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Biomedical subjects

M L Brown

Publications and source records attributed to M L Brown.

At least 55 records · Page 3Linked to original sources
PubMed1997

Parathyroid hyperplasia, thymic carcinoid and pituitary adenoma detected with technetium-99m-MIBI in MEN type I.

We report a case of a 57-yr-old woman with history of multiple endocrine neoplasia type I (MEN I). A 99mTc-sestamibi scan demonstrated a hyperplastic parathyroid gland, a large anterior mediastinal mass and a pituitary adenoma during a study done to evaluate recurrent hyperparathyroidism. The importance of this case is that much of the nonparathyroid pathology in patients with MEN I syndrome may be detected with this one study.

Carcinoid Tumor↗
PubMed1996

Protein and DNA requirements for the transcription factor IIIA-induced distortion of the 5 S rRNA gene promoter.

Transcription factor-induced DNA distortion has become a common theme in eukaryotic gene regulation. A number of techniques have been applied to the study of transcription factor-induced DNA bending and flexibility including electron microscopy, circular permutation gel analysis, helical phasing gel analysis and cyclisation kinetics in solution. We have applied these techniques in order to assess the role that specific DNA sequences and protein domains of transcription factor IIIA (TFIIIA) play in the TFIIIA-induced distortion of the Xenopus 5 S ribosomal RNA gene promoter. Electron spectroscopic imaging analysis of TFIIIA:DNA complexes indicate that TFIIIA binding involves compaction of the 5 S promoter into a precise three-dimensional hairpin-shaped structure. This compaction can be detected utilising circular permutation gel analysis and the distortion results in an apparent bend angle of 55 to 60 degrees near the centre of the TFIIIA binding site. Helical phasing analysis demonstrates that the 60 degrees bend angle as measured by circular permutation can be detected as a static bend directed towards the minor groove between bases +63 and +64 of the 5 S rRNA gene. The amplitude of the TFIIIA:5 S gene phasing signal is similar to the phasing signal obtained utilising bacterial CAP:DNA complexes with bend angles of approximately 90 degrees. These results are supported by phased ligase-mediated cyclisation kinetics in solution. Analysis of DNA deletion constructs indicate that the 5' A block of the internal 5 S gene promoter, which is required for transcriptional activity, is also required for TFIIIA-induced distortion of the 5 S gene promoter. Analysis of the N-terminal papain fragment of TFIIIA indicates that the 34 kDa zinc finger DNA binding domain is sufficient for compaction of the 5 S gene promoter. These results are discussed in relation to the modular model of TFIIIA:DNA interaction in which individual zinc fingers contribute to the protein-induced distortion of the DNA helix and overall DNA binding affinity in a complex, non-additive fashion.

Base Sequence↗
PubMed1996

Improvement in pulmonary function and elastic recoil after lung-reduction surgery for diffuse emphysema.

BACKGROUND: Pulmonary function may improve after surgical resection of the most severely affected lung tissue (lung-reduction surgery) in patients with diffuse emphysema. The basic mechanisms responsible for the improvement, however, are not known. METHODS: We studied 20 patients with diffuse emphysema before and at least three months after either a unilateral or a bilateral lung-reduction procedure. Clinical benefit was assessed by measurement of the six-minute walking distance and the transitional-dyspnea index, which is a subjective rating of the change from base line in functional impairment and the threshold for effort- and task- dependent dyspnea. Pressure-volume relations in the lungs were measured with static expiratory esophageal-balloon techniques, and right ventricular systolic function was assessed by echocardiography. RESULTS: The patients had significant improvement in the transitional-dyspnea index after surgery (P<0.001). The mean (+/-SD) coefficient of retraction, an indicator of elastic recoil of the lung, improved (from 1.3+/-0.6 cm of water per liter before surgery to 1.8+/-0.8 after, P<0.001). Sixteen patients with increased elastic recoil had a greater increase in the distance walked in six minutes than the other four patients, in whom recoil did not increase (P=0.02). The improved lung recoil led to disproportionate decreases in residual volume as compared with total lung capacity (16 percent vs. 6 percent), but the decreases in both values were significant (P<0.001). Forced expiratory volume in one second increased (from 0.87+/-0.36 to 1.11+/-0.45 liters, P<0.001). End-expiratory esophageal pressure also decreased (P=0.002). These improvements in lung mechanics led to a decrease in arterial partial pressure of carbon dioxide form 42+/-6 to 38+/-5 mm Hg (P=0.006). Furthermore, the fractional change in right ventricular area, an indicator of systolic function, increased from 0.33+/-0.11 to 0.38+/-0.010 (P=0.02). CONCLUSIONS: Lung-reduction surgery can produce increases in the elastic recoil of the lung in patients with diffuse emphysema, leading to short-term improvement in dyspnea and exercise tolerance.

