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Biomedical subjects

M Fried

Publications and source records attributed to M Fried.

At least 307 records · Page 17Linked to original sources
PubMed1988

To extract or not to extract in secretin radioimmunoassay?

The importance of an ethanol extraction procedure in the radioimmunoassay of plasma secretin was investigated. The extraction step led to a higher assay sensitivity of 0.35 fmol/ml, compared to 5.93 fmol/ml using unextracted samples. The rise of plasma secretin after infusion of a low dose of secretin (1 pmol.kg-1.h-1) in 10 healthy humans was only detected after sample extraction. Higher doses (3 and 9 pmol.kg-1.h-1) resulted in increments of plasma IRS (immunoreactive secretin), which could be recorded both with and without sample extraction. After a steak meal 7 of 10 subjects showed a significant increase of plasma secretin assaying extracted plasma samples. The secretin release occurred in spikes. The mean increase of plasma IRS in this group was 0.6 fmol/ml, the mean maximal secretin release above basal was 2.3 fmol/ml. Without sample extraction, plasma secretin was not significantly changed. We conclude that plasma samples should be extracted in order to detect physiological postprandial secretin release.

Animals↗
PubMed1988

Temporal relationships of cholecystokinin release, pancreatobiliary secretion, and gastric emptying of a mixed meal.

The influence of gastric emptying of nutrients on plasma cholecystokinin and pancreatobiliary functions is poorly understood. We therefore temporally related the emptying of fat, protein, and glucose of a mixed meal to release of the gut hormones cholecystokinin, pancreatic polypeptide, and peptide YY and outputs of trypsin, lipase, bilirubin, and bile salts. Five healthy volunteers with a multilumen duodenal tube ingested a mixed meal with phase-specific markers for the aqueous phase, liquid fat, solid fat, and solid protein phases. Duodenal passage was determined by intraduodenal infusion of a second set of phase-specific nonabsorbable markers. Plasma cholecystokinin levels and pancreatobiliary secretions rose to a maximum at 30-60 min and then gradually declined (p less than 0.01) despite continued entry of protein and fat into the duodenum throughout the whole 4-h experimental period. High levels of both pancreatic polypeptide and peptide YY were observed in the last 2 h of the experiment. Release of factors capable of inhibiting cholecystokinin release and subsequently pancreatobiliary secretion may be responsible for the observed time-course.

Adult↗
PubMed1988

The mouse surfeit locus contains a very tight cluster of four "housekeeping" genes that is conserved through evolution.

The four identified alternating transcription units (Surf-1 to Surf-4) in the mouse surfeit locus are very tightly clustered, no two neighboring units being separated by more than 73 base pairs and the Surf-2 and Surf-4 transcription units overlapping by 133 base pairs at their 3' ends. All four surfeit genes, which are unrelated by sequence similarity, were found to have the properties of "housekeeping" genes, being expressed in a variety of differentiated mouse cell lines and containing unmethylated CpG-rich islands in the vicinity of their 5' ends. The unusual organization of the four surfeit genes was found not to be unique to the mouse: the same juxtaposition of the genes was found to be conserved in a number of different mammals, including humans. The four human surfeit genes were also found to be transcriptionally active.

Animals↗
PubMed1988

The structure and function of the integrated polyoma virus DNA in 82-rat and 53-rat transformed cells.

Integrated viral sequences and adjacent cellular sequences from the polyoma virus (Py)-transformed 53-Rat and 82-Rat cell lines which contain two and three partial early regions respectively, each in a single viral insert, have been molecularly cloned. Each of the cloned partial early regions have been subcloned and assessed with regard to their transcription, translation products (T antigens, T Ags) and biological activity including their transforming ability. The 53-Rat 5.3 kb EcoRI fragment is an intact Py EcoRI linear genome (derived from within the tandem duplicated sequences) which transforms rat cells with high efficiency and produces infectious virus when circularized and transfected into mouse cells. The 82-Rat cell line expresses three novel T Ag species of 63K, 40K and 32K in addition to the Py middle and small T Ags. The 63K protein was found to be a truncated form of large T Ag produced as the result of an addition/deletion in early region B sequences unique to large T Ag. The 40K and 32K proteins are hybrid viral-cellular middle and large T Ags respectively, which are expressed from early region A that has been truncated by recombination with rat cellular DNA. Differences in the nuclear and cytoplasmic location of the different 82-Rat early region RNAs are due to RNA stability and/or transport from the nucleus to the cytoplasm most likely as a result of different cellular sequences at their 3' ends. Finally no common structural feature or sequence specificity was observed at the virus-host DNA joins of the two cell lines.

