Biomedical subjects

J M Herrmann

Publications and source records attributed to J M Herrmann.

At least 37 records · Page 2Linked to original sources

PubMed1999

Out of the ER--outfitters, escorts and guides.

The endoplasmic reticulum (ER) contains a variety of specialized proteins that interact with secretory proteins and facilitate their uptake into transport vesicles destined for the Golgi apparatus. These accessory proteins might induce and/or stabilize a conformation that is required for secretion competence or they might be directly involved in the sorting and uptake of secretory proteins into Golgi-bound vesicles. Recent efforts have aimed to identify and characterize the role of several of these substrate-specific accessory proteins.

Animals↗

PubMed1999

Erp1p and Erp2p, partners for Emp24p and Erv25p in a yeast p24 complex.

Six new members of the yeast p24 family have been identified and characterized. These six genes, named ERP1-ERP6 (for Emp24p- and Erv25p-related proteins) are not essential, but deletion of ERP1 or ERP2 causes defects in the transport of Gas1p, in the retention of BiP, and deletion of ERP1 results in the suppression of a temperature-sensitive mutation in SEC13 encoding a COPII vesicle coat protein. These phenotypes are similar to those caused by deletion of EMP24 or ERV25, two previously identified genes that encode related p24 proteins. Genetic and biochemical studies demonstrate that Erp1p and Erp2p function in a heteromeric complex with Emp24p and Erv25p.

Amino Acid Sequence↗

PubMed1999

High resolution imaging of normal and osteoarthritic cartilage with optical coherence tomography.

OBJECTIVE: We describe optical coherence tomography (OCT), a high resolution micron scale imaging technology, for assessment of osteoarthritic articular cartilage microstructure. OCT is analogous to ultrasound, measuring the intensity of backreflected infrared light rather than acoustical waves. METHODS: OCT imaging was performed on over 100 sites on 20 normal and osteoarthritic cartilage specimens in vitro. RESULTS: Microstructures that were identified included fibrillations, fibrosis, cartilage thickness, and new bone growth at resolutions between 5 and 15 microm. In addition, the polarization sensitivity of imaging suggested a diagnostic role of polarization spectroscopy. CONCLUSION: OCT represents an attractive new technology for intraarticular imaging due to its high resolution (greater than any available clinical technology), ability to be integrated into small arthroscopes, compact portable design, and relatively low cost.

Arthrography↗

PubMed1998

Oxa1p, an essential component of the N-tail protein export machinery in mitochondria.

A number of nuclear encoded inner membrane proteins of mitochondria span the membrane in such a manner that their N termini are located in the intermembrane space. Many of these proteins attain this membrane orientation by undergoing an export step from the matrix across the inner membrane. This export process, which resembles bacterial N-tail export from energetic and topogenic signal requirements, is facilitated by Oxa1p, a protein that has homologues throughout prokaryotes and eukaryotes. Oxa1p, as we have previously shown, is required to export the N and C termini of the mitochondrially encoded pCoxII to the intermembrane space. We demonstrate here that imported nuclear encoded proteins physically interact with Oxa1p and depend on Oxa1p for efficient export of their N termini to the intermembrane space. Furthermore, Oxa1p interacts with nascent polypeptide chains synthesized in mitochondria, including the fully synthesized pCoxII and CoxIII species. Thus, Oxa1p represents a component of a general export machinery of the mitochondrial inner membrane.

Cross-Linking Reagents↗

PubMed1998

COPII-cargo interactions direct protein sorting into ER-derived transport vesicles.

Vesicles coated with coat protein complex II (COPII) selectively transport molecules (cargo) and vesicle fusion proteins from the endoplasmic reticulum (ER) to the Golgi complex. We have investigated the role of coat proteins in cargo selection and recruitment. We isolated integral membrane and soluble cargo proteins destined for transport from the ER in complexes formed in the presence of Sar1 and Sec23/24, a subset of the COPII components, and GTP or GMP-PNP. Vesicle fusion proteins of the vSNARE family and Emp24, a member of a putative cargo carrier family, were also found in COPII complexes. The inclusion of amino-acid permease molecules into the complex depended on the presence of Shr3, a protein required for the permease to leave the ER. Resident ER proteins Sec61, BiP (Kar2) and Shr3 were not included in the complexes, indicating that the COPII components bound specifically to vesicle cargo. COPII-cargo complexes and putative cargo adaptor-cargo complexes were also isolated from COPII vesicles. Our results indicate that cargo packaging signals and soluble cargo adaptors are recognized by a recruitment complex comprising Sar1-GTP and Sec23/24.

