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At least 19 recordsLinked to original sources
PubMed2026

Platelet triggering receptor expressed on myeloid cells-like transcript 1 regulation in healthy donors and patients at risk of bleeding and thrombosis.

BACKGROUND: Triggering receptor expressed on myeloid cells-like transcript 1 (TLT-1), a platelet-specific &#x3b1;-granule protein, is implicated in hemostasis, but its regulation remains unclear. Platelet dysfunction contributes to trauma-induced coagulopathy (TIC) and thrombotic complications in trauma or mechanical circulatory support (MCS); however, underlying mechanisms remain poorly understood. OBJECTIVES: This study investigated the molecular mechanisms underlying soluble TLT (sTLT)-1 release and its role as a biomarker of platelet dysfunction in patients with severe trauma or receiving MCS. METHODS: TLT-1 dynamics on platelets exposed to glycoprotein (GP)VI ligand, coagulation, or shear stress in vitro were evaluated by ELISA and immunoblotting. sTLT-1 was measured in plasma from trauma or MCS-treated patients and healthy donors. Associations with TIC, injury severity, and mortality were assessed. RESULTS: Proteolysis of TLT-1 to release a 10- to 17-kDa fragment was metalloproteinase dependent and blocked by ADAM10 and ADAM17 inhibition. Unlike GPVI, platelet TLT-1 exposure increased following PAR-1 activation. sTLT-1 was elevated in trauma patients compared with controls and correlated with TIC (P < .05) and injury severity (P < .01). Receiver-operating characteristic analysis demonstrated discriminatory performance for TIC (area under the curve, 0.78; P = .011), with a Youden cutoff of 1.180 ng/mL yielding 89% sensitivity and 73% specificity. Platelet TLT-1 was basally expressed, mobilized 2.5-fold with activation, and shed in response to GPVI ligation and plasma recalcification. Shear-exposed platelets and plasma from MCS-treated patients exhibited elevated sTLT-1 levels. CONCLUSION: Unlike GPVI, TLT-1 increased on activated platelets and was regulated by ADAM10 and ADAM17. TLT-1 release is triggered by shear stress, GPVI ligands or activated factor X. Plasma sTLT-1 was associated with trauma severity and TIC.

Humans↗
PubMed2026

Hypoxia reprograms VEGF signaling to differentially control ADAMTS2 and ADAMTS3 expression in endothelial cells.

ADAMTS2/-3, key metalloproteinases involved in collagen processing and extracellular matrix dynamics, remain insufficiently characterized in terms of their transcriptional regulation under hypoxic and pro-angiogenic conditions. In this study, we demonstrate that VEGF&#x2081;&#x2086;&#x2085; robustly enhances ADAMTS2/-3 expression in endothelial cells, with hypoxia providing a striking amplification of this response. Bioinformatic analyses revealed that hypoxia and VEGF induced HIF-mediated and time-varying expression responses in ADAMTS2/-3. Using HUVECs exposed to CoCl&#x2082;-induced hypoxia, VEGF stimulation led to substantial increases in ADAMTS2 (approximately 19-fold at 3&#x202f;h) and ADAMTS3 (approximately 46-fold at 3&#x202f;h) mRNA levels, accompanied by concordant protein upregulation. Promoter-reporter assays revealed strong VEGF responsiveness in defined ADAMTS2 (-658/+112) and ADAMTS3 (-131/+40; -1340/+40) promoter fragments, particularly under hypoxic conditions. Pharmacological inhibition showed that JNK, MAPK/ERK, p38, and PI3K pathways each contributed partially to VEGF-mediated transcription, indicating multi-pathway convergence rather than single-pathway dependency. This finding is consistent with RNA-seq analyses showing that VEGF-related signaling is extensively re-regulated under hypoxic conditions. Extension of these analyses to MG-63 and SAOS-2 cell lines revealed modest but consistent VEGF-induced upregulation, supporting a tissue-independent regulatory axis. Collectively, these findings position ADAMTS2/-3 as potent hypoxia- and VEGF-responsive genes, uncovering their integration into HIF-1&#x3b1;-dependent transcriptional networks and VEGF-activated signaling cascades. This work highlights the relevance of ADAMTS2/-3 in angiogenesis-associated extracellular matrix remodeling and identifies them as promising biomarkers and potential therapeutic targets in hypoxia-driven vascular pathology.

