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Biomedical subjects

M A Miller

Publications and source records attributed to M A Miller.

At least 145 records · Page 8Linked to original sources

False-positive enzyme immunoassay test results for Chlamydia trachomatis because of contact of the collection swab with agar.

BACKGROUND: We noted an increased incidence of false-positive Chlamydia trachomatis enzyme immunoassay results using the Abbott IMx SELECT C. trachomatis EIA test when a single swab was used for urethral sampling for both gonococcal culture inoculation and chlamydial detection. GOALS: To evaluate if contact of the enzyme immunoassay collection swab with an agar produces false-positive chlamydial enzyme immunoassay results. STUDY DESIGN: Samples containing agar-based culture media were tested by two enzyme immunoassays and a ligase chain reaction technique. RESULTS: We report false-positive chlamydial enzyme immunoassay results using the Abbott IMx SELECT C. trachomatis EIA test if the collection swabs are in contact with gonococcal culture media (Modified New York City agar, chocolate, Thayer-Martin, or GC-lect) before insertion of the swab in the transport media of the enzyme immunoassay. The other assay results were negative. CONCLUSIONS: Using a single collection swab to screen for genital infections with gonococcal cultures and chlamydial enzyme immunoassay is inappropriate because it may lead to false-positive chlamydial enzyme immunoassay results, at least with the Abbott IMx SELECT C. trachomatis EIA test, incurring public health and financial consequences.

Agar↗

Optochin revisited: defining the optimal type of blood agar for presumptive identification of Streptococcus pneumoniae.

To determine the optimal media for optochin susceptibility testing of Streptococcus pneumoniae, we measured inhibition zones for 72 S. pneumoniae and 22 Streptococcus viridans isolates on three blood-containing media. Because 15.3, 0, and 22.2% of S. pneumoniae organisms were misidentified on Columbia agar, Trypticase soy agar (TSA), and Mueller-Hinton agar, respectively, each containing sheep blood, we recommend that TSA-sheep blood agar be used.

Animals↗

Effect of gastric acid suppressants on human gastric motility.

BACKGROUND: The effect of histamine H2 receptor antagonists on gastric emptying is controversial. AIMS: To determine the effects of ranitidine, famotidine, and omeprazole on gastric motility and emptying. PATIENTS AND METHODS: Fifteen normal subjects underwent simultaneous antroduodenal manometry, electrogastrography (EGG), and gastric emptying with dynamic antral scintigraphy (DAS). After 30 minutes of fasting manometry and EGG recording, subjects received either intravenous saline, ranitidine, or famotidine, followed by another 30 minutes recording and then three hours of postprandial recording after ingestion of a radiolabelled meal. Images were obtained every 10-15 minutes for three hours to measure gastric emptying and assess antral contractility. Similar testing was performed after omeprazole 20 mg daily for one week. RESULTS: Fasting antral phase III migrating motor complexes (MMCs) were more common after ranitidine (9/15 subjects, 60%), famotidine (12/15, 80%), and omeprazole (8/12, 67%) compared with placebo (4/14, 29%; p < 0.05). Postprandially, ranitidine, famotidine, and omeprazole slowed gastric emptying, increased the amplitude of DAS contractions, increased the EGG power, and increased the antral manometric motility index. CONCLUSIONS: Suppression of gastric acid secretion with therapeutic doses of gastric acid suppressants is associated with delayed gastric emptying but increased antral motility.

Adolescent↗

Contrasting endocrine responses to acute oral compared with intravenous sodium loading in normal humans.

