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S Buus

Publications and source records attributed to S Buus.

At least 109 records · Page 6Linked to original sources
PubMed1988

The T-cell accessory molecule CD4 recognizes a monomorphic determinant on isolated Ia.

The membrane protein CD4 is commonly found on mature T cells specific for antigen in association with class II major histocompatibility complex (MHC; Ia) proteins. This correlation has led to the suggestion that CD4 binds to a monomorphic region of the Ia molecule on the antigen-presenting cell (APC) and functions either by enhancing interaction between the T cell and the APC, or conversely, by transducing negative signals to the T cell. To address this hypothesis, we have made use of sublines from an unusual T hybrid that is class I MHC restricted but also CD4+. By incorporating purified MHC proteins into a planar membrane system, we show that different Ia molecules can greatly enhance the ability of a CD4+ but not a CD4- variant of this class I-restricted T hybrid to respond to isolated class I molecules. T-cell responses can be strongly augmented by the concurrent expression of CD4 on the T cell and any of four different Ia proteins on planar membranes, thus supporting the idea that CD4 binds to a monomorphic region of the Ia molecule and increases the avidity with which the T cell can interact with its target.

Animals↗
PubMed1988

Facts on the fragmentation of antigens in presenting cells, on the association of antigen fragments with MHC molecules in cell-free systems, and speculation on the cell biology of antigen processing.

The processing of a protein antigen is a multi-step event taking place in antigen-presenting cells. Processing is a prerequisite for the recognition of most antigens by T lymphocytes. The antigen is ingested by endocytosis, transported to an acid cellular compartment and subjected to proteolytic fragmentation. Some of the antigen fragments bind to MHC class II molecules and are transported to the surface of the antigen-presenting cell where the actual presentation to T lymphocytes occurs. The nature of the processed antigen, how and where it is derived and subsequently becomes associated with MHC molecules are the questions discussed in this review. To us, the entire concept of processing has appeal not only because it explains some hitherto well-established, but poorly understood, phenomena such as the fact that T lymphocytes focus their attention entirely upon antigens on other cells. It has appeal also because processing allows for a thorough scrutiny of all the proteins of a cell including both the proteins which have been taken up from the environment (mostly MHC class II-restricted) and the cell's own proteins (mostly MHC class I-restricted). Through the mechanism of processing fragments of all these proteins including "internal" fragments which are not present on the globular protein's surface are brought out on the cell surface in association with MHC molecules and displayed to the T-lymphocyte system. This allows for the identification and, if necessary, the destruction of cells which in their interior harbor abnormal proteins, be they derived from virus-encoded genes or other abnormal genes.

Antigen-Antibody Complex↗
PubMed1988

Temporal integration in normal hearing, cochlear impairment, and impairment simulated by masking.

To assess temporal integration in normal hearing, cochlear impairment, and impairment simulated by masking, absolute thresholds for tones were measured as a function of duration. Durations ranged from 500 ms down to 15 ms at 0.25 kHz, 8 ms at 1 kHz, and 2 ms at 4 and 14 kHz. An adaptive 2I, 2AFC procedure with feedback was used. On each trial, two 500-ms observation intervals, marked by lights, were presented with an interstimulus interval of 250 ms. The monaural signal was presented in the temporal center of one observation interval. The results for five normal and six impaired listeners show: (1) normal listeners' thresholds decrease by about 8 to 10 dB per decade of duration, as expected; (2) listeners with cochlear impairments generally show less temporal integration than normal listeners; and (3) listeners with impairments simulated using masking noise generally show the same amount of temporal integration as normal listeners tested in the quiet. The difference between real and simulated impairments indicates that the reduced temporal integration observed in impaired listeners probably is not due to splatter of energy to frequency regions where thresholds are low, but reflects reduced temporal integration per se.

Acoustic Stimulation↗
PubMed1987

The relation between major histocompatibility complex (MHC) restriction and the capacity of Ia to bind immunogenic peptides.

The capacity of purified I-Ad, I-Ed, I-Ak, and I-Ek to bind to protein derived peptides that have been previously reported to be T cell immunogens has been examined. For each of the 12 peptides studied strong binding to the relevant Ia restriction element was observed. All the peptides bound more than one Ia molecule; however, for 11 of 12 peptides, the dominant binding was to the restriction element, whereas in one instance the dominant binding was to a nonrestriction element. When the peptides were used to inhibit the presentation of antigen by prefixed accessory cells to T cells, an excellent correlation was found between the capacity of a peptide to inhibit the binding of an antigen to purified Ia and the capacity of the peptide to inhibit accessory cell presentation of the antigen. Thus, the binding of peptide to purified Ia is immunologically relevant, and Ia seems to be the only saturable molecule on the surface of the accessory cell involved in antigen presentation. Inhibition analysis also indicated that all peptides restricted to a particular Ia molecule competitively inhibited one another, suggesting that each Ia restriction element has a single binding site for antigen. Cross-linking of labeled peptides to Ia followed by electrophoretic analysis and autoradiography suggested that this single binding site is made up of portions of both alpha and beta chains of Ia.