Amino Acid Transport Systems↗

PubMed1998

Two- and three-dimensional high-resolution imaging of the human oviduct with optical coherence tomography.

OBJECTIVE: To evaluate the feasibility of optical coherence tomography, a new method of micron-scale imaging, for high-resolution assessment of the oviduct. Optical coherence tomography is analogous to ultrasound except that it measures the backreflection of infrared light rather than acoustical waves. DESIGN: The ampulla of a human fallopian tube was imaged in vitro using optical coherence tomography. Images were generated in 2 and 3 dimensions. SETTING: University. PATIENT(S): Samples were obtained from women who had undergone hysterectomy for leiomyomatosis. INTERVENTION(S): None MAIN OUTCOME MEASURE(S): The ability to perform imaging on a micron scale, which is a level of resolution higher than that of any currently available clinical technology. RESULT(S): Two- and three-dimensional data sets of the reflectance of a human fallopian tube were acquired. A volume of 5 x 5 x 2.5 mm (length x width x depth) was scanned. The axial resolution was 11 microm, and the lateral resolution at the focus was 20 microm. The data sets showed detailed structures of the fallopian tube. CONCLUSION(S): Our ability to obtain micron-scale two- and three-dimensional images of an in vitro oviduct suggests that it may be possible to identify and surgically treat tubal causes of infertility.

Diagnostic Imaging↗

PubMed1997

Insertion into the mitochondrial inner membrane of a polytopic protein, the nuclear-encoded Oxa1p.

Oxa1p, a nuclear-encoded protein of the mitochondrial inner membrane with five predicted transmembrane (TM) segments is synthesized as a precursor (pOxa1p) with an N-terminal presequence. It becomes imported in a process requiring the membrane potential, matrix ATP, mt-Hsp70 and the mitochondrial processing peptidase (MPP). After processing, the negatively charged N-terminus of Oxa1p (approximately 90 amino acid residues) is translocated back across the inner membrane into the intermembrane space and thereby attains its native N(out)-C(in) orientation. This export event is dependent on the membrane potential. Chimeric preproteins containing N-terminal stretches of increasing lengths of Oxa1p fused on mouse dehydrofolate reductase (DHFR) were imported into isolated mitochondria. In each case, their DHFR moieties crossed the inner membrane into the matrix. Thus Oxa1p apparently does not contain a stop transfer signal. Instead the TM segments are inserted into the membrane from the matrix side in a pairwise fashion. The sorting pathway of pOxa1p is suggested to combine the pathways of general import into the matrix with a bacterial-type export process. We postulate that at least two different sorting pathways exist in mitochondria for polytopic inner membrane proteins, the evolutionarily novel pathway for members of the ADP/ATP carrier family and a conserved Oxa1p-type pathway.

Adenosine Triphosphate↗

PubMed1997

[Contents of a "basic psychosomatic management" curriculum. Results of a 4-year concomitant evaluation].

The results of evaluations proceeding the educational seminar "Psychosomatic Primary Care" in South Baden are presented and analyzed. From 1991 to 1995, approximately 450 physicians took part in these courses. From critical feedback and suggestions for improvement obtained from participants following each course, recommendations for future seminars pertaining to content, structure, process, didactic and evaluation are presented.

Adult↗

PubMed1996

AAA proteases with catalytic sites on opposite membrane surfaces comprise a proteolytic system for the ATP-dependent degradation of inner membrane proteins in mitochondria.

