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A Jordan

Publications and source records attributed to A Jordan.

At least 19 recordsLinked to original sources
PubMed1996

The ribonucleotide reductase system of Lactococcus lactis. Characterization of an NrdEF enzyme and a new electron transport protein.

Escherichia coli contains the genetic information for three separate ribonucleotide reductases. Two of them (class I enzymes), coded by the nrdAB and nrdEF genes, respectively, contain a tyrosyl radical, whose generation requires oxygen. The NrdAB enzyme is physiologically active. The function of the nrdEF gene is not known. The third enzyme (class III), coded by nrdDG, operates during anaerobiosis. The DNA of Lactococcus lactis contains sequences homologous to the nrdDG genes. Surprisingly, an nrdD- mutant of L. lactis grew well under standard anaerobic growth conditions. The ribonucleotide reductase system of this mutant was shown to consist of an enzyme of the NrdEF-type and a small electron transport protein. The coding operon contains the nrdEF genes and two open reading frames, one of which (nrdH) codes for the small protein. The same gene organization is present in E. coli. We propose that the aerobic class I ribonucleotide reductases contain two subclasses, one coded by nrdAB, active in E. coli and eukaryotes (class Ia), the other coded by nrdEF, present in various microorganisms (class Ib). The NrdEF enzymes use NrdH proteins as electron transporter in place of thioredoxin or glutaredoxin used by NrdAB enzymes. The two classes also differ in their allosteric regulation by dATP.

Amino Acid Sequence↗
PubMed1996

Developing a new method to record care at home for children with cancer: an example of research and practice collaboration in a regional paediatric oncology unit.

Academics need to address the facilitation of nurses in practice to research and develop the care given to patients if nursing is to move closer towards a research-based profession. This paper describes a project involving collaboration between an academic department of nursing and nurses working in clinical practice providing care at home for children with cancer. The project involved an audit of the nursing care records for the service, and the development of a new style of record-keeping which described and quantified complex nursing care. The authors discuss the method and results of the project, describing the benefits of research and practice collaboration.

Child↗
PubMed1995

Two different operons for the same function: comparison of the Salmonella typhimurium nrdAB and nrdEF genes.

By using a P22 phage-mediated cloning system, the nrdAB genes of Salmonella typhimurium (St), encoding a ribonucleotide reductase (RR) of class I, have been isolated. The coding regions of the St nrdAB operon show a very high identity with those of the homologous operon of Escherichia coli (Ec). Nevertheless, there are significant differences in their promoter regions since, although the promoters of both operons present two DnaA boxes, these boxes are located downstream from the transcription start point in St, being upstream in Ec. Moreover, the deduced amino-acid sequences of the St nrdAB showed a very limited overall identity (28%) with the products of St nrdEF, which encode a second class-I RR. Expression of St nrdAB and nrdEF is inducible by hydroxyurea, an inhibitor of RR activity. Alignment of the promoter regions of the nrdAB and nrdEF operons of both St and Ec reveals the presence of a consensus sequence. St is the first organism from which two different RR belonging to the same biochemical class are known.

Base Sequence↗
PubMed1994

A second class I ribonucleotide reductase in Enterobacteriaceae: characterization of the Salmonella typhimurium enzyme.

The nrdA and nrdB genes of Escherichia coli and Salmonella typhimurium encode the R1 and R2 proteins that together form an active class I ribonucleotide reductase. Both organisms contain two additional chromosomal genes, nrdE and nrdF, whose corresponding protein sequences show some homology to the products of the genes nrdA and nrdB. When present on a plasmid, nrdE and nrdF together complement mutations in nrdA or nrdB. We have now obtained in nearly homogeneous form the two proteins encoded by the S. typhimurium nrdE and nrdF genes (R1E and R2F). They correspond to the R1 and R2 proteins. Each protein is a homodimer. Together they catalyze the reduction of CDP to dCDP, using dithiothreitol or reduced glutaredoxin, but not thioredoxin, as an electron donor. CDP reduction is strongly stimulated by low concentrations of dATP, presumably acting as an allosteric effector. Protein R2F contains an antiferromagnetically coupled dinuclear iron center and a tyrosyl free radical. The E. coli and S. typhimurium chromosome thus have maintained the information for a potentially active additional class I ribonucleotide reductase, whose role in vivo is as yet unknown. The allosteric regulation of this enzyme differs from that of the normally expressed reductase.

