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Biomedical subjects

M Fried

Publications and source records attributed to M Fried.

At least 181 records · Page 10Linked to original sources

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↗

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↗

Influence of orlistat on the regulation of gallbladder contraction in man: a randomized double-blind placebo-controlled crossover study.

Orlistat (tetrahydrolipstatin) is a potent inhibitor of gastric and pancreatic lipase activity causing a diminution of free fatty acids in the intestinal lumen. The release of cholecystokinin (CCK) critically depends on the presence of free fatty acids in the small intestine. Postprandial CCK release and gallbladder contraction might be decreased by orlistat, potentially resulting in an increased risk of gallstone formation. In this double-blind, placebo-controlled, six-way crossover study, six healthy volunteers ingested in a randomized order three isocaloric test meals (250 ml) of identical osmolality with either orlistat (200 mg) or placebo: (a) a pure-fat meal (25 g triglycerides), (b) a mixed meal containing fat (8 g; 29% of caloric content), protein (10 g; 17%), and dextrose (32 g; 54%), and (c) a fat-free meal containing albumin (25 g; 46%) and dextrose (32 g; 54%). Gallbladder volumes were determined by ultrasonography, and plasma CCK, pancreatic polypeptide and gastrin levels by RIA. Gall-bladder contraction (AUC, % x 90 min; difference of means +/- 95% CI) in subjects receiving orlistat or placebo did not significantly differ after intake of the pure-fat meal (443+/-1174), the mixed meal (313+/-1170), or the fat-free-meal (-760+/-1180). The release of CCK (AUC; pM x 90 min; difference of means +/- 95% CI) was not different between orlistat and placebo after ingestion of the pure-fat meal (-18+/-64), the mixed meal (-45+/-62), and the fat-free meal (27+/-63). Likewise, the release of pancreatic polypeptide and gastrin was similar after intake of the meals with either orlistat or placebo. A single dose of orlistat did not reduce gallbladder motility after ingestion of meals with differing fat contents. The safety of long-term treatment with orlistat with respect to gallstone formation remains to be determined.

Adult↗

Full-thickness foot burn of a pilgrim to Mecca.

This report relates to burns of the feet suffered by a pilgrim to Mecca who walked barefoot in the hot desert sun. He subsequently presented with full-thickness burn injuries to the soles of his feet. When the patient developed acute coronary insufficiency, immediate surgery could not be performed. He was therefore treated conservatively with salicylic acid and Silverol cream. Spontaneous closure of the wounds was achieved in the course of 2 months.

Acute Disease↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Primate homologues of rat TGN38: primary structure, expression and functional implications.

cDNAs encoding the human and macaque homologues of rat TGN38 have been cloned and sequenced. The proteins have a highly conserved N terminus (comprising the signal peptide) and C terminus (comprising part of the lumenal domain, the membrane spanning region and cytoplasmic tail) but vary in the other part of the lumenal domain, which contains the repeat region. Whereas rat TGN38 contains 6 tandem repeats of an 8mer, both primate proteins possess 14 tandem repeats of a 14mer sequence. The human protein, like rat TGN38, is localised primarily to the TGN but is present on the cell surface and returns via endosomes. This behaviour is consistent with conservation of the membrane spanning region and the cytoplasmic tail, which contain the retention and retrieval signals, respectively, for localisation in the TGN. The unexpected differences in the lumenal domain can best be rationalised by the fact that both types of repeat domains have most of the properties of mucins. We suggest that TGN38 homologues are mucin-like molecules that regulate membrane traffic to and from the TGN.

Amino Acid Sequence↗

Does Laparoscopic Gastric Banding Demand Sophisticated Measurement Devices?

