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Biomedical subjects

J Metzger

Publications and source records attributed to J Metzger.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Ileo-cecal segment as stomach substitute].

In clinical practice a long Roux-en-Y reconstruction is most often used for gastric replacement. Among various postgastrectomy symptoms, alcaline reflux is the most disturbing. A great variety of different pouch reconstructions with or without duodenal bypass only control reflux in part. The ileocoecal interposition has been placed between the oesophagus and the duodenum as a gastric substitute in 14 patients without postoperative mortality. This preliminary series demonstrates an excellent control of alcaline reflux and a good quality of life, according to the Eypasch score. Dysphagia or stasis in the distal oesophagus are absent as is gas bloating. This type of reconstruction, which is simpler than some of the pouch reconstructions, probably deserves more attention and may perhaps be perfected by varying the length of ileum and volume of ascending colon to be interposed.

Cecum↗
PubMed1997

Position- and orientation-independent activity of the Schizosaccharomyces pombe meiotic recombination hot spot M26.

The activity of the M26 meiotic recombination hot spot of Schizosaccharomyces pombe depends on the presence of the heptamer 5'-ATGACGT-3'. Transplacement of DNA fragments containing the ade6-M26 gene to other chromosomal loci has previously demonstrated that the heptamer functions in some, but not all, transplacements, suggesting that hot spot activity depends on chromosomal context. In this study, hot spot activity was tested in the absence of gross DNA changes by using site-directed mutagenesis to create the heptamer sequence at novel locations in the genome. When created by mutagenesis of 1-4 bp in the ade6 and ura4 genes, the heptamer was active as a recombination hot spot, in an orientation-independent manner, at all locations tested. Thus, the heptamer sequence can create an active hot spot in other chromosomal contexts, provided that the gross chromosomal structure is not altered; this result is consistent with the hypothesis that a specific higher-order chromatin structure is required for M26 hot spot activity.

DNA, Fungal↗
PubMed1997

Ileocecal interpositional graft as gastric replacement after total gastrectomy and distal esophagectomy.

The ileocecal interpositional graft is an alternative method for replacing the distal esophagus and the stomach. A pedunculated ileocecal interpositional graft rotated 180 degrees clock-wise and placed across the hiatus between the proximal esophagus and the duodenum could act as a reservoir and protect against reflux (ileocecal valve) while preserving the duodenal passage. Two patients underwent this operation (the first patient has been observed for 12 postoperative months). We also used this technique to replace the stomach alone below the diaphragm, a technique that had been abandoned in the surgical literature since 1952, although the concept and initial experiences were already promising at that time. In favor of these attractive features of the ileocecal interpositional graft as gastric replacement, we have begun a controlled examination of this method.

Adenocarcinoma↗
PubMed1997

Long-term prognostic significance of ventricular late potentials after a first acute myocardial infarction.

Ventricular late potentials (VLP) have been shown to be independent predictors of arrhythmic events after myocardial infarction. However, many studies have had one or more limitations: limited follow-up period, small study group, possible selection bias, inadequate statistical analysis, or inclusion of patients with previous infarction. The purpose of this study was to assess the long-term prognostic value of VLP in a large group of unselected patients after a first acute myocardial infarction. Time-domain signal averaging was performed in 458 patients (380 male, 78 female, mean age 59 +/- 11 years) a mean of 10 days (range 7 to 13 days) after a first acute myocardial infarction. The overall prevalence of VLP was 20% (90 of 458 patients). By univariate analysis a left ventricular ejection fraction <40% (p = 0.002) and the presence of an occluded infarct-related artery (p = 0.006) were the only statistically significant predictors for the development of VLP. During a median follow-up of 70 months, 21 (5%) patients died suddenly, and 11 (2%) patients had documented sustained ventricular tachycardia. The presence of VLP (p < 0.0001), older age (p = 0.02), and an occluded infarct-related artery (p = 0.045) were the only variables significantly associated with the occurrence of serious arrhythmic events during follow-up. The probability of having no arrhythmic events was 99% at 1 year and 96% at 5 years in the absence of VLP and 87% at 1 year and 80% at 5 years in the presence of VLP (4.6-fold increase in arrhythmic risk; 95% confidence interval: 2.3 to 9.1). VLPs are powerful predictors of serious arrhythmic events in patients after a first acute myocardial infarction, and their prognostic value, although waning with time, persists for at least 7 years. This study also provides further evidence that an open infarct-related artery may reduce the arrhythmic risk after myocardial infarction.

