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Biomedical subjects

H Kohler

Publications and source records attributed to H Kohler.

At least 109 records · Page 6Linked to original sources
PubMed1984

Monoclonal idiotope vaccine against Streptococcus pneumoniae infection.

A monoclonal anti-idiotope antibody coupled to a carrier protein was used to immunize BALB/c mice against a lethal Streptococcus pneumoniae infection. Vaccinated mice developed a high titer of antibody to phosphorylcholine, which is known to protect against infection with Streptococcus pneumoniae. Measurement of the median lethal dose of the bacteria indicated that anti-idiotope immunization significantly increased the resistance of BALB/c mice to the bacterial challenge. Antibody to an idiotope can thus be used as an antigen substitute for the induction of protective immunity.

Animals↗
PubMed1984

Pseudo-catalytic degradation of hydrogen peroxide in the lactoperoxidase/H2O2/iodide system.

Non-stoichiometric (excessive) consumption of hydrogen peroxide (H2O2), which was observed in various lactoperoxidase-catalysed reactions, was tested in the lactoperoxidase/H2O2/iodide system. In preliminary experiments the suitability of the system was tested with special regard to the triiodide (I-3) absorption and the I2/I-3 equilibrium. Triiodide equilibrium concentrations evaluated theoretically and experimentally were compared after adding a known amount of iodine (I2) to solutions containing variable I- concentrations. A close fit of the two methods was only obtained if experiments were carried out in pure aqueous or 0.001 M H2SO4 medium. The presence of various anions, e.g. OH- and Cl-, led to a measurable decrease in I-3 and I2 equilibrium concentrations. These ions are able to displace competitively I- in forming association products with I+ and I2. When I+ and I2 were generated enzymatically by lactoperoxidase and hydrogen peroxide, additional interactions with H2O2 were observed. Depending on the enzyme and iodide concentrations, variable amounts of H2O2 disappeared nonproductively. Due to its ambivalent redox reactivity, part of the H2O2 is not reduced to H2O in the enzyme-catalysed generation of iodine, but undergoes oxidation to O2 by an oxidized iodine compound. This suggests a pseudo-catalytic side reaction which can competitively interfere with the I2/I-3 generation or (and) the iodination reaction.

Catalysis↗
PubMed1984

Invertebrate recognition protein cross-reacts with an immunoglobulin idiotype.

To estimate the minimal structural requirements for cross-reaction of idiotypic determinants, we determined the capacity of monoclonal antibodies specific for the idiotype of the phosphorylcholine (PC)-binding myeloma protein TEPC-15 for cross-reactivities with the PC-binding, acute-phase protein C-reactive protein (CRP) and the hemagglutinin from the horseshoe crab Limulus polyphemus (limulin), which binds sialic acid and PC. Certain monoclonal antibodies (MAb) to the TEPC-15 idiotype showed strong cross-reactions with CRP and limulin when tested by enzyme-linked immunoadsorbent assays. The specificity of the cross-reactivities was confirmed by testing the binding of the reactive anti-TEPC-15 MAb to both CRP and limulin in the presence of p-nitrophenylphosphorylcholine (pNPPC), N-acetylneuraminic acid, and bovine submaxillary mucin. The binding of the MAb to both CRP and limulin was strongly decreased by pNPPC, partially decreased by free PC, and not affected by N-acetylneuraminic acid or bovine submaxillary mucin. Neither CRP nor limulin showed significant overall sequence homology to vertebrate immunoglobulins. However, CRP, limulin, and TEPC-15 variable region heavy chain (VH) shared short stretches of homology (8-10 amino acids) that mapped to a stretch comprised of the second complementarity determining region and third framework region of the TEPC-15 VH. These results might reflect either evolutionary convergence forced upon molecules of diverse evolutionary histories because of steric requirements of binding the same ligand, or a conservation of primitive combining site gene segments in evolution.

Animals↗
PubMed1984

Regulatory idiotopes. Induction of idiotype-recognizing helper T cells by free light and heavy chains.

