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Biomedical subjects

E J Sullivan

Publications and source records attributed to E J Sullivan.

At least 19 recordsLinked to original sources
PubMed2001

The spectrum of mutations in TSC1 and TSC2 in women with tuberous sclerosis and lymphangiomyomatosis.

Lymphangiomyomatosis (LAM) is a progressive and often fatal interstitial lung disease characterized by a diffuse proliferation of abnormal smooth muscle cells in the lungs. LAM is of unusual interest biologically because it affects almost exclusively young women. LAM can occur as an isolated disorder (sporadic LAM) or in association with tuberous sclerosis complex (TSC). Because only a minority of women with TSC develops symptomatic LAM, we hypothesized that a relationship might exist between the type of germline TSC1 or TSC2 gene mutation and the risk of developing LAM. We examined all 41 exons of the TSC2 gene and 21 coding exons of the TSC1 gene for mutations in a group of 14 women with both TSC and LAM using single-strand conformation polymorphism analysis. Seven mutations were found in TSC2 and one in TSC1. Of the seven patients with TSC2 mutations, two had the same in-frame exon 40 deletion and one had an exon 41 missense change. We conclude that germline mutations in the extreme carboxy-terminus of tuberin can result in LAM. Further studies will be required to determine whether mutations in exons 40 and 41 are associated with an increased incidence and/or severity of LAM in women with TSC.

Exons↗
PubMed2000

Pulmonary involvement in Niemann-Pick disease: case report and literature review.

Niemann-Pick disease (NPD) is a rare, inherited, autosomal recessive, lipid storage disease. The pathognomonic intracellular accumulation of sphingomyelin results in the production and accumulation of 'foam cells'. Interstitial lung disease is a rare manifestation of NPD. We present the case of a 48-year-old white female with NPD involving the lungs, liver and spleen. The chest radiograph showed bilateral, predominantly basal reticulonodular infiltrates and serial pulmonary function tests over a period of years showed preserved expiratory airflow and a severely decreased diffusion capacity for carbon monoxide (DLCO). In view of her visceral involvement, lack of neurological symptoms and survival into adulthood, we believe our patient represents a case of type B NPD. In this type of NPD, aside from prominent hepatosplenomegaly and sexual immaturity, significant pulmonary infiltration with 'Pick cells' has been reported. To date, no therapeutic modality has been shown to alter the natural history of this disease, which results in progressive debilitation and death. This case is unique in that it provides the longest physiological follow-up in the literature, and provides data on the natural history of pulmonary involvement in NPD.

Carbon Monoxide↗
PubMed2000

Role of Tc-99m MIBI in the evaluation of single pulmonary nodules: a preliminary report.

BACKGROUND: Survival in bronchial carcinoma is closely related to the stage of the disease at the time of diagnosis and a single pulmonary nodule represents a potentially curable stage. This study was conducted to assess the feasibility of using Tc-99m labelled 2-methoxy isobutyl isonitrile (MIBI) to differentiate benign from malignant single pulmonary nodules. METHODS: A prospective study was conducted in the outpatient pulmonary clinic at the Cleveland Clinic Foundation. Twenty five patients with single pulmonary nodules considered indeterminate by their physicians and undergoing a procedure for tissue diagnosis were evaluated by Tc-99m MIBI SPECT scanning prior to definitive testing. Assessment of MIBI uptake was done qualitatively (subjectively) and quantitatively and correlated with the histopathology and nodule size. RESULTS: Of the 21 patients with malignant lesions, 18 had increased uptake of MIBI corresponding to the location of the nodule and were considered positive. The predominant tumour types were large cell (n = 5) and adenocarcinoma (n = 10). All four patients with benign lesions had negative MIBI scans. For malignancy the overall specificity was 100%, sensitivity was 85.7%, positive predictive value was 100%, and negative predictive value was 57%. Quantitative uptake of MIBI correlated with the diameter of the nodule with a correlation coefficient of 0.61 by Spearman's rank sum test. This relationship was statistically significant (p = 0.02). CONCLUSION: This preliminary study suggests that Tc-99m MIBI has a very high specificity and positive predictive value for malignant single pulmonary nodules and might be a useful non-invasive diagnostic modality in their management.