BACKGROUND: One of the most frequently discussed issues used and a free space for the tip of the Endo-Babcock in gastric banding is the Problem of intraoperative upper gastric Pouch volume assessment and the calibration of the connecting stoma diameter. Having experience with more than 200 adjustable and non-adjustable laparoscopic gastric bandings in last 3 years, we started to study whether it is possible to assess the Pouch volume and stoma diameter by relying on anatomical landmarks and simple bougie calibration, rather than on sophisticated measuring devices. METHODS: We compared results of Postoperative pouch volume control measurements in a group of patients in whom a balloon method of Pouch volume measurement was performed during the gastric banding with a group of patients where no intraoperative measurements of the upper gastric pouch were done. In the latter group the Pouch volume was assessed according to the anatomical landmarks during the dissection: the cardia at the lesser curvature and the avascular area of gastrophrenic ligament at the greater curvature. In both groups endoscopic study 2 weeks following surgery was performed. Concerning stoma diameter we started with a prospective randomized study of two groups. In the first group, we intraoperatively measured by manometry the inside-stoma pressure. In the second group, a simple bougie calibration was used, and a space was left for the tip of the Endo-Babcock instrument between the stomach wall and the band. Postoperatively, the stoma diameters were compared, using the 'balloon catheter pulled through the stoma' method. RESULTS: Pouch volume: in the group operated according to surgeon's assessment of the anatomical landmarks, 96% of the patients' pouch volume did not exceed 60 ml at 2 weeks postoperative checkups The results were no different from the group of patients where intraoperative volume measurements were performed. The stoma diameter: a group of patients where intraoperative stoma pressure measurements were performed and a second group where a simple calibration bougie was instrument was left between stomach wall and band were compared prospectively. There was no statistical difference between the two groups in stoma diameter measured 2 weeks after operation by the 'balloon pull through' method. CONCLUSIONS: It is possible to rely on anatomical landmarks in constructing the upper gastric pouch. Postoperatively, five volume measurements did not show any statistical difference between the group in whom intraoperative Pouch volume measurements were performed and the group where anatomical landmarks were used. There was no statistical difference in postoperative stoma diameter measurements between the group where intraoperative stoma pressure measurements were performed before Closing the band and the group where just a calibration bougie was used and a free space for the tip of an endoscopic instrument was left between stomach wall and band. These measurements were made with the non-adjustable band. With the adjustable band, the stoma diameter measurements would be even less important.

Journal Article↗

Evaluation of delayed gastric emptying in diabetic patients with autonomic neuropathy by a new magnetic resonance imaging technique and radio-opaque markers.

OBJECTIVE: Our objective was to validate a new noninvasive magnetic resonance imaging (MRI) technique for diagnosis of delayed gastric emptying by using radio-opaque markers (ROMs) in diabetic patients with and without cardiovascular autonomic (CAN) and peripheral sensomotoric neuropathy (PSN). RESEARCH DESIGN AND METHODS: Fifteen diabetic outpatients were recruited, eight with CAN and PSN (group A, age 28-61 years, mean diabetes duration 27 years) and seven without CAN (group B, age 28-60 years, mean diabetes duration 16 years). Gastric emptying and motility were assessed with ROMs and MRI in random order. After an overnight fast either a test meal (451 kcal) containing a capsule with 10 ROMs is eaten and a supine plain abdominal X ray is taken after 6 h or 500 ml intralipid 10% (550 kcal) is swallowed for the MRI study, using a 1.5 Tesla Gyroscan ACS II (Philips, Eindohoven, The Netherlands). Computer-assisted segmentation of images was used to measure gastric emptying (T1/2, min) over 125 min, contraction frequency (F, min-1), mean contraction amplitude (CA, % basal), and velocity (V, cm/s). Blood glucose was kept constant at 5.0-8.0 mmol/l. RESULTS: In group A, 6.1 +/- 1.36 ROMs (mean +/- SE) were retained in the stomach after 6 h and 0 ROM in group B, indicating a significant delay of gastric emptying in patients with CAN. The MRI study revealed a significantly longer gastric emptying (P < 0.005) in group A (T1/2 = 124 +/- 10 min) as compared with group B (T1/2 = 85 +/- 18 min). There was no difference in F, CA, and V between the two groups: F 2.9 +/- 0.07 and 2.7 +/- 0.1 (min-1), CA 26.8 +/- 1.2 and 29.6 +/- 1.6 (% basal), V 0.43 +/- 0.02 and 0.40 +/- 0.02 (cm/s), respectively. CONCLUSIONS: MRI offers the possibility of visualizing and examining exactly the mechanisms responsible for gastric emptying and is characterized by a high specificity but a lower sensitivity as compared with ROMs, which proved to be an ideal screening test for diagnosis of gastroparesis in clinical practice.

Adult↗

Rapidly progressive portal hypertension 23 years after post-traumatic arterioportal fistula of the liver.

Intrahepatic arterioportal fistulas may occur after blunt abdominal trauma and lead to severe portal hypertension, which can be prevented by early diagnosis and treatment. The diagnostic workup of an asymptomatic young male with elevated transaminases revealed an arterioportal fistula secondary to a traumatic liver rupture during childhood, 23 yr earlier. Three years after initial diagnosis, the patient presented with gastrointestinal hemorrhage. Progression of portal hypertension had resulted in esophageal varices and ascites. After ligation of the right hepatic artery, the esophageal varices and ascites disappeared. Twelve months after surgery, the patient is asymptomatic without any signs of liver decompensation or recurrence of gastrointestinal hemorrhage. Our case demonstrates that rapid progression of portal hypertension with severe complication can occur in patients with arterioportal fistula after a long-lasting asymptomatic course of 23 yr. Simultaneous chronic hepatitis C may have a contributory role.

Accidents, Traffic↗