of aspergillosis.

Adolescent↗
PubMed2001

Histopathology of cryptococcosis and other fungal infections in patients with acquired immunodeficiency syndrome.

OBJECTIVE: To gain insight into the histopathologic characteristics of fungal infection in acquired immunodeficiency syndrome (AIDS). METHODS: A review was conducted of the histopathology for 162 patients with evident fungal infection. RESULTS: The microscopic appearance of esophageal candidiasis that was common in patients with single organ involvement revealed necrotic debris containing proliferating hyphae at the site of mucosal erosions without fungal invasion of underlying tissue. The incidence of oral and esophageal candidiasis was followed by that of pulmonary aspergillosis and Candida infection. Eighteen patients had generalized cryptococcosis, representing the commonest generalized fungal disease. The essential histologic features of the disease consisted of yeast cell proliferation with a histiocytic response, but only minor lymphocytic and neutrophilic components. This was different from the manifestations of both Candida and Aspergillus infections. The two histologic patterns recognized in the pulmonary cryptococcal lesions could be graded with respect to the degree and type of inflammatory reaction. The milder one consisted of small scattered foci of intra-alveolar cryptococcal proliferation with a histiocytic response. Another pattern involved massive cryptococcal infection, which might be simply more extensive than that in the former. Capillary involvement of alveolar septa was an important common finding in all 18 patients.

Acquired Immunodeficiency Syndrome↗
PubMed2000

[Deep-seated mycosis in patients with solid-organ transplantation--a study of autopsied cases in the United States].

Autopsies with solid-organ trans plantation (SOT) in UCLA Medical Center were reviewed, especially focussing on the deep-seated fungal infection and the incidence of fungal infections, causative fungi, and organs involved were evaluated. Deep-stated fungal infections were demonstrated in 21.0% of the patients with SOT. The incidence of fungal infections were 26.1% in kidney transplantation, which was the highest rate in SOT autopsies we reviewed, 25.0% in liver transplantation, 14.3% in lung transplantation, and 13.2% in heart transplantation. And the most common causative fungi were Aspergillus species, seen in 70.6% of SOT autopsies. In contrast, Candida species were observed in 25.5%. In addition, the incidence of deep-seated mycosis has been increasing since 1992, this was parallel to the increase of aspergillosis, most of which were found as a generalized spreading. In contrast, candidal lesions, were almost limited to the digestive tracts. The above suggests that from this standpoint, improvement of prophylactic and therapeutic technique against aspergillosis is the greatest problem in deep-seated mycosis in SOT patients.

Adolescent↗
PubMed1997

Multiple granular cell tumor: a case report and review of the literature.

BACKGROUND: Granular cell tumor was first described by Abrikossoff in 1926. It is rare and usually presents as a benign solitary lesion. Multifocal and malignant forms are known to occur. METHODS: This presentation illustrates an additional case of granular cell tumor. Clinical and histological features to distinguish malignant and benign forms are presented. RESULTS: Tumor can develop years after therapy for the primary lesion. Treatment recommendations are presented. CONCLUSIONS: Patients diagnosed with granular cell tumor require close follow-up. Radiographic evaluation for the presence of metastatic disease is necessary if a malignant variant is suspected.

Adult↗
PubMed1997

Male rats fed methyl- and folate-deficient diets with or without niacin develop hepatic carcinomas associated with decreased tissue NAD concentrations and altered poly(ADP-ribose) polymerase activity.

Folate is an essential cofactor in the generation of endogenous methionine, and there is evidence that folate deficiency exacerbates the effects of a diet low in choline and methionine, including alterations in poly(ADP-ribose) polymerase (PARP) activity, an enzyme associated with DNA replication and repair. Because PARP requires NAD as its substrate, we postulated that a deficiency of both folate and niacin would enhance the development of liver cancer in rats fed a diet deficient in methionine and choline. In two experiments, rats were fed choline- and folate-deficient, low methionine diets containing either 12 or 8% casein (12% MCFD, 8% MCFD) or 6% casein and 6% gelatin with niacin (MCFD) or without niacin (MCFND) and were compared with folate-supplemented controls. Liver NAD concentrations were lower in all methyl-deficient rats after 2-17 mo. At 17 mo, NAD concentrations in other tissues of rats fed these diets were also lower than in controls. Compared with control values, liver PARP activity was enhanced in rats fed the 12% MCFD diet but was lower in MCFND-fed rats following a further reduction in liver NAD concentration. These changes in PARP activity associated with lower NAD concentrations may slow DNA repair and enhance DNA damage. Only rats fed the MCFD and MCFND diets developed hepatocarcinomas after 12-17 mo. In Experiment 2, hepatocarcinomas were found in 100% of rats fed the MCFD and MCFND diets. These preliminary results indicate that folic acid deficiency enhances tumor development. Because tumors developed in 100% of the MCFD-fed rats and because tissue concentrations of NAD in these animals were also low, further studies are needed to clearly define the role of niacin in methyl-deficient rats.

