K-ras protooncogene mutations in feline pancreatic adenocarcinomas.
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Adenocarcinoma↗
Biomedical subjects
B Mayr
Publications and source records attributed to B Mayr.
K-ras mutations in canine pancreatic cancers.
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Adenocarcinoma↗
N-ras mutations in canine malignant melanomas.
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Animals↗
Successful jejunal nutrition therapy in a pregnant patient with apallic syndrome.
A 41-year-old woman was admitted in the 8th pregnancy week as a consequence of a left-sided media infarction. After alloprothetic aortic valve replacement, she had discontinued deliberately the mandatory anticoagulation treatment. Following an initial clinical stabilisation, a second insult with right-sided media total infarction occurred 3 weeks after admission. In the further course, she developed an apallic syndrome and required respirator therapy. The initial enteral nutrition therapy via naso-gastric tube, was continued via percutaneous endoscopic gastrostomy (PEG). Due to recurrent vomiting from the 24th pregnancy week, the PEG was changed into a PEG with jejunal position of the tube (JET-PEG). Via this access and simultaneous body impedance analysis (BIA) control, the further nutrition therapy could be continued uneventfully. In the 27th pregnancy week, the patient gave birth to a female newborn (birth weight: 820 g) by Caesarean section in pre-eclampsia. The foetal development was in accordance with the gestational period and uncomplicated in the further course. The mother could be released into ambulatory care where the above nutrition therapy was continued. Reports on a successful nutrition therapy of pregnant comatose patients are rare. To the best of our knowledge, this is the first case where JET-PEG and monitoring by repeated BIA measurement were used for the control of the enteral nutrition.
Adult↗
N-ras mutation in a canine lymphoma: short communication.
Lymphomas of dogs were investigated by molecular genetic methods. Regions of exon 1 and 2 of the N-ras gene, which harbours the mutation hot spots (codons 12, 13 and 61) were screened. A GGT [symbol: see text] GAT (glycine [symbol: see text] aspartic acid) mutation in codon 13 was present in a multicentric-type lymphoma of a 1-year-old male dog.
Animals↗
Secretion of free and protein-bound leptin from subcutaneous adipose tissue of lean and obese women.
Leptin circulates as a free (FL) and a protein-bound (BL) form, with the soluble leptin receptor (LR) as an important binding compound. Here we measured these components of leptin in serum and in the incubation medium of sc adipose tissue in healthy lean (n = 10) and obese (n = 13) female subjects using recently developed specific RIA systems. In addition, immunostaining for FL, BL, and LR in adipose tissue was performed. Serum FL levels were increased in the obese subjects (P < 0.0001), whereas BL and LR concentrations in serum of lean and obese subjects were similar. Both FL and BL were secreted from human preadipocytes and increased in parallel to the differentiation of the cells. In sc fat cell explants LR antibodies predominantly stained the fat cell membrane, whereas FL and BL antibodies revealed intracytoplasmatic adipocyte staining. The release of FL, BL, and LR from adipose tissue was increased in obese compared with lean subjects (P < 0.005 for FL; P < 0.02 for BL, and P < 0.01 for LR). In summary, fat cells are capable of releasing not only FL, but also BL and LR.
Adipocytes↗
Canine tumour suppressor gene p53 mutation in a case of anaplastic carcinoma of the intestine.
Tumours localised in the large bowel of dogs were subjected to molecular genetic studies. Highly conserved regions of the tumour suppressor gene p53, including typical tumour hot spots (codons 175, 245, 248, 249, 273 and 282), were analysed. A mutation CGG-->TGG (arginine-->tryptophan) was present in codon 249 in an anaplastic carcinoma in the caecum.
Animals↗
Tumour suppressor gene p53 mutation in a case of haemangiosarcoma of a dog.
Haemangiosarcomas of dogs were analysed by molecular genetic techniques. Regions of the tumour suppressor gene p53, including the well-known tumour hot spots (codons 175, 245, 248, 249, 273 and 282) were screened. A 24 bp deletion was detected in exon 5 of the gene.
