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Biomedical subjects

M Schubert

Publications and source records attributed to M Schubert.

At least 109 records · Page 6Linked to original sources
PubMed1994

Central and peripheral nervous system conduction in mitochondrial myopathy with chronic progressive external ophthalmoplegia.

Involvement of the peripheral and central nervous systems in mitochondrial myopathy with chronic progressive external ophthalmoplegia (CPEO) has been demonstrated clinically and electrophysiologically. Systematic electrophysiological investigations of the peripheral and central nervous systems, particularly of cortico-spinal tract function, however, are not available. We studied peripheral and central nervous system involvement in 28 patients with histologically and biochemically proven mitochondrial CPEO by motor and sensory nerve conduction tests, by somatosensory, auditory and visual evoked potentials and, for the first time, by transcranial magnetic stimulation. Nervous system involvement could be demonstrated in 24 patients, affecting the peripheral and central nervous systems in 18 and 10 patients, respectively. Evidence of cortico-spinal tract involvement was found in 4 patients, which was clinically expected in only 2. Therefore, dysfunction of the cortico-spinal tract in mitochondrial CPEO may occur more frequently than so far assumed. Generally, electrophysiological tests serve as valuable supplements to clinical examination in patients with mitochondrial CPEO and may be especially helpful in therapeutic studies, i.e., coenzyme Q administration.

Adolescent↗
PubMed1994

Histopathologic evaluation of proliferating cell nuclear antigen (PC10) in oral epithelial hyperplasias and premalignant lesions.

As the therapeutic options for malignant lesions expand, early accurate diagnosis of premalignancy is becoming increasingly important in the concept of cancer prevention. Because it has been hypothesized that abnormal cell proliferation is related to subsequent malignant transformation, many proliferation markers such as proliferating cell nuclear antigen have been studied in a variety of malignant tumors. In oral surface epithelium, proliferating cell nuclear antigen activity is restricted to basal layers of normal squamous mucosa. In this preliminary study, 169 formalin-fixed, paraffin-embedded oral epithelial lesions, including 28 carcinomas in situ, 82 epithelial dysplasias, 21 epithelial atypia, and 38 typical epithelial hyperplasias, were studied with a monoclonal antibody, PC10, to determine whether proliferating cell nuclear antigen suprabasal expression correlated with premalignancy. The findings revealed that with progression of lesions toward malignancy, there was a significant predilection for basal/suprabasal staining pattern for proliferating cell nuclear antigen as compared with the strictly basal staining pattern seen in normal and benign epithelial conditions. One unexpected staining pattern, suprabasal positive stain only, was also noted mostly in reactive hyperplasia and dysplasia. The data suggested that a positive basal/suprabasal staining pattern for proliferating cell nuclear antigen is indicative of premalignancy in oral epithelial lesions.

Antibodies, Monoclonal↗
PubMed1994

Assessment of human motor unit twitches--a comparison of spike-triggered averaging and intramuscular microstimulation.

We recorded twitches of single motor units (MUs) in the human first dorsal interosseus muscle using either spike-triggered averaging (STA; 236 MUs in 12 normal subjects) or low-rate intramuscular microstimulation of motor axons (IMS; 200 MUs in 20 normal subjects). We analysed twitch force (TF), maximal rate of rise of force (MRRF), contraction time (CT) and half-relaxation time (HRT). MRRF, CT and HRT were significantly smaller with STA than with IMS whereas TFs were fairly similar. Higher stimulus rates (up to 14 Hz) in IMS resembling the voluntary MU firing rates in STA were associated with a decrease of all twitch parameters because of partial fusion of the twitches (20 MUs). Concerning MRRF, CT and HRT, the reduced values matched those obtained by STA, suggesting that the underestimation of these parameters in STA can be mainly attributed to partial fusion. The reduction of TF with high rate IMS but not with STA reveals that other factors such as MU synchronization and non-linear force summation of MU contractions must counteract the effects of partial fusion in STA. We conclude that both STA and IMS are appropriate for assessing TFs in man while the time-dependent parameters MRRF, CT and HRT will be underestimated with STA.

Adult↗
PubMed1994

Functional morphology of the deep transverse metacarpal ligament.

