Biomedical subjects

A Kuhn

Publications and source records attributed to A Kuhn.

At least 73 records · Page 4Linked to original sources

PubMed2000

Vacuum-stimulated raman scattering based on adiabatic passage in a high-finesse optical cavity

We report on the first observation of stimulated Raman scattering from a Lambda-type three-level atom, where the stimulation is realized by the vacuum field of a high-finesse optical cavity. The scheme produces one intracavity photon by means of an adiabatic passage technique based on a counterintuitive interaction sequence between pump laser and cavity field. This photon leaves the cavity through the less-reflecting mirror. The emission rate shows a characteristic dependence on the cavity and pump detuning, and the observed spectra have a subnatural linewidth. The results are in excellent agreement with numerical simulations.

Journal Article↗

PubMed2000

YidC mediates membrane protein insertion in bacteria.

The basic machinery for the translocation of proteins into or across membranes is remarkably conserved from Escherichia coli to humans. In eukaryotes, proteins are inserted into the endoplasmic reticulum using the signal recognition particle (SRP) and the SRP receptor, as well as the integral membrane Sec61 trimeric complex (composed of alpha, beta and gamma subunits). In bacteria, most proteins are inserted by a related pathway that includes the SRP homologue Ffh, the SRP receptor FtsY, and the SecYEG trimeric complex, where Y and E are related to the Sec61 alpha and gamma subunits, respectively. Proteins in bacteria that exhibit no dependence on the Sec translocase were previously thought to insert into the membrane directly without the aid of a protein machinery. Here we show that membrane insertion of two Sec-independent proteins requires YidC. YidC is essential for E. coli viability and homologues are present in mitochondria and chloroplasts. Depletion of YidC also interferes with insertion of Sec-dependent membrane proteins, but it has only a minor effect on the export of secretory proteins. These results provide evidence for an additional component of the translocation machinery that is specialized for the integration of membrane proteins.

ATP-Binding Cassette Transporters↗

PubMed2000

[Idiopathic right ventricular tachycardia or arrhythmogenic right ventricular tachycardia?].

HISTORY: While cycling a 38-year-old man suddenly experienced palpitations associated with marked weakness. 90 min later his general practitioner, having diagnosed a ventricular tachycardia (VT) with a rate of 218/min, terminated it by a drug injection. INVESTIGATIONS: Electrocardiography (ECG), echocardiography and biventricular cardiac catheterization with right ventricular contrast injection failed to provide any evidence of structural abnormality. However, ergometry and EPS with programmed ventricular stimulation induced VT of identical morphology (left bundle branch bloc [LBBB] with right axis deviation [RAD]). TREATMENT AND COURSE: Idiopathic right-ventricular outflow tract tachycardia (IRVT) having been diagnosed, the patient was put on a maintenance dose of 50 mg/d atenolol. After 6 months without symptoms he again experienced several attacks of tachycardia. Resting ECG merely revealed an epsilon potential and negative T waves in V1-V3. Right ventricular contrast injection revealed inferolateral dyskinesia. EPS demonstrated both the known VT and a second, morphologically different one (LBBB with LAD). These findings indicated arrhythmogenic right-ventricular cardiomyopathy (ARCV). A cardioverter/defibrillator was implanted (ICD) and over the subsequent 8 months he had six episodes of VT which were quickly terminated by the ICD. CONCLUSION: At first presentation of right-ventricular outflow tract tachycardia it is often not possible to differentiate between IRVT and arrhythmogenic RV cardiomyopathy. The two being significantly different in prognosis and treatment, follow-up monitoring is essential to establish the definitive diagnosis.

Adult↗

PubMed2000

Analysis of the role of interfacial tryptophan residues in controlling the topology of membrane proteins.

