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Biomedical subjects

M E Brown

Publications and source records attributed to M E Brown.

At least 37 records · Page 2Linked to original sources

Pharmaceutical applications of the Prout-Tompkins rate equation.

More than 50 years ago, a paper by E.G. Prout and F.C. Tompkins was published in the Transactions of the Faraday Society. The paper dealt with the kinetics of the thermal decomposition of crystals of potassium permanganate, and suggested a rate equation, which has become known as the Prout-Tompkins equation, for use in the kinetic analysis of solid state reactions. The paper has been extensively cited in the literature. Applications of the Prout-Tompkins equation in pharmaceutical stability studies are reviewed in this short review.

Algorithms↗

Detection of water ice on Nereid.

We report the detection of the 1.5 and 2.0 micrometers absorption bands of water ice in the near-infrared reflection spectrum of Neptune's distant irregular satellite Nereid. The spectrum and albedo of Nereid appear intermediate between those of the Uranian satellites Umbriel and Oberon, suggesting a surface composed of a combination of water ice frost and a dark and spectrally neutral material. In contrast, the surface of Nereid appears dissimilar to those of the outer solar system minor planets Chiron, Pholus, and 1997 CU26. The spectrum thus provides support for the hypothesis that Nereid is a regular satellite formed in a circumplanetary environment rather than a captured object.

Astronomical Phenomena↗

Hunger in an adult patient population.

CONTEXT: Although clinical observations suggest that some patients experience hunger and food insecurity, there are limited data on the prevalence of hunger in adult patients. OBJECTIVE: To determine the prevalence of hunger and food insecurity in adult patients at an urban county hospital. DESIGN: Cross-sectional survey conducted in 1997. PATIENTS: The primary survey included all patients aged 18 years or older who were admitted to the medicine, surgery, and neurology services during a 2-week period, and all patients who attended the hospital's general medicine clinic during 1 week. A second survey included primary care patients who received insulin from the hospital pharmacy during a 1-month period. MAIN OUTCOME MEASURES: Rates of hunger and food insecurity. RESULTS: Of 709 eligible patients, 567 (participation rate, 80%) were interviewed in either the clinic (n=281) or hospital (n=286). An additional 170 patients who received insulin were interviewed by telephone (response rate, 75%). Of the primary sample, 68 (12%) respondents reported not having enough food, 75 (13%) reported not eating for an entire day, and 77 (14%) reported going hungry but not eating because they could not afford food. A total of 222 (40%) had received food stamps in the previous year and of those, 113 (50%) had their food stamps reduced or eliminated. Recipients whose food stamps had been eliminated or reduced were more likely to report not having enough food (18% vs 13%, P=.006), not eating for a whole day (20% vs 16%, P=.01), going hungry but not eating (20% vs 16%, P=.08), and cutting down on the size of meals or skipping meals (33% vs 27%, P=.01). In multivariate analysis, independent predictors of hunger included an annual income of less than $10000 (odds ratio [OR], 7.55; 95% CI, 3.01-18.92), drug use (OR, 3.56; 95% CI, 1.46-8.66), and a reduction in food stamp benefits (OR, 1.73; 95% CI, 1.01-2.96). Predictors of food insecurity included an annual income of less than $10000 (OR, 4.12; 95% confidence interval [CI], 1.98-8.58), drug use (OR, 2.11; 95% CI, 1.66-5.08), and a reduction in food stamps (OR, 2.02; 95% CI, 1.23-3.32). In addition, 103 (61%) patients in the sample of diabetics reported hypoglycemic reactions; 32 (31%) of these were attributed to inability to afford food. CONCLUSION: Hunger and food insecurity are common among patients seeking care at an urban county hospital.

Adult↗

Monitoring the consequences of uninsurance: a review of methodologies.

The proportion of the United States population without health insurance continues to grow. How will this affect the health of the nation? Prior research suggests that the uninsured are at risk for poor health outcomes. They use fewer medical services and have higher mortality rates than do insured persons. The episodic nature of uninsurance and its prevalence among disadvantaged groups makes it difficult to ascertain the health effects of uninsurance. The goal of this review is to assist researchers and policy makers in choosing methodologies to assess the effects of uninsurance. It provides a compendium of methods that have been used to examine the health consequences of uninsurance, the populations in which these methods have been used, and the strengths and weaknesses of different approaches. The review highlights the need for more longitudinal studies that focus on community-based samples of the uninsured.