Allosteric Regulation↗
PubMed1994

FDA recommendations for preclinical testing of gonadotropin releasing hormone (GnRH) analogues.

Gonadotropin-releasing hormone (GnRH) agonists and antagonists are synthetic analogues synthesized by modifications of the naturally occurring hypothalamic decapeptide GnRH. These modifications significantly increase the biological potency and duration of action of GnRH agonists as well as the solubility, potency, and duration of action of GnRH antagonists while decreasing GnRH antagonists toxicity. The field of GnRH analogues has expanded significantly during the past few years in terms of the number of analogues, therapeutic indications, formulations, and mode of administration. This paper provides recommendations for nonclinical testing of GnRH analogues and reflects the type and degree of toxicity testing expected by the Division. However, these recommendations are not formal guidelines in that alternative testing methods will be considered. Furthermore, these recommendations should not be used as guidance for testing of other new drugs.

Amino Acid Sequence↗
PubMed1994

Toxicology of depot medroxyprogesterone acetate.

Depo-Provera (depot-medroxyprogesterone acetate or DMPA), administered either subcutaneously or intramuscularly, has undergone a thorough toxicological evaluation in a number of animal species. DMPA has been tested in short- and long-term toxicity studies in rodents, rabbits, and monkeys. It has been examined for its effects on reproduction in mice, rats, and rabbits, and for carcinogenic potential in rats, mice, beagle dogs, and rhesus monkeys. Genotoxicity tests have been performed in vitro and in vivo. This paper describes the toxicology data submitted to the US FDA in support of the New Drug Application (NDA) for Depo-Provera as well as data published in the literature. When interpreted in the light of the available pharmacokinetic information, these data demonstrate that DMPA is not significantly different from other contraceptive progestogens in its toxic and tumorigenic potential.

Animals↗
PubMed1994

Regulatory considerations for oligonucleotide drugs: updated recommendations for pharmacology and toxicology studies.

This article describes pharmacology and toxicity studies for oligonucleotide drugs that are recommended for inclusion in the initial Investigational New Drug Application (IND), a first request to use an investigational drug in clinical trials. Recent observations of non-sequence-dependent cardiovascular toxicity and deaths in monkeys following intravenous infusions of phosphorothioates have raised a potential safety concern for oligonucleotide drugs. This concern should be considered by drug sponsors in designing pre-IND nonclinical development programs and Phase I clinical protocols. Pre-IND conduct of pharmacodynamic cardiovascular screening is highly recommended for defining safe clinical dosing regimens for phosphorothioate (and, possibly, other charged-backbone) oligomers. Additionally, drug sponsors are encouraged to (1) conduct research into-the mechanisms responsible for this dose-limiting toxicity, (2) institute liberal publication policies for research conducted under industrial sponsorship, and (3) communicate with reviewing divisions at FDA for updated guidance in this field when planning pre-IND safety studies. Recommendations for nonclinical studies during development of oligonucleotides will be modified as new information regarding the biological properties of oligonucleotides becomes available.

Animals↗
PubMed1994

Risk of hepatitis C in patients who received blood from donors subsequently shown to be carriers of hepatitis C virus.

A retrospective study was undertaken to identify recipients of blood from donors subsequently shown to be positive for hepatitis C virus using second-generation tests and polymerase chain reaction. The main aims were to determine the numbers of such recipients who were still alive and traceable, and to determine the risk of infection in this group. The feasibility and workload of this procedure, which is currently not practised in the U.K. or U.S.A., was also assessed. In the first six months of routine testing 42,697 donors were tested. Of 20 confirmed to be HCV-positive, 15 were regular donors. Eighty-three components were prepared from 63 anti-HCV positive previous donations from these donors. In all, nine recipients were found to be alive. All were positive for anti-HCV. We conclude that although this retrospective procedure is time-consuming and difficult, substantial numbers of infected recipients can be identified. The availability of treatment for chronic hepatitis C for such patients should encourage transfusion services to reassess current policies on the hepatitis C retrospective.

Blood Donors↗
PubMed1994

Cloning and sequencing of the genes from Salmonella typhimurium encoding a new bacterial ribonucleotide reductase.

