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Biomedical subjects

M A Miller

Publications and source records attributed to M A Miller.

At least 217 records · Page 12Linked to original sources
PubMed1995

X-ray absorption spectroscopic studies of the Fe(II) active site of catechol 2,3-dioxygenase. Implications for the extradiol cleavage mechanism.

The extradiol-cleaving catechol 2,3-dioxygenase (2,3-CTD) isolated from Pseudomonas putida mt-2 and its catechol and ternary E.S.NO complexes are characterized by X-ray absorption spectroscopy (XAS). The intensities of the 1s-->3d transitions in the pre-edge spectra of the uncomplexed enzyme and its substrate complex show that the Fe(II) center is five-coordinate in both complexes, in agreement with earlier magnetic circular dichroism studies [Mabrouk, P. A., Orville, A. M., Lipscomb, J. D., & Solomon, E. I. (1991) J. Am. Chem. Soc. 113, 4053-4061]. Analysis of the EXAFS region of uncomplexed 2,3-CTD shows five N/O ligand atoms 2.09 A from the active site Fe(II). In the 2,3-CTD.catechol complex, one N/O atom is located at 1.93 A and four N/O type ligands are at 2.10 A. By comparison with [FeII-(6TLA)(DBCH)](ClO4), the first well-characterized mononuclear Fe(II).catechol model complex, the 1.93 A scatterer is proposed to be the oxygen from the deprotonated hydroxyl group of the coordinated catecholate monoanion. Nitric oxide binds to the Fe(II) center in the enzyme.catechol complex without displacing the existing ligands, resulting in the formation of a six-coordinate complex, as indicated by the addition of a new N/O type scatterer at 1.74 A. Bond valence sum (BVS) analysis of the bond lengths derived from the EXAFS fits gives values that correspond to the iron oxidation states established for these complexes, thus lending credence to the coordination environment deduced for the iron center in those complexes. The present study provides the first evidence for a monoanionic substrate binding mode in an extradiol dioxygenase, which is distinct from the dianionic binding mode proposed for intradiol dioxygenases. We speculate that this difference in binding mode may have important ramifications for the site of aromatic ring cleavage in the subsequent oxygen insertion reactions.

Binding Sites↗
PubMed1995

The relationship of human papillomavirus to proliferation and ploidy in carcinoma of the anus.

BACKGROUND: Human papillomavirus (HPV) infections have been implicated in anogenital neoplasia in both sexes. In this study, the authors postulated that HPV infections induce squamous epithelium to become hyperproliferative and aneuploid. METHODS: To test this hypothesis, formalin fixed, paraffin embedded tissues were analyzed for the presence of HPV by in situ hybridization. S-phase fraction and DNA content were evaluated by flow cytometry. Proliferative indices also were analyzed using an antibody to proliferating cell nuclear antigen (PCNA). RESULTS: Human papillomavirus DNA was present in 48.1% of the carcinomas. All but one HPV-positive tumor contained HPV 16/18 DNA. The remaining tumor contained only HPV 6/11. No correlation was found between HPV status, patient age, or tumor differentiation. Thirty-three percent of tumors were aneuploid. Only two patients had aneuploid tumors that were HPV-negative; these patients received preoperative radiotherapy. The average S-phase fraction was significantly higher (P < 0.01) in HPV-positive versus HPV-negative lesions. The PCNA index for HPV positive tumors was also significantly higher than that observed in negative tumors (p < 0.003). CONCLUSION: The presence of HPV in tumor cells is significantly associated with an increased proliferative rate and aneuploid status of tumors compared with HPV-negative tumors. These findings are consistent with the fact that viral proteins binding to tumor suppressor gene proteins can deregulate the cell cycle and lead to genomic instability.

Aneuploidy↗
PubMed1995

Increased phosphotyrosine in breast cancer tissue is associated with a worse prognosis.

