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Biomedical subjects

B Arnold

Publications and source records attributed to B Arnold.

At least 55 records · Page 3Linked to original sources
PubMed1997

A role for Th2 cytokines in the suppression of CD8+ T cell-mediated graft rejection.

A major histocompatibility complex (MHC) class I-specific T cell receptor (TCR)-transgenic mouse was used to study classical-type transplantation tolerance in the adult. Engraftment of MHC class I-incompatible bone marrow and tolerance to donor-type skin grafts were obtained using dimethylmyeleran (DMM) as a myeloablative agent and a non-depleting anti-CD8 monoclonal antibody (mAb) as the sole immunosuppressant. Surprisingly, bone marrow engraftment was facilitated by host CD4+ T cells, a subset normally considered unable to reject class I MHC-incompatible grafts. A combination of mAb to interleukins (IL)-4 and -10 antagonized the "permissive" effects of host CD4+ T cells, indicating a possible role for Th2-type immunoregulation that can act on CD8+ T cells in this form of transplantation tolerance. The fate of graft-reactive T cells was monitored using anti-clonotypic antibodies. It was observed that bone marrow engraftment then led to peripheral deletion of mAb-blockaded, clonotype+ CD8+ T cells.

Animals↗
PubMed1997

[Reference curves for hearing surface scaling in clinical use].

METHODS: A commercially available system for the purpose of categorial loudness rating (WHF, WESTRA ELECTRONIC GmbH, Wertingen) was applied with 57 subjects with normal hearing to evaluate reference loudness level functions for 1/3-octave bandpass filtered noise and octave bandpass filtered environmental sounds. RESULTS: The procedure can be carried out with high reproducibility without effects of training due to repetition and only slight influence of subject sex, whereas the labeling of input device and temporal structure of the environmental sounds influence results, as does the center frequency. CONCLUSIONS: Our results showed deviations compared with the reference functions displayed in the WHF system.

Adolescent↗
PubMed1996

Adenoma of the middle ear mucosa.

Benign adenomas of the middle ear are rare tumors. To date, approximately 100 cases of adenomatous neoplasms of the middle ear space have been collected in the United States Armed Forces Institute of Pathology, Washington D.C. This report describes two cases of primary adenomatous neoplasms confined to the middle ear cleft seen at the Department of Otorhinolaryngology at Ludwig Maximilians University Hospital, Munich. Although tumors are derived from lining epithelium of the middle ear mucosa, the unique feature of our first case was based on its origin in the epitympanic part of the tympanic membrane. Histopathology was characterized by an adenomatous morphology without atypia or mitoses, proving its benign behavior. No evidence was found for invasion of adjacent tissue. Simple surgical removal afforded excellent prognosis. Clinical behavior, histological appearance, origin of tumors and differential diagnosis are discussed.

Adenoma↗
PubMed1996

Visualization of inner ear structures by three-dimensional high-resolution magnetic resonance imaging.

High-resolution computed tomography (CT) has long been the method of choice in the visualization of the petrous bone, the internal auditory canal, and the cerebellopontine angle. The introduction of magnetic resonance imaging (MRI), especially of the three-dimensional Fourier transformation constructive interference in steady state (3DFT-CISS), has proved to be superior in the detection of soft-tissue lesions in the inner ear. The aim of this study was to visualize small anatomic structures of the inner ear and cerebellopontine angle. The examinations were performed with a standard head coil on a 1.5-T Magnetom ("Vision"; Siemens, Erlangen, Germany). The three-dimensional reconstruction of the cochlea, semicircular canals, and vestibulum allowed detailed visualization, as well as the imaging of cranial nerves VII and VIII. Our results indicate that 3DFT-CISS MRI is a valuable diagnostic tool in the evaluation of inner ear anatomy and pathology; in most cases, however, it must be supplemented by HR-CT.

Aged↗
PubMed1995

T cell awareness of paternal alloantigens during pregnancy.