A plasmid library of Salmonella typhimurium was used to complement a temperature-sensitive nrdA mutant of Escherichia coli. Complementation was obtained with two different classes of plasmids, one carrying the E. coli nrdAB-like genes and the second containing an operon encoding a new bacterial ribonucleotide reductase. Plasmids harboring these new reductase genes also enable obligately anaerobic nrdB::Mud1 E. coli mutants to grow in the presence of oxygen. This operon consists of two open reading frames, which have been designated nrdE (2,145 bp) and nrdF (969 bp). The deduced amino acid sequences of the nrdE and nrdF products include the catalytically important residues conserved in ribonucleotide reductase enzymes of class I and show 25 and 28% overall identity with the R1 and R2 protein, respectively, of the aerobic ribonucleoside diphosphate reductase of E. coli. The 3' end of the sequenced 4.9-kb fragment corresponds to the upstream region of the previously published proU operon of both S. typhimurium and E. coli, indicating that the nrdEF genes are at 57 min on the chromosomal maps of these two bacterial species. Analysis of the nrdEF and proU sequences demonstrates that transcription of the nrdEF genes is in the clockwise direction on the S. typhimurium and E. coli maps.

Amino Acid Sequence↗
PubMed1994

Evaluation of the atypical cytologic smear. Validity of the 1991 Bethesda System.

The 1991 Bethesda System states that atypical squamous or glandular cells of undetermined significance should be further classified as reactive or premalignant/malignant. The validity of this qualification for identification of patients with cervical intraepithelial neoplasia (CIN) was tested. One hundred twenty-four cytologic smears with squamous atypia were reviewed retrospectively by two cytopathologists blind to the colposcopy results. The smears were classified as favoring either reactive or premalignant/malignant processes. Subjective criteria used in the classification were based on the pathologists' experience. All patients underwent colposcopy and selected biopsy under the direction of a gynecologic oncologist. Of the 124 atypical smears, 69 were classified as favoring reactive processes and 55 as favoring premalignant/malignant processes by cytopathologist 1. Cytopathologist 2 classified 68 as reactive and 56 as premalignant/malignant. Colposcopy and selected biopsy revealed the following lesions: 34 cases of human papillomavirus (27.4%), 17 of CIN 1 (13.7%), 4 of CIN 2 (3.2%), 2 of CIN 3 (1.6%) and 67 without pathology (54.0%). All six patients with squamous atypia and underlying CIN 2 and 3 lesions had their cytology classified as premalignant/malignant by the cytopathologists. In these patients this qualification had high sensitivity (100%) and negative predictive value (100%). The 1991 Bethesda System classification above, when applied to patients with squamous atypia, was effective in identifying patients with serious pathologic cervical lesions. If used as a triage method, colposcopy should be reserved for atypical lesions classified as premalignant/malignant, potentially decreasing the cost of health care without decreasing the quality of that care.

Adult↗
PubMed1994

Back pain, sciatica and disability following first-time conventional haemilaminectomy for lumbar disc herniation. Use of "Low Back Pain Rating Scale" as a postal questionnaire.

To determine the value of "Low Back Pain Rating Scale" as a postal questionnaire, a retrospective study was undertaken of patients who had undergone first-time lumbar disc surgery 14-72 months previously. Rate of response was 86% (261/304). From the results, it was concluded that 87% of the patients felt that a satisfactory surgical outcome was obtained; 67% had minor or major functional restrictions of their daily activities; 65% experienced significant low-back symptoms in the period prior to follow-up examination; and 57% experienced sciatica. Thirty-seven patients were receiving pensions in the postoperative period due to continued back pain. "Low Back Pain Rating Scale" used as a postal questionnaire was found to be useful in determining general overall assessment status in patients who had undergone lumbar surgery. This evaluation method could be used as a quality control in future studies regarding this patient group.

Adult↗
PubMed1994

Analysis of preoperative prognostic factors in first-time surgery for lumbar disc herniation, including Finneson's and modified Spengler's score systems.

In a retrospective study, 18 preoperative demographic and physical variables were evaluated for their preoperative prognostic value in 261 patients, following first-time lumbar disc surgery. Special reference was given to the Spengler and Finneson index-scores. "Low Back Pain Rating Scale" was used as the outcome assessment instrument. Comprehensive statistical analysis was undertaken in order to separate only the contingently independent variables. Gender was a highly significant prognostic factor. Other independently statistically significant prognostic factors include dermatomal hypoalgesia, smoking, and the Finneson index score. Results of the study are discussed with reference to the available literature.

Age Factors↗
PubMed1993

Regulatory considerations for evaluating the pharmacology and toxicology of antisense drugs.

