The effect of betaine accumulation by Escherichia coli K-12 on aminoglycoside activity.
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Aminoglycosides↗
Biomedical subjects
A Phillips
Publications and source records attributed to A Phillips.
Evaluation of Roche Amplicor PCR assay for Mycobacterium tuberculosis.
The Roche Amplicor Mycobacterium tuberculosis PCR test (RMtb-PCR) was compared with mycobacterial culture, with the BACTEC 460 system and inoculation on Lowenstein-Jensen media. Results were interpreted with an adjusted "gold standard" incorporating clinical diagnosis. A total of 1,480 clinical specimens from 1,155 patients, including tissues and fluids, as well as 141 specimens which demonstrated a positive growth index on the BACTEC 460 system were assessed. The sensitivity, specificity, and positive and negative predictive values of RMtb-PCR compared with the adjusted gold standard for clinical specimens were 79, 99, 93, and 98%, respectively. In smear-positive specimens, the sensitivity of RMtb-PCR was 98% versus 53% for smear-negative specimens. When RMtb-PCR was performed two times per week, PCR results were available an average of 21 days before the culture results. For specimens demonstrating a positive growth index on the BACTEC 460 system, RMtb-PCR had a sensitivity and specificity of 98 and 100%, respectively. This study demonstrates the value of a commercial nucleic acid amplification kit for rapid diagnosis of M. tuberculosis, particularly in smear-positive specimens or BACTEC culture-positive specimens.
Bacteriological Techniques↗
Induction of a novel conformation in the progesterone receptor by ZK299 involves a defined region of the carboxyl-terminal tail.
Progesterone receptor antagonists are a promising class of therapeutic drugs indicated for the treatment of a variety of reproductive conditions. Understanding their mechanism of action at the molecular level is an important prerequisite for the development of future generations of these drugs. Using limited proteolytic analysis to monitor conformational changes in the progesterone receptor, we can detect three distinct classes of progestin antagonist. The effect of the first, RU486, on the conformation of the carboxyl terminus of the receptor has been previously described. The second, exemplified by RWJ 47626, a nonsteroidal compound with in vitro antiprogestin activity, induces a proteolytic fragment pattern indistinguishable from that induced by the agonist R5020. Finally, ZK299 induces a fragment pattern intermediate between that induced by R5020 and RU486. Site-directed mutagenesis of the carboxyl-terminal tail of the progesterone receptor indicates that the region containing the putative activation function AF-2 is differentially exposed to proteolytic attack depending on the nature of the antagonist bound. The differentially exposed region is most accessible when the antagonist RU486 is bound, less accessible when the antagonist ZK299 is bound, and least accessible when the antagonist RWJ47626 or agonist R5020 is bound. The results suggest that multiple types of antiprogestin can be defined in terms of their effects on the conformation of the carboxyl-terminal activation function of the progesterone receptor.
Amino Acid Sequence↗
Nonsteroidal progesterone receptor ligands. 1. 3-Aryl-1-benzoyl-1,4,5,6-tetrahydropyridazines.
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Animals↗
Molecular characterization of a Galactomyces geotrichum lipase, another member of the cholinesterase/lipase family.
Geotrichum candidum secretes several lipase isoenzymes, differing in their selectively towards esters of long chain fatty acids with a cis-9 double bond. One group shows an absolute selectively towards these fatty acid esters, the other group has a more relaxed specificity and will also hydrolyze other long chain fatty acid esters. Galactomyces geotrichum secrets a lipase that has the same specificity as the latter group. The corresponding lipase gene was cloned from Galactomyces geotrichum. From an alignment of our enzymes' primary structure with those of different strains of Geotrichum candidum, remarkable conservation is evident and it is not yet possible to identify residues/structures responsible for differences in fatty acid specificity. Comparison of the GCL/GGL family with a variety of lipases from other sources, indicated that they are more related to mammalian than microbial lipases.
Amino Acid Sequence↗
As Canadians butt out, the developing world lights up.