We have previously demonstrated that phosphotyrosine can be identified in breast cancer cells using an immunohistochemical stain. We have subsequently used this technique to characterize 106 women with breast cancer (46 with Stage 1 and 60 with Stage 2) who have been followed for at least four years by one oncologist. We analyzed all primary breast cancer tissue using immunohistochemical staining and the amount of phosphotyrosine (PT) was scored on a 0 to 3 range. The PT score of the primary tumor was unrelated to either breast cancer stage or estrogen and progesterone receptor analysis, as high PT scores were noted in both disease stages and all receptor categories. We did find that patients with either no or trace (1+) amounts of PT survived longer than those patients with higher amounts of PT. The patients with low PT had significantly lower chance of relapse (Chi Square = 15.8, p < 0.001) and a lower mortality (Chi Square = 13.1, p = 0.001). We conclude that immunohistochemical methods to determine the PT score may identify patients at higher risk for disease relapse independent of tumor stage or hormonal status.

Breast Neoplasms↗
PubMed1995

Electron transfer between cytochrome c and cytochrome c peroxidase.

The reaction between cytochrome c (CC) and cytochrome c peroxidase (CcP) is a very attractive system for investigating the fundamental mechanism of biological electron transfer. The resting ferric state of CcP is oxidized by hydrogen peroxide to compound I (CMPI) containing an oxyferryl heme and an indolyl radical cation on Trp-191. CMPI is sequentially reduced to CMPII and then to the resting state CcP by two molecules of CC. In this review we discuss the use of a new ruthenium photoreduction technique and other rapid kinetic techniques to address the following important questions: (1) What is the initial electron acceptor in CMPI? (2) What are the true rates of electron transfer from CC to the radical cation and to the oxyferryl heme? (3) What are the binding domains and pathways for electron transfer from CC to the radical cation and the oxyferryl heme? (4) What is the mechanism for the complete reaction under physiological conditions?

Amino Acid Sequence↗
PubMed1995

Pituitary response to thyrotropin, corticotropin, and gonadotropin-releasing hormones in lactating cows treated with sometribove for a fourth consecutive lactation.

The effect of chronic treatment with recombinant methionyl bovine somatotropin (USAN, sometribove) on anterior pituitary secretions and its target organs was investigated in six control and six sometribove-treated British Friesian cows. Cows averaged 112 and 119 d postpartum in their fourth lactation of treatment and, except for one control, had active corpora lutea. During each lactation, treated cows received sometribove injections (500 mg) every 2 wk (injection cycle) starting 60 +/- 3 d postpartum. On Day 9 of one injection cycle, blood was sampled for 390 min, starting 30 min before an intravenous injection of thyrotropin (TRH, 0.33 microgram/kg), corticotropin (100 microgram), and gonadotropin (GnRH, 200 micrograms)-releasing hormones. Baseline somatotropin (bST) and adrenocorticotropin (ACTH) were higher in sometribove-treated cows vs. controls (3.27 vs. 1.03 ng/ml and 35.24 vs. 19.28 pg/ml, respectively). Baseline total thyroxine, free thyroxine, triiodothyronine, prolactin, follicle stimulating and luteinizing hormones, estradiol, and progesterone (P4) were similar across treatments. Circulating cortisol levels did not differ between control and sometribove cows, indicating a reduced adrenal ACTH responsiveness in the latter. Releasing factors induced similar changes across treatments in hormones studied with the following exceptions: a bST spike was seen in control cows only, cortisol response to ACTH was reduced in treated cows, and a significantly higher P4 concentration was detected in the plasma of sometribove-treated cows, suggesting increased ovarian responsiveness to GnRH-stimulated P4 output. The study demonstrated reduced bST response to TRH, consistent with physiologic feedback mechanisms, whereas the release profiles of the other pituitary hormones were unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1995

Nurses' educational preparation and attitudes toward cost containment.

This study examined attitudes toward cost-effectiveness among nurses who were stratified according to their highest educational nursing preparation (ie, diploma, associate degree, bachelor's degree). A convenience sample of 65 staff nurses from OR and intensive care settings participated. Descriptive statistics and one-way and two-way analyses of variance were used to analyze the data. Mean scores on the Blaney/Hobson Nursing Attitude Scale for the associate degree nurse (ADN), diploma, and bachelor of science in nursing (BSN) groups were 69.90, 76.65, and 81.27, respectively. The diploma- and BSN-prepared staff nurses had significantly more favorable attitudes toward cost-containment issues in nursing practice than did the ADN group (p = .05).

