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Biomedical subjects

J Weiss

Publications and source records attributed to J Weiss.

At least 109 records · Page 6Linked to original sources

Cell-wall determinants of the bactericidal action of group IIA phospholipase A2 against Gram-positive bacteria.

We have shown previously that a group IIA phospholipase A2 (PLA2) is responsible for the potent bactericidal activity of inflammatory fluids against many Gram-positive bacteria. To exert its antibacterial activity, this PLA2 must first bind and traverse the bacterial cell wall to produce the extensive degradation of membrane phospholipids (PL) required for bacterial killing. In this study, we have examined the properties of the cell-wall that may determine the potency of group IIA PLA2 action. Inhibition of bacterial growth by nutrient deprivation or a bacteriostatic antibiotic reversibly increased bacterial resistance to PLA2-triggered PL degradation and killing. Conversely, pretreatment of Staphylococcus aureus or Enterococcus faecium with subinhibitory doses of beta-lactam antibiotics increased the rate and extent of PL degradation and/or bacterial killing after addition of PLA2. Isogenic wild-type (lyt+) and autolysis-deficient (lyt-) strains of S. aureus were equally sensitive to the phospholipolytic action of PLA2, but killing and lysis was much greater in the lyt+ strain. Thus, changes in cell-wall cross-linking and/or autolytic activity can modulate PLA2 action either by affecting enzyme access to membrane PL or by the coupling of massive PL degradation to autolysin-dependent killing and bacterial lysis or both. Taken together, these findings suggest that the bacterial envelope sites engaged in cell growth may represent preferential sites for the action and cytotoxic consequences of group IIA PLA2 attack against Gram-positive bacteria.

Anti-Bacterial Agents↗

Risk of clot formation in femoral arterial sheaths maintained overnight for neuroangiographic procedures.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the presence of blood clots in femoral arterial sheaths maintained after cerebral angiography and the effect of heparinized saline on clot formation. METHODS: Twenty-three sheaths were evaluated in 18 patients. Sheaths were maintained for 14 to 80 hours (average, 33 hours; median, 24 hours). After the sheaths were removed, they were vigorously flushed with 60 mL of normal saline and the number and size of clots found in each sheath were recorded. Additionally, patients' age, catheter size, presence of heparin, amount of time the sheath was kept in the artery, and patients' coagulation status were recorded. RESULTS: Clots were found in 17 (74%) of the 23 sheaths. Ten catheters had continuous heparin drip, of which seven (70%) sustained clots. Of the 13 sheaths without heparin, 10 sustained clots (77%). The difference was not statistically significant. The average number of clots was 2.2, and the maximal length of clots ranged from 0.5 to 105 mm. No thromboembolic complications associated with sheath placement were encountered in our patient population. CONCLUSION: Blood clots are present in the vast majority of intraarterial sheaths maintained after cerebral angiography. These clots constitute a risk of thromboembolic complications in the event of repeat angiography. Sheath exchange should be considered before obtaining repeat cerebral angiograms.

Adolescent↗

Assessing and managing the patient with headaches.

Headaches are considered the most common type of pain; more than 40 million Americans seek treatment each year. A clear understanding of the types and possible causes of headache pain is essential to adequately assess and manage the patient with headaches. Headaches can be categorized as either primary or secondary to an underlying and usually treatable cause. Most headaches are primary; this includes migraine and variants, and cluster and tension-type headaches. Before assuming a primary diagnosis, however, the clinician must rule out headaches secondary to an underlying cause so that further investigation, treatment, or referral may be initiated.

Headache↗

Dorsoventral patterning in the Drosophila central nervous system: the vnd homeobox gene specifies ventral column identity.

