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Biomedical subjects

A Weiss

Publications and source records attributed to A Weiss.

At least 289 records · Page 16Linked to original sources

Age and exercise-related changes in myocardial mitochondria in mice.

A quantitative histochemical and an ultrastructural study was performed on the left ventricular myocardium of C57BL/6J female mice to evaluate the effects of aging and running exercise on mitochondrial structure and SDH activity. A comparison was made between 6-month-old ("young") and 27-month-old ("old") sedentary mice with age-matched mice subjected to running schedules (10 or 30 min/d) for 6 weeks. In longer-term studies, 27-month-old mice were given similar daily running schedules over a 10 month period ("long term runners"). No significant differences were found in SDH activity during the normal course of aging in mice (6 to 27 months of age), however, the response to running differed markedly in young versus old mice. "Young" trained mice showed significant increase in SDH activity compared with age-matched sedentary mice, whereas "old" trained mice showed significantly reduced SDH activity. Electron microscopy showed ultrastructural changes in mitochondria associated with aging including the development of large aggregations of mitochondria in subsarcolemmal and paranuclear sites. Running schedules, especially in aged runners, caused an increase in interfibrillar mitochondria hypertrophy, loss of matrix and cristae, incorporation of lipid inclusions and the formation of giant mitochondria. These abnormal mitochondrial changes are interpreted as being degenerative and possibly contributing to the reduced SDH levels found in cardiac myocytes of aged runners. Our results indicate that whereas regular exercise in young animals enhanced SDH activity, in aged mice it may be detrimental rather than beneficial.

Aging↗

[Risks of fine needle puncture--results of a survey in West Germany(German Society of Ultrasound in Medicine survey)].

The rate of complications in fine needle puncture was ascertained by an inquiry conducted among the members of the German Association of Ultrasound in Medicine (DEGUM). 337 complications had been registered in a total of 66,397 punctures, corresponding to a percentage of only 0.51%. 294 of these were mild, i.e. not requiring therapy (0.44%), 38 severe (0.057%) and 5 complications were fatal and resulted in death (0.0075%). Differences were slight in respect of the frequency of complications with reference to puncture technique and type of needle employed. Most complications were seen in fine needle puncture for obtaining histological material (0.67%) (cutting biopsy needles), compared with 0.54% in therapeutic puncture and 0.46% for obtaining cytological material. Among the puncture techniques, the use of a puncture transducer resulted in more complications (0.72%) compared with sonographically guided puncture (0.59%) and puncture in full view with 0.43%. Punctures with/fatal outcome had been conducted in 4 out 5 cases with so-called cutting biopsy needles. Results are identical with those obtained in the U.S.A. on a comparative basis. Compared with punctures with so-called coarse needles, fine needle puncture results in fewer complications on account of the smaller needle caliber. As with every intensive method, however, complications must be taken into account even with fine needle puncture.

Biopsy, Needle↗

At least two non-antigen-binding molecules are required for signal transduction by the T-cell antigen receptor.

In the T-cell somatic mutant J.CaM1, the T-cell antigen receptor complex is poorly coupled to the inositolphospholipid second messenger system; some antibodies against the invariant CD3 subunit of the receptor retain their agonist function in J.CaM1. Here we show by a combination of complementation assays that the mutation in J.CaM1 affects a molecule other than the antigen-binding Ti subunit, suggesting that Ti is coupled indirectly to the signal transduction apparatus through a pathway involving the CD3 complex. We also describe another mutant, J.CaM2, in which the receptor complex is completely uncoupled from inositolphospholipid hydrolysis. J.CaM2 defines an additional complementation group, suggesting that signal transduction by the antigen receptor depends on at least two molecules distinct from Ti.

Calcium↗

Acute pseudobulbar mutism due to discrete bilateral capsular infarction in the territory of the anterior choroidal artery.

Pseudobulbar mutism is rarely attributed to bilateral discrete posterior limb internal capsule-medial globus pallidus infarction. Few cases of bilateral anterior choroidal (AchA) artery territory infarction have been reported. We present 8 patients with ischaemic stroke in this location and vascular distribution who have a characterizable syndrome. All had the abrupt onset of inability to speak, swallow or phonate, accompanied by varying degrees of facial diplegia, hemiparesis, hemisensory loss, lethargy, neglect and change in affect. The appearance of clinical signs depends upon the presence of a new infarct contralateral to an older lesion in mirror position. The pathogenesis and progression of neurological deficit appears to be intimately related to hypertension. The role of intrinsic intracranial vascular pathology related to diabetes mellitus, embolism of cardiac origin and atherosclerosis is currently undefined. The prognosis for recovery is poor. Half of our patients died within a year of onset of symptoms. Capsular pseudobulbar mutism is recognized by the abrupt appearance of neurological deficit consistent with internal capsular pathology and is confirmed by CT scan or MRI.