Humans↗
PubMed1977

[Effect of chlortetracycline on the peptide spectrum of rat serum].

Application of chlortetracycline in rats resulted in the occurence of certain peptides in the blood-serum, which could not be detected in the serum of an untreated control group. These results were obtained by means of high voltage electrophoresis and paper electrophoresis of the serum of rats which was analyzed 1,3, and 13 hours respectively after a single dose of 50 mg chlortetracycline per 100 g body weight in comparison to an untreated control group. The new peptides could be found in the slight alkaline range 1 and 3 hours after application of chlortetracycline and in the strong acidic area of the electrochromatogram 13 hours thereafter. A more detailed investigation of the new peptides could demonstrate that the number of the following amino acids was reduced in the peptide chains after chlortetracycline: leucine, valine, serine, arginine, and lysine. On the other hand, amino acids, such as citrulline, sarcosine, alpha-aminobutyric acid, and ornithine, could be found which are normally not present in proteins.

Amino Acids↗
PubMed1977

The forms of vitamin B12 on the transcobalamins.

1. The transcobalamins from normal serum were obtained in two fractions. One contained transcobalamin I and transcobalamin III: the other contained transcobalamin II. The forms of vitamin B12 in the two fractions were then examined. 2. Methylcobalamin and adenosylcobalamin were found in both fractions. Hydroxocobalamin was found in the fraction containing transcobalamin I and transcobalamin III. Cyanocobalamin was found in both fractions in two cases, in the transcobalamin III fraction only in one case and was absent in one case.

Blood Proteins↗
PubMed1976

Modified nucleosides and 5'-end groups in purified mouse immunoglobulin light chain mRNA and rabbit globin mRNA detected by borohydride labelling.

The borohydride reaction has been used to investigate modified nucleosides and end groups in purified immunoglobulin light chain mRNA and rabbit globin mRNA. 1. The light chain mRNA was isolated from the microsomal fraction of MOPC 41A mouse myelomas, which secrete kappa chains, by two cycles of oligo(dT) cellulose chromatography and glycerol gradient centrifugation. The 12 S mRNA was active in a Krebs II ascites cell-free system and appeared to be homogenous as judged by gradient centrifugation, polyacrylamide gel electrophoresis in 98% formamide and fingerprint analysis of 125I-labelled mRNA. 2. End group labelling of the light chain and globin mRNAs by oxidation with periodate and reduction with boro[3H]hydride showed that the RNAs have a 5'-terminal 7-methyl guanosine in 5'-pyrophosphate linkage with the next nucleoside. 3. To detect any modified residues in the interior of chains, nucleosides in complete digests of the mRNAs were converted by the borohydride reaction to 3H-labelled nucleoside trialcohols, which were fractionated by two dimensional chromatography (the Randerath technique). The light chain mRNA was found to contain N6-methyl adenosine (1 mole) but the rabbit globin mRNAs lacked this nucleoside. Deficiencies in this technique for analysis of minor constituents in large RNAs were noted.

Animals↗
PubMed2024

A fast comparative genome browser for diverse bacteria and archaea.

Genome sequencing has revealed an incredible diversity of bacteria and archaea, but there are no fast and convenient tools for browsing across these genomes. It is cumbersome to view the prevalence of homologs for a protein of interest, or the gene neighborhoods of those homologs, across the diversity of the prokaryotes. We developed a web-based tool, fast.genomics, that uses two strategies to support fast browsing across the diversity of prokaryotes. First, the database of genomes is split up. The main database contains one representative from each of the 6,377 genera that have a high-quality genome, and additional databases for each taxonomic order contain up to 10 representatives of each species. Second, homologs of proteins of interest are identified quickly by using accelerated searches, usually in a few seconds. Once homologs are identified, fast.genomics can quickly show their prevalence across taxa, view their neighboring genes, or compare the prevalence of two different proteins. Fast.genomics is available at https://fast.genomics.lbl.gov.