Animals↗
PubMed1994

Effects of therapy with soluble tumour necrosis factor receptor fusion protein on pulmonary cytokine expression and lung injury following haemorrhage and resuscitation.

Acute lung injury frequently develops following haemorrhage, and is characterized by increased proinflammatory cytokine levels and massive neutrophil accumulation in the lung. Blood loss produces rapid increases in tumour necrosis factor-alpha (TNF-alpha) mRNA expression among pulmonary cell populations which precede the development of lung injury. In order to examine the role of TNF-alpha in producing acute inflammatory lung injury, we treated mice following haemorrhage and resuscitation with a TNF antagonist, composed of soluble dimeric human p80 TNF receptor linked to the Fc region of human IgG1 (sTNFR:Fc). Therapy with sTNFR:Fc prevented the post-haemorrhage increases in circulating and pulmonary TNF-alpha levels normally found following blood loss. Administration of sTNFR:Fc also diminished the increase in IL-1 beta, IL-6, TNF-alpha and interferon-gamma (IFN-gamma) mRNA normally found in the lungs following haemorrhage. However, therapy with sTNFR:Fc was not associated with improvement in the histologic parameters of post-haemorrhage lung injury, such as neutrophil infiltration and interstitial oedema. In contrast to the effects of sTNFR:Fc on cytokine mRNA levels among intraparenchymal pulmonary mononuclear cells, such therapy following haemorrhage was associated with increased amounts of mRNA for TNF-alpha among peripheral blood mononuclear cells, as well as increased IFN-gamma titres in serum and bronchoalveolar lavage (BAL) specimens. These results indicate that therapy with sTNFR:Fc in the post-haemorrhage period, although capable of decreasing proinflammatory cytokine expression in the lungs, does not prevent the development of acute lung injury in this setting.

Animals↗
PubMed1994

Hemorrhage and resuscitation induce alterations in cytokine expression and the development of acute lung injury.

Acute pulmonary injury occurs frequently following hemorrhage and injury. In order to better examine the sequence of events leading to lung injury in this setting, we investigated lung histology as well as in vivo mRNA levels for cytokines with proinflammatory and immunoregulatory properties (IL-1 beta, IL-6, IL-10, TNF-alpha, TGF-beta, IFN-gamma) over the 3 days following hemorrhage and resuscitation. Significant increases in mRNA levels for IL-1 beta, IL-6, IL-10, and IFN-gamma, but not TNF-alpha, were present among intraparenchymal pulmonary mononuclear cells obtained 1 and 3 days after hemorrhage. Among alveolar macrophages, TNF-alpha and IL-1 beta mRNA levels were increased 3 days after hemorrhage. Few changes in cytokine mRNA levels, with the exception of TNF-alpha at 3 days after hemorrhage, were present among peripheral blood mononuclear cells. Histologic examination of lungs from hemorrhaged animals showed no alterations 1 day after hemorrhage, but neutrophil and mononuclear cell infiltrates, edema, intra-alveolar hemorrhage, and fibrin generation were present 3 days after hemorrhage. These results suggest that hemorrhage-induced enhancement of proinflammatory cytokine gene transcription may be an important mechanism contributing to the frequent development of acute lung injury following blood loss and injury.

Animals↗
PubMed1994

Anti-transforming growth factor-beta monoclonal antibodies prevent lung injury in hemorrhaged mice.

Acute lung injury, characterized as the adult respiratory distress syndrome (ARDS), is a common clinical occurrence following blood loss and injury. We previously found increased levels of transforming growth factor (TGF)-beta 1 mRNA in murine intraparenchymal mononuclear cells and in alveolar macrophages within 1 h after hemorrhage. Because TGF-beta has potent proinflammatory and immunoregulatory properties, we investigated the effect of blocking TGF-beta with mAb on hemorrhage-induced pathology, cytokine mRNA levels in lungs, as well as survival from pneumonia. Mice treated with anti-TGF-beta mAb showed normal pulmonary histology 3 days after hemorrhage and resuscitation in contrast to the mononuclear and neutrophil infiltrates, intraalveolar hemorrhage, and interstitial edema found in hemorrhaged mice either treated with control antibody or not treated with any antibody. Decreased mRNA levels for IL-1 beta, TNF-alpha, IL-6, IL-10, and IFN-gamma as compared with untreated, hemorrhaged controls were present in intraparenchymal pulmonary mononuclear cells following therapy with anti-TGF-beta. In contrast, therapy with anti-TGF-beta increased mRNA levels for IL-1 beta and TNF-alpha in alveolar macrophages and for TGF-beta in peripheral blood mononuclear cells collected 3 days after hemorrhage. Administration of anti-TGF-beta to hemorrhaged mice did not correct the enhanced susceptibility to Pseudomonas aeruginosa pneumonia that exists after hemorrhage. These results suggest that TGF-beta has an important role in hemorrhage-induced acute lung injury, but does not contribute to the post-hemorrhage depression in pulmonary antibacterial response.