Acute Disease↗

Failure of charcoal-horse-blood broth with cephalexin to significantly increase rate of Bordetella isolation from clinical specimens.

In a field trial conducted in cooperation with pediatricians in private practice, 198 nasopharyngeal swabs from children with suspected whooping cough were placed into charcoal-horse-blood transport medium with cephalexin (40 mg/liter). After preincubation at 36 degrees C for 1 to 2 days, the transport systems were mailed to the laboratory. There, the swabs were plated onto charcoal-horse-blood agar with cephalexin and were subsequently incubated for 48 h in cephalexin-containing charcoal-horse-blood broth which was then subcultured onto the agar. Forty-six Bordetella pertussis strains and seven Bordetella parapertussis strains were isolated (Bordetella isolation rate, 26.8%). Only three (5.7%) of the 53 Bordetella strains were detected exclusively by use of the broth. This low rate of additional isolates is probably explained by the fact that the swabs had been submitted in charcoal-horse-blood transport medium which itself acts as an enrichment medium.

Blood↗

In situ reassociation of the regulatory and catalytic subunits of 3',5'-cyclic adenosine monophosphate-dependent protein kinase isoenzymes in AtT20 cells.

Dissociation and reassociation of regulatory (R) and catalytic (C) subunits of cAMP-dependent protein kinases I and II were studied in intact AtT20 cells. Cells were stimulated with 50 microM forskolin to raise intracellular cAMP levels and induce complete dissociation of R and C subunits. After the removal of forskolin from the incubation medium cAMP levels rapidly declined to basal levels. Reassociation of R and C subunits was monitored by immunoprecipitation of cAMP-dependent protein kinase activity using anti-R immunoglobulins. The time course for reassociation of R and C subunits paralleled the loss of cellular cAMP. Total cAMP-dependent protein kinase activity and the ratio of protein kinase I to protein kinase II seen 30 min after the removal of forskolin was the same as in control cells. Similar results were seen using crude AtT20 cell extracts treated with exogenous cAMP and Mg2+. Our data showed that after removal of a stimulus from AtT20 cells inactivation of both cAMP-dependent protein kinase isoenzymes occurred by the rapid reassociation of R and C subunits to form holoenzyme. Our studies also showed that half of the type I regulatory subunit (RI) present in control cells contained bound cAMP. This represented approximately 30% of the cellular cAMP in nonstimulated cells. The cAMP bound to RI was resistant to hydrolysis by cyclic nucleotide phosphodiesterase but was dissociated from RI in the presence of excess purified bovine heart C. The RI subunits devoid of C may function to sequester cAMP and, thereby, prevent the activation of cAMP-dependent protein kinase activity in nonstimulated AtT20 cells.

Animals↗

Whiplash syndrome. Fact or fiction?

A sprain/strain syndrome or "whiplash injury" is the most common cervical injury associated with rear-end impact motor vehicle accidents. This results in a complex injury, often associated with extensive soft tissue injury in the cervical spine. There is additional potential for long term alteration in neurologic, muscular, and skeletal function. Evaluation and treatment should follow standard orthopedic principles.

Humans↗

The computer. An orthopedic instrument.

The computer has become an important tool in orthopedic practice. Indeed, it is now invaluable and will soon be essential. It is still possible to run an orthopedic office without a computer--just as it is still possible to perform meniscectomy by arthrotomy--but that is not what most of us would do. The computer enhances efficiency, can improve business practice, assists in marketing, and helps store and retrieve medical information. The ultimate impact is not only on "business" functions but also on the quality of care.

Ambulatory Care Information Systems↗

Glucocorticoid hormone adversely affects the growth and regeneration of cartilage in vitro.

