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Biomedical subjects

W Schubert

Publications and source records attributed to W Schubert.

At least 55 records · Page 3Linked to original sources
PubMed1993

Pharmacokinetic evaluation of oral 17 beta-oestradiol and two different fat soluble analogues in ovariectomized women.

A randomised, single-blind comparative study was carried out in 9 ovariectomized women to evaluate the kinetics of single doses of three different steroid combinations: 0.150 mg desogestrel + 2.0 mg micronized 17 beta-oestradiol, 0.150 mg desogestrel + 0.500 mg 17 beta-oestradiol cyclo-octyl acetate and 0.150 mg desogestrel + 1.0 mg 17 beta-oestradiol decanoate. Serum levels of 17 beta-oestradiol and oestrone were measured, as well as the excretion of 17 beta-oestradiol and its metabolites (oestrone and oestriol) in urine. In relation to the doses given, higher peak serum concentrations of 17 beta-oestradiol were obtained after the two fat soluble analogues, while the AUCs were similar to that after micronised 17 beta-oestradiol. However, there was more extensive conversion of the micronised 17 beta-oestradiol preparation into oestrone compared to 17 beta-oestradiol cyclo-octyl acetate and 17 beta-oestradiol decanoate. The oestrone/17 beta-oestradiol serum concentration ratio was approximately 2.6 before tablet intake and remained essentially unchanged after intake of 17 beta-oestradiol cyclo-octyl acetate and 17 beta-oestradiol decanoate. After micronized 17 beta-oestradiol however, there was a 2-3-fold increase in the ratio at Cmax and slower elimination of 17 beta-oestradiol from plasma, which may be due to the fact that high serum oestrone levels may serve as a reservoir, since both a metabolite and also a precursor of 17 beta-oestradiol. The urinary excretion of 17 beta-oestradiol, oestrone and oestriol was highest after oral administration of micronized 17 beta-oestradiol compared to 17 beta-oestradiol cyclo-octyl acetate and 17 beta-oestradiol decanoate.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

APP+ T lymphocytes selectively sorted to endomysial tubes in polymyositis displace NCAM-expressing muscle fibers.

The characteristic pathogenic feature of polymyositis (PM) is muscle invasion by T lymphocytes penetrating the basal lamina and displacing the sarcolemma of normal muscle fibers (T cell invasion of endomysial tubes). Active forward movement of these T cells is indicated by cell extensions interdigitating with the muscle fiber surface. Here we describe for the first time high abundance of Alzheimer amyloid protein precursor (APP) in invasive T cells contacting the border of muscle fibers in PM. These are the sites of muscle fiber displacement. The percentage of APP+ T cells at these sites is significantly higher than in other neuromuscular disorders with inflammatory infiltrates suggesting a specific pathogenic function of these cells in PM. By using a new multiparameter immunofluorescence imaging procedure and confocal laser scanning microscopy, we show that APP+ T cells in PM are invasive front cells that penetrate the basal lamina of the endomysial tube and displace the muscle fiber. Mononuclear cells behind the invasive front are negative for APP or show much lower APP levels. Front T cells either express the CD8-CD4+APP+ or CD8+CD4-APP+ phenotypes, or are CD4+CD8+APP+ T cell chimeras. The highest APP concentration is found at the tip of T cell extensions interdigitating with the fiber surface. Although normal by morphological criteria, the same fibers show intense staining for the regeneration marker NCAM. This reactivity is highest at sites contacted by the APP+ T cells. The findings indicate that APP is specifically upregulated in T cells displacing muscle fibers in PM and suggest that NCAM, which may be abnormally regulated in these fibers, is a candidate molecule for interaction with APP.

Amyloid beta-Protein Precursor↗
PubMed1992

[Duplication of the alimentary canal in infants and children].

This is a review of 30 duplications of the alimentary tract in 28 patients treated at the Surgical Unit of the Children's Department of the Medical University of Pécs, Hungary and at the Department of Pediatric Surgery of the Medical Academy of Dresden, Germany, from 1964 to 1989. The ages of patients ranged from 1 day to 13 years, 80 per cent were less than 2 years of age at initial presentation. There were 6 thoracic, 20 abdominal and 2 thoracoabdominal duplications. Distended abdomen, vomiting, bowel obstruction and palpable abdominal mass were most frequently encountered. Plain thoracic and abdominal X-rays, ultrasonography, barium esophagogram, barium meal and enema were the most common diagnostic procedures. Emergency operative intervention was required in 18 patients. One infant died of an unrelated disease. Twenty-three duplications were cystic and 3 tubular. One patient had an appendiceal duplication, and another patient a flat lumenless duplication located on the perineum close to the anal opening. The surgical procedure--removal of the duplication--should not be more radical than necessary to eliminate the potential complaints and prevent recurrence. During surgery the common blood supply shared between the duplication and the native bowel must be carefully protected to avoid undue sacrifice of normal bowel.