The deep transverse metacarpal ligament extends in radio-ulnar direction between the palmar plates of the metacarpo-phalangeal joints of the second through fifth finger rays. Continuing along the path of the palmar plates, the ligament divides the spaces between the fingers at the metacarpo-phalangeal border into functional spaces bordered by the ligamentous apparatus of the metacarpophalangeal joint capsules and filled by blood-vessels, nerves and intrinsic hand muscles. Morphometric examinations of the deep transverse metacarpal ligament indicate a greater strain of the radial components between the index and middle finger in the transverse plane as well as an increased stressing of sagittal fiber plates connecting the extending apparatus with the deep transverse metacarpal ligament via the metacarpophalangeal force nucleus. Palmar, sagittally directed collagen fiber bundles representing a location of initial or recurrent connective tissue proliferation can be histologically demonstrated as a connection between peritendinous and perivascular connective tissue of the palmar interdigital space and the palmar aponeurosis.

Aged↗
PubMed1994

Versican is expressed in the proliferating zone in the epidermis and in association with the elastic network of the dermis.

The expression of the large chondroitin sulfate proteoglycan versican was studied in human adult skin. For this purpose, bacterial fusion proteins containing unique portions of the versican core protein were prepared. Polyclonal antibodies against the fusion proteins specifically reacted with versican from a proteoglycan fraction of MG63 osteosarcoma cells. In immunohistochemical experiments, the affinity-purified antibodies localized versican in the stratum basale of the epidermis, as well as in the papillary and reticular layers of the dermis. An apparent codistribution of versican with the various fiber forms of the elastic network of the dermis suggested an association of versican with microfibrils. Both dermal fibroblasts and keratinocytes expressed versican in culture during active cell proliferation. In line with the observation that versican is absent in the suprabasal layers of the epidermis where keratinocytes terminally differentiate, culture conditions promoting keratinocyte differentiation induced a down-regulation of versican synthesis. In Northern blots versican mRNA could be detected in extracts from proliferating keratinocytes and dermal fibroblasts. Comparison of RNA preparations from semi-confluent and confluent fibroblast cultures demonstrated decreasing amounts of versican mRNA at higher cell densities. This inverse correlation of versican expression and cell density was confirmed by indirect immunofluorescence staining of cultured fibroblasts and keratinocytes. The localization of versican in the basal zone of the epidermis as well as the density dependence of versican in cell cultures suggest a general function of versican in cell proliferation processes that may not solely be confined to the skin.

Adult↗
PubMed1994

[Expression of the extracellular matrix proteoglycan, versican, in human skin].

Extracellular matrix chondroitin/dermatan sulfate proteoglycans are present in a wide variety of tissues including cartilage, placenta, aorta, tendon, brain and skin. They possibly participate in cellular processes such as cell adhesion, migration and proliferation. Recently, we have determined the entire primary structure of the large fibroblast proteoglycan, versican, on the basis of its cDNA sequence. Versican belongs to the family of large aggregating proteoglycans. Other members of the family, which have been characterized in terms of their primary structure, are aggrecan in cartilage and neurocan isolated from brain tissues. Due to the extensive sequence similarities between these three proteoglycans in the N- and C-terminal domains and due to the high degree of carbohydrate substitution, the generation of antibodies monospecific for versican has been difficult. To avoid cross-reactivity with aggrecan and neurocan, we therefore prepared unique portions of versican in a bacterial expression system and used them to immunize rabbits (Zimmermann et al., 1994). The affinity-purified anti-fusion protein antibodies specifically reacted with intact versican from an osteosarcoma cell line. First immunohistochemical experiments on cryo-sections of human skin revealed anti-versican staining in the stratum basale of the epidermis, as well as in the papillary and reticular layers of the dermis. By indirect immunofluorescence, Northern and Western blotting we could demonstrate that both, dermal fibroblasts and keratinocytes express versican in primary cultures. A striking inverse correlation between versican expression and cell density was observed. Analogous to the in vivo situation, keratinocytes induced to terminally differentiate ceased to express versican.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Dorsal gliding and functional spaces of the metacarpophalangeal transition].

Although the relevance of capillary and gliding spaces of the back of the hand and the finger located dorsal to the extensor aponeurosis in the metacarpo-phalangeal region between the layers of the subdermal connective tissue is often emphasized clinically in inflammatory and acute traumatic occurrences, hardly any information has been published concerning the morphology of these spaces. By means of plastic-injection techniques, varying configurations of capillary spaces in the distal region of the dorsum manus of cadavers were found. The deep connective tissue spaces located dorsal to the extensor aponeurosis were shown to have proximal connections to the dorsal tendon sheaths of the carpus, whereas superficial gliding spaces tended to vary in their expanse depending on the subcutaneous and epifascial septa. The deep as well as the superficial capillary gliding spaces are adapted as mobilizing and limiting structures for the movements of the metacarpo-phalangeal joints and the various mechanical stresses of the skin of the back of the hand. A high degree of exactness in the reconstruction of the marginal elements of such functional spaces appears to be of special importance with regard to a total restoration of the functional capability of the metacarpo-phalangeal joint region.