Action Potentials↗
PubMed1997

[The Lichtenstein inguinal hernia-plasty: a simple and complication-free technique, especially suited for ambulatory surgery].

A consecutive series of 353 patients who underwent Lichtenstein mesh repair for inguinal hernia from the 1st of July 1994 to the 30th of July 1995 were studied. We analysed our indication, technique, complications, follow-up and outcome. Special consideration was given to the advantages and acceptance of day-case surgery. Our results suggest that the Lichtenstein repair should be considered as a new standard procedure, especially outside of hernia centres.

Absenteeism↗
PubMed1996

Protein engineering of lantibiotics.

Whereas protein engineering of enzymes and structural proteins nowadays is an established research tool for studying structure-function relationships of polypeptides and for improving their properties, the engineering of posttranslationally modified peptides, such as the lantibiotics, is just coming of age. The engineering of lantibiotics is less straightforward than that of unmodified proteins, since expression systems should be developed not only for the structural genes but also for the genes encoding the biosynthetic enzymes, immunity protein and regulatory proteins. Moreover, correct posttranslational modification of specific residues could in many cases be a prerequisite for production and secretion of the active lantibiotic, which limits the number of successful mutations one can apply. This paper describes the development of expression systems for the structural lantibiotic genes for nisin A, nisin Z, gallidermin, epidermin and Pep5, and gives examples of recently produced site-directed mutants of these lantibiotics. Characterization of the mutants yielded valuable information on biosynthetic requirements for production. Moreover, regions in the lantibiotics were identified that are of crucial importance for antimicrobial activity. Eventually, this knowledge will lead to the rational design of lantibiotics optimally suited for fighting specific undesirable microorganisms. The mutants are of additional value for studies directed towards the elucidation of the mode of action of lantibiotics.

Amino Acid Sequence↗
PubMed1996

Tachykinin NK1 receptor antagonists act centrally to inhibit emesis induced by the chemotherapeutic agent cisplatin in ferrets.

These studies have compared the pharmacological profile of two non-peptide human type neurokinin1 (hNK1) receptor selective antagonists, L-741,671 and a quaternised compound L-743,310. In radioligand binding studies L-741,671 and L-743,310 had high affinity for ferret and cloned hNK1 receptors [Ki (nM) ferret 0.7 and 0.1; human 0.03 and 0.06, respectively] but low affinity for rodent NK1 receptors [Ki (nM) 64 and 17, respectively] suggesting that ferret receptors have hNK1-like binding pharmacology. Studies in vivo showed that L-741,671 and L-743,310 had equivalent functional activity in the periphery (ID50s of 1.6 and 2 micrograms/kg i.v., respectively) as measured by inhibition of plasma protein extravasation evoked in the oesophagus of guinea pigs by resiniferatoxin (7 nmol/kg i.v.). Using an in situ brain perfusion technique in anaesthetised rats, L-741,671 was shown to be much more brain penetrant than the quaternary compound L-743,310 which had an entry rate similar to the poorly brain penetrant plasma marker inulin. These compounds thus provided an opportunity to compare the anti-emetic effects of equi-active hNK1 receptor antagonists with and without brain penetration to central NK1 receptor sites. When tested against cisplatin-induced emesis in ferrets, L-741,671 (0.3, 1 and 3 mg/kg i.v.) produced marked dose-dependent inhibition of retching and vomiting but L-743,310 was inactive at 3 and 10 micrograms/kg i.v. In contrast, direct central injection of L-741,671 and L-743,310 (30 micrograms) into the vicinity of the nucleus tractus solitarius or L-743,310 (200 micrograms) intracisternally was shown to inhibit retching and vomiting induced by i.v. cisplatin. L-741,671 and L-743,310 had equivalent functional activity, at the same dose, against cisplatin-induced emesis when injected centrally. These observations indicated that had L-743,310 penetrated into the brain after systemic administration it would have been active in the cisplatin-induced emesis assay and so show that brain penetration is essential for the anti-emetic action of systemically administered NK1 receptor antagonists.

