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Biomedical subjects

J Alder

Publications and source records attributed to J Alder.

At least 19 recordsLinked to original sources
PubMed2006

The direct pathway of human T-Cell allorecognition is not tolerized by stimulation with allogeneic peripheral blood mononuclear cells irradiated with high-dose ultraviolet B.

Transfusions of high-dose (> or =10,000 Joule/m(2)) ultraviolet-B (UVB)-irradiated allogeneic leukocytes in rodent models have been shown to induce immunologic tolerance that is mediated by allospecific regulatory CD4(+) T cells. Whether these regulatory T cells recognize alloantigens through the direct or indirect pathway of allorecognition is controversial. Here, we demonstrate that the proliferative response obtained in standard primary mixed leukocyte reactions (MLRs) with human peripheral blood mononuclear cells (PBMCs) reflected a CD4(+) T-cell-dependent direct pathway of allorecognition and that high-dose UVB irradiation of PBMCs totally inhibited their capacity to induce a proliferative alloresponse. Re-stimulation with gamma-irradiated PBMCs from the same allogeneic donor (secondary MLR) elicited a proliferative and Th1-deviated response that was similar to the response induced in unprimed PBMCs. Finally, high-dose UVB was found to induce a rapid and massive apoptosis of irradiated PBMCs. Collectively, these data indicate that leukocytes irradiated with high-dose UVB are unable to prime for unresponsiveness or immune deviation in T cells directly recognizing allogeneic major histocompatibility complex molecules. Because it is well-established that antigens within transfused apoptotic cells are captured by resident tolerogenic spleen dendritic cells, we propose that tolerance induced by transfusions of high-dose UVB-irradiated leukocytes primarily involve T cells indirectly recognizing alloantigens.

Apoptosis↗
PubMed2005

Effects of polycyclic aromatic hydrocarbons on germination and subsequent growth of grasses and legumes in freshly contaminated soil and soil with aged PAHs residues.

The relevance of germination trials for screening plants that may have potential for use in the phytoremediation of PAH contaminated land was evaluated. The germination and subsequent growth of 7 grass and legume species were evaluated in soil spiked with a pure PAH mixture or coal tar and soil from a former coking plant heavily contaminated with aged PAHs. None of these treatments adversely affected germination of the plants. However, apart from Lolium perenne all species exhibited reduced growth in the coking plant soil after 12 weeks growth when compared to the untreated soil. In the coal tar spiked soil 4 out of the 7 species showed reduced growth, as did 3 out of the 7 in the soil spiked with a mixture of 7 PAHs. Therefore, germination studies alone would not predict the success of subsequent growth of the species tested in the ranges of soil PAH levels studied.

Biodegradation, Environmental↗
PubMed2005

[Therapeutic concepts and therapy development in the framework of longterm treatment of victims of sexual and domestic violence].

Domestic violence differs from the nonrecurring trauma e.g. in the context of rape by a stranger in different aspects, emphasising the complexity of the victim's reaction and the enmeshment of the perpetrator The violence takes place in an established system of an intimate relationship which the woman was contracting voluntarily. Violence happens repeatedly and often several individuals (partner, children are directly and indirectly involved, which abide a relationship with the perpetrator Therefore the treatment of the posttraumatic stress disorder outstands in several aspects. The victims initially shows difficulties in talking about the experienced violence and are afraid to become unloyal; a therapeutic approach is often possible only after a fairly long time. Most authors agree that trauma therap the three phases (1 security and protection, psychoeducation and stabilisation, (2 trauma confrontation and (3 reintegration. Establishing a secure environment and intrapsychic stabilisation are a requirement for the therapeutic confrontation with the traumata in order to avoid re-traumatisation. Working with domestic violence victims is complex and demanding, experience in the work with trauma victims and regular supervision are fundamental.

Adolescent↗
PubMed2004

Acceptability and side-effects of Implanon in Switzerland: a retrospective study by the Implanon Swiss Study Group.

