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Biomedical subjects

C Mueller

Publications and source records attributed to C Mueller.

At least 37 records · Page 2Linked to original sources
PubMed1998

Central nervous correlates of chemical communication in humans.

The recording of chemosensory event-related potentials (CSERPs) has been established as an objective method in the assessment of central odor processing in humans. In the present study CSERPs were used to investigate whether human body odor is genetically determined by the major histocompatibility complex (MHC), referred to in humans as the human leukocyte antigen (HLA). The immunological function of the MHC is the discrimination of self/nonself within the immune system. In rodents it has been shown that body odor is significantly influenced by the MHC and that it can be discriminated by members of different species. To create a sufficiently large subject pool, 144 subjects were screened for their HLA class I loci A and B. During the electroencephalography (EEG) session the subjects (n = 40/20 women) were confronted with the body odor (axillary hair) of three different donors. Two donors (d1 and d2) were HLA-similar but had a different HLA type than the third donor (d3) and the perceiving subject. The third donor and the perceiver shared a similar HLA type. Half of the perceivers received odors from donors of the same sex, the other half smelt odors from donors of the opposite sex. In the EEG session subjects were presented with 200 trials. The odors were delivered through a constant flow olfactometer non-synchronously to breathing. The odor of d1 appeared frequently (p = 0.6) whereas the odors of d2 and d3 appeared each at a rate of p = 0.2. During half the trials the subjects were instructed to respond to the odor of d2, during the other half to the odor of d3. The EEG was recorded from Fz, Cz, Pz, F3, P3, F4 and P4 in reference to linked mastoids. First results show that male perceivers show enhanced potentials in response to male donors of a similar HLA type (d3). The CSERP results of the other groups as well as valence and attractiveness ratings will be discussed.

Adult↗
PubMed1998

Regulation of the DBP promoter by PAR proteins and in leukemic cells bearing an E2A/HLF translocation.

The D-site binding protein (DBP) is a member of the PAR domain subfamily of b/ZIP proteins, whose expression in the liver is highly sensitive to the growth state of that organ. This paper examines the regulation of the DBP promoter by C/EBP alpha and examines the role of autoregulation in its expression. Of four previously characterized proximal promoter sites, sites I and III are shown to bind C/EBP alpha, but cotransfection in Hep G2 cells of a C/EBP alpha expression vector is unable to transactivate the promoter. In contrast, the expression of DBP, particularly in conjunction with the related protein HLF, is able to dramatically upregulate expression directed by the proximal promoter. Deletion analysis and the use of single site reporter constructs demonstrate that sites II and IV are highly responsive to transactivation by DBP and HLF. The DBP promoter is active in the UOC-B1 cell line, which bears a 17:19 translocation resulting in the creation of an E2A:HLF fusion protein. The proteins binding to site IV are elevated in this line, suggesting that upregulation of DBP expression in response to inappropriate HLF activity may be mediated through this site.

Animals↗
PubMed1998

Male gonadal environment paradoxically promotes dacryoadenitis in nonobese diabetic mice.

Similar to pancreatic islets, submandibular glands are more rapidly infiltrated in female NOD mice than in males. The present comparative analysis of cellular infiltrations in lacrimal glands, however, revealed the opposite finding. At 12 wk of age, approximately 25% of male lacrimal tissue area is infiltrated, whereas age-matched female NOD mice still lack major signs of inflammation. T cells predominate in early stages of invasion, but B cells accumulate promptly in more advanced stages, and ultimately dominate over T cells. Dacryoadenitis is promoted by sex hormones, as suggested by the reduced infiltrations seen in orchidectomized NOD males (P < 0.01). It is also controlled by the local environment provided by the lacrimal tissue. Splenocytes from 4- and 20-wk-old female NOD mice cause massive lesions upon adoptive transfer into NOD male recipients while, conversely, female recipients develop barely any histological sign of infiltration, even after transfer of splenocytes from 20-wk-old donor males. These observations provide strong evidence for a dacryoadenitis-promoting role of male gonadal hormones in NOD mice, a finding that contrasts the known androgen-mediated protective effects on insulitis and submandibulitis in the same strain and on dacryoadenitis in other animal models of Sjögren's syndrome.

Adoptive Transfer↗
PubMed1998

Transient overexpression of CD4 enhances allelic exclusion of T-cell receptor (TCR) alpha chains and promotes positive selection of class II-restricted TCR-transgenic thymocytes.

