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Biomedical subjects

H Haupt

Publications and source records attributed to H Haupt.

At least 91 records · Page 5Linked to original sources
PubMed1991

The effect of the carbohydrate moiety upon the size and conformation of human plasma galactoglycoprotein as judged by electron microscopy and circular dichroism. Structural studies of a glycoprotein after stepwise enzymic carbohydrate removal.

Galactoglycoprotein is a unique human plasma protein [76% carbohydrate (23% N-acetylneuraminic acid, 20% galactose, 3% mannose, 1% fucose and 29% N-acetylgalactosamine plus N-acetylglucosamine) and 24% polypeptide, a single polypeptide chain of about 200 amino acid residues that is high in serine and threonine content] [Schmid, Mao, Kimura, Hayashi & Binette (1980) J. Biol. Chem. 255, 3221-3226]. Highly purified exoglycosidases with well-defined specificities were used to prepare five derivatives of galactoglycoprotein in which sequential residues of N-acetylneuraminic acid, galactose, N-acetylglucosamine, a second galactose and N-acetylgalactosamine were removed with 83% of the total carbohydrate cleaved. C.d. shows that native galactoglycoprotein and all derivatives in aqueous buffer are predominantly random coil, suggesting that removal of a large number of electrostatic net charges, as well as the major portion of the carbohydrate moiety, does not alter the secondary structure of the polypeptide chain. Examination of the size and conformation of tungsten-shadowed galactoglycoprotein and asialo and agalacto derivatives by electron microscopy shows the size and conformation of all three preparations to be similar, with only minor differences in particle length and width.

Antigens, CD↗
PubMed1991

Measurements of perilymphatic oxygen tension in guinea pigs exposed to loud sound.

Using different types of custom-made oxygen-sensitive microelectrodes, the perilymphatic oxygen partial pressure (PO2) was determined in anesthetized guinea pigs. Cochlear temperature, heart rate, and arterial blood pressure and acid-base status were monitored. The PO2 in the basal scala tympani perilymph (200 microns below the round window membrane) was found to be 53 +/- 17 mmHg (mean +/- SD) in 33 normal animals. In 11 guinea pigs exposed to loud sound for 15 min (10 kHz pure tone, 125 dB SPL) there was on average a continuous decline in the perilymphatic PO2, which was significant only 30 min post-exposure. A considerable variation in response was found in individual animals. Mean arterial blood pressures showed a slightly increasing time course, while heart rates did not change significantly during the whole period of the experiment. Arterial acid-base status and PO2 values remained within normal limits and did not change significantly. Cochlear microphonics and compound action potentials were substantially decreased after acoustic overstimulation. The results are discussed with due consideration of sources of error.

Acoustic Stimulation↗
PubMed1990

Cochlear blood flow following temporary occlusion of the cerebellar arteries.

In order to induce acute transient local blood flow impairment in the guinea pig cochlea, terminal vessels arising from the proximal and middle third of the basilar artery and from the rostral part of the collateral vertebral artery near their junction were occluded by temporary (1-2 min) compression. Clear identification of the anterior inferior cerebellar artery was impeded due to great variation in branching of the cerebellar arteries. To quantify the effect of the vascular occlusion on the cochlear microcirculation, laser Doppler flowmetry was used. Successive compression of the cerebellar arteries resulted in individually differentiated effects on the Doppler signal from the cochlea. In about half of the experiments there was a decrease in the laser signal to 25-55% of the initial level, while in the other cases no clear decrease occurred. Proximal obstruction of the basilar artery was found to reduce the cochlear blood flow up to 10-25% of its initial level, indicating that the Doppler signal primarily reflects microcirculation within the membranous cochlea. The findings are discussed with regard to their significance as an animal model for acute transient cochlear hypoxia.

Animals↗
PubMed1990

Laser Doppler measurements of cochlear blood flow during loud sound presentation.

The laser Doppler flowmeter may give responses to loud sound that reflect the vibration of cochlear structures rather than changes in cochlear blood flow. The present study demonstrates that the positive artifactual response (i.e., increased flow reading) to sound at frequencies above approximately 5 kHz can be eliminated by using flowmeters which have electronic filters at 4 and 12 kHz, limiting the bandwidth of the optical Doppler shifted frequency range to lower frequencies. However, when using the 4 kHz filter a "residual" immediate negative response to loud high-frequency sound (10 kHz tone at 125 dB SPL) is evident at the beginning of the exposure. These findings are discussed with regard to the suitability of the method for investigating the effect of sound/noise on cochlear blood flow.

Animals↗
PubMed1990

Laser light transmission and laser Doppler blood flow measurements on the human, rat and guinea pig cochlea.

In order to test the applicability of laser-Doppler flowmetry in monitoring cochlear blood flow clinically, the thickness and the helium-neon laser light transmission of specimens of human, rat and guinea pig promontory bone and human skin were determined. Furthermore, comparative laser-Doppler measurements were taken from the promontory in patients, rats and guinea pigs. Due to the different thicknesses of the promontory bone in different species, the light transmission was found to be considerably higher for the animal cochlea (rat, 15%; guinea pig, 6.6%) than the human cochlea (1.7%). However, a clearly higher laser-Doppler signal was recorded from both the human and the rat cochleas as compared with the guinea pig. The relative laser light attenuation by the human skin specimens corresponded to that of the human promontory bone. The findings are discussed with regard to the suitability of the laser-Doppler method for blood flow measurements in the human cochlea.

