Search PubMed⌕ Search

Biomedical subjects

H Fromm

Publications and source records attributed to H Fromm.

At least 91 records · Page 5Linked to original sources
PubMed1988

Ursodeoxycholic acid for adjuvant therapy with extracorporeal shock wave lithotripsy of gallstones.

Extracorporeal shock wave lithotripsy (ESWL) of gallstones is a new and experimental treatment. Recent data seem to indicate that the use of ursodeoxycholic acid (UDCA) after ESWL may optimize the results of the shock wave treatment. Most of the published data on the clinical use of such therapy emanate from two studies conducted in West Germany in approximately 300 patients. These subjects received combination therapy with UDCA and chenodeoxycholic acid (CDCA) before and after ESWL. The stone fragments gradually disappeared by 18 months after lithotripsy. No adverse effects attributable to the UDCA-CDCA treatment were noted. Several considerations support the view that adjuvant chemical dissolution therapy will be necessary for best results with ESWL, including compatibility of the rate of stone dissolution postlithotripsy with that of chemical dissolution rather than mechanical ejection; the common presence of cholesterol-supersaturated bile in gallstone patients, promoting reconglomeration of fragments; and decreased contractility of the gallbladder, which may improve after successful cholelitholytic therapy with UDCA. Placebo-controlled studies on the use of UDCA with ESWL are currently being conducted.

Chenodeoxycholic Acid↗
PubMed1987

Evidence for in vivo trans splicing of pre-mRNAs in tobacco chloroplasts.

The rps12 gene codes for chloroplast ribosomal protein S12. In the tobacco chloroplast genome (156 kbp circular DNA), exons II and III of this gene are separated by an intron of 536 bases and are present in two copies in the inverted repeat region, while exon I is located in the large single copy region at a distance of 90 kb and 126 kb from the two copies of exons II and III. These three exons were artificially combined in cloned DNA fragments and hybridized with tobacco chloroplast RNA. Electron microscopic analysis of RNA-DNA hybrids showed that exon I is transcribed as part of a polycistronic RNA containing upstream and downstream sequences; the same is true for exons II and III. Exon I is shown to be transcribed separately from exons II and III. In the most abundant class of the hybridized RNA molecules, exon I was covalently linked to exon II. In these molecules the sequences downstream of exon I and upstream of exon II are not present. These data indicate that maturation of rps12 pre-mRNAs in chloroplasts of tobacco involves trans splicing.

Chloroplasts↗
PubMed1987

Absence of significant role of bile acids in diarrhea of a heterogeneous group of postcholecystectomy patients.

Twenty-five postcholecystectomy (PC) patients who underwent a diagnostic work-up for persistent diarrhea and six control subjects were studied. Fourteen of the 25 patients were also characterized by conditions other than PC which could play a role in the pathogenesis of the diarrhea. However, none of the patients had evidence of ileal disease or resection. The average follow-up of the patients after the study was approximately 4.4 years. Excretion, composition, and aqueous-phase concentrations of fecal bile acids were analyzed using gas-liquid chromatography. Eleven of the 25 PC patients showed an increased fecal bile acid excretion. In three of the 11 patients, the magnitude of the bile acid loss, which ranged from 2.26 to 3.34 mmol/24 hr, indicated the presence of severe bile acid malabsorption. The fecal bile acid composition showed a significant shift from secondary to primary bile acids. In spite of the presence of marked bile acid malabsorption, the aqueous-phase concentrations of the dihydroxy bile acids, chenodeoxycholic and deoxycholic acids, did not, with one exception, reach the secretory level of 1.5 mM. The relatively low aqueous concentrations were the result of low bile acid solubility, due to an acidic fecal pH. Only two of nine patients, one with severe, and the other with equivocal bile acid malabsorption, who were treated with cholestyramine, showed an improvement of the diarrhea. The findings of subsecretory bile acid concentrations in the fecal aqueous phase and of inconsistent therapeutic responses to cholestyramine indicate that, in spite of the presence of bile acid malabsorption, the diarrhea was, with few exceptions, not bile acid-induced. The results of the study also suggest that the diarrhea in many PC patients is multifactorial in origin.