Aged↗
PubMed2000

Exogenous granulocyte-macrophage colony-stimulating factor administration for pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by the accumulation of lipoproteinaceous material within the alveoli. Recent data suggest that granulocyte-macrophage colony- stimulating factor (GM-CSF) may be involved in the pathogenesis of PAP. To extend this understanding and clarify whether GM-CSF replacement confers benefit, we report the preliminary results for the first four patients in an open-label study of GM-CSF treatment for moderate exacerbation of PAP. All four patients had idiopathic PAP confirmed by open lung biopsy. Subcutaneous GM-CSF was self-administered once daily for 12 wk (dose escalation from 3 to 9 microg/kg/d). Response was assessed from symptom scores, arterial blood gas measurements, pulmonary function testing, and chest radiographs. Three of the four patients experienced symptomatic, physiologic, and radiographic improvement with GM-CSF. Responders experienced sufficient improvement in oxygenation as to eliminate the need for supplemental oxygen, and one patient was removed from the waiting list for lung transplantation. Improved oxygenation was not apparent until 8 to 12 wk after the start of therapy. Notably, expected increases in the peripheral white blood cell count did not occur, suggesting lack of a hematopoietic response to exogenous GM-CSF in PAP. We conclude that GM-CSF appears to benefit a subset of patients with adult PAP, and may represent an alternative to whole-lung lavage in treating the disease.

Adult↗
PubMed1998

Pulmonary vasculitis.

Pulmonary vascular inflammation may be seen in a variety of primary lung diseases and in the setting of numerous systemic illnesses. This article reviews those entities in which pulmonary vasculitis represents a central feature of the pathologic process (Wegener's granulomatosis, Churg-Strauss syndrome, and pulmonary capillaritis). In addition, features of pulmonary involvement in other systemic vasculitides (Giant Cell Arteritis, Takayasu's Arteritis, and Behçet's disease) are described. Finally, general principles for the treatment of vasculitis are reviewed.

Humans↗
PubMed1996

Enhancing nursing competence with substance abusing clients.

Alcohol and other drug abuse, major threats to health, pose challenges for nurses in virtually every practice setting. Progress toward increasing nursing competence in the addictions field is being made through the development of practice standards and model curricula and through federal initiatives to increase faculty expertise in this field. The next critical step is to forge creative collaborative links with practice settings, links that assure that requisite learning is reality-based and in step with the future of health care. This article outlines progress toward improving nursing competence in substance abuse and suggests reality-based learning strategies as a future direction for this important goal for nursing education. Two successful models of collaboration between education and practice, designed to augment basic curriculum and improve nursing knowledge, skills and attitudes related to substance abuse, are described.

Alcoholics Anonymous↗
PubMed1994

Light-generated oligonucleotide arrays for rapid DNA sequence analysis.

In many areas of molecular biology there is a need to rapidly extract and analyze genetic information; however, current technologies for DNA sequence analysis are slow and labor intensive. We report here how modern photolithographic techniques can be used to facilitate sequence analysis by generating miniaturized arrays of densely packed oligonucleotide probes. These probe arrays, or DNA chips, can then be applied to parallel DNA hybridization analysis, directly yielding sequence information. In a preliminary experiment, a 1.28 x 1.28 cm array of 256 different octanucleotides was produced in 16 chemical reaction cycles, requiring 4 hr to complete. The hybridization pattern of fluorescently labeled oligonucleotide targets was then detected by epifluorescence microscopy. The fluorescence signals from complementary probes were 5-35 times stronger than those with single or double base-pair hybridization mismatches, demonstrating specificity in the identification of complementary sequences. This method should prove to be a powerful tool for rapid investigations in human genetics and diagnostics, pathogen detection, and DNA molecular recognition.