The Drosophila CNS develops from three columns of neuroectodermal cells along the dorsoventral (DV) axis: ventral, intermediate, and dorsal. In this and the accompanying paper, we investigate the role of two homeobox genes, vnd and ind, in establishing ventral and intermediate cell fates within the Drosophila CNS. During early neurogenesis, Vnd protein is restricted to ventral column neuroectoderm and neuroblasts; later it is detected in a complex pattern of neurons. We use molecular markers that distinguish ventral, intermediate, and dorsal column neuroectoderm and neuroblasts, and a cell lineage marker for selected neuroblasts, to show that loss of vnd transforms ventral into intermediate column identity and that specific ventral neuroblasts fail to form. Conversely, ectopic vnd produces an intermediate to ventral column transformation. Thus, vnd is necessary and sufficient to induce ventral fates and repress intermediate fates within the Drosophila CNS. Vertebrate homologs of vnd (Nkx2.1 and 2.2) are similarly expressed in the ventral CNS, raising the possibility that DV patterning within the CNS is evolutionarily conserved.

Animals↗

Mobilization of potent plasma bactericidal activity during systemic bacterial challenge. Role of group IIA phospholipase A2.

Extracellular mobilization of Group IIA 14-kD phospholipase A2 (PLA2) in glycogen-induced rabbit inflammatory peritoneal exudates is responsible for the potent bactericidal activity of the inflammatory fluid toward Staphylococcus aureus (1996. J. Clin. Invest. 97:250-257). Because similar levels of PLA2 are induced in plasma during systemic inflammation, we have tested whether this gives rise to plasma bactericidal activity not present in resting animals. Baboons were injected intravenously (i.v.) with a lethal dose of Escherichia coli and plasma or serum was collected before and at hourly intervals after injection. After infusion of bacteria, PLA2 levels in plasma and serum rose > 100-fold over 24 h to approximately 1 microg PLA2/ml. Serum collected at 24 h possessed potent bactericidal activity toward S. aureus, Streptococcus pyogenes, and encapsulated E. coli not exhibited by serum collected from unchallenged animals. Bactericidal activity toward S. aureus and S. pyogenes was nearly completely blocked by a monoclonal antibody to human Group IIA PLA2 and addition of purified human Group IIA PLA2 to prechallenge serum conferred potent antistaphylococcal and antistreptococcal activity equal to that of the 24 h post-challenge serum. PLA2-dependent bactericidal activity was enhanced approximately 10x by factor(s) present constitutively in serum or plasma. Bactericidal activity toward encapsulated E. coli was accompanied by extensive bacterial phospholipid degradation mediated, at least in part, by the mobilized Group IIA PLA2 but depended on the action of other bactericidal factors in the 24-h serum. These findings further demonstrate the contribution of Group IIA PLA2 to the antibacterial potency of biological fluids and suggest that mobilization of this enzyme during inflammation may play an important role in host defense against invading bacteria.

Animals↗

[Treatment of hypopituitarism in adults with growth hormone improves improves the thickness of the arterial intima].

BACKGROUND: Increased mortality of hypopituitary adults with atherosclerotic vascular disease is commonly explained by growth hormone deficiency and forms the main argument for the growth hormone replacement. At the same time it is known that the growth hormone-IGF-I axis stimulates the vessel wall proliferation as an initial step of atherosclerosis. Investigation of the arterial intima thickness in hypopituitary adults with duplex ultrasound system and its follow up during the growth hormone therapy may clarify these effects of growth hormone on the vessel wall. METHODS AND RESULTS: Luminal diameter, maximal blood flow velocity and arterial intima thickness of common carotid arteries was measured with colour duplex ultrasound system in 15 adults with hypopituitarism before and after one year therapy with recombinant growth hormone. The results were compared with healthy controls matched for gender, age, blood pressure and weight. The luminal diameter did not changed during the therapy with growth hormone and was the same in patients and controls. Maximal blood velocity in hypopituitary patients before the therapy was lower than in control subjects (74.8 +/- 13.9 cm/s vs. 94.0 +/- 21.0 cm/s), but the statistical difference was only borderline. Arterial intima thickness was significantly thinner in hypopituitary patients when compared with controls (0.56 +/- 0.1 mm vs. 0.71 +/- 0.12 mm, p < 0.001) but became thicker after the treatment and was not any more different from the controls (0.56 +/- 0.1 mm vs. 0.66 +/- 0.1 mm, p < 0.001). CONCLUSIONS: In hypopituitary adults the arterial intima thickness of common carotid arteries is less than in healthy controls. The reduced thickness was normalised after one year treatment with growth hormone. Atheromatous plaques were not found either before or after the treatment. Duplex ultrasound measurement may be one of the means of checking of the effects of growth hormone therapy.

