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Biomedical subjects

R S Brown

Publications and source records attributed to R S Brown.

At least 19 recordsLinked to original sources
PubMed1992

Ion detection limitations to mass resolution in matrix-assisted laser desorption time-of-flight mass spectrometry.

The ion detection process in a discrete-dynode electron multiplier can result in significant mass resolution losses in time-of-flight mass spectrometry (TOF-MS) for higher mass-to-charge (m/z) ion species. This resolution loss is attributed to propagation time delays and signal broadening in the ion detector. This is presumed to be due to the generation of a distribution of secondary ion species produced initially upon impact of a primary ion with the first dynode surface of the ion detector. Comparisons are made between the signals produced by a standard discrete dynode ion detector (which amplifies the negatively charged species produced by impact of a primary ion) and a detector modified to respond to only the positively charged secondary ion species produced by a primary ion impact. Ion signals for higher m/z ions with the standard detector geometry are seen to be due to a narrow signal component, most likely due to the generation of secondary electrons and/or very low mass secondary ions (H-), and a broad signal component, apparently due to secondary ions which take significant amounts of time to traverse the low potential fields between the first and second detector dynode. This results in ion signal tailing for higher m/z ion species. Numerical subtraction of the ion signal obtained with the standard and modified detector geometries (singly protonated molecular ion species of equine myoglobin) results in an improvement in mass resolution, such that a new adduct ion species (from trifluoroacetic acid) can be resolved.

Animals↗
PubMed1992

Optimizing signal and mass resolution for matrix-assisted laser desorption utilizing a linear time-of-flight mass spectrometer.

Results are presented for various instrumental configurations employed for matrix-assisted laser desorption mass spectrometry. Mass resolution is determined for a linear time-of-flight mass spectrometer for various lengths of the field-free region. A wire ion guide is utilized and is shown to improve ion transport efficiencies for longer field-free regions. It is also determined experimentally that a modest mass resolution increase is often obtained in configurations employing the wire ion guide when compared to the mass resolution obtained with the same geometry without the wire ion guide. Optimal applied potentials are determined for the wire ion guide. No mass dependence on the optimal applied potential (-100 V) for the wire ion guide is observed for samples of equine myoglobin (MW 16,951.5 Da) and a bacterial protease (MW 27,228.4 Da). The optimal applied voltage was also found to be identical (-100 V) for the singly through quadruply charged molecular ion species of rabbit gamma globulin (MW approximately 150,000 Da). It is shown that a 2 m flight tube with a wire ion guide provides better signal-to-noise mass spectra than a 1 m flight tube without the wire ion guide and can more than double the mass resolution obtainable. Utilization of a 4 m flight tube gives minimal mass resolution enhancement at the expense of signal-to-noise.

Animals↗
PubMed1992

Quantitative autoradiographic evaluation of the influence of protein dose on monoclonal antibody distribution in human ovarian adenocarcinoma xenografts.

We studied the effect of monoclonal antibody protein dose on the uniformity of radioiodinated antibody distribution within tumor masses using quantitative autoradiography. Groups (n = 11-13/group) of athymic nude mice with subcutaneous HTB77 human ovarian carcinoma xenografts were injected intraperitoneally with an 125I-labeled anticarcinoma-associated antigen murine monoclonal antibody, 5G6.4 using a high or a low protein dose (500 micrograms or 5 micrograms). At 6 days post-injection the macroscopic and microscopic intratumoral biodistribution of radiolabeled antibody was determined. The degree of heterogeneity of the labeled antibody distribution within each tumor was quantified and expressed as the coefficient of variation (CV) of the activity levels in serial histological sections. Tumors from mice given the 500-micrograms protein doses had substantially lower CV values, 0.327 +/- 0.027, than did tumors from animals given 5-micrograms protein doses, 0.458 +/- 0.041, (P = 0.0078), indicating that the higher protein dose resulted in more homogeneous distribution of radioactivity in tumors than did the lower dose. While the percentage of the injected dose reaching the tumor was comparable between groups, injecting the higher dose of protein resulted in significantly lower tumor to non-tumor uptake ratios than those obtained for the lower protein dose. These data indicate, in this system, that to achieve more uniform intratumoral antibody (and radiation for radioimmunotherapy) delivery, a relatively high protein dose must be administered. However, to obtain this increased uniformity, a substantial drop in tumor/background uptake ratios was seen. Quantitative autoradiographic evaluation of human tumor xenografts is a useful method to assess the intratumoral distribution of antibodies.

Adenocarcinoma↗
PubMed1992

Thyroid growth immunoglobulins in feline hyperthyroidism.

