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Biomedical subjects

R Hecker

Publications and source records attributed to R Hecker.

At least 19 recordsLinked to original sources
PubMed1992

Glycosylinositol phospholipid anchors of the scrapie and cellular prion proteins contain sialic acid.

The only identified component of the scrapie prion is PrPSc, a glycosylinositol phospholipid (GPI)-linked protein that is derived from the cellular isoform (PrPC) by an as yet unknown posttranslational event. Analysis of the PrPSc GPI has revealed six different glycoforms, three of which are unprecedented. Two of the glycoforms contain N-acetylneuraminic acid, which has not been previously reported as a component of any GPI. The largest form of the GPI is proposed to have a glycan core consisting of Man alpha-Man alpha-Man-(NeuAc-Gal-GalNAc-)Man-GlcN-Ino. Identical PrPSc GPI structures were found for two distinct isolates or "strains" of prions which specify different incubation times, neuropathology, and PrPSc distribution in brains of Syrian hamsters. Limited analysis of the PrPC GPI reveals that it also has sialylated glycoforms, arguing that the presence of this monosaccharide does not distinguish PrPC from PrPSc.

Carbohydrate Sequence↗
PubMed1992

Replication of distinct scrapie prion isolates is region specific in brains of transgenic mice and hamsters.

Scrapie prions are composed largely, if not entirely, of PrPSc molecules. The prion isolates Sc237 and 139H exhibit markedly different incubation times in Syrian, Armenian, and Chinese hamsters, as well as in transgenic (Tg) 81 mice expressing Syrian hamster PrP (SHaPrP). Repassage of prions from transgenic mice or Chinese hamsters into Syrian hamsters revealed that the original properties of the prion isolates are retained. When Syrian hamsters were first inoculated with 139H prions and subsequently challenged with Sc237 prions, the incubation period was determined by the faster Sc237 isolate. Regional mapping studies demonstrated different kinetics and patterns of PrPSc accumulation for Sc237 and 139H prions in the brains of Syrian hamsters as well as Tg(SHaPrP)7 mice. That distinct prion isolates induce different region-specific accumulations of PrPSc in brain suggests a novel mechanism for propagation of isolates whereby they replicate in particular sets of neurons. The prion isolates could be targeted to specific CNS cells by differing conformations of PrPSc, post-translational modifications of PrPSc such as Asn-linked glycosylation, or an as yet undetected macromolecule complexed with PrPSc in the prion.

Animals↗
PubMed1988

Analysis of RNA structures by temperature-gradient gel electrophoresis: viroid replication and processing.

The structure and structural transitions of single-stranded RNA were investigated by energy calculations and temperature-gradient gel electrophoresis. Most experiments have been carried out on RNA of mature viroids and their replication intermediates, which are RNA (-) strand oligomers and RNA (+) strand oligomers. The technique of temperature-gradient gel electrophoresis proved to be particularly useful for analysing co-existing structures. The secondary structure of lowest free energy for unit length and oligomeric replication intermediates is an extended rod-like structure similar to that of the mature circular viroid. When this structure is used as a model for calculations, there is a large degree of agreement between theoretical and experimental curves. Under particular solution conditions, however, (+) strand oligomers undergo a rearrangement from the extended structure to a branched structure, in which every two units form a region of three helices, together 28 bp long. This structure is called the tri-helical structure. The process of structure formation during the synthesis of oligomers could be followed: at first, a transient multi-branched structure is formed which is then transformed into the extended and the tri-helical structures. The region of the three stable helices serves to divide up the oligomeric (+) strand into structural units which may be recognized by cleavage and ligation enzymes, and be processed into circular mature viroids. Co-transcription of complementary (+) and (-) strands shows that energetically favored double-strand formation may at least partially be prohibited by stable secondary structures of the single strands. Natural replication intermediates have been analysed in respect to their subcellular location and their size distribution. They are associated with the nucleoli as was found earlier for mature viroids. Natural (-) strand oligomers are larger than (+) strand oligomers; both types show a periodicity in the size distribution of two units. The models of the structures, which are involved in viroid processing, are in accordance with recent infectivity data and with the results on natural replication intermediates.

Base Sequence↗
PubMed1988

Preliminary experience with a combined-modality approach to the management of oesophageal cancer.