CD4 contributes to antigen recognition of T cells by binding to class II MHC molecules. There is heterogeneity in expression of CD4 coreceptor among CD4+CD8+ thymocytes. We have investigated whether the expression level of coreceptor influences positive selection. Thymocytes of mice expressing transgenic lambda2(315)-Ig-light-chain/I-Ed specific TCR are poorly positively selected because they fail to allelically exclude endogenous TCR alpha chain genes and because there is no skewing towards CD4. Transient overexpression of CD4 during thymocyte development, in mice transgenic for both TCR and CD4, resulted in skewing towards CD4 in the periphery, reduced rearrangement and expression of endogenous alpha-chains, and decreased levels of thymocyte RAG-1 transcripts. Kinetic BrdU labeling experiments showed that single CD4+ thymocytes developed faster, representing the predominant population even in the cortex of the double transgenic thymi. These results demonstrate that increased coreceptor expression can compensate for poorly selectable TCR, supporting avidity and instructional models for positive selection of thymocytes.

Animals↗
PubMed1998

Exposure of casino employees to environmental tobacco smoke.

Environmental and medical evaluations were performed to evaluate occupational exposure to environmental tobacco smoke (ETS) among casino employees. Air concentrations of both nicotine and respirable dust were similar to those published in the literature for other non-industrial indoor environments. The geometric mean serum cotinine level of the 27 participants who provided serum samples was 1.34 nanograms per milliliter (ng/mL) (pre-shift) and 1.85 ng/mL (post-shift). Both measurements greatly exceeded the geometric mean value of 0.65 ng/mL for participants in the Third National Health and Nutrition Examination Survey (NHANES III) who reported exposure to ETS at work. This evaluation demonstrates that a sample of employees working in a casino gaming area were exposed to ETS at levels greater than those observed in a representative sample of the US population, and that the serum and urine cotinine of these employees increased during the workshift.

Adult↗
PubMed1998

Evaluation of Murex CMV DNA hybrid capture assay for detection and quantitation of cytomegalovirus infection in patients following allogeneic stem cell transplantation.

Murex hybrid capture DNA assay (HCS) is a solution hybridization antibody capture assay for detection and quantitation of cytomegalovirus (CMV) DNA in leukocytes. To determine whether CMV HCS is sensitive enough to initiate and monitor antiviral therapy after allogeneic stem cell transplantation (SCT), 51 consecutive SCT recipients were prospectively screened for the appearance of CMV infection by HCS, PCR, and culture assays from blood samples. Preemptive antiviral therapy was initiated after the second positive PCR result in all patients, as previously reported, and HCS was not considered for clinical decision making. A total of 417 samples were analyzed. Of these, 21 samples were found to be positive by PCR and HCS, 88 samples were PCR positive but HCS negative, and 308 were negative by both assays. Concordance of results between PCR and HCS and between HCS and blood culture was observed in 78.9 and 95.9% of the samples assayed, respectively. PCR was found to be more sensitive than HCS, and HCS was more sensitive than the blood culture assay (P < 0.0001). Four patients with symptomatic CMV infection were PCR positive prior to the onset of CMV-related symptoms, whereas HCS detected CMV DNA in three patients prior to and one at onset of CMV disease. The numbers of genomes per milliliter of blood were higher in patients with symptomatic CMV infection than in those with asymptomatic CMV infection (P = 0.06). None of the HCS-negative patients developed CMV disease. Thus, all patients with CMV disease were correctly identified by HCS; however, the lower sensitivity limit of the HCS assay may still be insufficient to allow diagnosis of CMV infection early enough to prevent CMV disease in patients following allogeneic SCT.

Adolescent↗
PubMed1998

Activated CD4+ and CD8+ cytotoxic cells are present in increased numbers in the intestinal mucosa from patients with active inflammatory bowel disease.

