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Biomedical subjects

A Mueller

Publications and source records attributed to A Mueller.

At least 55 records · Page 3Linked to original sources
PubMed1998

Homing of transgenic gammadelta T cells into murine vaginal epithelium.

The vaginal epithelium of normal mice contains lymphocytes of fetal thymic origin that express an invariant Vgamma4/Vdelta1 TCR. The apparent lack of other gammadelta TCR species suggests that a selection mechanism might operate to regulate the localization of gammadelta T cells at this anatomical site. Selection might be connected to the Vgamma4/Vdelta1 TCR or to some homing characteristic of the fetal thymic lineage that appears at day 17-18 of embryonic life. In the present studies, we investigated whether transgenic gammadelta cells expressing a TCR species characteristic of the subpopulation of gammadelta T cells found in the blood, spleen and lymph would translocate to the vaginal epithelium. We found that the transgenic Vgamma2 TCR+ cells did accumulate in the vagina of transgenic mice. Furthermore, like normal vaginal gammadelta T cells, the transgenic vaginal gammadelta T cells expressed the phenotype of recently activated memory/effector T cells (CD44(hi), CD62L-, CD45RB(lo), CD69+). Vaginal gammadelta T cells in normal mice do not express the CD2 and CD28 antigens, but both of these markers are present on transgenic vaginal gammadelta T cells. We observed that a small fraction of splenic transgenic gammadelta T cells had the same surface phenotype as the vaginal transgenic gammadelta T cells, raising the possibility that the gammadelta T cells present in the vaginal epithelium of transgenic mice originated from the peripheral lymphoid organs. Data in support of this possibility came from experiments in which co-incubation of splenic transgenic gammadelta T cells with vaginal epithelial cell suspensions induced the vaginal gammadelta phenotype on the splenic gammadelta T cells. The finding of transgenic gammadelta T cells in the vaginal epithelium suggests that homing of gammadelta T cells to this site is not restricted to gammadelta T cells that express the V4/NS1 invariant TCR. Furthermore, these findings imply that retention of gammadelta T cells in the vaginal epithelium of normal mice is affected by a Vgamma4/Vdelta1-specific mechanism. The finding of a significant level of apoptosis in the transgenic vaginal gammadelta T cells, but not in the normal vaginal gammadelta T cells, could reflect that the mechanism of retention of Vgamma4/Vdelta1 + in the vaginal epithelium involves selective survival at the site.

Animals↗
PubMed1997

A transgenic mouse model with cyclin D1 overexpression results in cell cycle, epidermal growth factor receptor, and p53 abnormalities.

The cyclin D1 oncogene is critical in the progression of the cell cycle through the G1 phase. It is frequently overexpressed in squamous cell carcinomas originating from the head/neck and esophagus. Yet, the functional consequences of aberrant cyclin D1 overexpression are not entirely understood apart from increased cell proliferation. To address this question, we have developed a transgenic mouse model in which the EBV ED-L2 promoter targets cyclin D1 to the stratified squamous epithelium in a tissue-specific fashion to the tongue and esophagus, thereby resulting in a dysplastic phenotype. We now demonstrate that the dysplastic phenotype is associated with increased cell proliferation based on proliferating cell nuclear antigen overexpression and abnormalities in cyclin-dependent kinase 4, epidermal growth factor receptor, and p53. In aggregate, these studies suggest that alterations in certain oncogenes and tumor suppressor genes occur early during head/neck and esophageal carcinogenesis.

Animals↗
PubMed1995

Potential role of Fc gamma R in early development of murine lymphoid cells: evidence for functional interaction between Fc gamma R on pre-thymocytes and an alternative, non-Ig ligand on thymic stromal cells.

During early development of the murine fetal thymus a fraction of Thy+ thymocytes express Fc gamma receptors. Concurrently, a small fraction of Thy- CD44- thymocytes bind recombinant soluble Fc gamma R. These findings suggested the possibility that Fc gamma R+ pre-T cells interact with a non-Ig ligand present on fetal thymic stromal cells. Evidence in support of this concept was the finding that experimental manipulation of this putative receptor-ligand pair by anti-receptor antibody or recombinant soluble Fc gamma R influenced the developmental pattern of alpha/beta-TCR+ T cells. The restricted expression of CD16 on some pre-B cells raises the possibility that an Fc gamma R-dependent step may play a similar role in B-cell development.

Animals↗
PubMed1994

Function of GABAA inhibition in specifying spatial frequency and orientation selectivities in cat striate cortex.