Feline hyperthyroidism bears a strong clinical and pathologic resemblance to toxic nodular goiter in humans. To evaluate whether the observed thyroid growth might be due to circulating thyroid antibodies, as has been postulated in humans, we studied the effect of purified immunoglobulin (Ig) G preparations on a rat thyroid follicular (FRTL-5) cell line. When compared with control, hyperthyroid cat IgG caused significantly increased [3H]-thymidine (Tdr) incorporation into DNA (p less than 0.02) and stimulated cellular proliferation 15-fold. Stimulation of 3H-Tdr incorporation tended to be biphasic and could be inhibited completely by a potent, specific TSH receptor blocking antibody. Hyperthyroid cat IgG also significantly inhibited 125I-bTSH binding to porcine thyroid membranes, an effect that could be reproduced using electrophoretically pure IgG and normal cat thyroid membranes. Unlike its effect on growth, hyperthyroid cat IgG did not stimulate intracellular cAMP, and there was no correlation between thyroid function in vivo and IgG growth-promoting activity in vitro. These data suggest that elevated titers of thyroid growth IgGs, probably acting through the TSH receptor, are present in feline hyperthyroidism and may play a role in goiter formation. Unlike growth, the thyroid hyperfunction observed is not IgG dependent. Further study of feline hyperthyroidism may contribute important insights into human nodular goiter and into the mediation of thyroid growth in general.

Adenylyl Cyclases↗
PubMed1992

Unsuspected morbid hypermagnesemia in elderly patients.

This study was designed to determine the incidence, etiology and consequences of severe hypermagnesemia. We retrospectively reviewed all hospital admissions over a 5-year period from 1984 to 1989 and identified 8 cases of severe hypermagnesemia (serum Mg > or = 6.0 mg/dl) due to magnesium ingestion. All but 1 patient were elderly (mean age 70 +/- 6 years). The etiology when identified was due to magnesium-containing cathartics (n = 3) or antacids (n = 3). The total amount of magnesium ingested was not excessive, but bowel disorders that may have enhanced absorption (such as active ulcer disease, gastritis, colitis, perforated viscus, massive gastric dilatation) were present in 7 of the 8 patients. Unexpectedly, only 1 had preexisting renal failure. Renal function was found to be normal in 1, only mildly to moderately impaired in 5 (creatinine < 3.6 mg/dl) and severely impaired in 2 (creatinine 7.6, 15.7 mg/dl). Clinical sequelae of hypermagnesemia were hypotension (n = 7), bradycardia (n = 2), respiratory depression (n = 3), EKG abnormalities (n = 6), depressed mental status (n = 5). Hypocalcemia (range 5.7-7.4 mg/dl) more severe than could be attributed to either hypoalbuminemia or acute renal failure was present in 7. A low anion gap (range-2 to 9) was present in 5. Most striking was the fact that despite clinical sequelae, the hypermagnesemia was unsuspected in 6 of the 8 cases. Hypermagnesemia can occur without severe renal insufficiency in association with bowel disease, particularly in elderly individuals, and may be a clinically unrecognized cause of cardiovascular dysfunction, hypocalcemia and neurologic or respiratory depression.

Aged↗
PubMed1992

Effect of atrial natriuretic peptide on potassium-stimulated aldosterone secretion: potential relevance to hypoaldosteronism in man.

Atrial natriuretic peptide (ANP) has been shown to suppress aldosterone secretion under certain circumstances, although the physiological significance of this is uncertain. We wondered if ANP would suppress potassium-stimulated aldosterone secretion in man and, if so, whether we might find high circulating levels of ANP in patients with the syndrome of acquired hypoaldosteronism. We studied seven healthy young subjects under two conditions: 1) infusion of KCl (0.5 mmol/kg) over 45 min, and 2) KCl infused with ANP (0.01 microgram/kg.min) for 60 min. We also evaluated ANP levels in eight elderly subjects with the syndrome of acquired hypoaldosteronism, as defined by hyperkalemia (mean serum K+, 5.3 +/- 0.1 mmol/L) associated with inappropriately low aldosterone levels (216 +/- 50 pmol/L). In the normal subjects, ANP almost completely suppressed the aldosterone response to KCl infusion (P less than 0.001, by analysis of variance) despite a similar rise in the serum potassium level with KCl alone (0.70 +/- 0.07 mmol/L) and KCl plus ANP (0.75 +/- 0.09 mmol/L). PRA fell slightly during KCl plus ANP treatment, but did not change during the infusion of KCl alone. ANP levels were approximately 800 pmol/L during the ANP infusion studies. Endogenous ANP levels in the hyperkalemic patients with hypoaldosteronism were markedly elevated at 1186 +/- 340 pmol/L (compared to 93 +/- 10 pmol/L in healthy elderly controls), a level that would be capable of suppressing the potassium-mediated aldosterone response. Exogenous infusion of ANP suppressed the aldosterone response to hyperkalemia, and ANP levels were found to be markedly elevated in a group of patients with hyperkalemia and hypoaldosteronism. We suggest that ANP may contribute to clinically significant hypoaldosteronism and hyperkalemia in the syndrome of acquired hypoaldosteronism.

