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Biomedical subjects

R Meier

Publications and source records attributed to R Meier.

At least 91 records · Page 5Linked to original sources
PubMed1996

Purification and cDNA cloning of SAPKK3, the major activator of RK/p38 in stress- and cytokine-stimulated monocytes and epithelial cells.

Two chromatographically distinct stress-activated protein kinase kinases (SAPKKs) have been identified in several mammalian cells, termed SAPKK2 and SAPKK3, which activate the MAP kinase family member RK/p38 but not JNK/SAPK in vitro. Here we demonstrate that SAPKK2 is identical or very closely related to the MAP kinase kinase family member MKK3. However, under our assay conditions, SAPKK3 was the major activator of RK/p38 detected in extracts prepared from stress- or interleukin-1-stimulated epithelial (KB) cells, from bacterial lipopolysaccharide and tumour necrosis factor alpha-stimulated THP1 monocytes or from rabbit skeletal muscle. The activated form of SAPKK3 was purified from muscle to near homogeneity, and tryptic peptide sequences were used to clone human and murine cDNAs encoding this enzyme. Human SAPKK3 comprised 334 amino acids and was 78% identical to MKK3. The murine and human SAPKK3 were 97% identical in their amino acid sequences. We also cloned a different murine cDNA that appears to encode a SAPKK3 protein truncated at the N-terminus. SAPKK3 is identical to the recently cloned MKK6.

Amino Acid Sequence↗
PubMed1996

Cellular stresses and cytokines activate multiple mitogen-activated-protein kinase kinase homologues in PC12 and KB cells.

The identities of the upstream activators of the mitogen-activated protein (MAP) kinase homologues termed stress-activated-protein (SAP) kinase-1 (also known as JNK or SAPK) and SAP kinase-2 (also known as p38, RK and CSBP) were investigated in rat PC12 cells and human KB cells after exposure to cellular stresses and cytokines. In PC12 cells, the same two upstream activators, SAP kinase kinase-1 (SAPKK-1) and SAPKK-2 were activated after exposure to osmotic shock, ultraviolet irradiation or the protein synthesis inhibitor anisomycin, and more weakly in response to sodium arsenite. SAPKK-1 was capable of activating both SAP kinase-1 and SAP kinase-2 and was similar, if not identical, to the previously described MAP kinase kinase homologue MKK4, as judged by immunological criteria and by its ability to be activated by MEK kinase in vitro. In contrast, SAPKK-2 activated SAP kinase-2, but not SAP kinase-1 in vitro. In KB cells, five distinct upstream activators of SAP kinase-1 and SAP kinase-2 were induced, namely SAPKK-1, SAPKK-2, SAPKK-3, SAPKK-4 and SAPKK-5, whose appearance depended on the nature of the stimulus. SAPKK-3, which was strongly induced by every stimulus tested (osmotic shock, ultraviolet irradiation, anisomycin or IL-1), accounted for about 95% of the SAP kinase-2 activator activity in these cells, did not activate SAP kinase-1 and eluted from Mono S at a lower salt concentration than SAPKK-2. SAPKK-4 and SAPKK-5 were also eluted from Mono S at higher NaC1 concentrations than SAPKK-3 and these enzymes activated SAP kinase-1 but not SAP kinase-2. SAPKK-4 was the only SAP kinase-1 activator induced by interleukin-1 or ultraviolet irradiation, while two SAP kinase-1 activators, SAPKK-1 and SAPKK-5, were induced by osmotic shock or anisomycin. SAPKK-2, SAPKK-3, SAPKK-4 and SAPKK-5, were not activated by MEK kinase in vitro, were separable from the major activator(s) of p42 MAP kinase, and were not recognised by anti-MKK4 antibodies. At least two of these enzymes are likely to be novel MAP kinase kinase homologues. Our results demonstrate unexpected complexity in the upstream regulation of stress and cytokine-stimulated kinase cascades and indicate that the selection of the appropriate SAPKK varies with both the stimulus and the cell type.

Amino Acid Sequence↗
PubMed1996

[Anesthesiologic problems in patients with fibrodysplasia ossificans progressiva].