This article focuses on pharmacology and toxicology data that should be included in an Investigational New Drug Application (IND), a request to use an investigational drug in clinical trials. In general, pharmacology and toxicology testing programs for antisense compounds are held to the same regulatory standards applied to other new therapeutic classes. Biological properties of oligonucleotide therapeutics are mentioned where they may pertain to clinical safety issues. Nonclinical data submitted to the IND should characterize the pharmacology, disposition, and toxicology of a new drug; these data form the basis for clinical risk assessment. Concomitant evaluation of pharmacokinetics allows for better interpretation of in vivo studies and increased accuracy of dose extrapolation to humans. Recommendations for nonclinical drug development will be modified as new information regarding the biological properties of oligonucleotides becomes available.

Animals↗
PubMed1993

Detection of parvovirus B19 in donated blood: a model system for screening by polymerase chain reaction.

A highly sensitive and rapid method for routinely screening large numbers of donated blood units for parvovirus B19 by the polymerase chain reaction (PCR) was developed. Over a 3-month trial period in Edinburgh, B19 DNA was detected in 6 of 20,000 consecutive units of blood (0.03%), in concentrations ranging from 2.4 x 10(4) to 5 x 10(10) copies of viral DNA per ml. Seroconversion for B19-specific immunoglobulin M and immunoglobulin G and disappearance of circulating B19 DNA occurred in the interval between donation and recall in four of the five implicated donors who could be recalled. B19 DNA was detected in 18 of 27 separate batches of non-heat-treated factor VIII and IX concentrate manufactured from donated plasma unscreened for B19 DNA. Dry-heat treatment at 80 degrees C for 72 h reduced but did not always eliminate detectable B19 from factor VIII concentrates, consistent with recent observations that current methods for virus inactivation during blood product manufacture are insufficient to entirely eliminate B19 infectivity. The methods developed in this study for PCR screening could be applied routinely to prevent transfusion of B19 in blood and blood products and could play an important role in the prevention of iatrogenic transmission of infection. PCR screening could also be used for detection and exclusion of a range of other transmission-associated viruses for which current serological detection methods are only partially effective.

Base Sequence↗
PubMed1992

Impaired cell-mediated immunity in experimental abdominal sepsis and the effect of interleukin 2.

A murine model of experimental sepsis, ie, cecal ligation and puncture, was used to determine the potential effects of infection on in vitro cell-mediated immunity. Following cecal ligation and puncture, in vitro responses of mouse splenocytes to mitogens (phytohemagglutinin and concanavalin A), the effects of in vitro interleukin 2 on these responses, and the impact of in vivo interleukin 2 on survival were studied. Compared with controls (sham cecal ligation and puncture), phytohemagglutinin responses 1 day after cecal ligation and puncture were enhanced (43% +/- 17%, n = 9), phytohemagglutinin and concanavalin A responses at day 4 were suppressed (45.5% +/- 4.4% and 57.5% +/- 5.6%), and, by day 7, phytohemagglutinin and concanavalin A responses were approaching values in mice treated by sham cecal ligation and puncture. Suppressed phytohemagglutinin responses at day 4 after cecal ligation and puncture were restored to normal with in vitro interleukin 2 (61,052 +/- 3407 cpm for cecal ligation and puncture and 64,643 +/- 4727 cpm for sham cecal ligation and puncture). Mortalities following cecal ligation and puncture were identical at day 1 after cecal ligation and puncture (6/20) for both interleukin 2- and vehicle-treated groups; thereafter, interleukin 2-treated groups fared better. At day 1 after cecal ligation and puncture, the mean spleen cell phytohemagglutinin response was enhanced (43.8% +/- 17%, n = 9) compared with sham cecal ligation and puncture (= 10). By day 4, the responses to both concanavalin A and phytohemagglutinin were suppressed (45.5% +/- 4.4% and 57.5% +/- 5.6%, respectively). Responses at day 7 approached those of controls given sham cecal ligation and puncture. Sepsis causing a temporary impairment of cell-mediated immunity may be a factor in the frequent coexistence of altered cell-mediated immunity and sepsis, and interleukin 2 may have a role in limiting the adverse effects of sepsis.

Abdomen↗
PubMed1992

FDA requirements for nonclinical testing of contraceptive steroids.

Written guidelines for the preclinical testing of contraceptive steroids have not been revised since 1968 despite the fact that many important changes have been implemented by the FDA's Division of Metabolism and Endocrine Drug Products. This paper describes the new preclinical testing requirements and the rationale for their implementation.

Animals↗