Adult↗
PubMed1995

Absorbable gelatin powder injection for transient vocal cord paralysis.

In the early 1900s, glottic insufficiency in patients with vocal cord paralysis was corrected by injecting paraffin intralaryngeally. Since then, injecting absorbable gelatin powder into the vocal cord has become an acceptable short-term solution for transient paralysis of a single vocal cord. Although relatively uncommon, this procedure has few complications and is an option for patients when vocal cord function is expected to return within one year.

Absorption↗
PubMed1995

Role of nuclear medicine in evaluating patients with suspected gastrointestinal motility disorders.

Functional symptoms caused by gastrointestinal motility disorders are relatively common in the general population. Knowledge of the relationship between symptoms and the underlying gastrointestinal dysmotility provides physicians with a framework for successful evaluation and treatment of patients with possible motor disorders of the gastrointestinal tract. Scintigraphy provides for noninvasive and quantitative assessment of physiological transit throughout the gastrointestinal tract, and it is extremely useful for diagnosing gastrointestinal motor dysfunction. The wide range of scintigraphic studies now available supplement other diagnostic tests for evaluation of all segments of the gastrointestinal tract.

Colon↗
PubMed1995

Anterior chamber contamination after uncomplicated phacoemulsification and intraocular lens implantation.

PURPOSE: To determine the frequency of anterior chamber contamination occurring during uncomplicated cataract surgery with intraocular lens implantation using phacoemulsification through a scleral tunnel incision. METHODS: In a prospective study, anterior chamber aspirates of one eye each of 103 consecutive ambulatory patients who underwent uncomplicated cataract surgery with lens implantation were cultured. The anterior chamber aspirate was withdrawn immediately upon the completion of surgery. Conjunctival cultures of the same eye were taken immediately before surgery, after the eye and periocular area had been prepared and draped. Multiple use topical medications used preoperatively on all patients were cultured at the end of the surgical day. RESULTS: Intraocular aspirates yielded positive cultures in five specimens (5%), four of which were identified as Staphylococcus epidermidis. Quantification disclosed colony counts ranging between 100 and 200 colony forming units per milliliter. Results of conjunctival cultures were positive in ten specimens (10%). Staphylococcus epidermidis was the most common isolate, identified in seven of the ten positive cultures. Positive intraocular and conjunctival culture results were not present concurrently in any patient. Microorganisms were recovered from the multiple use topical medications on nine of the 26 successive surgical days. Neisseria species was the most frequent isolate (7,44%), followed by S. epidermidis (5,31%). The frequency of contamination of the anterior chamber was independent of wound width (chi 2 = 0.869) and operative time (chi 2 = 4.77). CONCLUSION: Bacterial contamination of the anterior chamber was detected in five (5%) of the patients. This reduced incidence of contamination compared with that of previous studies may be related to the preoperative preparation, the surgical technique, or both. Contamination of the multiple use topical medications and bulbar conjunctiva define possible sources of pathogens that may enter the anterior chamber. The absence of any clinical ocular infection in all patients attests to the small inoculum sizes, as well as the ability of the anterior chamber to clear small bacterial loads.

Administration, Topical↗
PubMed1995

Hormonal and renal responses to neutral endopeptidase inhibition in normal humans on a low and on a high sodium intake.

Hormonal and renal effects of candoxatril, a neutral endopeptidase 24.11 inhibitor, were investigated in eight subjects equilibrated on a low sodium diet (10 mmol sodium per day) and a high sodium (350 mmol per day) diet. After candoxatril treatment, plasma ANP increased to a maximum at 2-4 h and declined to baseline within 24 h. The increases were relatively greater on the high sodium diet, which was also associated with increases in urinary sodium, with highest values at 4h. On the low sodium diet, the magnitude of the changes was significantly lower (24 h cumulative sodium excretion was 11.4 +/- 5.5 mmol on the low sodium diet and 73.1 +/- 25.6 mmol on the high sodium diet; P < 0.01). There were no significant effects on urinary potassium excretion, creatinine clearance or haematocrit. After candoxatril treatment there were reductions in PRA, especially on the low sodium diet. On either diet there were no effects on systemic blood pressure. These results demonstrate that dietary sodium intake is an important determinant of the renal and hormonal responses to neutral endopeptidase inhibition.