Responses of simple and complex cells in cat striate cortex were studied with moving sine-wave gratings before and during application of the GABAA receptor antagonist bicuculline methiodide. Both simple and complex cells exhibited a broadening of their spatial frequency tuning functions under bicuculline. This was especially evident at spatial frequencies lower than the ones the cell was responding to before the drug administration. The effects cannot be explained by response saturation and could be reversed by cessation of the iontophoresis. The results indicate that the band-pass response characteristics of the spatial frequency response functions of striate cells derive largely from intracortical inhibition. The findings have implications also for the orientation selectivity of cortical cells. Since many geniculate cells are tuned for stimulus orientation at higher spatial frequencies, suppression of the low-spatial-frequency component would remove some of the orientation non-specific response in striate cortical cells and contribute to their orientation selectivity.

Animals↗
PubMed1994

Early identification and remediation of phonological-processing deficits in first-grade children at risk for reading disabilities.

The present study assessed 486 first-quarter first graders on their reading and phonological-processing skills and intelligence. Based on this assessment, and using the classification data from Hurford et al.'s (1993) study, 99 children were identified as being at risk for reading difficulties: 53 children at risk for reading disabilities (RD) and 46 children at risk for becoming "garden-variety" poor readers (GV). Half of the RD and GV groups received the phonological-processing intervention. Posttraining assessment indicated that the training procedure not only was effective in increasing the phonological-processing skills of the trained participants, but also increased their reading ability. Both of the RD and GV trained groups benefited from the training. Analyses also indicated that the initial screening device was somewhat less accurate in the present study in identifying at-risk children than in our previous studies (85% vs. approximately 98%, respectively). The results of the present study indicate that it is possible to identify children at risk for reading difficulties and to significantly improve their phonological-processing and reading abilities.

Child↗
PubMed1994

Evidence for the occurrence of Schistosoma intercalatum at Albert Nile in northern Uganda.

During a field investigation in Rhino Camp at Albert Nile in northern Uganda, 77.8% of 636 persons excreted Schistosoma mansoni ova that were detected by the Kato-Katz method. Six patients, 8-17 years of age, had terminally spined schistosome eggs in their stools. These findings were confirmed when preserved specimens were examined at the Institute of Medical Parasitology in Bonn using a concentration technique. The mean +/- SD length of 36 terminally spined eggs was 156 +/- 6 microns and the mean +/- SD width was 59 +/- 3.6 microns. Urine filtration in the study patients revealed no schistosome eggs in the urine. It is concluded that these findings provide evidence for the occurrence of S. intercalatum at Albert Nile in northern Uganda.

Adolescent↗
PubMed1994

Urban Schistosoma mansoni near Enyau river in Arua town, Uganda.

Using the Kato Katz method for quantification of parasitic eggs in faeces, 500 individuals aged between 4 and 50 years, living along River Enyau, half a kilometre from Arua town, were studied to assess the prevalence of Schistosoma mansoni in the population. The overall prevalence of Schistosoma mansoni infection was 62%. The infection was highest among school children (71.1%, i.e. 199 out of 280). Villagers who lived along the immediate vicinity of the river had a 62.8% prevalence of infection (98 out of 156). School teachers and the members of their families had the lowest infection rate (20.3% i.e. 13 out of 64). The geometric mean egg output for males and females in the community studied was 203 and 179 eggs per gram of stool, respectively. 206 (41%) out of 500 individuals had mixed infections of S. mansoni and hookworms. The rate of orally transmitted intestinal helminths like Trichuris trichiura was very low (0.8%). Ascaris lumbricoides eggs were not found.

Adolescent↗
PubMed1992

[Differences in detectability of human immunodeficiency virus type 1 in tears and blood lymphocytes].

Reported data on the isolation of the human immunodeficiency virus type 1 (HIV-1) from tears are controversial. The purpose of the study was to try to isolate HIV-1 from tears in a large sample of HIV-1-positive patients at different stages of infection. 53 tear samples were obtained from 50 patients. Additionally isolation of HIV-1 from peripheral blood lymphocytes (PBL) was attempted. HIV-1 was isolated from none (= 0%) of the 53 tear samples. Isolation from PBL was successful depending on absolute CD4+ lymphocyte count and Walter Reed staging (Walter Reed stage 6: 83%; stage 2 to 5: 11%; p less than 0.0001). Treatment with zidovudine was not related to the frequency of HIV-1 isolation. These results suggest that tears of patients infected with HIV-1 contain low or no quantities of tissue-culture-infectious units of HIV-1. Nosocomial infection with HIV-1 from tears appears to be unlikely. The known precautions for the prevention of spread of viral disease in ophthalmological practice are sufficient and should be strictly followed.

Adolescent↗
PubMed1992

Fluorescence spectroscopy for identification of atherosclerotic tissue.