During pregnancy a semiallogeneic fetus survives despite the presence of maternal T cells specific for paternally inherited histocompatibility antigens. A mouse transgenic for a T cell receptor recognizing the major histocompatibility (MHC) antigen H-2Kb was used to follow the fate of T cells reactive to paternal alloantigens. In contrast to syngeneic and third-party allogeneic pregnancies, mice bearing a Kb-positive conceptus had reduced numbers of Kb-reactive T cells and accepted Kb-positive tumor grafts. T cell phenotype and responsiveness were restored after delivery. Thus, during pregnancy maternal T cells acquire a transient state of tolerance specific for paternal alloantigens.

Animals↗
PubMed1995

5HT3 receptor antagonists do not block nicotine induced hyperactivity in rats.

The effects of 5-HT3 receptor antagonists (ondansetron 0.1 mg kg-1 SC 30 min; bemesetron 0.03 mg kg-1 SC 45 min) on nicotine-induced increases in locomotor activity were measured in male Sprague-Dawley rats. Intermittent daily injections of nicotine (0.3-1.2 mg kg-1 SC 30 min) resulted in increased locomotor activity as measured by photocell counts. The effect of nicotine was not affected by administration of the 5-HT3 receptor antagonists at doses that are reported to block nicotine- and morphine-induced place-preference conditioning. Neither of the 5-HT3 receptor antagonists tested affected activity counts in vehicle treated animals. Nicotine-induced hyperactivity was blocked by the dopamine antagonist haloperidol (0.03 mg kg-1 SC 2 h) and by the nicotinic antagonist mecamylamine (1 mg kg-1 SC 1 min). The effects of a range of doses (0-1 mg kg-1) of the 5-HT3 receptor antagonists ondansetron, bemesetron, granisetron and tropisetron on hyperactivity induced by 0.6 mg kg-1 nicotine were then assessed. Only tropisetron at 1 mg kg-1 attenuated nicotine-induced hyperactivity. To demonstrate the efficacy of the present range of doses of the 5-HT3 receptor antagonists in this study, conditioned taste aversion experiments were conducted. Ondansetron (0.1 mg kg-1) failed to attenuate a conditioned taste aversion to saccharin induced by nicotine (0.6 mg kg-1), but did induce a reduction in saccharin preference in choice tests following three saccharin-ondansetron pairings.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

[Vascular, inflammatory and tumorous lesions of the temporal bone and cerebellopontile angle: applications of magnetic resonance tomography].

Advances in high resolution magnetic resonance imaging (MRI) allow the evaluation of the cerebellopontine angle and temporal bone. The purpose of our study was to demonstrate pathological and anatomical aberrations of cerebral arteries in relation to clinical symptoms. The study was carried out on a 1T MR whole body scanner (Impact, Siemens, Erlangen, Germany), using a head coil, a pre- and postcontrast ("Magnevist", Schering, Berlin, Germany) T1-weighted 2D-FLASH sequence and a T2-weighted turbo-spin echo sequence. We examined 22 patients suffering from asymmetric hearing loss, pulse-synchronous tinnitus, hemifacial spasm or facial palsy. The problem of a clear differentiation of meningiomas and acoustic neurinomas by means of MRI is discussed. We identified aberrant AICAs at the cerebellopontine angle in close contact with the V., VII. and VIII. cranial nerve. Inflammatory lesions of the facial and vestibulocochlear nerve were visualised successfully. The potential of the pre- and postcontrast 2D-FLASH sequence for the detection of a wide range of different lesions in the cerebellopontine angle and the temporal bone in MRI of the head was demonstrated.

Arteries↗
PubMed1995

[Screening program for selection of hearing loss in newborn infants instituted by the European Community].