The contribution of cell-mediated cytotoxicity to the pathogenesis of inflammatory bowel disease (IBD) is controversial, and results of in vitro assays vary according to experimental procedures. Therefore, we compared the frequency of cytotoxic effector cells in situ. On tissue sections of controls (n = 11), low frequencies of granzyme A and perforin mRNA-expressing cells are found in the lamina propria (1.77 +/- 0.15% and 1.46 +/- 0.12%, respectively) and in the epithelial cell layer (0.76 +/- 0.12% and 0.66 +/- 0.10%, respectively). In patients with IBD (n = 33), corresponding values were significantly (P < 0.02) higher, 6.1 +/- 0.40% and 5.92 +/- 0.57% for granzyme A and perforin expression in the lamina propria and 2.50 +/- 0.19% and 2.59 +/- 0.28%, respectively, in the epithelial compartment. Differences between ulcerative colitis and Crohn's disease are statistically not significant (P > 0.33). Activated cytotoxic cells are preferentially found at sites facing the intestinal lumen. Perforin mRNA-expressing cells are mainly CD8+ T cells. CD4+ T cells expressing perforin mRNA are mainly isolated from affected areas of patients with Crohn's disease. Immunostaining for perforin protein generally coincides with perforin mRNA in situ. These data demonstrate that cytotoxic cells are vigorously activated in situ in the intestinal mucosa of patients with active IBD.

Adult↗
PubMed1998

A new polyoxometalate complex inhibits retrovirus encoded reverse transcriptase activity in vitro and in vivo.

We examined the recently synthesized and characterized polyoxometalate compound (NH4)10[Co2Sb2W20 O70(H2O)6] (POM1). The inhibitory potency of POM1 was studied in tissue culture experiments with uninfected and Rous sarcoma virus (RSV)-infected chicken embryo fibroblasts (CEF) in vivo. We measured a considerable decrease in total cellular phosphotyrosine content in treated infected cells in vivo. POM1 treatment of SR-RSV-A infected CEF in vivo resulted in decreased pp60v-src activity, possibly due to a reduced rate of v-src translation caused by the inhibitory effect of POM1 on the RSV encoded reverse transcriptase activity (RT) activity. In further studies we were able to demonstrate the inhibitory effect of this complex on the RT activity of RSV in vitro and in vivo.

Animals↗
PubMed1998

A primer on lower extremity outcome measurement instruments.

Tracing the roots of lower extremity outcome scales is an interesting and somewhat bemusing journey. A large number of different grading methods can be found with limited reliability and/or validity testing. The usefulness of these instruments in the assessment of patient outcomes after lower extremity interventions is worrisome. This article focuses on the most commonly used scales and demonstrates an alarming and incestuous pattern of cross-validation with moderate to weak associations between potentially unreliable and crudely validated original instruments.

Activities of Daily Living↗
PubMed1998

Bulimic adolescents benefit from massage therapy.

Twenty-four female adolescent bulimic inpatients were randomly assigned to a massage therapy or a standard treatment (control) group. Results indicated that the massaged patients showed immediate reductions (both self-report and behavior observation) in anxiety and depression. In addition, by the last day of the therapy, they had lower depression scores, lower cortisol (stress) levels, higher dopamine levels, and showed improvement on several other psychological and behavioral measures. These findings suggest that massage therapy is effective as an adjunct treatment for bulimia.

Adolescent↗
PubMed1997

Prevention of autoimmune diabetes mellitus in NOD mice by transgenic expression of soluble tumor necrosis factor receptor p55.

The non-obese diabetic (NOD) mouse represents a relevant animal model of autoimmunity for insulin-dependent diabetes mellitus. The pathogenic role of tumor necrosis factor (TNF) in insulitis and beta cell destruction observed in these mice remains controversial, since injections of TNF or of anti-TNF antibodies have been reported to exert protection or acceleration of diabetes, depending on the timing of administration. In this study, we demonstrate that, in contrast to the non-transgenic littermates, NOD mice with permanent neutralization of TNF by high blood levels of soluble TNF receptor p55-human FcIgG3-fusion molecules resulting from the expression of a transgene are protected from spontaneous diabetes. They are also protected from accelerated forms of disease caused by transfer of NOD spleen cells or cyclophosphamide injections. This protection is associated with a marked decrease in the severity and incidence of insulitis and in the expression of the adhesion molecules MAdCAM-1 and ICAM-1 on the venules of pancreatic islets. These data suggest a central role for TNF-alpha in the mediation of insulitis and of the subsequent destruction of insulin-secreting beta-cells observed in NOD mice. They may be relevant to cell-mediated autoimmune diseases in general, in which treatment with soluble TNF receptors might be beneficial.

Animals↗
PubMed1997

CD5- CD8 alpha beta intestinal intraepithelial lymphocytes (IEL) are induced to express CD5 upon antigen-specific activation: CD5- and CD5+ CD8 alpha beta IEL do not represent separate T cell lineages.