Animals↗
PubMed1996

Evaluation of household dust mite exposure and levels of specific IgE and IgG antibodies in asthmatic patients enrolled in a trial of immunotherapy.

BACKGROUND: Monitoring the response to immunotherapy entails understanding exposure to relevant allergens. For the major indoor allergens, this requires sampling of dust from the patient's house. The objectives of this study were to measure indoor allergen levels during a controlled trial of dust mite immunotherapy for asthma and to relate these results to serum antibody levels. METHODS: Eighty-eight asthmatic patients with mite allergy from seven geographic areas in the United States were enrolled in and completed a course of immunotherapy with Dermatophagoides extract or placebo control. Sensitization was evaluated by quantitative measurements of IgG and IgE antibodies. Dust samples were assayed for group I mite (Der p 1 and Der f 1), cat (Fel d 1), and cockroach (Bla g 1) allergens by monoclonal antibody-based ELISA. RESULTS: Over the 4 years of the study, each of the houses had at least one sample that contained more than 2 micrograms of group I mite allergen per gram of dust. Mean mite allergen levels, however, varied over a wide range, from 0.2 microgram/gm or less to more than 50 micrograms/gm. IgE antibodies to mite were present in sera from 78% of the patients, whereas IgE antibodies to cat and cockroach allergens were found in sera from 34% and 11% of patients, respectively. Sixty-four percent of the patients had exposure and sensitization to mite, whereas the comparable figure for each of the other allergens was 5%. CONCLUSIONS: Examination of the results suggested that allergen exposure, relative to a trial of immunotherapy, could be expressed as (1) the maximum level found in the house, (2) the percentage of sites having greater than 2 micrograms/gm, or (3) the mean value at the site with the maximum level. This report provides a background for evaluating the clinical results of immunotherapy in these patients and a model for the way in which sensitization and exposure should be monitored in studies of this kind.

Adolescent↗
PubMed1995

Active and inactive transplacement of the M26 recombination hotspot in Schizosaccharomyces pombe.

The ade6-M26 mutation of the fission yeast Schizosaccharomyces pombe creates a meiotic recombination hotspot that elevates ade6 intragenic recombination approximately 10-15-fold. A heptanucleotide sequence including the M26 point mutation is required but not sufficient for hotspot activity. We studied the effects of plasmid and chromosomal context on M26 hotspot activity. The M26 hotspot was inactive on a multicopy plasmid containing M26 embedded within 3.0 or 5.9 kb of ade6 DNA. Random S. pombe genomic fragments totaling approximately 7 Mb did not activate the M26 hotspot on a plasmid. M26 hotspot activity was maintained when 3.0-, 4.4-, and 5.9-kb ade6-M26 DNA fragments, with various amounts of non-S. pombe plasmid DNA, were integrated at the ura4 chromosomal locus, but only in certain configurations relative to the ura4 gene and the cointegrated plasmid DNA. Several integrations created new M26-independent recombination hotspots. In all cases the non-ade6 DNA was located > 1 kb from the M26 site, and in some cases > 2 kb. Because the chromosomal context effect was transmitted over large distances, and did not appear to be mediated by a single discrete DNA sequence element, we infer that the local chromatin structure has a pronounced effect on M26 hotspot activity.

Chromosomes, Fungal↗
PubMed1995

Isolation and characterization of genetically engineered gallidermin and epidermin analogs.