Tryptophans have a high affinity for the membrane-water interface and have been suggested to play a role in determining the topology of membrane proteins. We investigated this potential role experimentally, using mutants of the single-spanning Pf3 coat protein, whose transmembrane topologies are sensitive to small changes in amino acid sequence. Mutants were constructed with varying numbers of tryptophans flanking the transmembrane region and translocation was assessed by an in vitro translation/translocation system. Translocation into Escherichia coli inner membrane vesicles could take place under a variety of experimental conditions, with co- or posttranslational assays and proton motive force-dependent or -independent mutants. It was found that translocation can even occur in pure lipid vesicles, under which conditions the tryptophans must directly interact with the lipids. However, under all these conditions tryptophans neither inhibited nor stimulated translocation, demonstrating that they do not affect topology and suggesting that this may be universal for tryptophans in membrane proteins. In contrast, we could demonstrate that lysines clearly prefer to stay on the cis-side of the membrane, in agreement with the positive-inside rule. A statistical analysis focusing on interfacially localized residues showed that in single-spanning membrane proteins lysines are indeed located on the inside, while tryptophans are preferentially localized at the outer interface. Since our experimental results show that the latter is not due to a topology-determining role, we propose instead that tryptophans fulfill a functional role as interfacially anchoring residues on the trans-side of the membrane.

Amino Acid Sequence↗

PubMed2000

Lupus erythematosus tumidus--a neglected subset of cutaneous Lupus erythematosus: report of 40 cases.

BACKGROUND: Lupus erythematosus tumidus (LET) is characterized clinically by erythematous, succulent, edematous, nonscarring plaques in sun-exposed areas. Results of histological examination show perivascular and periadnexal lymphocytic infiltration and interstitial mucin deposition. The main differential diagnoses are polymorphous light eruption, Jessner's lymphocytic infiltration of the skin, reticular erythematous mucinosis, and pseudolymphoma. Since its first description in 1930, LET has been documented rarely in the literature, and its clinical importance has not been fully appreciated. OBSERVATIONS: We characterized 40 patients with clinical and histological features of LET observed at our department from 1984 through 1998. The onset of the disease clustered in summer because of sun exposure, and 28 (70%) of the patients showed a remarkable photosensitivity confirmed by results of provocative phototesting. A complete resolution of the skin lesions was seen after systemic therapy with antimalarials and, in some cases, with local corticosteroids or spontaneously without any treatment. In 4 (10%) of the patients, antinuclear antibodies were detected; however, there was no evidence of underlying systemic involvement in any of the patients. CONCLUSIONS: Our data constitute the largest number of patients with LET collected until now. The clinical picture, extreme photosensitivity, histological findings, and effective treatment with antimalarials are so characteristic that LET should be considered as a separate entity and differentiated from other variants of cutaneous LE. Arch Dermatol. 2000;136:1033-1041

Adolescent↗

PubMed2000

[Annular erythema in Sjögren syndrome. A variant of cutaneous lupus erythematosus?].

Annular erythema has been recognised as a cutaneous manifestation of Sjögren's syndrome in the Asian literature and has been assumed to represent a distinct clinical entity. Since there are common pathophysiologic mechanisms, mainly the presence of anti-Ro/SSA or anti-La/SSB antibodies, it is difficult to separate the annular erythema from subacute cutaneous lupus erythematosus. Histological examination may reveal dermal mucin deposition resembling lupus erythematosus tumidus. We present a Chinese patient with widespread annular erythema, keratoconjunctivitis sicca, and anti-Ro/SSA antibodies. Clinical, histopathological, and immunogenetic findings are discussed reviewing the current literature, and the differences between annular erythema associated with Sjögren's syndrome and cutaneous lupus erythematosus are emphasized.

Adult↗

PubMed2000

[Rare cutaneous manifestaions of lupus erythematosus. A clinical overview].

Lupus erythematosus (LE) is a disease with a wide spectrum of cutaneous and systemic manifestations and has been the subject of many studies over several decades. Clinical features of patients with LE show a great variation, and for this reason it is difficult to develop a unifying concept of this disease. Consequently, this has led to the identification of subsets which have been defined by constellations of clinical and photobiological features, histological changes as well as laboratory abnormalities. Besides the characteristic classical forms such as systemic LE (SLE), subacute cutaneous LE (SCLE), and discoid LE (DLE), there are uncommon variants of LE which often lead to diagnostic difficulties. Bullous LE (BLE) and urticarial vasculitis are listed as characteristic but non-specific manifestations of systemic LE. LE tumidus (LET), LE hypertrophic/verrucous (LEHV), chilblain LE, and LE profundus (LEP) are uncommon subtypes of chronic cutaneous LE. Annular erythema and papulonodular mucinosis are further uncommon cutaneous manifestations of LE. This clinical review summarizes the typical features of the uncommon forms of LE in order to improve clinical diagnostic precision and to achieve a better differentiation of the subtypes.