Animals↗
PubMed1987

Immunological self, nonself discrimination.

The ability of immunodominant peptides derived from several antigen systems to compete with each other for T cell activation was studied. Only peptides restricted by a given transplantation antigen are mutually competitive. There is a correlation between haplotype restriction, ability to bind to the appropriate transplantation antigen, and ability to inhibit activation of other T cells restricted by the same transplantation antigen. An exception was noted in that a peptide derived from an antigen, bacteriophage lambda cI repressor, binds to the I-Ed molecule in a specific way, yet is not I-Ed-restricted. Comparison of the sequence of the repressor peptide with that of other peptides able to bind to (and be restricted by) I-Ed and a polymorphic region of the I-Ed molecule itself revealed a significant degree of homology. Thus, peptides restricted by a given class II molecule appear to be homologous to a portion of the class II molecule itself. The repressor-derived peptide is identical at several polymorphic residues at this site, and this may account for the failure of I-Ed to act as a restriction element. Comparison of antigenic peptide sequences with transplantation antigen sequences suggests a model that provides a basis for explaining self, nonself discrimination as well as alloreactivity.

Animals↗
PubMed1987

Level discrimination as a function of level for tones from 0.25 to 16 kHz.

Difference limens for level (delta L in dB = 20 log [(p + delta p)/p], where p is pressure) were measured as a function of level for tones at 0.25, 0.5, 1, 2, 4, 8, 10, 12, 14, and 16 kHz. At each frequency, test levels encompassed the range from near threshold to 95 dB SPL in steps of 10 dB or smaller. The stimulus duration was 500 ms and the interstimulus interval was 250 ms. An adaptive two-alternative forced-choice procedure with feedback was used. Results for six normal listeners show individual differences among listeners, but the general trends seen in the average data clearly are present in the individual data and show the following. First, the delta Ls at all but the highest frequencies are generally smaller at high levels than at low levels. Second, the delta Ls at equal SPLs are largely independent of frequency up to about 4 kHz, but increase with frequency above 4 kHz. Third, at 8 and 10 kHz, the delta Ls are clearly nonmonotonic functions of level, showing consistent deterioration in the mid-level delta Ls relative to the low- and high-level delta Ls. The present data are discussed qualitatively in terms of current models of level discrimination.

Acoustic Stimulation↗
PubMed1986

Isolation and characterization of antigen-Ia complexes involved in T cell recognition.

Using equilibrium dialysis, it has been previously demonstrated that immunogenic peptides bind specifically to the Ia molecules serving as restriction elements in the immune response to these antigens. Using gel filtration to study the formation of ovalbumin (OVA) peptide-I-Ad complexes, it is herein demonstrated that the complexes, once formed, are very stable (kd approximately equal to 3 X 10(-6) s-1), but the rate of complex formation is very slow (ka approximately 1 M-1 s-1 explaining the overall low equilibrium constant of approximately 2 X 10(-6) M. Treating the complexes with glutaraldehyde revealed that the ovalbumin peptide was cross-linked solely to the alpha chain of I-Ad. Planar membranes containing I-Ad-OVA complexes stimulated a T cell response with 2 X 10(4) less antigen than required when uncomplexed antigen was used, thus demonstrating the biologic importance of these complexes in antigen recognition.

Antigens↗
PubMed1986

Interaction between a "processed" ovalbumin peptide and Ia molecules.

The binding of 125I-labeled immunogenic peptides to purified Ia molecules in detergent solution was examined by equilibrium dialysis. We used the chicken ovalbumin peptide ovalbumin-(323-339)-Tyr, which is immunogenic in the BALB/c mouse and restricted to I-Ad. 125I-labeled ovalbumin-(323-339)-Tyr was shown to bind to I-Ad but not to I-Ed, I-Ek, or I-Ak. This binding was inhibited by unlabeled ovalbumin-(323-339) but not by ovalbumin-(329-339), which is the longest N-terminally truncated peptide that fails to stimulate any of the I-Ad-restricted hybridomas that have been raised to ovalbumin-(323-339)-Tyr. As a further specificity control, we also used the chicken egg lysozyme peptide Tyr-(46-61), which has recently been studied by similar methods [Babbitt, B. P., Allen, P. M., Matsueda, G., Haber, E. & Unanue, E. R. (1985) Nature (London) 317, 359-361]. We have confirmed that it bound to I-Ak but not to I-Ek, I-Ad, or I-Ed. Thus, a specific interaction between Ia and antigen that correlates with the major histocompatibility complex restriction was demonstrated, strongly arguing in favor of a determinant selection hypothesis for such restriction.