Archaea↗
PubMed1978

Effect of nutritional supplementation in pregnancy. I. Outcome of pregnancy.

Women judged to be at high risk of delivering low-birth-weight infants were assigned to one of three supplements--high-protein beverage, low-protein beverage, or a vitamin-mineral preparation--to determine the effect these nutritional supplements would have on the outcome of pregnancy. In comparing prenatal nutrient intake and the birth weight of their infants, no significant associations were found. However, since the women were well nourished and since the sample size was small, changes in birth weight may have gone undetected. Nevertheless, a trend of increased birth weight with higher protein intake was observed.

Adolescent↗
PubMed2025

Genetic haplotypes in VWA8, OSBPL6, and ADAMTS9-AS2 are associated with immune-related adverse effects in ICI-treated patients with cancer.

BACKGROUND: Immune-related adverse events (irAEs) remain largely unpredictable, potentially affecting multiple organ systems and occurring at almost any point during and even occasionally after immune checkpoint inhibitor (ICI) treatment. To identify populations at risk for these immune-mediated toxicities, we analyzed genetic characteristics and immune markers associated with clinically significant irAEs. METHODS: We carried out a genome-wide association study on 373 white patients receiving ICI treatment. We identified single nucleotide polymorphisms associated with irAEs. Blood cytokine profiling and peripheral blood mononuclear cell RNA sequencing were performed at pretreatment baseline and 6-8 weeks after ICI initiation. Findings were validated in two external cohorts. RESULTS: We identified genetic haplotypes in VWA8 (Von Willebrand Factor A Domain Containing 8), OSBPL6 (Oxysterol Binding Protein Like 6), and ADAMTS9-AS2 (ADAM Metallopeptidase With Thrombospondin Type 1 Motif 9 Antisense RNA 2) associated with grade &#x2265;2 irAEs. Patients carrying risk haplotypes for one or more genes exhibited significantly greater rates of grade &#x2265;2 (OR 3.02; 95%&#x2009;CI 1.83 to 5.02; p<0.001), grade &#x2265;3 (OR 3.59; 95%&#x2009;CI 1.93 to 6.64; p<0.001), and multiple type irAE (OR 2.60; 95%&#x2009;CI 1.53 to 4.39; p<0.001). Serum CCL3 levels were significantly elevated in individuals carrying risk haplotypes (p=0.03). Gene expression analysis demonstrated activated autoimmune and inflammatory pathways in the genetic risk group. CONCLUSIONS: Novel polymorphisms in VWA8, OSBPL6, and ADAMTS9-AS2 may impact immune pathways, promote inflammation, potentiate autoimmune phenotypes, and convey risk of irAE in ICI-treated patients.

Humans↗
PubMed1978

[A new method for testing the quality of food protein for maintenance metabolism. 1. Investigations into the amount of 15N excreted via the urine of 15N-labelled young rats fed various proteins].

Over a period of 7 days, 38 experimental rats were fed a casein diet with a supplementation of 6.6 mg 15N-excess (15N') in the form of ammonium acetate. From the 5th experimental day, groups of 4 or 5 rats each were fed, over 5 days, different protein carriers to meet the meintenance requirement (115 kcal/kg body weight 0.75). The 15N-excretion via the urine, in terms of % of N absorbed from the food protein, served as yardstick of protein quality under maintenance conditions. The least 15N-excretion rates were reciprocally relativated for this maximum value (reciprocal 15N excretion biological value). The least 15N-excretion values from the 2nd to the 5th experimental days allowed to establish the following order for protein quality under maintenance conditions: fish meal, casein, wheat, whole egg, soybean (assayprotein), yeast peas, gelatin. The very good quality of the wheat protein for the maintenance state is seen in relation with the high content of glutamic acid (33.5 g/16 g N) and aspartic acid (5.7 g/16 gN). The found lysine content of the wheat protein (3.1 g/16 g N) proved sufficient for maintenance conditions.

