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Biomedical subjects

P Miller

Publications and source records attributed to P Miller.

At least 19 recordsLinked to original sources

Irradiation of the bovine mitochondrial F1-ATPase previously inactivated with 5'-p-fluorosulfonylbenzoyl-8-azido-[3H]adenosine cross-links His-beta 427 to Tyr-beta 345 within the same beta subunit.

The bovine heart mitochondrial F1-ATPase (MF1) is inactivated by 5'-p'-fluorosulfonylbenzoyl-8-azidoadenosine (8-N3-FSBA) with an apparent Kd of 0.47 mM at pH 8.0 and 23 degrees C in the absence of light. Irradiation of dark-inactivated enzyme with long-wavelength UV light produced cross-linked dimers and, to a lesser extent, trimers made up of alpha and beta subunits. Two major radioactive peptides were resolved by high-performance liquid chromatography from tryptic digests of MF1 which had been inactivated with 8-N3-FSB[3H]A at pH 8.0 in the dark. Sequence analysis revealed that one contained Tyr-beta 368 and the other contained His-beta 427 which were labeled in the ratio of 18:15. Sequence analysis of radioactive tryptic peptides isolated from digests of irradiated MF1 derivatized with 8-N3-FSB[3H]A showed that photolysis induced cross-linking of His-427 to Tyr-345 within the same beta subunit in high yield. When MF1 derivatized with 8-N3-FSB[3H]A was irradiated in the presence of beta-mercaptoethanol, alpha-beta cross-links were eliminated, whereas those between His-beta 427 and Tyr-beta 345 were unaffected. Analysis of radioactive peptides in tryptic digests of MF1 derivatized with 8-N3-FSB[3H]A and then irradiated in the presence or absence of beta-mercaptoethanol showed that the nitrene generated from reagent attached to Tyr-beta 368 participates in formation of alpha-beta cross-links in the absence of beta-mercaptoethanol. Therefore, the nitrene generated from reagent tethered to His-beta 427 is shielded from solvent and reacts with the side chain of Tyr-beta 345. In contrast, the nitrene generated from reagent attached to Tyr-beta 368 is exposed to solvent, but in the absence of scavengers reacts with side chains present in the alpha subunit. Irradiation of MF1, partially inactivated with 8-N3-FSBA, led to loss of residual ATPase activity without affecting residual ITPase activity. The amount of photoinactivation was greater when partial dark inactivation was performed at pH 6.9, where modification of His-beta 427 predominates, than when performed at pH 8.0, where modification of Tyr-beta 368 predominates. This suggests that cross-linking of His-beta 427 to Tyr-beta 345, and not cross-linking of alpha and beta subunits, is responsible for the augmented inactivation induced by irradiation.

Adenosine

Use of the ASI titanium stent in the management of bladder outflow obstruction due to benign prostatic hyperplasia.

An expandable titanium intraprostatic stent was inserted into 30 patients with infravesical obstruction due to benign prostatic hyperplasia (BPH). All of the men were considered unsuitable for transurethral resection of the prostate as a result of comorbid conditions. In 25 patients effective micturition was reestablished with this technique. In 21 of these men, who have been followed for longer than 1 year, the mean maximum flow rate at 1 year was 10.8 ml. per second and the mean residual urine was 56 ml. Although urinary tract infections occurred subsequent to stent insertion in 10 individuals, these resolved after appropriate antibiotic treatment and no stents have had to be removed for this reason. Followup cystoscopy or examination by electron microscopy of those stents that have been removed has shown partial epithelialization of the stent surface in a proportion of patients, and a minor degree of incrustation occurred in 1 case. We conclude that an expandable intraprostatic titanium stent is an acceptable alternative to transurethral resection of the prostate or long-term catheterization in this particular group of high risk patients.

Aged

Post-lumbar puncture headaches: experience in 501 consecutive procedures.

To ascertain the frequency and risk factors for post-lumbar puncture headache, we studied all adults who had an ambulatory lumbar puncture (LP) in a 1-year period. Patients filled out a questionnaire detailing their headache experience on the day of, and the 6 days following, LP. Those who did not return the questionnaire were telephoned. We systematically collected and analyzed many items, including the lumbar puncturist's experience, the degree of difficulty of the LP, CSF findings, final diagnosis, and the patient's demographic characteristics. Patients reporting headache before LP were more likely to report post-LP headaches. In addition to this, younger female patients with a lower body mass index have the highest risk of developing post-LP headaches. CSF opening pressure, cells, and protein, patient's position during LP, the duration of recumbency following LP, and the amount of CSF removed at the time of LP did not influence the occurrence of headache.