Adult↗
PubMed1987

Modulation of bile secretion by hepatic low-density lipoprotein uptake and by chenodeoxycholic acid and ursodeoxycholic acid treatment in the hamster.

The effects of both apolipoprotein B,E receptor-dependent and receptor-independent uptake of low-density lipoprotein (LDL) in the liver on bile secretion were studied in bile fistula hamsters. Three groups of animals were studied after 4 wk of feeding either a control, chenodeoxycholic acid-, or ursodeoxycholic acid-containing diet. The hepatic receptor-dependent and receptor-independent uptake of LDL was related to both bile flow and biliary lipid secretion. The correlation with bile flow and biliary lipid secretion was positive for the receptor-dependent, but negative for the receptor-independent uptake of LDL. Although the receptor-mediated LDL uptake appeared to exert a strong influence on bile acid-independent bile flow, the receptor-independent uptake showed a significant relation with biliary bile acid excretion. Differences between the two mechanisms of LDL uptake were also evident in the biliary bile acid-cholesterol coupling, which was significantly stronger during receptor-independent than during receptor-dependent uptake of LDL. The effects of LDL uptake on bile secretion were modulated by the experimentally induced changes in both the content and composition of bile acids in the enterohepatic circulation.

Animals↗
PubMed1987

Modulation of low density lipoprotein receptor activity by bile acids: differential effects of chenodeoxycholic and ursodeoxycholic acids in the hamster.

Hamsters were fed chenodeoxycholic acid (CDC), ursodeoxycholic acid, (UDC), or no bile acid. [14C]Sucrose-labeled hamster low density lipoprotein (LDL) and methylated human LDL were infused intravenously to study LDL receptor-dependent and LDL receptor-independent organ uptake, respectively, of LDL. Biliary CDC increased during both CDC and UDC treatment. The UDC enrichment of bile after UDC feeding was relatively small. Bile acid synthesis was suppressed after both bile acid treatments. Under the condition of an acute bile fistula, the hamster LDL uptake increased in the liver, heart, and adrenals in the CDC-treated animals. During an intact enterohepatic circulation, the hepatic uptake of hamster LDL, which accounted for a major portion of the total uptake, was increased after UDC treatment. The hamster LDL uptake in the colon, which represented only a small fraction of the total uptake, increased after CDC treatment. When hamster LDL was infused at increasing concentrations, its uptake was significantly higher in the UDC-treated than in the control and CDC-treated animals. The methylated human LDL uptake showed no significant changes in the different treatment groups under either experimental condition. The study shows significantly different effects of CDC and UDC on LDL receptor activity. Since these differences are expressed in spite of a similar suppression of bile acid synthesis, UDC may directly influence LDL receptor activity.

Albumins↗
PubMed1986

The enigma of the gene coding for ribosomal protein S12 in the chloroplasts of Nicotiana.

A 2.9 kbp region from within the inverted repeat of Nicotiana chloroplast DNA hybridized with a chloroplast DNA fragment from Euglena containing the complete rps12 gene coding for ribosomal protein S12. Nucleotide sequencing within this region revealed the existance of two rps12 coding stretches interrupted by 540 bp having class II intron structure. Joining and decoding the exon regions produced a sequence of 85 amino acids colinear and 81% homologous to the S12 protein of Euglena chloroplasts and E. coli, starting from amino acid residue 38 to the stop codon. Immediately upstream of codon 38, conserved intron sequences were located. However, the 5' 37 codon of Nicotiana chloroplast rps12 could not be identified by electron microscopy of RNA-DNA hybrids within a DNA region extending 4000 bp upstream of codon 38, nor by computer search of a completely sequenced region extending for more than 9000 bp upstream of this codon. In E. coli, alteration in rps12 codons 42 or 87 causes streptomycin resistance. However, the nucleotide sequence of the identified rps12 exons in two Nicotiana chloroplast mutants resistant to streptomycin were found to be identical to that of wild type.

Amino Acid Sequence↗
PubMed1986

Gallstone dissolution treatment with a combination of chenodeoxycholic and ursodeoxycholic acids. Studies of safety, efficacy and effects on bile lithogenicity, bile acid pool, and serum lipids.

