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Biomedical subjects

K Weber

Publications and source records attributed to K Weber.

At least 343 records · Page 19Linked to original sources
PubMed1989

Injury biomechanics research: an essential element in the prevention of trauma.

The central aspects of injury biomechanics research are defined and research approaches described. These aspects include the identification and definition of impact injury mechanisms, the quantification of biomechanical response to impact, the determination of impact tolerance levels, and the development and use of injury assessment devices and techniques for evaluating injury prevention systems. The current status of knowledge and technology is then reviewed for the head, cervical spine, thorax, abdomen, and lower extremity. Important gaps are identified, and research priorities emphasizing functional impairment are proposed.

Abdominal Injuries↗
PubMed1989

Interaction of anti-DNA antibodies with synthetic polyanionic antigens.

Autoantibodies to DNA (anti-DNAab), found primarily in systemic lupus erythematosus (SLE), cross-react with a variety of antigens. The binding of these antibodies to naturally occurring mucopolysaccharides such as heparan and chondroitin sulfates has led to the suggestion that anti-DNAab have specificity for a polyanionic epitope. In this study, to avoid the use of endogenous immunogens to which humans may have become sensitized, we have used the synthetic polyanions, dextran sulfate (DS), polyvinyl sulfate (PVS) and the semi-synthetic antigen, pectic acid (PA) to evaluate this hypothesis using SLE sera (n = 15) and sera from healthy individuals (controls; n = 15, age and sex matched to SLE group). Inhibition of binding with 125I-DNA was optimal at 1 mg/ml for DS and PVS, and resulted in significant inhibition of binding by both SLE and control sera of native DNA (P less than 0.01, each group); no inhibition was observed with PA, nor was a significant inhibition observed with any antigen on binding of SLE or control sera groups to denatured DNA. We conclude that while on quantitative grounds reaction of anti-DNAab with polyanions may not be clinically relevant, it is clear that, unlike polycarboxylates (e.g. PA), polysulfated polymers, whether aliphatic, as in the case of PVS, or glycosidic, such as DS, react with a subpopulation of anti-DNAab in such a manner as to block significantly the ability of these antibodies to bind DNA.

Analysis of Variance↗
PubMed1989

Myogenesis in the mouse embryo: differential onset of expression of myogenic proteins and the involvement of titin in myofibril assembly.

Antibodies to muscle-specific proteins were used in immunofluorescence to monitor the development of skeletal muscle during mouse embryogenesis. At gestation day (g.d.) 9 a single layer of vimentin filament containing cells in the myotome domain of cervical somites begins to stain positively for myogenic proteins. The muscle-specific proteins are expressed in a specific order between g.d. 9 and 9.5. Desmin is detected first, then titin, then the muscle specific actin and myosin heavy chains, and finally nebulin. At g.d. 9.5 fibrous desmin structures are already present, while for the other myogenic proteins no structure can be detected. Some prefusion myoblasts display at g.d. 11 and 12 tiny and immature myofibrils. These reveal a periodic pattern of myosin, nebulin, and those titin epitopes known to occur at and close to the Z line. In contrast titin epitopes, which are present in mature myofibrils along the A band and at the A-I junction, are still randomly distributed. We propose, that the Z line connected structures and the A bands (myosin filaments) assemble independently, and that the known interaction of the I-Z-I brushes with the A bands occurs at a later developmental stage. After fusion of myoblasts to myotubes at g.d. 13 and 14 all titin epitopes show the myofibrillar banding pattern. The predominantly longitudinal orientation of desmin filaments seen in myoblasts and in early myotubes is transformed at g.d. 17 and 18 to distinct Z line connected striations. Vimentin, still present together with desmin in the myoblasts, is lost from the myotubes. Our results indicate that the putative elastic titin filaments act as integrators during skeletal muscle development. Some developmental aspects of eye and limb muscles are also described.

Actins↗
PubMed1989

Visualization of the polarity of isolated titin molecules: a single globular head on a long thin rod as the M band anchoring domain?