DESIGN: A multicenter, retrospective study of the single-rod contraceptive implant, Implanon (NV Organon, Oss, The Netherlands), was carried out in Switzerland in 1183 women. METHODS: Assessments included duration of use, bleeding pattern, side-effects and subjective acceptability and satisfaction with the method. RESULTS: A total of 991 women (84%) had at least one follow-up visit and 306 (26%) had two visits with a mean duration between insertion and follow-up of 224 days (7.4 months) and 347 days (11.4 months), respectively. Implanon was removed prematurely in 235 women (24%), primarily because of side-effects (20%) and for family planning reasons (4%). Side-effects leading to discontinuation were mainly bleeding disturbances (45%), acne (12%) and other reasons (15%). The mean duration between insertion and removal for discontinuers was 280 days (9.2 months). Side-effects related to bleeding (visit 1) included infrequent bleeding (28%), amenorrhea (33%), prolonged bleeding (15%), and metromenorrhagia (frequent and heavy bleeding) (16%). Other reported side-effects at visit 1 included dizziness (12%), acne (11%), mood swings (8%) and headache (5%). The incidence of side-effects reported at visit 2 was generally comparable to that at visit 1. CONCLUSIONS: The results of this study show that early discontinuation of implant use is primarily due to bleeding problems. Extensive counseling before implant insertion may help to prevent this. It is also important to develop an easy solution to successfully treating progestogen-induced bleeding disturbances.

Adult↗
PubMed2003

Retrospective evaluation of the treatment for breast cancer: how does the patient's personal experience of the treatment affect later adjustment to the illness?

The aim of the present study was the evaluation of patients' treatment experience for breast cancer and its possible associations with the illness adjustment process. To examine perception and experience of treatment during the diagnostic and the inpatient phase, as well as during chemo-and radiotherapy and during after-care, a self-compiled questionnaire was employed. To assess illness adjustment, the German version of the Hospital Anxiety and Depression Scale, the "Freiburger Fragebogen zur Krankheitsverarbeitung" and the "Veränderungsfragebogen des Erlebens und Verhaltens" were used. 126 patients participated in the study, all diagnosed for breast cancer during the past 5 years. We found an association between negative experience of all treatment phases (doctor-patient relationship, communication) and impaired adjustment process reflected by high anxiety and depression scores and more problematic coping strategies.

Adaptation, Psychological↗
PubMed2002

[Medical abortion with mifepristone and misoprostol: study of the efficacy, somatic tolerance and perception of medical abortion].

STUDY DESIGN: This prospective study examined the efficacy and somatic tolerance as well as the perception of the different phases of medical abortion with mifepristone and misoprostol. The subjective influence of counseling and accompanying on perception and psychic sequelae was evaluated. METHOD: The somatic data of the patients who had a medical abortion at Basel University Hospital of Gynecology and Obstetrics from December 1, 1999, to October 31, 2000, were identified in the case records. A questionnaire at the time of the abortion and a structured interview by telephone 6 months later were used to assess the perception of the abortion. RESULTS: Abortion with mifepristone and misoprostol was successful in 95.2% of cases. Counseling and accompanying were considered supportive by 90.4 and 73.7%, respectively. The psychological workup was without problems in 95.5%. CONCLUSION: Medical abortion with mifepristone and misoprostol was successful in 95.2%. Our concept of counseling and accompanying was well received and resulted in an uneventful psychological workup in most cases.

Abortifacient Agents, Nonsteroidal↗
PubMed2001

Novel erythromycin derivatives with aryl groups tethered to the C-6 position are potent protein synthesis inhibitors and active against multidrug-resistant respiratory pathogens.

A novel series of erythromycin derivatives has been discovered with potent activity against key respiratory pathogens, including those resistant to erythromycin. These compounds are characterized by having an aryl group tethered to the C-6 position of the erythronolide skeleton. Extensive structural modification of the C-6 moiety led to the discovery of several promising compounds with potent activity against both mef- and erm-mediated resistant Streptoccoccus pneumoniae. Preliminary mechanistic studies indicated that the new macrolides are potent protein synthesis inhibitors, which interact with methylated ribosomes isolated from resistant organisms. In experimental animal models, these compounds exhibited excellent in vivo efficacy and balanced pharmacokinetic profiles.

Animals↗
PubMed2001

Rab3A is required for brain-derived neurotrophic factor-induced synaptic plasticity: transcriptional analysis at the population and single-cell levels.