Previously, we have demonstrated the induction of T helper cells that recognize idiotype by antigen (19), idiotype (20), and antiidiotype (12). The T cell population has been characterized and found to recognize both the T15 and M167 myeloma proteins, which share PC binding specificity but differ in idiotypic specificities. In the present work, we used isolated heavy and light chains of T15 and M167 to generate T helper cells, and examined the response to trinitrophenyl (TNP)-T15 and TNP-M167. We found that the heavy chains induced a dose-dependent response to TNP-T15 and TNP-M167, while the light chain priming was ineffective. When isolated chains of a monoclonal anti-T15 antibody (F6-3) were used to induce idiotype-recognizing T cells, only the F6-3 light chains generated T cell help for TNP-T15 and TNP-M167. Evidently, the idiotypic determinant that is recognized by the T cells is not dependent upon the conformation of combined heavy and light chains. These data show that the Th2 helper cells for the T15/M167 idiotopes are induced by free heavy chains of T15 and M167; the Th1 T cells that interact with the Th2 population, of T15 and M167; the Th1 T cells that interact with the Th2 population, however, can be triggered by free light chains of an antiidiotypic hybridoma antibody. These provocative findings suggest a new model for the T helper cell network.

Animals↗
PubMed1984

Depletion and reaccumulation of follicular thyroglobulin (TG) in guinea-pig thyroid gland after short- and long-term administration of thyrotropin (TSH).

The relationships among the content and composition of soluble iodoproteins in thyroid gland, the serum Tg concentration and the morphological structure of gland were investigated in guinea-pigs during short-term and long-term TSH administration (2 I.U. per day for 1 to 28 days). A significant decrease in the content of Tg in the gland (from 6.50 mg to 1.32 mg/100 mg tissue), disappearance of 12 S iodoprotein, hypertrophy and hyperplasia of the follicular cells were observed in guinea-pigs treated with TSH up to 7 days. Later on, after depletion of follicular colloid, reaccumulation of colloid in the preexisting and newformed follicles (a marked increase of Tg and 12 S protein) and partial involution of the structural changes occurred. The serum Tg concentration increased during the whole period of TSH treatment (mean values from 100 to 500 micrograms/l). A marked positive correlation between serum Tg concentration and thyroid weight was found. Serum T3 and T4 concentrations increased transiently with maximal values on the 1st day (T3, from 0.86 to 3.26 nmol/l, T4, from 44 to 138 nmol/l) and decreased thereafter. The results imply that different regulatory mechanisms exist which control thyroid hormone secretion and transfer of Tg from the gland into blood circulation. The serum Tg level is directly dependent on the total bulk of thyroid tissue, but is considerably less dependent on the structure of the gland. The reaccumulation of colloid (Tg) in thyroid follicles of guinea-pigs treated with TSH is a result of the reduction of the stimulatory effect of TSH on the process of Tg degradation during chronic hormone application. Several different factors may be responsible for the appearance of refractoriness or desensitization of the thyroid to prolonged exogenous TSH stimulation.

Animals↗
PubMed1984

T-cell helper circuits.

T helper cells specific for trinitrophenylated PC-binding myeloma and hybridoma antibodies are induced by priming with PC antigen, idiotype or anti-idiotypic antibody. These T helper cells are specific for a shared idiotope present on T15 and M167. Priming with the isolated heavy chains of T15 or M167, or the light chain of anti-T15 hybridoma antibody is equally effective in generating T helper cells. Evidently, the idiotope that is recognized by T cells is not dependent upon the conformation of the 7s Ig molecule. Collectively, these and other findings indicate the existence of a TH1-TH2-B cellular circuit which is based on the recognition of idiotopic determinants on T cell receptors. The implications of these findings in terms of network theory are explored.

Animals↗
PubMed1983

Idiotype-recognizing T helper cells that are not idiotype specific.