TII, the extractable form of titin, was purified from myofibrils and separated by high resolution gel permeation chromatography into two fractions (TIIA and TIIB). Novel specimen orientation methods used before metal shadowing and EM result in striking pictures of the two forms. Molecules layered on mica become uniformly oriented when subjected to centrifugation. TIIB comprises a very homogeneous fraction. All molecules reveal a single globular head at one end on a long and very thin rod of uniform diameter. The lengths of the rods have a very narrow distribution (900 +/- 50 nm). TIIA molecules seem lateral oligomers of TIIB, attached to each other via the head regions. While dimers are the predominant species, trimers and some higher oligomers can also be discerned. Mild proteolysis destroys the heads and converts TIIA and TIIB into TIIB-like rods. Similar molecules also result from titin purified from myofibrils by certain established purification schemes. Headless titin molecules show in gel electrophoresis only the TII band, while head bearing molecules give rise to two additional polypeptides at 165 and 190 kD. Immunoelectron microscopy of myofibrils identifies both titin-associated proteins as M band constituents. We speculate that in the polar images of TII the globular head region corresponds to the M band end of the titin molecules. This hypothesis is supported by immunoelectron micrographs of TIIB molecules using titin antibodies of known epitope location in the half sarcomere. This proposal complements our previous immunoelectron microscopic data on myofibrils. They showed that epitopes present only on the nonextractable TI species locate to the Z line and its immediately adjacent region (Fürst, D. O., M. Osborn, R. Nave, and K. Weber. 1988. J. Cell Biol. 106:1563-1572). Thus, the two distinct ends of the titin molecule attach to Z and M band material respectively.

Animals↗
PubMed1989

Haemodynamic studies with a phasic release nitroglycerin patch system.

The use of transdermal nitroglycerin (GTN) patches in patients with coronary artery disease is of uncertain value as numerous investigators have failed to confirm clinical efficacy for more than 8h. This relatively short duration of action is an indication of rapidly developing tolerance due to the relatively constant GTN plasma levels following GTN patch application. We investigated the efficacy of a newly developed GTN patch with a discontinuous release profile in 28 patients with coronary heart disease. Two hours after initial administration, pulmonary capillary wedge (PCW) pressure decreased by 25.7% at rest and by 25.1% during exercise. Cardiac index at rest decreased by 12.2%. No significant changes were observed in systemic blood pressure and heart rate. No significant haemodynamic effects were apparent after 24h. Following renewed GTN patch application, a decrease in PCW pressure occurred, similar to that observed after acute administration. After 1 week of daily therapy, similar changes were observed: 24h after patch application, PCW was similar to baseline values but showed a significant decrease 2h after patch re-application. These data suggest that the phasic release GTN patch is not associated with tolerance to the haemodynamic effects during sustained once daily therapy.

Administration, Cutaneous↗
PubMed1989

Effects of spinal cord lesioning on somatosensory and neurogenic-motor evoked potentials.

Somatosensory (SEPs) and neurogenic-motor evoked potentials (NMEPs) were elicited from 16 hogs and two humans before, during, and after spinal cordotomy, dorsal, or ventral root rhizotomy. Results indicated that SEPs appear to be insensitive to the effects of motor tract lesioning in hogs and humans. In every case of motor paraplegia, SEPs remained unchanged in the presence of abnormal ischiatic/sciatic NMEPs. These results suggest that SEPs are not adequately sensitive to the functional status of the motor system in hogs and humans. Ischiatic/sciatic NMEPs remained unchanged after sensory tract lesioning, suggesting that these NMEPs are insensitive to the functional status of the sensory system. These results suggest that SEPs and NMEPs should be used in combination when monitoring spinal cord function during surgeries that place that structure at risk.

Animals↗
PubMed1989

Differential timing of nuclear lamin A/C expression in the various organs of the mouse embryo and the young animal: a developmental study.

In mouse embryos, acquisition of the nuclear lamin polypeptides A/C varies according to developmental stage and tissue type. In order to determine the precise time points and cell types in which lamin A/C are first observed, we have used two monoclonal antibodies in immunofluorescence studies of different tissues of developing mouse embryos and of young mice. One antibody (mAB346) is specific for lamins A and C, while the other (PKB8) detects lamins A, B and C. Dividing uterine development into three phases--germ layer formation, organogenesis and tissue differentiation--our results show that lamin A/C expression in the embryo proper is not observed until the third phase of development. Lamin A/C first appears at embryonic day 12 in muscle cells of the trunk, head and the appendages. Three days later it is also seen in cells of the epidermis where its appearance coincides with the time of stratification. In the simple epithelial of lung, liver, kidney and intestine, as well as in heart and brain, lamins A/C do not appear until well after birth. Embryonal carcinoma (EC) cells express lamin B but not lamin A/C. Lamin A/C expression is noted in some EC cells after they are induced to differentiate and in several differentiated teratocarcinoma cell lines. Our results suggest that commitment of a cell to a particular pathway of differentiation (assayed by cell-type-specific expression of intermediate filament proteins) usually occurs prior to the time that lamin A/C can be detected. Thus lamin A/C expression may serve as a limit on the plasticity of cells for further developmental events.