Child↗
PubMed1992

Alimentary tract duplications in infants and children.

This is a review of 30 duplications of the alimentary tract in 28 patients treated at the Surgical Unit of the Children's Department of the Medical University of Pécs, Hungary, and at the Department of Pediatric Surgery of the Medical Academy of Dresden, Germany, from 1964 to 1989. The ages of patients ranged from 1 day to 13 years, 80 percent were less than 2 years of age at initial presentation. There were 6 thoracic, 20 abdominal and 2 thoraco-abdominal duplications. Distended abdomen, vomiting, bowel obstruction and palpable abdominal mass were most frequently encountered. Plain thoracic and abdominal x-rays, ultrasonography, barium esophagogram, barium meal and enema were the most common diagnostic procedures. Emergency operative intervention was required in 18 patients. One infant died of an unrelated disease. Twenty-three duplications were cystic and 3 tubular. One patient had an appendiceal duplication, and another patient a flat lumenless duplication located on the perineum close to the anal opening. The surgical procedure--removal of the duplication--should not be more radical than necessary to eliminate the potential complaints and prevent recurrence. During surgery the common blood supply shared between the duplication and the native bowel must be carefully protected to avoid undue sacrifice of normal bowel.

Adolescent↗
PubMed1992

Silicone breast implants and immune disease.

Silicone was originally regarded as inert in the human body. Silicone medical devices have been associated with various complications that may involve an immune reaction to silicone or a silicone organic complex. There have been more than 80 cases reported in the medical literature of a varied systemic autoimmune illness in patients who have had various foreign materials placed in the breast. Controversy exists as to which complications have a cause and effect relationship, and which represent coincidental findings. It is difficult to distinguish between nonspecific local reactions and reactions that have an immunological basis. Approximately 1,000,000 to 2,000,000 women in the United States have had silicone breast implants inserted for reconstruction or augmentation mammaplasty; 28 of those patients have been reported to have developed a systemic autoimmune disease. Data on the 28 reported cases do not in any way prove a causal relationship between breast implants and immune disease. Given the natural incidence of autoimmune diseases, we would expect a coincidental occurrence in the United States of more than 1,000 cases of autoimmune disease in women who had undergone breast implant surgery. Additional information must be obtained to resolve the question. The true incidence of autoimmune disease in patients with implants needs to be determined. A prospective registry of implant patients should be established and comprehensive retrospective information obtained on the implant patient population. Further experimental work is necessary on the bioreactivity of silicone. Patients with implants and autoimmune disease, once identified, must be carefully evaluated by physicians who are experienced in the treatment of autoimmune disease.

Autoimmune Diseases↗
PubMed1992

Antigenic determinants of T lymphocyte alpha beta receptor and other leukocyte surface proteins as differential markers of skeletal muscle regeneration: detection of spatially and timely restricted patterns by MAM microscopy.

Different stages of human muscle regeneration have been identified by multiple antigen-mapping (MAM) microscopy at the level of a novel marker system. This immunofluorescence method allows the selective imaging of numerous antigen signals from cells or tissue sections. It is shown that 2 monoclonal antibodies (mAbs) against the common region of the alpha beta T lymphocyte antigen receptor (alpha beta and alpha TCR chains) and 3 mAbs against the leukocyte surface antigens Leu8, OKM5 and Leu19 recognize regenerating muscle cells at different time points of regeneration in human muscle sections. Paradoxically, these epitopes are not expressed by T lymphocytes or other mononuclear leukocytes invading regenerating muscle. Hence, presence of the corresponding antigens in muscle fibers may exclude their expression by muscle-invasive immune cells suggesting a function in muscle-specific cell-to-cell recognition. Simultaneous localization of these epitopes in Duchenne dystrophy reveals 10 different phenotypes of regenerating and normal infantile muscle cells due to different developmental stages during the myocyte differentiation. In adult muscle (mitochondrial myopathy) segmental muscle fiber necrosis is accompanied by high concentration of alpha beta/alpha TCR epitopes in the intact fiber ends, which are the target sites of myogenesis. The same sites are invaded by OKM5+ endomysial capillary sprouts that terminate at the tip of the alpha beta/alpha TCR reactive fiber ends. These hitherto unrecognized initial events of segmental muscle regeneration seem to be followed by fragmentation of the invasive capillaries into single endothelial cells, which then switch from the OKM5+ Leu19- through the OKM5+ Leu19+ to the OKM5- Leu19+ phenotype. This cell type exhibits the typical features of Leu19+ myogenic stem cells described earlier. The findings may give rise to a concept of muscle repair, in which the alpha beta/alpha TCR-related antigen, concentrated in fiber stumps, might provide positional information for invading endothelial cells. These cells appear to be a source of myogenic stem cells for regeneration.