Adult↗
PubMed1996

Use of gene tests to detect hereditary predisposition to cancer: what do we know about cost effectiveness?

Mutations in 4 genes associated with DNA repair have been shown to be associated with hereditary non-polyposis colon cancer (HNPCC) in families which display unusually high risk for colorectal cancer. Laboratory tests for mutations in these genes will soon be commercially available, raising the possibility that population-wide gene testing to identify individuals with an inherited susceptibility to colorectal cancer could be conducted. The purpose of our report is to explore the economic implications of conducting a program of population-wide screening for HNPCC compared with alternative programs which would be restricted to families already known to be at high risk for HNPCC. Rather than provide a definitive answer to these questions, our purpose is to indicate priority areas of research which need to be conducted before such a definitive analysis can be done. An exploratory analysis has been conducted to determine which factors are most important in determining the cost-effectiveness of a genetic testing program for HNPCC. The base case analysis focuses on current uncertainty about the population prevalence of the HNPCC genotype and phenotype, factors which are central to the cost-effectiveness of population-wide screening. Uncertainty in parameters related to the cost and effectiveness of screening and preventive interventions for HNPCC were explored using additional sensitivity analyses. Favorable levels of cost-effectiveness for population-wide screening are achieved only when the most favorable assumptions about HNPCC prevalence and the cost and effectiveness of screening and preventive interventions are made.

Colorectal Neoplasms, Hereditary Nonpolyposis↗
PubMed1996

Breast cancer control among the underserved--an overview.

This paper explores barriers to the use of standard screening and breast cancer treatment that result in systematic differences in health outcomes. We review available data on individual, socioeconomic, and health system determinants of access to standard breast cancer care, including screening, diagnostic, and treatment services. Based on this review, we discuss the combination of factors which result in underservice. We argue that a broad framework which considers health system and social class as well as individual factors is useful for analyzing how structures of health care delivery tend to provide less than standard care to women who are older, have less income, or are less educated, black, or Hispanic. Data collection efforts which do not include structural and socioeconomic variables may result in an incomplete or misleading understanding of the determinants of underservice. These factors also need to be considered in the design and evaluation of public health policies and interventions meant to ameliorate the effects of underservice.

Adult↗
PubMed1996

Unilateral thoracoscopic surgical approach for diffuse emphysema.

We evaluated the use of a lateral thoracoscopic approach for lung reduction surgery in patients with diffuse emphysema. Sixty-seven patients with a mean age of 61.9 years underwent operation. Operative side was determined by preoperative imaging. The procedures were laser ablation in 10 patients and stapler resection in 57 patients. Ten patients, including six of the 10 patients in the laser-only group had poor outcome (death or hospitalization longer than 30 days), leading us to abandon the laser technique. Of the remaining 57 patients undergoing primary stapled resection, duration of chest tube placement averaged 13 days (range 3 to 53 days) with a mean hospital stay of 17 days (range 6 to 99 days). Seven patients required ventilation for longer than 72 hours, six patients underwent conversion of the procedure to open thoracotomy, four patients acquired arrhythmias, and three patients were treated for empyema. There was one early death (1.7%), from cardiopulmonary failure. Forty patients returned for 3-month evaluation. Significant (p < 0.0001) improvements were seen in forced vital capacity (2.69 L after vs 2.26 L before) and forced expiration volume in 1 second (1.04 L after vs 0.82 L before), with 25 of 40 patients (63%) showing an improvement of more than 20%. Lung volume measures, in particular residual volume, fell significantly. Arterial blood gas analysis revealed that carbon dioxide tension fell significantly in patients with preoperative hypercapnia (carbon dioxide tension > 45 mm Hg, p = 0.018). Six-minute walk test results improved (894 feet after vs 784 feet before, p = 0.002), and symptomatic benefit was confirmed by significant improvement in the dyspnea index. The combination of both hypercapnia and reduced single-breath diffusing capacity for carbon monoxide was significantly more frequent (p = 0.0026) and was 86% specific (5 of 6 patients) in predicting serious postoperative risk. We conclude that the lateral thoracoscopic surgical approach to diffuse emphysema offers significant improvement in pulmonary mechanics and functional impairment. Patients with a combination of hypercapnia and reduced single-breath diffusing capacity for carbon monoxide should not be considered for this procedure because of significant perioperative risk.