Although rates of tobacco smoking in Canada have dropped dramatically over the last 30 years this is not a global trend. For every tonne of tobacco that Canadian adults gave up between 1970 and 1990, aggressive marketing by multinational tobacco companies has ensured that an additional 20 tonnes is now consumed in developing countries. The authors describe the dilemma faced by policymakers in their efforts to control the epidemic of tobacco smoking in the developing world: although tobacco consumption leads to increased rates of mortality and morbidity and lost productivity, its production creates employment, generates tax revenue and earns foreign exchange. Canadian experience has proved that trends in tobacco consumption can be reversed through policies that address not only health issues but also economic social and agricultural concerns. The authors propose a framework for harnessing expertise in the service of worldwide tobacco control.
Agriculture↗
Potent pituitary-gonadal axis suppression and extremely low anaphylactoid activity of a new gonadotropin releasing hormone (GnRH) receptor antagonist "azaline B".
We report here the biological characterization of azaline B, a new gonadotropin releasing hormone (GnRH) receptor antagonist, with the following amino acid sequence: [Ac-D-Nal1, D-Cpa2, D-Pal3, Aph5(atz), D-Aph6(atz), Ilys8, D-Ala10]-GnRH. Azaline B was shown to suppress several reproductive processes in rats including ovulation, and had very low anaphylactoid activity compared with other GnRH antagonists. Azaline B inhibited histrelin (a GnRH agonist)-mediated follicle stimulating hormone (FSH) and luteinizing hormone (LH) release from cultured rat pituitary cells. Three antagonists ([Nal-Glu]-GnRH, [Nal-Lys]-GnRH ("antide"), and azaline B) inhibited 0.1 nM histrelin-mediated gonadotropin release to baseline levels with EC50 values of approximately 0.6 nM. Azaline B, when injected s.c. into rats on the afternoon of proestrus, was more potent at inhibiting ovulation than either [Nal-Glu]-GnRH or [Nal-Lys]-GnRH. The relative order of antiovulatory potencies of the three antagonists was azaline B > [Nal-Glu]-GnRH > [Nal-Lys]-GnRH. Similar azaline B potency was shown by its ability to suppress gonadotropin levels in castrated rats. The improved selectivity of azaline B was demonstrated when it was compared with other GnRH antagonists in the cutaneous anaphylactoid assay (local wheal response) in rats. Results with azaline B were not significantly different from results with vehicle in this assay. [Nal-Glu]-GnRH was more than twice as potent as [Nal-Lys]-GnRH in stimulating a wheal response. Furthermore, the maximal wheal response produced by azaline B was only 0.6 times that of [Nal-Lys]-GnRH, currently one of the most selective antagonists identified. Finally, both azaline B and [Nal-Lys]-GnRH were much less potent than [Nal-Glu]-GnRH in the guinea pig cardiopulmonary anaphylactoid assay after i.v. administration. These data show that azaline B is a potent and selective GnRH receptor antagonist with little or no anaphylactoid activity in animal models, and therefore has potential for use in the treatment of many reproductive endocrine disorders, as well as for use as a contraceptive.
Amino Acid Sequence↗
Prospective randomised trial of chemotherapy given before radiotherapy in childhood medulloblastoma. International Society of Paediatric Oncology (SIOP) and the (German) Society of Paediatric Oncology (GPO): SIOP II.
In a multicentre randomised clinical trial 364 children with biopsy proven medulloblastoma were randomly assigned to receive or not pre-radiotherapy chemotherapy. Children with total or subtotal removal of the tumour, no evidence of invasive brain stem involvement, and no evidence of metastatic disease either within or without the cranium were designated "low risk", those with gross residual tumour, evidence of invasive brain stem involvement or metastases in the central nervous system were designated "high risk". All children were prescribed 55 Gy to the tumour bearing area. "Low risk" children could be randomised to "standard" radiotherapy 35 Gy to the craniospinal axis or "reduced" dose 25 Gy to the craniospinal axis. Chemotherapy consisted of vincristine, procarbazine, and methotrexate given in a 6-week module before radio-therapy, and for "high risk" children, vincristine and CCNU given after radiotherapy. No benefit for the receipt of pre-radiotherapy chemotherapy could be demonstrated for any group. In addition, a negative interaction was observed between the receipt of the chemotherapy and reduced dose radio-therapy with a particularly poor outcome being observed in this group of children.