Base Sequence↗
PubMed1993

Electrically induced calcium elevation, activation, and parthenogenetic development of bovine oocytes.

The influence of electrical stimulation on the level of intracellular Ca2+ in bovine oocytes, as well as activation and extent of parthenogenetic development, was investigated. Mature oocytes were electrically stimulated at 29 hr of maturation, and intracellular Ca2+ concentration was determined with the Ca2+ indicator fura-2 dextran (fura-2 D). The Ca2+ response of oocytes to a given electrical pulse was variable. Oocytes responded with either no Ca2+ rise from baseline (approximately 12 nM), a short-duration Ca2+ rise (from 12 nM to 300 nM) that returned to baseline within 2 min of the pulse, or a long-duration Ca2+ rise (from 12 nM to 1,000-2,000 nM) that never returned to baseline during the 8 min period over which the oocytes were monitored. In these oocytes, Ca2+ level returned to baseline when oocytes were removed from 0.30 M mannitol and placed in an ionic medium. Increasing field strength or pulse duration tended to increase the proportion of oocytes displaying a Ca2+ rise, and at 1.0 kVcm-1 for 40 microseconds, all oocytes displayed a long-duration Ca2+ elevation. Direct transfer of oocytes from culture medium to mannitol also triggered a Ca2+ rise. Multiple stimulations, either electrical or by transferring to mannitol, produced multiple Ca2+ rises. This mannitol-induced Ca2+ rise could be inhibited by first washing the oocytes in medium containing equal parts of 0.30 M mannitol and phosphate buffered saline (PBS). The level of Ca2+ stimulation affected activation and development of oocytes. Insufficient, or, conversely, excessive Ca2+ stimulation impaired development. Optimum development was obtained with 1) three pulses of 0.2 kVcm-1 for 20 microseconds, each pulse 22 min apart, after direct transfer of oocytes from culture medium to mannitol (22% blastocysts) or 2) three pulses of 1.0 kVcm-1 for 20 microseconds after transfer of oocytes from culture medium to medium containing equal parts mannitol and PBS, then to mannitol (24% blastocysts). This procedure avoided induction of a Ca2+ rise prior to the pulse. The results indicate that the level of Ca2+ stimulation can be regulated by incubation conditions prior to the pulse and, to some extent, by field strength and pulse duration. The level of electrical stimulation influenced oocyte Ca2+ response, activation, and parthenogenetic development.

Animals↗
PubMed1993

Histone H1 kinase activity in bovine oocytes following calcium stimulation.

The influence of number of Ca2+ stimulations on the profile of histone H1 kinase activity in bovine oocytes was investigated. A CA2+ stimulation consisted of transferring oocytes directly from culture medium to mannitol containing 100 microM Ca2+ and pulsing oocytes with a 0.2 kVcm-1, 20 microseconds discharge. One, three, or six Ca2+ stimulations were given, each 22 min apart. Oocytes were frozen from 0 to 8 hr after the first stimulation at indicated time points and assayed for histone H1 kinase activity. H1 kinase activity was quantified using a densitometer and expressed as a percent of activity in nonpulsed metaphase II oocytes. Stimulating oocytes in the absence of Ca2+ in the pulsing medium did not inactivate H1 kinase. In the presence of Ca2+, however, H1 kinase was rapidly inactivated after stimulation. A single stimulation decreased H1 kinase activity to 44% +/- 11% of its initial level in 1 hr. However, H1 kinase was dramatically reactivated at 2 hr after the stimulation and reached 122% +/- 22% of the initial activity at 6 hr. With three stimulations, basal H1 kinase activity was 21% +/- 3% and was obtained in 30 min. H1 kinase reactivation started at 4 hr after the first stimulation and level of activity reached 38% +/- 15% at 8 hr. Six stimulations also led to rapid H1 kinase inactivation and to a basal activity of 14% +/- 0.4%. With six stimulations, however, basal H1 kinase activity was maintained over at least 8 hr, and no reactivation occurred during this period. Basal H1 kinase activity obtained after six stimulations was similar to that of fertilized oocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