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Biomedical subjects

W Hansen

Publications and source records attributed to W Hansen.

At least 19 recordsLinked to original sources
PubMed2005

In vitro-generated regulatory T cells induced by Foxp3-retrovirus infection control murine contact allergy and systemic autoimmunity.

Regulatory T cells are promising candidates for the modulation of inflammation and autoimmunity. To generate regulatory T cells in vitro, we have infected naïve CD4+CD25- T cells with a retrovirus encoding the transcription factor Foxp3. Foxp3-infected T cells are similar to naturally occurring regulatory T cells as evidenced by surface marker expression and function. To investigate the effects of Foxp3-infected T cells on contact hypersensitivity (CHS) responses, sensitized mice were injected with Foxp3- or control virus-infected T cells. Only injection of Foxp3-infected T cells into sensitized mice significantly inhibited CHS compared to controls, indicating that Foxp3-infected T cells are suppressive in vivo. These findings prompted treatment of autoimmune-prone CD40L transgenic (tg) mice, which develop a severe systemic autoimmune disease including autoreactive T cells and autoantibodies, with Foxp3-infected T cells. Interestingly, injections of Foxp3-infected T cells into CD40L tg mice inhibited the ongoing development of autoimmune dermatitis and activation of cytotoxic CD8+ T cells. Strikingly, treatment with Foxp3-infected T cells reduced serum concentrations of antinuclear antibodies in CD40L tg mice, which was paralleled with reduced renal immunoglobulin depositions and increased kidney function. Together, these findings indicate that newly in vitro-generated regulatory T cells can be successfully used to treat inflammatory and ongoing autoimmune disorders.

Animals↗
PubMed2005

CD4+ T cell mediated intestinal immunity: chronic inflammation versus immune regulation.

BACKGROUND: Several studies have suggested that chronic inflammatory bowel disease may be a consequence of antigen specific recognition by appropriate T cells which expand and induce immunopathology. AIMS: We wished to investigate whether autoreactive CD4+ T cells can initiate the disease on recognition of enterocyte specific antigens directly and if induction of mucosal tolerance occurs. METHODS: Transgenic mice (VILLIN-HA) were generated that showed specific expression of haemagglutinin from influenza virus A exclusively in enterocytes of the intestinal epithelium. To investigate the impact of enterocyte specific haemagglutinin expression in an autoimmune environment, we mated VILLIN-HA mice with T cell receptor (TCR)-HA mice expressing an alpha/beta-TCR, which recognises an MHC class II restricted epitope of haemagglutinin, and analysed the HA specific T cells for induction of autoimmunity or tolerance. RESULTS: In VILLIN-HAxTCR-HA mice, incomplete central deletion of HA specific lymphocytes occurred. Peripheral HA specific lymphocytes showed an activated phenotype and increased infiltration into the intestinal mucosa, but not into other organs of double transgenic mice. Enterocyte specific lamina propria lymphocytes showed a dose dependent proliferative response on antigen stimulation whereas the proliferative capacity of intraepithelial lymphocytes was reduced. Mucosal lymphocytes from VILLIN-HAxTCR-HA mice secreted lower amounts of interferon gamma and interleukin (IL)-2 but higher levels of tumour necrosis factor alpha, monocyte chemoattractant protein 1, and IL-6. Mucosal immune reactions were accompanied by broad changes in the gene expression profile with expression of proinflammatory genes, but strikingly also a remarkable set of genes discussed in the context of peripheral induction of regulatory T cells, including IL-10, Nrp-1, and Foxp3. CONCLUSIONS: Enterocyte specific antigen expression is sufficient to trigger a specific CD4+ T cell response leading to mucosal infiltration. In our model, progression to overt clinical disease was counteracted most likely by induction of regulatory T cells.

Animals↗
PubMed2003

Spectroscopy of few-electron collective excitations in charge-tunable artificial atoms.

We report the investigation of electronic excitations in InGaAs self-assembled quantum dots using resonant inelastic light scattering. The dots can be charged via a gate by N=1, em leader,6 electrons. We observe excitations, which are identified as transitions of electrons, predominantly from the s to the p shell (s-p transitions) of the quasiatoms. We find that the s-p transition energy decreases and the observed band broadens, when the p shell is filled with 1 to 4 electrons. By a theoretical model, which takes into account the full Coulomb interaction in the few-electron artificial atom, we can confirm the experimental results to be an effect of the Coulomb interaction in the quantum dot.

