Biomedical subjects

M Schorr

Publications and source records attributed to M Schorr.

18 recordsLinked to original sources

PubMed2001

The phosphoinositide phosphatase Sac1p controls trafficking of the yeast Chs3p chitin synthase.

Phosphoinositide phosphatases play an essential but as yet not well-understood role in lipid-based signal transduction. Members of a subfamily of these enzymes share a specific domain that was first identified in the yeast Sac1 protein [1]. Sac1 homology domains were shown to exhibit 3- and 4-phosphatase activity in vitro [2, 3] and were also found, in addition to rat and yeast Sac1p, in yeast Inp/Sjl proteins [4, 5] and mammalian synaptojanins [6]. Despite the detailed in vitro characterization of the enzymatic properties of yeast Sac1p, the exact cellular function of this protein has remained obscure. We report here that Sac1p has a specific role in secretion and acts as an antagonist of the phosphatidylinositol 4-kinase Pik1p in Golgi trafficking. Elimination of Sac1p leads to excessive forward transport of chitin synthases and thus causes specific cell wall defects. Similar defects in membrane trafficking are caused by the overexpression of PIK1. Taken together, these findings provide strong evidence that the generation of PtdIns(4)P is sufficient to trigger forward transport from the Golgi to the plasma membrane and that Sac1p is critically required for the termination of this signal.

1-Phosphatidylinositol 4-Kinase↗

PubMed2001

Recurrent soft tissue abscesses caused by Legionella cincinnatiensis.

Recurrent soft tissue abscesses of the jaw, wrist, and arm developed in a 73-year-old housewife with nephrotic syndrome and immunoglobulin A(kappa) gammopathy of unknown etiology. Conventional cultures remained negative, despite visible gram-negative rods on microscopy. Broad-spectrum PCR revealed Legionella cincinnatiensis, which was confirmed by isolation of the organism on special Legionella medium. Infections due to Legionella species outside the lungs are rare. L. cincinnatiensis has been implicated in only four cases of clinical infection; these involved the lungs in three patients and the central nervous system in one patient. We conclude that broad-spectrum PCR can be a valuable tool for the evaluation of culture-negative infections with a high probability of bacterial origin and that Legionella might be an underdiagnosed cause of pyogenic soft tissue infection.

Abscess↗

PubMed2000

Antithrombin III and local serum application: adjuvant therapy in peritonitis.

BACKGROUND: Patients with diffuse peritonitis show an overall mortality of about 20%, probably caused by the breakdown of local defence mechanisms combined with a systemic outspread of bacteria and toxins, which often results in sepsis syndrome. DESIGN: In a prospective, randomized, controlled study 50 patients with diffuse secondary peritonitis were included. Patients in the therapy group were treated with an adjuvant medication consisting of a continuous intravenous infusion of antithrombin III and two intraperitoneal instillations of fresh frozen human donor serum. The aim of the study was the reduction of mortality and incidence of multiple organ failure. RESULTS: Mean antithrombin III plasma levels in the therapy group were raised above 140% for 4 days and were significantly higher than in the control group. With the intraperitoneal application of fresh frozen serum and antithrombin III opsonic capacity as well as thrombin, inhibitory activity in the exudate could be significantly elevated over 2 days. The 90-day-mortality rate was 6/26 (23%) in the control group and 6/24 (25%) in the therapy group. Although no improvement of mortality was achieved, a slight but not significant reduction of the severity of the multiple organ failure was seen. CONCLUSIONS: The chosen therapeutic approach was feasible and showed no side-effects. Yet, neither mortality nor multiple organ failure were significantly improved by the applied short-term adjuvant therapy. Thus, for future trials in severely-ill patients a longer treatment period and/or combinations of antithrombin III with other anti-inflammatory agents should be considered.

APACHE↗

PubMed1999

Colorectal cancer: A rational follow-up program adapted to patient's individual risk of recurrence and review of the literature.

Follow-up programs in patients with colorectal cancer have been criticized concerning their efficacy. Uniform programs for all patients as practised during the last decade did neither influence survival nor did they improve the number of secondary tumor resection for cure. Therefore we developed a follow-up program that stratifies according to patient s healthiness, residual tumor and the expected risk of tumor recurrence. Patients were divided into three categories: patients with low or high risk of tumor recurrence and patients treated for palliation. By such an approach the number of apparative examinations and the cost of a follow-up program could be theoretically reduced by more than 50%.

Colorectal Neoplasms↗

PubMed1999

Parental compliance with multiple immunization injections.

OBJECTIVE: To assess parents' (or caretakers') willingness to allow multiple immunization injections at a single visit. DESIGN: A survey of parental demographics and a medical record review to determine immunization status. SETTING: An inner-city pediatric clinic in Philadelphia, Pa. PARTICIPANTS: A convenience sample of 1059 patients who were due to receive 2 to 5 immunization injections at a single visit and their parents. Patients were excluded if parents had not previously witnessed at least 1 immunization. MAIN OUTCOME MEASURES: The number of immunizations due, the number of immunizations received, and the reasons for failure to immunize completely. RESULTS: Almost all (98.8%) of the children included in the study received all immunizations indicated at their visit. CONCLUSION: Despite potential parental resistance to multiple simultaneous immunization injections, this innercity population overwhelmingly complied with physicians' recommendations.

