Biomedical subjects
Publications and source records attributed to M Cramer.
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To increase the limited knowledge of the effects of digitalis on sinus nodal function in patients with sinus nodal dysfunction and to initiate an investigation into the mechanisms underlying its effects, 34 patients with sinus nodal dysfunction were studied. Twenty patients underwent determination of sinus cycle length, estimated sinoatrial conduction time and maximal corrected sinus recovery time before and after the administration of 0.75 mg of intravenous digoxin. For the group, sinus cycle length did not change, sinoatrial conduction time increased insignificantly and maximal corrected sinus recovery time shortened; however, individual variation occurred. The effects of acute digitalization appeared to predict the effects of chronic digitalis administration on sinus nodal function in the eight patients who subsequently continued to take digoxin. Fourteen patients received digoxin after vagal blockade with atropine. After vagal blockade, digoxin lengthened sinus cycle length, sinoatrial conduction time and maximal corrected sinus recovery time. The effects of digoxin administered after atropine could be antiadrenergic, direct, or both, and are opposite to those induced by atropine alone. Because these effects are similar to those of vagotonia yet are not apparent when the vagi are unblocked, digoxin may have direct excitatory, adrenergic or previously unrecognized vagolytic effects on sinus nodal function in man and their manifestation may be dependent on heart rate or autonomic tone.
The primary antibody response of C57BL/6 mice to the 4-hydroxy-3-nitrophenylacetyl (NP) hapten is restricted to antibody molecules expressing the NPb idiotype. This idiotype is a genetic marker for V genes in the heavy chain linkage group. In the secondary response, the frequency of NPb idiotype-positive molecules within the antibody population drops to very low values. Accordingly, isolated NP binding receptors from NP-sensitized B lymphocytes are largely devoid of this idiotype. In contrast, the NPb idiotype is expressed on the majority of the receptor fractions which we consider T-cell derived. This finding suggests that the antigen receptors of T lymphocytes may be restricted to the expression of major (germ-line encoded?) heavy chain idiotypes.
We have identified extracell potential changes associated with the electrical activity of the canine sinoatrial pacemaker. Small nonpolarizable electrodes and low frequency high gain amplification were used to record unipolar electrograms from both the epicardial and the endocardial surfaces of the canine sinus node. Initially in vitro studies were performed so that transmembrane action potential changes could be recorded simultaneously with the extracell potentials. The sinus nodal electrogram showed two characteristic potentials when the electrode was in immediate proximity to pacemaking cells: (1) During phase 4 there was a steady slope of about -30 to -100 muv/sec, and (2) during the transition from phase 4 to phase 0 of the transmembrane action potential the slope of the electrogram increased smoothly to approximately -400 to -1,000 muv/sec. These potentials were followed by high frequency deflections as cells in the surrounding atrium depolarized. Tetrodotoxin (5 mg/liter) rendered the atrial muscle inexcitable and delayed and then abolished the high frequency activity in the sinus electrogram, which then appeared as a continuous smooth tracing similar to the sinus pacemaker action potential but reversed in polarity. We then recorded these small localized potentials from the in situ canine heart. Sinus nodal electrograms could be obtained from beating hearts with hand held probes on the epicardial surface and with conventional recording catheters on the endocardial surface. The results demonstrate that the canine sinus node gives rise to detectable and characteristic changes in extracell potential and suggest that similar potentials can be recorded from man to evaluate sinus nodal function.
Hapten-binding receptor material was isolated from sensitized rabbit lymphocytes by a method described previously for murine receptor material. The material was separated into a fraction expressing immunoglobulin determinants (anti-Ig+ fraction) and a fraction lacking known class and type-specific determinants of Ig constant domains (anti-Ig- fraction). We present evidence in support of the notion that--in analogy to the mouse system--the anti-Ig+ fraction is B-cell-derived, whereas the anti-Ig- fraction originates from T lymphocytes. Receptors of the anti-Ig- phenotype are found to express a locus allotypic determinants and, thus, appear to carry variable portions of immunoglobulin heavy chains.
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Antigen-binding receptors of T lymphocytes were analyzed in two different ways. First, the idiotypic properties of T helper cells are studied using anti-idiotypic antisera prepared against isolated antibodies specific for A-CHO. These anti-idiotypic antisera are defined by immunogenetic and immunochemical means with respect to their reactivity with heavy- or light-chain-associated idiotypic determinants. Second, antigen-binding receptors are isolated from enriched T-and B-lymphocyte preparations and compared with respect to their reactivity with antigen and with class- or allotype-specific anti-Ig antisera. The results provide an incomplete picture of the T-cell receptor which shares with antibodies the variable region of the heavy chain but probably no other variable or constant portion.