Adult↗
PubMed1992

Pneumocystis carinii pneumonia (PCP) and your child: a parent information booklet.

A parent education booklet describing Pneumocystis carinii pneumonia (PCP) was prepared by the Pediatric Branch of the National Cancer Institute. In addition to information about prophylaxis and treatment of PCP, the booklet discusses overall care of children infected with human immunodeficiency virus.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Localization of Alzheimer beta A4 amyloid precursor protein at central and peripheral synaptic sites.

We have recently shown that the amyloid beta A4 precursor protein (APP) is synthesized in neurons and undergoes fast axonal transport to synaptic sites [Koo et al., Proc. Natl. Acad. Sci. U.S.A., 87 (1990) 1561-1565]. Using immunofluorescence, laser confocal microscopy and immunoelectron microscopy with simultaneous detection of APP and synaptophysin, we now report a preferential localization of APP at synaptic sites of human and rat brain and at neuromuscular junctions. APP is further found on vesicular elements of neuronal perikarya, dendrites and axons. The synaptic localization of APP implies (1) a role of APP in physiological synaptic activity and (2) a potential and early impairment of central synapses when synaptic APP is converted to beta A4 amyloid during the pathological evolution of Alzheimer's disease and Down's syndrome.

Amyloid beta-Protein Precursor↗
PubMed1991

Chest-wall deformity after tissue expansion for breast reconstruction.

A prospective longitudinal study of chest-wall deformity after tissue expansion for breast reconstruction was performed in 19 women. CT imaging was a sensitive method for detecting occult deformity. Using a semiquantitative scale for measuring deformity, all patients and 94 percent of expanders had some thoracic abnormality after tissue expansion. Rib and chest-wall contour changes were observed under 81 and 68 percent of the expanders, respectively. Routine chest roentgenograms were not a sensitive method for evaluating these deformities. The magnitude of deformity after unilateral expansion was not significantly different from that after bilateral expansion. Linear regression analysis indicated that early periprosthetic capsular contracture was negatively correlated with chest wall deformity. Only one patient experienced a clinically noticeable complication from chest compression--transient postexpansion exertional dyspnea. After removing the expanders and placing permanent implants along with capsulotomy, the mean deformity index decreased by 57 percent after 10.5 months median follow-up, which was highly significant (p less than 0.001). Our findings suggest that chest-wall deformity is a common occurrence after tissue expansion in patients undergoing breast reconstruction and is usually of minor clinical significance.

Female↗
PubMed1991

Mechanisms of amyloid deposition in Alzheimer's disease.

At the cellular level, Alzheimer's disease (AD) must be the result of neuronal dysfunction and degeneration leading to a reduction in synaptic density. Filamentous deposits of amyloid, which define the disease at the molecular level, occur within perikarya, axons, dendrites, and terminals of neurons as neurofibrillary tangles (NFT), in the extracellular neuropil as amyloid plaques (APC), and around blood vessels as amyloid congophilic angiopathy (ACA). These fibrillar amyloid protein aggregates are also found in the brain of all individuals with Down's syndrome after the age of 30 years. The amyloid deposits apparently occur in the terminal zones of neurons that develop NFT. It is suggested that amyloid deposition is of fundamental significance in AD and that a thorough understanding of amyloid formation will eventually lead to successful therapeutic intervention in AD. As elucidation of the reasons behind amyloid deposition must shed some light on the pathogenesis of AD, we review the current state of knowledge on the nature of the AD amyloid protein, its origin, and its formation. Although there is yet no agreement about the chemical nature of the amyloid protein of NFT, the major constituent of both APC and ACA has been shown to be a 4.5-kD amyloid protein originally termed "beta-protein" or "amyloid A4" which we now denote as "beta A4." Amyloid beta A4 protein is proteolytically derived from a transmembrane protein termed amyloid precursor protein (APP) which is encoded by a widely expressed gene on chromosome 21. Our present results are consistent with the possibility that amyloid formation requires membrane damage or APP molecules that are not or are incorrectly integrated into membranes. To allow the generation of the C-terminus of beta A4, one proteolytic cleavage step has to occur in the sequence that normally forms the transmembrane domain of the APP proteins. This cleavage is crucial for amyloid formation because we could show that the ability of synthetic beta A4 to form amyloid depositions is mainly based on hydrophobic parts of the sequence that have to interact with each other and build up large aggregates under physiologic conditions. Membrane association of APP is expected to interfere with this cleavage and the process of aggregation.