Adult↗

Identification of an inhibin receptor in gonadal tumors from inhibin alpha-subunit knockout mice.

Inhibins and activins are dimeric proteins that are functional antagonists and are structurally related to the transforming growth factor-beta (TGFbeta) family of growth and differentiation factors. Receptors for activin and TGFbeta have been identified as dimers of serine-threonine kinase subunits that regulate cytoplasmic proteins known as Smads. Despite major advances in our understanding of activin and TGFbeta receptors and signaling pathways, little is known about inhibin receptors or the mechanism by which this molecule provides a functionally antagonistic signal to activin. Studies described in this paper indicate that an independent inhibin receptor exists. Numerous tissues were examined for inhibin-specific binding sites, including the developing embryo, in which the spinal ganglion and trigeminal ganglion-bound iodinated inhibin A. Sex cord stromal tumors, derived from male and female inhibin alpha-subunit-deficient mice, were also identified as a source of inhibin receptor. Abundant inhibin and few activin binding sites were identified in tumor tissue sections by in situ ligand binding using iodinated recombinant human inhibin A and 125I-labeled recombinant human inhibin A. Tumor cell binding was specific for each ligand (competed by excess unlabeled homologous ligand and not competed by heterologous ligand). Based on these results and the relative abundance and homogeneity of tumor tissues versus the embryonic ganglion, tumor tissues were homogenized, membrane proteins were purified, and putative inhibin receptors were isolated using an inhibin affinity column. Four proteins were eluted from the column that bind iodinated inhibin but not iodinated activin. These data suggest that inhibin-specific membrane-associated proteins (receptors) exist.

Activin Receptors↗

[Amicrobial intertriginous pustulosis in autoimmune diseases--a new entity?].

During the last decade an unusual amicrobial intertriginous pustulosis has been described in association with autoimmune disease in sixteen female patients. The clinical hallmark is a sterile pustular dermatosis preferentially located in intertriginous regions that responds to local or systemic corticosteroids. Histologic features are subcorneal sometimes spongiform neutrophilic pustules. We report an additional patient suffering from this unusual dermatosis. An overview of the patients described to date and a review of the literature are given in an attempt to delineate this amicrobial intertriginous pustulosis from the known pustular dermatoses.

Adrenal Cortex Hormones↗

Introduction of apoptosis by high proinsulin and glucose in cultured human umbilical vein endothelial cells is mediated by reactive oxygen species.

There is much evidence that diabetes and hyperglycaemia contribute to the impairment of endothelial function and induce severe changes in the proliferation, the adhesive and synthetic properties of endothelial cells. Induction of apoptosis could represent one mechanism to prevent the new accumulation of those vascular defects and to allow generation of vascular endothelium. In this study, we demonstrate that high concentrations of glucose or proinsulin induce apoptosis in human umbilical endothelial cells by three independent methods (DNA fragmentation, fluorescence activated cell sorting analysis, and morphology). The number of apoptotic cells was increased by glucose (30 mmol/l or proinsulin (100 nmol/l) from less than 10% to about 30%. Activation of protein kinase C (PKC) largely prevented the induction of apoptosis, whereas inhibition of PKC further increased the number of apoptotic cells. Similar changes as induced by glucose were also observed after incubation of the cells with the non-metabolisable 3-O-methylglucose. These findings indicate that hyperglycaemic conditions stimulate the induction of apoptosis in endothelial cells by a mechanism which is independent from the formation of diacylglycerol and the activation of PKC. The induction of apoptosis by the non-metabolisable glucose suggests that formation of oxygen derived radicals by autoxidative processes is involved and may lead to an activation of transcription factors such as nuclear transcription factor-kappaB (NF-kappaB) transferring the activation signal into the nucleus and leading to changes in gene expression necessary for induction of apoptosis.

Apoptosis↗

Wave propagation in cardiac tissue and effects of intracellular calcium dynamics (computer simulation study).

