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Biomedical subjects

S Miller

Publications and source records attributed to S Miller.

At least 433 records · Page 24Linked to original sources

Intrahypothalamic microinfusion of corticotropin-releasing factor elevates blood glucose and free fatty acids in rats.

Three experiments examined whether intrahypothalamic microinfusions of corticotropin releasing factor (CRF) can affect circulating levels of the metabolic fuels, glucose and free fatty acids. Infusions of CRF into the paraventricular nucleus dose-dependently increased serum glucose levels; greater increases were seen in acute than in chronic preparations. The greater effectiveness could not be accounted for by anesthetization per se. CRF infusion into the ventromedial nucleus did not affect serum glucose. Infusions into both sites, however, significantly increased serum free fatty acids. Neither glucose nor free fatty acids were altered by infusions into the lateral hypothalamus or the caudate-putamen. These data suggest that the previously identified CRF binding sites and CRF neuronal terminals in the paraventricular and ventromedial nuclei may be involved in the central regulation of metabolic fuel release. Additionally, it appears that the importance of CRF in the paraventricular nucleus in regulating serum glucose may be greater under some conditions than others.

Animals↗

Polyvinylpyrrolidone iodine: corneal toxicology and epithelial healing in a rabbit model.

Polyvinylpyrrolidone-iodine (PVP-I) is a biocompatible broad spectrum antimicrobial that is widely used as an ophthalmic pre-operative prepping agent. In order to determine if PVP-I is safe for treating corneal ulcers and conjunctivitis, we evaluated the ocular toxicity of frequent dosing in a rabbit model. We evaluated ocular irritation in 18 rabbits according to the McDonald-Shadduck method. Concentrations of 0.5% PVP-I or less were practically non-irritating when administered six times per day. We evaluated corneal epithelial wound healing in 16 rabbits with standardized abrasions. Concentrations of 0.33% PVP-I showed epithelial healing comparable to gentamicin treated eyes and untreated controls. Concentrations of 0.5% PVP-I delayed epithelial healing by one day. Because of its broad spectrum and apparently low toxicity, PVP-I may be a useful treatment for corneal ulcers, keratitis and conjunctivitis.

Animals↗

Local infusion of prostaglandin E1 stimulates mandibular bone formation in vivo.

The maintenance of alveolar bone is a major clinical objective in dentistry. This is particularly difficult following such local inflammatory episodes as those of periodontitis or the loss of dentition (residual ridge resorption). We present evidence from beagle dogs that local infusion of prostaglandin E1 (PGE) for 3 weeks at doses of 500 to 2000 micrograms per week produces a dramatic, localized formation of alveolar bone in the mandible which exhibits a normal lamellar architecture and mineralization pattern when evaluated by fluorescence microscopy and microradiography. Whether this newly formed bone becomes functionally integrated into the skeleton and can replace bone lost from surgical resections or trauma remains to be established. Nevertheless, these data indicate that predictable local osteogenesis may eventually be produced by infusions of PGE.

Alprostadil↗

Sentence reception in noise from one versus two sources: effects of aging and hearing loss.

Sentence reception thresholds (SRTs) and babble detection thresholds (BDTs) were measured for signals presented from loudspeakers located at 0 deg and 90 deg azimuth. In addition, the S/B ratios necessary to achieve SRT in the presence of a 12-talker babble were determined under three conditions in which the speech and babble were presented from the same or spatially separated loudspeakers. In the first experiment, normal-hearing subjects were tested on two occasions. The results were highly reliable, with standard errors of the test-retest differences of less than 1dB for all conditions. In the second experiment, SRTs, BDTs, and S/B ratios were measured for three normal-hearing groups (less than or equal to 39, 40-54, and greater than or equal to 55 years) and for a fourth group with presbycusis (greater than or equal to 55 years). Presbycusics had higher SRTs and BDTs than all other groups regardless of age, and the oldest normals had higher thresholds than younger subjects. Presbycusics required higher S/B ratios than any of the normal groups, and the oldest normal group needed a higher S/B ratio compared to the youngest group. All groups demonstrated a significant advantage in S/B ratio when the sentences and babble sources were spatially separated compared to when they were presented from the same loudspeaker. There was no significant difference in the magnitude of advantage due to spatial separation of speech and noise between the normal groups regardless of age, but the presbycusics had significantly smaller advantages than all normals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A serendipitous isolate of Histoplasma capsulatum.