Early identification of hearing impairment in children poses a major problem for clinical research and development. In the last two years we determined the hearing sensitivity of 1202 newborns, small infants and children. 52.4% of the children exhibited risk factors for hearing impairment in their medical history. The majority of children was referred to our department by pediatricians (52%), who first suspected hearing impairment, 40% by parents, 3.5% by otolaryngologists, 3% by educators, and 1.5% by general practitioners. The following examinations were performed: transiently evoked otoacoustic emissions (TEOAE), impedance audiometry, auropalpebralreflex, behavioral observation audiometry, and, if necessary, auditory brain stem response (ABR) with air and bone-conducted clicks as well as frequency-following responses at 500 Hz tone burst. In 378 children TEOAE were recorded on both sides, in 151 at least on one side. These results were confirmed by the other techniques. Only three children presented false negative results of TEOAE on one side. Two of these children had a middle ear effusion and a threshold of 35 dB, one had retrocochlear hearing loss. The absence of TEOAE in both ears in 155 children as well as in one ear in 16 children was detected by ABR. Seventy-seven patients showed no response on both sides, 25 on one side, although a hearing impairment more than 25 dB could not be verified by ABR. This high number of false positive results is explained in 77 cases (76%) by a middle ear dysfunction during the recording of TEOAE, when ABR was performed following adenotomy and paracentesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

[Pulsatile tinnitus as a key symptom of glomus tumor: diagnostic value of magnetic resonance tomography].

The aim of this study was to evaluate the diagnostic value of modern imaging tools in pulsatile tinnitus, which might be apparent in a variety of different diseases. While computed tomography (CT) and digital subtraction angiography (DSA) have been the methods of choice in the diagnostic management of this symptom and its related diseases, the technical progress in the development of MRI and MRA highly recommends these techniques as additional yet sufficient imaging tools. The authors demonstrate 2 representative cases of pulsatile tinnitus (one patient with glomus tumour, one patient with jugular bulb deformity) and the adequate diagnostic procedure in terms of imaging tools. It is concluded that a routine MRI-examination might allow a diagnosis with high sensitivity and specificity. Still, digital subtraction angiography and computed tomography remain indispensable in the diagnostic management of pulsatile tinnitus.

Adult↗
PubMed1995

Long life span of tolerant T cells and the role of antigen in maintenance of peripheral tolerance.

To follow the fate of tolerant T cells in vivo we used a transgenic mouse model in which peripheral T cell tolerance was based on a non-deletional mechanism. These mice expressed two transgenes: the MHC class I molecule Kb under the keratin IV promoter on keratinocytes (2.4 KerIV-Kb) and an anti-Kb TCR identified by the anti-clonotypic antibody Désiré-1 (DES-TCR). Although these mice were tolerant to Kb skin grafts, CD8+DES+ T cells were present in their lymphoid organs in the same numbers as in Kb-reactive DES-TCR single-transgenic mice. The unresponsiveness towards Kb grafts suggested previous contact of the CD8+DES+ T cells with the Kb molecule on keratinocytes, but the evidence was indirect. The present study demonstrates enhanced levels of activation markers like CD44 and CD2 on the tolerant T cells, indicating contact with the Kb molecule. Continuous presence of antigen was required for maintenance of the tolerant state as shown by transfer of tolerant T cells into Kb-negative nu/nu BALB/c mice. Three days after cell transfer most recipients were still tolerant and accepted Kb-positive skin grafts, but 2 weeks after transfer the transferred cells had recovered their responsiveness and rejected Kb grafts. In order to see if contact with the tolerogen would eventually drive the tolerant cells into cell death, the life span of tolerant CD8+DES+ cells was measured in thymectomized DES-TCR x 2.4 KerIV-Kb double-transgenic mice. The tolerant cells were found to have a life span of at least 8 weeks, which was comparable with the life span of non-tolerant CD8+DES+ cells from DES-TCR single-transgenic mice. Thus, tolerant T cell populations can be long-lived and need continuous contact with the tolerogen to remain tolerant.

Animals↗
PubMed1995

The myelodysplastic syndromes: an analysis of prognostic factors in 226 cases from a single institution.