Diagnosis, Differential↗

PubMed2000

Sediment toxicity assessment: comparison of standard and new testing designs.

Standard methods of sediment toxicity testing are fairly well accepted; however, as with all else, evolution of these methods is inevitable. We compared a standard ASTM 10-day amphipod toxicity testing method with smaller, 48- and 96-h test methods using very toxic and reference sediments. In addition we compared parallel exposures of single species, either the amphipod Ampelisca abdita or the mysid Americamysis bahia, to multiple species, mysid, and amphipod, cohabiting the same types of chambers. These comparisons were performed for both water-only and sediment-water tests. Results of the comparison of the standard ASTM 10-day amphipod test with the smaller, 48- and 96-h test chambers indicate that survival was high in both test designs using the reference sediment. With toxic sediments, complete mortality occurred in less than 48 h using the smaller experimental chambers and only after 96 h in the larger experimental chambers. We concluded that although time to death is shorter in the smaller, shorter exposure chambers, there was no overall change in mortality for the organisms, and that the smaller chambers were predictive of the results obtained with larger chambers and longer exposures. For multiple species testing in whole sediment exposures there was no change in toxicity to either the amphipod or the mysid when they cohabited the same chamber. In contrast, for water-only exposures, A. bahia demonstrated less sensitivity when cohabiting the same chamber as A. abdita. Therefore, during whole sediment testing we can add A. bahia and A. abdita to the same test chamber without changing the toxicity to either species; however, in our 10-ml water-only exposures, the species should be tested separately.

Animals↗

PubMed2000

Treatment of nonmelanotic hyperpigmentation with the Q-switched ruby laser.

Hyperpigmentation of the skin is often refractory to conventional therapies, but has significant cosmetic implications if located on visible areas. Because laser systems are capable of removing pigment deposits caused by selective photothermolysis, we addressed the issue of whether the Q-switched ruby laser could be a useful alternative in the treatment of nonmelanotic hyperpigmented skin lesions. We report the successful treatment of a patient with hyperpigmentation caused by iatrogenic human herpesvirus 8-associated Kaposi's sarcoma and a patient with hyperpigmentation caused by long-term antimalarial therapy for cutaneous lupus erythematosus. In both patients, clinical lightening of the darkly pigmented lesions was seen after a single treatment, and a significant improvement was observed after 3 laser applications. The patients tolerated the laser therapy well without any short-term side effects and did not experience either scarring or considerable textural skin changes. Histologic examination was performed before and after laser treatment to confirm the reduction of the pigment deposits. Our data indicate that treatment of nonmelanotic skin hyperpigmentation with the Q-switched ruby laser might be a safe and powerful therapeutic method.

Aged↗

PubMed2000

Periprosthetic breast capsules contain the fibrogenic cytokines TGF-beta1 and TGF-beta2, suggesting possible new treatment approaches.

Periprosthetic breast capsules composed of fibrotic collagenous material with increased collagen production are not dissimilar to other fibrotic conditions occurring in other organs. Fibrosis in the lung, liver, kidney, and skin has been associated with overproduction of the fibrogenic isoforms of transforming growth factor beta (TGF-beta1 and TGF-beta2). If periprosthetic breast capsules contained high levels of these cytokines, possibly new treatment approaches for capsular contraction could be proposed. Breast implant capsules of 35 patients harvested at the time of explantation were examined using indirect immunohistochemistry. Staining intensity for TGF-beta1 and TGF-beta2 was measured in all specimens. Immunohistochemical staining for TGF-beta1 and TGF-beta2 revealed that these two cytokines were present in all capsules analyzed. Minimal TGF-beta1 and TGF-beta2 were found in normal breast tissue. Levels of control vs. TGF-beta1 and control vs. TGF-beta2 were significant (p = 0.004 and p < 0.001 respectively). The presence of TGF-beta isoforms that are known to be fibrogenic may suggest new therapeutic approaches, which are being investigated for other fibrotic conditions.