This is a report of an unexpected laboratory diagnosis of Histoplasma capsulatum. The fungus was isolated from an acute cellulitic lesion on the forearm of an elderly male patient with a functioning renal transplant. The patient resides within the environs of Brisbane and has not travelled outside Australia. We consider the isolation of H. capsulatum from a rare site in a patient resident in a non-endemic area indicative of a latent opportunistic infection in an immunocompromised patient.

Histoplasma↗

High-affinity L-arabinose transport operon. Nucleotide sequence and analysis of gene products.

The nucleotide sequence of the "high-affinity" L-arabinose transport operon has been determined 3' from the regulatory region and found to contain three open reading frames designated araF, araG and araH. The first gene 3' to the regulatory region, araF, encodes the 23-residue signal peptide and the 306-residue mature form of the L-arabinose binding protein (33,200 Mr). The binding protein, which has been described elsewhere, is hydrophilic, soluble and found in the periplasm of Escherichia coli. This gene is followed by an intragenic space of 72 nucleotides, which contains a region of dyad symmetry 23 nucleotides long capable of forming an 11-member stem-loop. The second gene, designated araG, contains an open reading frame capable of encoding an equally hydrophilic protein containing 504 residues (55,000 Mr). Following a 14-nucleotide spacer, which does not appear to have any secondary structure, the third open reading frame, herein designated araH, is capable of encoding a hydrophobic protein containing 329 residues (34,000 Mr) that can only be envisioned as having an integral membrane location. 3' to araH there is a T-rich region containing a 24-nucleotide area of dyad symmetry centered 55 nucleotides from the termination codon. Analysis of the derived primary sequences of the araG and araH products indicates the nature and potential features of these components. The araG protein was found to possess internal homology between its amino and carboxyl-terminal halves, suggesting a common origin. The araG gene product has been shown to be homologous to the rbsA gene product, the hisP product, the ptsB product and the malK product, all of which presumably play similar roles in their respective transport systems. Putative ATP binding sites are observed within the regions of homology. The araH gene product has been shown to be homologous to the rbsC gene product, which is the first observed homology between two purported membrane proteins.

Amino Acids↗

Interior and surface of monomeric proteins.

The solvent-accessible surface area (As) of 46 monomeric proteins is calculated using atomic co-ordinates from high-resolution and well-refined crystal structures. The As of these proteins can be determined to within 1 to 2% and that of their individual residues to within 10 to 20%. The As values of proteins are correlated with their molecular weight (Mr) in the range 4000 to 35,000: the power law As = 6.3 M0.73 predicts protein As values to within 4% on average. The average water-accessible surface is found to be 57% non-polar, 24% polar and 19% charged, with 5% root-mean-square variations. The molecular surface buried inside the protein is 58% non-polar, 39% polar and 4% charged. The buried surface contains more uncharged polar groups (mostly peptides) than the surface that remains accessible, but many fewer charged groups. On average, 15% of residues in small proteins and 32% in larger ones may be classed as "buried residues", having less than 5% of their surface accessible to the solvent. The accessibilities of most other residues are evenly distributed in the range 5 to 50%. Although the fraction of buried residues increases with molecular weight, the amino acid compositions of the protein interior and surface show no systematic variation with molecular weight, except for small proteins that are often very rich in buried cysteines. From amino acid compositions of protein surfaces and interiors we calculate an effective coefficient of partition for each type of residue, and derive an implied set of transfer free energy values. This is compared with other sets of partition coefficients derived directly from experimental data. The extent to which groups of residues (charged, polar and non-polar) are buried within proteins correlates well with their hydrophobicity derived from amino acid transfer experiments. Within these three groups, the correlation is low.

Amino Acid Sequence↗

Sensitive method for the measurement of amiodarone and desethylamiodarone in serum and tissue and its application to disposition studies.