Animals↗
PubMed1977

Influence of dexamethasone on the recrudescence of Anaplasma marginale in splenectomized calves.

Dexamethasone was administered at the dose rate of 0.2 mg/kg of body weight to 11 splenectomized Anaplasma-carrier calves (groups 1 and 3) on Monday, Wednesday, and Friday for 3 weeks. Observations were made on these calves and on 7 nontreated, comparable calves (group 2) to determine the influence of treatment on carrier infections. Dexamethasone treatment was associated in every instance with an exacerbation of the Anaplasma parasitemia and a decrease in packed red cell volume. The episode of acute anaplasmosis was of short duration, resembling the primary response, except that complement-fixation response did not increase accordingly. Serum protein electrophoresis of serums from 4 calves (group 3) undergoing the drug-induced response failed to show any significant change during the 3-week treatment period, but did show a significant increase in gamma-globulin immediately after treatment.

Anaplasmosis↗
PubMed1978

[New method of checking the quality of food proteins required for maintenance. 2. 15N excretion in feces of test rats labelled with 15N after feeding with different protein sources].

For 7 days 37 test rats received a casein diet with an extra of 6.6 mg 15N-excess in the form of ammonium acetate. From the eighth test day onwards 4 resp. 5 rats each received various protein sources under maintenance conditions (115 kcal/kg body mass0,75). The atom-% 15N-excess was determined in feces, blood liver and muscles (urine cf. 1st information). The endogenous quota of N in the feces was calculated as follows: (formula: see text). The numerical value of the TCA-soluble fraction of N in the total blood was corrected by the decrease of the atom-%15N' in the last 12 hours (time for the passage of the fecel matter from small intestines to excretion). Since the endogenously excreted N-amount varied greatly according to different feed, a scale is proposed as biologic value of food proteins, which exclusively refers to the metabolic fecal nitrogen (MFN) under conditions of maintenance (abbr. MFN-BV). A proposal for its definition is: (formula: see text). Above that, a total BV is suggested which also refers to maintenance metabolism. The total BV is calculated as follows: (formula: see text). The following values were ascertained for MFN-BV and total BV: casein = 80 and 82; complete egg=68 and 67; fish meal=61 and 86; Torula yeast=31 and 46; peas=41 and 43; soya (assay protein)=73 and 61; wheat=47 and 71; gelatin=64 and 42. Finally, the recommendation is given to include in feed tables real digestibility values for food proteins ascertained with the 15N method. In the above mentioned order the following values of the real digestibility of proteins were ascertained with the 15N method and classical methods: casein=98.2 and 97.2; complete egg=100.0 and 98.7; fish meal=96.9 and 93.4; Torula yeast=83.0 and 67.6; peas=97.1 and 85.6; soya (assay protein)=98.3 and 96.4; wheat=95.7 and 87.3; gelatin=99.1 and 96.0. *cf. 1st information Bergner et al. (1978)

Animals↗
PubMed1978

Metabolic and cellular profile testing in calves under feedlot conditions: protein fractions and lactate dehydrogenase isoenzymes--reference values.

Serum protein and lactate dehydrogenase (LDH) isoenzyme values were determined for frozen serum samples from crossbred yearling feedlot cattle on feed for 56 days. The mean percentage values for serum protein components from 114 samples were: albumin, 46.5; alpha-globulin, 10.4; beta-globulin, 18.7; gamma-globulin, 23.8. For LDH isoenzymes, they were: LDH1, 36.5; LDH2, 24.7; LDH3, 16.9; LDH4, 12.0; LDH5, 9.1. These values are compared with values from dairy cattle.