Adolescent

Medical students' knowledge of and exposure to cleft palate.

To compare the knowledge and experience of medical students in 1989 with that of those surveyed in 1973, a questionnaire about the various aspects of cleft palate was completed by 209 medical students from West Virginia University and the Louisiana State University Medical Center at Shreveport and New Orleans. Results revealed that 1989 students were more familiar with the embryology of cleft palate, racial and gender differences, and intellectual and psychologic issues (p less than .05). In contrast, the 1973 students were more able to define cleft palate, submucous cleft palate, and pharyngeal flap. There was no difference between the two groups of students in the amount of clinical exposure to cleft palate. These findings support the need for greater emphasis on cleft palate at the pre- and postdoctoral levels, as well as within continuing education programs. As part of current programs, the standard of practice of multidisciplinary team management for an individual with cleft palate should be underscored.

Cleft Palate

[Vocals in silence and noise. A simple test of resistance of intelligibility in noisy environment].

We have all noticed that there was no coincidence between the conventional audiometric tests--tonal, vocal, Metz tests--and the degree of impairment of understandability in noisy environments that the patients report. Some of them handle this problem better than these conventional tests suggest, others less well. The aim of this study is to take account of this dominating functional complaint: impairment in noisy conditions, and to assess it in order to follow up its evolution after medical, surgical and prosthetic treatments. The aim of the authors has been to describe an easy examination to be implemented in any ENT surgery fitted with a free-field vocal testing equipment. The results show that this test cas differentiate between "noise-resistant" subjects and those that do not "resist" well. The discussion defines the limitations of this test, which are due to its deliberate simplicity, and the caution required for its psychoacoustic and physiological interpretation. The conclusion confirms its merits, since it can discriminate and help choose more accurate tests--temporal tests, frequency selectiveness charts, twin-ear tests, cognitive AEP.

Audiometry, Speech

Induction of chronic human immunodeficiency virus infection is blocked in vitro by a methylphosphonate oligodeoxynucleoside targeted to a U3 enhancer element.

Oligodeoxynucleosides with internucleoside methylphosphonate linkages complementary to regions within U3 of human immunodeficiency virus type 1 were evaluated for their ability to block phorbol myristate acetate upregulation of virus in chronically infected promonocytic and T-lymphoblastoid cell lines. One such oligomer, targeted to an NF-kappa B enhancer element, inhibited phorbol myristate acetate induction of viral replication and tat-mediated trans activation of the human immunodeficiency virus long terminal repeat. The effect of this construct is contrasted with classical antisense methylphosphonate-derivatized oligomers complementary to initiation codon and splice acceptor sites of human immunodeficiency virus structural and regulatory genes. Its activity suggests a novel application of the modified oligonucleotide strategy in the blockade of viral induction from latently infected cells.

Antiviral Agents

Physical properties of DNA and chromatin isolated from G1- and S-phase HeLa S-3 cells. Effects of histone H1 phosphorylation and stage-specific nonhistone chromosomal proteins on the molar ellipticity of native and reconstituted nucleoproteins during thermal denaturation.

To help delineate how changes in chromatin organization are related to DNA replication and transcription during the HeLa S-3 cell cycle, we have extended previous studies of the composition and structure of chromatin in synchronized G1- and S-HASE CELLS. By analyzing changes in molar ellipticity at 276 nm ([theta 276]) during thermal denaturation, it was found that double-helical DNA molecules in native chromatin have different optical activities and thermal stabilities at these two stages of the cell cycle. Furthermore, profiles of d[theta 276]/dT vs. T indicate that native G1- and S-phase chromatins contain different families of DNA superstructures. To help determine the causes and functional significance of these chromatin reorganizations during the cell cycle, we compared the optical activities and thermal stabilities of DNA in native chromatin with protein-free DNA and DNA in nucleoproteins reconstituted in vitro by NaCl-urea gradient dialysis. In addition, we examined levels of histone phosphorylation, histone acetylation, and types of histone and nonhistone chromosomal proteins (NHCP) found in G1- and S-phase cells and in purified hydroxylapatite, (HAP) fractions of these nuclear proteins which were used for in vitro reconstitution. The results of the present studies indicate that changes in H1-DNA-NHCP interactions occur in vivo, are associated with the phosphorylation of histone 1 molecules, and appear to be responsible for the relaxation of compact G1-phase chromatin superstructures into more open S-phase configurations during the HeLa S-3 cell cycle.

Cell Cycle

Tumorigenicity of embryonal carcinoma as an assay to study control of malignancy by the murine blastocyst.