Adult↗

Systemic challenge with endotoxin stimulates corticotropin-releasing hormone and arginine vasopressin secretion into hypophyseal portal blood: coincidence with gonadotropin-releasing hormone suppression.

We tested the hypothesis that systemic immune/inflammatory challenge (endotoxin) activates the neuroendocrine stress axis centrally by stimulating the secretion of CRH and arginine vasopressin (AVP) into hypophyseal portal blood. In addition, we examined the temporal association between this stimulation of the stress neuropeptides and the inhibition of pulsatile GnRH and LH secretion. Using alert, normally behaving ewes, hypophyseal portal and peripheral blood were sampled simultaneously at 10-min intervals for 14 h. Temperature was monitored remotely by telemetry at the same interval. Endotoxin (400 ng/kg, i.v. bolus) or saline as a control was injected after a 4-h baseline period. Portal blood was assayed for CRH, AVP, and GnRH, and peripheral blood was assayed for cortisol, progesterone, and LH. In controls, hypophyseal portal CRH and AVP remained just above or at assay sensitivity, and cortisol showed a regular rhythmic pattern unaffected by saline and typical of basal secretion. In contrast, endotoxin potently stimulated CRH and AVP secretion into portal blood, and cortisol and progesterone into peripheral blood. Both CRH and AVP generally rose and fell simultaneously, although the peak of the AVP response was approximately 10-fold greater than that of CRH. The AVP in portal blood was not due to recirculation of hormone secreted into the peripheral circulation by the posterior pituitary gland, because the AVP increase in peripheral blood was negligible relative to the marked increase in portal blood. The stimulation of CRH and AVP coincided with significant suppression of GnRH and LH pulsatile secretion in these same ewes and with the generation of fever. We conclude that endotoxin induces central activation of the neuroendocrine stress axis, stimulating both CRH and AVP release into the hypophyseal portal blood of conscious, normally behaving ewes. This response is temporally coupled to inhibition of pulsatile GnRH and LH release as well as with stimulation of adrenal cortisol and progesterone secretion and generation of fever.

Animals↗

Build consensus and develop collaborative practice guidelines.

With differing treatment guidelines available from many sources, collaborating advanced practice nurses and physicians at this facility recognized the need for one clear, acceptable set. Survey results show that clinicians incorporate all or most of the guidelines into practice (91%).

Ambulatory Care↗

The response of Jupiter's magnetosphere to an outburst on Io.

A 6-month-long monitoring campaign of the Io plasma torus and neutral cloud was conducted to determine the characteristics of their interaction. During the observations, a large outburst of material from Io-inferred to be caused by the eruption of a volcanic plume on Io-caused a transient increase in the neutral cloud and plasma torus masses. The response of the plasma torus to this outburst shows that the interaction between Io and Jupiter's magnetosphere is stabilized by a feedback mechanism in which increases in the plasma torus mass cause a nonlinear increase in loss from the plasma torus, limiting plasma buildup.

Atmosphere↗

Analysis of basic fibroblast growth factor in rats with inherited retinal degeneration.

In RCS rats, photoreceptors degenerate between postnatal days 20 and 60, secondary to a genetic defect expressed in the neonatal retinal pigmented epithelium (RPE). Previous work has shown delay of the photoreceptor degeneration in this model by intraocular injection of basic fibroblast growth factor (bFGF). Evidence is presented here, from bFGF immunostaining and Northern analysis of bFGF mRNA, for reduced bFGF expression in uncultured RPE of dystrophic RCS pups. It is also shown that in the mutant eyes angiogenesis in the underlying choroid, which normally occurs between postnatal days 7 and 10, is markedly delayed, with irregular distribution of vessels, consistent with a reduction in this known angiogenesis factor. Mutational analysis of the bFGF transcript and gene by denaturing gradient gel electrophoresis and Southern analysis did not, however, reveal abnormalities in the coding sequence of this gene in RCS rats.