OBJECTIVE: Vessel perforation and limited steerability of the laser light are the major limitations of laser angioplasty. To improve steerability fluorescence spectroscopy has been proposed for identification of atherosclerotic plaques. The aim was to investigate this. METHODS: Fluorescence spectroscopy with three different excitation wavelengths (325 nm, 380 nm, 450 nm) was tested in an emission range of 400 nm to 600 nm. Intensity ratios at 480/420 nm were determined in different types of blood vessels. Necropsy material from 40 patients (punch biopsies of 4 mm diameter from the coronary and carotid artery as well as from the ascending and descending aorta) was studied spectroscopically. Histological alterations of the vessel wall were assessed by a semiquantitative score (0 to 10 points): (a) normal tissue, 0 to 2 points (mean = 0.25; n = 38); (b) mild atherosclerotic lesions, 3 to 5 points (mean = 3.35; n = 39); (c) severe atherosclerotic lesions, greater than or equal to 6 points (mean = 6.75; n = 43). RESULTS: Best spectroscopic results were obtained with an excitation wavelength of 325 nm. In samples with severe atherosclerotic lesions the fluorescence spectra showed a significant reduction of the emitted wavelength intensities when compared to normal tissue. There was a clear separation of the fluorescence spectra between normal and mild as well as between normal and severe atherosclerotic lesions; normal tissue showed an increased intensity in the range from 420 nm to 540 nm, whereas atherosclerotic lesions had no or only a small peak at 480 nm. There was a significant correlation between the semiquantitative score (n = 120) and the fluorescence ratio at 480/420 nm (excitation wavelength 325 nm) with a correlation coefficient of 0.87. The spectroscopic results showed no differences between the samples taken from different types of vessels. CONCLUSIONS: Fluorescence spectroscopy allows a reliable identification of normal and atherosclerotic lesions. The close correlation between the emitted light intensity ratio at 480/420 nm and the histological alterations of the vessel wall suggests a relationship between vessel wall fluorescence and the atherosclerotic alterations of the wall.

Adolescent↗
PubMed1988

Correlation of DNA flow cytometric results and other prognostic factors in primary breast cancer.

The percentage of cells in S-phase and DNA-ploidy have been measured in 300 primary mammary carcinomas by means of DNA-flow cytometry (FCM). The data were compared with the age and menopausal status of the patients as well as with the size, regional lymph-node involvement, histologic type, grade and concentration of estrogen (ER) and progesterone (PR) receptors of the tumors. A DNA-diploid distribution of the G0/1-peak was found in 37.6% of the cases. The mean percentage of S-phase fractions was 4.83. DNA-aneuploid tumors had significantly higher amounts of S-phase fractions (6.12%) than DNA-diploid tumors (2.66%). There was also a significant correlation between the DNA measurement data (DNA-ploidy and S-phase fractions) and histologic grade, as well as the content of ER and PR, but not between DNA-ploidy, S-phase fractions, tumor size (T) and evidence of axillary lymph-node metastases. DNA-FCM gives a biological characterization of the tumor in addition to the histopathologic examination. The method can be used as a routine procedure because of the reliability and reproducibility of the results as well as the short time needed for the measurements.

Age Factors↗
PubMed1988

Immunoglobulin (Fc) receptors on murine T- and B-lymphocytes: investigations using tumor models.

Lymphoid tumors are productive experimental models for the study of lymphocyte immunoglobulin receptors. Investigations with Fc receptor expressing lymphoid tumor cells have generated much useful information about: (a) the developmental expression of the different classes of Fc receptors on lymphoid cells of the T- and B-lineages; (b) the biochemical steps involved in the regulation of Fc receptor expression on lymphoid cells; (c) the structures of lymphoid cell Fc receptors and their genes; (d) the signals that induce alterations in the expression of Fc receptors on lymphoid cells; and (e) the molecular specificity of the binding of immunoglobulin to lymphoid cells Fc receptors. In addition, tumors that secrete immunoglobulins are providing useful models for analysis of the mechanisms by which B-cells influence Fc receptor expression and function on T-cells. An interesting, bi-directional immunoregulatory circuit involving Fc epsilon R+ host T-cells and IgE-secreting hybridoma cells has been identified that could prove useful in the analysis of the regulation of epsilon heavy chain expression. The studies discussed in this article and elsewhere in this volume serve to emphasize that, in addition to being clonal sources of key molecules such as Fc receptors and their messenger RNAs, lymphoid tumor cells that express Fc receptors are powerful and unique experimental models for investigating the developmental biology, regulation and function of lymphocyte Fc receptors.

Animals↗
PubMed1983

The use of brain slices in central nervous system pharmacology.