Aged↗
PubMed1990

[Chemistry and clinical significance of human plasma proteins].

Enormous progress has been made in the course of the past few years in the various fields of plasma protein research. The primary and disulfide bridge structures are now known for almost all of the 120 proteins thus far isolated from human plasma, including trace and ultratrace proteins as well as a number of genetic variants. Genetic cloning and the derivation of the amino-acid sequence from the nucleotide sequence have played a decisive role here. However, we are only in possession of the exact three-dimensional structure for a small number of plasma proteins. The major problem in this respect is, at present, the lack of suitable protein crystals for X-ray structure analysis. We still do not know the physiological function of a large number of plasma proteins, despite the fact that they, in part, have been well characterised both physically and chemically and could be assigned to their respective protein families on the basis of their amino-acid sequence. The development of techniques for protein structure determination is relatively well advanced today, yet we lack methods of illuminating the structure-function relationship. There are more than 20 different highly purified protein preparations in virus-safe form available today for substitution therapy. To this effect new purification procedures have been developed which pay particular attention to virus elimination and inactivation. Should present indications be confirmed, one may assume that further plasma proteins (e. g. proteinase inhibitors, apolipoproteins, fibronectin) could be of significance in therapy and prophylaxis. Unlimited amounts of human blood are not available. Gene technology offers a promising alternative, at least for the production of plasma protein administered to patients in small amounts. Work is being done intensively on various blood coagulation factors and proteinase inhibitors at the moment, and factor VIII: C is already being successfully used for the treatment of patients with hemophilia A. However, it will no doubt take years before recombinant plasma proteins are in a position to extensively replace traditional preparations. In the field of diagnostic investigation with plasma proteins immunochemical methods of determination have assumed an increasing significance during the course of the last two decades. Particularly the development of automated techniques which allow serial quantification of individual proteins, has made protein profiling for diagnosis and monitoring in a number of diseases a routine procedure in many clinical laboratories.

Amino Acid Sequence↗
PubMed1989

The arrangement of disulfide loops in human alpha 2-HS glycoprotein. Similarity to the disulfide bridge structures of cystatins and kininogens.

The complete disulfide loop structure of human alpha 2-HS glycoprotein has been elucidated. alpha 2-HS glycoprotein isolated from human plasma was found to be a two-chain protein composed of a heavy and a light chain. The heavy chain comprises the A-chain of alpha 2-HS glycoprotein (Yoshioka, Y., Gejyo, F., Marti, T., Rickli, E. E., Bürgi, W., Offner, G. D., Troxler, R. F., and Schmid, K. (1986) J. Biol. Chem. 261, 1665-1676) and part of the connecting peptide which has been predicted from the corresponding cDNA sequence (Lee, C. C., Bowman, B. H., and Yang, F. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 4403-4407), whereas the light chain corresponds to the beta-chain of alpha 2-HS glycoprotein (Gejyo, F., Chang, J. L., Bürgi, W., Schmid, K., Offner, G. D., Troxler, R. F., Van Halbeek, H., Dorland, L., Gerwig, G. J., Vliegenthart, J. F. G. (1983) J. Biol. Chem. 258, 4966-4971). Twelve half-cystine residues are present in the alpha 2-HS glycoprotein molecule, and 11 of them are positioned in the heavy chain and a single one in the light chain of the molecule; they form six disulfide bridges. The first and the last half-cystine residues of the amino acid sequence of alpha 2-HS glycoprotein are engaged in the formation of a loop spanning the extreme NH2- and COOH-terminal portions of the molecule, thereby connecting the heavy and light chains. The other 10 half-cystines residues are linked consecutively in the heavy chain and form five loops which span 4-19 amino acid residues. Among them are two pairs of loops which are characterized by mutual sequence homology. The particular arrangement of disulfide loops in alpha 2-HS glycoprotein is similar to the patterns of linearly arranged and tandemly repeated disulfide loops of cysteine proteinase inhibitors, i.e. the cystatins and the kininogens. It is concluded that alpha 2-HS glycoprotein represents a structural prototype of a novel family among the cystatin superfamily, characterized by the presence of two cystatin-like building blocks. Extensive similarity among the NH2-terminal sequences of alpha 2-HS glycoprotein and human histidine-rich glycoprotein suggest that the latter protein is another candidate protein of this new family.

Amino Acid Sequence↗
PubMed1989

Haemorheologic studies in patients with reduced coronary vasodilator capacity but normal coronary angiogram (syndrome X).