Animals↗

Do patients use marijuana as an antidepressant?

Several lines of evidence suggest that cannabis may have antidepressant effects. However, methodologic limitations in available studies make the results difficult to interpret. We review this literature and present five cases in which the evidence seems particularly clear that marijuana produced a direct antidepressant effect. If true, these observations argue that many patients may use marijuana to "self-treat" depressive symptoms.

Adolescent↗

The secretion of active recombinant human gastric lipase by Saccharomyces cerevisiae.

The expression of the complete human gastric lipase (HGL) gene in Saceharomyces cerevisiae grown in defined medium resulted in the secretion of active recombinant HGL (rec.HGL) to levels of up to approximately 11 mg/liter. Of the total measurable HGL activity, 90% was detected by assaying intact cells, suggesting that the majority of rec.HGL produced was secreted but stayed attached to the cell wall. The remaining 10% was present in the growth medium and from this source active rec.HGL was purified 300-fold by a combination of hydrophobic interaction and ion-exchange chromatography. Rec.HGL migrated on reduced SDS-PAGE as three bands with estimated molecular masses of 47,45, and 43 kDa. All three forms cross-reacted with an antibody raised to natural HGL and their treatment with Endo H showed them to be N-linked glycosylation variants of a single polypeptide. The 47-kDa species was isolated using lentil lectin Sepharose 4B and shown to possess a specific activity comparable to that of the natural enzyme. Rec.HGL had an acid pH activity optimum using either tributyrin or olive oil as substrate and did not lose activity if incubated in the presence of pepsin at pH 2.0. These results demonstrate that HGL secreted by Saccharomyces cerevisiae retained those properties of the natural enzyme required for its use in the treatment of pancreatic insufficiency.

Chromatography, Agarose↗

Protein-bound and unbound forms of plasma cortisol in piglets after castration at seven or 14 days of age.

Male piglets from seven litters were used to evaluate the long-term effects of castration and age at castration on the concentrations of cortisol and its distribution in peripheral plasma. The piglets were allotted to one of three groups of 12 animals according to whether they had been castrated at seven or 14 days old or left intact. The animals were weighed and blood samples were collected from the anterior vena cava at three, seven, 10, 14, 17, 21, 28, 35 and 42 days of age. The plasma concentrations of albumin, total protein, cortisol, and the percentage distribution of cortisol among corticosteroid binding globulin-bound (CBG-bound), albumin-bound and unbound forms, were determined. Castration at seven or 14 days of age had no effect on any of the parameters measured. In all the piglets, the percentage of unbound cortisol decreased (P < 0.001) from 24.5 to 11.6 per cent over the period of sampling. The percentage of CBG-bound cortisol increased (P < 0.001) from 19 per cent on day 17 to 47 per cent on day 21, and albumin-bound cortisol declined from 61 to 37 per cent over the same period. These results agree with previous findings of age-related changes in the percentage distribution of cortisol in the piglet and demonstrate that these patterns are unaffected by castration.

Age Factors↗

The fragment R collision: W. M. Keck telescope observations of SL9.

The W. M. Keck telescope was used to observe the impact of comet Shoemaker-Levy 9 (SL9) fragment R at a wavelength of 2.3 micrometers on 21 July 1994. The data showed three outbursts. The first flash lasted about 40 seconds and was followed 1 minute after its peak by a second flash that lasted about 3 minutes. A third, longer lasting flare began 6 minutes after the first flash and lasted for 10 minutes. At its maximum brightness, the flare outshone Jupiter. The two short flashes are probably associated with the initial meteor trail and the subsequent fireball, respectively. The bright flare occurred when the impact site rotated into view. These data show that the explosion ejected material at least 1300 kilometers above the visible cloud tops. The luminosity of the impact site during the long bright flare was probably maintained by the release of gravitational potential energy, as this material fell back onto the lower atmosphere.

Atmosphere↗

Cell cycle-dependent regulation of p185neu: a relationship between disruption of this regulation and transformation.