Journal Article↗
PubMed2003

Neutron spectrometry in mixed fields: proportional counter spectrometers.

Proton recoil proportional counters have been successfully used in many laboratories worldwide for more than 30 years in order to measure high-resolution neutron energy spectra. The method is well elaborated and understood, nevertheless high expertise is required for its proper application. Table 4.1 summarises typical basic data for proton recoil proportional counters and the requirements for their application. It is noteworthy that any limiting parameter can vary to a certain degree depending on the quality of the detectors used (design, gas purity, response functions, etc) and their response matrices, the data analysis and the unfolding procedures applied with a correct evaluation of the uncertainties involved. It is also important to lend a critical eye to details during measurements (e.g. environmental and electronics problems) as well as in subsequent analysis and unfolding (e.g. oscillations due to unfolding artefacts or inadequacies in detector response matrices). It is recommended that any spectrometry system (procedures for measurement and data evaluation) should be tested and validated in well-known neutron fields e.g. 252Cf standard fission or 241Am-Be. One should, however, expect that, due to different room scatter conditions, deviations from the ISO spectra may occur, especially for low neutron energies. In order to demonstrate the capability of the recoil proton counter technique, two examples of typical neutron spectra are shown in Figures 4.20 and 4.21, both measured in mixed neutron-gamma fields at nuclear research reactors.

Calibration↗
PubMed2000

Hsp72 induction: a potential molecular mediator of the delay phenomenon.

The molecular basis of enhanced ischemic tissue survival in flaps preconditioned by surgical delay is poorly understood. Because elevated expression of so-called heat shock or stress proteins has been shown to protect tissues/organs against ischemic injury, the authors examined whether the levels of the most highly induced stress protein-hsp72-were elevated in delayed muscle flaps using a rat muscle flap model. Bilateral latissimus dorsi muscle flaps based on the thoracodorsal vessels were elevated in 16 male Sprague-Dawley rats. For each animal, one side was selected randomly to undergo preconditioning by surgical delay for a 7-day period prior to elevation. Delay was accomplished by preserving the thoracodorsal pedicle and a single large distal intercostal perforating vessel. After bilateral flap elevation, latissimus dorsi tissue was harvested from proximal, central, and distal flap segments 0, 1, 3, and 7 days postoperatively (N = 4 for each group), and was analyzed for the expression of hsp72 via Western blot analysis. At the time of harvest, flap viability was assessed by staining with nitroblue tetrazolium. Flap perfusion was measured prior to muscle elevation and harvest using laser Doppler flowmetry. The results demonstrate that delayed muscle flaps had significantly greater total perfusion (p < 0.05) and survival (p < 0.03) 1, 3, and 7 days after elevation compared with the acutely elevated control tissue. Western blot analysis revealed that tissues harvested from the delayed flaps expressed substantially higher levels of hsp72 compared with the acutely elevated control samples. Segmental analysis also revealed a proximal > middle > distal expression of hsp72 in the delayed flaps (p < 0.05). Flap preconditioning by surgical delay increases the expression of hsp72. Moreover, regional differences in hsp72 gene expression are associated with differences in perfusion and survival of delayed muscle flaps. These results indicate that hsp72 may play a substantial role in mediating the delay phenomenon.

Analysis of Variance↗
PubMed1998

CCAAT-enhancer binding protein alpha is expressed in activated microglial cells after brain injury.

Microglial cells play important roles in brain injury and repair and are implicated in diseases such as Alzheimer's disease, Creutzfeldt-Jacob disease, multiple sclerosis, the Aids Dementia Complex and stroke. Despite their importance in neuropathology, the underlying molecular basis for the activation of microglia after brain injury is not understood. We show, using RT-PCR, in situ hybridisation, immunocytochemistry, and electrophoretic mobility shift assay, that the CCAAT-enhancer binding protein alpha (C/EBP alpha), a sequence specific DNA-binding protein, is induced in microglial cells, but not astrocytes or neurons, after hypoxic-ischemic brain injury. These results suggest that C/EBP alpha might regulate gene expression and consequentially have a role in the activation and/or proliferation of microglia following brain injury.

Animals↗
PubMed1997

A sensitive method for the detection of murine C-type retroviruses.