A bioassay, based on tumorigenicity, has been developed to determine the mechanism whereby the blastocyst of the mouse controls malignant expression of embryonal carcinoma. The assay is based upon the incidence of tumors obtained when known numbers of cells of the 402AX strain of embryonal carcinoma are injected into strain 129 mice, compared to the incidence obtained when the same number of embryonal carcinoma cells are incorporated into Swiss-Webster blastocysts that are then injected in strain 129 animals. The results indicate that the blastocyst can regulate one embryonal carcinoma cell consistently; it may have a slight effect on three, but it cannot regulate four or five of them. The position of the embryonal carcinoma cell in the blastocyst is important. Regulation occurs if the embryonal carcinoma cell is placed in the blastocoele cavity, but enhancement of tumorigenicity is obtained if it is placed between the zona pellucida and the trophectoderm. By contrast, the blastocyst is unable to regulate a single B-16 melanoma cell placed in the blastocoele cavity, indicating a degree of specificity for the regulatory process.

Animals

Videotaping epileptic attacks during stereoelectroencephalography.

Relating the onset of clinical attacks as recorded on a videotape to surface and depth electrographic events improves our ability to define the local or diffuse origin of seizures. In two patients with complex partial seizures, all 14 attacks appeared 3 to 6 seconds after focal discharges began in the amygdala or hippocampus. This meant that the spread of focal electroencephalographic (EEG) paroxysms caused the eventual clinical seizure. In two other patients with 392 generalized seizures and secondary bilateral synchronous paroxysms, a significant number of clinical attacks preceded the first depth or surface electrographic event. This suggested that the attacks originated from brain regions remote from the recording electrodes.

Adult

Maternal hyperthermia as a possible cause of anencephaly.

Mothers of anencephalic infants were asked about febrile illness and sauna bathing during their pregnancies. In 7 of 63 affected pregnancies (11%), a history of maternal hyperthermia near the presumed time of anterior neural-groove closure was given. 5 had fever with a maximum recorded temperature ranging from 38.9 to 40.0 degrees C, each case being secondary to a different type of illness. The other 2 had possible hyperthermia episodes as a consequence of sauna bathing, with no infectious agent involved. The frequencies of hyperthermia at the same period of gestation in two control groups were 0% and 0.1%. This excess frequency of maternal hyperthermia at the period of anterior neural-groove closure, and the differing natures of its causes, imply that hyperthermia itself may be an aetiological factor in anencephaly.

Adult

Time courses of the anti-anaphylactic and anti-inflammatory effects of dexamethasone in the rat and mouse.

1 The time course of the activity of dexamethasone has been studied in a variety of anaphylactic and inflammatory reactions in the rat and the mouse. 2 The times of peak activity of dexamethasone, expressed as time between oral dosage and induction of response, and the approximate ED50 values (mg/kg) found were: anaphylactic bronchoconstriction in rats, 12-24 h, ED50 1.8; passive cutaneous anaphylaxis in rats, 6 h, ED50 0.04; cutaneous reactions to histamine in rats, 4 h, ED50 0.01; carrageenin-induced paw oedema in rats, 4 h, ED50 0.03; pinnal anaphylaxis in mice, 6 h, ED50 0.82; histamine-induced pinnal reactions in mice, 6 h, ED50 0.05. 3 In rats, the characteristics of the inhibitory effects of dexamethasone indicate a differential activity against anaphylactic and inflammatory reactions and between different types of inflammatory reactions. Possible reasons for these differences are discussed. 4 In mice there was little difference between the inhibition by dexamethasone of cutaneous allergic and histamine-induced reactions. 5 Pinnal anaphylaxis in mice was potentiated by dexamethasone given 1-2 h before challenge.

Anaphylaxis

Proglonged epileptic twilight states: continuous recordings with nasopharyngeal electrodes and videotape analysis.

Confusion, speech arrest, automatic behavior, and amnesia characterize the prolonged twilight states of both petit mal and psychomotor status. However, in psychomotor status two electroclinical phases were differentiated: (1) A continuous twilight state with partial responsiveness and reactive automatisms interrupted by (2) staring, total loss of responsiveness, and stereotyped automatisms. During the first phase, with reactive behavior, the EEG showed bilateral diffuse slowing. During the second phase, with stereotyped automatisms, there were spreading right temporal 4- to 12-Hz discharges. Petit mal status had one continuous twilight state, during which both stereotyped and reactive automatisms merged as 1.5- to 4-Hz spike-wave complexes, and bimedial temporal 4-Hz discharges' appeared in the EEG.

Adult