Animals↗
PubMed1989

Repetitive titin epitopes with a 42 nm spacing coincide in relative position with known A band striations also identified by major myosin-associated proteins. An immunoelectron-microscopical study on myofibrils.

A direct titin-thick filament interaction in certain regions of the A band is suggested by results using four new monoclonal antibodies specific for titin in immunoelectron microscopy. Antibodies T30, T31 and T32 identify quasi-repeats in the titin molecule characterized by a 42-43 nm repeat spacing. These stripes seem to coincide with striations established by others on negatively stained cryosections of the A band. Antibodies T30 and T32 recognize epitopes matching five or two of the seven striations per half sacromere known to harbor both the myosin-associated C-protein and an 86K (K = 10(3) Mr) protein. Antibody T31 labels two stripes in the P zone, which correspond to the two positions where decoration is seen with 86K protein, but not with C-protein. The single titin epitope defined by antibody T33 is located 55 nm prior to the center of the M band. This position seems to coincide with the M7 striation defined by others on negatively stained A bands. The T33 epitope position proves that the titin molecule, which is known to be anchored at the Z line, also penetrates into the complex architecture of the M band. The titin epitopes described here enable us to begin to correlate known ultrastructural aspects of the interior part of the A band with the disposition of the titin molecule in the sarcomere. They raise the question of whether there is a regular interaction pattern between titin and the thick filaments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Coexpression of intermediate filaments in squamous cell carcinomas of upper aerodigestive tract before and after radiation and chemotherapy.

Frozen sections of 48 squamous cell carcinomas and seven undifferentiated carcinomas of the upper aerodigestive tract were investigated immunohistochemically with monoclonal antibodies specific for keratin, vimentin, desmin, neurofilaments, and glial fibrillary acidic proteins. In nine squamous cell carcinomas (19%) and six undifferentiated carcinomas (86%) obtained before treatment coexpression of keratin and vimentin was detected in some tumor cells by double immunofluorescence studies. Nine squamous cell carcinomas expressed neurofilaments in scattered tumor cells. Coexpression of vimentin or neurofilaments was seen especially in the peripheral cell layer of the tumor nests and did not seem to correlate with the degree of differentiation. Three undifferentiated carcinomas additionally expressed desmin, and one tumor contained neurofilaments. Glial fibrillary acidic proteins were not detected. Increased coexpression of keratin with vimentin, desmin, or neurofilaments was seen in some tumors that were studied before and after radiation/chemotherapy, suggesting that the intermediate filament profile of tumor cells can be altered by external influences.

Carcinoma, Squamous Cell↗
PubMed1989

Differential distribution of alpha-tubulin isotypes in Euplotes eurystomus determined by confocal immunofluorescence microscopy.

Detergent permeabilized Euplotes eurystomus (a fresh water hypotrichous ciliate) was reacted with monoclonal and polyclonal antibodies specific for either detyrosinated or tyrosinated alpha-tubulin (Glu- or Tyr-tubulin). The isolated cytoskeleton-nuclear complex was examined by Western immunoblotting and by immunofluorescent and electron microscopic methods. Both Glu- and Tyr-tubulins were detected by immunoblot analysis. Immunofluorescent microscopy indicated that the alpha-tubulin isotypes are concentrated in different regions of permeabilized cells: Glu-tubulin is located primarily in cirri, membranelles, and surrounding the macro- and micronuclei. Tyr-tubulin is principally at the bases of cirri and membranelles. This differential distribution of alpha-tubulin isotypes is discussed in terms of current concepts concerning the correlation of tubulin post-translational modifications to microtubule stability. Confocal immunofluorescent imaging was of critical importance in clearly differentiating the Glu-tubulin isotype surrounding the macro- and micronuclei from a brilliantly fluorescent environment originating from cytoskeletal structures. In conjunction with conventional and stereo-electron microscopy, confocal optical microscopy provided convincing evidence for a "basket" of microtubules surrounding both nuclei.

Animals↗
PubMed1989

Leukocyte-common antigen and vimentin are reliable adjuncts in the diagnosis of non-Hodgkin's lymphoma in fine needle aspirates.