There is evidence in animals and in humans for accelerated natriuresis after oral compared with intravenous sodium loading. To assess the role of atrial natriuretic peptide (ANP) as a contributory mechanism, we compared the hormonal responses to an intravenous sodium load and to the same sodium load taken orally in three separate groups of healthy subjects in balance on low, normal, or high sodium intake. On each diet, there was a trend for an early delay in sodium excretion, followed by increased natriuresis after the oral compared with intravenous sodium load. On all levels of dietary sodium intake, there was a significant (approximately 2-fold) increase in plasma ANP levels after intravenous saline infusion. There was a significant suppression of the renin system both after oral and intravenous sodium loading. However, there was no acute increase in plasma ANP levels after the oral sodium load, except on the very low sodium intake. This striking and unexpected observation suggests that changes in plasma ANP levels appear to play little role in the early response to an acute oral sodium load in subjects with sodium intake in the range of 150-350 mmol/day. Endocrine mechanisms for the accelerated increase in sodium excretion after oral compared with intravenous sodium loading remain to be elucidated.

Adult↗

Implications of early sonographic evaluation of parapneumonic effusions in children with pneumonia.

OBJECTIVE: To devise a clinically relevant grading system for the sonographic evaluation of parapneumonic effusions, and to evaluate length of hospital stay as a function of treatment approach and sonographic grades. METHODS: Chest sonograms of 46 pediatric patients diagnosed with empyemas and admitted to two medical centers in the last 8 years were retrospectively evaluated using a grading system based on the degree of fibrinous organization within the parapneumonic effusions. Hospital charts were reviewed to determine the method of treatment and length of hospital stay. Patients were divided into two treatment groups: nonoperative (n = 26) (antibiotics alone, or combined with thoracentesis, or tube thoracostomy) and operative (n = 20) (open decortication, or video thoracoscopy and pleural debridement). Patients in the nonoperative group were further subdivided into two groups: those who received antibiotics alone (n = 11) and those who received antibiotics plus nonoperative drainage thoracentesis and/or tube thoracostomy (n = 15). Within each treatment group, patients were subdivided into two ultrasound grades: low (no evidence of organization) and high (evidence of organization such as fronds, septations, or loculations). Student's t test was performed to compare the lengths of hospital stay for each of the treatment groups and ultrasound grades. RESULTS: The length of hospitalization was no different for patients with low-grade ultrasounds in the nonoperative (9.8 days) and operative groups (8.0 days). In contrast, length of hospitalization was significantly shorter for patients with high-grade sonograms in the operative group (8.6 days), when compared with the nonoperative group (16.4 days). Length of hospitalization for patients in the nonoperative group with high-grade sonograms was significantly longer (16.4 days) than for those with low-grade ultrasounds (9.8 days). Furthermore, when the nonoperative patients were divided into an antibiotics alone group and a nonoperative drainage group, the patients with low-grade sonograms had no difference in the length of hospitalization (9.0 days vs. 10.4 days), whereas those patients with high-grade sonograms in the nonoperative drainage group had a significantly longer hospitalization (19.9 days) than the antibiotics alone (high-grade) group (11.4 days). CONCLUSIONS: Patients with a low-grade sonogram had similar length of hospitalization if treated with either nonoperative or operative measures. Patients with high-grade sonograms had significantly shorter length of hospitalization when treated with decortication. Our retrospective study suggests that patients with high-grade ultrasound studies treated nonoperatively do not benefit from pleural drainage procedures or chest tube placement. This study demonstrates the usefulness of early sonographic evaluation of parapneumonic effusions. A prospective study evaluating the usefulness of sonographic assessment of severity of disease in the treatment of children with parapneumonic effusions is warranted on the basis of our retrospective data.

Adolescent↗

Intestinal plasmacytoma in an African hedgehog.

A 3-yr-old male African hedgehog (Atelerix albiventris) had anorexia and weight loss for 1 wk before its death. The colon and mesocolon were diffusely infiltrated by a neoplastic proliferation of round cells with plasmacytoid features. A diagnosis of intestinal plasmacytoma was made and confirmed by electron microscopy. No other organs appeared to be affected. This is the first description of intestinal plasmacytoma in a hedgehog.

Animals↗

Morphometric analysis of endometrial periglandular fibrosis in mares.

