Inharmonicity detection

Detection of mistuned partials in otherwise harmonic complex tones was investigated in naïve subjects of three different age groups. Signals were presented at constant sensation level to compensate for differences in hearing sensitivity and to specifically examine age-related changes in inharmonicity perception. Performance was measured under two conditions, monaural signal presentation and dichotic signal-noise presentation, with the latter aiming at the influence of contralateral distractor sounds. Stimuli were complex tones with ten harmonics and 125-Hz fundamental frequency. Mistuning detection was measured for the first, second, fourth, and eighth harmonic. In a three-interval, three-alternative forced-choice procedure, subjects were required to distinguish a complex tone containing one mistuned partial from two reference tones, with all partials at their harmonic frequencies. Thresholds were measured as the amount of frequency shift necessary for the mistuning to be detected. Performance deteriorated moderately with age for the two higher partials tested, but not for the lower ones. Thresholds for dichotic signal/noise presentation did not differ significantly from monaural ones in any of the age groups. Results are discussed in relation to hypotheses of harmonicity perception in auditory scene analysis and with respect to the investigation of patients suffering form respective deficits due to acquired brain lesions.     

Osteochondral grafts in growing rabbits

Summary In 60-day (group A) and 90-day (group B) old rabbits a standardized osteochondral graft was taken from the distal articular surface of the femur and replanted immediately. Five animals in each group were observed at 9 different times between 3 days and 6 months. On histological and autoradiographic (³⁵S-sulphate) examination the following were found: In group A there was no ³⁵S uptake in the deep layers of the articular cartilage between 3 days and 1 week; in most cases there was normal articular cartilage in the transplants at 2 weeks to 6 months. In group B later changes (3 weeks—6 months), affecting the greater part of the articular cartilage, were observed. These changes appeared to be irreversible and were found in about 1/3 of the cases. The other 2/3 showed completely normal articular cartilage.Fluorescence-microscopic (after tetracycline administration), microradiographic and microangiographic (Indian ink) studies revealed the following: Revascularization of the subchondral bone took place after 3–5 days. The ossification process in the subchondral area was restored within 5–7 days. The osseous part of the transplants healed by primary bone union within 1–2 weeks. The revascularization took place more rapidly in group A.At the longest observation times (8 weeks and 6 months) in both groups slight flattening of the transplant area was seen, probably as a result of slightly retarded growth of the bone within the transplant.Supported by grants from the Swedish Medical Research Council, Project No. 17 X-138-08 A.     

The subchondral bone plate of the femoral head in adult rabbits

Summary The mineralized structures and spontaneous remodelling of the subcondral bone-plate in the femoral head of adult rabbits of different ages were studied by microradiography and fluorescence microscopy after administration of Tetracycline between 8 months and 2 days before death. In animals over 1 year of age the subchondral bone-plate was constructed of evenly mineralized osteones, located mainly in the immediate vicinity of the calcified articular cartilage and lamellar bone bordering on the medullary cavity. In some small areas lamellar bone was the only bone tissue separating the medullary cavity from the calcified articular cartilage. In adult animals between 8 and 10 months of age the subchondral boneplate was absent in minor areas, chiefly in the lateral parts of the femoral head. In the fluorescence microscopic study in animals older than 1 year (a) the osteones in the subchondral bone showed a very low labelling frequency, (b) fluorescence was observed mainly on the lamellar bone surfaces bordering on the medullary cavity and (c) the labelling in the cortical part of the subchondral bone was still present up to 8 months after administration of the Tetracycline. The cancellous bone of the epiphysis showed a low labelling frequency which was of the same order as that in the lamellar surfaces belonging morphologically to the subchondral bone plate.From these observations it was concluded that (1) the cortical part of the subchondral bone-plate in rabbits over 1 year of age undergoes a low degree of spontaneous remodelling and (2) the cancellous bone of the epiphysis and the lamellar bone belonging morphologically to the subchondral bone-plate undergo low but similarly spontaneous remodelling. Duplicate fluorescence of the tidemark observed in a number of animals was considered to indicate that the mineralization of the articular cartilage with increasing age slowly progresses towards the articular surface.     