Animals↗
Metathesis-based monoliths: influence of polymerization conditions on the separation of biomolecules.
Monolithic materials were prepared by transition metal-catalyzed ring-opening metathesis copolymerization of norborn-2-ene and 1,4,4a,5,8,8a-hexahydro-1,4,5,8-exo,endo-dimethanonaphthalene within the confines of surface-derivatized borosilicate columns in the presence of the porogenic solvents toluene and 2-propanol using Cl2(PCy3)2Ru(=CHPh) (1) as initiator. Relevant physicochemical data of the porous structure (specific surface area (sigma), pore volume (Vp), volume fraction of pores (epsilon(p)), and intermicroglobule volume (epsilon(z))) of the monolithic columns were determined by inverse size exclusion chromatography in tetrahydrofuran. Mean particle diameters were determined via electron microscopy. The influence of variations in polymerization conditions in terms of stoichiometry of the monomers and porogenic solvents on the chromatographic separation of the oligodeoxynucleotides dT12-dT18 and eight model proteins (ribonuclease A, insulin, cytochrome c, lysocyme, alpha-lactalbumin, alpha-chymotrypsinogen, beta-lactoglobulin B, catalase) were studied. Also, the role of additional phosphine on the entire polymerization setup and the associated chromatographic separations was elucidated. Relevant chromatographic data as well as differences between the separation of oligodeoxynucleotides and proteins may directly be attributed to the above-mentioned physicochemical properties of the metathesis-based monoliths. Finally, DSC-TGA-MS investigations on various monoliths of different composition and age were carried out in order to provide information on stability and oxidation behavior.
Animals↗
Chiral beta-cyclodextrin-based polymer supports prepared via ring-opening metathesis graft-polymerization.
A series of norborn-2-ene-derivatized beta-cyclodextrins (beta-CDs), 6-O-(norborn-2-ene-5-carboxyl)-beta-CD (1), tetrakis(6-O-norborn-2-ene-5-carboxyl)-beta-CD (2), (3), 6-O-(6-norborn-2-ene-5-car-6-O-(7-oxanorborn-2-ene-5-carboxyl)-beta-CD bonylaminohexoyl)-beta-CD (4), 6-O-(norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD (5), tris(6-O-norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD (6), tetrakis(6-O-norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD (7) and hexakis(6-O-norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD (8), have been synthesized. Compounds 1-3 were prepared via reaction of beta-CD with norborn-2-ene-5-carboxylic chloride and 7-oxanorborn-2-ene-5-carboxylic chloride, respectively; compounds 5-8 were synthesized from norborn-2-ene-5-yl-methyldichlorosilane and beta-CD, respectively. Compound 4 was accessible by reaction of norbom-2-ene-5-carboxylaminohexoyl chloride with beta-CD. Compounds 1-8 were surface grafted onto norborn-2-ene-derivatized silica-based supports using ring-opening metathesis polymerization employing the ruthenium-based initiator bis(tricyclohexylphosphino)benzylideneruthenium dichloride [Cl2Ru(CHC6H5)(PCy3)2, Cy=cyclohexyl, 9]. Generally speaking, the resulting chiral stationary phases (CSPs) I-VIII may be prepared with high reproducibility and may be used within a pH of 2-10. Thus, relative standard deviations (sigman-1) of the mean resolution (Rs) are <7%. The CSPs were used for the enantioselective separation of beta-blockers, N-dansyl-, N-3,5-dinitrobenzoyl- and Fmoc-protected amino acids and were characterized in terms of chemical stability, selectivity (alpha') and resolution (Rs). Additionally, the role of the spacer as well as influences of capacity and the degree of substitution of the beta-CD moiety on the separation characteristics were determined.
Cyclodextrins↗
Influences of surface chemistry on the separation behavior of stationary phases for reversed-phase and ion-exchange chromatography: a comparison of coated and grafted supports prepared by ring-opening metathesis polymerization.