Gallidermin (Gdm) and epidermin (Epi) are highly homologous tetracyclic polypeptide antibiotics that are ribosomally synthesized by a Staphylococcus gallinarum strain and a Staphylococcus epidermidis strain, respectively. These antibiotics are secreted into media and are distinguished by the presence of the unusual amino acids lanthionine, 3-methyllanthionine, didehydrobutyrine, and S-(2-aminovinyl)-D-cysteine, which are formed by posttranslational modification. To study the substrate specificities of the modifying enzymes and to obtain variants that exhibit altered or new biological activities, we changed certain amino acids by performing site-specific mutagenesis with the Gdm and Epi structural genes (gdmA and epiA, respectively). S. epidermidis Tü3298/EMS6, an epiA mutant of the Epi-producing strain, was used as the expression host. This mutant synthesized Epi, Gdm, or analogs of these antibiotics when the appropriate genes were introduced on a plasmid. No Epi or Gdm analogs were isolated from the supernatant when (i) hydroxyamino acids involved in thioether amino acid formation were replaced by nonhydroxyamino acids (S3N and S19A); (ii) C residues involved in thioether bridging were deleted (delta C21, C22 and delta C22); or (iii) a ring amino acid was replaced by an amino acid having a completely different character (G10E and Y20G). A strong decrease in production was observed when S residues involved in thioether amino acid formation were replaced by T residues (S16T and S19T). A number of conservative changes at positions 6, 12, and 14 on the Gdm backbone were tolerated and led to analogs that had altered biological properties, such as enhanced antimicrobial activity (L6V) or a remarkable resistance to proteolytic degradation (A12L and Dhb14P). The T14S substitution led to simultaneous production of two Gdm species formed by incomplete posttranslational modification (dehydration) of the S-14 residue. The fully modified Dhb14Dha analog exhibited antimicrobial activity similar to that of Gdm, whereas the Dhb14S analog was less active. Both peptides were more sensitive to tryptic cleavage than Gdm was.

Amino Acid Sequence↗
PubMed1995

[Pseudotumor calcinosis in renal failure].

Tumoral Calcinosis is a rare clinical entity characterized by the presence of calcified, periarticular masses, as seen on radiographs. A severe case in a patient with chronic renal failure is presented and the complex etiology of this disease is discussed.

Adult↗
PubMed1995

[Small bowel injuries in blunt abdominal trauma--a diagnostic problem!].

AIMS: Injuries of the small bowel following a blunt abdominal trauma are rare (incidence 6%). The diagnosis is difficult and therefore often missed. The aim of this paper is to acquire an useful diagnostic sequence of our own results in comparison to the literature. METHODS: The diagnostic procedures and the time of the final diagnosis of 13 patients with this rare injury have been retrospectively analysed. RESULTS: Two of these 13 patients died in the emergency room. Five of the remaining 11 patients had signs of peritonitis at the first examination. These were confirmed by findings either in peritoneal lavage (3), ultrasound (1) or X-ray (1). Patients without signs of peritonitis revealed no pathological signs at the first examination with these diagnostic tools. Correct diagnosis was achieved on 7/11 patients within 24 hours. The diagnosis of small bowel injury was confirmed by the rest of the patients (n = 4) after an average of 11 days after trauma. DISCUSSION/CONCLUSION: Initial assessment with diagnostic tools as ultrasound, peritoneal lavage or X-ray is poor. Therefore repetitive controls (Nowadays by ultrasound) are indicated. The CT is a valuable tool to detect an organ lesion in hemodynamic stable patients with positive proof of liquid in the ultrasound. Today the value of the diagnostic laparoscopy is not established. It should be considered that a local ischemia due to the blunt trauma can cause a delayed perforation.

Abdomen↗
PubMed1994

Elucidation of the structure of SA-FF22, a lanthionine-containing antibacterial peptide produced by Streptococcus pyogenes strain FF22.

The antibacterial peptide SA-FF22, produced by the pathogen Streptococcus pyogenes strain FF22 was purified and features of its primary and secondary structure were characterised. Mass spectrometry demonstrated the pure peptide had a mass of 2794Da while, amino acid analysis revealed the presence of the unusual, thioether amino acids lanthionine and 3-methyllanthionine; thus SA-FF22 is a member of the group of antibacterial polypeptides termed lantibiotics. Furthermore, amino acid sequencing showed a unique sequence which was blocked at position 23 by a residue of the unsaturated amino acid 2,3-didehydrobutyrine. Carboxypeptidase-Y digestion could be used to demonstrate that serine occupies the C-terminal position only after complete oxidation of the thioether amino acid bridges, suggesting that the three-dimensional structure of the native peptide may prevent access of the enzyme to the C-terminus. Fragmentation of the native peptide with a variety of proteolytic enzymes failed to yield a peptide containing less than all three of the cross-linked lanthionine and methyllanthionine residues and demonstrated that all three thioether bridges overlapped. Analysis of the circular dichroism of SA-FF22 in various concentrations of 2,2,2-trifluoroethanol in water, SDS micelles and in the presence of artificial phospholipid vesicles suggested that there is significant change in its secondary structure from aqueous to lipophilic environments.

Alanine↗