The mechanism of selective protein degradation of membrane proteins in mitochondria has been studied employing a model protein that is subject to rapid proteolysis within the inner membrane. Protein degradation was mediated by two different proteases: (i) the m-AAA protease, a protease complex consisting of multiple copies of the ATP-dependent metallopeptidases Yta1Op (Afg3p) and Yta12p (Rcalp); and (ii) by Ymelp (Ytallp) that also is embedded in the inner membrane. Ymelp, highly homologous to Yta1Op and Yta12p, forms a complex of approximately 850 kDa in the inner membrane and exerts ATP-dependent metallopeptidase activity. While the m-AAA protease exposes catalytic sites to the mitochondrial matrix, Ymelp is active in the intermembrane space. The Ymelp complex was therefore termed 'i-AAA protease'. Analysis of the proteolytic fragments indicated cleavage of the model polypeptide at the inner and outer membrane surface and within the membrane-spanning domain. Thus, two AAA proteases with their catalytic sites on opposite membrane surfaces constitute a novel proteolytic system for the degradation of membrane proteins in mitochondria.

ATP-Dependent Proteases↗

PubMed1996

Role of the mitochondrial DnaJ homolog Mdj1p as a chaperone for mitochondrially synthesized and imported proteins.

Mdj1p, a DnaJ homolog in the mitochondria of Saccharomyces cerevisiae, is involved in the folding of proteins in the mitochondrial matrix. In this capacity, Mdj1p cooperates with mitochondrial Hsp70 (mt-Hsp70). Here, we analyzed the role of Mdj1p as a chaperone for newly synthesized proteins encoded by mitochondrial DNA and for nucleus-encoded proteins as they enter the mitochondrial matrix. A series of conditional mutants of mdj1 was constructed. Mutations in the various functional domains led to a partial loss of Mdj1p function. The mutant Mdj1 proteins were defective in protecting the tester protein firefly luciferase against heat-induced aggregation in isolated mitochondria. The mitochondrially encoded var1 protein showed enhanced aggregation after synthesis in mdj1 mutant mitochondria. Mdj1p and mt-Hsp70 were found in a complex with nascent polypeptide chains on mitochondrial ribosomes. Mdj1p was not found to interact with translocation intermediates of imported proteins spanning the two membranes and exposing short segments into the matrix, in accordance with the lack of requirement of Mdj1p in the mt-Hsp70-mediated protein import into mitochondria. On the other hand, precursor proteins in transit which had further entered the matrix were found in a complex with Mdj1p. Our results suggest that Mdj1p together with mt-Hsp70 plays an important role as a chaperone for mitochondrially synthesized polypeptide chains emerging from the ribosome and for translocating proteins at a late import step.

DNA, Fungal↗

PubMed1995

Topogenesis of cytochrome oxidase subunit II. Mechanisms of protein export from the mitochondrial matrix.

Cytochrome c oxidase subunit II (COXII) in yeast mitochondria is synthesized as a precursor (preCOXII) and is sorted across the inner membrane, whereby both N and C termini become exposed to the intermembrane space. We describe here how this process can be experimentally dissected into a number of distinct stages. Our results demonstrate that the translation of COXII is not obligatorily coupled to translocation. Insertion into the inner membrane and export of the N- and C-terminal domains require an energized inner membrane. The export of COXII is independent of both maturation by the Imp1p protease and assembly into the cytochrome c oxidase complex. When linked to a mitochondrial matrix-targeting sequence, the N-terminal portion of preCOXII (fused to mouse dihydrofolate reductase) can be imported into the mitochondrial matrix. Following accumulation in the matrix, this chimeric protein can become exported across the inner membrane, delivering the N terminus into the intermembrane space where it undergoes processing by the Imp1p protease. This export process displays a number of similarities to bacterial protein export and supports the view that the principles of sorting are conserved from prokaryotes to eukaryotic organelles.

Animals↗

PubMed1994

Mitochondrial heat shock protein 70, a molecular chaperone for proteins encoded by mitochondrial DNA.