The cause of syndrome X, i.e. typical angina, positive exercise test, normal coronary angiogram, normal resting cardiac function, but reduced coronary vasodilator capacity is still unknown. The purpose of the study was to investigate blood fluidity as a possible cause of syndrome X. Haematocrit, plasma viscosity, erythrocyte aggregation, and erythrocyte deformability were examined in 14 patients with syndrome X (group 1), 24 patients with typical angina, positive exercise test, but normal coronary vasodilator capacity (group 2), and 37 patients with atypical chest pain and normal coronary arteries (control group). Coronary vasodilator capacity was determined by the argon method. Compared with normals, patients with syndrome X showed an elevated plasma viscosity (1.31 +/- 0.05 mPas vs 1.26 +/- 0.04 mPas, 2P less than 0.01), an elevated erythrocyte photometric aggregation index (141 +/- 27% vs 100 +/- 23%, 2P less than 0.01) and a reduced erythrocyte filterability (0.51 +/- 0.12 vs 0.66 +/- 0.09, 2P less than 0.01). Significant differences in the haemorheologic parameters between group 1, group 2 and the control group, however, were not detected. Multiple regression analysis did not reveal a significant relationship between coronary vasodilator capacity and the haemorheologic parameters tested. The data suggest that the reduction in coronary vasodilator capacity in patients with syndrome X cannot be attributed to haemorheologic alterations.

Adult↗
PubMed1989

[Physiological parameters of guinea pigs under long-term anesthesia with controlled respiration].

56 guinea pigs were anesthetized with a mixture of alpha-chloralose and a small dose of ethyl urethane injected i.p. in order to compare the chloralose-urethane anesthesia with neuroleptanesthesia, a mixture of droperidol-fentanyl and a small induction dose of Na-pentobarbital was injected i.p. to 14 animals. All animals were maintained at constant body temperature of 38 degrees C and artificially respirated via a tracheal cannula monitoring the end expiratory CO2 concentration. Mean arterial blood pressure (carotid artery) and heart rate were continuously recorded. Arterial acid-base status and pO2 were tested. Mean arterial blood pressure and heart rate were found to be somewhat higher in the neuroleptanesthetized animals. Under chloralose-urethane anesthesia and neuroleptanesthesia the mean arterial blood pressure amounted to 56 and 62 mm Hg, respectively. These findings correspond to data given in the literature concerning the mean pressure in unanesthetized guinea pigs. The mean heart rates of 295 and 316 min-1, respectively are somewhat higher compared to the normal range. Under both anesthesias, the arterial acid-base status was within the normal limits of unanesthetized animals. The mean arterial pO2 of 80.9 and 76.5 mm Hg was relatively low. The present studies have shown that chloralose-urethane as well as droperidol-fentanyl with pentobarbital are useful, under controlled artificial respiration, to achieve long-term anesthesia maintaining nearly normal systemic circulatory and respiratory conditions.

Anesthesia↗
PubMed1988

Complete amino acid sequence of human plasma Zn-alpha 2-glycoprotein and its homology to histocompatibility antigens.

In the present study the complete amino acid sequence of human plasma Zn-alpha 2-glycoprotein was determined. This protein whose biological function is unknown consists of a single polypeptide chain of 276 amino acid residues including 8 tryptophan residues and has a pyroglutamyl residue at the amino terminus. The location of the two disulfide bonds in the polypeptide chain was also established. The three glycans, whose structure was elucidated with the aid of 500 MHz 1H NMR spectroscopy, were sialylated N-biantennas. The molecular weight calculated from the polypeptide and carbohydrate structure is 38,478, which is close to the reported value of approximately equal to 41,000 based on physicochemical measurements. The predicted secondary structure appeared to be comprised of 23% alpha-helix, 27% beta-sheet, and 22% beta-turns. The three N-glycans were found to be located in beta-turn regions. An unexpected finding was made by computer analysis of the sequence data; this revealed that Zn-alpha 2-glycoprotein is closely related to antigens of the major histocompatibility complex in amino acid sequence and in domain structure. There was an unusually high degree of sequence homology with the alpha chains of class I histocompatibility antigens. Moreover, this plasma protein was shown to be a member of the immunoglobulin gene superfamily. Zn-alpha 2-glycoprotein appears to be a truncated secretory major histocompatibility complex-related molecule, and it may have a role in the expression of the immune response.

Amino Acid Sequence↗
PubMed1988

[Crystallized human plasma proteins. I. Albumin, transthyretin, retinol-binding protein, ceruloplasmin and beta 2-glycoprotein I].

The presently known possibilities and conditions for achieving the crystallization of Albumin, Transthyretin, Retinol-binding Protein, Ceruloplasmin and beta 2-Glycoprotein I are described with respect to our own experiences. For isolating some proteins the crystallization gives rise to a real purification step. Sometimes degrees of purity near to 98 till 99% will be reached. Furthermore crystalline proteins are very important for the determination of the three-dimensional structure by aid of the X-ray diffraction analysis. For this purpose large single crystals are needed with minimum requirements of 0.4 mm length for all the three dimensions. Additionally the crystals must have a high degree of order on the molecular level and should allow recording of the diffraction pattern out to 3 A resolution. From the five proteins described here the three dimensional molecular structure of Transthyretin and Retinol-binding Protein could be elucidated by using the method of the X-ray diffraction analysis.

Ceruloplasmin↗