A neural cocktail-party processor

Sensory segmentation is an outstanding unsolved problem of theoretical, practical and technical importance. The basic idea of a solution is described in the form of a model. The response of neurons within the sensory field is temporally unstable. Segmentation is expressed by synchronization within segments and desynchronization between segments. Correlations are generated by an autonomous pattern formation process. Neuronal coupling is the result both of peripheral evidence (similarity of local quality) and of central evidence (common membership in a stored pattern). The model is consistent with known anatomy and physiology. However, a new physiological function, synaptic modulation, has to be postulated. The present paper restricts explicit treatment to the peripheral evidence represented by amplitude modulations globally present in all components of a sound spectrum. Generalization to arbitrary sensory qualities will be the subject of a later paper. The model is an application and illustration of the Correlation Theory of brain function.This work has been supported by Grant I/37-821 of the Stiftung Volkswagenwerk.     

Antigenic reactivity: Molecular delineation of monohaptenic anaphylactogens

Anaphylactogenic, monohaptenic conjugates carrying a 2,4-dinitro-5-carboxyphenyl substituent as haptenic group and either one of two types of auxiliary groups essential for their anaphylactogenicity were studied. The “hydrocarbon auxiliary groups” require the presence of a hydrocarbon structure such as aliphatic chains of discrete length or planar rings such as provided by phenyl- or nicotinoyl residues and become particularly effective in conjunction with a carboxylate group. The benzylpenicilloyl group is an effective auxiliary structure, but the thiazolidine ring as such is not. It appears that the distance between haptenic and hydrocarbon auxiliary groups can be quite large. The “carbohydrate auxiliary group” becomes effective via a different mechanism. It requires disaccharide residues or two closely connected monosaccharides. Single monosaccharides are ineffective. A concept of interest with regard to drug allergy is the possibility that attachment of a single haptenic molecule to a glycoprotein constitutes an anaphylactogen.     

Immunosuppression as a high-risk factor in the development of condyloma acuminatum and squamous neoplasia of the cervix

The iatrogenic immunosuppression in renal transplant recipients has been associated with an increased incidence of malignancy in these patients. Among 132 female transplant recipients at risk for the development of squamous lesions of the cervix, 11 (8.5%) developed cervical condylomas. Six (4.5%) of the 11 patients developed cervical neoplasia. The average age of the patients at the time of initial diagnosis was 32.2 years. The lag time from transplantation to the diagnosis of the condyloma was 22.4 months, and the lag time from transplantation to the diagnosis of cervical neoplasia was 38.0 months. The increased incidence of condylomas as well as of intraepithelial neoplasia of the cervix in this group of patients with an established higher risk of malignancy supports the hypothesis that condylomas may represent a precursor lesion of cervical cancer. Immunosuppression should be included among the high-risk factors in the development of cervical neoplasia.     

Proton-translocating ATPase and lysosomal cystine transport

A proton-translocating ATPase was identified in highly purified lysosomes from Epstein-Barr virus-transformed human lymphoblasts. Activity of this ATPase caused acidification of highly purified, fluorescein isothiocyanate dextran-loaded lysosomes and correlated with the ATP-dependent efflux of lysosomal cystine. The lysosomal ATPase was distinct from mitochondrial F1-ATPase in its responses to a variety of inhibitors. Although ATP-dependent lysosomal cystine efflux is not demonstrable in cultured lymphoblasts from individuals with nephropathic cystinosis, ATPase activity and acidification in lysosomes from these cells is comparable to that in noncystinotic lysosomes. ATPase activity in lymphoblasts from normal individuals was 543 +/- 79 nmol/mg/min while in lymphoblasts from cystinotic individuals this activity was 541 +/- 25 nmol/mg/min. ATP-dependent acidification of lysosomes from normals was -0.5 +/- 0.1 pH units compared to -0.5 +/- 0.1 pH units in cystinotic lysosomes. Activity of the lysosomal proton-translocating ATPase is a necessary, but not sufficient, condition for lysosomal cystine efflux.     

Mechanism of complement-induced stimulation of prostacyclin production by isolated rabbit peritoneum

The interaction between the complement system and prostaglandin synthesis has not thoroughly been explored, although both mediators are known to be involved in inflammatory reactions and endotoxic shock. When rabbit peritoneum, a rich source of prostacyclin forming activity was incubated in serum in which the complement system was activated (CVF, LPS, zymosan), the tissue produced significantly more PGI2, when compared with appropriate controls, indicating that by activation of the complement, factors were generated that stimulated PGI2 biosynthesis. Further results indicated that tryptic cleavage products of complement factor C3 and C5 also led to the appearance of PGI2 releasing principles with a molecular weight of about 7000-11000. The stimulation of PGI2 biosynthesis was explained by enhanced release of AA, and not due to increased activity of cyclo-oxygenase or PGI2 synthetase. Our results suggest that complement-derived products may promote the supply of prostaglandins at the site of inflammation.     

