Biomedical subjects

C R Mueller

Publications and source records attributed to C R Mueller.

10 recordsLinked to original sources

PubMed1992

The carbamyl phosphate synthetase promoter contains multiple binding sites for C/EBP-related proteins.

The promoter of the gene (CPS) encoding rat carbamyl phosphate synthetase I has been mapped 5' to a segment of about 525 nucleotides upstream from the transcription start point and, when analyzed in liver nuclear extracts, contained six well-defined protein-recognition elements, designated CPS sites I-VI. All six elements were recognized, with varying affinities, by CAAT and enhancer-binding protein (C/EBP alpha) produced in bacteria. Oligodeoxyribonucleotides corresponding to CPS site II or to the C/EBP alpha-recognition element of the ALB promoter, site D, competed with the six CPS-promoter elements in footprinting assays. However, mutagenesis of the C/EBP alpha-recognition element, 5'-GTTGCAAC, at the core of site II was sufficient to abolish transactivation of the CPS promoter by C/EBP alpha in co-transfected HepG2 cells. These findings indicate that the CPS promoter contains multiple recognition elements for factors with DNA-binding specificities similar to C/EBP proteins. Activation by C/EBP alpha, however, requires promoter site II.

Animals↗

PubMed1992

Effective palliative treatment of metastatic carcinoid tumors with intra-arterial chemotherapy/chemoembolization combined with octreotide acetate.

Survival in patients with metastatic carcinoid tumors is dependent on control of tumor growth and adequate palliation of vasoactive amine-induced symptoms of flushing, diarrhea, wheezing, and valvular heart disease. Eight patients with carcinoid tumors metastatic to the liver were treated with long-term octreotide acetate therapy (100 to 500 micrograms three times a day), intra-arterial 5-fluorouracil infusion (2 g/day x 5 days), and hepatic tumor chemoembolization. All eight patients became asymptomatic and have remained so with a mean follow-up duration of 22 months from the time of first infusion. Following institution of subcutaneous octreotide acetate, intra-arterial infusion, and tumor chemoembolization, all patients are alive with a mean survival of 40 months from the time of diagnosis of carcinoid syndrome (range: 2 to 108 months). Four patients had greater than a 50% decrease in tumor size after therapy (mean follow-up duration: 10.6 months), and the other four patients have had stable disease after institution of therapy. It appears that combinations of long-term subcutaneous administration of octreotide acetate, intra-arterial 5-fluorouracil, and tumor chemoembolization effectively control progressive liver metastasis and provide excellent symptomatic palliation in patients with hepatic metastasis from functional carcinoid tumors.

Carcinoid Tumor↗

PubMed1992

The down-regulation of albumin transcription during regeneration is due to the loss of HNF-1 and the D-site transcription factors.

Liver regeneration has served as an important in vivo model for studying the control of differentiation. The molecular mechanisms responsible for the negative regulation of the albumin promoter during regeneration have not been examined previously. Changes in the proteins interacting with the albumin promoter were characterized using nuclear extracts prepared from the livers of rats undergoing chemically induced regeneration. Reduction in the activities of both hepatocyte nuclear factor-1 (HNF-1) and factors binding to the D site are responsible for the loss of albumin transcription during regeneration. No evidence for the involvement of a transcriptional repressor in this process was found.

Albumins↗

PubMed1991

Acute gastric pH changes alter intraluminal but not plasma peptide levels.