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In previous publications it was shown by avidity measurements, cross-reactivity patterns and genetic analyses, that the tetrapeptide T-T-G-G is the immuno-dominant epitope of the synthetic polypeptide (T, G)-A--L. In the present study this close immunological relationship between the random multichain copolymer (T, G)-A--L and the ordered analogue (T-T-G-G)-A--L is extended by two additional criteria. First, the immune response against (T-T-G-G)-A--L in H-2k nonresponder mouse strains can be reconstituted to high antibody levels by complexing this antigen to methylated bovine serum albumin, as was tested earlier for (T,G)-A--L. The antibodies elicited upon reconstitution in both antigenic systems are directed mainly against the same determinant, T-T-G-G. Second, isoelectric focusing analysis of specific antisera developed with radiolabeled antigen revealed restricted 7 S IgG antibody populations in high responder and reconstituted high and low responder mice. The spectra were found to be of similar complexity in the (T,G)-A--L and in the (T-T-G-G)-A--L system. From these data it was concluded that the repertoires of specific B cells to T-T-G-G are very similar in high and low responder strains, and the defect in the H-2k low responder systems should be located at the level of T-B cell cooperation.
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In response to community needs and pressures, increasing numbers of small crisis centers and hotline services have emerged. This emergence of services has been possible in part because of the mounting number of eager and interested volunteers. These services want and need training for the volunteers. This article examines the problem of evaluating the kind of information and the kind of training that hotline volunteers were given in a brief training program.
This study focused on some of the determinants of schematic interactional distance based on an analysis of social learning processes. It was hypothesized that closer interpersonal constructions would be associated with a more positive rather than negative self-concept, a greater rather than lesser degree of trust, and a covert positive rather than negative self-disclosure to a significant other. One hundred fifty-nine male and female undergraduate students were administered the Tennessee Self Concept Scale and Jourard's Self-Disclosure Questionnaire. Of these Ss, 82 were also given either positive or negative covert self-disclosure conditions. Interactional distances consisted of "Self" placements in relation to several key social target representations. The results supported the hypothesis regarding the relationship between self-concept and psychological distance, but only for females. There was also a tendency for more trusting females to produce closer distances than less trusting females. These results, as well as the obtained significant sex differences in distancing responses and in renditions of vertical displacements, were discussed within the context of culturally determined sex role differences.
Immune responsiveness to the streptococcal group polysaccharides at the clonal level can conveniently be monitored by analytical isoelectric focusing combined with autoradiography. The parameters investigated in this paper can be summarized as follows: [1] Within the first week after injection antistreptococcal p0lysaccharide responses are characterized by IgM antibodies, followed by subclass restriction in Balb/c mice to IgG2a antibodies. [2] The clonal pattern of specific IgG2a antibodies established in the second week after immunization does not change within the following 6 weeks. [3] Persistence of a specific response pattern established within a primary immunization course holds for Balb/c mice and rabbits for as long as 12 to 13 months. [4] Repeated immunization courses in mice and rabbits maintain established clonal antibody patterns in toto. Temporal variations of clonal expression are generally quantitative rather than qualitative. B-cell memory within this system is therefore stable and long-lived.
The immune response of nine inbred and one outbred strain of mice to the streptococcal group A polysaccharide was investigated with respect to magnitude and restriction. Analytical isoelectric focusing served as a tool to estimate the degree of restriction of Group A polysaccharide-specific antibodies. It proved feasible to distinguish low and intermediate from high responder strains, and to delineate strain-specificity of isoelectric focusing spectra of the immune sera. For example, immune sera of BALB/c mice, restricted high responders, and of C57BL/6 mice, heterogeneous low responders, had distinct focusing properties. Responsiveness was a dominant autosomal genetic trait in C57BL/6 x BALB/c F(1) hybrid mice, irrespective of the maternal and the paternal genotype; the immune sera of these mice had their own, rather uniform isoelectric focusing spectra whereby structural genes of the low responder strain were expressed to predominant levels in 81% of the hybrids. Responsiveness in C57BL/6 x BALB/c F(2) progeny segregated into 79% high and 21% low responders, and showed no genetic linkage to the following characteristics: hair color, sex, H-2 type, and Ig allotype of the heavy chain. The isoelectric focusing properties of these immune sera indicated segregation into patterns like BALB/c mice (40%), F(1) hybrids (48%), and C57BL/6 mice (12%). Since this segregation is independent of any of the above criteria in these F(2) mice a regulatory gene(s) is postulated that controls the clonal pattern of the immune response.