Fibrodysplasia ossificans progressiva (FOP) is a rare, congenital disease of the striated muscular system, ligaments and fascia; it leads to complete ossification in adult life. The disease usually begins in the first decade of life and is accompanied by abnormalities of the hands and feet that have already begun to occur at birth. There is no effective therapy. Although some of these patients have to undergo an operation, there is very little information available on anaesthetic procedures. CASE REPORT. A 49-year-old-woman came to the anaesthetic ward for amputation of her left foot with the diagnosis of fibrodysplasia ossificans progressive (FOP) and an infection resistant to any antibiotic treatment. Except for her left elbow, she could not move any of her extremities. Her back and neck were stiff (Figs. 1, 2), she could not open her mouth more than 2.5 cm, and her teeth were full of cavities and loose (Fig. 3). Aspiration of gastric content some time ago was known. Lung function showed a restrictive pattern. She suffered from kyphoscoliosis and needed chronic nasal administration of O2. With this therapy the arterial blood gas analysis was normal. Right bundle-branch block on the electrocardiogram was found. She was in a wheelchair and was completely dependent on the help of others. She was taking no medicine at the time of admission. A second operation was necessary because of reactive bone proliferation with a danger of skin perforation. DISCUSSION. This rare and congenital disease was first described in 1648 by G. Patin [14] and again in 1736 by J. Freke [10]. Since then, the progressive ossification of striated muscles, ligaments and facia has been described more than 600 times. Despite this fact, descriptions of anaesthetic procedures are rare. Because of the neck stiffness, the small mouth opening, the poor teeth and the recently observed history of aspiration, fiberoptic nasal intubation when the patient is awake was found to be the best choice. The possibility of atlanto-axial subluxation in such cases [2, 4] favored this procedure. Other authors have used blind nasal intubation [11], ketamine without intubation [18], or even local anaesthesia for a cesarean section [21]. Newer publications [13, 20] promote fiberoptic intubation and general anaesthesia with or without muscle relaxation. In this case propofol/fentanyl/ N2O/O2 without muscle relaxation was used for the first operation and etomidate/fentanyl/ethran/ N2O/O2 without muscle relaxation for the second procedure. During both anaesthesias important hypotension with good response to a generous volume supply was seen. The patient recovered well. Unfortunately, she died a few weeks later from suicide. The goal of this case report is to emphasize the value of the fibrobronchoscope in patients with FOP.

Adult↗
PubMed1996

Evaluation of the efficacy and safety of flumazenil in the treatment of portal systemic encephalopathy: a double blind, randomised, placebo controlled multicentre study.

BACKGROUND: Portal systemic encephalopathy (PSE) is a complex neuropsychiatric syndrome associated with hepatic failure. Small scale studies have shown the benzodiazepine receptor antagonist flumazenil to be effective in ameliorating PSE. AIMS: To determine the efficacy of flumazenil in patients with non-comatous mild to moderate PSE (stages I to III) due to severe chronic liver disease. PATIENTS: 49 male and female adults without symptoms of severe bleeding and sepsis and who screened negative for benzodiazepine in both blood and urine, were included in the study. METHODS: Patients were randomised to receive either three sequential bolus injections of flumazenil (0.4, 0.8, and 1 mg) or placebo at one minute intervals, followed by intravenous infusions of either flumazenil (1 mg/h) or placebo for three hours. Clinical PSE grading and vital signs were assessed hourly during baseline and post-treatment periods and half hourly during treatment. The main outcome measures were improvement in group average PSE score and reduction of two points in individual PSE score (clinically relevant improvement). RESULTS: The mean average improvement in the PSE score in the subjects treated with flumazenil was not statistically significantly different from placebo. However, for patients showing clinically relevant improvement, the difference between flumazenil and placebo was statistically significant (seven of 28 v none of 21; p = 0.015). Flumazenil was well tolerated. CONCLUSIONS: A subgroup of patients with PSE resulting from chronic liver disease may benefit from the administration of flumazenil.

Chronic Disease↗
PubMed1996

[Chronic inflammatory bowel diseases and nutrition].