Alcohol-fixed fine needle aspirates of 82 non-Hodgkin's malignant lymphomas (NHLs) were tested for the presence of vimentin and leukocyte-common antigen (LCA) by means of monoclonal antibodies (MAbs) and indirect immunofluorescence. All NHLs stained positively for vimentin; the staining was strong in all except three cases. Of the 69 NHLs tested for LCA, 1 (a large cell T-cell lymphoma) was negative while the staining was weak in 6. Thus, vimentin and LCA MAbs are sensitive, specific and reliable complementary diagnostic adjuncts that are useful in the definitive diagnosis of NHLs in alcohol-fixed fine needle aspirates. Their presence in the aspirate confirmed a cytologic diagnosis of NHL in 47 cases, helped to diagnose NHL in 31 cases in which a cytologic differential diagnosis with small cell anaplastic carcinoma could not be made with confidence and helped to change the initial cytologic diagnosis of anaplastic carcinoma to NHL in 4 cases.

Antigens, Differentiation↗
PubMed1989

[Recent aspects of emergency service responsibilities for public health services].

Today's emergency and first-aid systems are a challenge to Public Health offices which they must meet diligently and competently within the framework of health care and defence against health hazards. Close cooperation with fire brigades and first-aid and emergency service organizations is mandatory especially in case of threatening major disasters (for example, accidents involving large amounts of toxic matter). There are gaps in the immediate care and service systems in case of emergencies. Public Health offices are called upon to close these gaps by active participation, if required, at the site of the disaster, in the management and supervision of first-aid and other measures in the fight against the sequels of major disasters or catastrophes. Innovative concepts regarding the future development of public emergency and first-aid services have been worked out.

Disaster Planning↗
PubMed1989

[Diagnosis of sleep apnea: required equipment for staged diagnosis].

In view of the high prevalence of sleep apnoea (SA) a stepped concept for diagnosis and therapy is needed. Such a concept requires appropriate instrumentation. The apparative requirement for a five-stage concept, and the experience gained with it, are presented, in particular these newly introduced stages: screening instrument, based on an analysis of heart rate and breathing sounds, and a mobile sleep laboratory based on oxygen saturation measurement combined with inductive plethysmography and four further parameters. Experience obtained with such a stepped concept demonstrates its efficiency and necessity in the diagnosis of sleep-related breathing disturbances.

Electrocardiography, Ambulatory↗
PubMed1989

The p36 substrate of pp60src kinase is located at the cytoplasmic surface of the plasma membrane of fibroblasts; an immunoelectron microscopic analysis.

p36, a member of the family of Ca2+/lipid-binding proteins, is a major cellular substrate for the tyrosine kinase encoded by the src oncogene. It occurs in two distinct physical states, as either a monomer or a heterotetramer (protein I), which comprises two copies each of p36 and a p11 polypeptide. Immunofluorescence microscopy and cell fractionation studies suggest that p36 and p11 are located underneath the plasma membrane. To investigate whether p36 is indeed associated with the plasma membrane, we have examined its cellular distribution at the electron microscopic level with gold-labeled antibodies. In human fibroblasts, p36 is clearly associated with the cytoplasmic side of the plasma membrane and shows a uniform and regular distribution. Decoration with monoclonal antibodies against p11 reveals the same distribution, suggesting that the p36(2)p11(2) complex (protein I) occurs in the cell in a strict association with the plasma membrane. Titration experiments show that this association is Ca2+ dependent and still occurs at physiological Ca2+ concentrations (10(-7) M). Fodrin, a non-erythroid spectrin, known to bind p36 in vitro, shows a very similar distribution on the cytoplasmic side of the plasma membrane. The results suggest that in a resting and unstimulated cell p36 and p11 reside as a complex bound to the inner side of the plasma membrane.

Antibodies, Monoclonal↗
PubMed1989

Endothelial cells help in the diagnosis of primary versus metastatic carcinoma of the liver in fine needle aspirates. An immunofluorescence study with vimentin and endothelial cell-specific antibodies.

Fine needle aspirates of 5 primary hepatocellular carcinomas and 24 carcinomas metastatic to the liver were studied using vimentin and endothelial cell-specific monoclonal antibodies. Numerous endothelial cells dispersed and in bundles overlying clumps of tumor cells were positively stained by both antibodies in smears of primary hepatocellular carcinomas while such cells were rare or absent in metastatic carcinomas, with the exception of clear cell carcinoma of the kidney. It is concluded that endothelial cells, if present in large numbers in fine needle aspirates of a hepatic carcinoma and arranged in bundles that envelope the clumps of tumor cells, can (1) suggest the presence of a primary hepatocarcinoma and (2) narrow the differential diagnosis with the most common metastatic cancers to renal cell carcinoma.

Antibodies, Monoclonal↗