Mitochondrial heat shock protein 70 (mt-Hsp70) has been shown to play an important role in facilitating import into, as well as folding and assembly of nuclear-encoded proteins in the mitochondrial matrix. Here, we describe a role for mt-Hsp70 in chaperoning proteins encoded by mitochondrial DNA and synthesized within mitochondria. The availability of mt-Hsp70 function influences the pattern of proteins synthesized in mitochondria of yeast both in vivo and in vitro. In particular, we show that mt-Hsp70 acts in maintaining the var1 protein, the only mitochondrially encoded subunit of mitochondrial ribosomes, in an assembly competent state, especially under heat stress conditions. Furthermore, mt-Hsp70 helps to facilitate assembly of mitochondrially encoded subunits of the ATP synthase complex. By interacting with the ATP-ase 9 oligomer, mt-Hsp70 promotes assembly of ATP-ase 6, and thereby protects the latter protein from proteolytic degradation. Thus mt-Hsp70 by acting as a chaperone for proteins encoded by the mitochondrial DNA, has a critical role in the assembly of supra-molecular complexes.

DNA, Mitochondrial↗

PubMed1994

[Which patients benefit from treatment with respiratory feedback?].

The physiological and psychological data of 82 patients with essential hypertension, who participated in the treatment group of a respiratory feedback (RFB) evaluation (Franck et al. 1994), were examined, using clusteranalysis, to detect and to describe therapy responders and nonresponders. For patients with usual personality characteristics, active coping strategies and interest in games and technics the best blood-pressure decrease (systolic bp: 13.05 mmHg, diastolic bp: 10.63 mmHg) was found. Furthermore patients, who stopped RFB-treatment have been compared with patients, who finished the treatment program. Patients, who stopped the RFB-treatment, had more psychological symptoms in the sense of psychosomatic complaints.

Biofeedback, Psychology↗

PubMed1992

Glycoprotein IV of bovine herpesvirus 1-expressing cell line complements and rescues a conditionally lethal viral mutant.

Glycoprotein IV (gIV) of bovine herpesvirus 1 (BHV-1), a homolog of herpes simplex virus glycoprotein D, represents a major component of the viral envelope and a dominant immunogen. To analyze the functional role of gIV during BHV-1 replication, cell line BUIV3-7, which constitutively expresses gIV, was constructed and used for the isolation of gIV- BHV-1 mutant 80-221, in which the gIV gene was replaced by a lacZ expression cassette. On complementing gIV-expressing cells, the gIV- BHV-1 replicated normally but was unable to form plaques and infectious progeny on noncomplementing cells. Further analysis showed that gIV is essential for BHV-1 entry into target cells, whereas viral gene expression, DNA replication, and envelopment appear unchanged in both noncomplementing and complementing cells infected with phenotypically complemented gIV- BHV-1. The block in entry could be overcome by polyethylene glycol-induced membrane fusion. After passaging of gIV- BHV-1 on complementing cells, a rescued variant, BHV-1res, was isolated and shown to underexpress gIV in comparison with its wild-type parent. Comparison of the penetration kinetics of BHV-1 wild type, phenotypically complemented gIV- BHV-1, and BHV-1res indicated that penetration efficiency correlated with the amount of gIV present in virus particles. In conclusion, we show that gIV of BHV-1 is an essential component of the virion involved in virus entry and that the amount of gIV in the viral envelope modulates the penetration efficiency of the virus.

Animals↗

PubMed1988

Effects of celiprolol on serum lipids in systemic hypertension.

Antihypertensive therapy with celiprolol lowers blood pressure by selectively blocking beta 1 adrenoceptors. It also exhibits vasodilatory and bronchosparing effects and is not cardiodepressive. Because many beta blockers are often suspected of adversely raising serum lipid levels, especially triglycerides, a special investigation of lipids in hypertensive subjects was performed. The preliminary findings in a series of 14 patients (average age 39.7 years) with essential hypertension (World Health Organization stages I to II) who were treated with celiprolol for a period of 6 months are presented. Serum levels of total cholesterol and low-density lipoprotein remained virtually unchanged during treatment. There was, however, a tendency for triglyceride levels to fall with celiprolol treatment, a trend that became significant after 4 weeks. Moreover, high-density lipoproteins tended to increase with treatment and were significantly increased after 2 weeks. In contrast to findings obtained with other beta-blocking agents, no increases in total serum lipids were observed during celiprolol treatment. Blood pressure values of the subjects treated decreased significantly from a mean value (measured in the upright position) of 151/99 to 131/87 mm Hg. Blood pressure values taken in the supine position were also significantly reduced. No significant changes were noted in a variety of laboratory parameters, including blood count, blood coagulation time, blood sugar concentration, liver and kidney tests, electrolyte levels and urinalysis. The significance of these results, which suggest that celiprolol is not associated with adverse changes of lipids and may even positively influence blood chemistry, is discussed.