Adult↗
PubMed1992

Biases in perception and reporting following a perceived toxic exposure.

Reactions to chemical exposures often include fears of future illness, cancerphobia, reports of multiple chemical sensitivity, and other ill-defined complaints. Frequently, these complaints occur at levels of exposure not known to cause physiological harm. Although frequently dismissed as hysterical or hypochondriacal reactions, these complaints, along with other indefinite symptoms, may be better understood in terms of biases in perception and reporting. In this paper, we outline various sources of perceptual and response biases including prior beliefs, the media, influential others, reconstructed personal histories, self-perceptions, and the forensic environment. It is recommended that a thorough understanding of symptom-reporting and psychological distress following a chemical exposure involves consideration of these issues.

Arousal↗
PubMed1992

Fear of future illness, chemical AIDS, and cancerphobia: a review.

A review of the literature indicates that fear of future illness shares many characteristics with a wide variety of conditions. Concepts such as hypochondriasis, adjustment disorders, generalized anxiety, and mass hysteria must be considered. Also, factors such as reporting bias, influential others, collective behavior, political groups, and litigation appear to induce symptom reporting from patients complaining of fear of illness and cancerphobia. Cancerphobia may result in impairment ranging from avoidance behaviors to cognitive dysfunctions. Various treatment modalities have been used successfully in treating cancerphobia, and the prognosis is typically good. Complaints of chemical AIDS, universal allergy, or twentieth century disease have little medical or empirical support and require further investigation. Researchers and clinicians must recognize multiple factors contribute to fear of future illness or cancerphobic complaints, and additional research must be undertaken if a thorough understanding of fear of future illness, cancerphobia, and perceptions of chemical AIDS is to be obtained.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Determination of the physical structure of biological materials at biosensor interfaces by techniques of increasing magnification from microscopic to molecular scale.

Chemical selectivity of biosensors is derived from biological materials interfaced to the surface of transducing devices. Molecular recognition events lead to macroscopic function suitable for analytical measurements. The structure-function relationships of biochemical species at interfaces must be established to characterize and optimize biosensor operation. The techniques of ellipsometry, fluorescence microscopy, electron microscopy, and scanning tunneling microscopy are used to investigate the structure of monolayers and multilayers of proteins and lipids at interfaces that are prepared by Langmuir-Blodgett techniques and by self-assembly from bulk solution. The relative merits and limitations of the measurement techniques in the determination of aspects of interfacial structure are considered.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1991

The administration of folic acid to institutionalized epileptic adults with phenytoin-induced gingival hyperplasia. A double-blind, randomized, placebo-controlled, parallel study.

Twenty severely retarded institutionalized epileptic adults with phenytoin-induced gingival hyperplasia were divided into two groups and received a daily 3 mg capsule of either folic acid or lactose for 16 weeks in a randomized, double-blind, parallel study. Serum folate and phenytoin levels were recorded at baseline and on completion of the study. Twelve areas of the gingiva on each patient were graded at 4-week intervals for 16 weeks with respect to the three indexes: hyperplasia, gingival health, and plaque index. There were no significant differences between treatment groups for any of the three indexes over time. The poststudy serum folate levels were three times baseline levels for the active drug group (p less than 0.001) but unchanged in the placebo group. Phenytoin blood levels that began within the therapeutic window (10 to 20 micrograms/ml) tended to remain within the therapeutic window for both groups, with no reported seizure activity. A single daily oral 3 mg capsule of folic acid did not show efficacy as the sole therapeutic agent in the reduction of phenytoin-induced gingival hyperplasia.

Adult↗
PubMed1991

Localization by in situ hybridization of three 3p probes with respect to the breakpoint in a t(3;8) in hereditary renal cell carcinoma.