A series of poly(norborn-2-ene) (poly-NBE), poly(7-oxanorborne-2-ene-5,6-dicarboxylic acid) (poly-ONDCA), as well as poly(norborn-2-ene-co-7-oxanorborne-2-ene-5,6-dicarboxylic acid) (poly-NBE-co-ONDCA) based silica supports were prepared via ring-opening metathesis polymerization (ROMP) using both coating and grafting techniques. Poly-NBE-grafted and poly-NBE-coated supports were used for the reversed-phase separation of phenols; poly-NBE, poly-ONDCA as well as poly-NBE-co-ONDCA-grafted supports were used for comparative studies on the separation of a series of anilines and lutidines. As expected, grafted supports possess superior separation capabilities compared to their coated analogues. Compared to pure poly-NBE- and poly-ONDCA-grafted stationary phases, supports consisting of poly-NBE-co-ONDCA block-copolymers possess both hydrophobic and ion-exchange sites and represent optimum stationary phases for the separation of isomeric basic analytes.
Chromatography, Ion Exchange↗
Comparative analysis of ras proto-oncogene mutations in selected mammalian tumors.
Point mutations within ras proto-oncogenes are frequently detected in human malignancies and in different types of experimentally induced tumors in animals. In contrast to findings in experimental animal models of carcinogenesis, little is known about the incidence of ras mutations in naturally occurring animal tumors. In the present study, we investigated whether point mutations, particularly within the mutational hot-spot codons 12, 13, and 61, occur at comparable frequencies in human malignancies and spontaneously occurring tumors in other mammalian species. Two hundred seventy-nine of the most frequent canine and feline neoplasms were analyzed for changes in mutational hot-spot regions of the N-, Ki-, and Ha-ras genes. DNA fragments from exons 1 and 2 of all three ras genes were amplified by polymerase chain reaction, and the presence of point mutations was assessed by single-strand conformation polymorphism analysis and direct sequencing of amplified products. Only one sample, a case of canine melanoma, exhibited an Ha-ras mutation. Thus, our data strongly suggested that ras mutations at the hot-spot loci are apparently very rare and do not play a major role in the pathogenesis of the spontaneously occurring canine and feline tumors investigated. These observations were in marked contrast to those in experimental rodent models of carcinogen-induced mammary and skin tumors that described a consistent association with Ha- or Ki-ras activation. The role of ras oncogene activation in related human malignancies therefore cannot be readily inferred from studies of experimental carcinogenesis in animal models.
Animals↗
Familial isolated parathyroid adenoma in a consanguineous family.
The 23-year-old Caucasian male propositus presented with symptomatic hypercalcemia, hypophosphatemia and normocalciuria for 2 months. His 29-year-old brother had undergone an operation for recurrent parathyroid adenoma at age 26 and 28. No other member of the family was affected. His father and mother were second-degree relatives. Laboratory studies showed primary hyperparathyroidism (pHPT), while the remaining endocrine studies and genetic testing for multiple endocrine neoplasia 1 and 2A were normal. Technetium-cardiolite scintigraphy and ultrasound scans revealed a parathyroid mass at the left lower neck. Apart from bilateral hearing loss due to gentamicin treatment as a pre-term child, the patient was in of good health. Signs or symptoms of other endocrinopathies were absent. The patient was referred for parathyroidectomy with subsequent autotransplantation of the remaining glands into his sternocleidomastoid muscle. Histological examination revealed an adenoma with oncocytic differentiation, similar to that seen in his brother. The disease may follow a recessive mode of inheritance or may be due to a dominant germ-cell mutation in one of the parents. The presented case may ultimately help in elucidating the molecular genetic basis of this rare form of pHPT.
Adenoma↗
Identification of novel CBFA1/RUNX2 mutations causing cleidocranial dysplasia.