OBJECTIVES: To develop an objective, quantifiable assay for endometrial periglandular fibrosis (EPF) and correlate assay results with histologic and ultrastructural changes in equine endometrial biopsy specimens. SAMPLE POPULATION: Endometrial biopsy specimens from 70 mares from 3 to 27 years old in estrus. PROCEDURE: In a double-blinded study design, endometrial biopsy specimens were graded histologically (modified Kenney classification) for EPF and inflammation. Endometrial periglandular collagen volume fraction (%EPCVF) was determined by light microscopic image analysis of picrosirius red-stained sections. Specimens from selected mares were examined by transmission electron microscopy. RESULTS: %EPCVF values varied significantly among the 4 modified Kenney EPF categories (I, IIA, IIB, and III) and increased with increasing age of mares. Morphologically, EPF consisted of concentric layers of transformed fibroblasts with myofibroblastic features and deposition of fibrillar collagen around unaltered glandular basal laminae. CONCLUSIONS AND CLINICAL RELEVANCE: %EPCVF correlates well with morphologic changes in endometrial biopsy specimens. Determination of %EPCVF could be useful in evaluation and clinical management of subfertile mares and in investigations of the pathogenesis of EPF.

Animals↗

GALR1 galanin receptor mRNA is co-expressed by galanin neurons but not cholinergic neurons in the rat basal forebrain.

The neuropeptide galanin (GAL) has been proposed to be an inhibitory modulator of cholinergic transmission in the hippocampus and may impair memory by directly affecting the activity of basal forebrain (BF) cholinergic neurons. Alternatively, GAL may act indirectly and modulate the activity of other neurotransmitter systems which, in turn, influence cholinergic transmission. We have used double in situ hybridization histochemistry to evaluate the co-expression of the GAL receptor subtype, GALR1, within cholinergic neurons in the medial septum/diagonal band of adult male rats. In alternate brain sections, we assessed the co-expression of GALR1 mRNA within another forebrain cell group implicated in memory functions, the neurons of the bed nucleus of the stria terminalis (BNST) and medial amygdala (AMe) which co-express vasopressin (VP) and GAL and project to septo-hippocampus. Despite the abundance of GALR1 mRNA-expressing neurons in the cholinergic BF, we found no evidence for the co-expression of this receptor subtype within cholinergic neurons in the medial septum/diagonal band. In contrast, we detected an extensive co-expression (95%) of GALR1 mRNA within extrahypothalamic VP/GAL neurons. These results do not support the idea that GAL, acting via the GALR1 receptor, directly impairs BF cholinergic neurons but suggest, instead, that non-cholinergic neurons in the BF may play a role in mediating the inhibitory actions of GAL on cholinergic function. However, our findings provide anatomical evidence that GAL could directly modulate the activity and/or secretion pattern of extrahypothalmic VP/GAL neurons into septo-hippocampal regions.

Acetylcholine↗

Estrogen regulates galanin but not tyrosine hydroxylase gene expression in the rat locus ceruleus.

The neuropeptide galanin (GAL) is coexpressed by the majority of noradrenergic neurons in the rat locus ceruleus (LC) and may function as an inhibitory modulator of noradrenergic transmission. Because estrogen has been shown to induce GAL expression in other brain regions and modulate noradrenergic transmission, we used in situ hybridization histochemistry to assess the effects of chronic estrogen treatment on GAL and tyrosine hydroxylase (TH) gene expression in the LC of ovariectomized female rats. We found that GAL mRNA levels were significantly elevated in rats implanted with a Silastic capsule containing estradiol compared to sham-implanted controls. Both the average optical density (P < or = 0.05) and the labelling area (P < or = 0.007) differed significantly between the groups. In contrast, TH gene expression measured in alternate brain sections did not differ between the groups. If GAL functions as an inhibitory modulator of noradrenergic transmission as postulated, these findings suggest that chronic estrogen treatment could reduce the noradrenergic tone of the brain in the absence of significant alterations in TH expression by enhancing the level of cosecreted GAL.