We followed alpha beta T cell receptor (TCR) usage in subsets of gut intraepithelial lymphocytes (IEL) in major histocompatibility complex class I-restricted alpha beta TCR-transgenic (tg) mice. The proportion of tg alpha beta TCR+ CD8 alpha beta IEL is reduced compared with CD8+ splenocytes of the same animal, particularly under conventional conditions of maintenance. Further fractionation of CD8 alpha beta IEL according to the expression level of surface CD5 revealed that in conventionally housed animals tg TCR+ CD5- CD8 alpha beta IEL are as frequent as in specific pathogen-free (SPF) mice, whereas tg TCR+ CD5int or, even more pronounced, tg TCR+ CD5hi CD8 alpha beta IEL are greatly diminished when compared with mice kept under SPF conditions. Upon antigen-specific stimulation of CD5- CD8 alpha beta IEL in vitro, CD5 surface expression is up-regulated on a large fraction of cells within 48 h. Up-regulation of CD5 surface expression is further enhanced by the presence of the anti-alpha IEL monoclonal antibody 2E7. This clearly demonstrates that CD5-, and CD5+ CD8 alpha beta IEL cannot be considered as separate T cell lineages.

Animals↗
PubMed1997

Regulation and function of the CXC chemokine ENA-78 in monocytes and its role in disease.

Epithelial neutrophil-activating protein 78 (ENA-78) is a member of the CXC chemokines and acts as a potent chemoattractant and activator of neutrophil function. On stimulation in vitro, ENA-78 is highly expressed in many cell types. ENA-78 protein levels are strongly elevated in synovial fluid and blood of patients with rheumatoid arthritis. By in situ hybridization and immunofluorescence staining, ENA-78 has been recognized as a major CXC chemokine expressed in epithelial cells of the intestinal mucosa of patients with Crohn's disease, ulcerative colitis, and acute appendicitis. A high expression of ENA-78 and interleukin-8 (IL-8) was also observed in the exocrine tissue of patients with chronic pancreatitis (CP). It is interesting to note that expression of IP-10, MIP-1alpha, and MCP-1 is high in healthy pancreatic tissue but low in tissue of patients with CP, suggesting a mutually exclusive expression of the ELR-CXC vs. non-ELR-CXC/CC chemokines. High-resolution studies of intracellular chemokines has revealed specific immunoreactivity for ENA-78 associated with the endoplasmic reticulum of many cell types. In contrast, GROalpha immunoreactivity was exclusively localized in the nucleus. Despite their common effects on neutrophil functions, the differential intracellular localization of ENA-78 and GROalpha suggests additional roles for these two chemokines in normal cell biology.

Arthritis, Rheumatoid↗
PubMed1997

Ocular flutter and truncal ataxia may be associated with enterovirus infection.

We report on three patients who presented a rare, uniform clinical syndrome consisting of ocular flutter and truncal ataxia. In all patients the symptoms followed an upper respiratory infection and resolved without sequelae within a few weeks. Previous reports have emphasized the apparent relationship of this entity to infectious disease, but the infectious agent remained uncertain. In one patient we could find a significant rise in antibody titres to enterovirus. We are not aware of any other similar documented case.

Adult↗
PubMed1997

Cytotoxic cells are activated in cellular infiltrates of alcoholic chronic pancreatitis.

BACKGROUND & AIMS: Perforin messenger RNA (mRNA) expression has been shown to be a specific in vivo activation marker for cytotoxic cells. In this study, the contribution of cell-mediated cytotoxicity in the pathogenesis of alcoholic chronic pancreatitis is assessed. METHODS: Tissue sections of patients with alcoholic chronic pancreatitis were analyzed for perforin mRNA expression by in situ hybridization. In a further step, the phenotype and the relative frequency of perforin mRNA-expressing cells were determined. RESULTS: In the normal pancreas, perforin mRNA-expressing cells are rarely present (mean, 0.3 cells/mm2). In contrast, the frequency of perforin mRNA-expressing cells is increased severalfold in diseased tissue specimens (mean, 6.6 cells/mm2). The frequency of perforin mRNA-expressing cells is high in the CD56+ (18%) and CD8+ cell population (12%) but low in the CD4+ cell population (1%). CONCLUSIONS: The significantly elevated frequencies of perforin mRNA-expressing cells in the pancreas of patients with alcoholic chronic pancreatitis suggest an involvement of cell-mediated cytotoxicity in the pathogenesis of this disease. The preferential localization of these activated cells close to areas with parenchyma provides circumstantial evidence that autoreactive cytotoxic cells may contribute to tissue destruction in alcoholic chronic pancreatitis.

Cell Separation↗