Core binding factor A1 (CBFA1/RUNX2) is a runt-like transcription factor essential for osteoblast differentiation. Haplotype insufficiency causes cleidocranial dysplasia (CCD), a syndrome featuring supernumerary tooth buds, delayed tooth eruption, patent fontanels, Wormian bones, short stature, dysplasia of the clavicles, growth retardation and hypoplasia of the distal phalanges. We identified novel CBFAI/RUNX2 mutations after PCR and direct sequencing of patient leukocyte DNA. In family 1 mother and son are affected by CCD. Both carry the missense mutation R190W (CGG > TGG). This nucleotide change introduced a BsmI restriction site, which was used to independently confirm the mutation. It was absent in healthy members of the family. Family 2, in which father and daughter are affected by CCD, shows a deletion of nucleotide C821. This deletion causes a frameshift mutation with premature stop after the insertion of 18 aberrant amino acids. Healthy family members did not have this mutation. The clavicular dysplasia was more pronounced with the R19OW mutation, while the bone density was markedly reduced in individuals with either mutation, suggesting a previously underemphasized increased risk for osteoporosis in CCD.
Adolescent↗
Transcriptional regulation by the phosphorylation-dependent factor CREB.
The transcription factor CREB -- for 'cyclic AMP response element-binding protein' -- functions in glucose homeostasis, growth-factor-dependent cell survival, and has been implicated in learning and memory. CREB is phosphorylated in response to various signals, but how is specificity achieved in these signalling pathways?
Activating Transcription Factor 1↗
Lack of sequence variation in sporadic bovine leucosis in regions of tumour suppressor genes p53 and p16.
Regions of the promoter and exons 5-8 of the tumour suppressor gene p53 were analysed in 25 cases of sporadic bovine leucosis. The study included 17 cases of juvenile leucosis, five cases of adult leucosis and three cases of skin leucosis. Exon 2 of tumour suppressor gene p16 was also investigated in the same samples. No sequence variations were present in the analysed areas of the genes. In p53, this fact represents a clear difference in comparison with enzootic bovine leucosis. In p16, no comparative data are available.
Amino Acid Sequence↗
Free and protein bound leptin are distinct and independently controlled factors in energy regulation.
AIMS/HYPOTHESIS: Leptin exerts important regulating effects on energy homeostasis and could have a central role in our understanding of obesity, diabetes mellitus and the metabolic syndrome. Leptin circulates in a free and protein bound form. The aim of the present study was to test whether both fractions of the leptin system can be selectively regulated and thus serve independent physiological roles. METHODS: Using specific radioimmunoassays we measured both leptin components in relation to BMI in healthy subjects before and after weight reduction and in hyperthyroid patients during correction of thyrotoxicosis. In the latter group body composition and resting energy expenditure was monitored. In addition, we measured serum and cerebrospinal fluid concentrations of free and bound leptin in patients with neurological disorders. RESULTS: Under all conditions free leptin concentrations reflected body fat mass. Bound leptin concentrations decreased during weight reduction but also after treatment of hyperthyroidism despite an increase in fat mass. Direct measurement of resting energy expenditure and bound leptin in hyperthyroid patients and under thyrostatic treatment showed a significant positive correlation of both variables. In contrast to free leptin whose transport into the cerebrospinal fluid appears to be saturated at low physiological concentrations of serum free leptin, bound leptin concentrations in the cerebrospinal fluid increased in parallel to serum concentrations over the whole physiologically relevant range. CONCLUSION/INTERPRETATION: Our data indicate a distinct role of free and bound leptin in the feedback regulating energy intake and expenditure and could have important implications for our understanding of the physiology and pathophysiology of leptin-dependent signalling.
Adolescent↗
Absence of p21 WAF1 and p27 kip1 gene mutations in various feline tumours.
The coding regions of tumour suppressor and cell cycle regulatory genes p21 WAF1 and p27 Kip1 were investigated in 101 feline tumours of various types. No damaging mutations were present in the analysed areas of the genes.
Adenocarcinoma↗