Three 3p probes were localized by in situ hybridization on chromosomes from a carrier of a balanced t(3;8) associated with renal cell cancer. For one of the probes (pH3E4/D3S48), a previous localization in 3p21 was confirmed; for a second probe (pHF12-32/D3S2), a broader localization could be confined to 3p21. Both probes appeared to be located distal to the breakpoint in 3p. The third probe (pMS1-37/D3S3) was localized to 3p14, in accordance with a previous localization. This probe, however, hybridized very weakly or not at all to either of the translocation products, although it is known from Southern analysis that the D3S3 sequence is present on one of them. We assume that this probe is located close to the breakpoint on 3p and that distortion of the higher-order chromosomal structure in this region is causing the failure of the in situ hybridization.

Carcinoma, Renal Cell↗
PubMed1991

Ion permeability through bilayer lipid membranes for biosensor development: control by chemical modification of interfacial regions between phase domains.

Based on the results of studies on cystic fibrosis, which implicated hydroxystearic acid (HSA) as a contributing factor in altered biomembrane function, solvent-free bilayer lipid membranes (BLMs) and monolayer films were prepared from a lipid mixture containing (by mass) 34% phosphatidylcholine, 19% dipalmitoylphosphatidyl serine, 47% cholesterol and variable amounts of 10- and 12-HSA (0-50%). Ion currents, resulting from K+ permeation through BLMs that were supported in 0.1 mol dm-3 KCl solutions buffered to pH 7.4, were monitored with use of a d.c. circuit. The structures of monolayer films at the air-water interface of a Langmuir-Blodgett trough were studied by pressure-area correlations and by further correlation with microscopic phase separation as revealed by fluorescence microscopy. In order to elucidate the role of the hydroxyl moieties in ion permeability, the transmembrane ion current was corrected for the effect of the negative surface charge of the carboxylic acid by replacement of the HSA component with stearic acid. The ion current was found to increase with the molar proportion of the HSAs. Two models for ion conduction through BLMs were considered: 'hopping' via hydrophilic sites within the hydrophobic zone of the BLMs, introduced by the hydroxyl moiety of 10- or 12-HSA; and transport through interfacial regions between phase domains that represent areas of low steric density and low structural order within monolayers. Although the two mechanisms are not distinct, the ion permeability results indicate a change in the response of ion current to HSA concentration at 35 mol-%, suggesting a change in the relative proportion of the mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Biosensing Techniques↗
PubMed1991

Prevalence of thyroid deficiency in pregnant women.

OBJECTIVE: The present study was designed to determine the current prevalence of gestational hypothyroidism, since maternal thyroxine deficiency is associated with poor obstetric outcomes and mental retardation in the surviving offspring. DESIGN: TSH concentrations were measured in the sera of women at 15-18 weeks of gestation. Those sera with TSH concentrations above 6 mU/l and the two sera closest in order with TSH concentrations below 6 mU/l were further analysed for T4, FT4, TBG, and antithyroid antibodies. Study criteria for hypothyroidism were sera with elevated concentrations of TSH plus both a free T4 concentration and a total T4 concentration and/or T4/TBG ratio more than two standard deviations below the mean for the control pregnant women. PATIENTS: The sera were from 2000 consecutive women in Maine being tested for alpha-fetoprotein concentration at 15-18 weeks of gestation. RESULTS: TSH concentrations above 6 mU/l were found in the sera of 49 women, 2.5% of the pregnant women. Six women with elevated TSH concentrations (range 6.9-54 mU/l) had both a FT4 concentration and a T4/TBG ratio and/or a T4 concentration more than two standard deviations below the respective control means, meeting the study criteria for thyroid deficiency, and thus giving a prevalence of 0.3%. The remaining 43 women with elevated TSH concentrations were classified as having compensated thyroid disease although some may have been hypothyroid. Fifty-eight per cent of women with TSH concentrations above 6 mU/l and 90% of the women with elevated TSH concentrations and at least one thyroxine index more than two standard deviations below the control means had positive titres of antithyroid antibodies as opposed to 11% of the controls. CONCLUSIONS: Although it is not known what severity of maternal thyroid deficiency is necessary to cause fetal brain damage, the present data indicate a sufficiently high prevalence of thyroid dysfunction to demand investigation of the mental development of the offspring of women with thyroid dysfunction and of the effect of replacement therapy.

Adult↗
PubMed1991

On the mechanism of drug-induced gingival hyperplasia.

Proposed mechanisms of the side effect of drug-induced gingival hyperplasia are reviewed. Hypotheses with regard to inflammation from bacterial plaque, increased sulfated glycosaminoglycans, immunoglobulins, gingival fibroblast phenotype population differences, epithelial growth factor, pharmacokinetics and tissuebinding, collagenase activation, disruption of fibroblast cellular sodium/calcium flux, folic acid and a combination hypothesis are evaluated.

Dental Plaque↗