Adolescent↗
Gap junction regulation in the uterus and ovaries of immature rats by estrogen and progesterone.
The effects of estrogen (E2) and progesterone (P) were examined on the expression levels of multiple gap junction (GJ) gene products (alpha 1 = Cx43, beta 1 = Cx32, beta 2 = Cx26) in the uterus and ovaries of immature rats by immunohistochemistry, electron microscopy and northern blot analysis. E2 induced the expression of alpha 1 connexin in the uterus (specifically in the myometrium and in endometrial stroma proximal to luminal epithelium) and ovaries. The E2-induced alpha 1 expression was completely suppressed by P in the uterus, but only partly in ovaries. Steroid hormones also modulated the quantity, size, and distribution of beta 1 and beta 2 containing junctional plaques along lateral cell borders in polarized luminal and glandular uterine epithelia. Small GJs were detected at basolateral regions in proliferative luminal epithelium following administration of E2. In contrast, large GJs were localized at subapical-lateral cell borders of the secretory epithelium following P-treatment. The co-administration of E2 + P had a synergistic effect on beta 1 and beta 2 expression in the luminal epithelium, but an inhibitory effect on beta 2 expression in glandular epithelium. Myometrial GJs were detected in freeze-fracture replicas as aggregates containing regularly arranged particles with particle free zones. In contrast, GJs in secretory epithelium contained particles which were arranged in a non-crystalline fashion. These GJs contained domains of mixed and segregated beta 1 and beta 2 antigens within a single plaque as revealed by laser scanning confocal microscopy analysis of immuno-double-labeled secretory epithelium. The demonstration of segregated antigens within a single GJ plaque indicates the possibility of multiple channel populations formed by homo-oligomeric connexons. These results suggest that different connexins can be differentially regulated by steroid hormones in different cell types, and that the same steroid hormone can have different effects on the same connexin in different cell types.
Amino Acid Sequence↗
Can ultrasound probes and coupling gel be a source of nosocomial infection in patients undergoing sonography? An in vivo and in vitro study.
OBJECTIVE: At our institution, ultrasound probes are wiped with a clean, dry, soft, absorbent paper towel after each procedure as a basic standard of probe disinfection. However, it was unclear if this provided a sufficient level of decontamination. This study was designed to determine if the ultrasound probe and coupling gel can act as a vector of nosocomial infection and to describe a cost-effective method of probe handling that allows optimal control of infection. SUBJECTS AND METHODS: In the first part of the study, the ultrasound probe was exposed to the disrupted skin of patients recruited from our inpatient population, using our routine scanning technique to look for subcutaneous collections. Twenty-seven patients were scanned: 17 with surgical wounds, seven with surgical drains, four with enteric stomas, three with biopsy sites, and three with ulcers or excoriation. Fifteen patients had a discharge associated with their disrupted skin, and seven patients had culture-proved skin infections. Each probe was wiped with a clean, dry paper towel after scanning, then immersed in a brain-heart infusion (BHI) broth, and the solution was cultured. In the second part of the study, the ultrasound probe was exposed to a large inoculum of bacteria. Sixty-one probes were used to scan fields of confluent growth of bacteria on agar plates. Twenty-six probes were cleaned by wiping with a dry, clean paper towel, and 25 probes were cleaned by wiping with a dry, clean paper towel followed by immersion in Hibidil (0.05% chlorhexidine weight/volume). Ten probes functioned as controls and were not cleaned after exposure to the bacteria. Each probe was then immersed in BHI broth, and the solution was cultured. In the third part of the study, the coupling gel was evaluated as a culture medium for bacterial growth. Twenty-five agar plates were inoculated with a confluent growth of bacteria. Half of the surface of each agar plate was covered with coupling gel, and the remaining surface was left unexposed. The resulting bacterial growth on each side of the plates was compared. RESULTS: One of the 27 probes exposed to patients with disrupted skin grew Staphylococcus epidermidis (skin flora). For probes exposed to a large inoculum of bacteria, we found no statistically significant difference in the number of probes that showed bacterial growth on culture between probes cleaned by wiping with a towel and those cleaned with