Capillaries↗
PubMed1994

[Loudness scaling. A procedure for quantitative recruitment detection].

Direct loudness scaling has been known as an audiological tool for about four decades. Although numerous publications have shown its clinical importance, loudness scaling has not been used in audiology and hearing aid fitting until now. This might be due to the lack of audiometers equipped with loudness scaling devices as well as missing evidence for its clinical applicability. In this study normal data for a single-step direct scaling procedure were established and loudness determinations of 105 patients with sensorineural hearing losses collected. The results show that normal level loudness functions exhibit very similar shapes for narrow band stimulation in the frequency range of 500 to 4000 Hz. However, loudness scaling is affected by the gender of the subjects: females scale systematically louder than do males. In hearing-impaired subjects the slopes of the level loudness functions tend to decrease with increasing hearing loss, indicating negative recruitment. This holds particularly true in the high-frequency range, e.g. at 4000 Hz. Our long-term experience with single-step direct loudness scaling has proven its clinical feasibility in typical patients of an audiology unit. Loudness scaling will prove useful for the localization of hearing impairments, as it can be employed as a quantitative indicator of recruitment without any restrictive preconditions. In addition, it allows the evaluation of hearing aids and cochlear implants by frequency-specific gain measurement.

Audiometry, Pure-Tone↗
PubMed1993

A randomized controlled trial of pentoxifylline for the prevention of regimen-related toxicities in patients undergoing allogeneic marrow transplantation.

This study evaluated the effect of pentoxifylline (PTX) on the incidence of regimen-related toxicity in patients receiving allogeneic marrow transplants from related donors. All patients received a regimen of methotrexate and cyclosporine as prophylaxis against acute graft-versus-host disease (GVHD). Patients were randomized to receive PTX or a placebo for 70 days and the outcome was examined in a blinded fashion. Forty-four patients were evaluate in each study arm. PTX had no significant effect on engraftment, the incidence of GVHD, venocclusive disease of the liver, infection, the need for oxygen, posttransplant survival, or the duration of hospitalization. Patients receiving PTX were significantly more likely to develop major elevations of serum creatinine levels. PTX was poorly tolerated and induced significantly more vomiting than the placebo. PTX as administered in this randomized study was associated with significant toxicity and offered no benefit in reducing transplant-related morbidity or mortality.

Adolescent↗
PubMed1993

Activation of high-threshold motor units in man by transcranial magnetic stimulation.

Motor units (MUs) with low voluntary recruitment thresholds are the first to be activated by transcranial magnetic stimulation. It is not clear, however, if high-threshold MUs can also be activated and if they contribute to motor evoked potentials (MEPs). We therefore studied 11 high-threshold motor units in the first dorsal interosseous muscle of 11 healthy subjects. Voluntary recruitment thresholds ranged from 22 to 41% (29.5 +/- 5.6%; mean +/- S.D.) of maximal muscle force. When MUs were driven at their recruitment thresholds, transcranial magnetic stimuli were applied to the vertex. Peri-stimulus time histograms of MU discharges were constructed. All MUs studied revealed a period of increased firing probability at 19-27 ms after the stimulus (primary peak). Stimulus intensities were lower by 10-57% of the maximal stimulator output than required to produce near maximal MEPs in conventional surface EMG recordings in the same subjects. We conclude that high-threshold MUs can be activated by transcranial magnetic stimulation and that they contribute to conventionally recorded MEPs.

Adult↗
PubMed1993

Protein adsorption onto poly(ether urethane ureas) containing Methacrol 2138F: a surface-active amphiphilic additive.

