Acute panniculitis: a report of 2 cases.
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Acute Disease↗
Biomedical subjects
J John
Publications and source records attributed to J John.
In vitro phosphorylation studies of a conserved region of the transcription factor ATF1.
A large family of mammalian transcription factors including multiple variants of CREB, CREM and ATF1 have been implicated in signal transduction by cAMP and other cellular pathways. Although the roles of some members of the family have been characterised the function of ATF1 is poorly understood. We have identified one or more key serine residues that are required for a phosphorylation-induced conformational change in ATF1. The critical serines map to a putative transcriptional activation domain of ATF1 and affect the stability of ATF1 DNA-binding. Intriguingly phosphorylation is modulated by ATF1 homodimerization and by ATF1 binding to DNA. One of the key serine residues required for ATF1 phosphorylation is not conserved in CREB and CREM suggesting that it is likely to determine some specialised function of ATF1.
Activating Transcription Factors↗
Kinetic and structural analysis of the Mg(2+)-binding site of the guanine nucleotide-binding protein p21H-ras.
The coordination and binding of the Mg2+ ion in the nucleotide-binding site of p21 have been investigated using site-directed mutagenesis, kinetic methods, and phosphorous NMR. Mg2+ in the p21.nucleotide.Mg2+ complex appears to be in fast equilibrium with the solvent. The dissociation constant between Mg2+ and the p21.GDP complex was determined to be 2.8 microM. It decreases 30- or 16-fold on substituting Ser-17 or Asp-57 with alanine, respectively, whereas the T35A mutation has no effect. All three mutations influence the dissociation constants and the association and dissociation rate constants of the interaction between guanine nucleotides and p21, but to a different degree. We conclude that Thr-35 is only complexed to Mg2+ in the GTP conformation and both Asp-57 and Ser-17 appear to be critical for both GDP and GTP binding. 31P NMR spectra of the GDP and Gpp(NH)p (guanosine-5'-(beta,gamma-imido)triphosphate) complexes of mutated p21 show a remarkable perturbation of the guanine nucleotide-binding site compared to wild-type protein. The mutant proteins show reduced GTPase rates, which are not stimulated by the GTPase-activating protein GAP. p21(S17A) has been reported to function just as p21(S17N) as a dominant negative inhibitor of normal p21. We find that it inhibits oncogenic p21-induced survival of primary neurons.
Amino Acid Sequence↗
Short course ciprofloxacin therapy for enteric fever.
A short course of ciprofloxacin, 750 mgm b.i.d. for 7 days was found to be effective in the treatment of enteric fever in 21 hospitalized patients with S.typhi (18) and S.paratyphi A(3). Median time for fever response was 3 days. All isolates were susceptible to ciprofloxacin (MIC 0.0078-0.062 mcgm/ml). The mean serum peak and trough levels were 5.4 and 1.6 mcgm/ml respectively. Stool cultures were free of Salmonellae on follow up (11-24 weeks). Two developed recurrence of paratyphoid fever, 17 days and 4 months after therapy.
Adult↗
A model for understanding benefit segmentation in preventive health care.
The marketing of traditional health care services, such as hospital and physician services, has matured with the integration of research from the medical sociology discipline and the marketing literature. In this article, we present a model to illustrate how an understanding of predispositions to health care behavior, integrated with benefit segmentation analysis, can contribute to more focused and effective marketing strategies for health-related products and services.
Attitude to Health↗
Mutational and kinetic analyses of the GTPase-activating protein (GAP)-p21 interaction: the C-terminal domain of GAP is not sufficient for full activity.
The GTPase-activating protein (GAP) stimulates the GTPase reaction of p21 by 5 orders of magnitude such that the kcat of the reaction is increased to 19 s-1. Mutations of residues in loop L1 (Gly-12 and Gly-13), in loop L2 (Thr-35 and Asp-38), and in loop L4 (Gln-61 and Glu-63) influence the reaction in different ways, but all of these mutant p21 proteins still form complexes with GAP. The C-terminal domain of the human GAP gene product, GAP334, which comprises residues 714 to 1047, is 20 times less active than full-length GAP on a molar basis and has a fourfold lower affinity. This finding indicates that the N terminus of GAP containing the SH2 domains modifies the interaction between the catalytic domain and p21.