Animals↗
PubMed1994

Pathological features of inflammatory bowel disease in childhood.

Inflammatory bowel disease (IBD) in childhood is realistically interpreted to mean ulcerative colitis (UC) and Crohn's disease of the colon. Their gross and microscopic features are discussed along with the differential diagnosis from other childhood conditions associated with bloody diarrhea.

Child↗
PubMed1993

Frequency and distribution of occult micrometastases in lymph nodes of patients with non-small-cell lung carcinoma.

BACKGROUND: Accurate assessment of the presence and absence of tumor in the regional lymph nodes is critical in assessment of prognosis for patients with lung cancer. Development of sensitive immunohistochemical techniques and specific monoclonal antibodies has increased our capacity, in melanoma and breast cancer, to detect small groups of tumor cells or even single tumor cells in lymph nodes that appear to be tumor free in conventionally stained sections. PURPOSE: This retrospective study was designed to assess whether use of a polyclonal antikeratin reagent in immunohistochemical analysis offers any advantage over conventional histopathology in detection of regional lymph node metastases in non-small-cell lung cancer. METHODS: Paraffin-embedded tissue sections from regional lymph nodes of 65 patients with non-small-cell lung cancer were studied. We examined tissue from 588 nodes of 60 patients with a diagnosis of disease confined to the lung and from 72 nodes of five patients with a diagnosis of metastasis to some nodes. A polyclonal antikeratin antibody was applied to the lymph node tissue sections, using the avidin-biotin complex immunoperoxidase technique. RESULTS: Single tumor cells and small clusters of tumor cells (occult micrometastases) not visible on routine evaluation were readily detected in 38 (63%) of the 60 patients whose nodes appeared to be negative on examination of hematoxylin-eosin-stained slides. In the five patients with a diagnosis of node-positive non-small-cell lung cancer, five (10%) of 51 nodes that were tumor free on conventional examination contained metastases. Metastatic tumor cells were most often located in the subcapsular or medullary sinuses. The lymph nodes that contained occult tumor cells were those located nearest to the tumor, mainly in peribronchial and hilar locations. The median survival of patients with occult metastases (1977 days) was shorter than that of patients whose nodes contained no tumor (2456 days) but was longer than that of patients whose nodes contained metastases detectable on hematoxylin-eosin-stained slides (927 days). CONCLUSIONS: Our results suggest that, in patients with non-small-cell lung cancer, metastatic involvement of regional lymph nodes is more frequent than was previously determined by the conventional histologic method and substantially more frequent than in other tumor types, such as melanoma and breast cancer. IMPLICATIONS: The high frequency of occult nodal metastases in non-small-cell lung cancer makes it clear that, without immunohistochemistry, disease is understaged in many patients. Therefore, it seems essential that immunohistochemical evaluation of the lymph nodes be undertaken in clinical trials.

Adult↗
PubMed1993

Bronchiolitis obliterans organizing pneumonia in polymyositis. A case report with longterm survival.

In 1973, a 36-year-old black woman with dyspnea on exertion, Raynaud's phenomenon and arthralgia was first seen at the University of California at Los Angeles Medical Center. Her chest roentgenography showed bilateral basilar infiltration, open lung biopsy revealed bronchiolitis obliterans with organizing pneumonia (BOOP) and muscle biopsy was consistent with inflammatory myopathy. She has been followed for 18 years, has responded well to conservative treatment, initially with alternate day prednisone, with added azathioprine for the past 8 years, and remained fully employed. The favorable prognosis of this case is consistent with that of the BOOP category proposed by Tazelaar, et al in 1990. We conclude that a careful histological subclassification is suggested before initiating aggressive therapy in patients with polymyositis and interstitial lung disease.