Sixteen patients with radiolucent gallstones were treated with a combination of chenodeoxycholic and ursodeoxycholic acids for an average of 19 months. Liver tests remained normal in all patients. In nine of 15 patients (60%), in whom the gallbladder visualized during an oral cholecystogram, gallstones dissolved after one year, in eight of them, partially, and in the remaining one, completely. After two years, partial dissolution became complete in three patients, and partial dissolution occurred in 1 additional patient. Changes in lithogenic index and bile acid pool size were statistically not significant. Biliary content of chenodeoxycholic acid increased significantly from 25.7 +/- 3.53 to 45.2 +/- 3.31 (mean +/- SE)% and that of ursodeoxycholic acid from 2.6 +/- 0.52 to 34.6 +/- 2.45%. There were no discernible changes in serum triglycerides, total cholesterol, and HDL cholesterol. The findings suggest that the chenodeoxycholic-ursodeoxycholic acid combination provides a safe and efficacious treatment for some cholesterol gallstones.

Bile↗
PubMed1986

Gallstone dissolution therapy. Current status and future prospects.

Findings by several groups of investigators have provided a reliable data base that supports a nonoperative approach toward the management of so-called silent gallstones. Considerable progress has been made in the medical dissolution treatment of selected patients with cholesterol gallstones. Ursodeoxycholic acid, and, more recently, a combination of ursodeoxycholic and chenodeoxycholic acids have been shown to be both effective and safe in dissolving gallstones that are predominantly composed of cholesterol. A drawback of the bile acid dissolution therapy lies in a significant recurrence rate after treatment is discontinued. Currently, several new methods of gallstone treatment are under study, which involve either the injection of a cholelitholytic solution, such as methyl tert-butyl ether, into the gallbladder or the use of mechanical means, such as excorporeally induced shock waves, to disintegrate gallstones. These treatments, however, are effective only if the stones are composed mainly of cholesterol without significant admixtures of calcium salts, pigment, or mucus. Most of the treatment failures are probably related to the presence of calcifications that are not visible on conventional radiographs. Future improvements of gallstone dissolution therapy can be expected from the following possible developments: improvement in ability to predict gallstone composition; dissolution of calcium salt-, pigment-, and mucus-containing stones; early treatment, before calcifications occur; combination of chemical and mechanical methods of treatment; stimulation of gallbladder contraction; prevention of stone recurrence after dissolution; and synthesis of new cholelitholytic agents.

Bile Acids and Salts↗
PubMed1986

Bile acid-induced diarrhoea.

Three types of bile acid-induced diarrhoea can be distinguished. The best documented and most common entity is represented by type I bile acid malabsorption, which occurs as the result of a pathologically, anatomically defined ileopathy. Type II bile acid malabsorption is found in the setting of a morphologically completely normal ileum. This primary disorder of bile acid transport, which has been described in only a few paediatric and adult patients, appears to be rare. The third variety of bile acid malabsorption is characterized by the history of a previous cholecystectomy and/or by the presence of other gastroenterological conditions. Severe bile acid malabsorption is relatively uncommon in the type III syndrome. Even in the presence of severe bile acid malabsorption, patients with this condition are rarely found to have secretory concentrations of faecal bile acids, and/or rarely respond satisfactorily to cholestyramine. Present data suggest that bile acids play no significant role in the pathogenesis of idiopathic diarrhoea. A careful history, the measurement of stool weight and pH, a therapeutic trial of cholestyramine and the performance of a bile acid test, such as a bile acid breath test, can be used to establish the diagnosis of bile acid diarrhoea. Cholestyramine is the treatment of choice and is virtually always effective in this syndrome.

Bile Acids and Salts↗
PubMed1985

Isolation and identification of delta 6-lithocholenic acid (3 alpha-hydroxy-5 beta-6-cholen-24-oic acid) as an intestinal bacterial metabolite of chenodeoxycholic acid in man.