A high-performance liquid chromatographic (HPLC) method for the measurement of amiodarone (AM) and its metabolite(s) in serum and tissues was developed. The method uses a 5-micron silica column, methanol containing 0.02% perchloric acid at pH 4 as the mobile phase, and ultraviolet detection at 240 nm. The standard curves for AM and desethylamiodarone (DAM) were linear for serum (range 0.025-6.0 microgram/ml) and tissues (range 0.1-0.5 micrograms for 10-25 mg wet weight). There was a significant decrease as a function of time in AM and DAM concentrations in patients' sera left at ambient temperature in the presence of light. This HPLC method was applied to studies on serum AM elimination kinetics in patients and on tissue uptake during chronic AM administration to rabbits. The elimination half-life (5.8 h) of AM after a 5 mg/kg intravenous dose to a patient was similar to that after acute oral doses. AM, being lipophilic, accumulated maximally in the fat tissue (56 micrograms/g wet weight), followed by lung and liver in rabbits injected with AM for six weeks. The latter two tissues also contained nearly equal quantities of DAM. The high concentrations of AM and DAM in the liver and lungs may be related to the hepatic toxicity and pulmonary fibrosis associated with chronic AM therapy. Two new metabolites were found in the lung and bile of AM-treated rabbits, but these have not yet been identified.

Amiodarone↗

Amiodarone efficacy in a young population: relationship to serum amiodarone and desethylamiodarone levels.

Serum amiodarone and desethylamiodarone levels were measured in children and young adults receiving chronic amiodarone therapy. The study population consisted of 34 children and young adults with ventricular tachycardia (36%), atrial flutter (36%), and recurrent supraventricular tachycardia (27%). The mean age was 12.9 +/- 8.6 years (range 4 months to 23 years) and the mean daily dose of amiodarone was 6.6 +/- 3.7 mg/kg/day (range 2.5 to 25 mg). Serum amiodarone and desethylamiodarone levels after 10.1 months (range 1 to 40 months) were 0.85 +/- 0.63 microgram/ml and 0.67 +/- 0.42 microgram/ml, respectively. In three patients for whom amiodarone therapy was unsuccessful, serum amiodarone levels were 0.27, 0.85, and 1.18 micrograms/ml. There was no significant correlation between serum amiodarone or desethylamiodarone levels and dosage of amiodarone. Four patients, all 13 years or older, developed toxicity (skin rash [one patient], keratopathy [two patients], and hyperthyroidism [one patient]). There was no correlation between serum amiodarone and desethylamiodarone levels and toxicity; although there was a trend toward elevated reverse serum triiodothyronine levels in patients who developed toxicity, the values fell within the range of those patients without toxic side effects. Serum amiodarone levels do not appear to be of great value in predicting efficacy and toxicity of amiodarone in children and young adults receiving chronic drug therapy.

Adolescent↗

Age differences in the consistency of cardiovascular response patterns in healthy women.

To determine if response consistency is higher in older women, twenty young adult (mean = 20 years) and twenty-two elderly (mean = 82 years) women participated in a 20-min stress protocol including serial subtraction, anxiety and anger imagery tasks. All subjects were healthy and free of diagnosed cardiovascular disease. Heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) responses to the tasks were assessed. To allow comparisons of the effects of stress on different cardiovascular parameters, all baseline-stress change scores were converted to z-scores. Forty-two 3(parameter)X3(stressor) matrices of z-scores, one for each subject, were created. Intraclass correlations computed using these matrices revealed greater consistency of response hierarchies (e.g., DBP greater than SBP greater than HR) among elderly subjects. Possible mechanisms for this effect are discussed.

Adolescent↗

Birth weight and gestational age standards based on regional perinatal network data: an analysis of risk factors.

The most frequently used set of gestational age-birth weight curves in the United States is the Colorado (C) standard published in 1963. To investigate the usefulness of this standard in an urban population at sea level, we examined the birth weight vs gestational age data from 56,675 singleton liveborn infants born between 1982 and 1985 in the University of Illinois (UI) perinatal network of 13 hospitals. Between 32 and 42 weeks, the UI 10th, median, and 90th percentile weights were significantly higher than those of Colorado. At term gestations the Colorado 10th and 90th percentile weights were the same as the UI 3rd and 80th percentile weights, respectively. Using the UI and Colorado standards for 10th and 90th percentile weights, the study sample was divided into five subgroups. To evaluate the risk prevalence, we examined the frequency of neonatal death, low, and very low Apgar scores (below seven and three, respectively), respiratory distress, maternal hypertension, and diabetes in the five subgroups. The highest frequency of adverse factors was seen in infants classified as small for gestational age (SGA) by both standards, but overall, the size-for-gestation grouping was better accomplished using the UI rather than the C standard. In 9188 infants (16.2%) classified into wrong weight-gestation subgroups using the Colorado standard, the prevalence of actual risk factors was at variance with the group to which they were assigned. This included 3632 (6.4%) SGA infants who were grouped as appropriate for gestational age (AGA), and 5556 (9.8%) AGA infants grouped as large for gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