Two hundred and twenty-six patients were diagnosed with myelodysplastic syndrome (MDS), according to the French-American-British (FAB) criteria, over a 13-year period, and studied retrospectively in a single institution in order to study indicators which were prognostically significant. Analysis of clinical and laboratory data indicated that the FAB classification, the Bournemouth, Dusseldorf, Goasguen, Sanz and FAB Scoring Systems were all good predictors of survival. We found advancing age, haemoglobin (Hb) < or = 9 g/dl, platelet count < or = 50 x 10(9)/l, increased peripheral total white cell count (WCC) and monocytosis, increased bone marrow blasts, dysgranulopoiesis, and bone marrow fibrosis were significant adverse prognostic variables. The commonest complication and cause of death was infection; however, infective episodes were not significantly associated with low neutrophil counts (either < or = 1.5 x 10(9)/l or < or = 0.8 x 10(9)/l) and there was also no significant association between neutropenia and survival. These findings indicate that neutrophil dysfunction plays an important role in the clinical progression of patients with MDS. The effect of new therapeutic modalities, such as the haemopoietic growth factors, on reducing infective episodes may be as significant as their effect on increasing neutrophil counts.

Adult↗
PubMed1995

Smoking cessation in pregnancy: a survey of the medical and nursing directors of public antenatal clinics in Australia.

Smoking is a major cause of adverse pregnancy outcomes. However limited data are available documenting the perceptions of care providers in this area. This mail survey undertaken in 1992-1993 aimed to assess the smoking cessation practices of Australian public antenatal clinics. Questionnaires were returned by 140 (80%) of the 175 eligible hospitals, 83 (48%) medical directors and 108 (62%) nursing directors. Smoking advice was rated an essential activity at the first antenatal visit by 69% of responding directors. Nonetheless, only 12% of clinics indicated they offered relevant training and 4% reported written policies. Results also indicate senior staff may have suboptimal levels of awareness of smoking risks. Clinics used a narrow array of strategies to promote cessation. Almost one-third of directors said they advised smokers to cut down rather than stop smoking completely. There is a need for antenatal clinics to implement integrated strategies for the detection and treatment of pregnant smokers including staff training and modifications to the clinics' environment. In addition, major health promotion agencies need to develop effective smoking cessation programmes designed specifically for use in antenatal clinics and to monitor their on-going implementation.

Australia↗
PubMed1994

Levels of peripheral T cell tolerance induced by different doses of tolerogen.

Antigen-specific immunosuppression requires an understanding of the parameters that control peripheral T cell tolerance. A liver-specific inducible promoter was used to drive the expression of the major histocompatibility complex antigen Kb in transgenic mice. Minute amounts of Kb, expressed exclusively on hepatocytes, induced tolerance by partial down-regulation of the T cell receptor (TCR) on the self-reactive CD8+ cells. Contact of these tolerant T cells with high concentrations of Kb after induction led to complete down-regulation of TCR. Thus, tolerant T cells are susceptible to further tolerogenic signals and reach different levels of tolerance depending on antigen dose.

Animals↗
PubMed1994

Tolerance induction as a multi-step process.

Tolerant T cells are characterized by their partial or full resistance to activation by antigen. We investigated whether tolerant T cells were still receptive to further tolerogenic signals. T cells expressing a transgenic T cell receptor (TCR) specific for the major histocompatibility complex (MHC) class I molecule Kb were deleted in mice carrying Kb but not in mice expressing the mutant Kb-molecule Kbm1 [TCR (H-2bm1 x k) mice]. These T cells were tolerant in vivo but could be activated in vitro by the Kb antigen. This in vitro reactivity was abolished after the tolerant T cells encountered Kb-positive cells that had been intravenously injected. Furthermore, in TCR (H-2bm1 x k) mice expressing Kb only on hepatocytes, no T lymphocytes bearing the transgenic TCR could be found in the periphery, indicating that the additional contact with Kb on hepatocytes led to deletion of the tolerant T cells. These findings demonstrate that tolerance induction can be a multi-step process.