Amino Acid Sequence↗
Why are older patients and less educated patients less satisfied with health care quality?
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Adult↗
How to improve occupancy rates by educating the health care consumer.
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Bed Occupancy↗
Getting patients to answer: what affects response rates?
Even scientifically validated and reliable surveys are an exercise in futility if response rates are low. The author's study raises the issue of whether the hospital experience itself, among other factors, influences the likelihood of patients' willingness to respond to surveys about their hospital experience. The research questions are framed as testable hypotheses with guidelines for future research. Examining these hypotheses contributes valuable insights for improving the response rates in patient satisfaction surveys.
Adult↗
Patient satisfaction: the impact of past experience.
The effects of previous hospital experiences on satisfaction with subsequent hospital experiences are significant and cannot be ignored. The study findings suggest that prior satisfaction with the health care system in general and with the same hospital when applicable has a significant influence on patient evaluations of current hospital experience. Suggestions are offered to manage the effects of prior satisfaction on patient evaluations of current hospital experience.
Adolescent↗
Trauma versus critical care: it is time to end the debate.
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Critical Care↗
High-frequency mutagenesis of human cells and characterization of a mutant unresponsive to both alpha and gamma interferons.
2fTGH is a human cell line containing the selectable marker guanine phosphoribosyltransferase regulated by alpha interferon (IFN-alpha). Two IFN-alpha-unresponsive mutants were isolated previously at a low frequency (ca. 10(-8)) by selecting mutagenized 2fTGH cells in selective medium containing 6-thioguanine and IFN-alpha. By using five rounds of mutagenesis, mutants can be isolated at an appreciably higher frequency, greater than 3 x 10(-7). Five new mutants have been isolated, and all are recessive, as are the two mutants we described previously. The seven mutants are in four complementation groups (U1-U4). Since several different types of mutants unresponsive to IFN-alpha have been isolated with high frequency, related approaches may succeed with other cytokines or growth factors. Mutants in the two new complementation groups U3 and U4 are unresponsive to IFN-alpha and, surprisingly, also unresponsive to IFN-gamma. They are also partially defective in response to double-stranded RNA. These results indicate that the signaling pathways for the two types of IFN and double-stranded RNA share common components or that their function depends on common enzymes or transcription factors. IFN receptors are unaffected in mutants U3A and U4A. A major defect appears to be in the synthesis or activation of E, the transcription factor mediating the primary response to type I (alpha/beta) IFNs. Band-shift complementation assays show that U3A contains the E gamma subunit but does not contain an active E alpha subunit after treatment with IFN-alpha.
Aminacrine↗
[Drug interactions in the prescriptions of patients before and after a heart infarct: results of the MONICA Augsburg heart infarct registry].
The prescriptions of 603 patients who had survived acute myocardial infarction (AMI) for at least one year and were registered from 1 Oct 84 to 31 Dec 86 in the Coronary Event Register of the MONICA project Augsburg were analyzed for the presence of drug-drug interactions with the aid of a computerized drug information system (SMA). Prior to AMI, 59% of patients were treated (average of 2 active substance per patient), 100% were treated on release from hospital (4.5 active substances), and 96% one year after AMI (5.8 active substances). Potential drug-drug interactions were found in 18% of patients before AMI, 65% on discharge from hospital, and 66% one year after AMI. While the potential frequency and severity of interactions are minor on average, prescriptions frequently contain several interactions. Calculations show that at least 5-6% of all prescriptions after AMI will produce interactions, so that drug safety for this high-risk patient group can be enhanced by a drug information system. Beta-blockers are the substance group most frequently involved in potential interactions in AMI patients.
Adult↗
Isolation and characterization of a new mutant human cell line unresponsive to alpha and beta interferons.