In this study T helper cells that recognize idiotypes as carriers for a hapten-specific B cell response were analyzed under limiting dilution conditions. T helper cells, induced by phosphorylcholine-hemocyanin (PC-Hy) priming, recognize trinitrophenylated TEPC-15 and MOPC-167 (TNP-T15, TNP-167) equally well. Limiting dilution analysis indicates identical frequencies of helper cells for TNP-T15 and TNP-167. Double immunization protocols using TNP-T15 and TNP-167 fail to demonstrate additive effects. Inhibition of carrier recognition in vitro using free hapten, PC, and unconjugated T15 or M167 indicates identical specificities of helper cells for T15 and M167. Collectively, these results provide strong evidence that PC-Hy priming induces only one population of idiotype-recognizing helper cells that are unable to distinguish between the T15 and the M167 idiotopes. The helper cell induction circuit was further analyzed. PC-Hy priming induces T15/167-specific helper T cells in X-linked immune defect-expressing F1 mice. This indicates that a B cell response to PC is not required to induce idiotype-recognizing T cells. Adoptive cotransfer of B cells from PC-Hy-primed mice together with normal T cells fails to induce idiotype-recognizing T cells. These results indicate the existence of a T helper1-T helper2 induction loop. In this scheme, the T helper1 cell carries T15-like receptors and the T helper2 cells, anti-T15-like receptors. Monoclonal antiidiotypic antibodies specific for T15 also induce a T15/167-recognizing T helper cell population. This finding demonstrates that idiotope-specific priming induces non-idiotype-specific T cells. Evidently, the idiotypic T cell network is based on a different selection of idiotope determinants than the selection of the B cell idiotype network.

Animals↗
PubMed1983

Amino acid sequence of the N alpha-terminal 201 residues of human erythrocyte membrane band 3.

We have determined the amino acid sequence of the N alpha-terminal portion of band 3, the anion transport protein of the human erythrocyte membrane. The material analyzed was a 201-residue, 23,053-Da fragment cleaved from the cytoplasmic end of band 3 by S-cyanylation. The sequence had these notable features. 1) The N alpha-terminal region was extraordinarily acidic, second only to a segment of similar size from the sigma factor of Escherichia coli RNA polymerase. The first 33 residues contained 6 aspartic acid and 12 glutamic acid residues, no basic residue, and a blocked N alpha-amino group. 2) The first 11 residues of the protein had a striking resemblance to the following 11 residues. 3) In contrast to the acidic N alpha-terminal third, the COOH-terminal two-thirds of the 23,053-Da fragment had a predominantly basic character. The highly acidic character of the N alpha-terminal portion of band 3 accounts for the capacity of this part of the protein to bind glycolytic enzymes in a highly electrostatic fashion, presumably through interaction with their cationic substrate-binding sites.

Amino Acid Sequence↗
PubMed1983

Idiotype-specific T-helper cells.

In the present study we investigated the induction and fine specificity of T-helper cells that recognize idiotypes. The data presented show that both low-dose priming with anti-T15 antiserum and priming with PC-Hy are effective in stimulating T15-specific T help. Phosphorylcholine-hemocyanin priming can generate these T cells in either PC-responding or nonresponding strains of mice. Furthermore, the PC-primed T-helper cells can also recognize another anti-PC myeloma, M167, that is idiotypically different from T15. The fine specificity of the anti-PC-idiotype recognizing T-helper cells was examined by studying the effect of in vitro inhibitors on the T-cell help. Both PC and PC-BSA as well as T15 and M167 had an inhibitory effect on the T help. Free T15 and M167 heavy chains also blocked the helper activity for T15; T15 and M167 light chains had no effect, however. Viewed collectively, these results show that PC-Hy priming induces T-helper cells that recognize idiotypic determinants common to both T15 and M167, and that the proteins' H chain is the major structural component of the determinant. Finally, the generation of these idiotype-recognizing T cells was found to occur by way of a T-T interaction loop, based on the finding that T-helper cells are induced by PC-Hy priming in animals that lack PC-responding B cells.

Animals↗
PubMed1983

Binding of phosphorylcholine by non-immunoglobulin molecules on mouse B cells.

Phosphorylcholine (PC), a molecule found in the cell wall of most serotypes of pneumococcus, has been used extensively as a probe for the study of network interactions during immune responses. The frequency of B lymphocytes capable of interacting with PC has not been directly examined. We used immunofluorescence to study the binding of PC and monoclonal anti-TEPC15 anti-idiotopic antibodies to murine lymphocytes. In addition to identifying PC-specific Ig molecules, PC was bound by a non-Ig molecule on the surface of a relatively large subset of B cells; this non-Ig marker shared an idiotypic determinant with the PC-binding myeloma protein HOPC8 (H8). PC-bearing R36a pneumococci bind to a similar subset of lymphocytes. This binding is inhibited specifically by PC coupled to bovine serum albumin and also by a monoclonal anti-H8 antibody. We suggest that bacterial interaction with B cells through non-Ig molecules capable of binding a dominant antigen like PC may possess functional significance, possibly during the events that lead to antibody induction by these microorganisms.