Animals↗
PubMed1988

One of the tightly clustered genes of the mouse surfeit locus is a highly expressed member of a multigene family whose other members are predominantly processed pseudogenes.

The mouse surfeit locus is unusual in that it contains a number of closely clustered genes (Surf-1, -2, and -4) that alternate in their direction of transcription (T. Williams, J. Yon, C. Huxley, and M. Fried, Proc. Natl. Acad. Sci. USA 85:3527-3530, 1988). The heterogeneous 5' ends of Surf-1 and Surf-2 are separated by 15 to 73 base pairs (bp), and the 3' ends of Surf-2 and Surf-4 overlap by 133 bp (T. Williams and M. Fried, Mol. Cell. Biol. 6:4558-4569, 1986; T. Williams and M. Fried, Nature (London) 322:275-279, 1986). A fourth gene in this locus, Surf-3, which is a member of a multigene family, has been identified. The poly(A) addition site of Surf-3 lies only 70 bp from the poly(A) addition site of Surf-1. Transcription of Surf-3 has been studied in the absence of the other members of its multigene family after transfection of a cloned genomic mouse DNA fragment, containing the Surf-3 gene, into heterologous monkey cells. Surf-3 specifies a highly expressed 1.0-kilobase mRNA that contains a long open reading frame of 266 amino acids, which would encode a highly basic polypeptide (23% Arg plus Lys). The other members of the Surf-3 multigene family are predominantly, if not entirely, intronless pseudogenes with the hallmarks of being generated by reverse transcription. The role of the very tight clustering on regulation of expression of the genes in the surfeit locus is discussed.

Amino Acid Sequence↗
PubMed1988

Evaluation of disease activity in rheumatic patients by leucocyte adhesiveness/aggregation.

Previous work has shown that leucocyte adhesiveness/aggregation (LAA), as measured by the leukergy test, correlates well with disease severity in rheumatic patients. As LAA is probably a manifestation of the acute phase reaction various components of the acute phase reaction were measured in order to identify the best marker of disease activity. In addition to LAA, the following variables were measured in 79 patients with various rheumatic diseases and in 10 controls: white blood cell and platelet counts, erythrocyte sedimentation rate, haptoglobin, fibrinogen, C reactive protein, albumin, globulin, caeruloplasmin, alpha 1, alpha 2, beta, and gamma globulin, and haemoglobin concentrations. Patients were graded according to the state of their disease as mild, moderate, or severe. The extent of leucocyte adhesiveness/aggregation in peripheral blood proved to be the best laboratory variable for the grading of disease activity. Correct grading was obtained in 63% of the patients by means of the LAA, compared with 48% with C reactive protein, 41% with caeruloplasmin, 40% with haptoglobin, and 32% with haemoglobin. It is suggested that LAA of the peripheral blood during inflammation may be used as a reliable marker of disease severity.

Adolescent↗
PubMed1988

Release of secretin along the canine small intestine.

The profile of secretin release along the entire canine small intestine was examined in this study. Four equal loops of the small gut, from the duodenal bulb to the ileocoecal valve, were isolated. In eight anesthetized dogs the four segments were perfused for 40 min each in random order with an acidified (pH 2.5) emulsion of 20 mM oleic acid. In four dogs control experiments were performed using 0.15 M saline. Secretin release in portal venous blood was measured by a sensitive radioimmunoassay. Although secretin was mainly released in the first quarter of the small intestine (310 pM X 40 min), large amounts of secretin, 33% of the total secretin release, were liberated in the second quarter of the small intestine (164 pM X 40 min). Minute amounts of secretin (23 pM X 40 min) were released in the third quarter, whereas perfusion of the last quarter of the small gut failed to release secretin. We conclude that the major portion of secretin is releasable in the first quarter of the small gut. High amounts of secretin can be liberated in the second quarter of intestine, an area that is probably never exposed to pH below 4.5 (the known threshold for secretin release by acid), but is still exposed to fatty acids (other releasers of secretin).

Animals↗
PubMed1987

Hepatocellular carcinoma in a long-term survivor of acute lymphocytic leukemia.

Hepatocellular carcinoma (HCC) occurred in a 28-year-old woman treated for acute lymphocytic leukemia (ALL) with methotrexate (MTX) and 6-mercaptopurine (6-MP), off all therapy for 15 years, who was also heterozygous for alpha-1 antitrypsin (alpha-1 AT) deficiency. MTXD is responsible for the development of HCC in this patient. The literature concerning the incidence of HCC in patients treated with MTX and 6-MP and in alpha-1 antitrypsin deficiencies is reviewed.

Adult↗
PubMed1987

[Hypertensive crisis after withdrawal of clonidine and nadolol. Case report and review of the literature].