Previously we described human cell line 2fTGH, in which expression of guanine phosphoribosyltransferase is tightly controlled by the upstream region of interferon (IFN)-stimulated human gene 6-16. After mutagenesis of 2fTGH and selection with 6-thioguanine and IFN-alpha, we isolated 11.1, a recessive mutant that does not respond to IFN-alpha. We now describe U2, a second recessive mutant, selected similarly, that complements 11.1. U2 had no response to IFN-alpha or IFN-beta, and its response to IFN-gamma was partially defective. Although many genes did respond to IFN-gamma in U2, the 9-27 gene did not and the antiviral response of U2 cells to IFN-gamma was greatly reduced. Band shift assays showed that none of the transcription factors normally induced in 2fTGH cells by IFN-alpha (E and M) or IFN-gamma (G) were induced in U2. However, extracts of untreated U2 cells gave rise to a novel band that was increased by treatment with IFN-gamma but not IFN-alpha. Band shift complementation assays revealed that untreated and IFN-gamma-treated U2 cells lack the functional E gamma subunit of transcription factor E and that IFN-alpha-treated U2 cells do contain the functional E alpha subunit.
Aminacrine↗
Three-dimensional structure of p21 in the active conformation and analysis of an oncogenic mutant.
The three-dimensional structure of the active guanosine triphosphate (GTP)-analogue-containing complex of the H-ras-encoded p21 has been determined. It was necessary to correct the topology of p21 as published earlier. The structure analysis shows all of the interactions between protein and GTP and how the important cofactor Mg2+ is bound. From the oncogenic mutants of p21 crystallized, a Gly12 to Arg mutation has been analyzed in detail. It shows that the overall structure of the mutant is not perturbed and that the side chain of Arg12 is coming close to the gamma-phosphate for an interaction.
Allosteric Regulation↗
Improving quality through patient-provider communication.
Though three hospitals and their patient populations were similar, one hospital was rated significantly higher on quality by its patients than were the other hospitals. Patients at that hospital felt significantly more confident that their hospital performed reliably and that they would have successful medical outcomes than did patients at the other hospitals. Analysis of patient responses shows that communicativeness (information giving and taking) and understanding (interest shown in patient's personal concerns) of medical personnel were significantly different across the three hospitals. Results underscore the importance of educating medical consumers about their medical needs and of understanding and responding to their psychosocial needs.
Attitude to Health↗
Three-dimensional structures of H-ras p21 mutants: molecular basis for their inability to function as signal switch molecules.
The X-ray structures of the guanine nucleotide binding domains (amino acids 1-166) of five mutants of the H-ras oncogene product p21 were determined. The mutations described are Gly-12----Arg, Gly-12----Val, Gln-61----His, Gln-61----Leu, which are all oncogenic, and the effector region mutant Asp-38----Glu. The resolutions of the crystal structures range from 2.0 to 2.6 A. Cellular and mutant p21 proteins are almost identical, and the only significant differences are seen in loop L4 and in the vicinity of the gamma-phosphate. For the Gly-12 mutants the larger side chains interfere with GTP binding and/or hydrolysis. Gln-61 in cellular p21 adopts a conformation where it is able to catalyze GTP hydrolysis. This conformation has not been found for the mutants of Gln-61. Furthermore, Leu-61 cannot activate the nucleophilic water because of the chemical nature of its side chain. The D38E mutation preserves its ability to bind GAP.
Adenosine Triphosphate↗
Inhibition of GTPase activating protein stimulation of Ras-p21 GTPase by the Krev-1 gene product.
Krev-1 is known to suppress transformation by ras. However, the mechanism of the suppression is unclear. The protein product of Krev-1, Rap1A-p21, is identical to Ras-p21 proteins in the region where interaction with guanosine triphosphatase (GTPase) activating protein (GAP) is believed to occur. Therefore, the ability of GAP to interact with Rap1A-p21 was tested. Rap1A-p21 was not activated by GAP but bound tightly to GAP and was an effective competitive inhibitor of GAP-mediated Ras-GTPase activity. Binding of GAP to Rap1A-p21 was strictly guanosine triphosphate (GTP)-dependent. The ability of Rap1A-p21 to bind tightly to GAP may account for Krev-1 suppression of transformation by ras. This may occur by preventing interaction of GAP with Ras-p21 or with other cellular proteins necessary for GAP-mediated Ras GTPase activity.
Binding, Competitive↗