A RT-PCR assay was developed for group-specific detection of murine C-type retroviruses using a nested set of degenerated primers. To distinguish exogenous viruses from related, but silent endogenous viruses, a DNAse I pretreatment of supernatants is applied. This is followed by a heat inactivation/denaturation step. The PCR method is ultrasensitive. which enables the detection of 100 attogram of MoMuLV proviral DNA or up to 1-10 infectious mouse C-type retroviruses in 10 microl supernatant of infected cells. The high specificity of the method allows the differentiation between mouse C-type retroviruses and related retroviruses of the A, B, and D type and C-type retroviruses found in other species. It serves as a valuable tool for the screening of animal cell cultures for contaminations with mouse retroviruses, e.g. hybridomas or recombinant cell lines producing foreign proteins.

3T3 Cells↗
PubMed1993

Prenatal diagnosis by in situ hybridization on uncultured amniocytes: reduced sensitivity and potential risk of misdiagnosis in blood-stained samples.

Maternal cell contamination was assessed in 18 macroscopically blood-stained amniotic fluid samples from male fetuses. The samples were analysed by double-target fluorescent in situ hybridization (ISH) with Y and X chromosome-specific probes. The only sample with an aberrant karyotype (47,XY, + 18) was also analysed by hybridization with a chromosome 18-specific probe. An interpretation of extensive maternal cell contamination was made in two samples, one of which was the sample with trisomy 18. ISH with the chromosome 18-specific probe on this latter sample showed that the sensitivity of the ISH method for chromosome enumeration of uncultured amniotic fluid samples may be reduced in blood-stained samples. It was calculated that by using ISH for chromosome enumeration of the two extensively contaminated samples, a case of trisomy 21 might have been overlooked in both samples, while a case of trisomy 18 might only have been overlooked in one of the samples. It is concluded that ISH should not be used for chromosome enumeration of uncultured amniotic fluid samples that are macroscopically blood-stained without further technical developments.

Amniotic Fluid↗
PubMed1993

Severe human infections caused by Vibrio metschnikovii.

Vibrio metschnikovii is largely distributed in the aquatic environment; human infections are rarely observed. A fatal case of septicemia in a patient with liver cirrhosis, renal insufficiency, and diabetes is described. A second case in a 82-year-old woman with septicemia, respiratory problems, and infected leg lesions is reported; she was successfully treated.

Aged↗
PubMed1993

The constipated serviceman: prevalence among deployed U.S. troops.

The prevalence of constipation in deployed servicemen was determined in a sample of military personnel aboard the USS Iwo Jima LPH 2 during Operation Desert Shield. Results were obtained from a bowel function questionnaire issued to 500 deployed marines and sailors. When constipation is defined as no bowel movement for greater than 3 days, 3.9% of the Marine/sailor personnel are constipated when in their home environment as compared to 6.0% when they are aboard ship and 30.2% while in the field. Alternatively, when constipation is defined as the presence of certain anorectal complaints (hard stools, straining, painful defecation, and bleeding with defecation), the incidence is 7.2% when at home as compared to 10.4% aboard ship and 34.1% in the field. These results confirm that whether constipation is defined as infrequent bowel movements or presence of symptoms of constipation, significantly more servicemen will be constipated when in the field as compared to their home environment. Since approximately one-third of Navy/Marine Corps personnel deployed in a field environment will be constipated, preventive measures ought to be evaluated.

Adolescent↗
PubMed1993

Prevalence and severity of urinary incontinence in ambulatory adults: an UPRNet study.

BACKGROUND: Although urinary incontinence (UI) is a common and costly problem, its prevalence and severity in ambulatory patients is not well established. The main objectives of this study were to define the prevalence and severity of urinary incontinence in adult men and women who came to a primary care office for health care, to determine if these patients had ever told a health care provider about this problem, and to determine if they would be interested in treatment if it were available and effective. METHODS: Men and women aged 20 years and over who came to family physicians' offices seeking health care for any reason during an 11-week period were the subjects of a survey by an anonymous questionnaire. Five family practice offices in UPRNet (the Upper Peninsula Research Network), a research network in Michigan, participated. We defined "current urinary incontinence" as any degree of incontinence in the past 12 months. RESULTS: Of the 2830 study participants, 33% had current urinary incontinence (95% confidence interval [CI] 31% to 35%). Incontinence was experienced by 11% of the men and 43% of the women. Urinary incontinence constituting a social or hygienic problem was reported by 5% of the men and 23% of the women (17% overall). Of those with current UI, 72% had not told a health care provider. Of the patients who had not told a physician, 37% said they would seek care if they knew tests and effective treatment were available. CONCLUSIONS: Urinary incontinence is a common problem among those seen in primary care settings, and its presence is often not known to the health care provider.

Adult↗