A synchronous chemoradiotherapy schedule of modest dosage has been used in 36 patients with oesophageal cancer since July 1984 at the Royal Adelaide Hospital. The schedule, which comprises two five-day continuous infusions of 5-fluorouracil, each of which is followed by a short cisplatin infusion, together with 30-35 Gy of megavoltage irradiation over three weeks, has been used alone, or before surgical resection or further chemo-irradiation. It has been extremely well tolerated and has caused complete endoscopic resolution of disease before surgery or further chemo-irradiation in 69% of patients. At the end of the full course of treatment, complete relief of dysphagia has been achieved in 27 (84%) of the 32 patients in whom this symptom was present at the start of treatment. The median duration of relief has not yet been reached with a median follow-up of over one year. This degree of palliation is significantly better than that which was achieved in a series of patients who were treated radically either by surgery or radiation alone between the years 1978 and 1983 at the Royal Adelaide Hospital. The 12- and 18-month actuarial survival figures of 72% and 55%, respectively, for the 30 patients in this series whose disease remained apparently localized to the thorax at presentation, compare very favourably with the corresponding figures for the much more highly-selected group of patients who were treated surgically between 1978 and 1983.

Actuarial Analysis↗
PubMed1988

Early gastric cancer: 52 cases of combined experience of two south Australian teaching hospitals.

Fifty-two patients with early gastric cancer are described. At presentation, the average age was 60 years and the male:female ratio was 3:2. The patients had presenting symptoms indistinguishable from those due to benign peptic ulcer disease. Endoscopic examination with multiple biopsies was the most accurate means of diagnosis, with an overall 93% detection rate. The tumours were located predominantly along the lesser curve (75%) and in the antrum (64%), with ulcerated or depressed lesions most common and flat lesions least common. Approximately 58% of lesions were of intestinal type, submucosal invasion was seen in 45% and lymph node metastases had occurred in 7% of cases. Lesser curve and antral lesions were more likely to be ulcerated. Ulcerated lesions were on average, the same size as non-ulcerated lesions. Body lesions were larger than antral lesions and lesions which had spread to the submucosa were larger than mucosal lesions. Diffuse-type lesions were more likely to be ulcerated than intestinal-type lesions and dysplasia was more commonly associated with intestinal-type lesions than with diffuse or mixed-type lesions. The crude 5-year survival rate was 80%, but only one death was associated with a recurrence of gastric cancer.

Adenocarcinoma↗
PubMed1988

Olsalazine in the treatment of active ulcerative colitis: a placebo controlled clinical trial and assessment of drug disposition.

The efficacy, safety and disposition of olsalazine was assessed in patients with left-sided ulcerative colitis or proctitis in a double-blind placebo controlled trial. Thirty patients with a mild-to-moderate attack of ulcerative colitis were randomly allocated to olsalazine capsules, 1 g b.d., or placebo for 6 weeks. Good clinical response was found in six patients receiving olsalazine and in two receiving placebo. Improvement in sigmoidoscopic findings and histological appearance of rectal biopsies was also seen more often in olsalazine-treated patients. Plasma concentrations of olsalazine were significantly higher in patients who improved. Olsalazine showed an advantage over placebo which needs to be confirmed by further studies; it was safe in sulphasalazine-sensitive patients but appeared to cause watery diarrhoea in two patients.

Aminosalicylic Acids↗
PubMed1987

Chromatographic separation of DNA restriction fragments.

Reversed-phase liquid chromatography (RPC-5) was the first chromatographic technique to be successfully applied to DNA restriction fragments. Size-exclusion high-performance liquid chromatography (HPLC) has the advantage of wide variability in buffer conditions but is restricted to an upper size limit at 800 base pairs. Anion-exchange HPLC is most versatile and may best be scaled up for the preparation of milligram amounts of specific DNA fragments. The preparation of the sample before and after chromatography is described. Because several applications of DNA fragments will be complemented by RNA fragments, their preparation and purification is included. Disposable small-scale columns are available for processing many samples. Future medical applications of HPLC of DNA fragments concern medical microbiology, human genetics and forensic medicine.

Animals↗
PubMed1986

Osseous hypomobility.

An interesting case of hypomobility involving a 13-year-old Mexican girl is presented. The patient had been unable to open her mouth more than 1 mm since she suffered a fall at the age of 5. A surgical procedure was performed to correct the disability.

Adolescent↗
PubMed1985

High-performance liquid chromatography of DNA restriction fragments.

High-performance liquid chromatography on Nucleogen-DEAE 4000-10 has been applied to several problems of the isolation of DNA restriction fragments. Large amounts of DNA fragments of high purity are necessary for biophysical studies and for molecular hybridization in basic research, as well as in medical diagnosis. The influence of various parameters, such as buffer, pH, eluting salt, gradient slope, flow-rate and the addition of urea on the resolution of fragments by high-performance liquid chromatography were studied on an analytical scale, and the optimal conditions were then used for the large-scale preparation of milligram amounts. The best resolution of fragments between 25 and 1500 base pairs was obtained with a linear gradient from 500 mM to 1200 mM sodium chloride in 6 M urea -30 mM sodium phosphate (pH 6.0). Quantitative data are given for the purity and recovery of the sample, and the capacity and lifetime of the column. The following applications of high-performance liquid chromatography of restriction fragments are described: preparation of 2 mg of fragments, separation of 1 mg of DNA insert from 7 mg of its plasmid vector, and analysis of DNA-RNA hybrids.