Adult↗
PubMed1996

H2-M3wt-restricted, Listeria monocytogenes-specific CD8 T cells recognize a novel, hydrophobic, protease-resistant, periodate-sensitive antigen.

Mice infected with Listeria monocytogenes (LM) generate H2-M3wt-restricted CD8 effectors which recognize a heat-killed LM-associated antigen (HAA) presented by macrophages. To characterize HAA, we extracted a bioactive component from LM using SDS or NaOH. Extracted HAA aggregated in hydrophilic solvents but dissociated in the presence of SDS into a smaller subunit which migrated in Sephadex G-200 between chymotrypsinogen (25 kDa) and cytochrome c (12.5 kDa). HAA bioactivity and size was unaffected by proteinase K under conditions which degraded virtually all detectable protein. HAA was also unaffected by other proteases, RNase and DNase, but HAA bioactivity was destroyed by periodate, an agent that degrades carbohydrates. These studies demonstrate that H2-M3wt can present a hydrophobic, non-peptide, microbial antigen, probably glycolipid in origin, to CD8 T cells.

Animals↗
PubMed1996

The effects of acute exercise on gallbladder function in an adult female population.

It has been suggested that aerobic exercise influences gallstone disease pathogenesis through its effects on gallbladder motility. The purpose of the present investigation was to examine the effects of acute aerobic exercise on gallbladder emptying. Gallbladder function was evaluated, via cholescintigraphy, in 12 healthy females after undergoing two experimental trials [i.e., postprandial (P) and exercise + postprandial (E + P))]. In the E + P trial, 60 min after injection of 99mTc disofenin, subjects exercised for 30 min at 65.3 +/- 0.9%, (mean +/- SEM) of VO2 peak on a recumbent leg ergometer, and then ingested 8 oz of a liquid meal to promote gallbladder emptying. In the P trial the meal was administered at the same time relative to the E + P trial; however, for the 30 min prior to meal ingestion subjects remained in a resting supine position. Postprandial gallbladder ejection fraction (EF) was nonsignificantly higher in the E + P trial (49.4 +/- 5.1%) than in the P trial (46.6 +/- 6.7%). Results of this study also indicated that during a fasted state the gallbladder undergoes significant periods of spontaneous emptying both at rest EF = 25 +/- 5.6% (P < 0.02) and during exercise EF = 17 +/- 4.3% (P < 0.01). In conclusion, the results of this study indicate that 30 min of aerobic exercise at 65% of VO2 peak does not effect gallbladder motility in a healthy, premenopausal, female population.

Adult↗
PubMed1996

Parathyroid adenomas: accurate detection and localization with Tc-99m sestamibi SPECT.