Animals↗
PubMed1986

Large, but not small, antigens require time- and temperature-dependent processing in accessory cells before they can be recognized by T cells.

We have studied if antigens of different size and structure all require processing in antigen-presenting cells of guinea-pigs before they can be recognized by T cells. The method of mild paraformaldehyde fixation was used to stop antigen-processing in the antigen-presenting cells. As a measure of antigen presentation we used the proliferative response of appropriately primed T cells during a co-culture with the paraformaldehyde-fixed and antigen-exposed presenting cells. We demonstrate that the large synthetic polypeptide antigen, dinitrophenyl-poly-L-lysine, requires processing. After an initial time-lag of 30 min this antigen is fully processed within 2 to 4 of culture at 37 degrees C. In contrast, the immunogenic heptapeptide, angiotensin III, can be presented by pre-fixed accessory cells, viz. without any prior processing. Antigen processing was found to be temperature-dependent and consequently energy-requiring. Processing is strongly inhibited by the lysosomotrophic drug, chloroquine, suggesting a lysosomal involvement in antigen processing. The existence of a minor, non-lysosomal pathway is suggested, since small amounts of antigen were processed even at 10 degrees C, at which temperature no transport to and from the lysosomes can occur.

Angiotensin III↗
PubMed1986

Decision rules in detection of simple and complex tones.

Detection of simple and complex tones in the presence of a 64-dB SPL uniformly masking noise was examined in two experiments. In both experiments, the signals were either pure tones (220, 1100, or 3850 Hz) or an 18-tone complex consisting of equally intense components between 110 and 7260 Hz. In experiment 1, psychometric functions were obtained for detection in a 2I, 2AFC task. Results for eight normal listeners show that the psychometric functions are parallel for simple and complex tones. As expected, the masked thresholds for the pure tones are 43-44 dB SPL independent of frequency; the masked threshold for the complex tone is about 37 dB SPL per tone. These results indicate that the simultaneous presence of signal energy in many auditory channels aids detection. In experiment 2, psychometric functions were obtained with all four signals presented in random order within a block of trials. Results for four normal listeners show that the psychometric functions are parallel to one another and to those obtained in experiment 1. The thresholds are elevated to about 46 dB for the pure tones and to 40.5 dB for the complex tone. These results are nearly, but not quite, consistent with a multiband energy-detector model using an optimum decision rule; it appears that listeners may only make an unweighted sum of decision variables across an optimum selection of channels.

Acoustic Stimulation↗
PubMed1986

A group-specific inhibitor of lysosomal cysteine proteinases selectively inhibits both proteolytic degradation and presentation of the antigen dinitrophenyl-poly-L-lysine by guinea pig accessory cells to T cells.

A limited intralysosomal proteolytic degradation is probably a key event in the accessory cell processing of large protein antigens before their presentation to T cells. With the aid of highly specific inhibitors of proteinases, we have examined the role of proteolysis in the presentation of antigens by guinea pig accessory cells. The proteinase inhibitor benzyloxycarbonyl-phenylalanylalanine-diazomethyl-ketone, which selectively inhibits cysteine proteinases, was used to block this set of enzymes in cultured cells. We demonstrate that the selective inhibition of the cysteine proteinases of antigen-presenting cells causes a profound inhibition of both the proteolytic degradation and the presentation of the synthetic antigen dinitrophenyl-poly-L-lysine. In contrast, the presentation of another synthetic antigen, the copolymer of L-glutamic acid and L-alanine, was enhanced by the same inhibitor. Another inhibitor, pepstatin A, which selectively blocks aspartic proteinases, did not block the presentation of dinitrophenyl-poly-L-lysine. The results identify cysteine proteinases, probably lysosomal, as one of the groups of enzymes involved in antigen processing.

Animals↗
PubMed1986

Oligopeptide antigens of the angiotensin lineage compete for presentation by paraformaldehyde-treated accessory cells to T cells.