Analysis of Variance↗

A synthetic peptide administered with IL-12 elicits immunity to Listeria monocytogenes.

IL-12 is a pivotal cytokine signal for the development of Th1-type cellular responses that are required for control of intracellular pathogens. We previously demonstrated that coinjection of IL-12 with heat-killed Listeria monocytogenes, which was not immunogenic when injected alone, elicited intense Ag-specific T cell responses that conferred protection against subsequent challenge with Listeria. Herein we describe the remarkable finding that a nonimmunogenic synthetic peptide corresponding to a dominant MHC class II (H-2k)-restricted listerial determinant, when coinjected i.p. with murine IL-12, elicited potent Ag-specific immune responses that conferred protective immunity against Listeria.

Amino Acid Sequence↗

Fluoride binding in hemoproteins: the importance of the distal cavity structure.

The electronic absorption and resonance Raman spectra of the fluoride complexes of various peroxidases and selected site-directed mutants have been studied at pH 5.0, and compared to the spectra obtained for the myoglobin-F adduct. It is shown that the electronic absorption maxima depend on the degree of conjugation between the porphyrin macrocycle and the vinyl substituents. Moreover, it is confirmed that the wavelength of the CT1 band is a sensitive probe of axial ligand polarity and of its interaction with the distal protein residues. The results highlight the different mechanism of stabilization of the fluoride ligand exerted by the distal residues in myoglobin and peroxidases. In peroxidases, the Arg is determinant in controlling the ligand binding via a strong hydrogen bond between the positively charged guanidinium group and the anion. Mutation of Arg to Leu decreases the stability of the complex by 900-fold, suggesting that this interaction stabilizes the complex by 4 kcal/mol. The distal His also contributes to the stability of the fluoride complex, presumably by accepting a proton from HF and hydrogen-bonding, through a water molecule, to the anion. Mutation of His to Leu decreases the stability of the fluoride complex by 30-fold, suggesting that this interaction is much weaker than the interaction with the distal Arg. For Mb, the distal His is solely responsible for stabilization of the exogenous ligand.

Binding Sites↗

Repair of a facial defect with an interpolation skin flap in a cat.

A 9-year-old domestic shorthair cat was referred for removal of a rostrally located fibrosarcoma on the face, which had previously recurred twice following excision. A wide excision was performed, using a neodymium:yttrium-aluminumgarnet (Nd:YAG) laser, resulting in a facial defect that could not be closed by primary suture. An interpolation skin flap was elevated, using skin from the side of the cat's face, and sutured in place over the defect. Recurrence of the tumor at the medial canthus of the left eye, which was observed 4 months after surgery, was treated by laser excision and cryotherapy. Other recurrences of the fibrosarcoma were not noticed for 2.5 years after referral, at which time the cat was euthanatized for other reasons. Necropsy revealed that the fibrosarcoma had not recurred. In this cat, an interpolation skin flap was useful in repairing a large rostral facial defect. Care should be taken when elevating this flap to preserve the palpebral nerve.

Animals↗

Cytochrome c/cytochrome c peroxidase complex: effect of binding-site mutations on the thermodynamics of complex formation.

The cytochrome c/cytochrome c peroxidase system has been extensively investigated as a model for long-range electron transfer in biology. Two models for the structure of the one-to-one cytochrome c/cytochrome c peroxidase complex in solution exist: one is based upon computer docking of the two proteins and the second is based upon the structure of the complex in the crystalline state. Titration calorimetry is used to investigate the interaction of horse ferricytochrome c with baker's yeast cytochrome c peroxidase and with six cytochrome c peroxidase mutants. Five of the six peroxidase mutants eliminate a negative charge in the cytochrome c binding site by replacing a side-chain carboxylate with an amide. The sixth mutation replaces a surface alanine residue with phenylalanine. The binding affinity between cytochrome c and the cytochrome c peroxidase mutants varies from no significant change in comparison to the wild-type enzyme to a 4-fold decrease in the equilibrium association constant. The pattern of decreasing cytochrome c binding affinity for the cytochrome c peroxidase mutants is consistent with the cytochrome c binding domain defined by X-ray crystallography [Pelletier, H., & Kraut, J. (1992) Science 258, 1748-1755]. For those mutants which have lower affinity for cytochrome c, the lower affinity is due to a decrease in the entropy change upon complex formation, consistent with the difference in hydration of carboxylate and amide groups.