Adolescent↗

PubMed1998

B1 kinin receptor activity in pigs is associated with pre-existing infection.

Bradykinin (BK) and related kinins are potent inflammatory mediators produced during acute and chronic inflammation. The effects of these kinins are mediated via the stimulation of either a B2 or a B1 receptor. The B1 receptor is not normally present but its expression can be induced within 4 h by a variety of noxious stimuli, specifically, gram-negative bacteria or bacterial lipopolysaccharide (LPS) given to healthy animals. This study compared the cardiovascular response of healthy pigs and pigs diagnosed with a pre-existing spontaneously acquired infection to BK, a B2 receptor agonist, and des-Arg9-BK, a B1 receptor agonist. Eighty-eight percent of the animals diagnosed with an established infection based on a standardized clinical evaluation demonstrated increased sensitivity and responsiveness to des-Arg9-BK but normal responsiveness to BK and acetylcholine. In contrast, only 15% of healthy animals showed elevated responses to des-Arg9-BK. The response to des-Arg9-BK and BK in each group was characterised as B1 and B2, respectively, using the selective B1 and B2 antagonists Lys0-Leu8-des-Arg9-BK and Hoe 140, respectively. This study demonstrates the existence and function of the B1 receptor in animals with a previously acquired infection. These observations lend validity to animal experiments with LPS infusion in order to model bacterial inflammation.

Acetylcholine↗

PubMed1997

[Patient-oriented, risk-adapted tumor aftercare in patients with colorectal carcinoma].

Follow-up programs in patients with colorectal cancer have been criticized concerning their efficacy. Uniform programs for all patients as practised during the last decade did neither influence survival nor did they improve the number of secondary tumor resection for cure. Therefore we developed a follow-up program that considers patient's healthiness, status of resection in primary operative therapy and the risk of tumor recurrence depending on postoperative tumor staging. Because of these considerations we divided patients into three groups: Patients with low risk, high risk and patients treated with palliative aspects. Thus costs of follow-up programs could be reduced to more than 50%.

Aftercare↗

PubMed1996

Expression of ciliary neurotrophic factor is maintained in spinal motor neurons of amyotrophic lateral sclerosis.

Ciliary neurotrophic factor (CNTF) was originally identified as a potent survival factor for a variety of neuronal cell types in vitro and in vivo and in particular in spinal motor neurons of embryonic chick and rat. Using a monoclonal antibody against CNTF (clone 4-68) we analysed the expression of CNTF in paraffin sections of seven human brains and spinal cords immunocytochemically using the ABC method and compared these results with sections of the spinal cords of patients suffering from amyotrophic lateral sclerosis (ALS). In normal human tissue of the central nervous system CNTF immunoreactivity was found in most of the motor neurons of the motor cortex and ventral horn, neurons of the nucleus oculomotorius, intermediolateralis, thoracicus, ependymal cells as well as in smooth muscle cells and endothelial cells of small arteries. A reduced number of astrocytes showed a positive immunocytochemical reaction. In peripheral nerves and nerve roots of the spinal cord we also found a positive staining of Schwann cells and some axons. These immunoreactions could be confirmed by Western blot analyses. Next we analysed postmortem paraffin sections of the spinal cord of seven patients suffering from ALS (age range 30-76 years, female/male = 4:3). We found CNTF immunoreactivity in most of the motor neurons of the ventral horn in 5 cases. In two cases the number of positively stained motor neurons was less. From these results we conclude that CNTF is expressed in a high number of upper and lower motor neurons in the human CNS and that its expression is maintained in ALS patients.

Aged↗

PubMed1996

Effect of combined B1 and B2 kinin receptor blockade in porcine endotoxin shock.

In order to investigate the contribution of kinin receptor antagonism in the treatment of LPS-induced shock we conducted a randomized study with anaesthetized piglets. Before randomization the animals were stratified according to predetermined health criteria under baseline conditions. One group of control animals received LPS from S. abortus equi (2 micrograms/kg/h i.v. for 8 h) and saline (Group 1). Another group received LPS and the B2 antagonist CP-0127 (3 micrograms/kg/min), beginning 1 h after LPS (Group 2). Group 3 received LPS and the B2 antagonist in the aforementioned doses, and the B1 antagonist Leu9-des-Arg10-kallidin (3 micrograms/kg/min), also beginning 1 h after LPS. Overall survival figures after 8 h of LPS infusion were: Group 1, 10/22 (45%); Group 2, 10/17 (59%); Group 3, 10/28 (36%). Fifty percent (29/58) of animals that were healthy at baseline survived, but only 11% (1/9) of sick animals survived (Log Rank p = 0.0001). In the subset of healthy animals, survival rates for Groups 2 and 3 were 77% and 38%, respectively (p = 0.0519). It appears, therefore, that B2 blockade attenuates LPS-induced mortality whereas additional B1 blockade seems to reverse these beneficial effects. This suggests that in this animal model the B1 receptor does not serve the same purpose as the B2 receptor, and that up-regulation of B1 receptors during LPS shock may be an important mechanism of host defence.

Animals↗

PubMed1974