Gastric acidity is influenced by systemic and local peptide effects. Previous work by others has shown that intraluminally secreted peptides may have a role in local control of gastric acidity; however, the response of these peptides to acute changes in gastric pH is unknown. To determine the effects of acute changes in pH on systemic and intraluminal peptide levels, 14 normal volunteers underwent placement of a nasogastric tube after an overnight fast. Blood and gastric fluid were analyzed on a control day, 2 hours after completion of 24 hours of aluminum-magnesium antacid therapy and after 24 hours of H2 blockade. Plasma and acid-alcohol-extracted gastric peptide levels were measured with specific radioimmunoassays. Specimens were subdivided into two groups: 28 gastric fluid specimens with a pH less than 4 and 10 specimens with a pH greater than 4. In the patients with a pH greater than 4, the luminal peptides, motilin, neurotensin, pancreatic polypeptide, somatostatin, substance P, and gastrin, were decreased by 50% to 90% and gastrin-releasing peptide was decreased by 36% compared with specimens with a pH less than 4. Conversely, intraluminal vasoactive intestinal polypeptide and calcitonin levels were elevated by 60% and 27%, respectively, in the samples with a pH greater than 4. Intraluminal peptide concentrations are responsive to changes in intragastric pH; however, this response was not seen in plasma peptide levels.

Antacids↗

PubMed1990

DBP, a liver-enriched transcriptional activator, is expressed late in ontogeny and its tissue specificity is determined posttranscriptionally.

The full-length cDNA for a transcriptional activator, DBP, that binds to the D site of the albumin promoter has been cloned. DBP belongs to a family of related transcription factors including Fos, Jun, CREB, and C/EBP, which share a conserved basic domain. However, unlike most other members of this family, DBP does not contain a "leucine zipper" structure. Among several rat tissues tested, significant levels of its protein are only observed in liver; yet, with the exception of testis, DBP mRNA is present in all of the examined tissues. DBP as well as its mRNA accumulate to significant levels only in adult animals. During chemically induced liver regeneration, DBP expression is rapidly down-regulated, suggesting that DBP may be involved in the proliferation control of hepatocytes. This cell growth-dependent expression of DBP, in contrast to its tissue specificity, appears to be controlled at the level of mRNA accumulation.

Aging↗

PubMed1990

Differential in vitro transcription from the promoter of a rat alpha 2u globulin gene in liver and spleen nuclear extracts.

When used in an in vitro transcription assay, the promoter of a cloned alpha 2u globulin gene is much more active in liver than in spleen nuclear extracts. Promoter deletion experiments suggest that both positive and negative regulatory mechanisms may be involved in the differential in vitro transcription from the alpha 2u globulin promoter in these two nuclear extracts. Interestingly, removal of promoter elements upstream from position -74 results in a significant increase of in vitro transcription in spleen but not in liver nuclear extracts, and thus reduces the difference in transcription observed with longer alpha 2u promoters in these two extracts. Deletion of additional nucleotides to position -43 strongly reduces the in vitro transcription efficiency of the promoter in extracts from both tissues. None of the examined promoters containing between 3000 and 22 nucleotides of 5' flanking regions are differentially transcribed in liver nuclear extracts from either male or female rats. Thus, in contrast to cell-type specificity, sex-specificity could not be observed in our in vitro transcription experiments. DNase I protection experiments with crude nuclear extracts and partially or highly purified nuclear proteins suggests the presence of six recognition sites for DNA-binding factors between the TATA element and position -210. Some of these factors could be identified as proteins that also bind to elements within the albumin gene promoter.

Alpha-Globulins↗

PubMed1988

The polyomavirus enhancer comprises multiple functional elements.

The polyomavirus enhancer occupies 244 base pairs within noncoding sequences between the early and late transcription units. To define more precisely the DNA sequences that make up the enhancer, we cloned it together with the viral early promoter upstream of a reporter gene, isolated mutants bearing deletions introduced in vitro in the enhancer, and measured the capacity of the various mutant genomes to express the cat gene after transient transfection into mouse 3T3 cells. Analysis of a large number of deletion mutants revealed that the enhancer is between 102 and 172 base pairs long and can be divided into at least three functional elements. Relative to the entire enhancer, individual elements possessed little or no enhancer activity. However, pairs of elements enhanced transcription to levels much higher than the sum of individual elements approximating the activity of the complete enhancer. These findings support the view that the polyomavirus enhancer is composed of multiple sequence elements that function combinatorily and imply that a measure of cooperation exists in the interaction between cellular protein factors bound to their cognate sites in the enhancer and the transcriptional machinery of the cell.