Adult↗
PubMed1995

Variation in cancer risk estimates for exposure to powerline frequency electromagnetic fields: a meta-analysis comparing EMF measurement methods.

We used meta-analysis to synthesize the findings from eleven case-control studies on cancer risks in humans exposed to 50-60 Hertz powerline electromagnetic fields (EMFs). Pooled estimates of risk are derived for different EMF measurement methods and types of cancer. EMF measurement methods are classified as: wiring configuration codes, distance to power distribution equipment, spot measurements of magnetic fields, and calculated indices based on distance to power distribution equipment and historic load data. Pooled odds ratios depicting the risk of cancer by each measurement type are presented for all cancers combined, leukemia for all age groups and childhood leukemia. The wire code measurement technique was associated with a significantly increased risk for all three cancer types, while spot measures consistently showed non-significant odds ratios. Distance measures and the calculated indices produced risk estimates which were significant only for leukemia.

Adult↗
PubMed1995

Testing of susceptibility of Mycobacterium tuberculosis to pyrazinamide: comparison of Bactec method with pyrazinamidase assay.

The susceptibility of 428 clinical isolates of Mycobacterium tuberculosis to pyrazinamide was assessed by the Bactec method and the Wayne pyrazinamidase assay. The correlation between the two tests was 98.2 and 100% for susceptible and resistant strains, respectively. False resistance was seen in four (0.8%) strains with the Bactec test, and false-susceptible results occurred in two (0.5%) pyrazinamidase assays. The Bactec test is rapid and reliable, and the Bactec results correlate well with the pyrazinamidase test results, although some strains did not grow well in the test medium.

Antitubercular Agents↗
PubMed1995

Effect of amino acid substitutions on calmodulin binding and cytolytic properties of the LLP-1 peptide segment of human immunodeficiency virus type 1 transmembrane protein.

Previous studies have identified two highly basic amphipathic helical regions in the human immunodeficiency virus type 1 transmembrane protein that, in vitro, display both cytolytic and calmodulin-binding and -inhibitory properties that could contribute to cellular dysfunctions and cytopathogenesis during a persistent viral infection. In the current study, the structural specificity of the cytolytic and calmodulin-binding activities of the human immunodeficiency virus type 1 lentivirus lytic peptide (LLP-1) are examined with synthetic peptide homologs and analogs. The results of these studies demonstrate that even minor changes in LLP-1 amino acid content can markedly affect these properties, suggesting that sequence variation in these highly conserved LLP sequences may correlate with alterations in viral cytopathic properties.

Amino Acid Sequence↗
PubMed1995

Galanin-binding sites in the female rat brain are regulated across puberty yet similar to the male pattern in adulthood.

The neuropeptide galanin (GAL) has been implicated in a variety of neuroendocrine functions and has been shown to be regulated by gonadal hormones in several brain regions. We have used slice binding and quantitative autoradiography techniques to determine whether the activation of GAL pathways across puberty in female rats is associated with changes in the density of GAL binding in telencephalic and diencephalic regions as we previously observed in male rats. We have also asked whether sex differences in GAL immunoreactivity and GAL gene expression detected in some brain regions would be paralleled by sex differences in 125I-GAL-binding density in adult male and female rat brains. To control for intrinsic differences in the level of endogenous GAL synthesis and release, brain slices from prepubertal female and adult male and female rats were treated with guanosine 5'-triphosphate (GTP) to induce dissociation of endogenous GAL from its binding sites prior to incubation with radiolabeled ligand. 125I-GAL binding was significantly reduced in seven brain regions of adult compared with prepubertal female rats. These regions included the islands of Calleja (p < or = 0.03), the medial amygdaloid nucleus, posterodorsal division (p < or = 0.05), median eminence (p < or = 0.02), medial habenular nucleus (p < or = 0.05), rhomboid thalamic nucleus (p < or = 0.05), and paraventricular (p < or = 0.05) and intermediodorsal (p < or = 0.02) thalamic nuclei. Only one region, the lateral preoptic area, exhibited significantly enhanced 125I-GAL binding in adult female (p < or = 0.04) compared with prepubertal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