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.     

Characterization of a reovirus isolate from a rattle snake,Crotalus viridis,with neurological dysfunction

Summary A virus isolate from the brain of a rattle snake with central nervous system (CNS) symptoms was identified as a reovirus. The isolate did not agglutinate pig erythrocytes and was not neutralized by antisera against avian reovirus S1133 and mammalian reovirus type 3. The cytopathic effect in Vero cells was characterized by formation of syncytial giant cells. Electrophoretic analysis of the genome revealed 10 segments of dsRNA. The isolate displayed characteristics distinct from avian and mammalian reoviruses.     

Age-dependent alterations of microtubule-associated enzyme activities from bovine brain (protein kinase, adenosine triphosphatase, guanosine triphosphatase)

Microtubules have been isolated from immature (3-4 weeks' old) and old (11-13 years' old) bovine brains. Quantitative studies revealed that the concentration of extractable microtubule protein per gram of wet brain decreased from 0.47 mg (immature animals) to 0.34 mg (old animals). The major components of microtubule protein (tubulin and high-molecular-weight microtubule-associated proteins) do not undergo an age-correlated change. Determination of the endogenous protein kinase activity revealed that the activity associated with "immature" calf brain microtubules was six times higher than the activity present in "old" preparations. In contrast, the stimulatory effect of cyclic AMP on protein phosphorylation in microtubules from old bovine brains exceeds nine-fold the value obtained from immature animals. After addition of casein (exogenous acceptor), the basal activities increased in both preparations without altering the age-correlated difference in the specific activity. By comparing the radioactivity pattern of sodium dodecyl sulfate polyacrylamide gels after autophosphorylation of microtubule protein with [gamma-32P]ATP, 1.5 moles of phosphate per mole of high-molecular-weight microtubule-associated protein were estimated to be incorporated in preparations from immature animals and 0.9 mole of phosphate per mole of associated protein in the experiments with "old" microtubule protein. Adenosine triphosphatase activity, associated with the high-molecular-weight microtubule-associated protein 1, was determined to be 15% reduced in preparations from old animals, compared to the activity in "young" preparations. In contrast, the guanosine triphosphatase activity increased five-fold during ageing; the higher activity of this enzyme was observed both during the initial and the steady-state phases of microtubule formation.     

Irreversible shock of rats after acute renal vein thrombosis

Summary After occlusion of the renal veins rats die quickly in progressive shock (within 4.5 h), but after ligating the renal hilum of both Kidneys they survive 27 h. To learn why renal vein occlusion is so rapidly lethal, and what substances are given off and by what method from the hemorrhagically infarcted kidneys, we studied eight groups of rats, each containing at least seven animals. The groups differed in the combination of hilar structures (renal veins, ureters, lymphatics) ligated. We compared: survival times, changes in blood pressure, blood volume, levels of plasma kinins, adenosine, and lactate, changes of blood pH, responses to Indomethacin, Trasylol^®, and plasma expanders, tubular and capillary flow rates, histopathological changes in organs and cerebral blood flow and changes in the blood coagulation system. Our results suggest that the venous stasis, anoxia, and hemorrhagic necrosis caused by bilateral venous occlusion release into renal lymphatics toxic substances which reach the systemic circulation and induce irreversible shock. We have excluded prostaglandins and adenosine as the toxic substances inducing shock but could not rule out an action of the kallikrein-kinin-system. We postulate that the striking degenerative changes occurring in the arterioles of the brain after bilateral venous occlusion may mean these vessels are especially susceptible to high levels of lactic acid and that this may explain why these animals die so quickly. Our conclusions should help not only in understanding why high levels of lactate in shock portend a poor prognosis but also help in formulating appropriate therapy for circulatory failure of renal origin and for protracted hypotension after extensive tissue injury.The studies were supported by the German Research Foundation within the SFB 90 Cardiovasculäres SystemPresented in part: Jäckh and Steinhausen, 1976; Dallenbach et al., 1978; Zimmerhackl et al., 1979We dedicate this paper to Wilhelm Doerr, Dr. med., Professor of Pathology, University of Heidelberg on the occasion of his 65th birthday (August 25th, 1979)