Animals↗
PubMed1994

[Differential diagnosis of benign middle ear tumors].

Adenomas of the middle ear are quite rare tumours of the ear and of recent recognition. Two cases of adenomatous neoplasms confined to the middle ear are presented. Usually these tumours are located on the promontorium or in the hypotympanon. The unique feature of the first described case is based on its origin in the epitympanic pouch of the tympanic membrane. The second case originated from the mucosa in the hypotympanon. The third case is a tumour-like lesion which was not distinguishable on clinical grounds from a jugulo-tympanic paraganglioma or a middle ear adenoma. The adenomas of the middle ear are histopathologically characterised by differentiated glandular structures within fibrous tissue and recurrences are rarely observed. Surgical removal by the endaural route gives an excellent prognosis as shown by the literature and our own clinical cases.

Adenoma↗
PubMed1993

Distinct requirements of positive and negative selection for selecting cell type and CD8 interaction.

We investigated the requirements of positive and negative selection in the thymus for CD8 interaction and the selecting cell type. Thymic epithelial cells are known to mediate positive selection, whereas thymocytes fail to do so. The reason for this failure could be either the low amount of MHC class I molecules on thymocytes or the lack of other properties required for positive selection. To address this question a CD2.Kb transgenic mouse was prepared in which the expression of the Kb gene is under control of the CD2 promoter. In these mice the thymocytes exhibited very high levels of Kb. The mice were crossed with two TCR transgenic mice expressing either the Des.TCR (anti-Kb), which is positively selected on Kk and negatively on Kb, and the 2C.TCR (anti-Ld) with positive selection on Kb and negative on Ld. Despite the high Kb expression on thymocytes in CD2.Kb x 2C.TCR mice no positive selection was observed, whereas efficient negative selection was found in CD2.Kb x Des.TCR F1 mice. Thus, although thymocytes can negatively select, even a strong increase of MHC class I expression cannot convert them into positively selecting cells. This is consistent with the notion that thymic epithelium is specialized for positive selection, but the respective difference between thymocytes and thymic epithelium is not clear. The influence of CD8 was investigated using transgenic mice expressing a Kk/A2 or a Kb/A2 hybrid gene in which the promoter, the alpha 1, alpha 2 domains were of mouse origin and the alpha 3 domain of human origin. Because the murine CD8 molecule does not efficiently bind to human HLA class I, in these mice the CD8 interaction was impaired. In Kb/A2 x 2C.TCR and Kk/A2 x Des.TCR mice no positive selection of the respective TCR was found, whereas in Kb/A2 x Des.TCR mice negative selection was still functional. Altogether, the results indicate that positive selection depends more strictly on CD8 interaction and cell type than negative selection.

Animals↗
PubMed1993

Isolation and purification of a squamous cell carcinoma of the head and neck-associated antigen identified by autologous antibody.

We have previously shown that detection of autologous antibody activity to squamous cell carcinoma of the head and neck may be augmented by dissociation of immune complexes. Western blot analysis with autologous antibody has identified a 60 kDa squamous cell carcinoma of the head and neck-associated antigen in spent media and immune complex-dissociated serum ultrafiltrate not recognized by normal human sera. Antigen-containing fractions of spent media were eluted from anion exchange columns immediately after serum albumin indicating that the antigen has an acidic pI < 4. Preparative purification of the squamous cell carcinoma antigen was accomplished by anion exchange of concentrated spent media (protein concentration 300 mg/ml) followed by lectin affinity chromatography with a Triticum vulgaris column. A single 60 kDa band was detected by silver stain and Western blot in antigen-containing fractions eluted following lectin affinity chromatography and SDS-PAGE. Final concentration of the antigen was determined to be 1 microgram/ml of protein with relative activity increased 1600 x over unfractionated spent media. We conclude that a squamous cell carcinoma of the head and neck-associated antigen, detected by autologous antibody, is an acidic 60 kDa glycoprotein.

Antibodies↗