Apical portion of condylar cartilage of neonatal mice served as an experimental model to study the in vitro effects of elevated concentration of triamcinolone, a fluorinated synthetic analogue of cortisol on cartilage cell growth and development. Triamcinolone acetonide (10(-6) M) led to a significant decrease in the proliferative rate of chondroprogenitor cells along with an inhibition of the chondrogenic differentiation pathway. By 5 days in culture, control explants exhibited a pronounced increase in size and succeeded to reconstitute their native form. In hormone-treated cultures, the explants also elongated yet the increase was due to an accelerated cellular hypertrophy rather than increase in cell number. The findings of the present study which were based upon quantitative 3H-thymidine autoradiography as well as upon determination of 3H-thymidine incorporation suggest that in vitro corticosteroid hormone depresses pre-chondroblasts proliferation along with an interference in the normal differentiative pathway of the above cells.

Animals↗

Functional competency of T cell antigen receptors in human thymus.

The T cell antigen receptor is likely to play a role in both positive and negative selection in the thymus. Three populations of thymocytes can be distinguished by the level of expression of the CD3-alpha/beta-chain heterodimer of the T cell antigen receptor (CD3/Ti alpha/beta) complex. Cells which fail to express these receptors or express low levels of receptors are contained in a population of thymocytes which express low levels of the CD5 antigen and are predominantly CD4+/CD8+. Thus, these cells appear to be relatively immature phenotypically. In contrast, the cells which express high levels of CD3/Ti alpha/beta co-express high levels of CD5 and are predominantly contained in the more mature single positive cells which express either CD4 or CD8. With the calcium-sensitive dye, Indo-1, and immunofluorescence, we demonstrated that, despite the relative phenotypic immaturity of cells which express low levels of CD3/Ti alpha/beta, these antigen receptors are able to mediate transmembrane signaling when stimulated with CD3 monoclonal antibodies. Although increases in calcium were observed in these CD3/Ti alpha/beta-low expressing cells in response to anti-CD3, no proliferative response was observed, even in the presence of phorbol myristate acetate. Proliferative responses were observed in the more mature cells which express high levels of CD3/Ti alpha/beta. These results suggest that, rather than a defect in the functional capability of the antigen receptor complex to mediate transmembrane signaling events, cellular responses to signals generated by the antigen receptor may differ at various stages of thymocyte development.

Antigens, Differentiation, T-Lymphocyte↗

The T-cell antigen receptor regulates sustained increases in cytoplasmic free Ca2+ through extracellular Ca2+ influx and ongoing intracellular Ca2+ mobilization.

Signal transduction by the T-cell antigen receptor involves the turnover of polyphosphoinositides and an increase in the concentration of cytoplasmic free Ca2+ ([Ca2+]i). This increase in [Ca2+]i is due initially to the release of Ca2+ from intracellular stores, but is sustained by the influx of extracellular Ca2+. To examine the regulation of sustained antigen-receptor-mediated increases in [Ca2+]i, we studied the relationships between extracellular Ca2+ influx, the mobilization of Ca2+ from intracellular stores, and the contents of inositol polyphosphates after stimulation of the antigen receptor on a human T-cell line, Jurkat. We demonstrate that sustained antigen-receptor-mediated increases in [Ca2+]i are associated with ongoing depletion of intracellular Ca2+ stores. When antigen-receptor-ligand interactions are disrupted, [Ca2+]i and inositol 1,4,5-trisphosphate return to basal values over 3 min. Under these conditions, intracellular Ca2+ stores are repleted if extracellular Ca2+ is present. There is a tight temporal relationship between the fall in [Ca2+]i, the return of inositol 1,4,5-trisphosphate to basal values, and the repletion of intracellular Ca2+ stores. Reversal of the increase in [Ca2+]i preceeds any fall in inositol tetrakisphosphate by 2 min. These studies suggest that sustained antigen-receptor-induced increases in [Ca2+]i, although dependent on extracellular Ca2+ influx, are also regulated by ongoing inositol 1,4,5-trisphosphate-mediated intracellular Ca2+ mobilization. In addition, an elevated concentration of inositol tetrakisphosphate in itself is insufficient to sustain an increase in [Ca2+]i within Jurkat cells.

Antibodies, Monoclonal↗

Evidence that the T cell antigen receptor may not be involved in cytotoxicity mediated by gamma/delta and alpha/beta thymic cell lines.