Computer simulation using Luo-Rudy I1 model of ventricular myocyte showed that intracellular calcium dynamics become irregular in case of high rate stimulation. This causes the transition from stationary to nonstationary spiral wave and its breakup in 2D model of cardiac tissue. Obtained results suggest how ventricular fibrillation may occur due to the abnormalities of intracellular calcium dynamics. The short review of existing cardiac cell models with calcium dynamics is presented.

Animals↗

Morphological and histochemical ageing changes in patellar articular cartilage of the rat.

The aim of this study was to investigate the variation in cartilage characteristics with age. Fresh-frozen cryostat sections of the patellar articular cartilage of the rat were used to demonstrate the enzyme activity of succinate dehydrogenase, lactate dehydrogenase, alkaline phosphatase, and acid phosphatase in the different layers and at different ages. Light microscopic techniques were used to analyse quantitative features such as thickness, cell density and the histological characteristics of the articular cartilage. The results indicate that cell density is significantly affected by age. Furthermore, it depends on the distance from the surface. The most marked decline in cell density occurred between months 3 and 6. The thickness of the articular cartilage also varies with age. The reduction in cartilage thickness was most striking between months 3 and 6. Differentiation into the histological layers is obvious after 3 months. Glycolytic enzymes were strongly reactive in all regions and at all ages, whereas aerobic activity declines with age. The metabolic and morphological changes in ageing cartilage contribute to trophic disorders and deterioration of the functional cartilaginous situation in adult cartilage.

Acid Phosphatase↗

Role of the bactericidal/permeability-increasing protein in host defence.

Much has been learned recently about the structure and function of 55 kDa bactericidal/permeability-increasing protein (BPI), a member of a genomically conserved lipid-interactive protein family. Analysis of BPI fragments and the crystal structure of human BPI have established that BPI consists of two functionally distinct domains: a potently antibacterial and anti-endotoxin amino-terminal domain (approximately 20 kDa) and a carboxy-terminal portion that imparts opsonic activity to BPI. A recombinant amino-terminal fragment (rBPI21) protects animals against the effects of Gram-negative bacteria and endotoxin. In man, rBPI21 is nontoxic and non-immunogenic and is in Phase II/III clinical trials with apparent therapeutic benefit.

Animals↗

How bacteria initiate inflammation: aspects of the emerging story.

Recent studies have shown that bacteria possess an array of proinflammatory molecules in addition to the extensively studied lipopolysaccharide and superantigens. These bacterial molecules include soluble and membrane-associated inducers of cytokine release, inducers of host cell apoptosis, and immunostimulatory DNA. There is therefore much greater diversity in the class of molecules and mechanisms by which bacteria engage the host immune system than previously appreciated.

Apoptosis↗

Clinical-radiological evaluation of poststernotomy wound infection.

The presumption that computed tomography is the "gold standard" imaging method for diagnosing poststernotomy sternal wound infection was never validated. This study was designed to evaluate the accuracy and role of computed tomography in diagnosing the extent of infectious complications following sternotomy. A high postoperative infection recurrence rate in our earliest cases (30 percent, 1984 to 1988) motivated us to assess whether this modality enables the surgeon to choose the optimal surgical approach, which will make it possible to reduce morbidity and mortality rates. Two-hundred three patients with poststernotomy sternal wound infections were operated upon between 1984 and 1993. All pertinent clinical and radiological data of these patients were collected retrospectively and reinterpreted by an unbiased radiologist; the radiological data were correlated both to the intraoperative clinical findings and to histological interpretation of the surgical specimens. The study group available for statistical analysis included 160 patients. Predictive statistical analysis confirmed that computed tomography is a highly reliable imaging method for identifying the different pathologies as soft tissue, sternum mediastinal infections, in sternal wound infection with overall sensitivity of 93.5 percent and specificity of 81.7 percent. New radiographic findings were identified for the distinction of costochondral infection. This complication was, and still is, a major deceptive clinical problem in these patients and the major contributor to recurrences. We propose a sternal wound infection classification system that outlines the recommended approach for each clinical-radiological condition. Since computerized tomography was found to be a highly accurate modality, we strongly believe that the surgeon should take its pathological-radiographic findings into serious consideration, even if there are no "clear-cut" clinical signs for an existing or recurring infection.

Adolescent↗