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R M Krause

Publications and source records attributed to R M Krause.

89 records · Page 5Linked to original sources

Studies on the immunochemistry of streptococcal mucopeptide.

Streptococcal mucopeptide, solubilized by either ultrasonic treatment or lysozyme, gave a precipitin reaction with rabbit antimucopeptide serum. A haptenic inhibitor of this reaction, which was composed of alanine, glutamic acid, and lysine in a mole ratio of 4:1:1, was isolated from a Streptomyces albus enzymes digest of Group D cell walls by ion exchange chromatography. When selected antisera were employed, greater than 90% inhibition of the mucopeptide quantitative precipitin reaction was achieved with 2 mg/ml of this inhibitor, whereas a hexosamine fraction with minimal concentrations of amino acid residues was inactive in this respect. These results suggest that the peptide moiety is an antigenic determinant of mucopeptide. Preliminary results indicate that the hexosamine polymer of the mucopeptide is a secondary antigenic determinant.

Antigen-Antibody Reactions↗

Characteristics of streptococcal group-specific antibody isolated from hyperimmune rabbits.

Intravenous immunization of New Zealand red rabbits with streptococcal group-specific bacterial vaccines yielded sera which possessed markedly elevated gamma-globulin. The sera of one rabbit immunized with Group A-variant vaccine possessed 55 mg/ml of gamma-globulin. The bulk of this gamma-globulin, identified as gamma(G)-globulin, was homogeneous by zone electrophoresis and of specificity directed against the Group A-variant carbohydrate antigen. L chains isolated from specific antibody obtained from an immune precipitate were distributed as a single band on starch gel electrophoresis, whereas the normal gamma-globulin traveled as a diffuse smear. These data suggest that the rabbit streptococcal Group A-variant antibodies possess a limited range of physicochemical properties and electrophoretic mobility compared to that generally observed for the normal complement of gamma-globulin.

Adsorption↗

Enhanced resistance to streptococcal infection induced in mice by cell wall mucopeptide.

The streptococcal cell wall mucopeptide when injected into mice either intraperitoneally or intravenously enhances the resitance to subsequent challenge with virulent Group A streptococci. Rabbits which are injected intravenously with solubilized mucopeptide develop a fever response which has a resemblance to that achieved with endotoxin. Mice which survive 6 to 7 weeks after challenge with virulent Group A streptococci yield at autopsy search Group A streptococci serologically identical to the challenge organisms. A preparative dose of cell walls injected into mice prior to challenge diminished this late recovery of streptococci. Group A-variant streptococci were recovered from mice which survived challenge and carried the organisms for several weeks. Filterable bacterial forms, which grew on L form media, were recovered from infected mice. The serologic type of the L forms was identical to that of the challenge organisms.

Animals↗

Human skeletal muscle has a voltage-gated proton current.

A voltage-gated proton current, IH, was studied with the whole-cell patch-clamp technique in human myotubes obtained from biopsies of human muscle. Studies of the reversal potential of IH during substitution of K+, Na+, Ca2+, Cl-, Cs+, and H+ in the extracellular solution indicated that protons were the major charge carriers of IH. This current is similar in many respects, but not identical, to the proton currents already described in other cell types. IH is activated by depolarization and it can be affected by extracellular pH. IH can be blocked by external divalent cations including Ca2+. This block is voltage-dependent, being more efficient at hyperpolarized than at depolarized voltages. The voltage-dependent properties of IH and its ability to be affected by pH and extracellular Ca2+ suggest that IH might be used by muscle cells to extrude protons during action potentials.

Aspartic Acid↗

Antibodies to streptococcal carbohydrate: substitutes for the myeloma proteins.

Antibodies to streptococcal carbohydrates have been employed in a number of ways as substitutes for the myeloma proteins in studies of the structures of antibody molecules and the development of the immune response. This review concentrates on the chemical nature of the streptococcal polysaccharides and on structural studies of the variable regions of the light chains of rabbit anitbodies to the group A-variant polysaccharide produced by hyperimmunization. The chemistry of the group A-variant polysaccharide has now been clarified, and this information has explained the frequently reported difficulty in the preparation of precipitating antisera to this antigen. The group A-variant vaccine is a potent antigen, but the bulk of the antibody is nonprecipitating because it is directed against the noreducing terminal sugar of the nonbranched rhamnose polymer. Chemical studies of the light chains of homogeneous rabbit antibodies reveal two hypervariable regions and a J sequence that joins the variable region to the constant region. Although the precise topographic highlights of the antigen-binding site hae yet to be determined, these structural studies have extended our knowledge of the structure and diversity of antibody molecules.

Animals↗

Electrophysiology: a method to investigate the functional properties of ligand-gated channels.

Ligand-gated channels (LGCs) play a fundamental role in the fast transmission of electrical activity from neuron to neuron and/or to effector cells. Studies of LGCs in isolation have become possible since the identification of genes coding for these membrane proteins together with the establishment of reconstitution techniques in host systems. Methods for electrophysiological investigations of LGCs reconstituted either in the Xenopus oocytes or stably tranfected in cell lines are discussed. Functional studies of reconstituted receptors enable fast determination of LGCs' pharmacological profiles and comparison of their physiological properties. Combination of molecular engineering with physiological measurements allows studies with unpreceeding resolution and it is now possible to examine at the amino-acid level the contribution of some residues in the formation of the ligand-binding site or the ionic channel domains.

Acetylcholine↗

Syphilis during 1900-1910: similarities to present-day AIDS.

At the beginning of the 20th century, despite 20 years of intensive bacteriologic research, the cause of syphilis was unknown; no diagnostic test and no treatment had been found. Syphilis was one of the leading causes of morbidity and mortality, and those who had the disease were burdened with a social stigma. It was considered a disease of "bad blood." But success was soon to follow. In only 10 years, from 1900 to 1910, the Treponema pallidum was discovered as the cause of syphilis. Animal models were developed for research. The Wassermann test was "invented" for serologic diagnosis, and Paul Ehrlich proved that salvarsan, or 606, was effective for the treatment of syphilis. This success was preceded by 300 failures with related arsenical compounds. The scientific, medical, social, ethical, and economic issues of that day have recurred again with the AIDS epidemic. This earlier drama, therefore, is reflected in the current decade, but the success of Ehrlich, Wassermann, and others in the fight against syphilis is an optimistic omen that researchers will be equally successful in the fight against acquired immune deficiency syndrome (AIDS).

History, 20th Century↗

"The beginning of health is to know the disease".

There is public impatience over the pace of medical progress. Some say prevention and health have not been well served by the research community. Rather than devising extended investigations, scientists should apply now what we know now. Activists argue that, although research on a better understanding of disease must continue, a companion effort to develop strategies for health promotion and disease prevention should exist. The national effort should emphasize "health" and not "disease," as the names of the various NIH Institutes would imply. I disagree with that proposed direction of prevention research. It is not possible to divorce research on health from research on disease. Are the secrets of nature open to us through mere observation? Does not research require the perturbation of a system in order to make valid observations on the nature of that system? This, after all, is the nature of the scientific method. Disease is, itself, a perturbation of the state of health and it is through our research on disease that we learn how to prevent it. I believe that the National Institutes of Health does devote equal time to the study of health. For it is my thesis that by studying disease we have, in fact, given our total time to the study of health. "The beginning of health is to know the disease."

Health Promotion↗