Animal Feed↗
PubMed1978

Thermodynamics of protein cross-links.

The thermal transitions of native lysozyme and a well-characterized cross-linked derivative of lysozyme [Imoto, T., and Rupley, J. A. (1973), J. Mol. Biol. 80, 657] have been studied in 1.94 M guanidine hydrochloride at pH 2. The observed increase in the melting temperature from 32.4 degrees C for native lysozyme to 61.8 degrees C for the cross-linked derivative corresponds to a calculated 5.2 kcal/mol increase in the free energy of denaturation. This free-energy change is attributed to the decreased entropy of the unfolded polypeptide chain following introduction of a cross-link and is shown to compare well with theoretical predictions. The possibility that an introduction of a cross-link could also affect the enthalpy of an unfolded protein was investigated. The heats of reduction of bovine serum albumin and lysozyme by dithioerythritol in 6 M guanidine hydrochloride were determined and compared to that for the model peptide, oxidized glutathione. The near identity of the observed heats was taken as evidence that the introduction of cross-links into a random-coil protein does not, in general, introduce strain.

Chemical Phenomena↗
PubMed1976

[Kearns' syndrome (author's transl)].

Kearns' syndrome, a rare cause of chronic progressive ophthalmoplegia was observed in three patients aged 15 to 54 years. Apart from the chronic progressive external ophthalmoplegia the syndrome consists of retinal changes and cardiac conduction defects in all cases, as well as other signs indicating damage to the nervous system. High tone deafness and vestibular damage as well as an increase in CSF protein are common. Endocrine disorders and skeletal anomalies may occur. The cause is unknown. The ophthalmoplegia may be of neurogenic origin. Adams-Stokes attacks following disturbances of cardiac rhythm may be prevented by timely implantation of a cardiac pacemaker.

Adams-Stokes Syndrome↗
PubMed1978

The disposition and metabolism of flurbiprofen in several species including man.

Flurbiprofen was rapidly absorbed in all species studied. 2. Half-lives of elimination measured 0 to 12 h after a single dose were: mouse 3.4 h, rat 2.5 h, dog 10.1 h, baboon 3.1 h and man 3.9 h. A second phase of elimination was seen in the dog. Flurbiprofen accumulated in the circulation of the dog on repeated dosing. 3. After dosing with [14C]flurbiprofen, tissue levels of radioactivity in dog and baboon were similar to that in plasma. In the rat, levels were slightly elevated in liver, kidney, large intestine and thyroid after repeated dosing. 4. The dog excreted equal amounts of radioactivity in urine and faeces. In other species renal excretion was the more important route. 5. Six metabolites have been detected, the most important being: 2-(2-fluoro-4'-hydroxy-4-biphenylyl)propionic acid (metabolite 1), 2-(i-fluoro-3',4'-dihydroxy-4-biphenylyl)propionic acid (metabolite 2) and 2-(2-fluoro-3'-hydroxy-4'-methoxy-4-biphenylyl)propionic acid (metabolite 3). The proportions of the metabolites and the extents of their conjugation varied among the species. 6. Metabolites were detected in the circulation of rat, mouse and baboon but not in dog and man. 7. Flurbiprofen did not affect the hepatic drug-metabolizing enzyme system of rat. 8. Flurbiprofen was extensively bound to serum protein of rat, dog, baboon and man.

Adolescent↗
PubMed1978

Laboratory Diagnosis of sickling hemoglobinopathies.

Sickle cell trait is present in about 8% of black Americans, and clinically significant sickling disorders are common in this population. These disorders can be accurately defined by combinations of quantitative hemoglobin electrophoresis at alkaline pH, citrate agar electrophoresis, solubility tests for sickle hemoglobin, fetal hemoglobin measurements, blood counts, erythrocyte indices and family studies. Unusual types of sickling hemoglobinopathies may require more extensive, specialized study. An unquestioned diagnosis should be prerequisite for any subsequent genetic counseling.

Anemia, Sickle Cell↗