The heptapeptide antigen angiotensin III can be presented to guinea pig T cells by paraformaldehyde-treated antigen-presenting cells, which are incapable of processing antigens and presumably cannot even ingest them. We demonstrate here that the decapeptide angiotensin I can outcompete angiotensin III for presentation by paraformaldehyde-treated antigen-presenting cells. It seems likely that the competition is for a site on the surface of the presenting cell. This extends earlier findings of competition for presentation between antigens. We also demonstrate that the antigens of the angiotensin series are highly susceptible to proteolytic destruction in cultures containing prefixed accessory cells. The proteases responsible for the destruction of these peptides are apparently located in the plasma membrane of accessory cells. These enzymes represent a methodologic problem in studies of competition between antigens for presentation; but since they presumably are active also in untreated cells, they may play a physiologic role in the normal immune response.

Angiotensin II↗
PubMed1986

Food intake and nutritional status after gastrectomy.

Food intake and nutritional status was studied in 67 patients, who had had a gastrectomy 2-30 years earlier, and in a randomly selected, matched group of healthy persons. The gastrectomized patients weighed less than the control persons (women 56.4 +/- 9.5 vs 61.4 +/- 6.9 kg; P less than 0.05; men 72.4 +/- 12.5 vs 77.7 +/- 9.2 kg; P less than 0.02). Compared to the controls the gastrectomized women had a significantly lower fat-free mass (37.8 +/- 4.1 vs 40.7 +/- 4.3 kg; P less than 0.02), whereas the gastrectomized men had a lower fat mass (17.0 +/- 7.8 vs 21.2 +/- 6.0 kg; P less than 0.01). The serum concentration of alkaline phosphatase was raised and the concentration of calcium, phosphorus and 25-hydroxycholecalciferol reduced in the gastrectomized group. None of these results could be explained from the nutritional study as both the intake of energy and protein and the intake of calcium and vitamin D was about the same in the operated and the healthy controls. The serum concentration of 25-hydroxycholecalciferol was significantly higher in the gastrectomized persons taking supplementary vitamin D (21.9 +/- 12.0 vs 11.7 +/- 6.5 ng/ml). A daily supplement of 10 micrograms of vitamin D secured normal serum values. As the serum level of 25-hydroxycholecalciferol is correlated to the degree of osteomalacia, all gastrectomized patients should have at least 10 micrograms vitamin D as a supplement once a day.

Alkaline Phosphatase↗
PubMed1985

Release from masking caused by envelope fluctuations.

This paper examines how short-term energy fluctuations in a masker affect the thresholds for tones at frequencies above those of the masker. Two equally intense tones at 1060 and 1075 Hz produce up to 25 dB less masking than does a 1075-Hz tone set to the overall level of the two-tone complex. At wider frequency separations, two-tone complexes also produce less masking than the pure tone. These results indicate that envelope fluctuations in a masker, whose spectrum is confined to a single critical band, may result in release from masking. The release from masking probably is related to the comodulation masking release reported by Hall et al. [J. Acoust. Soc. Am. 76, 50-56 (1984b)] for modulated-noise maskers with bandwidths greater than one critical band. Further measurements with maskers, whose intensity level in the critical band around 1 kHz was 90 dB SPL, show similar masking by a pure tone and a 625- to 1075-Hz bandpass noise, but less masking by narrow-band noises. These results are inconsistent with a simple frequency selective energy-detector model and indicate that the auditory system can use periods of low masker energy as brief as a few ms to enhance detection of a tone. The results also imply that the upward spread of excitation is best represented by masking patterns for noises with bandwidths of several critical bands.

Acoustic Stimulation↗
PubMed1985

Postoperative myocardial performance during glucose-induced hypophosphatemia.

Long-lasting hypophosphatemia was previously found to diminish myocardial performance. The present study aimed to elucidate if postoperative glucose-induced hypophosphatemia is of importance for myocardial performance. Sixteen patients undergoing elective colonic or rectal surgery were given 100 g glucose intravenously (as 20% glucose solution) on the first and second postoperative days. The infusion rate was 0.3 g/kg/hour. On both days the glucose infusion caused significant fall in P-phosphate (0.94 to 0.67 and 0.71 to 0.47 mmol/l, respectively). No changes were seen in P-calcium, P-potassium or P-sodium. Measurements of stroke volume and frequency, central venous pressure and mean arterial pressure were made immediately before and after the glucose infusions. Stroke volume and cardiac output were unaffected during the infusions, and also from the first to the second postoperative day. As the preload (central venous pressure) and the afterload (arterial pressure) similarly were unchanged by the glucose infusion, glucose-induced hypophosphatemia following elective surgery was judged to lack importance for the myocardial performance.

Aged↗