Hibidil. Furthermore, the resulting bacterial growth in both sets of probes was scant and was not considered clinically significant. All 10 control probes showed clinically significant growth in all cases. As for evaluation of the coupling gel as a culture medium, the gel permitted bacterial growth and did not show any evidence of bacteriocidal or bacteriostatic properties. CONCLUSION: Ultrasound probes that are wiped with a paper towel until they are visibly clean do not contribute to nosocomial infections. Additional antiseptic solutions such as Hibidil are not necessary. We suggest that probes be simply wiped with a clean, dry, nonsterile paper towel between procedures, including probes used on contaminated scanning fields, open wounds, and cutaneous infections. After the final procedure of the day, probes should be cleaned with a liquid cleaning solution such as Hibidil to remove all traces of coupling gel, which could support the overnight growth of bacteria. This would decontaminate the probes and prevent the overnight growth of bacteria. This method would be both a cost-effective and time-efficient protocol for controlling infection.
Bacteria↗
Bellagio statement on tobacco and sustainable development.
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Global Health↗
Why do people sue doctors? A study of patients and relatives taking legal action.
To examine the reasons patients and their relatives take legal action, we surveyed 227 patients and relatives who were taking legal action through five firms of plaintiff medical negligence solicitors. Over 70% of respondents were seriously affected by incidents that gave rise to litigation with long-term effects on work, social life, and family relationships. Intense emotions were aroused and continued to be felt for a long time. The decision to take legal action was determined not only by the original injury, but also by insensitive handling and poor communication after the original incident. Where explanations were given, less than 15% were considered satisfactory. Four main themes emerged from the analysis of reasons for litigation: concern with standards of care--both patients and relatives wanted to prevent similar incidents in the future; the need for an explanation--to know how the injury happened and why; compensation--for actual losses, pain and suffering or to provide care in the future for an injured person; and accountability--a belief that the staff or organisation should have to account for their actions. Patients taking legal action wanted greater honesty, an appreciation of the severity of the trauma they had suffered, and assurances that lessons had been learnt from their experiences. A no-fault compensation system, however well intended, would not address all patients' concerns. If litigation is viewed solely as a legal and financial problem, many fundamental issues will not be addressed or resolved.
Adolescent↗
Survival differences in European patients with AIDS, 1979-89. The AIDS in Europe Study Group.
OBJECTIVES: To examine the pattern of survival and factors associated with the outcome of disease in patients with AIDS. DESIGN: Inception cohort. Data collected retrospectively from patients' charts. SETTING: 52 clinical centres in 17 European countries. SUBJECTS: 6578 adults diagnosed with AIDS from 1 January 1979 to 31 December 1989. MAIN OUTCOME MEASURES: Survival after the time of diagnosis. RESULTS: The median survival after diagnosis was 17 months, with an estimated survival at three years of 16% (95% confidence interval 15% to 17%). Patients diagnosed in southern Europe had a shorter survival, particularly immediately after the time of diagnosis, compared with patients diagnosed in central and northern Europe (survival at one year (95% confidence interval) 54% (52% to 56%) 66% (64% to 68%), 65% (63% to 66%), respectively. The three year survival, however, was similar for all regions. The regional differences in survival were less pronounced for patients diagnosed in 1989 compared with earlier years. Improved survival in recent years was observed for patients with a variety of manifestations used to define AIDS but was significant only for patients diagnosed with Pneumocystis carinii pneumonia. The three year survival, however, remains unchanged over time. CONCLUSIONS: Survival of AIDS patients seems to vary within Europe, being shorter in southern than central and northern Europe. The magnitude of these differences, however, has declined gradually over time. Short term survival has improved in recent years, but the long term prognosis has remained equally poor, reflecting the fact that the underlying infection with HIV and many of the complicating diseases remains essentially uncontrolled.
