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Biomedical subjects

M Fried

Publications and source records attributed to M Fried.

At least 19 recordsLinked to original sources
PubMed1996

The amplicons in HL60 cells contain novel cellular sequences linked to MYC locus DNA.

We have previously determined that the amplified DNA present in the HL60 promyelocytic leukaemia cell line contained 70 kb of continuous DNA sequences around the c-myc gene. In the work presented here we have further defined the HL60 amplicon and find it to be of the order of 160 kb and to contain a large region of DNA from chromosome 8q24 that is located at least 260 kb telomeric to the c-myc gene, joined to the 70 kb of DNA from the c-myc gene region. The novel chromosome 8 DNA coamplified sequences are not lost during multiple passage of HL60 cells since the composition of the chimeric amplicon is the same in both early passage HL60 cells containing only double minutes (DMs) and late passage isolates containing homogeneous staining regions (HSRs) at different chromosomal locations. This shows that the HL60 HSRs found in late passage cells are not generated anew but are directly derived from the precursor DMs. The HL60 cells contain two copies of chromosome 8, each with different polymorphic markers. Both these chromosome 8 homologues retain a c-myc gene as well as the region containing the coamplified DNA sequences indicating that the HL60 amplicons were not generated by simple DNA deletion. The constraint to maintain the novel DNA sequences coamplified with c-myc gene DNA suggests that these sequences may play some role in maintaining the growth potential and/or differentiation capacity of the HL60 cells.

Chromosomes, Human, Pair 8↗
PubMed1996

[Helicobacter pylori and ulcer disease: diagnosis and treatment 1995].

The association between Helicobacter pylori infection and type-B gastritis as well as peptic ulcer disease is established. Eradication of this organism effectively eliminates ulcer recurrence. Furthermore, seroepidemiologic studies suggest a role for Helicobacter pylori in gastric malignancies. For patients with peptic ulcer disease, the determination of Helicobacter pylori infection is recommended and, if positive, should be followed by an eradication therapy.

Algorithms↗
PubMed1996

[Effect of non-steroidal antirheumatic agents on the gastrointestinal tract: clinical aspects and pathophysiology].

The major gastrointestinal side effects of non-steroidal antiinflammatory drugs (NSAID) mainly occur in the stomach and duodenum. Acute mucosal lesions are almost always seen but only 50% of patients complain of upper abdominal discomfort. NSAIDs elevate the risk of ulcerations of the stomach or duodenum 4 to 5 fold. Side effects in the small bowel are due to elevated intestinal permeability which may lead to inflammatory reactions, chronic blood loss and iron deficiency. Ulceration, perforation and strictures of the small and large bowel may also occur in rare cases.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

[Prevention and therapy of NSAID-induced ulcers: fact versus myth].

Non-steroidal antiinflammatory drugs (NSAIDs) are responsible for dyspeptic symptoms in more than 50% of patients. Symptomatic ulcers and ulcer complications occur in less than 5%. In order to avoid these complications during prolonged treatment, the lowest possible NSAID dose should be chosen. Furthermore, NSAIDs can often be replaced by paracetamol. Prophylaxis of NSAIDs and ulcers with misoprostol is only indicated in a small risk group of patients (eg: advanced age, history of ulcer and for gastrointestinal bleeding, concurrent corticosteroid treatment and significant comorbidity) and only if NSAIDs are given for several months. NSAIDs-induced ulcers should be treated with omeprazole in a dose of 20-40 mg daily.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

[Detection of RET-proto-oncogene mutations in the diagnosis of Type 2 endocrine neoplasia (MEN 2)].

We have analyzed 95 blood- and 25 paraffin-derived DNA samples of 120 individuals from Switzerland (MEN 2 family members and patients with medullary thyroid carcinoma or pheochromocytoma) for the presence of RET protooncogene mutations in exons 10, 11, 13, 14 and 16, where recently germline point mutations have been identified in more than 95% of patients with MEN 2A, familial medullary thyroid carcinoma (FMTC) and MEN 2B. Molecular DNA screening of samples was performed by non-radioactive single strand conformation polymorphism (SSCP) and heteroduplex gel electrophoresis method followed by mutation analysis of PCR products by direct cycle sequencing using an automated DNA sequencer. We identified 12 MEN 2A/FMSC and 6 MEN 2B families with 29 gene carriers. Ten different types of mutations were identified in the MEN 2A/FMTC families (620 Cys-->Arg, 618 Cys-->Ser, Gly, 611 Cys-->Tyr; 634 Cys-->Arg, Tyr, Trp, Phe, Ser, Gly) and all 6 MEN 2B families had a 918 Met-->Thr point mutation. Our results indicate that PCR-based DNA testing for RET point mutations is a rapid, accurate and reproducible method of identifying MEN 2 gene carriers using blood or tissue DNA. Early detection of gene carriers allows preventive thyroidectomy without neck dissection or parathyroid transplantation, and non-gene carriers can be released from biochemical testing. Furthermore, it is shown that the distribution and localization of RET mutations in MEN 2 families from Switzerland concur with combined results of larger series and that a "founder effect" of MEN 2 can be excluded for this country.