Aging↗
PubMed1991

Triple immunofluorescence confocal laser scanning microscopy: spatial correlation of novel cellular differentiation markers in human muscle biopsies.

Two different methods for triple immunofluorescence imaging with a confocal laser scanning microscope (CLSM) are described. The methods enable spatial "mapping" of 3 different epitope distribution patterns simultaneously in one tissue section. The key to triple imaging includes: (a) specific immunolabeling with 3 different mouse monoclonal antibodies (mAbs), (b) localization of the antibody binding sites by 3 different dyes, (c) spectral isolation of each dye by using selective band pass or long pass emission filters, (d) computerized imaging of the fluorescences as colored overlays or as selective signals in each optical section through the tissue in the z-direction. Method 1 consists of the combination of fluorescein isothiocyanate (FITC), phycoerythrin R (PE), and Texas Red (TR) as fluorescent markers. These dyes can be imaged by using 488 nm and 543 nm excitation laser lines. In method 2 aminomethyl coumarin acetic acid (AMCA) was combined with FITC and PE. For this application the CLSM was adapted to ultraviolet microscopy that enabled the use of 3 laser lines (364 nm, 488 nm, 543 nm) for excitations. Cryostat sections of diagnostic human muscle biopsies (n = 9) were studied which were normal by ordinary light microscopic examination. Sections were incubated with mAbs specific for: (1) the fast myosin heavy chain (My32); (2) the major histocompatibility class II antigen HLA-DR; (3) the lymph node homing receptor Leu8, and (4) the cell adhesion receptor OKM5 (CD36). By combining these mAbs in triple staining procedures, 3 capillary types and 4 different phenotypes expressed by muscle fibers were identified simultaneously. The mAbs Leu8 and OKM5, widely used as leukocyte typing antibodies in the blood, exhibit hitherto unrecognized specificities for antigens displayed by muscle fibers. At the level of these markers, specific spatial correlations between OKM5 reactive capillaries and both OKM5 reactive and nonreactive muscle fiber types become visible. The presented results provide direct evidence for cellular complexity and novel insight into the immunoanatomical architecture of skeletal muscle. The methods may be of general significance for the construction and quantification of three-dimensional multiparameter "maps" of cells and tissues.

Adult↗
PubMed1990

[Myohyperplasia of the lung arterioles in congenital diaphragmatic defects].

The ratio of lumen/wall thickness of pulmonary arterioles was measured in patients who died post-operatively due to a congenital diaphragmatic defect. This was compared to normal arterioles in healthy newborn lungs. The wall musculature of pulmonary arterioles was 2.8 times thicker than in normal arterioles of newborn lungs. The main cause of this enormous wall thickness is a genuine growth of substance, i.e. myohyperplasia. Myohypertrophia can be an additional reason.

Arteries↗
PubMed1990

[Therapy of traumatic hemobilia].

Haematobilia is caused by a pathological linking of the arterial vascular system and intrahepatic or extrahepatic bile ducts. This report presents the case of a traumatic haematobilia in a child. Possibilities to achieve safe diagnosis are discussed and suggestions for treatment are considered. In the case presented here, occlusion of the arteriobiliar shunt is effected by means of a rejectable balloon catheter according to Serbinenko. This method has been successfully tried in neurosurgery and developed further, and can be applied to similar disease patterns in disciplines other than neurosurgery.

Abdominal Injuries↗
PubMed1990

[Personal experiences with covering burns in children with amnion].

The different methods of local treatment of burns are still controversial. Aims of good local are the therapy prevention of fluid loss, loss of proteins, electrolytes, heat and energy, prevention eg. reduction of wound infections, preservation and acceleration of regeneration of remained own skin, influence on good formation of scars eg. preparing of high value as possible transplant-ground for eventual necessary skin transplantation. Experience in covering juvenile burn-injuries with lyophilized Human-Amnion were gathered in our department for more than 15 years. The treatment of patients with this "biological bandage" and results were demonstrated. In our opinion the method of primary amnion covering of juvenile burn-injuries is superior to other procedures.

Amnion↗