Interaction of B7RP-1 with ICOS Negatively Regulates Antigen Presentation by B Cells

Stimulation of T cells through the T cell receptor is insufficient for optimal T cell activation. A second activation signal is necessary, being usually provided by the costimulatory molecule CD28. Recently, additional costimulatory pathways have been identified, including inducible costimulator (ICOS) and its ligand B7RP-1. We have examined the role of the B7RP-1/ICOS costimulatory pathway on antigen presentation by B cells, using the I-A^k and I-E^k-positive CH27 B cell line and several different T cell lines. We found that CH27 expressed B7RP-1 and PD-L1 whereas the T cell lines expressed ICOS and PD-1. In the presence of HEL, the T cell hybridomas C10 and 3A9 released IL-2, which is indicative of antigen-specific T cell activation by the CH27 cells. Unexpectedly, blocking antibodies for B7RP-1 and ICOS enhanced the IL-2 response in both T cells. As expected, an increase in the production of IL-2 was seen when blocking antibodies for PD-1 were used. Blocking with antibodies for I-A^k, CD28, B7.1, and B7.2 lead to a decrease in IL-2 production. Additionally we tested a Th1 and a Th2 T cell clone. Blockade of B7RP-1/ICOS lead to an increased IFN- response in Th1 cells (A.E7) and an increased IL-4 response in Th2 cells (D10.G4.1). Intracellular staining also showed an increase in cytokine production when the B7RP-1/ICOS pathway was blocked. In conclusion, the B7RP-1/ICOS pathway is negatively regulating T cell activation by B cells and may play a role similar to that of the PD-L1/PD-1 pathway.     

Effects of isolated and combined exposures to whole-body vibration and noise on auditory-event related brain potentials and psychophysical assessment

Summary Auditory event-related brain potentials (ERP) in response to two different tone stimuli (1.1 kHz or 1 kHz, 80 dB, 50 ms; given by headphones at a regular interstimulus interval of 5 s with a probability distribution of 70:30) were recorded from 12 healthy male subjects (Ss) during four different conditions with two repetitions: A - 60 dBA white noise (wN), no wholebody vibration (WBV); B - 60 dBA wN plus sinusoidal WBV in the a_z-direction with a frequency of 2.01 Hz and acceleration of 2 m ·s^–2 root mean square; C - 80 dBA wN, no WBV; D - 80 dBA wN plus WBV. Each condition consisted of two runs of about 11 min interrupted by a break of 4 min. During the break with continuing exposure, but without auditory stimuli, Ss judged the difficulty of the tone-detection task and intensity of noise by means of cross-modality matching (CMM). Vibration-synchronous activity in the electrocardiogram was eliminated by a subtraction-technique. Noise caused an attenuation of the N1 and P2 amplitudes and prolongation of P3 latencies. The WBV did not cause systematic ERP effects. Condition B was associated with higher N1 and smaller P3 amplitudes. The factor condition had a significant effect on the peak latencies of P3 to target stimuli and the task difficulty judged by CMM. Both effects exhibited significant linear increases in the sequence of conditions A, B, C, D. For the evaluation of exposure conditions at work, it can be suggested that noise has a strong systematic effect which can be enhanced by WBV. The P3 latency is considered as an advantageous measure for the detection of objective effects of physical environmental factors, correlating with relevant subjective responses.     

Histomorphometry of bone marrow biopsies in primary osteomyelofibrosis/-sclerosis (agnogenic myeloid metaplasia) - correlations between clinical and morphological features

Summary Histomorphometry was performed on representative trephine biopsies of the bone marrow on admission of 50 patients (21 male, 29 female-age 67 years) with so-called primary osteomyelofibrosis/-sclerosis (OMF) not preceded by any other subtype of chronic myeloproliferative disorders. This study was firstly aimed at testing correlations between histological features (amount of haematopoiesis, cytological aspects of mega-karyocytes, density of reticulin and collagen fibres and degree of osteosclerosis) and laboratory data, as well as spleen size and duration of relevant prediagnostic symptoms. Secondly, we concentrated on a discrimination of OMF patients into two sub-groups according to bone marrow morphology and clinical variables. Statistical evaluation of histomorphometric variables and haematological findings disclosed that there was a progressive fibro-osteosclerotic process in the evolution of disease features. Increase in medullary fibrosis was significantly paralleled by an abnormal or pleomorphic megakaryopoiesis in the bone marrow: there was an increase in irregularity of perimeters for megakaryocytes and naked nuclei combined with smaller sizes of these elements including the nuclei. Additionally, there was a greater number of pycnotic bare nuclei. A number of morphometric features (density of fibres, degree of osteosclerosis, amount of haematopoiesis) were associated with corresponding clinical data (spleen size, length of preclinical history). By consideration of a set of basic histomorphometric variables our co-hort of 50 patients could be divided into an early hyperplastic subtype with no or minimal medullary reticulin and another group with conspicuous fibrotic and osteosclerotic alterations of the bone marrow. It was noticeable that we found no significant correlation between amount of haematopoiesis or marrow cellularity with splenomegaly. This result suggests that splenic haematopoiesis (myeloid metaplasia) may represent an autonomous or neoplastic process and not only compensation for a failing fibro-osteosclerotic bone marrow.Supported by a grant from the Deutsche Forschungsgemeinschaft (DFG-Th 390/1-1)