Structure and function of p185neu receptor tyrosine kinase were found to be regulated in a cell cycle-dependent manner. In M phase, p185neu is hyperphosphorylated at serine and/or threonine residues. The phosphotyrosine [Tyr(P)] content of p185neu is at its highest level in G0/G1 phase, decreases through S and G2 phases, and reaches its lowest level in M phase. Phospholipase C-gamma (PLC-gamma) and GTPase-activating protein (GAP), substrates of p185neu, also have a similar profile of Tyr(P) content during the cell cycle. These results, along with in vitro immune complex kinase assays, suggest that the tyrosine kinase activity of p185neu is least active in M phase. Interestingly, the mutation-activated neu oncogene (neu*)-encoded protein product, p185neu* escaped from cell cycle regulation. Taken together, we demonstrate in this report that the structure and function of p185neu are regulated in a cell cycle-dependent manner, yet p185neu* escapes from this regulation and remains active through the cell cycle. Disruption of this cell cycle regulation may define a mechanism for p185neu*-mediated cellular transformation.

3T3 Cells↗

Acquired cor triatriatum after orthotopic cardiac transplantation.

Orthotopic cardiac transplantation was performed in a 42-year-old woman with idiopathic cardiomyopathy. Postoperative right ventricular failure developed and a transesophageal echocardiogram demonstrated acquired cor triatriatum with marked obstruction to mitral valve inflow and severe right ventricular dilatation. At reexploration, redundant donor atrial tissue was excised correcting the cor triatriatum. She was alive and well with normal hemodynamic parameters 12 months after transplantation.

Adult↗

An improved left ventricular cannula for chronic dynamic blood pump support.

Ventricular unloading with dynamic blood pumps can be markedly affected by the geometry of the cannula tip within the ventricular chamber. Due to the ability of these pumps to develop significant negative inflow pressure, existing cannula tips designed for passively filling blood pumps can be predisposed to inflow occlusion by intraventricular anatomic structures. A novel "trumpet" mouth cannula was constructed to overcome this limiting problem. This design was based on two criteria: to provide additional stenting to the ventricular apex, and to assure placement of the tip opening relative to the endocardial surface. This prototype cannula was evaluated in vivo against conventional caged, blunt, and tapered designs to assess anatomic and hemodynamic interaction within the ventricular apex. Post mortem examination revealed the inflow tract to be devoid of myocardial obstruction in all cases. These initial studies indicate that a trumpet mouth cannula can provide satisfactory hemodynamic performance required by dynamic blood pumps.

Animals↗

Cytotoxic T lymphocyte response to hepatitis C virus-derived peptides containing the HLA A2.1 binding motif.

The HLA class I-restricted cytotoxic T lymphocyte (CTL) response is a major defense mechanism in viral infections. It has been suggested that the CTL response may contribute to viral clearance and liver cell injury during hepatitis C virus (HCV) infection. To test this hypothesis requires an understanding of the characteristics of HCV-specific cytotoxic effector cells and identification of the target antigens to which they respond. To begin this process we stimulated peripheral blood mononuclear cells (PBMC) from a group of HLA-A2 positive patients with chronic hepatitis C with a panel of 130 HCV-derived peptides containing the HLA-A2 binding motif. Effector cells were tested for their capacity to lyse HLA-A2-matched target cells that were either sensitized with peptide or infected with a vaccinia virus construct containing HCV sequences. Using this approach we have identified nine immunogenic peptides in HCV, three of which are derived from the putative core protein, three from the nonstructural (NS) 3 domain, two from NS4 and one from NS5. Selected responses were shown to be HLA-A2 restricted, mediated by CD8+ T cells and to recognize endogenously synthesized viral antigen. Unexpectedly, peptide-specific CTL responses could also be induced in sero-negative individuals, suggesting in vitro activation of naive CTL precursors. The precursor frequency of peptide-specific CTL was 10 to 100-fold higher in infected patients compared to uninfected controls, and the responses were greatly diminished by removal of CD45 RO+ (memory) T cells. Further quantitative studies are clearly required to establish whether a correlation exists between the HCV-specific CTL response and the clinical course of this disease. Definition of the molecular targets of the human CTL response to HCV creates this opportunity, and may also contribute to the development of a T cell-based HCV vaccine.

Amino Acid Sequence↗