PURPOSE: To evaluate the ability to detect and localize parathyroid adenomas with technetium-99m sestamibi single photon emission computed tomography (SPECT). MATERIALS AND METHODS: Forty-seven adult patients underwent Tc-99m sestamibi SPECT. Early (15-30 minutes after injection) and delayed (2-4 hours after injection) images were acquired. Thirty-three patients were examined for initial parathyroid surgery; the remaining 14, for repeat surgery because of persistent or recurrent hyperparathyroidism. SPECT reprojection images viewed in a rotating cine-display mode were read independently by two nuclear medicine physicians who were blinded to the results of other localization studies. Thirty-seven patients underwent subsequent neck exploration. SPECT findings were compared with surgical and histopathologic findings. RESULTS: In the 37 patients who underwent surgery, parathyroid adenomas were confirmed in 34 (92%) and hyperplasia in three (8%). In 31 patients, adenomas were correctly detected and localized with early SPECT images (sensitivity, 91%). In contrast, the sensitivity of delayed SPECT images was 74% (25 of 34 patients) for detection and 32% (11 of 34 patients) for localization. Early SPECT images were significantly better for localization (P < .001) and detection (P = .03). CONCLUSION: For Tc-99m sestamibi parathyroid imaging, early SPECT images were the most accurate in the detection and localization of parathyroid adenomas.

Adenoma↗
PubMed1996

Changes in lung volume and volume of emphysema after unilateral lung reduction surgery: analysis with CT lung densitometry.

PURPOSE: To evaluate changes in volume of the lungs and volume of emphysema after unilateral lung reduction surgery (ULRS) by using computed tomographic (CT) lung densitometry. MATERIALS AND METHODS: Twenty-eight patients underwent CT before and 3 months after ULRS. With use of a density mask software program and a three-dimensional graphics workstation, CT scans were analyzed to define the volume of the lungs and the volume of emphysema. Pre- and postoperative mean CT numbers were determined. RESULTS: After ULRS, the surgically reduced lung volume decreased 22%, and the intact opposite lung volume increased 4%. Emphysema in the surgically reduced lung decreased 14% and was unchanged in the intact opposite lung. Mean CT numbers in the surgically reduced lung increased 26 HU but were unchanged in the intact opposite lung. CONCLUSION: The effects of ULRS on each lung can be evaluated by using CT lung densitometry and a three-dimensional graphics workstation. ULRS reduces emphysema and lung volume in the surgically reduced lung without statistically significant worsening of contralateral emphysema at 3 months.

Adult↗
PubMed1996

Prostanoid production in rabbit corpus cavernosum: I. regulation by oxygen tension.

PURPOSE: To investigate the effects of oxygen tension on prostanoid synthesis in rabbit penile corpus cavernosum tissue (RCC) in organ culture. MATERIALS AND METHODS: Strips of rabbit corpus cavernosum were incubated in organ culture media under varying oxygen conditions (0%, 12% and 21% oxygen), in the presence or absence of acetylcholine and arachidonate stimulation. Prostanoids were measured in collected media by radioimmunoassay. Prostaglandin H synthase (PGHS) protein levels and mRNA PGHS expression were measured under both 0% and 21% oxygen conditions. RESULTS: Basal and acetylcholine-stimulated PGI2 release was progressively diminished as a function of diminishing oxygen tension (pO2 from approximately 165 to 25 mm.Hg). The basal and stimulated production of other prostanoids, thromboxane A2, PGF2alpha, and PGE2, was also significantly inhibited under 0% oxygen (approximately 25 mm.Hg) conditions. However, incubation under 0% oxygen did not alter PGHS protein levels nor mRNA PGHS expression. Cavernosal strips incubated under 0% oxygen but supplemented with exogenous arachidonate (10 microM.) maintained significantly lower PGI2 production than tissues exposed to 21% oxygen (approximately 165 mm.Hg). CONCLUSIONS: These data demonstrate that oxygen tension regulates prostaglandin production in corporal tissue. The reduction in prostanoid production during hypoxia can be attributed to inhibition of PGHS activity rather than the expression of the enzyme. In view of the role of PGI2 as an inhibitor of platelet aggregation and white cell-endothelial adhesion, our findings may provide mechanistic insight into the alteration in corporal blood homeostasis ischemic-hypoxic priapism.

Acetylcholine↗
PubMed1996

Prostanoid production in rabbit corpus cavernosum. II. Inhibition by oxidative stress.