Animals↗

PubMed1988

Lactational response to soybean meal, heated soybean meal, and extruded soybeans with ruminally protected methionine.

Seventy-three high producing Holstein cows were arranged in a 3 X 2 factorial to evaluate three protein supplements (soybean meal, heat-treated soybean meal, and extruded blend of soybeans and soybean meal) without or with 15 g/head/d of ruminally protected DL-methionine during wk 4 through 16 postpartum. Total mixed diets contained (DM basis) 30% corn silage, 15% alfalfa hay, and 55% of the respective concentrate mix. Milk production was higher when cows were fed either heated soybean product instead of soybean meal. Methionine supplementation increased production when fed with soybean meal (32.2 and 33.8 kg/d) but not when fed with heat-treated soybean meal (34.5 and 33.0 kg/d) or extruded soybeans (36.2 and 34.4 kg/d). Milk fat percentages were lower with extruded soybeans (3.01, 2.93, and 2.66) and were similar without (2.83) or with (2.90) supplemental methionine. Milk protein percentages were highest when fed soybean meal, lowest with extruded soybeans (3.02, 2.92, and 2.87), and higher with supplemental methionine (2.91 and 2.96). Dry matter intake was higher when fed supplemental methionine (20.0 and 21.3 kg/d). Production of milk in early lactation high producing dairy cows was increased by supplementing a soybean meal diet with ruminally protected methionine or by replacing the soybean meal with heat-treated soybean meal, soybeans, or a mixture of the two.

Animal Feed↗

PubMed1987

Protected methionine supplementation with extruded blend of soybeans and soybean meal for dairy cows.

Methionine may be the first amino acid limiting milk production in early lactation cows. To evaluate this further, 23 high producing Holstein cows (9 multiparous and 14 primiparous) were fed an extruded blend of soybeans and soybean meal (40:60) without or with 15 g of added DL-methionine as 50 g of ruminally protected methionine product during wk 4 to 16 postpartum. Cows were fed a 15.8% crude protein total mixed ration consisting of 30% (dry basis) corn silage, 15% alfalfa hay, and 55% concentrate mix. Covariant-adjusted yields of milk (35.3 and 33.9 kg/d) and solids-corrected milk (29.3 and 28.2 kg/d) were lower for cows fed ruminally protected methionine, whereas yields of 4% fat-corrected milk (28.2 and 27.4 kg/d) were similar. Percentages of fat (2.68 and 2.69) and solids-not-fat (8.82 and 8.83) were similar, and percentages of protein (2.86 and 2.90) were higher from cows fed supplemental methionine. Dry matter intakes (20.5 and 21.6 kg/d) were higher for cows fed ruminally protected methionine. Methionine concentrations in arterial and venous serum were elevated slightly by feeding supplemental methionine. Although methionine was still the first-limiting amino acid as calculated by two different methods, supplementation of this diet with ruminally protected methionine did not increase production of early lactation cows.

Animal Feed↗

PubMedDate not supplied

Phase I-II trial of hyperthermic isolated limb perfusion with cisplatin in the treatment of high risk malignant melanoma of the extremities.

Between 1983 and 1990, 59 patients with malignant melanoma were retrospectively reviewed to assess the safety, efficacy and the maximal tolerated dose of cisplatin used in hyperthermic isolated limb perfusion. The median follow-up was 29 months (range 3-54 months). The local recurrence rate was 12% in Stage I, 33% in Stage II and 30% in Stage III patients. The maximal tolerated dose of cisplatin in hyperthermic isolated limb perfusion was 3.2 mg/kg for forequarter perfusions and 6 mg/kg for hindquarter perfusions based on lean body weight. At these dosages, there is an 8% major complication rate and only one patient experienced long-term sequelae. Hyperthermic isolated limb perfusion using cisplatin in the dosages of 3-6 mg/kg lean body weight is associated with low morbidity and appears to have efficacy comparable to L-phenylalanine mustard for the control of locally recurrent malignant melanoma.

Chemotherapy, Cancer, Regional Perfusion↗