The clonidine withdrawal syndrome occurs in at least 1.2% of patients following withdrawal of the drug. Its frequency is influenced by length of treatment, daily dosage and degree of hypertension. The combination of clonidine with beta blockers favours the development of hypertensive crisis following clonidine withdrawal. The case is presented of a 49-year-old female who had had chronic renal insufficiency and hypertension for several years and who developed a hypertensive crisis after cessation of therapy with clonidine and nadolol. An overshoot hypertension after clonidine withdrawal should be treated with vasodilatatory drugs such as nitroprusside; calcium antagonists and ACE inhibitors also offer a possible new approach. It is advisable to reduce the clonidine dose slowly, and combination with labetalol or calcium antagonists during clonidine withdrawal seems to have favourable results. Beta blockers should be discontinued well before the cessation of clonidine treatment.

Clonidine↗
PubMed1987

Structure of an inverted duplication formed as a first step in a gene amplification event: implications for a model of gene amplification.

Inverted duplications have been observed to be a common feature of gene amplification in mammalian cells and appear to be generated as a primary event in the amplification process (Ford et al., 1985; Ford and Fried, 1986). The structural features of the amplified inverted duplication, containing the polyoma virus oncogene middle T-antigen, were analysed in transformed 3B rat cells. No unusual sequences such as transposition elements were detected at the site of the inversion. The inversion was generated by a simple illegitimate recombination event in which only a single nucleotide directly at the point of the inversion cannot be accounted for from the sequence of the two parental strands. Possible structural (hairpin formation) and sequence (rich AT) features may have been involved in the illegitimate recombination event at the inversion join. In the cellular DNA near one of its joins with polyoma virus DNA an unusual sequence of 198 bp composed of 99 consecutive purine-pyrimidine pairs has been detected. A model for the generation of amplified DNA containing inverted duplications is proposed.

Animals↗
PubMed1987

Passage of salivary amylase through the stomach in humans.

With an inhibitor assay technique rates of passage of salivary and pancreatic isoamylase through the jejunum were measured in six healthy volunteers after different liquid, intragastric meals. In all subjects and in 13/17 experiments, more than 2500 units of salivary amylase were passed over 200 postcibal minutes. Salivary amylase comprised 13.8 +/- 3.9% (mean +/- SEM) of the total amylase and appeared predominantly as single, distinct peak. The inhibitor method was validated by isoelectric focusing (r = 0.988; P less than 0.001; N = 7). The frequency of detection of salivary amylase in gastric or jejunal samples fell as gastric pH fell below 3.0. In vitro, amylase was inactivated in gastric juice as pH fell between 3.8 and 3.3. Salivary amylase accounted for 11% of total amylase output in a normal and 27% in an achlorhydric subject after a hamburger meal. We conclude that amylase should not be measured in postprandial studies of pancreatic secretion in humans without correction for salivary amylase.

Adult↗
PubMed1987

Polyomavirus early region alternative poly(A) site: 3'-end heterogeneity and altered splicing pattern.

The position of an alternative polyadenylation [poly(A)] site at the 3' end of the polyomavirus middle T antigen (T-Ag) coding sequences suggests the possibility of a functional role for this site in early gene regulation. The fine structure of this alternative poly(A) site was determined by cDNA sequence and 3' S1 analyses. Cleavage-poly(A) was found to be heterogeneous, occurring at multiple CA dinucleotides downstream from the AATAAA signal sequence. About 50% of the alternative poly(A) takes place upstream from the middle T-Ag stop codon. In addition, the pattern of splicing of transcripts with the alternative poly(A) site differed from that with the major poly(A) site at the end of the early region. The ratio of the small and middle T-Ag splices to the large T-Ag splice for the alternative poly(A)+ mRNAs is about 2.5 times that found for mRNAs with the major poly(A) site. The altered splicing pattern and 3'-end heterogeneity of the alternative poly(A)+ mRNAs would result in preferential translation of small T-Ag (to a greater degree) and middle T-Ag over large T-Ag at later times in the polyomavirus lytic cycle.

Animals↗
PubMed1987

[Rational diagnosis and therapy of irritable colon].

The irritable bowel syndrome is a common motility disorder of the gut characterized by constipation, diarrhea and abdominal pain. Symptoms are markedly influenced by psychological factors. The diagnosis is based on typical symptoms and exclusion of organic diseases. Psychological support by the physician is an important part of the patients' treatment. High fiber diets and bulking agents may be prescribed in addition. Antispasmodic and antidiarrheal drugs should be given only the shortest time possible, while psychotropic drugs are seldom necessary.

Colonic Diseases, Functional↗