Surface characterization and protein adsorption studies were carried out on a series of additive dispersed and additive coated poly(ether urethane ureas), PEUUs, to characterize early events in the blood compatibility of these materials. A hypothesis that is based on surface hydrophilicity, surface flexibility, and adsorption media has been developed to understand the modulated adsorption of plasma proteins by PEUU additives. Electron spectroscopy for chemical analysis (ESCA) and contact angle analysis were performed on two PEUU formulation as well as on PEUU formulations modified with Methacrol 2138F (co[diisopropylaminoethyl methacrylate (DIPAM)/decyl methacrylate (DM)][3/1]) or acrylate or methacrylate polymer or copolymer analogs of Methacrol 2138F. Methacrol 2138F is a commercially used amphiphilic copolymethacrylate. ESCA showed that the PEUUs loaded with Methacrol 2138F or with its hydrophilic component, homopoly (DIPAM) (h-(DIPAM)), had a higher percentage of nitrogen at their surfaces than did the base PEUUs. Contact angle analysis also showed that the air side of PEUU formulations loaded with Methacrol 2138F were more hydrophobic than was the air side of base PEUUs when films were cast from dimethylacetamide. However, during contact angle testing, the air side of PEUU films loaded with Methacrol 2138F rapidly became more hydrophilic than did the air side of the base PEUU films. A radioimmunoassay and whole or diluted human plasma were also used to characterize the presence of the proteins fibrinogen, immunoglobulin G, factor VIII/von Willebrand factor, Hageman factor (factor XII), and albumin, on the surface of the same PEUUs as analyzed by ESCA and contact angle. The protein adsorption assay showed that PEUU films loaded or coated with Methacrol 2138F, with a copolyacrylate analog of Methacrol 2138F (co(diisopropylaminoethyl acrylate [DIPAA]/decyl acrylate [DA]) [3/1]), or with the hydrophilic polyacrylate or polymethacrylate component analogs of Methacrol 2138F (h-DIPAM or h-DIPAA) adsorbed significantly lower amounts of the proteins than did either the base PEUU formulations or the homopoly(decyl methacrylate) (h-DM) or homopoly(decyl acrylate) (h-DA) coated or loaded PEUUs.

Adsorption↗
PubMed1993

Protein adsorption and endothelial cell attachment and proliferation on PAPI-based additive modified poly(ether urethane ureas).

To better understand vascular interactions with poly(ether urethane urea) (PEUU) materials, protein adsorption, and endothelial cell attachment and proliferation assays were performed on a base PEUU formulation, on PEUU formulations loaded with hydrophobic and amphiphilic poly(methylene-[polyphenyl isocyanate]) (PAPI) based additives, and on PEUU formulations in which some of the polymer chains had been endcapped with either diisopropylaminoethyl (DIPAA) or decyl (DA) moieties. Protein adsorption experiments with PAPI-based additives showed that additive loaded PEUU formulations adsorbed significantly lower amounts of the studied proteins than did the unloaded PEUU. Protein adsorption to the DA and DIPAA endcapped PEUU films was found not to vary consistently from that of the unloaded PEUU film. Endothelial cell attachment and proliferation experiments with PAPI-DA and polyethylene glycol-PAPI-DA (PEG-PAPI-DA) loaded PEUU films showed that many of the films exhibited attachment and proliferation that was significantly enhanced compared to PEUU A' and that approached or equaled that of the tissue culture polystyrene control. Experiments with PAPI-DIPAA and PEG-PAPI-DIPAA loaded PEUU films exhibited attachment and proliferation data that was often below 10% of the tissue culture polystyrene control values. Experiments with the DA and DIPAA endcapped PEUU films showed endothelial cell attachment and proliferation that was statistically indistinguishable from the PEUU A' values. Contact angle analysis was carried out on the endcapped PEUU films, on the PAPI-based additive loaded PEUU films, and on PEUU A' using the sessile drop method. The advancing and receding contact angle behavior of the PAPI-based additive loaded PEUU films deviated markedly from the behavior of PEUU A', suggesting that the additives were present at the PEUU-water interface. The contact angle behavior of the endcapped PEUUs was similar to that of PEUU A', suggesting that the DA and DIPAA endcap moieties did not exist at the hydrated PEUU surface in appreciable quantities. To explain the differences in protein adsorption and endothelial cell behavior on the air side of additive loaded PEUUs when compared to the base PEUU, it was assumed that the additives near this region of the solvent swollen PEUU matrix may have migrated to, at, or near the PEUU-air interface during film formation, creating an additive enriched PEUU surface region.(ABSTRACT TRUNCATED AT 400 WORDS)

Adsorption↗
PubMed1993

[Morphologic causes and consequences of fracture of the distal radius].

Age and stress related changes in the distal epiphysis of the radius are viewed as cause and effect of losses in stability due to pathological stress. 15 in 97 distal radii show typical osseous alterations which can be evidenced after healing of a radial fracture by means of determining the subchondral cortex density. A dorsally directed inclination of the distal radius epiphysis following a healed fracture often be observed. This inclination leads to a redirecting of the resultant force vector which in turn results in a thickening of the subchondral corticalis directed towards the palmar socket margin. The densitometric evaluation based on X-ray depictions enables the morphological characterisation of the restructuring of corticalis and spongiosa in long bones as cause and effect of a fracture.

