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Biomedical subjects

H Fromm

Publications and source records attributed to H Fromm.

At least 73 records · Page 4Linked to original sources
PubMed1991

Increased paracellular permeability in intrahepatic cholestasis induced by carmustine (BCNU) in rats.

Carmustine [i.e., 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)] is a drug with cholestatic potency both in experimental animals and in humans. To study the mechanisms involved in the development of the hepatic lesions, early changes in liver function in rats pretreated with the drug were investigated. Dosages and sampling times that did not result in hepatocellular injury, as indicated by release of marker enzymes, were applied. In isolated perfused livers from pretreated rats, bile flow and maximal secretion rate of taurocholate were decreased. An increase in biliary [14C]sucrose clearance suggested enhanced permeability of the bile tract and was correlated with increased inorganic phosphate concentration in bile. To assess the contribution of paracellular and transcellular pathways of sucrose, [14C]sucrose access into bile was analyzed by biliary off-kinetics after omission of the radioactive marker from the perfusion medium. An improved method was developed to quantitate the permeability of the bile tract by applying the classical flow equation to the paracellular portion of biliary sucrose clearance. With this method it was shown that pretreatment of rats with BCNU resulted in an increase in both diffusion and convection of paracellular sucrose from perfusate into bile. Accordingly, the fast access of horseradish peroxidase from perfusate into bile was facilitated in isolated perfused livers of BCNU-treated rats. The results indicate that an increase in paracellular permeability is an early alteration that may contribute to the development of hepatotoxic lesions caused by BCNU. It is shown that inert solute clearance can be used to assess paracellular permeability if the paracellular fraction is determined.

1-Naphthylisothiocyanate↗
PubMed1990

[Ferritin in myeloproliferative diseases].

Serum ferritin concentration was studied in 79 patients with chronic granulocytic leukemia (CGL), 14 patients with polycythemia vera (PV), eleven patients with osteomyelosclerosis (OMS) and four patients with megakaryocytic myelosis (MM). Pretreatment serum ferritin concentrations were found to be normal or slightly decreased in patients with PV, OMS, MM and in the chronic phase of CGL. Patients entering the blastic crisis of CGL had highly increased serum ferritin concentrations. The severity of hyperferritinemia in these patients depended on the cytomorphological type of the blastic crisis. Highest levels of serum ferritin concentration were found in the immature myeloblastic type according to the M1- and M2-type of the FAB-classification of acute leukemias (i.e. 30-fold and 18-fold increased). In contrast, the rise of the serum ferritin concentration in the more mature types of blastic crisis was less pronounced (i.e. nine-fold in the M3-type and six-fold in the M4- and M5-type of blastic crisis). Patients with complete remission after bone marrow transplantation had normal serum ferritin concentrations. Investigation of the intracellular ferritin concentration showed, that the serum ferritin levels paralleled the intracellular ferritin concentration within the leukemic blasts: During the myeloic blastic crisis the intracellular ferritin concentration was found to be 17-fold increased compared to the intracellular ferritin concentrations in the chronic phase of CGL. Thus, our data support the concept that an increased synthesis of ferritin by the leukemic blasts is responsible for the increased serum ferritin concentration during the blastic crisis of CGL.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗
PubMed1990

Densely calcified gallstone treated successfully with piezoelectric lithotripsy.

A patient with biliary pain and a densely calcified gallbladder stone was treated successfully with piezoelectric extracorporeal shock-wave lithotripsy. The gallstone was fragmented to particles of less than 1-2 mm in diameter in a single 1-h session. The procedure was performed in the outpatient setting and required no anesthesia or analgesia. Follow-up sonograms showed that clearance of residual fragments from the gallbladder had occurred within 1 wk. Our encouraging treatment result suggests the need for future research to be directed towards broadening the currently recommended criteria for biliary lithotripsy, which currently exclude treatment of densely calcified gallstones.

Biliary Tract Diseases↗
PubMed1990

Effects of bile acid depletion and of ursodeoxycholic and chenodeoxycholic acids on biliary protein secretion in the hamster.

The effect of changes of both the rate of secretion and the composition of bile acids on biliary proteins was studied in a bile fistula hamster model. Biliary protein secretion as well as bile flow and bile acid secretion were studied in response to intravenous infusions of low, medium and high doses of ursodeoxycholic acid and chenodeoxycholic acid in comparison to the infusion of the normal saline carrier (control) solution. The control-infused animals showed a marked and statistically significant increase in both the concentration and total excretion of biliary proteins. All three doses of ursodeoxycholic acid either prevented the increase of protein concentration or led to its decrease. The low and medium doses of chenodeoxycholic acid had similar effects. However, the high dose of this bile acid was cholestatic and increased the biliary protein concentration. The results of the study indicate that decreases in bile acid secretion, as they occur after an interruption of the enterohepatic circulation, may lead to major increases in biliary protein concentration. The study also shows that these changes in protein secretion, which may promote nucleation, are reversed by the cholelitholytic bile acids, ursodeoxycholic acid and chenodeoxycholic acid.

Animals↗
PubMed1989

Ribosomal protein S12 as a site for streptomycin resistance in Nicotiana chloroplasts.

A streptomycin resistant Nicotiana plastome mutant, X/strR6, was subjected to molecular analysis. In this mutant, a single nucleotide transition, C----T, in the chloroplast gene for ribosomal protein S12 alters codon 90 from proline to serine while the nucleotide sequence of the chloroplast 16 S rRNA gene is identical to that of the wild type. Mutant X/strR6 thus differs from several previously reported streptomycin resistant chloroplast mutants which are altered in the gene for 16 S rRNA.