Fecal bacterial biotransformation studies of chenodeoxycholic acid were performed. Incubations were carried out for 30-s to 12-h time intervals. delta 6-Lithocholenic acid was isolated by thin-layer chromatography. Its structure was confirmed by gas-liquid chromatography and mass spectrometry. The proportion of chenodeoxycholic acid biotransformed to delta 6-lithocholenic acid consistently ranged from 5.5 to 14.0%.

Aerobiosis↗
PubMed1985

Value of serum determinations for prediction of increased ursodeoxycholic and chenodeoxycholic levels in bile.

The correlation between biliary and serum levels of ursodeoxycholic and chenodeoxycholic acids was studied in a double-blind controlled manner in 39 patients before and during treatment with ursodeoxycholic acid, 800 mg/day; ursodeoxycholic acid, 400 mg/day; chenodeoxycholic acid, 750 mg/day; chenodeoxycholic acid, 375 mg/day; and placebo, respectively. On a total of 74 occasions, fasting duodenal bile and venous blood samples were obtained simultaneously. Biliary bile acid composition was determined by gas-liquid chromatography and serum ursodeoxycholic and chenodeoxycholic acid concentrations by radioimmunoassays. There was a much closer correlation between the biliary and serum levels of ursodeoxycholic acid (r = 0.8184, P less than 0.001) than between those of chenodeoxycholic acid (r = 0.4707, P less than 0.01). In contrast to serum chenodeoxycholic, which showed many overlaps between pre- and posttreatment values, serum ursodeoxycholic acid proved to be a very sensitive, specific, and convenient means of predicting the presence of increased levels of ursodeoxycholic acid in the enterohepatic cycle.

Bile↗
PubMed1983

Effects of jejunoileal bypass on the enterohepatic circulation of bile acids, bacterial flora in the upper small intestine, and absorption of vitamin B12.

Eleven morbidly obese patients were studied before and at various time intervals after jejunoileal bypass (JIB). Bile acid deconjugation was assessed with the bile acid breath test and bile acid absorption by analyzing the fecal excretion of both radioactively labeled and unlabeled bile acids. In addition, aerobic and anaerobic cultures of upper small intestinal aspirates, the Schilling vitamin B12 absorption test, and fecal fat analysis were performed. All patients developed marked diarrhea and steatorrhea after JIB. The bile acid breath test was positive in all 11 patients after JIB. In 7 of the 11 patients, this test was already slightly positive before JIB. In every instance, however, the bile acid breath test became significantly more abnormal after the bypass operation. The fecal excretion of labeled bile acids increased significantly. However, the increase in the quantitative excretion of the bile acids did not reach statistical significance. The concentrations of bile acids in fecal water were considerably below the levels required to induce diarrhea. This was mainly the result of a low fecal pH and consequent low aqueous solubility. Jejunoileal bypass effected a major shift in fecal bile acids from the secondary bile acids, lithocholic acid and deoxycholic acid, to the respective primary compounds, chenodeoxycholic acid and cholic acid. There were no significant changes in the small bowel bacteriologic findings after JIB. In 5 out of the 9 patients in whom bacteriologic studies were performed, the cultures were positive before the operation. The Schilling vitamin B12 absorption test showed in all patients a significant drop in the 24-hour urinary 57Co excretion rate after JIB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Clone bank of Nicotiana tabacum chloroplast DNA: mapping of the alpha, beta and epsilon subunits of the ATPase coupling factor, the large subunit of ribulosebisphosphate carboxylase, and the 32-kDal membrane protein.

All of the PstI restriction fragments of the chloroplast DNA of Nicotiana tabacum have been cloned in the plasmid vector pBR322. The cloned fragment sizes range from 0.8 to 26 kb, are stable, and can be amplified by chloramphenicol with varying efficiencies. Using these clones we have detailed a PstI physical map of the tobacco chloroplast genome. Selected clones of SalI, BamHI and PstI fragments were used to localize the map positions of the alpha, beta, and epsilon subunits of the chloroplast ATPase coupling factor, the large subunit of ribulosediphosphate carboxylase and the 32-kDal membrane protein. The gene products of these clones were characterized by RNA transcript sizing, immunoprecipitation of maxicell-directed protein synthesis, and hybrid-arrested translation.

Chloroplasts↗