Breast↗

PubMed2000

Evolutionarily related insertion pathways of bacterial, mitochondrial, and thylakoid membrane proteins.

The inner membranes of eubacteria and mitochondria, as well as the chloroplast thylakoid membrane, contain essential proteins that function in oxidative phosphorylation and electron transport processes or in photosynthesis. Because most of the organellar proteins are nuclear encoded, they are synthesized in the cytoplasm and subsequently imported into the organelle before they are inserted into the membrane. This review focuses on the pathways of protein insertion into the inner membrane of eubacteria and mitochondria and into the chloroplast thylakoid membrane. In many respects, insertion of proteins into the inner membrane of bacteria is a process similar to that used by proteins of the thylakoid membrane. In both of these systems a signal recognition particle (SRP) and a SecYE-translocase are involved, as in translocation into the endoplasmic reticulum. The pathway of proteins into the mitochondrial membranes appears to be different in that it involves no SecYE-like components. A conservative pathway, recently identified in mitochondria, involves the Oxa1 protein for the insertion of proteins from the matrix. The presence of Oxa1 homologues in eubacteria and chloroplasts suggests that this pathway is evolutionarily conserved.

Bacterial Proteins↗

PubMed2000

Successful treatment of discoid lupus erythematosus with argon laser.

Vascular lesions with telangiectasias on visible areas, such as the face, are common in discoid lupus erythematosus (DLE); however, an efficient management of these skin lesions can sometimes be difficult. Since argon laser light is able to specifically coagulate vascular structures, it has been used in the treatment of various vascular skin malformations. Therefore, we addressed the issue whether argon laser treatment could be a therapeutic alternative for this disease. Here, we report on a patient with DLE, who suffered from long-standing erythematous, telangiectatic plaques on the face refractory to standard regimens of therapy. After 2 laser applications, a significant improvement was observed and after 5 sessions of argon laser therapy the treated skin lesions had completely resolved with an excellent cosmetic result. The patient tolerated the laser treatment well without any short-term side effects. These data indicate that argon laser therapy might be a powerful alternative approach in the treatment of vascular skin lesions of DLE.

Argon↗

PubMed1999

Hydrophobic forces drive spontaneous membrane insertion of the bacteriophage Pf3 coat protein without topological control.

Bacterial integral inner membrane proteins are either translocated across the lipid bilayer using an energy-driven enzyme, such as the Sec translocase, or they might interact directly with the membrane due to hydrophobic forces. We report that the single-spanning Pf3 coat protein is spontaneously inserted into the membrane of Escherichia coli and requires the electrical component of the membrane potential (DeltaPsi) to translocate its N-terminal region. This results in a final N(out)C(in) orientation of the protein in the cytoplasmic membrane, due the potential-driven translocation of the aspartyl residue at position 18 in the hydrophilic N-terminal tail. Uncharged protein tails are only translocated when the hydrophobic transmembrane region of the protein has been extended. An extended transmembrane anchor allows membrane insertion in the absence of an electrochemical membrane potential, but also causes the loss of a strict determination of the topology.

Adenosine Triphosphatases↗

PubMed1999

[Periorbital edema as the initial symptom of lupus erythematosus profundus. Case report and discussion of the literature].

Periorbital edema may occur initially or in the course of a wide variety of diseases. One of these diseases is lupus panniculitis, a variant of lupus erythematosus, characterized by firm subcutaneous nodules that may ulcerate with subsequent scar formation. We present a case of lupus panniculitis in which the periorbital edema was the initial manifestation. Knowledge about the differential diagnostic possibilities of periorbital edema as well as the different variants of cutaneous lupus erythematosus is important to reach the correct diagnosis.

Diagnosis, Differential↗

PubMed1999

A molecular switch in SecA protein couples ATP hydrolysis to protein translocation.