Animals↗
PubMed1982

Risk-taking and the human bereitschaftspotential.

The effects of response probability and feedback predictability on the human Bereitschaftspotential (BP) were examined in a probability-matching paradigm. The subjects were to guess, by pressing one of two buttons, which of two possible feedback lights could be lighted. The a priori probabilities (30%-70%) of the feedback were known to the subjects. This task was performed both when the feedback was unpredictable and when it was perfectly predictable from the prior information. The BP was enhanced only when the subjects guessed the improbable feedback when it was unpredictable, thereby putting themselves 'at risk.' This effect seemed to be independent of any concurrent contingent negative variation. The results indicate that the BP is sensitive to trial-by-trial variation of the psychological state, which is in some way related to intention.

Adolescent↗
PubMed1982

Experimental conditions leading to a low degree of thyroglobulin iodination without loss in coupling efficiency.

The hormone content of in vitro iodinated thyroglobulin is a constant fraction of the iodine content of the protein under most, but not all, experimental conditions. In contrast, in vivo iodinated human thyroglobulin may contain as little as 10% or as much as 50% of its total iodine in the T4 molecules. Surprisingly, in some poorly iodinated thyroglobulins up to 30% of the iodine may be found in T4. The mechanism of the apparent dissociation between iodination and coupling efficiency (i.e. percentage of total iodine present as iodothyronines) may be dilution of pre-existing high iodinated thyroglobulin stores by non-iodinated prethyroglobulin. This hypothesis was tested by feeding rate PTU and KClo4 for 9 days and injecting T4 during the last 2 days. Thyroglobulin iodination dropped from 0.9 ot 0.13% but the coupling efficiency remained unchanged at 25.7 and 23.9%. The exchange of highly iodinated thyroglobulin molecules for non-iodinated ones is one of the two in vivo mechanisms suggested so far which can lead to an apparent dissociation of thyroglobulin iodination and coupling efficiency.

Animals↗
PubMed1982

[Physical exercise in patients with angina pectoris of effort].

Results of physical training in 37 patients with the ischaemic heart disease with angina of effort are given, 31 one them had had myocardial infarction. Training on bicycle ergometer lasted 2 1/2 to 10 months. After exercise 75% of patients showed enhanced threshold capability, the "double product" (the heart rate x systolic AP) decreased at the expense of the pulse deceleration and decrease of the systolic AP with the standard exercise of 50 W. The maximum size of the "double product" under exercise and also with the appearance of angina remained unchanged. The heart volume after exercises did not change. Changes in haemodynamics depended on the initial functional state of the myocardium, which was evaluated by the degree of rise of the diastolic pressure in the pulmonary artery (DPPA) with 50 W exercise and according to the functional curves of the left ventricle traced by comparing DPPA and the minute volume. In patients with "good" myocardial function (DPPA not lower than 30 mm Hg) after exercises the stroke and minute volumes increased with the threshold exercise, DPPA decreased with 50 W, functional curve of the left ventricle approached the functional curve of healthy individuals. Patients with "bad" function (DPPA over 30 mm Hg and higher did not show) changes in haemodynamics and in the functional curve of the left ventricle.

Adult↗
PubMed1981

Reaccumulation of thyroglobulin and colloid in rat and mouse thyroid follicles during intense thyrotropin stimulation. A clue to the pathogenesis of colloid goiters.