Buffers↗
PubMed1985

Antibiotic-associated colitis due to Clostridium difficile: double-blind comparison of vancomycin with bacitracin.

A randomized double-blind study was carried out in patients with unresolving antibiotic-associated colitis due to Clostridium difficile, to compare the effect of bacitracin (80,000 U/day) with vancomycin (500 mg/day) on the resolution of symptoms, clearance of organism, and prevention of relapse. Forty-two patients with colitis, 9 of whom had a pseudomembrane, were randomized, 21 patients to each treatment group. The two groups were comparable in age, disease severity, and antibiotic exposure. For a 50% reduction in stool frequency the mean times (+/- SE) were 4.1 +/- 0.4 days for bacitracin and 4.2 +/- 0.4 days for vancomycin. Sixteen patients (76%) had symptom resolution after 7 days of treatment with bacitracin, compared with 18 patients (86%) given vancomycin. Patients who failed to respond were crossed over (blind) to the alternative antibiotic, but tended to be refractory to the alternative medication as well. Vancomycin-treated patients had negative toxin (83% vs. 53%, p = 0.04) and negative stool cultures (81% vs. 52%, p = 0.02) more frequently than did those patients given bacitracin. Similar numbers of patients in each group had symptomatic relapse during 1 mo of follow-up, but most of them relapsed yet again after blinded crossover therapy. Although bacitracin was significantly less effective than vancomycin in clearing C. difficile from the stools, both were of similar value in the control of symptoms in a group of patients with predominantly nonpseudomembranous colitis. In view of its low cost, bacitracin is a reasonable first-line alternative to vancomycin in the treatment of antibiotic-associated colitis.

Adult↗
PubMed1985

[Automatic contour search and segmentation of sonographic transverse sectional pictures of the uterus with regard to optimization of individual isodose planning in uterine cancer].

Intrauterine ultrasonography has proved to be an adequate method to represent the normal myometrium as well as its pathologic modifications, especially for the assessment of localization and extent of malignant processes. So for the first time, intracavitary radiotherapy of the carcinoma of the body, especially the afterloading technique, can work by means of the produced crossections with a precisely defined target volume, because the sonographic probe and the afterloading probe have identical geometric configurations. A method is presented which allows a computer-assisted determination of the tumor volume by means of the segmentation of organ sections and a pseudo-threedimensional projection in combination with the energy dose distribution of the radioactive source.

Brachytherapy↗
PubMed1984

Clostridium difficile colitis.

We reviewed all rectal biopsies performed on patients with proven C. difficile infection between 1977 and 1982 (36 patients). All patients were symptomatic and all had received antibiotic treatment recently, the commonest antibiotic treatment being ampicillin or amoxycillin. There was poor correlation between the histological appearances and the severity of symptoms. A range of histological appearances was observed: normal (8%), congestion and edema (8%), nonspecific colitis (3%), infective colitis (28%) and pseudomembranous colitis (53%) (PMC). Most cases of PMC showed 'early' features, involving predominantly the surface epithelium, where attenuation and inflammation, intraepithelial microabscesses, and small eruptive lesions were seen. Recognition of these features, in the context of an acute infective-type colitis, may lead to early diagnosis of C. difficile colitis.

Adult↗
PubMed1983

The influence of smoking on the healing of duodenal ulcer treated with oxmetidine or cimetidine.

The influence of smoking on duodenal ulcer healing was examined during a double blind study of 83 patients randomly allocated to oxmetidine or cimetidine treatment. Smoking habits were recorded but patients were not advised to change these. Smokers and nonsmokers were similar clinically and did not differ in compliance with medication. Both H2-receptor antagonists were equally effective and after four weeks of treatment ulcers were healed in 76% of patients. Ulcer healing occurred significantly less frequently in smokers (69%) than nonsmokers (89%). Smokers with healed ulcers consumed fewer cigarettes per day (mean +/- SE: 15.8 +/- 1.4) than those whose ulcers did not heal (22.2 +/- 2.7). When smokers were grouped according to daily cigarette consumption, a direct relationship was found between increasing cigarette consumption and decreasing frequency of ulcer healing. No reduction in ulcer healing was apparent in patients who smoked nine cigarettes a day, or less.

Cimetidine↗