Adult↗
PubMed1992

17 alpha-Z-[125I]iodovinyloestradiol and its 3-acetate: chemical synthesis in vivo distribution studies in the rat. Comparison of tissue accumulation and metabolic stability with 17 alpha-E-[125I]iodovinyl and 16 alpha-[125I]iodo oestradiols.

Certain oestrogens on substitution with halogens, have been shown to retain receptor binding affinity and accumulate in target tissues and therefore could, when labelled with gamma-emitting halogen isotope, act as radiopharmaceuticals for the imaging of receptor positive breast tumours. In order to evaluate putative radiopharmaceuticals, 17 alpha-Z-iodovinyloestradiol ((17 alpha,20Z)-21-iodo-19-norpregna-1,3,5(10),20-tetraene-3,17 beta-diol) and its 3-acetate have been chemically synthesized and labelled with 125I. Tissue distribution studies in female rats have been compared to those obtained using 17 alpha-E-[125I]iodovinyloestradiol ((17 alpha,20E)-21-[125I]iodo-19-norpregna-1,3,5(10),20-tetraene-3,17 beta-diol) and its 3-acetate and to 16 alpha-[125I]iodo oestradiol (1,3,5(10)-estratien-16 alpha-[125I]iodo-3,17 beta-diol). All compounds showed a similar tissue distribution with the highest concentrations (cpm/g tissue) in the thyroid greater than liver greater than uterus greater than kidney greater than lung greater than blood greater than heart, spleen. The concentration in the uterus was highest after injection of 17 alpha-Z-iodovinyloestradiols or 16 alpha-iodo oestradiol. Target (uterus) to background (blood) tissue ratios were highest after injection of 17 alpha-Z-iodovinyloestradiol-3-acetate and 16 alpha-iodo oestradiol (6:1). Deiodination in vivo took place to a small degree, amounting to 1.6%, 0.9% and 0.35% of the injected dose after 4 hr with the 17 alpha-Z, 17 alpha-E and 16 alpha compounds, respectively. For reasons of chemical expediency and consideration of the biological results 17 alpha-Z-iodovinyloestradiol-3-acetate is the compound of choice for the detection of oestrogen receptor positive tissues.

Animals↗
PubMed1992

Production and utilisation of antibodies directed against oestrone sulphate using specific hapten synthesis.

Oestrone-3-sulphate (E13S) is an important metabolite of oestrone. Studies in cattle had previously shown that it is synthesised in the gravid uterus by the foetus, but not by the corpus luteum. Progesterone measurement in milk by radioimmunoassay (RIA) is routinely carried out in some laboratories as a pregnancy test for cattle. The major drawback of progesterone measurement in milk, by RIA, as a pregnancy test was the failure to detect the lack of conceptus in those cows where early embryonic death had occurred but the corpus luteum still persisted thereby giving false positive results. We have developed a direct RIA for E13S by raising antibodies to an immunogen prepared from a specific hapten synthesised by an unambiguous chemical synthesis. The sensitivity of the RIA in milk was found to be 0.368 nmol/l. The levels of E13S in non-pregnant cows are undetectable but during a viable pregnancy, the levels are elevated to greater than 0.40 nmol/l by day 100. There was no cross-reactions in the assay with any free oestrogens. The measurement of this metabolite of oestrone promises to provide an accurate marker for the detection of a viable conceptus in cattle.

Animals↗
PubMed1990

The synthesis of E-17 alpha-[131I]iodo-vinyl oestradiol and evaluation of its use as a radiotracer for oestrogen receptor positive breast tumours.

17 alpha-Iodo-vinyl oestradiol binds with high affinity to the oestrogen receptor, is metabolically stable and has been shown to accumulate in oestrogen sensitive tissues of rodents. We have synthesised this compound and its 3-acetate, labelled with carrier free 125I and shown the accumulation of both compounds in rat uterus. 17 alpha-Iodo-vinyl oestradiol-3-acetate was prepared labelled with carrier free 131I and administered to twelve patients with suspected breast cancer, approximately 1 h before surgical removal of the primary tumour mass. At the time of surgery a sample of the tumour and a peripheral blood sample were taken. The ratio of radioactivity in the tumour to blood was determined. All tumours accumulated radioactivity and ratios ranged from 1.5:1 to 3.7:1. There was no correlation between the degree of accumulation and either cytosolic oestrogen or progesterone receptor concentration in the tumour. Analysis of blood revealed a single circulating species, 17 alpha-iodo-vinyl oestradiol. The results show that 17 alpha-iodo-vinyl oestradiol is metabolically stable and accumulates in breast tumours though this accumulation is not sufficient to permit imaging.

Animals↗