After culture in IL-2, thymocytes expressing either TCR-alpha/beta or -gamma/delta acquired the ability to lyse hematopoietic and solid tumor cell targets without deliberate immunization or apparent restriction by the MHC. Moreover, TCR-alpha/beta- and TCR-gamma/delta-bearing thymic cell lines demonstrated an essentially identical spectrum of cytolysis against several tumor cell targets. Cytotoxicity was not inhibited by antibodies against CD3 or CD2 and modulation of the CD3/TCR complex also failed to affect cytotoxicity. Thus, non-MHC-restricted cytotoxicity can be mediated by thymocytes with either TCR-alpha/beta or TCR-gamma/delta, but the TCR may not be responsible for target recognition.

Antibodies↗

The role of protein kinase C in transmembrane signaling by the T cell antigen receptor complex. Effects of stimulation with soluble or immobilized CD3 antibodies.

Phorbol esters, such as phorbol myristate acetate (PMA), are known to be potent co-stimulants with calcium ionophores for activation of T lymphocytes. The most extensively studied intracellular effect of PMA is its ability to activate the cytoplasmic enzyme protein kinase C (pkC). Herein, we examined the role of pkC activation during T cell activation. During physiologic activation, this enzyme is activated by diacylglycerol which is generated through the hydrolysis of polyphosphoinositides. Therefore, we studied the activation of T lymphocytes induced by a synthetic diacylglycerol, dioctanoylglycerol. In contrast to PMA, this compound can be metabolized in T cells and presumably more closely mimics physiologic activation of pkC. Dioctanoylglycerol together with reagents that induce increases in intracellular free Ca2+ concentration, Ca2+ ionophores, or anti-cluster designation (CD)3 monoclonal antibodies (mAb) were able to induce interleukin 2 receptor expression and proliferation of T lymphocytes. Previous studies have demonstrated that the stimulation of T cells via the CD3/T cell antigen receptor complex by mAb against CD3 leads to an increase in cytoplasmic free Ca2+ and to an activation of pkC. Paradoxically, however, soluble CD3 antibodies do not cause proliferation of resting purified T cells. Inasmuch as immobilization of CD3 mAb has been shown to influence the agonist properties of such antibodies, we compared the ability of soluble and immobilized CD3 mAb to activate pkC. We demonstrated herein that soluble CD3 mAb cause only a very transient activation of pkC in the T cell leukemic line Jurkat. This pkC activation is markedly prolonged when Jurkat cells are stimulated with immobilized rather than soluble CD3 antibodies. These studies suggest that activation of pkC plays a major role in T cell activation and that the activation of pkC is influenced by the form in which CD3 mAb is presented to T cells.

Antibodies, Monoclonal↗

Molecular diversity of the human T-gamma constant region genes.

The human T cell antigen-receptor gamma chain, which is expressed on the surface of a subpopulation of CD3+ T lymphocytes, exhibits size polymorphism and varies in its ability to form disulfide bonds with a second polypeptide. Analysis of both genomic and complementary DNA clones encoding the human gamma polypeptide shows differences in lengths of the coding portions of the two constant region genes, C gamma 1 and C gamma 2. A single second-exon segment is always present in the C gamma 1 gene. C gamma 2 alleles containing either duplicated or triplicated second-exon segments are present in the normal human population and are expressed as messenger RNAs. Furthermore, a cysteine residue, encoded by the second exon of C gamma 1 and probably involved in interchain disulfide bridging, is absent in all C gamma 2 second-exon segments. These differences between C gamma 1 and the two alleles of C gamma 2 may explain the variability in molecular weight and disulfide bonding of gamma molecules expressed in different cells.

Base Sequence↗

Cell surface T3 expression requires the presence of both alpha- and beta-chains of the T cell receptor.

We have identified a surface T3- Jurkat variant which has a defective alpha-chain but which possesses an intact beta-chain. The transfection of a functional mouse alpha-chain into this human T cell induces the expression of surface T3 molecules associated with mouse alpha-human beta-heterodimers detected by anticlonotypic antibodies. Treatment of the transfectant with anti-T3, anti-mouse Ti-alpha, or anti-human Ti-beta antibodies clears all Ti-T3 complexes from the surface. These results demonstrate that functional alpha- and beta-chains are both required for expression of T3 on the cell membrane, and that the Ti heterodimers present and associated with T3 on Jurkat cells involve only alpha- and beta-chains.

Antibodies, Monoclonal↗