Base Sequence↗
PubMed1989

Bile acid-lipoprotein interactions: effects of ursodeoxycholic acid (ursodiol).

Several studies in the hamster model were undertaken to investigate known and recently disclosed metabolic interactions between bile acids and lipoproteins, particularly between ursodiol and low-density-lipoprotein (LDL) receptors. Three groups of animals, receiving a control 0.027% cholesterol diet, supplementation with 0.1% ursodiol, or supplementation with 0.1% chenodeoxycholic acid, were treated for four weeks. Both bile acids suppressed bile acid synthesis. Chenodeoxycholic acid significantly increased serum total cholesterol compared to ursodiol, and high-density-lipoprotein (HDL) cholesterol decreased significantly with chenodeoxycholic acid compared to ursodiol and control. Since the rate of bile acid synthesis is known to influence LDL receptor activity, LDL uptake under these conditions of synthesis suppression was measured. The animals received infusions of hamster LDL and methylated human LDL. Uptake of hamster LDL (occurring by both receptor-dependent and receptor-independent mechanisms) was significantly higher in the ursodiol-treated group than in the others. Human LDL uptake (occurring only by receptor-independent mechanisms) was not significantly affected by either treatment. The mechanisms by which ursodiol apparently directly stimulates the LDL receptor remain speculative but may involve alteration of cell membrane fluidity, change in the rate of LDL receptor cycling, and increase in the number of LDL receptors.

Animals↗
PubMed1989

Gallstone dissolution therapy with ursodiol. Patient selection.

Ursodeoxycholic acid (ursodiol) has been shown to be an effective oral agent for dissolution of gallstones that also has a favorable safety profile. In the selection of patients as candidates for this treatment, stone characteristics and the functional status of the gallbladder are the two most important criteria. Small, primarily cholesterol stones (radiolucent on plain film) are the most suitable for oral dissolution therapy. In addition, a functioning gallbladder (as evidenced by visualization on oral cholecystogram) is required to concentrate the ursodiol-enriched bile and effect stone dissolution. Ursodiol should not be used during pregnancy, in women likely to become pregnant, or in severe acute or chronic intrahepatic cholestasis. Acute cholestasis and common bile duct obstruction also preclude this treatment. Screening tests include basic laboratory tests of liver function, sonographic evaluation of the gallbladder and biliary tree, plain film of the abdomen, and oral cholecystogram. Since few patients meet all the selection criteria ideally, the decision to undertake treatment with ursodiol must be based on the entire clinical profile and on the patient's willingness to accept the predicted likelihood of success.

Age Factors↗
PubMed1989

Interaction of potentially toxic bile acids with human plasma proteins: binding of lithocholic (3 alpha-hydroxy-5 beta-cholan-24-oic) acid to lipoproteins and albumin.

The binding of lithocholic acid to different plasma fractions was studied. When whole plasma was incubated for 8 hr, approximately 25% of the incubated [14C]lithocholic acid was bound to the lipoprotein and lipoprotein-free, albumin-rich fractions. An average of 87.6% of the bound-lithocholic acid was present in the lipoprotein-free, albumin-rich fraction, 7.2% in high density lipoproteins, 2.2% in low density lipoproteins, 1.0% in intermediate density lipoproteins and 2.0% in very low density lipoproteins. Expressed as binding per microgram protein, considerably less [14C]lithocholic acid was bound to the lipoprotein-free, albumin-rich fraction, than to the lipoproteins. The binding of [14C]lithocholic acid after the incubation of the isolated plasma fractions was similar to that found after the incubation of whole plasma. The highest transfer of [14C]lithocholic acid occurred from the lipoprotein-free, albumin-rich fraction to the lipoprotein fractions. The studies indicate, that, although the largest amount of lithocholic acid is bound to the lipoprotein-free, albumin-rich fraction, per microgram protein, the binding of lithocholic acid to lipoproteins is more pronounced and stable than that bound to the lipoprotein-free, albumin-rich fraction. Since lipoproteins, in contrast to albumin, are internalized by most tissues, they may be important carriers into cells of lithocholic acid and other potentially toxic or tumorigenic bile acids.

Humans↗
PubMed1989

An octopine synthase enhancer element directs tissue-specific expression and binds ASF-1, a factor from tobacco nuclear extracts.

We have investigated the expression pattern conferred by a cis-regulatory element (-212 to -154) from the upstream region of the octopine synthase (ocs) gene in transgenic tobacco plants. Analysis of beta-glucuronidase expression driven by the ocs regulatory element revealed a pattern that is tissue-specific and developmentally regulated. In young seedlings, expression is confined primarily to root tips. In older seedlings, expression is stronger and becomes apparent also in the shoot apex. Insertion of a 16-base pair palindromic sequence (-193 to -178), which is included in the regulatory element, into an rbcS promoter results in the expression of rbcS in roots. The 16-base pair palindrome binds activation sequence factor (ASF)-1, a factor from tobacco nuclear extracts that interacts with the sequence between -83 to -63, designated as activation sequence (as)-1, of the cauliflower mosaic virus 35S promoter [Lam et al. (1989). Proc. Natl. Acad. Sci. USA 86, in press]. The in vivo expression patterns and in vitro binding properties of the ocs palindromic sequence are remarkably similar to those of the as-1 element of the cauliflower mosaic virus 35S promoter. These results suggest the involvement of ASF-1 in the transcriptional regulation of the ocs promoter and the 35S promoter.

Amino Acid Oxidoreductases↗