Brain-derived neurotrophic factor (BDNF) modulates synaptic strength in hippocampal neurons, in addition to promoting survival and differentiation. To identify genes involved in trophic regulation of synaptic plasticity, we have used a multidisciplinary approach of differential display and family-specific slot blots in combination with whole-cell patch-clamp recordings of dissociated hippocampal neurons. Three hour exposure to BDNF elicited a 2.6-fold increase in synaptic charge and a concomitant induction of 11 genes as revealed by differential display, including the small GTP-binding vesicular trafficking protein Rab3A and the enzyme guanylate cyclase (GC). Slot blot analysis on a population of neurons confirmed an average of 3.1-fold induction of these clones. In contrast, individual pyramidal-like neurons that were first characterized electrophysiologically in the presence of BDNF and subjected to transcriptional analysis displayed more robust increases (4.8-fold), emphasizing the neuronal heterogeneity. Transcriptional changes of Rab3A and GC were accompanied by translational regulation, shown by Western blot analysis. Furthermore, a number of GC-associated and Rab3A effector molecules were induced by BDNF at either the gene or protein levels. The functional role of Rab3A in BDNF-induced synaptic plasticity was assessed using cells derived from Rab3A knock-out mice. These neurons failed to show an increase in synaptic charge in response to BDNF at 10 min; however a late response to BDNF was detected at 20 min. This late response was similar in time course to that induced by postsynaptic activation of glutamate receptors. Our results demonstrate a requirement for Rab3A and may reveal a temporal distinction between presynaptic and postsynaptic mechanisms of BDNF-induced synaptic plasticity associated with learning and memory.

Animals↗
PubMed2001

[Psychosocial and psychosomatic basic competence of the gynecologist--from intrinsic conviction to a learnable curriculum].

The gynecologist is confronted with many tasks for which she/he needs psychosocial competence: patient education and health promotion, counselling, and management of psychosocial problems during the various phases of a woman's life cycle, care for patients with chronic diseases. To obtain this competence, a curriculum is needed which comprises elements of psychology, psychosocial medicine, and psychiatry adapted to the specific needs in women's health care. Knowledge and skills derived from communications theory and practice include the semiotic and pragmatic model of communication, physician- and patient-centered communication, counselling for health behavior changes, breaking bad and sad news, coping, and supportive counselling.

Communication↗
PubMed2001

[Psychosocial and psychosomatic basic competence of the gynecologist--from intrinsic conviction to a learnable curriculum. (2. Biosychosocial model and basic psychiatric therapy].

Besides the communicative skills and medical interviewing techniques (part 1 in Gynäkol Geburtshilfliche Rundsch 2001;41:158-165), it is the biopsychosocial model of health and disease which constitutes the second important element of the basic psychosomatic and psychosocial competence of the gynecologist. According to this model biological-somatic and psychosocial factors are concomitantly and equally taken into account during the diagnostic and therapeutic process. To conceptualize the possible pathology of psychosocial factors, the following categories have proven helpful in everyday work: behavior, stress, conflicts and developmental defects and disturbances. These categories are not objectively measurable, but they are accessible for the gynecologist in the consultation by means of the three following functions: assessment and monitoring of the patient's problems (somatic, psychological, social) by patient-centered communication; establishment, maintenance and termination of a therapeutic helpful relationship by perception of and response to emotions; development of a problem-solving plan and help for its realization by means of information giving and influencing behavioral changes.

Adult↗
PubMed1999

Second-generation peptidomimetic inhibitors of protein farnesyltransferase demonstrating improved cellular potency and significant in vivo efficacy.

The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core aryl ring resulted in inhibitors of equal or less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumor-derived cell line.

Alkyl and Aryl Transferases↗
PubMed1999

Generation of cerebellar granule neurons in vivo by transplantation of BMP-treated neural progenitor cells.