The etiology of inflammatory bowel disease is still unknown. Several potential mechanisms are discussed. The etiological and therapeutic importance of nutrition is controversial. Though changes in dietary habits and incidence of inflammatory bowel disease during the last century were in parallel, no specific nutritional factor has been isolated. No dietary prophylaxis of inflammatory bowel disease is yet known; all dietary therapies in inflammatory bowel disease aim to improve nutritional support and to diminish inflammation by bowel rest. Children and adolescents gain in weight and height. Total parenteral nutrition will not substantially reduce disease activity and operation rates. Total parenteral nutrition can only be recommended in ulcerative colitis patients with severe disease in the initial phase and in Crohn's patients with severe malnutrition and intestinal complications. Enteral nutrition support is less effective in ulcerative colitis than in Crohn's disease. Reported remission rates on enteral nutrition are 25% for ulcerative colitis and up to 80% for Crohn. However, in active Crohn's disease enteral nutrition is less effective than standard therapy with methylprednisolone and sulfasalizine. It is generally believed that nutrition therapy in combination with drugs is the best treatment modality. There is no evidence to support the importance of any combination of the formula diets such as elemental, oligopeptide, or polymeric formulations. Administration of formula diets by nasogastric tubes all show similar remission rates. Whether newer diets supplemented with arginine, glutamine, omega-3-fatty acids or short chain fatty acids increase remission rates is not known. Further studies in this field are warranted.

Adolescent↗
PubMed1996

[2 cases of Whipple disease with different outcomes].

Whipple's disease is a rare infectious disease with systemic manifestation on different organs. In 1992 the typical rod-shaped bacillus was identified as a gram-negative actinomycete with distinctive morphologic characteristics and named as Tropheryma whippelii. The diagnosis is established by demonstrating the presence of PAS-positive macrophages in the mucosa, with large cytoplasmatic granules. We present two cases of Whipple's disease with different outcomes. Both were treated with the same antibiotics (penicillin/streptomycin). With this treatment one patient recovered completely. In a follow-up over 7 years no relapse occurred. The second patient died only 4 weeks after the diagnosis was established.

Actinomycetales Infections↗
PubMed1995

[How reliable is the measurement of colonic transit time using a marker technique?].

Radioopaque markers are well established tools to determine segmental and total colonic transit time. However, since no data are available on intraindividual reproducibility, in this study reproducibility was assessed in 14 health male and 12 healthy female volunteers. The mean segmental colonic transit and total colonic transit time were not significantly different for the two measurements. Colonic transit time was consistently shorter in males than in females. The menstrual phase did not show a significant influence in the latter. The intraindividual variations of the colonic transit times were acceptable with a reproducibility coefficient of 20 h.

Adult↗
PubMed1995

SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1.

A class of pyridinyl imidazoles inhibit the MAP kinase homologue, termed here reactivating kinase (RK) [Lee et al. (1994) Nature 372, 739-746]. We now show that one of these compounds (SB 203580) inhibits RK in vitro (IC50 = 0.6 microM), suppresses the activation of MAPKAP kinase-2 and prevents the phosphorylation of heat shock protein (HSP) 27 in response to interleukin-1, cellular stresses and bacterial endotoxin in vivo. These results establish that MAPKAP kinase-2 is a physiological RK substrate, and that HSP27 is phosphorylated by MAPKAP kinase-2 in vivo. The specificity of SB 203580 was indicated by its failure to inhibit 12 other protein kinases in vitro, and by its lack of effect on the activation of RK kinase and other MAP kinase cascades in vivo. We suggest that SB 203580 will be useful for identifying other physiological roles and targets of RK and MAPKAP kinase-2.

Amino Acid Sequence↗
PubMed1995

[Enteral feeding in tumor patients].

Malnutrition is often a leading sign in cancer patients. Cancer cachexia influences the prognosis of patients in a negative way in that malnutrition decreases the immune response resulting in increased infectious complications. Intensified nutritional support often improves the quality of life. However, no decrease in tumor-associated mortality or increase in survival has thus far been demonstrated.

Humans↗
PubMed1995

[Practical guidelines for the administration of artificial nutrition at home (home nutrition) (SAEPE; Swiss Work Group for Enteral and Parenteral Nutrition)].

The number of outpatients with major difficulties in feeding themselves is constantly growing. This results into severe malnutrition resulting in increased infection rate, physical disabilities, skin sores, increased therapeutic costs and poor quality of life. Home nutritional support can cover all nutritional needs but requires appropriate indications, optimal technical management and cautious ethical evaluation. In addition, the overall costs should be covered by an insurance at the time of home nutritional support prescription. Swiss home nutritional support recommendations for practising physicians are presented.

Enteral Nutrition↗