SecA, the dimeric ATPase subunit of bacterial protein translocase, catalyses translocation during ATP-driven membrane cycling at SecYEG. We now show that the SecA protomer comprises two structural modules: the ATPase N-domain, containing the nucleotide binding sites NBD1 and NBD2, and the regulatory C-domain. The C-domain binds to the N-domain in each protomer and to the C-domain of another protomer to form SecA dimers. NBD1 is sufficient for single rounds of SecA ATP hydrolysis. Multiple ATP turnovers at NBD1 require both the NBD2 site acting in cis and a conserved C-domain sequence operating in trans. This intramolecular regulator of ATP hydrolysis (IRA) mediates N-/C-domain binding and acts as a molecular switch: it suppresses ATP hydrolysis in cytoplasmic SecA while it releases hydrolysis in SecY-bound SecA during translocation. We propose that the IRA switch couples ATP binding and hydrolysis to SecA membrane insertion/deinsertion and substrate translocation by controlling nucleotide-regulated relative motions between the N-domain and the C-domain. The IRA switch is a novel essential component of the protein translocation catalytic pathway.

Adenosine Diphosphate↗

PubMed1999

[Primary stability of cement-free press-fit acetabulum cups. In vitro displacement studies].

The initial stability of 6 different hemispherical press-fit titanium acetabular cups was investigated by lever-out tests using a foam model. Each cup was implanted in a standardised manner into machined PVC-foam blocks with an underreaming of 1/2/3 mm, and levered out 5 times. A computer recorded the load-displacement curves. Both insertion forces and lever-out forces increased with increasing press-fit from 1 to 2 mm. With underreaming of 2 mm, insertion forces varied between 9 and 34 Nm, and lever-out torques between 13 and 23 Nm. The cup made up of multi-layer irregular titanium wire mesh had the highest initial stability of all the cups tested. 3 mm underreaming was associated with insertion difficulties, so that lever-out is difficult to compare with that with 1 and 2 mm. The amount of contact on the equatorial rim, where we saw the most attrition after lever-out, is the most important factor for determining the lever-out torque. The quality of the PVC foam blocks, the accuracy of reaming, and the definition of cup insertion are very important parameters for test reproduction. Since the trials were conducted under laboratory conditions, translation of the results to the intraoperative situation should be undertaken only with certain reservations.

Acetabulum↗

PubMed1998

Differential use of the signal recognition particle translocase targeting pathway for inner membrane protein assembly in Escherichia coli.

Assembly of several inner membrane proteins-leader peptidase (Lep), a Lep derivative (Lep-inv) that inserts with an inverted topology compared with the wild-type protein, the phage M13 procoat protein, and a procoat derivative (H1-procoat) with the hydrophobic core of the signal peptide replaced by a stretch from the first transmembrane segment in Lep-has been studied in vitro and in Escherichia coli strains that are conditional for the expression of either the 54 homologue (Ffh) or 4.5S RNA, which are the two components of the E. coli signal recognition particle (SRP), or SecE, an essential core component of the E. coli preprotein translocase. Membrane insertion has also been tested in a SecB null strain. Lep, Lep-inv, and H1-procoat require SRP for correct assembly into the inner membrane; in contrast, we find that wild-type procoat does not. Lep and, surprisingly, Lep-inv and H1-procoat fail to insert properly when SecE is depleted, whereas insertion of wild-type procoat is unaffected under these conditions. None of the proteins depend on SecB for assembly. These observations indicate that inner membrane proteins can assemble either by a mechanism in which SRP delivers the protein at the preprotein translocase or by what appears to be a direct integration into the lipid bilayer. The observed change in assembly mechanism when the hydrophobicity of the procoat signal peptide is increased demonstrates that the assembly of an inner membrane protein can be rerouted between different pathways.

Bacterial Proteins↗

PubMed1998

Mitotic phosphorylation of the TBP-containing factor SL1 represses ribosomal gene transcription.

Entry into mitosis is accompanied by a global repression of transcription. To investigate the molecular mechanisms which shut-down rRNA synthesis during mitosis, we have compared RNA polymerase I (Pol I) transcription in extracts from asynchronous and mitotic HeLa cells. We show by several experimental approaches that phosphorylation by cdc2/cyclin B inactivates the TBP-containing factor SL1 and thus abrogates Pol I transcription during mitosis. This finding links the cell's cycle with the transcriptional activity of Pol I and suggests a common mechanism for mitotic silencing of all three classes of nuclear RNA polymerases, i.e. reversible inactivation of the respective TBP-TAF complexes by (a) mitotic kinase(s).

Adenine↗