Adrenal Gland Neoplasms↗
PubMed1996

Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta.

Women are particularly susceptible to malaria during first and second pregnancies, even though they may have developed immunity over years of residence in endemic areas. Plasmodium falciparum-infected red blood cells (IRBCs) were obtained from human placentas. These IRBCs bound to purified chondroitin sulfate A (CSA) but not to other extracellular matrix proteins or to other known IRBC receptors. IRBCs from nonpregnant donors did not bind to CSA. Placental IRBCs adhered to sections of fresh-frozen human placenta with an anatomic distribution similar to that of naturally infected placentas, and this adhesion was competitively inhibited by purified CSA. Thus, adhesion to CSA appears to select for a subpopulation of parasites that causes maternal malaria.

Adhesiveness↗
PubMed1996

cDNA sequence analysis and expression of the expression of the ribosomal protein S24 during oogenesis and embryonic development of the sea urchin Paracentrotus lividus.

A gene for the Paracentrotus lividus ribosomal protein S24, called P1-S24, has been isolated and sequenced. Ribosomal protein P1-S24 consists 130 amino acids and has a molecular weight of 14869 Da. Sequence analysis shows a high percentage (90%) identity with the corresponding gene of Strongylocentrotus purpuratus. Hybridization of the cDNA to digested sperm DNA suggests that P1-S24 is represented in no more than two copies. Studies of the temporal expression of P1-S24 gene indicate a good correlation between this and the expression of the rRNA genes both during oogenesis and embryonic development.

Amino Acid Sequence↗
PubMed1996

The human L35a ribosomal protein (RPL35A) gene is located at chromosome band 3q29-qter.

Using a polymerase chain reaction (PCR)-based strategy that distinguishes functional intron-containing genes from pseudogenes, the chromosomal location of the human intron-containing L35a ribosomal protein gene (rpL35a, HGMW-approved symbol RPL35A) was previously deduced to be onchromosome 18 using DNAs from a panel of human-rodent somatic cell hybrids. The inability to detect rpL35a in a human-hamster somatic cell hybrid containing only human chromosome 18 led to a reinvestigation of the chromosomal location of the human rpL35a gene. A clone containing intron 2 of rpL35a was isolated, sequenced, and used to isolate a P1 clone containing the human intron-containing rpL35a gene. By fluorescence in situ hybridization (FISH) analysis with the P1 clone as a probe, the rpL35a gene was located on chromosome band 3q29-qter. This location was confirmed by positive PCR analysis of a human-hamster somatic cell hybrid containing only human chromosome 3. The problem of using only human-rodent somatic cell hybrids for chromosome location is discussed.

Amino Acid Sequence↗
PubMed1996

Appropriateness and diagnostic yield of upper gastrointestinal endoscopy in an open-access endoscopy unit.

BACKGROUND AND STUDY AIMS: This prospective study tested the appropriateness of referrals for upper gastrointestinal endoscopy in an open-access endoscopy unit, using the criteria of the American Society for Gastrointestinal Endoscopy. It also examined whether there was any relationship between appropriateness of use and the presence of significant lesions detected by endoscopy. METHODS: Four hundred fifty consecutive upper gastrointestinal endoscopies were studied prospectively. The referral indication was recorded by the endoscopist before the procedure was performed, and was compared with the current criteria of the American Society for Gastrointestinal Endoscopy and with endoscopic findings. RESULTS: The appropriateness of referral was assessed in 442 consecutive endoscopies. Of these, 252 (57%) were judged to be appropriate. In 168 (88%) of the 190 endoscopies rated as inappropriate, the reason was that the patient had not undergone empirical anti-ulcer therapy before endoscopy. The probability of finding a significant lesion did not differ between the endoscopies judged to be appropriate (50%) and those judged to be inappropriate (46%) CONCLUSIONS: Upper gastrointestinal endoscopy was frequently used for inappropriate indications. The main reason for inappropriate use was insufficient treatment, or no treatment, of dyspeptic symptoms prior to endoscopy. In this study, the criteria for appropriateness did not predict the probability of finding a significant endoscopic lesion.

Adult↗
PubMed1996

The Surf-6 gene of the mouse surfeit locus encodes a novel nucleolar protein.