Cerebellar granule neurons, the most abundant class of CNS neurons, have a critical role in cerebellar function. Granule neurons are generated at the dorsal border of the mesencephalon and metencephalon, the rhombic lip. In the mouse embryo, rhombic lip cells express a number of granule neuron markers, notably the bHLH transcription factor Math1. Dorsal midline cells adjacent to the rhombic lip express Bmp6, Bmp7 and Gdf7, three genes encoding peptide growth factors of the bone morphogenetic protein (BMP) family. These BMPs induced the expression of granule neuron markers in cultured neural tissue. Moreover, BMP-treated neural cells formed mature granule neurons after transplantation into the early postnatal cerebellum, suggesting that BMPs initiate the program of granule cell specification.

Animals↗
PubMed1999

Neurogenetics of the cerebellar system.

The development of the cerebellum occurs in four basic steps. During the first epoch, genes that mark the cerebellar territory are expressed in a restricted pattern along the anterioposterior axis of the embryo. In the second, an embryonic region termed the rhombic lip generates precursors of the granule cell population of the cerebellar cortex, and the lateral pontine nucleus and olivary nucleus of the brain stem. In the third period, the program of neurogenesis of the granule neuron gives rise to the formation of the fundamental layers of the cerebellum and to the pattern of foliation. Concomitantly, programs of gene expression define the principal neuronal classes, the granule cell and Purkinje cell, that will establish the cerebellar circuitry in the postnatal period. Understanding the molecular mechanisms underlying these steps of development is likely to yield important insights into malformations such as Joubert syndrome.

Animals↗
PubMed1998

Synthesis and structure-activity relationships of 2-pyridones: II. 8-(Fluoro-substituted pyrrolidinyl)-2-pyridones as antibacterial agents.

The 8-position side chain of 2-pyridones is believed to be involved in the binding with bacterial DNA gyrase to form the ternary complex, making them very important for the activity of 2-pyridones. A series of 2-pyridones having fluoro-substituted amines at the 8-position has been synthesized and their antibacterial activities and parmacokinetic properties are reported.

Animals↗
PubMed1997

Genes involved in cerebellar cell specification and differentiation.

The conservation of transcriptional regulatory mechanisms across species, combined with the restricted expression of these molecules in time and space within the embryo, has offered new insights into CNS cell specification. Studies examining transcriptional control in the generation of specific cell classes within the cerebellar cortex have been particularly elucidative.

Animals↗
PubMed1996

Synthesis and structure-activity relationships of 2-pyridones: a novel series of potent DNA gyrase inhibitors as antibacterial agents.

Two novel series of 2-pyridones were synthesized by transposition of the nitrogen of 4-quinolones to the bridgehead position. This subtle interchange of the nitrogen atom with a carbon atom yielded two novel heterocyclic nuclei, pyrido[1,2-alpha]pyrimidine and quinolizine, which had not previously been evaluated as antibacterial agents and were found to be potent inhibitors of DNA gyrase. Quinolizines with a methyl group at the 9-position such as (S)-45a (ABT-719) demonstrate exceptional broad spectrum antibacterial activity. Most notably, they are active against resistant bacteria such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant strains of enterococci, and ciprofloxacin-resistant organisms. In addition, 2-pyridones also possess favorable physiochemical and pharmacokinetic properties. These 2-pyridones were synthesized from the commercially available starting materials by 10-17 linear transformations. The structure of an adduct yielded by this sequence, (S)-45a (ABT-719), was determined by X-ray crystallographic analysis.

Animals↗
PubMed1996

Costs and Effectiveness of Education and Enforcement, Cairns Section of the Great Barrier Reef Marine Park

Education, not enforcement, is the preferred management tool to gain acceptance for management prescriptions in marine protected areas. The cost and effectiveness of education and enforcement programs is difficult to estimate. In the management of the Cairns Section of the Great Barrier Reef Marine Park from 1985 to 1991, the cost and effectiveness of the two programs were evaluated using an awareness survey and an analysis of annual reports. Both programs were effective in meeting program objectives. Education costs per person were approximately a tenth the cost of enforcement; however, the total cost for education programs was twice that of enforcement programs. Education and enforcement programs interact together with other management activities, and neither program can totally replace the other. Some users will willingly comply with management measures, other users will comply in response to education, but there will be another group who will only respond to enforcement activities. There will also be users who persistently disregard park rules and regulations and will continue to present a problem to managers. For these individuals, education in association with enforcement actions are necessary.

Journal Article↗