Animals↗

Nerve growth factor induces galanin gene expression in the rat basal forebrain: implications for the treatment of cholinergic dysfunction.

Nerve growth factor (NGF) is a potential treatment for cholinergic dysfunction associated with Alzheimer's disease (AD). In rats, NGF activates gene expression of the acetylcholine synthetic enzyme choline acetyltransferase (ChAT) and prevents age- and lesion-induced degeneration of basal forebrain (BF) cholinergic neurons. Cholinergic neurons in the BF coexpress galanin (GAL), a neuropeptide that has been shown to impair performance on memory tasks possibly through the inhibition of cholinergic memory pathways. NGF up-regulates both ChAT and GAL gene expression in cultured pheochromocytoma cells; however, the effect of chronic in vivo NGF administration on GAL gene expression within the BF has not been studied. We used in situ hybridization and quantitative autoradiography to assess GAL and ChAT gene expression within the BF of adult male rats following chronic intracerebroventricular infusion of NGF or cytochrome c. We now report that, in addition to stimulating ChAT gene expression, NGF strongly up-regulated the GAL gene in the rat cholinergic BF. NGF had no effect on GAL gene expression in other noncholinergic forebrain regions. NGF induction of GAL gene expression in the BF was specific, because gene expression for another neuropeptide, neurotensin, present within noncholinergic BF neurons was unchanged. Our data provide the first evidence that in vivo NGF administration up-regulates GAL gene expression in the cholinergic BF. These results suggest that the concurrent induction of GAL in the BF could limit the ameliorating actions of NGF on cholinergic dysfunction.

Animals↗

Health risk assessment practices in the U.S. Food and Drug Administration.

The U.S. Food and Drug Administration (FDA) regulates a wide variety of consumer products. Safety issues involve chemical and microbial contaminants in food, biologies, and medical devices; side effects from prescription and nonprescription drugs; residues of animal drugs in food; and radiation from electronic devices. Because of this wide diversity, the legal standards, rules, and policies governing the regulation of these products differ considerably. Hence, risk assessment and risk management practices within the FDA are of necessity quite diverse. This paper presents a summary of risk assessment practices at each of the product centers of the FDA (Center for Food Safety and Applied Nutrition, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, Center for Devices and Radiological Health, and Center for Veterinary Medicine) and of the development of risk assessment procedures at the National Center for Toxicological Research.

Animals↗

Life changes scaling for the 1990s.

Three decades ago, results from a proportionate scaling study of life change events was published in this journal. The events, listed by rank order of their mean life change values, comprised the Social Readjustment Rating Scale (SRRS). Ten years later, 42 of the 43 original events were rescaled. In this second study, an additional 44 events were added to the original list. In the present report, the original plus the later-developed events were scaled once again by persons chosen to closely approximate subjects enrolled in the initial study. Comparing the average life change intensity scores across 30 years, a 45% increase in mean values was seen. These recently derived life change magnitudes, for both the original list of events plus the later-developed events, provide values appropriate for use in the 1990s. In the original study, effects of subjects' demographic characteristics were noted briefly in a table. In the present investigation, varying influences of gender, age, marital status, and education were explored in more detail. Several significant differences were discovered, with gender showing a very pronounced influence on scaling results. Discussion of these results included composition requirements for a life changes questionnaire.

Adult↗