The Surfeit locus contains the tightest cluster of mammalian genes so far described. The five Surfeit genes (Surf-1 to -5) that have been previously isolated and characterized do not share any DNA or amino acid sequence homology. These Surfeit genes appear to be housekeeping genes, with the Surf-3 gene encoding the 1.7a ribosomal protein and the Surf-4 gene encoding an integral membrane protein most likely associated with the endoplasmic reticulum. In this work, we have isolated the Surf-6 gene, a sixth member of the Surfeit locus. The Surf-6 gene contains four exons spanning a genomic region of 14 kb and specifies a mRNA of 2,571 bases. Surf-6 has features common to housekeeping genes because its transcript is present in every tissue tested, its 5' end is associated with a CpG-rich island, and its promoter does not contain a canonical TATA box. The Surf-6 long open reading frame encodes a novel highly basic polypeptide of 355 amino acids (28% Arg and Lys). By immunofluorescence and immunoblot analyses, the Surf-6 protein has been found to be located in the nucleolus and by immunocytochemical microscopy to be localized predominantly in the nucleolar granular component, a structure that is involved in ribosome maturation. These results indicate that the novel Surf-6 gene is involved in a nucleolar function.

Amino Acid Sequence↗
PubMed1996

Surfeit locus gene homologs are widely distributed in invertebrate genomes.

The mouse Surfeit locus contains six sequence-unrelated genes (Surf-1 to -6) arranged in the tightest gene cluster so far described for mammals. The organization and juxtaposition of five of the Surfeit genes (Surf-1 to -5) are conserved between mammals and birds, and this may reflect a functional or regulatory requirement for the gene clustering. We have undertaken an evolutionary study to determine whether the Surfeit genes are conserved and clustered in invertebrate genomes. Drosophila melanogaster and Caenorhabditis elegans homologs of the mouse Surf-4 gene, which encodes an integral membrane protein associated with the endoplasmic reticulum, have been isolated. The amino acid sequences of the Drosophila and C. elegans homologs are highly conserved in comparison with the mouse Surf-4 protein. In particular, a dilysine motif implicated in endoplasmic reticulum localization of the mouse protein is conserved in the invertebrate homologs. We show that the Drosophila Surf-4 gene, which is transcribed from a TATA-less promoter, is not closely associated with other Drosophila Surfeit gene homologs but rather is located upstream from sequences encoding a homolog of a yeast seryl-tRNA synthetase protein. There are at least two closely linked Surf-3/rpL7a genes or highly polymorphic alleles of a single Surf-3/rpL7a gene in the C. elegans genome. The chromosomal locations of the C. elegans Surf-1, Surf-3/rpL7a, and Surf-4 genes have been determined. In D. melanogaster the Surf-3/rpL7a, Surf-4, and Surf-5 gene homologs and in C. elegans the Surf-1, Surf-3/rpL7a, Surf-4, and Surf-5 gene homologs are located on completely different chromosomes, suggesting that any requirement for the tight clustering of the genes in the Surfeit locus is restricted to vertebrate lineages.

Amino Acid Sequence↗
PubMed1996

Bacterial overgrowth during treatment with omeprazole compared with cimetidine: a prospective randomised double blind study.

BACKGROUND: Gastric and duodenal bacterial overgrowth frequently occurs in conditions where diminished acid secretion is present. Omeprazole inhibits acid secretion more effectively than cimetidine and might therefore more frequently cause bacterial overgrowth. AIM: This controlled prospective study compared the incidence of gastric and duodenal bacterial overgrowth in patients treated with omeprazole or cimetidine. METHODS: 47 outpatients with peptic disease were randomly assigned to a four week treatment regimen with omeprazole 20 mg or cimetidine 800 mg daily. Gastric and duodenal juice were obtained during upper gastrointestinal endoscopy and plated for anaerobic and aerobic organisms. RESULTS: Bacterial overgrowth (> or = 10(5) cfu/ml) was present in 53% of the patients receiving omeprazole and in 17% receiving cimetidine (p < 0.05). The mean (SEM) number of gastric and duodenal bacterial counts was 6.0 (0.2) and 5.0 (0.2) respectively in the omeprazole group and 4.0 (0.2) and 4.0 (0.1) in the cimetidine group (p < 0.001 and < 0.01; respectively). Faecal type bacteria were found in 30% of the patients with bacterial overgrowth. Basal gastric pH was higher in patients treated with omeprazole compared with cimetidine (4.2 (0.5) versus 2.0 (0.2); p < 0.001) and in patients with bacterial overgrowth compared with those without bacterial overgrowth (5.1 (0.6) versus 2.0 (0.1); p < 0.0001). The nitrate, nitrite, and nitrosamine values in gastric juice did not increase after treatment with either cimetidine or omeprazole. Serum concentrations of vitamin B12, beta carotene, and albumin were similar before and after treatment with both drugs. CONCLUSIONS: These results show that the incidence of gastric and duodenal bacterial overgrowth is considerably higher in patients treated with omeprazole compared with cimetidine. This can be explained by more pronounced inhibition of gastric acid secretion. No patient developed signs of malabsorption or an increase of N-nitroso compounds. The clinical significance of these findings needs to be assessed in studies with long-term treatment with omeprazole, in particular in patients belonging to high risk groups such as HIV infected and intensive care units patients.