Adult↗

PubMed1988

Reduction of left ventricular hypertrophy in hypertensive patients after treatment with celiprolol.

Long-term treatment with celiprolol, a new cardioselective beta blocker, significantly reduced blood pressure in 14 patients with essential hypertension (World Health Organization stages I to II). Heart rates remained within the normal range throughout treatment and no significant side effects were observed. In 4 patients, end-systolic septum thickness was measured, and evidence was obtained that the extent of left ventricular hypertrophy was reduced. These findings indicate that celiprolol can be used for the successful long-term treatment of essential hypertension, and that such treatment reduces left ventricular hypertrophy induced by high blood pressure.

Adult↗

PubMed1988

A long-term study of the effects of celiprolol on blood pressure and lipid-associated risk factors.

In a 12-month study of 12 patients with essential hypertension treated with once-daily celiprolol, 200 mg, mean supine blood pressure was reduced from 162/102 to 134/84 mm Hg (p less than 0.005)and standing pressures from 155/101 to 134/88 mm Hg (p less than 0.05). Similarly, heart rate fell from 83 to 71 beats/min in the supine position and from 90 to 79 beats/min in the standing position. Serum cholesterol level also fell from 5.35 to 4.78 mmol/L (p less than 0.01) and was accompanied by a nonsignificant loss of body weight. Lipid electrophoresis showed a nonsignificant increase in the high-density lipid fraction, from 1.2 to 1.7 mmol/L, and a significant decrease in the low-density lipid fraction, from 3.4 to 2.7 mmol/L (p less than 0.01). Serum triglyceride levels also decreased from 1.85 to 1.37 mmol/L (p less than 0.02), and low-density lipid-high-density lipid ratio fell from 3.29 to 2.03 (p less than 0.02). There was an unexpected reduction in serum fibrinogen levels, from 288 to 253 mg/dl (p less than 0.01). Aside from a slight reduction in the fasting blood glucose, there were no other significant changes in the urine or blood parameters, and no adverse drug effects occurred. It is likely that celiprolol's effect in reducing fibrinogen levels may minimize the increase in blood viscosity associated with the hypertensive state, whereas its effects on fibrinogen may herald a reduction in hypertensive complications such as thrombosis or retinal "cotton wool exudates." This warrants further investigation."

Adrenergic beta-Antagonists↗

PubMed1988

Lipid profile improvement following celiprolol.

Many beta-blockers adversely affect serum lipid levels. We have, therefore, monitored blood pressure and serum lipids in 22 patients (mean age: 42.5 years) with essential hypertension (WHO stages I-II) who were treated with celiprolol for 4 weeks, and in 12 patients (mean age: 39.8 years) with essential hypertension (WHO stages I-II) who received celiprolol for 12 months. Standing blood pressure was significantly reduced after 4 weeks and 12 months of treatment, and there were slight decreases in serum cholesterol. In addition, serum triglyceride levels decreased significantly after 4 weeks, and there was a smaller decrease in the patients treated for 12 months. The pathologically elevated pre-treatment lipid values were, therefore, reduced to levels within the normal range. Analysis by lipid electrophoresis showed an increase in the high density lipoprotein (HDL) fraction and a decrease in both the low density lipoprotein (LDL) fraction and the LDL/HDL ratio. During the long-term study there was also a significant reduction in serum fibrinogen. Our results show that celiprolol does not adversely alter serum lipids, and it may even have a beneficial effect on these variables.

Adrenergic beta-Antagonists↗