Growth and the inducibility of mycelium formation in Candida albicans: a single-cell analysis using a perfusion chamber

In Candida albicans, cells actively growing in the budding form cannot be immediately induced to form a mycelium until they enter stationary phase. However, if exponential phase cells are starved for a minimum of 10 to 20 min, they are inducible. Using a video-monitored perfusion chamber, we found that starved cells were able to form mycelia regardless of their position in the budding cycle. When starved exponential cells were released into fresh nutrient medium at high temperature and pH, conditions conducive to mycelium formation, unbudded cells evaginated after an average lag period of 75 min and then grew exclusively in the mycelial form. Depending upon the volume, or maturity, of the bud, budded cells entered two different avenues of outgrowth leading to mycelium formation. If the daughter bud was small, growth resumed by apical elongation of the bud, leading to a 'shmoo' shape which tapered into an apical mycelium. If the daughter bud was large, the cell underwent a sequence of evaginations: first, the mother cell evaginated after an average period of 75 min; then the daughter bud evaginated 40 min later. Both evaginations then grew in the mycelial form. In this latter sequence, the evagination on the mother cell was positioned non-randomly, occurring in the majority of cells adjacent to the bud. All buds undergoing evagination contained a nucleus, but roughly 20% of buds undergoing apical elongation did not.     

Homogeneity of the HLA-Linked SB2 and SB3 specificities demonstrated by cloned alloreactive T cells

The HLA-linked "SB" antigens comprise a new segregant series of B-cell alloantigens mapping between HLA-DR and glyoxylase. They can be detected by secondary proliferative responses of lymphocytes primed against HLA-A, B, C, DR, MB- and MT-compatible stimulators. To asses genetic complexity of the SB-gene region, alloreactive cloned T-cell lines were derived from four reagents detecting specificities designated SB2 and SB3. In two families, products detected by seven different clones segregated with the HLA haplotypes bearing the SB2 or SB3 specificities as recognized by the uncloned reagents. There were no indications that the cloned cells differed from the oligoclonal reagents in their fine specificity. In contrast to previous results with an SB4-associated specificity, in population studies of 25 SB2-positive and 23 SB3-positive donors, no evidence could be found for subtypes of either specificity. Thus, even at the level of recognition by cloned T-cells, both SB2 and SB3 appear to be remarkably homogeneous in the population.     

Effects of temperature changes on thymidine kinase in heat- and cold-sensitive cell-cycle mutants and ‘wild-type’ murine P-815 cells

Two heat-sensitive (arrested in G1 at 39.5°C) and two cold-sensitive (arrested in G1 at 33°C) clonal cell-cycle mutants that had been isolated from the same clone (K 21), of the murine mastocytoma P-815 cell line, were tested for thymidine kinase (EC 2.7.1.21) activity. After shift of mutant cells to the nonpermissive temperature, thymidine kinase activity decreased, and minimal levels (i.e., less than 3% of those observed for ‘wild-type’ K 21 cells at the respective temperature) were attained within 16 h in heat-sensitive and after 3–4 days in cold-sensitive mutants, which is in good agreement with kinetics of accumulation of heat-sensitive and cold-sensitive cells in G1 phase. After return of arrested mutant cells to the permissive temperature, thymidine kinase of heat-sensitive cells increased rapidly and in parallel with entry of cells into the S phase. In cultures of cold-sensitive cells, however, initiation of DNA synthesis preceded the increase of thymidine kinase activity by approx. one cell-cycle time. Thymidine kinase activities in revertants of the heat-sensitive and cold-sensitive mutants were similar to those of ‘wild-type’ cells. In ‘wild-type’ K 21 cells incubated at 39.5°C, thymidine kinase activity was approx. 30% of that at 33°C. This difference is attributable, at least in part, to a higher rate of inactivation of the enzyme at 39.5°C, as determined in cultures incubated with cycloheximide. The rapid increase of thymidine kinase activity that occurred after shift of K 21 cells and of arrested heat-sensitive mutant cells from 39.5°C to 33°C was inhibited by actinomycin D and cycloheximide.