Adult↗
PubMed1996

Role of antrum in regulation of pancreaticobiliary secretion in humans.

Little is known about the role of the gastric phase in the postprandial pancreaticobiliary response. We evaluated the effect of antral distension on pancreatic, biliary, and gastric secretions and on the release of cholecystokinin (CCK), gastrin, and pancreatic polypeptide in five healthy volunteers. Studies were performed using a duodenal tube with an inflatable balloon in the antrum and a separate gastric tube. Outputs were compared with responses to a maximal CCK stimulus (caerulein), and the role of cholinergic mechanisms was investigated using atropine. Graded antral distension by 50-, 200-, and 350-ml balloon volumes and constant antral distension by 350 ml elicited a marked stimulation of pancreaticobiliary secretions. Mean lipase outputs amounted to 52-60%, and mean bilirubin outputs reached 14-22% of maximal. Atropine completely abolished pancreaticobiliary responses to antral distension. Antral distension did not affect bicarbonate and gastric secretions. Plasma pancreatic polypeptide levels increased markedly during antral distension, and this effect was completely suppressed by atropine. There were no changes in circulating gastrin and CCK. These data demonstrate that antral distension with already small volumes of 50 ml elicits a hitherto unknown potent stimulatory effect, indicating a major role of the antrum in the postprandial pancreaticobiliary response in humans, which is mediated by cholinergic mechanisms.

Adult↗
PubMed1996

Measurement of proximal and distal gastric motility with magnetic resonance imaging.

The precise motor mechanisms associated with gastric emptying of nutrient liquids are unclear, in part because of difficulties in measuring the motility from the proximal and distal stomach simultaneously. We have now examined proximal and distal gastric motility, using a novel magnetic resonance imaging (MRI) technique. In seven healthy volunteers (4 males, 3 females; 27-37 yr), gastric emptying and motility were determined on two occasions after ingestion of 500 ml 10% and 25% dextrose labeled with 1 mM gadolinium tetraazacyclododecane tetraacetic acid, using a 1.5-tesla Philips Gyroscan ACS II scanner. Gastric emptying was determined every 15 min with a series of transaxial scans. After each series of transaxial scans, 120 coronal scans, 1.2 s apart, were performed through the antrum and proximal stomach. For each coronal slice the diameters of the proximal stomach and the antrum were measured to determine the number of contractions per minute and depth (%basal diameter). Gastric emptying (half-emptying time) was faster after ingestion of 10% compared with 25% dextrose (49 +/- 15 vs. 118 +/- 37 min; P < 0.01). After both meals, the diameter of the proximal stomach remained relatively constant, whereas there were marked fluctuations in the diameter of the antrum. Mean (+/- SD) frequency (2.8 +/- 0.6 vs. 2.0 +/- 0.8/min; P < 0.001) and depth (40 +/- 17% vs. 34 +/- 16%; P < 0.04) of antral contractions were higher after 10% dextrose compared with 25% dextrose. Rapid MRI techniques allow simultaneous measurement of both gastric emptying and motor function of different gastric regions. The increase in the frequency and depth of distal gastric contractions during ingestion of 10% compared with 25% dextrose supports the concept that the antrum contributes to the regulation of gastric emptying of nutrient liquids.

Adult↗
PubMed1996

Role of cholecystokinin as a regulator of solid and liquid gastric emptying in humans.

The role of endogenous cholecystokinin (CCK) in the regulation of gastric emptying remains controversial. We therefore studied the effect of the CCK-A receptor antagonist loxiglumide on gastric emptying of a high-caloric solid-liquid meal in humans. Gastric emptying was assessed in eight volunteers using intravenous loxiglumide or placebo in a randomized double-blind order. Subjects were studied by a dual-headed gamma camera after ingestion of a pancake (570 kcal) labeled with 99mTc-sulfur colloid and 500 ml 10% glucose containing 111In-diethylenetriamine pentaacetic acid. Plasma CCK was measured by a specific radioimmunoassay. Loxiglumide markedly accelerated gastric emptying of both phases of the meal. The lag period was shortened by 26% (P < 0.03); the area under the emptying curve and half-emptying time of solid emptying were lowered by 19 and 24% (P < 0.02) and of liquid emptying by 18 and 24% (P < 0.04), respectively. Plasma CCK levels were higher during infusion of loxiglumide compared with placebo (P < 0.02). These data demonstrate that post-prandially released CCK is a major regulator of gastric emptying of physiological meals containing both solid and liquid components.

Adult↗