Aged↗
PubMed1993

Molecular characterization of the enniatin synthetase gene encoding a multifunctional enzyme catalysing N-methyldepsipeptide formation in Fusarium scirpi.

The gene encoding the multifunctional enzyme enniatin synthetase from Fusarium scirpi (esyn1) was isolated and characterized by transcriptional mapping and expression studies in Escherichia coli. This is the first example of a gene encoding an N-methyl peptide synthetase. The nucleotide sequence revealed an open reading frame of 9393 bp encoding a protein of 3131 amino acids (M(r) 346,900). Two domains designated EA and EB within the protein were identified which share similarity to each other and to microbial peptide synthetase domains. In contrast to the N-terminal domain EA, the carboxyl terminal domain EB is interrupted by a 434-amino-acid portion which shows local similarity to a motif apparently conserved within adenine and cytosine RNA and DNA methyltransferases and therefore seems to harbour the N-methyl-transferase function of the multienzyme.

Amino Acid Sequence↗
PubMed1993

Viral liposomes released from insect cells infected with recombinant baculovirus expressing the matrix protein of vesicular stomatitis virus.

The matrix (M) protein of vesicular stomatitis virus (VSV) has been found to promote assembly and budding of virions as well as down-regulating of VSV transcription. Large quantities of M protein can be produced in insect cells infected with recombinant baculovirus expressing the VSV M gene under control of the polyhedrin promoter. Analysis by pulse-chase experiments and density gradient centrifugation revealed that the [35S]methionine-labeled M protein synthesized in insect cells is released into the extracellular medium in association with lipid vesicles (liposomes). Electron microscopy and immunogold labeling showed that M protein expressed in insect cells induced the formation on plasma membrane of vesicles containing M protein, which are released from the cell surface in the form of liposomes. The baculovirus vector itself or recombinants expressing VSV glycoprotein (G) or nucleocapsid (N) protein did not produce the formation of vesicles in infected cells. The baculovirus-expressed M protein retains biological activity as demonstrated by its capacity to inhibit transcription when reconstituted with VSV nucleocapsids in vitro. These data suggest that M protein has the capacity to associate with the plasma membrane of infected cells and, in so doing, causes evagination of the membrane to form a vesicle which is released from the cell. This observation leads to the postulate, which requires further proof, that the VSV M protein can induce the formation and budding of liposomes from the cell membrane surface.

Animals↗
PubMed1992

Multitarget-ribozyme directed to cleave at up to nine highly conserved HIV-1 env RNA regions inhibits HIV-1 replication--potential effectiveness against most presently sequenced HIV-1 isolates.

Several mono-, di-, tetra-, penta- and nonaribozymes were developed. These multitarget-ribozymes were targeted to cleave HIV-1 env RNA at up to nine different conserved sites. Each multitarget-ribozyme consisted of a chain of up to nine hammerhead motifs, each flanked by a different targeting sequence. The multitarget-ribozymes were functional in vitro and gave rise to multiple, specific partial and/or complete RNA digestion products. Per RNA copy, multitarget-ribozymes were more efficient than monoribozymes or ribozymes targeting a subset of the same sites. In contrast to monoribozymes, a 400nt nonaribozyme, targeted to cleave at nine different sites within a 1.3kb HIV-1 env RNA substrate, was active and showed the same specificity of cleavage when it was part of a large 3.3kb transcript. We conclude that multitarget-ribozymes retain the specificity of monoribozymes, but they are more efficient per ribozyme RNA copy and they remain active when they are part of a large transcript. A tetra-, penta- or nonaribozyme under control of the SV40 late promoter, the beta-actin gene promoter or the HIV-1 LTR, respectively, were cotransfected with the infectious HIV-1 DNA clone pNL4-3 into permissive HeLa T4 cells. Each cotransfection resulted in a specific inhibition of HIV-1 replication as determined by syncytia formation and p24 antigen release. In addition, coexpression of the nonaribozyme with an HIV-1 env RNA transcript resulted in the specific dramatic reduction of the env transcript. We conclude that the multitarget-ribozymes are also functional intracellularly. A nucleotide sequence comparison of the target sites indicates that the multitarget-ribozymes could potentially be effective against all thirty HIV-1 isolates presently sequenced. Their use may help to slow the selection of viral escape mutants and thereby prolong their effectiveness. We anticipate that multitarget-ribozymes will also be more effective in the successful targeting of less variable cellular RNAs.

Base Sequence↗