Since Marine's observations some 50 years ago, it has been generally accepted that colloid goiters invariably result from colloid repletion of originally hyperplastic goiters after cessation of the goitrogenic stimulus. However, clinical observations suggest that many goiters never go through a stage of hyperplasia, but are colloid-rich from the beginning. We have injected rats and mice with thyrotropin (TSH), three times a day for 4 d, while the animals were kept on an iodine-rich diet (HID). Additional groups of animals were fed an iodine-poor diet (LID) or a diet containing 0.15% propylthiouracil (PTU) or 1% sodium perchlorate (ClO4). At intervals, thyroid weight, DNA, iodine and thyroglobulin content, thyroglobulin iodination, and intracellular droplet formation were measured. Histologic sections were also prepared and stained with periodic acid Schiff. Furthermore, thyroxine concentration was measured in the serum. Thyroglobulin content dropped by approximately 30% in HID animals but by 60% in all other groups 1 d after starting TSH. Thereafter, thyroglobulin reaccumulation occurred and droplet formation correspondingly decreased despite continuous heavy TSH stimulation. The largest amount of thyroglobulin was reaccumulated in HID animals followed by the PTU/LID groups, whereas no reaccumulation was observed in the ClO4 group. Reaccumulation of thyroglobulin only occurred if there was concomitant organification of at least some iodine. The subsequent phases of depletion and reaccumulation of thyroglobulin were mirrored by the morphology of the follicular lumina, the staining properties of the colloid and the serum T4 concentration. These observations suggest that endocytosis gradually becomes refractory to continuous TSH stimulation if a certain minimal amount of iodine is available for organic binding. Thus, primarily colloid-rich goiters may form in the presence of continuously higher than normal thyrotropin levels without a previous stage of follicular hyperplasia. The view should be revised that accumulation of colloid and intense thyrotropin stimulation are mutually exclusive events.

Animals↗
PubMed1981

Regulation of clones responding to dextran B1355S. II. Response of T-dependent and T-independent precursors.

The existence of precursors for TI and TD alpha 1 leads to 3 dextran antigens in BALB/c mice was demonstrated. A T-dependent dextran antigen was prepared by coupling dextran B1355S to hemocyanin and subsequent digestion with dextranase. The PFC response of BALB/c mice primed with hemocyanin to dextran-hemocyanin was found to be 8 times higher than in unprimed animals. The splenic focus assay was adapted for the analysis of precursors responding to T-dependent and T-independent dextran antigens. Pretreatment of recipients with anti-thymocyte serum abolished the response in fragment cultures to dextran-hemocyanin but did not affect the response to dextran B1355S. The frequencies of precursors in the adult BALB/c mouse responding to dextran and dextran-hemocyanin were determined by limiting dilution analysis. The frequency of T-dependent precursors was found to be almost 3 times greater than the frequency of T-independent precursors.

Animals↗
PubMed1979

Low molecular weight intracellular iodocompounds with long intrathyroidal half-life: remnants of thyroglobulin hydrolysis?

In this paper additional information on low molecular weight, soluble, intrathyroidal iodocompounds with slow metabolic rate is provided. These compounds have previously been localized autoradiographically within the follicular cells. Radioiodide was administered to rats on a normal iodine intake (6--7 microgram/day) for 80 days to approach isotopic equilibration of the intrathyroidal iodine with the dietary radioiodide. When the isotope was omitted from the diet the intrathyroidal radioiodine was released with an apparent half-life of approximately 12 days. When the individual soluble components carrying radioiodine were analyzed after separation on Sephadex G-200, different apparent half-lives were found, the half-life of thyroglobulin (Tgb) being roughly 10 days and that of the low molecular weight iodocomounds being in the order of 60 to 100 days or more. In addition to the soluble low molecular weight iodocompounds, the radioactivity in the particulate fraction increased by 100% during the tracer washout when compared to Tgb and the total soluble fraction. The soluble slow turnover iodocompounds contained a higher percentage of carbohydrate and total iodine than Tgb, while the relative amounts of each sugar analyzed (hexoses, fucose, hexosamine and sialic acid) were close to those in Tgb. Sephadex G-25 chromatography of the low molecular weight iodocompounds obtained after Sephadex G-200 separation resulted in the separation of 4 peaks. Two peaks identified as iodopeptides could be further analyzed. The carbohydrate composition of these peptides was similar to that of 2 glycopeptides obtained after in vitro enzymatic hydrolysis of purified Tgb with pronase. Slow equilibration with radioiodine, long apparent intrathyroidal half-life and carbohydrate content similar to that of Tgb, taken together with previously published data on intracellular localization of soluble intrathyroidal iodocompounds, suggest that the low molecular weight iodocompounds are products of in vivo hydrolysis of engulfed Tgb droplets.

Animals↗