Acquired Immunodeficiency Syndrome↗
Characterization of a cDNA from Arabidopsis thaliana encoding a potential thiol protease whose expression is induced independently by wilting and abscisic acid.
The sequence and expression characteristics are described of a wilt-inducible gene in Arabidopsis thaliana. A1494 encodes a potential thiol protease whose mRNA accumulates rapidly in shoot tissue upon the loss of turgor. A1494 mRNA levels peaked after ca. 4 h and declined thereafter. Dehydration also induced rapid biosynthesis of the phytohormone abscisic acid (ABA), which continued for at least 9 h. Exogenous ABA induced the accumulation of A1494 mRNA, with kinetics similar to those after wilting. Rehydration of wilted shoots led to a rapid decline in the content of both ABA and A1494 mRNA. Wilting and ABA independently induced A1494 expression as evidenced by the effects of ABA and wilting on the ABA-deficient aba-1 and ABA-insensitive abi-1 and abi-3 genotypes. A1494 mRNA was not detectable in aba-1 shoots but accumulated rapidly after either wilting or ABA treatment, whereas the shoot ABA content was increased only by ABA treatment. ABA had no effect on A1494 mRNA levels in the abi-1 and abi-3 mutants but wilting did result in enhanced A1494 expression. Heat shock had only a minor effect on A1494 mRNA levels, whereas exposure to low temperature resulted in substantial accumulation of A1494 mRNA in wild-type shoots. However, this latter response, unlike that to drought, was mediated exclusively via ABA synthesis as demonstrated by the lack of A1494 mRNA accumulation in cold-treated aba-1 shoots.
Abscisic Acid↗
Pre-natal screening for Down's syndrome.
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Down Syndrome↗
Fatal Capnocytophaga canimorsus (DF-2) septicaemia. A case report.
A 45-year-old man died 2 months after being bitten on the hand by a dog. He developed the rare but characteristic clinical picture of fulminant septicaemia and peripheral gangrene caused by a Gram-negative bacillus, Capnocytophaga canimorsus, previously known as dysgonic fermenter type 2 (DF-2), which is an occasional commensal in the oral flora of dogs and cats. This disease must be anticipated and dog bites appropriately managed to avoid the mortality associated with infection by this micro-organism. Initial treatment includes appropriate prophylactic antibiotics and debridement, while early exchange transfusion and emergency amputation may be of value in fulminant cases.
Animals↗
CD4+ counts before and after switching to monoclonal high-purity factor VIII concentrate in HIV-infected haemophilic patients.
Allogenic proteins that contaminate intermediate purity clotting factor concentrates may activate the immune system of HIV-infected haemophilic patients. In 37 haemophilic patients infected with HIV who had originally been treated with intermediate purity factor VIII concentrate and then changed to monoclonally-purified high purity factor VIII concentrate the rates of CD4+ decline (10(9)/l per year) were 0.06 before and 0.02 after a switch to high purity products (p = 0.01). The median follow-up of patients after the switch to high purity products was 1.7 years (range 0.2 to 3 years). This significant change in the rate of CD4 decline was independent of the starting CD4 count, age and antiretroviral therapy. This result is consistent with those from randomised trials of the introduction of high-purity concentrate. Given the strong association between the CD4+ count and survival, treatment with high purity rather than intermediate purity clotting factor concentrate may confer a survival benefit for HIV-infected haemophilic patients.
AIDS-Related Opportunistic Infections↗
Identification of the larvae of the Simulium damnosum complex from Nigeria by analysis of cuticular hydrocarbons.
The larvae of three sibling species of the Simulium damnosum complex were studied with a view to identification, using a Gas Liquid Chromatograph to analyze the hydrocarbons in the cuticular wax extracts. Multivariate statistics were applied to the chromatographic data to differentiate three sibling species: S. damnosum s.s., S. squamosum and S. yahense. Paired comparisons between the species gave greater than 96% correct classifications in all cases.
Animals↗