Brain slice preparations have most frequently been employed to answer questions of a biochemical or physiological nature. Nevertheless, in vitro brain slices also have considerable value as pharmacological tools with which to study the physiological actions of neurotransmitters and drugs on the central nervous system. Several aspects of the slice preparation facilitate this type of analysis. Because drugs can be applied and tested in a relatively quantitative manner, many classical pharmacological techniques (e.g., dose-response curves, tests for competitive vs. noncompetitive antagonism) can be used to examine drug responses. At the simplest level, these techniques facilitate the differentiation of specific (primarily receptor-mediated) and nonspecific actions of drugs and neurotransmitters. As another consequence, the electrophysiological actions of drugs can be directly compared to their biochemical effects in vitro (receptor binding, activation or inhibition of adenylate cyclase, etc.). Ultimately, parallel studies of this type can be used to establish mechanisms of action for various neurotransmitters, particularly those that may employ biochemical substrates as second messengers. In this paper we describe in general terms many of the advantages of the slice preparation as a neuropharmacological tool. Some of the criteria useful in determining the involvement of various receptors in drug-induced changes in electrophysiological responses are discussed in detail. Finally, the responses of hippocampal slices to various adrenergic agents are used to illustrate the way in which various features of this preparation can be exploited pharmacologically. The results of these experiments constitute a significant advance in terms of our understanding of the neuropharmacology of catecholamine responses in this brain region.

Animals↗
PubMed1981

Coupling between H+ transport and anaerobic glycolysis in turtle urinary bladder: effect of inhibitors of H+ ATPase.

The coupling between H+ transport (JH) and anaerobic glycolysis was examined in vitro in an anaerobic preparation of turtle urinary bladder. JH was measured as the short-circuit current after Na+ transport was abolished with ouabain and by pH stat titration. The media were gassed with N2 and 1% CO2 (PO2 less than 0.5 mm Hg) and contained 10 mM glucose. Under these conditions, JH was not inhibited by 3 mM serosal (S) cyanide or by 0.1 mM mucosal (M) dinitrophenol. Control anaerobic lactate production (Jlac) of 47 bladders was plotted as a function of simultaneously measured JH. The slope of Jlac on JH was 0.58 0.12 with an intercept for Jlac at JH = 0 of 0.55 micromol/hr. Values for delta Jlac/delta JH were determined in groups of individual bladders when JH was inhibited by an opposing pH gradient (0.55 0.16), by acetazolamide (0.58 0.19) and by dicyclohexylcarbodiimide, DCCD (0.58 0.14). The constancy of delto Jlac/ delta JH indicates a high degree of coupling between JH and Jlac. Since the anaerobic metabolism of glucose produces one ATP for each lactate formed, the delta Jlac/ delta JH values can be used to estimate the stoichiometry of H+ translocation. The movement of slightly less than 2H+ ions is coupled to the hydrolysis of one ATP. During anaerobiosis (absence of mitochondrial ATPase function) the acidification pump was not inhibited by M addition of oligomycin but was inhibited by M addition of DCCD and Dio-9, inhibitors of H+ flow in the proteolipid portion of H+-translocating ATPases. DCCD inhibited anaerobic JH without change in delta Jlac/delta JH or basal Jlac and, therefore, acted primarily on the H+ pump. S addition of vanadate also inhibited JH, but the inhibition was associated with an increase in Jlac. The site of this apparent uncoupling remains to be defined. The acidification pump of the luminal cell membrane of the turtle bladder has H+-ATPase characteristics that differ from mitochondrial ATPase in that H+ transport is oligomycin-resistant and vanadate-sensitive. As judged from the flows of H+ and lactate, the H+/ATP stoichiometry of the pump is about 2.

Adenosine Triphosphatases↗
PubMed1980

Electrophysiological interactions of enkephalins with neuronal circuitry in the rat hippocampus. I. Effects on pyramidal cell activity.

Effects of enkephalins on hippocampal pyramidal cell activity were studied in situ and in the in vitro hippocampal slice. Active enkephalin derivatives produced a dose-dependent naloxone-reversible excitation in both preparations whereas inactive enkephalin derivatives had no effect. Several different types of experiments, carried out in the slice, strongly suggest that this excitation is due to blockade of inhibitory pathways. First, when the pyramidal cell population spike is increased during enkephalin administration, no change is seen in the simultaneously recorded EPSP. Second, the magnitude of the enkephalin effect is highly correlated with the amount of inhibition, as judged by paired-pulse stimulation, initially present in the slice. Third, if inhibitory pathways are depressed by a brief period of hypoxia, enkephalin has little effect. Finally, enkephalin responses are mimicked by picrotoxin, which selectively antagonizes inhibitory input to the pyramidal neuron. Since enkephalins do not block the effects of GABA, the putative inhibitory transmitter, these data suggest that opioid peptides depress the inhibitory interneurons and disinhibit the pyramidal cells.

Animals↗