PURPOSE: To investigate the effects of reoxygenation following hypoxia on prostanoid production in rabbit penile corpus cavernosum tissue (RCC) in organ culture. MATERIALS AND METHODS: Strips of RCC were incubated in organ culture media under either 21% O2 (control, PO2 approximately 167 mm.Hg) or 0% O2 (hypoxia, PO2 approximately 27 mm.Hg) followed by a reoxygenation period with 21% O2, in the presence or absence of exogenous arachidonate, Tiron or catalase. Prostanoids were measured in collected media by radioimmunoassay. Malondialdehyde levels were measured in RCC following exposure to either control or hypoxia-reoxygenation conditions. RESULTS: Under hypoxic conditions, basal release of prostanoids (PGI2, PGF2 alpha, PGE2 and TXB2) was inhibited. Although this inhibition was reversible upon reoxygenation, the recovery was delayed, requiring at least 2 hours of exposure to 21% oxygen to reestablish prostanoid production. Reoxygenation also caused lipid peroxidation as measured by an increase in malondialdehyde levels. When reoxygenation was done in the presence of exogenous arachidonate, recovery of PGI2 production was complete by 1 hour. Reoxygenation in the presence of a scavenger of reactive oxygen species (Tiron) or catalase significantly improved the recovery rate of PGI2 production. CONCLUSIONS: These results show that reoxygenation of hypoxic tissue generates oxidative stress that interferes with the recovery of prostanoid production by alteration of a biosynthetic point(s) upstream from prostaglandin H synthase (PGHS) including, at least, phospholipid peroxidation.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed1995

The use of gene tests to detect hereditary predisposition to cancer: economic considerations.

Several mutations recently have been shown to be associated with hereditary nonpolyposis colon cancer (HNPCC) in families displaying unusually strong predisposition to colorectal cancer. Laboratory tests to detect such gene mutations soon will be commercially available, raising the possibility for population-wide screening. The purpose of this study was to explore the economic implications of conducting a population-wide screening for HNPCC compared with restricted screening among members of the families at high risk. An exploratory analysis was performed to determine which factors are most important in determining the cost-effectiveness of such a testing program. The base-case analysis focuses on current uncertainty about the population prevalence of the HNPCC genotype and phenotype. The uncertainty with regard to parameters related to the cost-effectiveness of screening and preventive interventions for HNPCC were explored, using additional sensitivity analyses. Cost-effectiveness is achieved for population-wide screening only when assumptions most favorable to that outcome are made regarding the HNPCC prevalence, the cost and effectiveness of screening, and preventive intervention. Information on the population prevalence of HNPCC genotypes and the penetrance of these genotypes is essential for making policy decisions. Additional information is needed regarding the determinants of the cost of genetic testing and counseling, the efficacy of preventive regimens for individuals at high risk, and the accuracy and cost of alternative methods of identifying families at risk.

Adult↗
PubMed1995

A method for characterizing transition concertedness from polymer dynamics computer simulations.

A statistical method based on classifying the transitions among a set of dihedral angles within an "energy transfer window" is developed, and used to analyze Brownian (BD) and molecular dynamics (MD) simulations of the acyl chains in a lipid bilayer, and MD of neat hexadecane. It is shown for the BD simulation that when a transition of the dihedral angle in the center of the chain occurs, a transition of a particular next nearest neighbor (or angle 2-apart) will follow concertedly with a probability of approximately 0.10 within a time window of approximately 3 ps. The MD bilayer simulations, which are based on a more flexible model of the hydrocarbon chains, yield corresponding concerted transition probabilities of approximately 0.083 and window sizes of 1-2 ps. An analysis of angles 4-apart yields concerted transition probabilities of 0.03 and 0.04 for the BD and MD bilayer simulations, respectively, and window sizes close to those of the corresponding 2-apart cases. Statistical hypothesis testing very strongly rejects the assertion that these follower transitions are occurring at random. Similar analysis reveals marginal or no evidence of concertedness between 1-apart (nearest neighbor) and between 3-apart dihedral angle transitions. The pattern of concertedness for hexadecane is qualitatively similar to that of the lipid chains, although concertedness is somewhat stronger for the 3-apart transitions and somewhat weaker for those 4-apart. Finally, it is suggested that the diffusion of small solute molecules in membranes is better facilitated by nonconcerted transitions, which are associated with relatively large displacements of the chains, than by concerted transitions, which do little to change the chain shape.

1,2-Dipalmitoylphosphatidylcholine↗